Lubrication regime of the contact between fat and bone in bovine tissue

Fat pads are masses of encapsulated adipose tissue located throughout the human body. Whilst a number of studies describe these soft tissues anatomically little is known about their biomechanics, and surgeons may excise them arthroscopically if they hinder visual inspection of the joint or bursa. By measuring the coefficient of friction between, and performing Sommerfeld analysis of, the surfaces approximating the in vivo conjuncture, this contact has been shown to have a coefficient of friction of the order of 0.01. The system appears to be lubricated hydrodynamically, thus possibly promoting low levels of wear. It is suggested that one of the functions of fat pads associated with subtendinous bursae and synovial joints is to generate a hydrodynamic lubricating layer between the opposing surfaces

Genetic variation associated with circulating monocyte count in the eMERGE Network

With white blood cell count emerging as an important risk factor for chronic inflammatory diseases, genetic associations of differential leukocyte types, specifically monocyte count, are providing novel candidate genes and pathways to further investigate. Circulating monocytes play a critical role in vascular diseases such as in the formation of atherosclerotic plaque. We performed a joint and ancestry-stratified genome-wide association analyses to identify variants specifically associated with monocyte count in 11 014 subjects in the electronic Medical Records and Genomics Network. In the joint and European ancestry samples, we identified novel associations in the chromosome 16 interferon regulatory factor 8 (IRF8) gene (P-value = 2.78×10(−16), β = −0.22). Other monocyte associations include novel missense variants in the chemokine-binding protein 2 (CCBP2) gene (P-value = 1.88×10(−7), β = 0.30) and a region of replication found in ribophorin I (RPN1) (P-value = 2.63×10(−16), β = −0.23) on chromosome 3. The CCBP2 and RPN1 region is located near GATA binding protein2 gene that has been previously shown to be associated with coronary heart disease. On chromosome 9, we found a novel association in the prostaglandin reductase 1 gene (P-value = 2.29×10(−7), β = 0.16), which is downstream from lysophosphatidic acid receptor 1. This region has previously been shown to be associated with monocyte count. We also replicated monocyte associations of genome-wide significance (P-value = 5.68×10(−17), β = −0.23) at the integrin, alpha 4 gene on chromosome 2. The novel IRF8 results and further replications provide supporting evidence of genetic regions associated with monocyte count

Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.

We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Abiraterone acetate plus prednisolone with or without enzalutamide for patients with metastatic prostate cancer starting androgen deprivation therapy: final results from two randomised phase 3 trials of the STAMPEDE platform protocol

Background: Abiraterone acetate plus prednisolone (herein referred to as abiraterone) or enzalutamide added at the start of androgen deprivation therapy improves outcomes for patients with metastatic prostate cancer. Here, we aimed to evaluate long-term outcomes and test whether combining enzalutamide with abiraterone and androgen deprivation therapy improves survival. Methods: We analysed two open-label, randomised, controlled, phase 3 trials of the STAMPEDE platform protocol, with no overlapping controls, conducted at 117 sites in the UK and Switzerland. Eligible patients (no age restriction) had metastatic, histologically-confirmed prostate adenocarcinoma; a WHO performance status of 0–2; and adequate haematological, renal, and liver function. Patients were randomly assigned (1:1) using a computerised algorithm and a minimisation technique to either standard of care (androgen deprivation therapy; docetaxel 75 mg/m2 intravenously for six cycles with prednisolone 10 mg orally once per day allowed from Dec 17, 2015) or standard of care plus abiraterone acetate 1000 mg and prednisolone 5 mg (in the abiraterone trial) orally or abiraterone acetate and prednisolone plus enzalutamide 160 mg orally once a day (in the abiraterone and enzalutamide trial). Patients were stratified by centre, age, WHO performance status, type of androgen deprivation therapy, use of aspirin or non-steroidal anti-inflammatory drugs, pelvic nodal status, planned radiotherapy, and planned docetaxel use. The primary outcome was overall survival assessed in the intention-to-treat population. Safety was assessed in all patients who started treatment. A fixed-effects meta-analysis of individual patient data was used to compare differences in survival between the two trials. STAMPEDE is registered with ClinicalTrials.gov (NCT00268476) and ISRCTN (ISRCTN78818544). Findings: Between Nov 15, 2011, and Jan 17, 2014, 1003 patients were randomly assigned to standard of care (n=502) or standard of care plus abiraterone (n=501) in the abiraterone trial. Between July 29, 2014, and March 31, 2016, 916 patients were randomly assigned to standard of care (n=454) or standard of care plus abiraterone and enzalutamide (n=462) in the abiraterone and enzalutamide trial. Median follow-up was 96 months (IQR 86–107) in the abiraterone trial and 72 months (61–74) in the abiraterone and enzalutamide trial. In the abiraterone trial, median overall survival was 76·6 months (95% CI 67·8–86·9) in the abiraterone group versus 45·7 months (41·6–52·0) in the standard of care group (hazard ratio [HR] 0·62 [95% CI 0·53–0·73]; p&lt;0·0001). In the abiraterone and enzalutamide trial, median overall survival was 73·1 months (61·9–81·3) in the abiraterone and enzalutamide group versus 51·8 months (45·3–59·0) in the standard of care group (HR 0·65 [0·55–0·77]; p&lt;0·0001). We found no difference in the treatment effect between these two trials (interaction HR 1·05 [0·83–1·32]; pinteraction=0·71) or between-trial heterogeneity (I2 p=0·70). In the first 5 years of treatment, grade 3–5 toxic effects were higher when abiraterone was added to standard of care (271 [54%] of 498 vs 192 [38%] of 502 with standard of care) and the highest toxic effects were seen when abiraterone and enzalutamide were added to standard of care (302 [68%] of 445 vs 204 [45%] of 454 with standard of care). Cardiac causes were the most common cause of death due to adverse events (five [1%] with standard of care plus abiraterone and enzalutamide [two attributed to treatment] and one (&lt;1%) with standard of care in the abiraterone trial). Interpretation: Enzalutamide and abiraterone should not be combined for patients with prostate cancer starting long-term androgen deprivation therapy. Clinically important improvements in survival from addition of abiraterone to androgen deprivation therapy are maintained for longer than 7 years. Funding: Cancer Research UK, UK Medical Research Council, Swiss Group for Clinical Cancer Research, Janssen, and Astellas

