An unexpectedly large count of trees in the West African Sahara and Sahel.

A large proportion of dryland trees and shrubs (hereafter referred to collectively as trees) grow in isolation, without canopy closure. These non-forest trees have a crucial role in biodiversity, and provide ecosystem services such as carbon storage, food resources and shelter for humans and animals1,2. However, most public interest relating to trees is devoted to forests, and trees outside of forests are not well-documented3. Here we map the crown size of each tree more than 3 m2 in size over a land area that spans 1.3 million km2 in the West African Sahara, Sahel and sub-humid zone, using submetre-resolution satellite imagery and deep learning4. We detected over 1.8 billion individual trees (13.4 trees per hectare), with a median crown size of 12 m2, along a rainfall gradient from 0 to 1,000 mm per year. The canopy cover increases from 0.1% (0.7 trees per hectare) in hyper-arid areas, through 1.6% (9.9 trees per hectare) in arid and 5.6% (30.1 trees per hectare) in semi-arid zones, to 13.3% (47 trees per hectare) in sub-humid areas. Although the overall canopy cover is low, the relatively high density of isolated trees challenges prevailing narratives about dryland desertification5-7, and even the desert shows a surprisingly high tree density. Our assessment suggests a way to monitor trees outside of forests globally, and to explore their role in mitigating degradation, climate change and poverty.

Baseline characteristics and outcomes of children with cancer in the English-speaking Caribbean: A multinational retrospective cohort.

BACKGROUND: English-speaking Caribbean (ESC) childhood cancer outcomes are unknown. PROCEDURE: Through the SickKids-Caribbean Initiative (SCI), we established a multicenter childhood cancer database across seven centers in six ESC countries. Data managers entered patient demographics, disease, treatment, and outcome data. Data collection commenced in 2013, with retrospective collection to 2011 and subsequent prospective collection. RESULTS: A total of 367 children were diagnosed between 2011 and 2015 with a median age of 5.7 years (interquartile range 2.9-10.6 years). One hundred thirty (35.4%) patients were diagnosed with leukemia, 30 (8.2%) with lymphoma, and 149 (40.6%) with solid tumors. A relative paucity of children with brain tumors was seen (N = 58, 15.8%). Two-year event-free survival (EFS) for the cohort was 48.5% ± 3.2%; 2-year overall survival (OS) was 55.1% ± 3.1%. Children with acute lymphoblastic leukemia (ALL) and Wilms tumor (WT) experienced better 2-year EFS (62.1% ± 6.4% and 66.7% ± 10.1%), while dismal outcomes were seen in children with acute myeloid leukemia (AML; 22.7 ± 9.6%), rhabdomyosarcoma (21.0% ± 17.0%), and medulloblastoma (21.4% ± 17.8%). Of 108 deaths with known cause, 58 (53.7%) were attributed to disease and 50 (46.3%) to treatment complications. Death within 60 days of diagnosis was relatively common in acute leukemia [13/98 (13.3%) ALL, 8/26 (30.8%) AML]. Despite this, traditional prognosticators adversely impacted outcome in ALL, including higher age, higher white blood cell count, and T-cell lineage. CONCLUSIONS: ESC childhood cancer outcomes are significantly inferior to high-income country outcomes. Based on these data, interventions for improving supportive care and modifying treatment protocols are under way. Continued data collection will allow evaluation of interventions and ensure maximal outcome improvements.

Vegetation dynamics and rainfall sensitivity of the Amazon.

