Status, trends and future dynamics of biodiversity and ecosystems underpinning nature's contributions to people

Biodiversity at the species and ecosystem levels is currently under multiple threats almost everywhere in the Asia-Pacific region, and in many areas the situation is now critical (well established). Of the various ecosystems, lowland evergreen forests, alpine ecosystems, limestone karsts, inland wetlands, and estuarine and coastal habitats are most threatened (well established). Genetic diversity within species, both wild and domestic, is also decreasing in many cases as a result of decreasing ranges (established but incomplete). In several countries there has been a small increase in the forest cover which is mostly attributed to monoculture forestry plantations and enabling policies of the governments. Forest fires associated with rapid loss of forest cover is leading to enormous environmental and socio-economic loss (well established) {3.2.1; 3.2.2; 3.2.3; 3.2.4; 3.2.5; 3.3.1}. There has been a steady decline in the populations of large vertebrates due to poaching and illegal trade in wildlife parts and products in the Asia-Pacific region (well established). As a result, most of these species now survive only in the best-managed protected areas (well established). Widespread loss of large vertebrates has had a measureable impact on several forest functions and services, including seed dispersal (established but incomplete). Australia has the highest rate of mammal extinction (>10 per cent) of any continent globally. Bird extinctions on individual Pacific islands range from 15.4 per cent to 87.5 per cent for those with good fossil records, and these extinctions have resulted in the loss of many ecological functions previously performed by birds (well established). Besides wildlife, there is a massive regional trade in timber, traditional medicines and other products (well established). Without adequate protection, remediation and proper policies, the current decline in biodiversity and nature's contributions to people on land, in freshwaters, and in the sea will threaten the quality of life of future generations in the Asia-Pacific region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.7; 3.2.2.1; 3.3.1} With the current rate of human population growth, expansion of urban industrial environments, transformation of agriculture in favour of high yielding varieties, transforming forests to uniform plantations of oil palm, rubber or timber trees, the biodiversity and nature's contributions to people in the Asia-Pacific region are likely to be adversely affected in the coming decades (well established). It is predicted that most of the biodiversity in the next few decades may be confined to protected areas or in places where the local communities have taken the lead in local level conservation in lieu of economic incentives and equitable compensation by the stake-holders. Unprecedented increase in human population of the Asia-Pacific region has stressed the fragile ecosystems to their limits; while arable cropping has been extended to sites which were not entirely suitable for it, resulting in soil degradation and erosion (well established) {3.2.1.1; 3.2.1.2; 3.2.1.5; 3.2.2.2; 3.2.2.4; 3.3; 3.3.1; 3.3.6; 3.4}. Freshwater ecosystems in the Asia-Pacific region support more than 28 per cent of aquatic and semi-aquatic species but nearly 37 per cent of these species are threatened due to anthropogenic and climatic drivers (well established). Cumulative impacts of global warming and damming of rivers in some of the river basins will have significant negative impacts on fish production and environmental flows (well established). Likewise, degradation of wetlands has had severe negative impacts on migratory waterfowl, fish production and local livelihoods (well established). However, there are scientific data gaps on the current status of biodiversity and nature's contributions to people in most of the river basins, inland wetlands and peatlands of the region {3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.2.4}. Coastal and marine habitats are likewise threatened due to commercial aquaculture, overfishing, and pollution affecting biodiversity and nature's contributions to people (well established). Detailed analyses of fisheries production in the region have shown severe decline in recent decades. It is projected that if unsustainable fishing practices continue, there could be no exploitable stocks of fish by as early as 2048. This could lead to trophic cascades and collapse of marine ecosystems (established but incomplete). Loss of seagrass beds which forms main diet of several threatened species such as dugong is a major concern (well established). There is a need to conduct systematic and region-wide assessment of fisheries stocks and coastal habitat in the region to aid conservation, management and restoration. {3.1.3.1; 3.2.3.3; 3.2.3.6; 3.2.4.6; 3.4}. Mangrove ecosystems in the Asia-Pacific region are most diverse in the world. They support a rich biodiversity