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Travel time to cities in 2015 is quantified in a high-resolution global map that will be useful for socio-economic policy design and conservation research. The roads to equality Resources that sustain human wellbeing, such as education, jobs and health services, are distributed unequally, with higher concentrations in dense urban areas. Increasing access to such opportunities and services is a key factor in the advancement of fair and sustainable development. Integrating multiple large data sources for road and city geography, Daniel Weiss and colleagues have created a high-resolution global map that quantifies travel time to cities in the year 2015. This map provides a detailed view of the heterogeneity in accessibility to cities around the world, serving not just as a potential indicator for development but also as an input for future models in areas such as conservation biology. The economic and man-made resources that sustain human wellbeing are not distributed evenly across the world, but are instead heavily concentrated in cities. Poor access to opportunities and services offered by urban centres (a function of distance, transport infrastructure, and the spatial distribution of cities) is a major barrier to improved livelihoods and overall development. Advancing accessibility worldwide underpins the equity agenda of ‘leaving no one behind’ established by the Sustainable Development Goals of the United Nations 1 . This has renewed international efforts to accurately measure accessibility and generate a metric that can inform the design and implementation of development policies. The only previous attempt to reliably map accessibility worldwide, which was published nearly a decade ago 2 , predated the baseline for the Sustainable Development Goals and excluded the recent expansion in infrastructure networks, particularly in lower-resource settings. In parallel, new data sources provided by Open Street Map and Google now capture transportation networks with unprecedented detail and precision. Here we develop and validate a map that quantifies travel time to cities for 2015 at a spatial resolution of approximately one by one kilometre by integrating ten global-scale surfaces that characterize factors affecting human movement rates and 13,840 high-density urban centres within an established geospatial-modelling framework. Our results highlight disparities in accessibility relative to wealth as 50.9% of individuals living in low-income settings (concentrated in sub-Saharan Africa) reside within an hour of a city compared to 90.7% of individuals in high-income settings. By further triangulating this map against socioeconomic datasets, we demonstrate how access to urban centres stratifies the economic, educational, and health status of humanity.

Rotation sutures are a popular method of temporarily correcting involutional entropion. The permanence of the procedure depends on a fibrotic scar along the suture tracks. Sutures which create generous scars would probably produce the most satisfactory results. In this study 4-0 chromic gut, nylon, and silk sutures were evaluated in rabbit lower eyelids for their ability to create histologically demonstrable fibrous tracks. All three sutures incited inflammatory cells and fibroblastic activity with collagen formation at two and four weeks. Residual scar tracks were observed at six weeks (two weeks after suture removal) also. Human specimens showed similar types of scar formation from the sutures. It was apparent that all three sutures create fibrotic scars along their tracks sufficient to correct, at least temporarily, involutional entropion.

Carbon emissions and their ocean impactsAnthropogenic CO2 emissions directly affect atmospheric chemistry but also have a strong influence on the oceans. Gattuso et al. review how the physics, chemistry, and ecology of the oceans might be affected based on two CO2 emission trajectories: one business as usual and one with aggressive reductions. Ocean warming, acidification, sea-level rise, and the expansion of oxygen minimum zones will continue to have distinct impacts on marine communities and ecosystems. The path that humanity takes regarding CO2 emissions will largely determine the severity of these phenomena.Science, this issue 10.1126/science.aac4722 The ocean moderates anthropogenic climate change at the cost of profound alterations of its physics, chemistry, ecology, and services. Here, we evaluate and compare the risks of impacts on marine and coastal ecosystems-and the goods and services they provide-for growing cumulative carbon emissions under two contrasting emissions scenarios. The current emissions trajectory would rapidly and significantly alter many ecosystems and the associated services on which humans heavily depend. A reduced emissions scenario-consistent with the Copenhagen Accord's goal of a global temperature increase of less than 2 degree C-is much more favorable to the ocean but still substantially alters important marine ecosystems and associated goods and services. The management options to address ocean impacts narrow as the ocean warms and acidifies. Consequently, any new climate regime that fails to minimize ocean impacts would be incomplete and inadequate.

