Changes in parrot diversity after human arrival to the Caribbean.

Humans did not arrive on most of the world's islands until relatively recently, making islands favorable places for disentangling the timing and magnitude of natural and anthropogenic impacts on species diversity and distributions. Here, we focus on Amazona parrots in the Caribbean, which have close relationships with humans (e.g., as pets as well as sources of meat and colorful feathers). Caribbean parrots also have substantial fossil and archaeological records that span the Holocene. We leverage this exemplary record to showcase how combining ancient and modern DNA, along with radiometric dating, can shed light on diversification and extinction dynamics and answer long-standing questions about the magnitude of human impacts in the region. Our results reveal a striking loss of parrot diversity, much of which took place during human occupation of the islands. The most widespread species, the Cuban Parrot, exhibits interisland divergences throughout the Pleistocene. Within this radiation, we identified an extinct, genetically distinct lineage that survived on the Turks and Caicos until Indigenous human settlement of the islands. We also found that the narrowly distributed Hispaniolan Parrot had a natural range that once included The Bahamas; it thus became "endemic" to Hispaniola during the late Holocene. The Hispaniolan Parrot also likely was introduced by Indigenous people to Grand Turk and Montserrat, two islands where it is now also extirpated. Our research demonstrates that genetic information spanning paleontological, archaeological, and modern contexts is essential to understand the role of humans in altering the diversity and distribution of biota.

Molnupiravir plus usual care versus usual care alone as early treatment for adults with COVID-19 at increased risk of adverse outcomes (PANORAMIC): an open-label, platform-adaptive randomised controlled trial.

BACKGROUND: The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. METHODS: PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older-or aged 18 years or older with relevant comorbidities-and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (<50 years vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. FINDINGS: Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81-1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. INTERPRETATION: Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. FUNDING: UK National Institute for Health and Care Research.

Parasite escape mechanisms drive morphological diversification in avian lice.

Organisms that have repeatedly evolved similar morphologies owing to the same selective pressures provide excellent cases in which to examine specific morphological changes and their relevance to the ecology and evolution of taxa. Hosts of permanent parasites act as an independent evolutionary experiment, as parasites on these hosts are thought to be undergoing similar selective pressures. Parasitic feather lice have repeatedly diversified into convergent ecomorphs in different microhabitats on their avian hosts. We quantified specific morphological characters to determine (i) which traits are associated with each ecomorph, (ii) the quantitative differences between these ecomorphs, and (iii) if there is evidence of displacement among co-occurring lice as might be expected under louse-louse competition on the host. We used nano-computed tomography scan data of 89 specimens, belonging to four repeatedly evolved ecomorphs, to examine their mandibular muscle volume, limb length and three-dimensional head shape data. Here, we find evidence that lice repeatedly evolve similar morphologies as a mechanism to escape host defences, but also diverge into different ecomorphs related to the way they escape these defences. Lice that co-occur with other genera on a host exhibit greater morphological divergence, indicating a potential role of competition in evolutionary divergence.

Effects of climate change on Lepidoptera pollen loads and their pollination services in space and time.

Shifts in flowering time among plant communities as a result of climate change, including extreme weather events, are a growing concern. These plant phenological changes may affect the quantity and quality of food sources for specialized insect pollinators. Plant-pollinator interactions are threatened by habitat alterations and biodiversity loss, and changes in these interactions may lead to declines in flower visitors and pollination services. Most prior research has focused on short-term plant-pollinator interactions, which do not accurately capture changes in pollination services. Here, we characterized long-term plant-pollinator interactions and identified potential risks to specialized butterfly species due to habitat loss, fragmented landscapes, and changes in plant assemblages. We used 21 years of historical data from museum specimens to track the potential effects of direct and indirect changes in precipitation, temperature, monsoons, and wildfires on plant-pollinator mutualism in the Great Basin and Sierra Nevada. We found decreased pollen richness associated with butterflies within sites, as well as an increase in pollen grain abundance of drought-tolerant plants, particularly in the past 10 years. Moreover, increased global temperatures and the intensity and frequency of precipitation and wildfires were negatively correlated with pollen diversity. Our findings have important implications for understanding plant-pollinator interactions and the pollination services affected by global warming.

Late Cenozoic history and the role of Beringia in assembling a Holarctic cestode species complex.

The dynamic climate history that drove sea level fluctuation during past glacial periods mediated the movement of organisms between Asia and North America via the Bering Land Bridge. Investigations of the biogeographic histories of small mammals and their parasites demonstrate facets of a complex history of episodic geographic colonization and refugial isolation that structured diversity across the Holarctic. We use a large multi-locus nuclear DNA sequence dataset to robustly resolve relationships within the cestode genus Arostrilepis (Cyclophyllidea: Hymenolepididae), a widespread parasite of predominantly arvicoline rodents (voles, lemmings). Using this phylogeny, we confirm that several Asian Arostrilepis lineages colonized North America during up to four distinct glacial periods in association with different rodent hosts, consistent with taxon-pulse dynamics. A previously inferred westward dispersal across the land bridge is rejected. We also refine interpretations of past host colonization, providing evidence for several distinct episodes of expanding host range, which probably contributed to diversification by Arostrilepis. Finally, Arostrilepis is shown to be paraphyletic with respect to Hymenandrya thomomyis, a parasite of pocket gophers, confirming that ancient Arostrilepis species colonized new host lineages upon arriving in North America.

Oral combined contraceptives induce liver mitochondrial reactive oxygen species and whole-body metabolic adaptations in female mice.

Compared to age-matched men, pre-menopausal women show greater resilience against cardiovascular disease (CVD), hepatic steatosis, diabetes and obesity - findings that are widely attributed to oestrogen. However, meta-analysis data suggest that current use of oral combined contraceptives (OC) is a risk factor for myocardial infarction, and OC use further compounds with metabolic disease risk factors to increase CVD susceptibility. While mitochondrial function in tissues such as the liver and skeletal muscle is an emerging mechanism by which oestrogen may confer its protection, effects of OC use on mitochondria and metabolism in the context of disease risk remain unexplored. To answer this question, female C57Bl/6J mice were fed a high fat diet and treated with vehicle or OCs for 3, 12 or 20 weeks (n = 6 to 12 per group) at a dose and ratio that mimic the human condition of cycle cessation in the low oestrogen, high progesterone stage. Liver and skeletal muscle mitochondrial function (respiratory capacity, H2 O2 , coupling) was measured along with clinical outcomes of cardiometabolic disease such as obesity, glucose tolerance, hepatic steatosis and aortic atherosclerosis. The main findings indicate that regardless of treatment duration, OCs robustly increase hepatic mitochondrial H2 O2 levels, likely due to diminished antioxidant capacity, but have no impact on muscle mitochondrial H2 O2 . Furthermore, OC-treated mice had lower adiposity and hepatic triglyceride content compared to control mice despite reduced wheel running, spontaneous physical activity and total energy expenditure. Together, these studies describe tissue-specific effects of OC use on mitochondria as well as variable impacts on markers of metabolic disease susceptibility. KEY POINTS: Oestrogen loss in women increases risk for cardiometabolic diseases, a link that has been partially attributed to negative impacts on mitochondria and energy metabolism. To study the effect of oral combined contraceptives (OCs) on hepatic and skeletal muscle mitochondria and whole-body energy metabolism, we used an animal model of OCs which mimics the human condition of cessation of hormonal cycling in the low oestrogen, high progesterone state. OC-treated mice have increased hepatic mitochondrial oxidative stress and decreased physical activity and energy expenditure, despite displaying lower adiposity and liver fat at this time point. These pre-clinical data reveal tissue-specific effects of OCs that likely underlie the clinical findings of increased cardiometabolic disease in women who use OCs compared to non-users, when matched for obesity.