and provide a range of provisioning, regulating and supporting services, which are crucial for the livelihood of local communities (well established). Both mangrove and intertidal habitats form a buffer from siltation for offshore coral reefs protection hence affecting productivity of reefs including seagrass. However, up to 75 per cent of the mangroves have been degraded or converted in recent decades (well established). The conversion of mangroves to aquaculture, rice, oil palm, and other land-use changes is leading to the loss of the buffer between sea and land which can reduce the impact of natural disasters such as cyclones and tsunamis. It is projected that rise in sea level due to global warming would pose the biggest threat to mangroves, thereby affecting nature's contributions to people especially in Bangladesh, Philippines, New Zealand, Viet Nam and China (well established) {3.2.3.1; 3.2.3.2; 3.3.4}. There has been a steady increase in the number, abundance and impacts of invasive alien species in the Asia-Pacific region, negatively affecting native biodiversity, ecosystem functioning and socio-cultural environments (well established). The total annual loss caused by invasive alien species has been estimated at US$35.5 billion in SE Asia and US$9B in Australia. Costs to agriculture due to invasive alien species are likewise immense in the region {3.2.1.1; 3.2.1.2; 3.2.1.4; 3.2.1.5; 3.2.1.6; 3.2.1.7; 3.2.2.1; 3.2.2.2; 3.2.2.3; 3.2.3.6; 3.3.5}. There has been a nearly 30 per cent decline in biocultural diversity in the Asia-Pacific region since the 1970s (well established). Decline of linguistic diversity has been catastrophic in the indigenous Australian and Trans-New Guinean families, as a result of a shifting away from small indigenous languages towards larger, national or regional languages (well established). Linguistic and biological diversity often coincide in the Asia-Pacific region and parallel strategies need to be developed for their conservation. National conservation priorities should take into consideration the bioculturally rich areas that are facing great threats {3.2.5; 3.2.5.2; 3.2.5.4; 3.4}. Protected Area coverage in the Asia-Pacific region has increased substantially since last three decades. Despite this progress, however, at least 75 per cent of Key Biodiversity Areas remain unprotected, suggesting that the region is not on track to conserve areas of particular importance for biodiversity, as called for under Aichi Target 11 (well established). Oceania has the highest overall Protected Area coverage in the region. North-East Asia has the highest proportion of Key Biodiversity Areas covered by Protected Areas, but only 1 per cent of its marine area is protected (well established) {3.2.5.6; 3.2.6; 3.2.6.1}. The Asia-Pacific region has high levels of endemism, and some 25 per cent of the region’s endemic species are facing high extinction risks as per the IUCN Red List. Endemic species in some subregions face an extinction risk as high as 46 per cent of endemic species threatened in South Asia (well established). South-East Asia has the greatest number of threatened species and the fastest increases in extinction risk (Red List Index) in the Asia-Pacific region. North Asian endemic species extinction risk is also higher than the regional average; the high percentage of Data Deficient species (36 per cent) indicates that more research and conservation action are needed for endemic species in this subregion (well established) {3.2.1; 3.2.2; 3.2.6.2; 3.3.4}. Some aspects of biodiversity have recently started to recover in several countries in the Asia-Pacific region (established but incomplete). This recovery has resulted from various changes, including population concentration in cities, increased agricultural production per unit area, increasing conservation awareness among citizens, and the enabling policies of the governments. Future trends of biodiversity in the Asia-Pacific region will largely depend on whether other countries will follow this recovering trajectory by stabilizing land/sea use change, manage their natural resources sustainably, and cooperating with each other in meeting the Aichi Targets and the Sustainable Development Goals {3.2.1.5; 3.2.3.5; 3.3.1; 3.3.3; 3.3.6}. Given that the scientific information on the status and trends of biodiversity and nature's contributions to people is not available uniformly across all ecosystems and habitats in the region, the national governments are encouraged to initiate systematic documentation and monitoring of health of ecosystems and ecosystem flows (established but incomplete). Saving terrestrial fauna especially big mammals and other fauna that require large roaming areas such as Orangutans, proboscis monkey, hornbills, tigers, Sumatran rhinoceros, gaurs and Asian elephants can be done by connecting large tracts of forests with wildlife corridors or through rehabilitation projects; the same goes for coastal and marine, freshwater and other ecosystems in the region {3.2.1.1; 3.2.2.4; 3.3.4; 3.4}