Biodiversity is essential to food security and nutrition locally and globally. By reviewing the global state of edible plants and highlighting key neglected and underutilized species, we attempt to unlock plant food resources and explore the role of fungi, which along with the wealth of traditional knowledge about their uses and practices, could help support sustainable agriculture while ensuring better protection of the environment and the continued delivery of its ecosystem services. This work will inform a wide range of user communities, including scientists, conservation and development organizations, policymakers, and the public of the importance of biodiversity beyond mainstream crops. Societal Impact Statement Biodiversity is essential to food security and nutrition locally and globally. By reviewing the global state of edible plants and highlighting key neglected and underutilized species (NUS), we attempt to unlock plant food resources and explore the role of fungi, which along with the wealth of traditional knowledge about their uses and practices, could help support sustainable agriculture while ensuring better protection of the environment and the continued delivery of its ecosystem services. This work will inform a wide range of user communities, including scientists, conservation and development organizations, policymakers, and the public of the importance of biodiversity beyond mainstream crops. Summary As the world's population is increasing, humanity is facing both shortages (hunger) and excesses (obesity) of calorie and nutrient intakes. Biodiversity is fundamental to addressing this double challenge, which involves a far better understanding of the global state of food resources. Current estimates suggest that there are at least 7,039 edible plant species, in a broad taxonomic sense, which includes 7,014 vascular plants. This is in striking contrast to the small handful of food crops that provide the majority of humanity's calorie and nutrient intake. Most of these 7,039 edible species have additional uses, the most common being medicines (70%), materials (59%), and environmental uses (40%). Species of major food crops display centers of diversity, as previously proposed, while the rest of edible plants follow latitudinal distribution patterns similarly to the total plant diversity, with higher species richness at lower latitudes. The International Union for Conservation of Nature Red List includes global conservation assessments for at least 30% of edible plants, with ca. 86% of them conserved ex situ. However, at least 11% of those species recorded are threatened. We highlight multipurpose NUS of plants from different regions of the world, which could be key for a more resilient, sustainable, biodiverse, and community participation‐driven new “green revolution.” Furthermore, we explore how fungi could diversify and increase the nutritional value of our diets. NUS, along with the wealth of traditional knowledge about their uses and practices, offer a largely untapped resource to support food security and sustainable agriculture. However, for these natural resources to be unlocked, enhanced collaboration among stakeholders is vital.

Plants and fungi have provided, or inspired, key pharmaceuticals for global health challenges, including cancer, heart disease, dementia, and malaria, and are valued as traditional medicines worldwide. Global demand for medicinal plants and fungi has threatened certain species, contributing to biodiversity loss and depletion of natural resources that are important for the health of humanity. We consider the evolving role of plants and fungi in global healthcare as new challenges to human health and to biodiversity arise. We present current and emerging scientific approaches, to uncover and preserve nature‐based health solutions for the future, through harmonization with biodiversity conservation strategies. Societal Impact Statement Plants and fungi have provided, or inspired, key pharmaceuticals for global health challenges, including cancer, heart disease, dementia, and malaria, and are valued as traditional medicines worldwide. Global demand for medicinal plants and fungi has threatened certain species, contributing to biodiversity loss and depletion of natural resources that are important for the health of humanity. We consider the evolving role of plants and fungi in global healthcare as new challenges to human health and to biodiversity arise. We present current and emerging scientific approaches, to uncover and preserve nature‐based health solutions for the future, through harmonization with biodiversity conservation strategies. Summary Non‐communicable diseases, including cardiovascular disease, cancer, and diabetes, are the main causes of deaths globally, and communicable diseases such as malaria and tuberculosis affect billions of people. Plants and fungi have provided key pharmaceuticals in our armory against these global health challenges, while in some regions of the world, they continue to have a central role in healthcare systems as traditional medicines. Consequently, global demand for plants and fungi in healthcare has threatened certain medicinal species, and is a driving factor in biodiversity loss. Yet the future of therapeutics from nature is evolving. Scientific advances are enabling the untapped potential of the world's plants and fungi to be explored for their medicinal value, and to reveal other roles they may have for improving health and well‐being; this demonstrates the value of natural capital as an incentive for biodiversity conservation. Emerging technologies also offer new hope for safeguarding essential medicines for the future, by revealing more sustainable solutions for sourcing key natural products. This review discusses recent developments and future approaches for the discovery of natural products as medicines, for health and well‐being, and strategies to harmonize the therapeutic use of biodiversity with its proactive conservation through nature‐based solutions.