We show that the vegetation canopy of the Amazon rainforest is highly sensitive to changes in precipitation patterns and that reduction in rainfall since 2000 has diminished vegetation greenness across large parts of Amazonia. Large-scale directional declines in vegetation greenness may indicate decreases in carbon uptake and substantial changes in the energy balance of the Amazon. We use improved estimates of surface reflectance from satellite data to show a close link between reductions in annual precipitation, El Niño southern oscillation events, and photosynthetic activity across tropical and subtropical Amazonia. We report that, since the year 2000, precipitation has declined across 69% of the tropical evergreen forest (5.4 million km(2)) and across 80% of the subtropical grasslands (3.3 million km(2)). These reductions, which coincided with a decline in terrestrial water storage, account for about 55% of a satellite-observed widespread decline in the normalized difference vegetation index (NDVI). During El Niño events, NDVI was reduced about 16.6% across an area of up to 1.6 million km(2) compared with average conditions. Several global circulation models suggest that a rise in equatorial sea surface temperature and related displacement of the intertropical convergence zone could lead to considerable drying of tropical forests in the 21st century. Our results provide evidence that persistent drying could degrade Amazonian forest canopies, which would have cascading effects on global carbon and climate dynamics.

Biodistribution and Efficacy of Low Temperature-Sensitive Liposome Encapsulated Docetaxel Combined with Mild Hyperthermia in a Mouse Model of Prostate Cancer.

PURPOSE: Low temperature sensitive liposome (LTSL) encapsulated docetaxel were combined with mild hyperthermia (40-42°C) to investigate in vivo biodistribution and efficacy against a castrate resistant prostate cancer. METHOD: Female athymic nude mice with human prostate PC-3 M-luciferase cells grown subcutaneously into the right hind leg were randomized into six groups: saline (+/- heat), free docetaxel (+/- heat), and LTSL docetaxel (+/- heat). Treatment (15 mg docetaxel/kg) was administered via tail vein once tumors reached a size of 200-300 mm(3). Mice tumor volumes and body weights were recorded for up to 60 days. Docetaxel concentrations of harvested tumor and organ/tissue homogenates were determined by LC-MS. Histological evaluation (Mean vessel density, Ki67 proliferation, Caspase-3 apoptosis) of saline, free Docetaxel and LTSL docetaxel (+/- heat n = 3-5) was performed to determine molecular mechanism responsible for tumor cell killing. RESULT: LTSL/heat resulted in significantly higher tumor docetaxel concentrations (4.7-fold greater compared to free docetaxel). Adding heat to LTSL Docetaxel or free docetaxel treatment resulted in significantly greater survival and growth delay compared to other treatments (p < 0.05). Differences in body weight between all Docetaxel treatments were not reduced by >10% and were not statistically different from each other. Molecular markers such as caspase-3 were upregulated, and Ki67 expression was significantly decreased in the chemo-hyperthermia group. Vessel density was similar post treatment, but the heated group had reduced vessel area, suggesting thermal enhancement in efficacy by reduction in functional perfusion. CONCLUSION: This technique of hyperthermia sensitization and enhanced docetaxel delivery has potential for clinical translation for prostate cancer treatment.

A 7-day team-based model of care in general medicine: implementation and outcomes at 12 months.

BACKGROUND: Demand for inpatient beds is increasing whilst supply is diminishing. General medical services are feeling this demand as the ageing population presents more patients with undifferentiated illness traditionally cared for by this service. Redesign efforts need to focus on improving the quality and speed of decision-making to utilise resources efficiently. AIMS: The aim of this study was to improve patient flow through general medical services by undertaking a comprehensive redesign process targeting each stage of the patient journey. METHODS: We utilised a rapid improvement event to identify waste and design a new model of care (MOC) that eliminated as much waste as possible. The model had three main elements: (i) ward-based teams; (ii) 7-day per week standard work; and (iii) pull systems to operate for all transfers and referrals. Here, we analyse the first 12 months of the new MOC with regard to key outcomes: length of stay, occupancy, weekend discharges, clinical incidents and Medical Emergency Team (MET) calls, emergency department length of stay and National Emergency Access Target (NEAT) performance and elective surgical throughput. RESULTS: The new MOC resulted in a 0.88-day reduction in length of stay. This resulted in reduced general medical bed occupancy of 19 beds. Weekend discharges improved by 54.6%. There were no significant increases in serious clinical incidents or MET calls. Emergency department admitted NEAT performance improved also. CONCLUSION: Redesign of the general medicine model of care eliminating waste has resulted in a significant improvement in patient flow and reduced length of stay without compromising quality of care.

Correction: A multi-proxy assessment of the impact of environmental instability on Late Holocene (4500-3800 BP) Native American villages of the Georgia coast.

[This corrects the article DOI: 10.1371/journal.pone.0258979.].

Mapping every adult baobab (Adansonia digitata L.) across the Sahel and relationships to rural livelihoods.

The baobab tree (Adansonia digitata L.) is an integral part of rural livelihoods throughout the African continent. However, the combined effects of climate change and increasing global demand for baobab products are currently exerting pressure on the sustainable utilization of these resources. Here we use sub-metre-resolution satellite imagery to identify the presence of nearly 2.8 million (underestimation bias 27.1%) baobab trees in the Sahel, a dryland region of 2.4 million km2. This achievement is considered an essential step towards an improved management and monitoring system of valuable woody species. Using Senegal as a case country, we find that 94% of rural buildings have at least one baobab tree in their immediate surroundings and that the abundance of baobabs is associated with a higher likelihood of people consuming a highly nutritious food group: dark green leafy vegetables. The generated database showcases the feasibility of mapping the location of single tree species at a sub-continental scale, providing vital information in times when deforestation and climate change cause the extinction of numerous tree species.

Magnetic resonance imaging (MRI)-guided transurethral ultrasound therapy of the prostate: a preclinical study with radiological and pathological correlation using customised MRI-based moulds.

OBJECTIVE: To characterise the feasibility and safety of a novel transurethral ultrasound (US)-therapy device combined with real-time multi-plane magnetic resonance imaging (MRI)-based temperature monitoring and temperature feedback control, to enable spatiotemporally precise regional ablation of simulated prostate gland lesions in a preclinical canine model. To correlate ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. MATERIALS AND METHODS: Three dogs were treated with three targeted ablations each, using a prototype MRI-guided transurethral US-therapy system (Philips Healthcare, Vantaa, Finland). MRI provided images for treatment planning, guidance, real-time multi-planar thermometry, as well as post-treatment evaluation of efficacy. After treatment, specimens underwent histopathological analysis to determine the extent of necrosis and cell viability. Statistical analyses (Pearson's correlation, Student's t-test) were used to evaluate the correlation between ablation volumes measured with intra-procedural cumulative thermal damage estimates, post-procedural MRI, and histopathology. RESULTS: MRI combined with a transurethral US-therapy device enabled multi-planar temperature monitoring at the target as well as in surrounding tissues, allowing for safe, targeted, and controlled ablations of prescribed lesions. Ablated volumes measured by cumulative thermal dose positively correlated with volumes determined by histopathological analysis (r(2) 0.83, P < 0.001). Post-procedural contrast-enhanced and diffusion-weighted MRI showed a positive correlation with non-viable areas on histopathological analysis (r(2) 0.89, P < 0.001, and r(2) 0.91, P = 0.003, respectively). Additionally, there was a positive correlation between ablated volumes according to cumulative thermal dose and volumes identified on post-procedural contrast-enhanced MRI (r(2) 0.77, P < 0.01). There was no difference in mean ablation volumes assessed with the various analysis methods (P > 0.05, Student's t-test). CONCLUSIONS: MRI-guided transurethral US therapy enabled safe and targeted ablations of prescribed lesions in a preclinical canine prostate model. Ablation volumes were reliably predicted by intra- and post-procedural imaging. Clinical studies are needed to confirm the feasibility, safety, oncological control, and functional outcomes of this therapy in patients in whom focal therapy is indicated.

Keratin 13 point mutation underlies the hereditary mucosal epithelial disorder white sponge nevus.

Although pathogenic keratin mutations have been well characterized in inherited epidermal disorders, analogous defects in keratins expressed in non-epidermal epithelia have yet to be described. White sponge nevus (WSN) is a rare autosomal dominant disorder of non-cornifying squamous epithelial differentiation that presents clinically as bilateral white, soft, thick plaques of the oral mucosa. Less frequently the mucous membranes of the nose, esophagus, genitalia and rectum are involved. Histopathological features, including epithelial thickening, parakeratosis, extensive vacuolization of the suprabasal keratinocytes and compact aggregates of keratin intermediate filaments (KIF) in the upper spinous layers, resemble those found in epidermal disorders due to keratin defects. We analysed a multigenerational family with WSN and found cosegregation of the disease with the keratin gene cluster on chromosome 17. We identified a missense mutation in one allele of keratin 13 that leads to proline substitution for a conserved leucine. The mutation occurred within the conserved 1A region of the helical rod domain, which is critical for KIF stability and is the site of most pathogenic keratin mutations. This mutation enlarges the spectrum of keratins with disease-causing defects to include mucosally expressed keratin 13, and extends the known keratin diseases to disorders of non-cornifying stratified squamous epithelia.

Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis.

We recently mapped the disease locus for severe autosomal recessive lamellar ichthyosis (LI) to chromosome 14q11 and showed complete linkage with TGM1, the gene encoding transglutaminase 1. We have now identified point mutations in TGM1 in two of the multiplex LI families used in the linkage study. Each nucleotide change causes a non-conservative amino acid substitution of histidine for one of two adjacent arginine residues in exon 3 of the gene (Arg141His, Arg142His). Within the transglutaminase family, these arginines are invariant within a conserved region, distant from the catalytic site of the enzyme. We hypothesize that these mutations adversely affect formation of crosslinks essential in production of cornified cell envelopes and a normal stratum corneum layer of the skin.

Sjögren-Larsson syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene.

Sjögren-Larsson syndrome (SLS) is an inherited neurocutaneous disorder characterized by mental retardation, spasticity and ichthyosis. SLS patients have a profound deficiency in fatty aldehyde dehydrogenase (FALDH) activity. We have now cloned the human FALDH cDNA and show that it maps to the SLS locus on chromosome 17p11.2. Sequence analysis of FALDH amplified from fibroblast mRNA and genomic DNA from 3 unrelated SLS patients reveals distinct mutations, including deletions, an insertion and a point mutation. The cloning of FALDH and the identification of mutations in SLS patients opens up possibilities for developing therapeutic approaches to ameliorate the neurologic and cutaneous symptoms of the disease.

Mutations in the human connexin gene GJB3 cause erythrokeratodermia variabilis.

Erythrokeratodermia variabilis (EKV, OMIM 133200) is an autosomal dominant genodermatosis with considerable intra- and interfamilial variability. It has a disfiguring phenotype characterized by the independent occurrence of two morphologic features: transient figurate red patches and localized or generalized hyperkeratosis. Both features can be triggered by external factors such as trauma to the skin. After initial linkage to the RH locus on 1p, EKV was mapped to an interval of 2.6 cM on 1p34-p35, and a candidate gene (GJA4) encoding the gap junction protein alpha-4 (connexin 31, Cx31) was excluded by sequence analysis. Evidence in mouse suggesting that the EKV region harbours a cluster of epidermally expressed connexin genes led us to characterize the human homologues of GJB3 (encoding Cx31) and GJB5 (encoding Cx31.1). GJB3, GJB5 and GJA4 were localized to a 1.1-Mb YAC in the candidate interval. We detected heterozygous missense mutations in GJB3 in four EKV families leading to substitution of a conserved glycine by charged residues (G12R and G12D), or change of a cysteine (C86S). These mutations are predicted to interfere with normal Cx31 structure and function, possibly due to a dominant inhibitory effect. Our results implicate Cx31 in the pathogenesis of EKV, and provide evidence that intercellular communication mediated by Cx31 is crucial for epidermal differentiation and response to external factors.

Linkage of epidermolytic hyperkeratosis to the type II keratin gene cluster on chromosome 12q.

We investigated the molecular genetics of epidermolytic hyperkeratosis (EHK), a dominant disorder characterized by epidermal blistering, hyperkeratosis, vacuolar degeneration and clumping of keratin filaments. Based on this pathology, we have excluded by linkage analysis several candidate genes for the disease; in contrast, complete linkage was obtained with the type II keratin, K1, on 12q11-q13. Linkage in this region of chromosome 12 was confirmed using several other markers, and multi-locus linkage analyses further supported this location. Keratins are excellent EHK gene candidates since their expression is specific to the suprabasal epidermal layers. In the pedigree studied here, a type II keratin gene, very probably K1, is implicated as the site of the molecular defect causing EHK.

Mutation of a new gene causes a unique form of Hermansky-Pudlak syndrome in a genetic isolate of central Puerto Rico.

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and a storage pool deficiency due to an absence of platelet dense bodies. Lysosomal ceroid lipofuscinosis, pulmonary fibrosis and granulomatous colitis are occasional manifestations of the disease. HPS occurs with a frequency of one in 1800 in north-west Puerto Rico due to a founder effect. Several non-Puerto Rican patients also have mutations in HPS1, which produces a protein of unknown function. Another gene, ADTB3A, causes HPS in the pearl mouse and in two brothers with HPS-2 (refs. 11,12). ADTB3A encodes a coat protein involved in vesicle formation, implicating HPS as a disorder of membrane trafficking. We sought to identify other HPS-causing genes. Using homozygosity mapping on pooled DNA of 6 families from central Puerto Rico, we localized a new HPS susceptibility gene to a 1.6-cM interval on chromosome 3q24. The gene, HPS3, has 17 exons, and a putative 113.7-kD product expected to reveal how new vesicles form in specialized cells. The homozygous, disease-causing mutation is a large deletion and represents the second example of a founder mutation causing HPS on the small island of Puerto Rico. We also present an allele-specific assay for diagnosing individuals heterozygous or homozygous for this mutation.

Nation-wide mapping of tree-level aboveground carbon stocks in Rwanda.

Trees sustain livelihoods and mitigate climate change but a predominance of trees outside forests and limited resources make it difficult for many tropical countries to conduct automated nation-wide inventories. Here, we propose an approach to map the carbon stock of each individual overstory tree at the national scale of Rwanda using aerial imagery from 2008 and deep learning. We show that 72% of the mapped trees are located in farmlands and savannas and 17% in plantations, accounting for 48.6% of the national aboveground carbon stocks. Natural forests cover 11% of the total tree count and 51.4% of the national carbon stocks, with an overall carbon stock uncertainty of 16.9%. The mapping of all trees allows partitioning to any landscapes classification and is urgently needed for effective planning and monitoring of restoration activities as well as for optimization of carbon sequestration, biodiversity and economic benefits of trees.

More than one quarter of Africa's tree cover is found outside areas previously classified as forest.

The consistent monitoring of trees both inside and outside of forests is key to sustainable land management. Current monitoring systems either ignore trees outside forests or are too expensive to be applied consistently across countries on a repeated basis. Here we use the PlanetScope nanosatellite constellation, which delivers global very high-resolution daily imagery, to map both forest and non-forest tree cover for continental Africa using images from a single year. Our prototype map of 2019 (RMSE = 9.57%, bias = -6.9%). demonstrates that a precise assessment of all tree-based ecosystems is possible at continental scale, and reveals that 29% of tree cover is found outside areas previously classified as tree cover in state-of-the-art maps, such as in croplands and grassland. Such accurate mapping of tree cover down to the level of individual trees and consistent among countries has the potential to redefine land use impacts in non-forest landscapes, move beyond the need for forest definitions, and build the basis for natural climate solutions and tree-related studies.

Sinks for nitrogen inputs in terrestrial ecosystems: a meta-analysis of 15N tracer field studies.

Effects of anthropogenic nitrogen (N) deposition and the ability of terrestrial ecosystems to store carbon (C) depend in part on the amount of N retained in the system and its partitioning among plant and soil pools. We conducted a meta-analysis of studies at 48 sites across four continents that used enriched 15N isotope tracers in order to synthesize information about total ecosystem N retention (i.e., total ecosystem 15N recovery in plant and soil pools) across natural systems and N partitioning among ecosystem pools. The greatest recoveries of ecosystem 15N tracer occurred in shrublands (mean, 89.5%) and wetlands (84.8%) followed by forests (74.9%) and grasslands (51.8%). In the short term (< 1 week after 15N tracer application), total ecosystem 15N recovery was negatively correlated with fine-root and soil 15N natural abundance, and organic soil C and N concentration but was positively correlated with mean annual temperature and mineral soil C:N. In the longer term (3-18 months after 15N tracer application), total ecosystem 15N retention was negatively correlated with foliar natural-abundance 15N but was positively correlated with mineral soil C and N concentration and C:N, showing that plant and soil natural-abundance 15N and soil C:N are good indicators of total ecosystem N retention. Foliar N concentration was not significantly related to ecosystem 15N tracer recovery, suggesting that plant N status is not a good predictor of total ecosystem N retention. Because the largest ecosystem sinks for 15N tracer were below ground in forests, shrublands, and grasslands, we conclude that growth enhancement and potential for increased C storage in aboveground biomass from atmospheric N deposition is likely to be modest in these ecosystems. Total ecosystem 15N recovery decreased with N fertilization, with an apparent threshold fertilization rate of 46 kg N x ha(-1) x yr(-1) above which most ecosystems showed net losses of applied 15N tracer in response to N fertilizer addition.

Prediction of a Rift Valley fever outbreak.

El Niño/Southern Oscillation related climate anomalies were analyzed by using a combination of satellite measurements of elevated sea-surface temperatures and subsequent elevated rainfall and satellite-derived normalized difference vegetation index data. A Rift Valley fever (RVF) risk mapping model using these climate data predicted areas where outbreaks of RVF in humans and animals were expected and occurred in the Horn of Africa from December 2006 to May 2007. The predictions were subsequently confirmed by entomological and epidemiological field investigations of virus activity in the areas identified as at risk. Accurate spatial and temporal predictions of disease activity, as it occurred first in southern Somalia and then through much of Kenya before affecting northern Tanzania, provided a 2 to 6 week period of warning for the Horn of Africa that facilitated disease outbreak response and mitigation activities. To our knowledge, this is the first prospective prediction of a RVF outbreak.

A multi-proxy assessment of the impact of environmental instability on Late Holocene (4500-3800 BP) Native American villages of the Georgia coast.

Circular shell rings along the South Atlantic Coast of North America are the remnants of some of the earliest villages that emerged during the Late Archaic (5000-3000 BP). Many of these villages, however, were abandoned during the Terminal Late Archaic (ca 3800-3000 BP). We combine Bayesian chronological modeling with mollusk shell geochemistry and oyster paleobiology to understand the nature and timing of environmental change associated with the emergence and abandonment of circular shell ring villages on Sapelo Island, Georgia. Our Bayesian models indicate that Native Americans occupied the three Sapelo shell rings at varying times with some generational overlap. By the end of the complex's occupation, only Ring III was occupied before abandonment ca. 3845 BP. Ring III also consists of statistically smaller oysters harvested from less saline estuaries compared to earlier occupations. Integrating shell biochemical and paleobiological data with recent tree ring analyses shows a clear pattern of environmental fluctuations throughout the period in which the rings were occupied. We argue that as the environment became unstable around 4300 BP, aggregation at villages provided a way to effectively manage fisheries that are highly sensitive to environmental change. However, with the eventual collapse of oyster fisheries and subsequent rebound in environmental conditions ca. post-3800 BP, people dispersed from shell rings, and shifted to non-marine subsistence economies and other types of settlements. This study provides the most comprehensive evidence for correlations between large-scale environmental change and societal transformations on the Georgia coast during the Late Archaic period.