Long-distance dispersal of pigeons and doves generated new ecological opportunities for host-switching and adaptive radiation by their parasites.

Adaptive radiation is an important mechanism of organismal diversification and can be triggered by new ecological opportunities. Although poorly studied in this regard, parasites are an ideal group in which to study adaptive radiations because of their close associations with host species. Both experimental and comparative studies suggest that the ectoparasitic wing lice of pigeons and doves have adaptively radiated, leading to differences in body size and overall coloration. Here, we show that long-distance dispersal by dove hosts was central to parasite diversification because it provided new ecological opportunities for parasites to speciate after host-switching. We further show that among extant parasite lineages host-switching decreased over time, with cospeciation becoming the more dominant mode of parasite speciation. Taken together, our results suggest that host dispersal, followed by host-switching, provided novel ecological opportunities that facilitated adaptive radiation by parasites.

Molecular phylogenetics of the avian feather louse Philopterus-complex (Phthiraptera: Philopteridae).

The avian feather louse Philopterus-complex (Phthiraptera: Ischnocera: Philopteridae) currently contains 12 genera that have been grouped together because of shared morphological characteristics. Although previously lumped into a single genus (Philopterus), more recent morphological treatments have separated the group into several different genera. Here we evaluate the status of these genera using DNA sequence data from 118 ingroup specimens belonging to ten genera in the Philopterus-complex: Australophilopterus Mey, 2004, Cinclosomicola Mey 2004, Clayiella Eichler, 1940, Corcorides Mey, 2004, Mayriphilopterus Mey, 2004, Paraphilopterus Mey 2004, Philopteroides Mey 2004, Philopterus Nitzsch, 1818, Tyranniphilopterus Mey, 2004, and Vinceopterus Gustafsson, Lei, Chu, Zou, and Bush, 2019. Our sampling includes 97 new louse-host association records. Our analyses suggest that the genus Debeauxoecus Conci, 1941, parasitic on pittas (Aves: Pittidae), is outside of the Philopterus-complex, and that there is strong support for the monophyly of a group containing the remaining genera from the complex. Some diverse genera, such as Philopterus (sensu stricto) and Mayriphilopterus are supported as monophyletic, whereas the genera Australophilopterus, Philopteroides, and Tyranniphilopterus are not. The present study is the largest phylogenetic reconstruction of avian lice belonging to the Philopterus-complex to date and suggests that further generic revision is needed in the group to integrate molecular and morphological information.

Rates of niche and phenotype evolution lag behind diversification in a temperate radiation.

Environmental change can create opportunities for increased rates of lineage diversification, but continued species accumulation has been hypothesized to lead to slowdowns via competitive exclusion and niche partitioning. Such density-dependent models imply tight linkages between diversification and trait evolution, but there are plausible alternative models. Little is known about the association between diversification and key ecological and phenotypic traits at broad phylogenetic and spatial scales. Do trait evolutionary rates coincide with rates of diversification, are there lags among these rates, or is diversification niche-neutral? To address these questions, we combine a deeply sampled phylogeny for a major flowering plant clade-Saxifragales-with phenotype and niche data to examine temporal patterns of evolutionary rates. The considerable phenotypic and habitat diversity of Saxifragales is greatest in temperate biomes. Global expansion of these habitats since the mid-Miocene provided ecological opportunities that, with density-dependent adaptive radiation, should result in simultaneous rate increases for diversification, niche, and phenotype, followed by decreases with habitat saturation. Instead, we find that these rates have significantly different timings, with increases in diversification occurring at the mid-Miocene Climatic Optimum (∼15 Mya), followed by increases in niche and phenotypic evolutionary rates by ∼5 Mya; all rates increase exponentially to the present. We attribute this surprising lack of temporal coincidence to initial niche-neutral diversification followed by ecological and phenotypic divergence coincident with more extreme cold and dry habitats that proliferated into the Pleistocene. A lack of density-dependence contrasts with investigations of other cosmopolitan lineages, suggesting alternative patterns may be common in the diversification of temperate lineages.

Effect of Self-monitoring of Blood Pressure on Blood Pressure Control in Pregnant Individuals With Chronic or Gestational Hypertension: The BUMP 2 Randomized Clinical Trial.

Importance: Inadequate management of elevated blood pressure is a significant contributing factor to maternal deaths. The role of blood pressure self-monitoring in pregnancy in improving clinical outcomes for the pregnant individual and infant is unclear. Objective: To evaluate the effect of blood pressure self-monitoring, compared with usual care alone, on blood pressure control and other related maternal and infant outcomes, in individuals with pregnancy hypertension. Design, Setting, and Participants: Unblinded, randomized clinical trial that recruited between November 2018 and September 2019 in 15 hospital maternity units in England. Individuals with chronic hypertension (enrolled up to 37 weeks' gestation) or with gestational hypertension (enrolled between 20 and 37 weeks' gestation). Final follow-up was in May 2020. Interventions: Participants were randomized to either blood pressure self-monitoring using a validated monitor and a secure telemonitoring system in addition to usual care (n = 430) or to usual care alone (n = 420). Usual care comprised blood pressure measured by health care professionals at regular antenatal clinics. Main Outcomes and Measures: The primary maternal outcome was the difference in mean systolic blood pressure recorded by health care professionals between randomization and birth. Results: Among 454 participants with chronic hypertension (mean age, 36 years; mean gestation at entry, 20 weeks) and 396 with gestational hypertension (mean age, 34 years; mean gestation at entry, 33 weeks) who were randomized, primary outcome data were available from 444 (97.8%) and 377 (95.2%), respectively. In the chronic hypertension cohort, there was no statistically significant difference in mean systolic blood pressure for the self-monitoring groups vs the usual care group (133.8 mm Hg vs 133.6 mm Hg, respectively; adjusted mean difference, 0.03 mm Hg [95% CI, -1.73 to 1.79]). In the gestational hypertension cohort, there was also no significant difference in mean systolic blood pressure (137.6 mm Hg compared with 137.2 mm Hg; adjusted mean difference, -0.03 mm Hg [95% CI, -2.29 to 2.24]). There were 8 serious adverse events in the self-monitoring group (4 in each cohort) and 3 in the usual care group (2 in the chronic hypertension cohort and 1 in the gestational hypertension cohort). Conclusions and Relevance: Among pregnant individuals with chronic or gestational hypertension, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly improved clinic-based blood pressure control. Trial Registration: ClinicalTrials.gov Identifier: NCT03334149.

Effect of Self-monitoring of Blood Pressure on Diagnosis of Hypertension During Higher-Risk Pregnancy: The BUMP 1 Randomized Clinical Trial.

Importance: Inadequate management of elevated blood pressure (BP) is a significant contributing factor to maternal deaths. Self-monitoring of BP in the general population has been shown to improve the diagnosis and management of hypertension; however, little is known about its use in pregnancy. Objective: To determine whether self-monitoring of BP in higher-risk pregnancies leads to earlier detection of pregnancy hypertension. Design, Setting, and Participants: Unblinded, randomized clinical trial that included 2441 pregnant individuals at higher risk of preeclampsia and recruited at a mean of 20 weeks' gestation from 15 hospital maternity units in England between November 2018 and October 2019. Final follow-up was completed in April 2020. Interventions: Participating individuals were randomized to either BP self-monitoring with telemonitoring (n = 1223) plus usual care or usual antenatal care alone (n = 1218) without access to telemonitored BP. Main Outcomes and Measures: The primary outcome was time to first recorded hypertension measured by a health care professional. Results: Among 2441 participants who were randomized (mean [SD] age, 33 [5.6] years; mean gestation, 20 [1.6] weeks), 2346 (96%) completed the trial. The time from randomization to clinic recording of hypertension was not significantly different between individuals in the self-monitoring group (mean [SD], 104.3 [32.6] days) vs in the usual care group (mean [SD], 106.2 [32.0] days) (mean difference, -1.6 days [95% CI, -8.1 to 4.9]; P = .64). Eighteen serious adverse events were reported during the trial with none judged as related to the intervention (12 [1%] in the self-monitoring group vs 6 [0.5%] in the usual care group). Conclusions and Relevance: Among pregnant individuals at higher risk of preeclampsia, blood pressure self-monitoring with telemonitoring, compared with usual care, did not lead to significantly earlier clinic-based detection of hypertension. Trial Registration: ClinicalTrials.gov Identifier: NCT03334149.