Breast cancer incidence, stage, treatment and survival in ethnic groups in South East England

Studies from the US have shown variations in breast cancer incidence, stage distribution, treatment and survival between ethnic groups. Data on 35 631 women diagnosed with breast cancer in South East England between 1998 and 2003 with self-assigned ethnicity information available were analysed. Results are reported for White, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African and Chinese women. Age-standardised breast cancer incidence rate ratios, patterns of stage of disease at diagnosis, treatment, overall and breast cancer-specific survival were examined. All ethnic groups studied had lower age-standardised breast cancer incidence rates than White women, with Bangladeshi women having the lowest rate ratio (0.23, 95% CI: 0.20–0.26). White women were the most likely to have a stage recorded at diagnosis (adjusted proportion 75%), and least likely to be diagnosed with metastatic disease (7%). Black African women were the least likely to have a record of cancer surgery (63%) or hormone therapy (32%), and most likely to receive chemotherapy (38%). After fully adjusting for age, socioeconomic deprivation, stage of disease and treatment received, there was no significant variation in breast cancer-specific survival. However, Black African women had significantly worse overall survival (hazard ratio 1.24, P=0.025). These findings suggest that a strategy of earlier detection should be pursued in Black and South Asian women

The relationship between SF-6D utility scores and lifestyle factors across three life-stages: Evidence from the Australian Longitudinal Study on Women’s Health

Purpose: To investigate how SF-6D utility scores change with age between generations of women, and to quantify the relationship of SF-6D with lifestyle factors across life-stages. Methods: Up to seven waves of self-reported, longitudinal data were drawn for the 1973-78 (young, N=13772), 1946-51 (mid-age, N=12792), 1921-26 (older, N=9972) cohorts from the Australian Longitudinal Study on Women’s Health. Mixed effects models were employed for analysis. Results: Young and mid-age women had similar average SF-6D scores at baseline (0.63-0.64), which remained consistent over 16 year period. However, older women had lower scores at baseline at 0.57 which steadily declined over 15 years. Across cohorts, low education attainment, greater difficulty in managing on income, obesity, physical inactivity, heavy smoking, non-drinking and increasing stress levels were associated with lower SF-6D scores. The magnitude of effect varied between cohorts. SF-6D scores were lower amongst young women with high risk drinking behaviours than low-risk drinkers. Mid-age women who were underweight, never married, or underwent surgical menopause also reported lower SF-6D scores. Older women who lived in remote areas, who were ex-smokers, or were underweight reported lower SF-6D scores. Conclusion: The SF-6D utility score is sensitive to differences in lifestyle factors across adult lifestages. Gradual loss of physical functioning may explain the steady decline in health for older women. Key factors associated with SF-6D include physical activity, body mass index, menopause status, smoking, alcohol use and stress. Factors associated with poorer SF-6D scores vary in type and magnitude at different life stages

How Darwinian models inform therapeutic failure initiated by clonal heterogeneity in cancer medicine

Carcinogenesis is an evolutionary process that establishes the ‘hallmarks of cancer' by natural selection of cell clones that have acquired advantageous heritable characteristics. Evolutionary adaptation has also been proposed as a mechanism that promotes drug resistance during systemic cancer therapy. This review summarises the evidence for the evolution of resistance to cytotoxic and targeted anti-cancer drugs according to Darwinian models and highlights the roles of genomic instability and high intra-tumour genetic heterogeneity as major accelerators of this evolutionary process. Clinical implications and strategies that may prevent the evolution of resistance or target the origins of genetic heterogeneity are discussed. New technologies to measure intra-tumour heterogeneity and translational research on serial biopsies of cancer lesions during and after therapeutic intervention are identified as key areas to further the understanding of determinants and mechanisms of the evolution of drug resistance

Functional Characterization of Circulating Tumor Cells with a Prostate-Cancer-Specific Microfluidic Device

Cancer metastasis accounts for the majority of cancer-related deaths owing to poor response to anticancer therapies. Molecular understanding of metastasis-associated drug resistance remains elusive due to the scarcity of available tumor tissue. Isolation of circulating tumor cells (CTCs) from the peripheral blood of patients has emerged as a valid alternative source of tumor tissue that can be subjected to molecular characterization. However, issues with low purity and sensitivity have impeded adoption to clinical practice. Here we report a novel method to capture and molecularly characterize CTCs isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. We have developed a geometrically enhanced differential immunocapture (GEDI) microfluidic device that combines an anti-prostate specific membrane antigen (PSMA) antibody with a 3D geometry that captures CTCs while minimizing nonspecific leukocyte adhesion. Enumeration of GEDI-captured CTCs (defined as intact, nucleated PSMA+/CD45− cells) revealed a median of 54 cells per ml identified in CRPC patients versus 3 in healthy donors. Direct comparison with the commercially available CellSearch® revealed a 2–400 fold higher sensitivity achieved with the GEDI device. Confocal microscopy of patient-derived GEDI-captured CTCs identified the TMPRSS2:ERG fusion protein, while sequencing identified specific androgen receptor point mutation (T868A) in blood samples spiked with only 50 PC C4-2 cells. On-chip treatment of patient-derived CTCs with docetaxel and paclitaxel allowed monitoring of drug-target engagement by means of microtubule bundling. CTCs isolated from docetaxel-resistant CRPC patients did not show any evidence of drug activity. These measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents

Minimal residual disease and circulating tumor cells in breast cancer

Tumor cell dissemination in bone marrow or other organs is thought to represent an important step in the metastatic process. The detection of bone marrow disseminated tumor cells is associated with worse outcome in early breast cancer. Moreover, the detection of peripheral blood circulating tumor cells is an adverse prognostic factor in metastatic breast cancer, and emerging data suggest that this is also true for early disease. Beyond enumeration, the characterization of these cells has the potential to improve risk assessment, treatment selection and monitoring, and the development of novel therapeutic agents, and to advance our understanding of the biology of metastasis

Clinical relevance and biology of circulating tumor cells

Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer