African rainforests: past, present and future

In recent decades, there has been a surge of interest in tropical forests, as there is increased appreciation of the rich biodiversity they host and the many roles they play in the functioning of the Earth system at local, regional and global scales. Of the world’s major tropical forest regions, most research and policy attention has focused on the Amazon region, the world’s largest tropical forest bloc, and to a lesser extent on South East Asia, the third largest tropical forest region. By contrast, the world’s second largest tropical forest region, the tropical forests of Central and West Africa (termed the Guineo-Congolian region) have been relatively neglected. This has been for a number of reasons, including challenging and fragmented politics, civil conflicts and logistical as well as infrastructure challenges. Nevertheless, there is an extensive amount of research activity in the African rainforest zone that has rarely been compiled in a single interdisciplinary volume. This review paper synthesizes the insights emerging from the theme issue on ‘African rainforests: past, present and future’ of Philosophical Transactions of the Royal Society.JRC.H.5-Land Resources Managemen

The past, present and future of Africa's rainforests

The Africanwet tropics contain the second largest area of tropical rainforest in the world (second only toAmazonia), accounting for roughly 30% of global rainforest cover, the lush green heart of an otherwise generally dry continent. These rainforests have global significance and value as reservoirs of biodiversity, as stores and sinks of atmospheric carbon, as regulators of flow of mighty rivers, as sources of moisture to the atmosphere and engines of the global atmospheric circulation, as a key component of the Earth system and its biogeochemical cycles, and as providers of resources and ecosystem services to local communities and the region’s nations. They also have a unique and particular history of changes in climate and human pressure, and face a range of contemporary pressures. Over the twenty-first century, the African rainforest realmhas the potential to witness massive change, both through an expansion of deforestation, hunting and logging, and through the effects of global climate change. This Theme Issue presents a multidisciplinary perspective on the nature and ecology of the African rainforest biome, and examines the current pressures and future threats to this biome. Compared with the other major rainforest regions, Amazonia and Southeast Asia, the African rainforest realm remains understudied, and in particular there have been very few attempts at interdisciplinary synthesis. This Theme Issue is an attempt to address this deficit, and explores what we know about the African rainforests and the threats they face, and what we need to know is this century of rapid change. In some ways, this can be viewed as a complement to similar Theme Issues of this journal focused on the rainforests of Amazonia [1,2] and Southeast Asia [3].JRC.H.5-Land Resources Managemen

Climate change alters impacts of extreme climate events on a tropical perennial tree crop

Anthropogenic climate change causes more frequent and intense fluctuations in the El Niño Southern Oscillation (ENSO). Understanding the effects of ENSO on agricultural systems is crucial for predicting and ameliorating impacts on lives and livelihoods, particularly in perennial tree crops, which may show both instantaneous and delayed responses. Using cocoa production in Ghana as a model system, we analyse the impact of ENSO on annual production and climate over the last 70 years. We report that in recent decades, El Niño years experience reductions in cocoa production followed by several years of increased production, and that this pattern has significantly shifted compared with prior to the 1980s. ENSO phase appears to affect the climate in Ghana, and over the same time period, we see corresponding significant shifts in the climatic conditions resulting from ENSO extremes, with increasing temperature and water stress. We attribute these changes to anthropogenic climate change, and our results illustrate the big data analyses necessary to improve understanding of perennial crop responses to climate change in general, and climate extremes in particular

Proximity to forest mediates trade-offs between yields and biodiversity of birds in oil palm smallholdings

There is much debate about how best to mitigate the effects of agricultural expansion on biodiversity, especially in the tropics. Recent studies have emphasized that proximity to natural habitats can enhance farmland biodiversity, yet few studies have examined whether or not such proximity mediates local trade-offs between yields and biodiversity, and hence alters conclusions about the ecological benefits of alternative farming strategies. Here we examine yield-biodiversity trade-offs, focusing on birds in oil palm smallholdings at different distances from remaining areas of forest, including a large forest reserve, in Ghana. We found significantly fewer birds on higher-yielding than lower-yielding farms, in terms of both species richness and abundance. For forest specialist birds (likely to be highly vulnerable to conversion of land to agriculture) we also found a greater trade-off (i.e., lower richness and abundance for a given yield) at farms further from forest, to the extent that increasing distance to the nearest forest from 1 to 10 km had a similar effect as a 3- to 5-fold increase in fruit yield brought about by increased intensification. Our study highlights the importance of accounting for the effects of natural forest in the landscape when considering agricultural policies for biodiversity protection, underlining the importance of a landscape-scale approach to conservation

Effect of Pembrolizumab Plus Neoadjuvant Chemotherapy on Pathologic Complete Response in Women With Early-Stage Breast Cancer: An Analysis of the Ongoing Phase 2 Adaptively Randomized I-SPY2 Trial.