Partisanship, Policy, and Americans' Evaluations of State-Level COVID-19 Policies Prior to the 2020 Election.

The COVID-19 pandemic was a key policy issue during the 2020 election in the United States. As such, it is important to analyze how voters evaluated government responses to the pandemic. To this end, in this article, we examine factors that influenced Americans' evaluations of state-level COVID-19 policy responses. We find that during the pandemic onset period, Americans typically rated their state governments' responses more favorably if their governor was a co-partisan. In contrast, during the re-opening period, we find that Democrats relied on both partisanship and policy to evaluate their state-level responses, while Republicans continued to rely solely on partisanship. We contend that given the complex policy environment surrounding COVID-19, Americans may have not been fully aware of the policies their state governments adopted, so they relied on partisan cues to help them evaluate their state-level policy responses. But by the re-opening period, Americans likely had enough time to better understand state-level policy responses; this allowed Democrats to also evaluate their state-level responses based on policy. These findings shed light on how Americans evaluated COVID-19 responses just prior to the 2020 election.

Burden of respiratory syncytial virus infection in community-dwelling older adults in Europe (RESCEU): an international prospective cohort study.

BACKGROUND: Respiratory syncytial virus (RSV) infection in older adults is recognised as an important health issue. We aimed to assess the community burden of RSV in Europe in older adults aged ≥60 years. METHODS: This international, prospective, observational cohort study is part of work by the REspiratory Syncytial virus Consortium in EUrope (RESCEU). Participants were recruited through general practitioners' (GPs) offices before two independent RSV seasons. Participants reported weekly about symptoms of acute respiratory tract infection (ARTI) during one RSV season. ARTI patients were tested for RSV during home visits and completed a daily symptom diary. RSV illness included PCR-confirmed ARTI and those showing seroconversion over the season. RSV ARTI was based on PCR alone (ClinicalTrials.gov, NCT03621930). RESULTS: We recruited 1040 participants (527 in season 2017-2018 and 513 in season 2018-2019) with a median age of 75 years (range 60-100 years). Of these, 1023 (99%) lived independently at home at baseline. RSV illness incidence was 22 out of 527 (4.2%) and 37 out of 513 (7.2%) in the respective seasons. RSV illness did not affect frailty or cardiopulmonary status during the course of the study. No patients were hospitalised or died from RSV illness. In the 36 patients with PCR confirmed RSV ARTI, symptom duration averaged 19 days, while a doctor's visit took place in 11 out of 36 cases (31%). RSV ARTI could not be differentiated clinically from all other ARTIs based on symptoms. CONCLUSION: This European study showed that RSV is prevalent in community-dwelling older adults and rarely causes severe disease. This suggests that watchful waiting, using a continuity of care approach to identify those who do need more intensive care, is often justified when RSV is suspected in family practice.

Disentangling lousy relationships: Comparative phylogenomics of two sucking louse lineages parasitizing chipmunks.