Background Clozapine is an antipsychotic drug with unique efficacy, and it is the only recommended treatment for treatment-resistant schizophrenia (TRS: failure to respond to at least two different antipsychotics). However, clozapine is also associated with a range of adverse effects which restrict its use, including blood dyscrasias, for which haematological monitoring is required. As treatment resistance is recognised earlier in the illness, the question of whether clozapine should be prescribed in children and young people is increasingly important. However, most research to date has been in older, chronic patients, and evidence regarding the efficacy and safety of clozapine in people under age 25 is lacking. The CLEAR (CLozapine in EARly psychosis) trial will assess whether clozapine is more effective than treatment as usual (TAU), at the level of clinical symptoms, patient rated outcomes, quality of life and cost-effectiveness in people below 25 years of age. Additionally, a nested biomarker study will investigate the mechanisms of action of clozapine compared to TAU. Methods and design This is the protocol of a multi-centre, open label, blind-rated, randomised controlled effectiveness trial of clozapine vs TAU (any other oral antipsychotic monotherapy licenced in the British National Formulary) for 12 weeks in 260 children and young people with TRS (12–24 years old). Aim and objectives The primary outcome is the change in blind-rated Positive and Negative Syndrome Scale scores at 12 weeks from baseline. Secondary outcomes include blind-rated Clinical Global Impression, patient-rated outcomes, quality of life, adverse effects, and treatment adherence. Patients will be followed up for 12 months and will be invited to give consent for longer term follow-up using clinical records and potential re-contact for further research. For mechanism of action, change in brain magnetic resonance imaging (MRI) biomarkers and peripheral inflammatory markers will be measured over 12 weeks. Discussion The CLEAR trial will contribute knowledge on clozapine effectiveness, safety and cost-effectiveness compared to standard antipsychotics in young people with TRS, and the results may guide future clinical treatment recommendation for early psychosis. Trial registration ISRCTN Number: 37176025, IRAS Number: 1004947. Trial status In set-up. Protocol version 4.0 01/08/23. Current up to date protocol available here: https://fundingawards.nihr.ac.uk/award/NIHR131175# /.

At solar minimum, the solar wind is observed at high solar latitudes as a predominantly fast (> 500 km/s), highly Alfvenic, rarefied stream of plasma originating deep within coronal holes, while near the ecliptic plane it is interspersed with a more variable slow (< 500 kms) wind. The precise origins of the slow wind streams are less certain, with theories and observations supporting sources from the tips of helmet streamers, interchange reconnection near coronal hole boundaries, and origins within coronal holes with highly diverging magnetic fields. The heating mechanism required to drive the solar wind is also an open question and candidate mechanisms include Alfven wave turbulence, heating by reconnection in nanoflares, ion cyclotron wave heating and acceleration by thermal gradients1. At 1 au, the wind is mixed and evolved and much of the diagnostic structure of these sources and processes has been lost. Here we present new measurements from Parker Solar Probe at 36 to 54 solar radii that show clear evidence of slow, Alfvenic solar wind emerging from a small equatorial coronal hole. The measured magnetic field exhibits patches of large, intermittent reversals associated with jets of plasma and enhanced Poynting flux and interspersed in a smoother and less turbulent flow with near-radial magnetic field. Furthermore, plasma wave measurements suggest electron and ion velocity-space micro-instabilities that have been identified with plasma heating and thermalization processes. Our measurements suggest an impulsive mechanism associated with solar wind energization and a heating role for micro-instabilities and provide strong evidence for low latitude coronal holes as a significant contribution to the source of the slow solar wind.

A research priority for Plasmodium vivax malaria is to improve our understanding of the spatial distribution of risk and its relationship with the burden of P. vivax disease in human populations. The aim of the research outlined in this article is to provide a contemporary evidence-based map of the global spatial extent of P. vivax malaria, together with estimates of the human population at risk (PAR) of any level of transmission in 2009. The most recent P. vivax case-reporting data that could be obtained for all malaria endemic countries were used to classify risk into three classes: malaria free, unstable (<0.1 case per 1,000 people per annum (p.a.)) and stable (> or =0.1 case per 1,000 p.a.) P. vivax malaria transmission. Risk areas were further constrained using temperature and aridity data based upon their relationship with parasite and vector bionomics. Medical intelligence was used to refine the spatial extent of risk in specific areas where transmission was reported to be absent (e.g., large urban areas and malaria-free islands). The PAR under each level of transmission was then derived by combining the categorical risk map with a high resolution population surface adjusted to 2009. The exclusion of large Duffy negative populations in Africa from the PAR totals was achieved using independent modelling of the gene frequency of this genetic trait. It was estimated that 2.85 billion people were exposed to some risk of P. vivax transmission in 2009, with 57.1% of them living in areas of unstable transmission. The vast majority (2.59 billion, 91.0%) were located in Central and South East (CSE) Asia, whilst the remainder were located in America (0.16 billion, 5.5%) and in the Africa+ region (0.10 billion, 3.5%). Despite evidence of ubiquitous risk of P. vivax infection in Africa, the very high prevalence of Duffy negativity throughout Central and West Africa reduced the PAR estimates substantially. After more than a century of development and control, P. vivax remains more widely distributed than P. falciparum and is a potential cause of morbidity and mortality amongst the 2.85 billion people living at risk of infection, the majority of whom are in the tropical belt of CSE Asia. The probability of infection is reduced massively across Africa by the frequency of the Duffy negative trait, but transmission does occur on the continent and is a concern for Duffy positive locals and travellers. The final map provides the spatial limits on which the endemicity of P. vivax transmission can be mapped to support future cartographic-based burden estimations.

Signalling at dopamine D2/D3 receptors is thought to underlie motivated behaviour, pleasure experiences and emotional expression based on animal studies, but it is unclear if this is the case in humans or how this relates to neural processing of reward stimuli. Using a randomised, double-blind, placebo-controlled, crossover neuroimaging study, we show in healthy humans that sustained dopamine D2/D3 receptor antagonism for 7 days results in negative symptoms (impairments in motivated behaviour, hedonic experience, verbal and emotional expression) and that this is related to blunted striatal response to reward stimuli. In contrast, 7 days of partial D2/D3 agonism does not disrupt reward signalling, motivated behaviour or hedonic experience. Both D2/D3 antagonism and partial agonism induce motor impairments, which are not related to striatal reward response. These findings identify a central role for D2/D3 signalling and reward processing in the mechanism underlying motivated behaviour and emotional responses in humans, with implications for understanding neuropsychiatric disorders such as schizophrenia and Parkinson’s disease. Osugo et al show in healthy humans that sustained dopamine D2/D3 receptor antagonism impairs motivated behaviour, hedonic experience, and emotional expression, and that this is related to blunted striatal reward response following D2/D3 antagonism.

Offspring of parents with major mood disorders (MDDs) are at increased risk for early psychopathology. We aim to compare the rates of neurodevelopmental disorders in offspring of parents with bipolar disorder, major depressive disorder, and controls. We established a lifetime diagnosis of neurodevelopmental disorders [attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorder, communication disorders, intellectual disabilities, specific learning disorders, and motor disorders] using the Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime Version in 400 participants (mean age 11.3 + s.d. 3.9 years), including 93 offspring of parents with bipolar disorder, 182 offspring of parents with major depressive disorder, and 125 control offspring of parents with no mood disorder. Neurodevelopmental disorders were elevated in offspring of parents with bipolar disorder [odds ratio (OR) 2.34, 95% confidence interval (CI) 1.23-4.47, = 0.010] and major depressive disorder (OR 1.87, 95% CI 1.03-3.39, = 0.035) compared to controls. This difference was driven by the rates of ADHD, which were highest among offspring of parents with bipolar disorder (30.1%), intermediate in offspring of parents with major depressive disorder (24.2%), and lowest in controls (14.4%). There were no significant differences in frequencies of other neurodevelopmental disorders between the three groups. Chronic course of mood disorder in parents was associated with higher rates of any neurodevelopmental disorder and higher rates of ADHD in offspring. Our findings suggest monitoring for ADHD and other neurodevelopmental disorders in offspring of parents with MDDs may be indicated to improve early diagnosis and treatment.