Fine-mapping analysis including over 254,000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes

Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development

Taking the pulse of Earth's tropical forests using networks of highly distributed plots

Tropical forests are the most diverse and productive ecosystems on Earth. While better understanding of these forests is critical for our collective future, until quite recently efforts to measure and monitor them have been largely disconnected. Networking is essential to discover the answers to questions that transcend borders and the horizons of funding agencies. Here we show how a global community is responding to the challenges of tropical ecosystem research with diverse teams measuring forests tree-by-tree in thousands of long-term plots. We review the major scientific discoveries of this work and show how this process is changing tropical forest science. Our core approach involves linking long-term grassroots initiatives with standardized protocols and data management to generate robust scaled-up results. By connecting tropical researchers and elevating their status, our Social Research Network model recognises the key role of the data originator in scientific discovery. Conceived in 1999 with RAINFOR (South America), our permanent plot networks have been adapted to Africa (AfriTRON) and Southeast Asia (T-FORCES) and widely emulated worldwide. Now these multiple initiatives are integrated via ForestPlots.net cyber-infrastructure, linking colleagues from 54 countries across 24 plot networks. Collectively these are transforming understanding of tropical forests and their biospheric role. Together we have discovered how, where and why forest carbon and biodiversity are responding to climate change, and how they feedback on it. This long-term pan-tropical collaboration has revealed a large long-term carbon sink and its trends, as well as making clear which drivers are most important, which forest processes are affected, where they are changing, what the lags are, and the likely future responses of tropical forests as the climate continues to change. By leveraging a remarkably old technology, plot networks are sparking a very modern revolution in tropical forest science. In the future, humanity can benefit greatly by nurturing the grassroots communities now collectively capable of generating unique, long-term understanding of Earth's most precious forests. Resumen Los bosques tropicales son los ecosistemas más diversos y productivos del mundo y entender su funcionamiento es crítico para nuestro futuro colectivo. Sin embargo, hasta hace muy poco, los esfuerzos para medirlos y monitorearlos han estado muy desconectados. El trabajo en redes es esencial para descubrir las respuestas a preguntas que trascienden las fronteras y los plazos de las agencias de financiamiento. Aquí mostramos cómo una comunidad global está respondiendo a los desafíos de la investigación en ecosistemas tropicales a través de diversos equipos realizando mediciones árbol por árbol en miles de parcelas permanentes de largo plazo. Revisamos los descubrimientos más importantes de este trabajo y discutimos cómo este proceso está cambiando la ciencia relacionada a los bosques tropicales. El enfoque central de nuestro esfuerzo implica la conexión de iniciativas locales de largo plazo con protocolos estandarizados y manejo de datos para producir resultados que se puedan trasladar a múltiples escalas. Conectando investigadores tropicales, elevando su posición y estatus, nuestro modelo de Red Social de Investigación reconoce el rol fundamental que tienen, para el descubrimiento científico, quienes generan o producen los datos. Concebida en 1999 con RAINFOR (Suramérica), nuestras redes de parcelas permanentes han sido adaptadas en África (AfriTRON) y el sureste asiático (T-FORCES) y ampliamente replicadas en el mundo. Actualmente todas estas iniciativas están integradas a través de la ciber-infraestructura de ForestPlots.net, conectando colegas de 54 países en 24 redes diferentes de parcelas. Colectivamente, estas redes están transformando nuestro conocimiento sobre los bosques tropicales y el rol de éstos en la biósfera. Juntos hemos descubierto cómo, dónde y porqué el carbono y la biodiversidad de los bosques tropicales está respondiendo al cambio climático y cómo se retroalimentan. Esta colaboración pan-tropical de largo plazo ha expuesto un gran sumidero de carbono y sus tendencias, mostrando claramente cuáles son los factores más importantes, qué procesos se ven afectados, dónde ocurren los cambios, los tiempos de reacción y las probables respuestas futuras mientras el clima continúa cambiando. Apalancando lo que realmente es una tecnología antigua, las redes de parcelas están generando una verdadera y moderna revolución en la ciencia tropical. En el futuro, la humanidad puede beneficiarse enormemente si se nutren y cultivan comunidades de investigadores de base, actualmente con la capacidad de generar información única y de largo plazo para entender los que probablemente son los bosques más preciados de la tierra. Resumo Florestas tropicais são os ecossistemas mais diversos e produtivos da Terra. Embora uma boa compreensão destas florestas seja crucial para o nosso futuro coletivo, até muito recentemente os esforços de medições e monitoramento foram amplamente desconexos. É essencial formarmos redes para obtermos respostas que transcendem fronteiras e horizontes de agências financiadoras. Neste estudo nós mostramos como uma comunidade global está respondendo aos desafios da pesquisa de ecossistemas tropicais, com equipes diversas medindo florestas, árvore por árvore, em milhares de parcelas monitoradas à longo prazo. Nós revisamos as maiores descobertas científicas deste trabalho, e mostramos também como este processo está mudando a ciência de florestas tropicais. Nossa abordagem principal envolve unir iniciativas de base a protocolos padronizados e gerenciamento de dados a fim de gerar resultados robustos em escalas ampliadas. Ao conectar pesquisadores tropicais e elevar seus status, nosso modelo de Rede de Pesquisa Social reconhece o papel-chave do produtor dos dados na descoberta científica. Concebida em 1999 com o RAINFOR (América do Sul), nossa rede de parcelas permanentes foi adaptada para África (AfriTRON) e Sudeste asiático (T-FORCES), e tem sido extensamente reproduzida em todo o mundo. Agora estas múltiplas iniciativas estão integradas através de uma infraestrutura cibernética do ForestPlots.net, conectando colegas de 54 países de 24 redes de parcelas. Estas iniciativas estão transformando coletivamente o entendimento das florestas tropicais e seus papéis na biosfera. Juntos nós descobrimos como, onde e por que o carbono e a biodiversidade da floresta estão respondendo às mudanças climáticas, e seus efeitos de retroalimentação. Esta duradoura colaboração pantropical revelou um grande sumidouro de carbono persistente e suas tendências, assim como tem evidenciado quais direcionadores são mais importantes, quais processos florestais são mais afetados, onde eles estão mudando, seus atrasos no tempo de resposta, e as prováveis respostas das florestas tropicais conforme o clima continua a mudar. Dessa forma, aproveitando uma notável tecnologia antiga, redes de parcelas acendem faíscas de uma moderna revolução na ciência das florestas tropicais. No futuro a humanidade pode se beneficiar incentivando estas comunidades basais que agora são coletivamente capazes de gerar conhecimentos únicos e duradouros sobre as florestas mais preciosas da Terra. Résume Les forêts tropicales sont les écosystèmes les plus diversifiés et les plus productifs de la planète. Si une meilleure compréhension de ces forêts est essentielle pour notre avenir collectif, jusqu'à tout récemment, les efforts déployés pour les mesurer et les surveiller ont été largement déconnectés. La mise en réseau est essentielle pour découvrir les réponses à des questions qui dépassent les frontières et les horizons des organismes de financement. Nous montrons ici comment une communauté mondiale relève les défis de la recherche sur les écosystèmes tropicaux avec diverses équipes qui mesurent les forêts arbre après arbre dans de milliers de parcelles permanentes. Nous passons en revue les principales découvertes scientifiques de ces travaux et montrons comment ce processus modifie la science des forêts tropicales. Notre approche principale consiste à relier les initiatives de base à long terme à des protocoles standardisés et une