Importance: Approximately 25% of patients with early-stage breast cancer who receive (neo)adjuvant chemotherapy experience a recurrence within 5 years. Improvements in therapy are greatly needed. Objective: To determine if pembrolizumab plus neoadjuvant chemotherapy (NACT) in early-stage breast cancer is likely to be successful in a 300-patient, confirmatory randomized phase 3 neoadjuvant clinical trial. Design, Setting, and Participants: The I-SPY2 study is an ongoing open-label, multicenter, adaptively randomized phase 2 platform trial for high-risk, stage II/III breast cancer, evaluating multiple investigational arms in parallel. Standard NACT serves as the common control arm; investigational agent(s) are added to this backbone. Patients with ERBB2 (formerly HER2)-negative breast cancer were eligible for randomization to pembrolizumab between November 2015 and November 2016. Interventions: Participants were randomized to receive taxane- and anthracycline-based NACT with or without pembrolizumab, followed by definitive surgery. Main Outcomes and Measures: The primary end point was pathologic complete response (pCR). Secondary end points were residual cancer burden (RCB) and 3-year event-free and distant recurrence-free survival. Investigational arms graduated when demonstrating an 85% predictive probability of success in a hypothetical confirmatory phase 3 trial. Results: Of the 250 women included in the final analysis, 181 were randomized to the standard NACT control group (median [range] age, 47 [24.77] years). Sixty-nine women (median [range] age, 50 [27-71] years) were randomized to 4 cycles of pembrolizumab in combination with weekly paclitaxel followed by AC; 40 hormone receptor (HR)-positive and 29 triple-negative. Pembrolizumab graduated in all 3 biomarker signatures studied. Final estimated pCR rates, evaluated in March 2017, were 44% vs 17%, 30% vs 13%, and 60% vs 22% for pembrolizumab vs control in the ERBB2-negative, HR-positive/ERBB2-negative, and triple-negative cohorts, respectively. Pembrolizumab shifted the RCB distribution to a lower disease burden for each cohort evaluated. Adverse events included immune-related endocrinopathies, notably thyroid abnormalities (13.0%) and adrenal insufficiency (8.7%). Achieving a pCR appeared predictive of long-term outcome, where patients with pCR following pembrolizumab plus chemotherapy had high event-free survival rates (93% at 3 years with 2.8 years\u27 median follow-up). Conclusions and Relevance: When added to standard neoadjuvant chemotherapy, pembrolizumab more than doubled the estimated pCR rates for both HR-positive/ERBB2-negative and triple-negative breast cancer, indicating that checkpoint blockade in women with early-stage, high-risk, ERBB2-negative breast cancer is highly likely to succeed in a phase 3 trial. Pembrolizumab was the first of 10 agents to graduate in the HR-positive/ERBB2-negative signature. Trial Registration: ClinicalTrials.gov Identifier: NCT01042379

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

ATR and H2AX Cooperate in Maintaining Genome Stability under Replication Stress*S⃞

Chromosomal abnormalities are frequently caused by problems encountered during DNA replication. Although the ATR-Chk1 pathway has previously been implicated in preventing the collapse of stalled replication forks into double-strand breaks (DSB), the importance of the response to fork collapse in ATR-deficient cells has not been well characterized. Herein, we demonstrate that, upon stalled replication, ATR deficiency leads to the phosphorylation of H2AX by ATM and DNA-PKcs and to the focal accumulation of Rad51, a marker of homologous recombination and fork restart. Because H2AX has been shown to play a facilitative role in homologous recombination, we hypothesized that H2AX participates in Rad51-mediated suppression of DSBs generated in the absence of ATR. Consistent with this model, increased Rad51 focal accumulation in ATR-deficient cells is largely dependent on H2AX, and dual deficiencies in ATR and H2AX lead to synergistic increases in chromatid breaks and translocations. Importantly, the ATM and DNA-PK phosphorylation site on H2AX (Ser139) is required for genome stabilization in the absence of ATR; therefore, phosphorylation of H2AX by ATM and DNA-PKcs plays a pivotal role in suppressing DSBs during DNA synthesis in instances of ATR pathway failure. These results imply that ATR-dependent fork stabilization and H2AX/ATM/DNA-PKcs-dependent restart pathways cooperatively suppress double-strand breaks as a layered response network when replication stalls