The evolution of obligate parasites is often interpreted in light of their hosts' evolutionary history. An expanded approach is to examine the histories of multiple lineages of parasites that inhabit similar environments on a particular host lineage. Western North American chipmunks (genus Tamias) have a broad distribution, a history of divergence with gene flow, and host two species of sucking lice (Anoplura), Hoplopleura arboricola and Neohaematopinus pacificus. From total genomic sequencing, we obtained sequences of over 1100 loci sampled across the genomes of these lice to compare their evolutionary histories and examine the roles of host association in structuring louse relationships. Within each louse species, clades are largely associated with closely related chipmunk host species. Exceptions to this pattern appear to have a biogeographic component, but differ between the two louse species. Phylogenetic relationships among these major louse clades, in both species, are not congruent with chipmunk relationships. In the context of host associations, each louse lineage has a different evolutionary history, supporting the hypothesis that host-parasite assemblages vary both across the landscape and with the taxa under investigation. In addition, the louse Hoplopleura erratica (parasitizing the eastern Tamias striatus) is embedded within H. arboricola, rendering it paraphyletic. This phylogenetic result, together with comparable divergences within H. arboricola, indicate a need for taxonomic revision. Both host divergence and biogeographic components shape parasite diversification as demonstrated by the distinctive diversification patterns of these two independently evolving lineages that parasitize the same hosts.

Ancient DNA from the extinct Haitian cave-rail (Nesotrochis steganinos) suggests a biogeographic connection between the Caribbean and Old World.

Worldwide decline in biodiversity during the Holocene has impeded a comprehensive understanding of pre-human biodiversity and biogeography. This is especially true on islands, because many recently extinct island taxa were morphologically unique, complicating assessment of their evolutionary relationships using morphology alone. The Caribbean remains an avian hotspot but was more diverse before human arrival in the Holocene. Among the recently extinct lineages is the enigmatic genus Nesotrochis, comprising three flightless species. Based on morphology, Nesotrochis has been considered an aberrant rail (Rallidae) or related to flufftails (Sarothruridae). We recovered a nearly complete mitochondrial genome of Nesotrochis steganinos from fossils, discovering that it is not a rallid but instead is sister to Sarothruridae, volant birds now restricted to Africa and New Guinea, and the recently extinct, flightless Aptornithidae of New Zealand. This result suggests a widespread or highly dispersive most recent common ancestor of the group. Prior to human settlement, the Caribbean avifauna had a far more cosmopolitan origin than is evident from extant species.

Phylogenomics and the evolution of hemipteroid insects.

Hemipteroid insects (Paraneoptera), with over 10% of all known insect diversity, are a major component of terrestrial and aquatic ecosystems. Previous phylogenetic analyses have not consistently resolved the relationships among major hemipteroid lineages. We provide maximum likelihood-based phylogenomic analyses of a taxonomically comprehensive dataset comprising sequences of 2,395 single-copy, protein-coding genes for 193 samples of hemipteroid insects and outgroups. These analyses yield a well-supported phylogeny for hemipteroid insects. Monophyly of each of the three hemipteroid orders (Psocodea, Thysanoptera, and Hemiptera) is strongly supported, as are most relationships among suborders and families. Thysanoptera (thrips) is strongly supported as sister to Hemiptera. However, as in a recent large-scale analysis sampling all insect orders, trees from our data matrices support Psocodea (bark lice and parasitic lice) as the sister group to the holometabolous insects (those with complete metamorphosis). In contrast, four-cluster likelihood mapping of these data does not support this result. A molecular dating analysis using 23 fossil calibration points suggests hemipteroid insects began diversifying before the Carboniferous, over 365 million years ago. We also explore implications for understanding the timing of diversification, the evolution of morphological traits, and the evolution of mitochondrial genome organization. These results provide a phylogenetic framework for future studies of the group.

Extensive in situ radiation of feather lice on tinamous.