gestion de données afin de générer des résultats solides à grande échelle. En reliant les chercheurs tropicaux et en élevant leur statut, notre modèle de réseau de recherche sociale reconnaît le rôle clé de l'auteur des données dans la découverte scientifique. Conçus en 1999 avec RAINFOR (Amérique du Sud), nos réseaux de parcelles permanentes ont été adaptés à l'Afrique (AfriTRON) et à l'Asie du Sud-Est (T-FORCES) et largement imités dans le monde entier. Ces multiples initiatives sont désormais intégrées via l'infrastructure ForestPlots.net, qui relie des collègues de 54 pays à travers 24 réseaux de parcelles. Ensemble, elles transforment la compréhension des forêts tropicales et de leur rôle biosphérique. Ensemble, nous avons découvert comment, où et pourquoi le carbone forestier et la biodiversité réagissent au changement climatique, et comment ils y réagissent. Cette collaboration pan-tropicale à long terme a révélé un important puits de carbone à long terme et ses tendances, tout en mettant en évidence les facteurs les plus importants, les processus forestiers qui sont affectés, les endroits où ils changent, les décalages et les réactions futures probables des forêts tropicales à mesure que le climat continue de changer. En tirant parti d'une technologie remarquablement ancienne, les réseaux de parcelles déclenchent une révolution très moderne dans la science des forêts tropicales. À l'avenir, l'humanité pourra grandement bénéficier du soutien des communautés de base qui sont maintenant collectivement capables de générer une compréhension unique et à long terme des forêts les plus précieuses de la Terre. Abstrak Hutan tropika adalah di antara ekosistem yang paling produktif dan mempunyai kepelbagaian biodiversiti yang tinggi di seluruh dunia. Walaupun pemahaman mengenai hutan tropika amat penting untuk masa depan kita, usaha-usaha untuk mengkaji dan mengawas hutah-hutan tersebut baru sekarang menjadi lebih diperhubungkan. Perangkaian adalah sangat penting untuk mencari jawapan kepada soalan-soalan yang menjangkaui sempadan dan batasan agensi pendanaan. Di sini kami menunjukkan bagaimana sebuah komuniti global bertindak balas terhadap cabaran penyelidikan ekosistem tropika melalui penglibatan pelbagai kumpulan yang mengukur hutan secara pokok demi pokok dalam beribu-ribu plot jangka panjang. Kami meninjau semula penemuan saintifik utama daripada kerja ini dan menunjukkan bagaimana proses ini sedang mengubah bidang sains hutan tropika. Teras pendekatan kami memberi tumpuan terhadap penghubungan inisiatif akar umbi jangka panjang dengan protokol standar serta pengurusan data untuk mendapatkan hasil skala besar yang kukuh. Dengan menghubungkan penyelidik-penyelidik tropika dan meningkatkan status mereka, model Rangkaian Penyelidikan Sosial kami mengiktiraf kepentingan peranan pengasas data dalam penemuan saintifik. Bermula dengan pengasasan RAINFOR (Amerika Selatan) pada tahun 1999, rangkaian-rangkaian plot kekal kami kemudian disesuaikan untuk Afrika (AfriTRON) dan Asia Tenggara (T-FORCES) dan selanjutnya telah banyak dicontohi di seluruh dunia. Kini, inisiatif-inisiatif tersebut disepadukan melalui infrastruktur siber ForestPlots.net yang menghubungkan rakan sekerja dari 54 negara di 24 buah rangkaian plot. Secara kolektif, rangkaian ini sedang mengubah pemahaman tentang hutan tropika dan peranannya dalam biosfera. Kami telah bekerjasama untuk menemukan bagaimana, di mana dan mengapa karbon serta biodiversiti hutan bertindak balas terhadap perubahan iklim dan juga bagaimana mereka saling bermaklum balas. Kolaborasi pan-tropika jangka panjang ini telah mendedahkan sebuah sinki karbon jangka panjang serta arah alirannya dan juga menjelaskan pemandu-pemandu perubahan yang terpenting, di mana dan bagaimana proses hutan terjejas, masa susul yang ada dan kemungkinan tindakbalas hutan tropika pada perubahan iklim secara berterusan di masa depan. Dengan memanfaatkan pendekatan lama, rangkaian plot sedang menyalakan revolusi yang amat moden dalam sains hutan tropika. Pada masa akan datang, manusia sejagat akan banyak mendapat manfaat jika memupuk komuniti-komuniti akar umbi yang kini berkemampuan secara kolektif menghasilkan pemahaman unik dan jangka panjang mengenai hutan-hutan yang paling berharga di dunia