Tinamous host the highest generic diversity of lice of any group of birds, as well as hosting representatives of all four avian feather louse ecomorphs. Although the generic diversity of tinamou feather lice is well documented, few attempts have been made to reconstruct the phylogenetic relationships among these lice. To test whether tinamou feather lice form a monophyletic group as a whole, we used whole-genome sequencing to estimate a higher-level phylogeny of tinamou feather lice, together with a broad diversity of other avian feather louse groups. In total, we analysed sequences from over 1000 genes for 48 genera of avian lice using both concatenated and coalescent approaches to estimate the phylogeny of this diverse group of avian feather lice. Although the body louse ecomorph of tinamou feather lice formed a monophyletic group, they did not strictly form a monophyletic group together with the other three ecomorphs of tinamou feather lice. In particular, a clade comprised of several feather louse genera, mainly from South America, is nested phylogenetically within tinamou lice, which also have their main centre of diversity in South America. These results suggest in situ radiation of these parasites in South America.

Impacts of Inference Method and Data set Filtering on Phylogenomic Resolution in a Rapid Radiation of Ground Squirrels (Xerinae: Marmotini).

Phylogenomic data sets are illuminating many areas of the Tree of Life. However, the large size of these data sets alone may be insufficient to resolve problematic nodes in the most rapid evolutionary radiations, because inferences in zones of extraordinarily low phylogenetic signal can be sensitive to the model and method of inference, as well as the information content of loci employed. We used a data set of $>$3950 ultraconserved element (UCE) loci from a classic mammalian radiation, ground-dwelling squirrels of the tribe Marmotini (Sciuridae: Xerinae), to assess sensitivity of phylogenetic estimates to varying per-locus information content across four different inference methods (RAxML, ASTRAL, NJst, and SVDquartets). Persistent discordance was found in topology and bootstrap support between concatenation- and coalescent-based inferences; among methods within the coalescent framework; and within all methods in response to different filtering scenarios. Contrary to some recent empirical UCE-based studies, filtering by information content did not promote complete among-method concordance. Nevertheless, filtering did improve concordance relative to randomly selected locus sets, largely via improved consistency of two-step summary methods (particularly NJst) under conditions of higher average per-locus variation (and thus increasing gene tree precision). The benefits of phylogenomic data set filtering are variable among classes of inference methods and across different evolutionary scenarios, reiterating the complexities of resolving rapid radiations, even with robust taxon and character sampling.

Effect of Antihypertensive Medication Reduction vs Usual Care on Short-term Blood Pressure Control in Patients With Hypertension Aged 80 Years and Older: The OPTIMISE Randomized Clinical Trial.

Importance: Deprescribing of antihypertensive medications is recommended for some older patients with polypharmacy and multimorbidity when the benefits of continued treatment may not outweigh the harms. Objective: This study aimed to establish whether antihypertensive medication reduction is possible without significant changes in systolic blood pressure control or adverse events during 12-week follow-up. Design, Setting, and Participants: The Optimising Treatment for Mild Systolic Hypertension in the Elderly (OPTIMISE) study was a randomized, unblinded, noninferiority trial conducted in 69 primary care sites in England. Participants, whose primary care physician considered them appropriate for medication reduction, were aged 80 years and older, had systolic blood pressure lower than 150 mm Hg, and were receiving at least 2 antihypertensive medications were included. Participants enrolled between April 2017 and September 2018 and underwent follow-up until January 2019. Interventions: Participants were randomized (1:1 ratio) to a strategy of antihypertensive medication reduction (removal of 1 drug [intervention], n = 282) or usual care (control, n = 287), in which no medication changes were mandated. Main Outcomes and Measures: The primary outcome was systolic blood pressure lower than 150 mm Hg at 12-week follow-up. The prespecified noninferiority margin was a relative risk (RR) of 0.90. Secondary outcomes included the proportion of participants maintaining medication reduction and differences in blood pressure, frailty, quality of life, adverse effects, and serious adverse events. Results: Among 569 patients randomized (mean age, 84.8 years; 276 [48.5%] women; median of 2 antihypertensive medications prescribed at baseline), 534 (93.8%) completed the trial. Overall, 229 (86.4%) patients in the intervention group and 236 (87.7%) patients in the control group had a systolic blood pressure lower than 150 mm Hg at 12 weeks (adjusted RR, 0.98 [97.5% 1-sided CI, 0.92 to ∞]). Of 7 prespecified secondary end points, 5 showed no significant difference. Medication reduction was sustained in 187 (66.3%) participants at 12 weeks. Mean change in systolic blood pressure was 3.4 mm Hg (95% CI, 1.1 to 5.8 mm Hg) higher in the intervention group compared with the control group. Twelve (4.3%) participants in the intervention group and 7 (2.4%) in the control group reported at least 1 serious adverse event (adjusted RR, 1.72 [95% CI, 0.7 to 4.3]). Conclusions and Relevance: Among older patients treated with multiple antihypertensive medications, a strategy of medication reduction, compared with usual care, was noninferior with regard to systolic blood pressure control at 12 weeks. The findings suggest antihypertensive medication reduction in some older patients with hypertension is not associated with substantial change in blood pressure control, although further research is needed to understand long-term clinical outcomes. Trial Registration: EudraCT Identifier: 2016-004236-38; ISRCTN identifier: 97503221.

COVID-19 Policy Response and the Rise of the Sub-National Governments.

We examine the roles of sub-national and national governments in Canada and the United States vis-à-vis the protective public health response in the onset phase of the global coronavirus disease 2019 (COVID-19) pandemic. This period was characterized in both countries by incomplete information as well as by uncertainty regarding which level of government should be responsible for which policies. The crisis represents an opportunity to study how national and sub-national governments respond to such policy challenges. In this article, we present a unique dataset that catalogues the policy responses of US states and Canadian provinces as well as those of the respective federal governments: the Protective Policy Index (PPI). We then compare the United States and Canada along several dimensions, including the absolute values of sub-national levels of the index relative to the total protections enjoyed by citizens, the relationship between early threat (as measured by the mortality rate near the start of the public health crisis) and the evolution of the PPI, and finally the institutional and legislative origins of the protective health policies. We find that the sub-national contribution to policy is more important for both the United States and Canada than are their national-level policies, and it is unrelated in scope to our early threat measure. We also show that the institutional origin of the policies as evidenced by the COVID-19 response differs greatly between the two countries and has implications for the evolution of federalism in each.

Nous examinons le rôle des gouvernements infranationaux et nationaux du Canada et des États-Unis dans l'adoption de mesures de protection de la santé publique au stade initial de la pandémie mondiale de COVID­19. Cette période a été caractérisée dans les deux pays par des informations incomplètes ainsi que par une incertitude quant à l'ordre de gouvernement responsable de telle ou telle politique. La crise offre l'occasion d'étudier comment les gouvernements nationaux et infranationaux relèvent ces défis politiques. Dans l'article qui suit, nous présentons un ensemble de données unique qui répertorie les décisions politiques des États américains et des provinces canadiennes en matière de protection, ainsi que celles des gouvernements fédéraux respectifs : l'indice de politique de protection (IPP). Nous comparons ensuite les États-Unis et le Canada selon plusieurs dimensions, notamment les valeurs absolues des niveaux infranationaux de l'IPP par rapport aux protections totales dont bénéficient les citoyens, la relation entre la « menace précoce ¼ (mesurée selon les taux de mortalité à l'approche du début de la crise de santé publique) et l'évolution de l'IPP et, enfin, les origines institutionnelles­législatives des politiques de protection de la santé. Nous constatons que la contribution infranationale à la politique est plus importante pour les deux pays mais qu'elle n'est pas liée à notre mesure de la « menace précoce ¼. Nous démontrons également que l'origine institutionnelle des politiques diffère grandement entre les deux pays et que cela a des répercussions sur l'évolution du fédéralisme.