Circulating microRNAs as biomarkers to assist the management of the malignant germ-cell-tumour subtype choriocarcinoma.

Germ-cell-tumours (GCTs) are heterogeneous and management is complex. The current conventional biomarkers, alpha-fetoprotein and human-chorionic-gonadotropin (HCG), have limited utility for diagnosis/follow-up as secretion is restricted to specific malignant-GCT subtypes and long half-life can make interpretation and clinical decision-making challenging. We sought to identify circulating microRNAs that reflected choriocarcinoma disease activity more accurately than HCG in a metastatic primary mediastinal nonseminomatous-GCT (PMNSGCT) case with elevated diagnostic serum HCG (>250,000U/L), consistent with pure choriocarcinoma. We undertook comprehensive microRNA profiling (n=754 microRNAs) using two 384-well TaqMan Low-Density-Array cards in 16 serum samples; 10 from PMNSGCT diagnosis/follow-up and six controls. Key findings underwent confirmatory qRT-PCR. We identified a serum panel of choriocarcinoma-specific ‘chromosome-19-microRNA-cluster’ (C19MC) microRNAs that were highly elevated at diagnosis but fell rapidly on treatment and normalised before the second full chemotherapy course. We also re-confirmed serum elevation of the previously identified malignant-GCT marker miR-371a-3p at diagnosis. These circulating microRNA markers reflected choriocarcinoma disease activity more accurately than serum HCG and real-time knowledge would have assisted clinical decision-making. With further study, these microRNA markers will facilitate future management of such patients and are likely to result in improved outcomes.Acknowledgment of research support: The authors acknowledge grant funding from the St. Baldrick’s Foundation [reference 358099], the Isaac Newton Trust [reference 15.40f], the Medical Research Council [reference MR/R001146/1] and Addenbrooke’s Charitable Trust [reference 23/17 B (iv)]. We are grateful for support from the Max Williamson Fund and from Christiane and Alan Hodson, in memory of their daughter Olivia. The funders were not involved in study design, data collection or interpretation, or decision to submit for publication

Biogeographic distribution of five Antarctic cyanobacteria using large-scale k-mer searching with sourmash branchwater

Cyanobacteria form diverse communities and are important primary producers in Antarctic freshwater environments, but their geographic distribution patterns in Antarctica and globally are still unresolved. There are however few genomes of cultured cyanobacteria from Antarctica available and therefore metagenome-assembled genomes (MAGs) from Antarctic cyanobacteria microbial mats provide an opportunity to explore distribution of uncultured taxa. These MAGs also allow comparison with metagenomes of cyanobacteria enriched communities from a range of habitats, geographic locations, and climates. However, most MAGs do not contain 16S rRNA gene sequences, making a 16S rRNA gene-based biogeography comparison difficult. An alternative technique is to use large-scale k-mer searching to find genomes of interest in public metagenomes. This paper presents the results of k-mer based searches for 5 Antarctic cyanobacteria MAGs from Lake Fryxell and Lake Vanda, assigned the names Phormidium pseudopriestleyi FRX01, Microcoleus sp. MP8IB2.171, Leptolyngbya sp. BulkMat.35, Pseudanabaenaceae cyanobacterium MP8IB2.15, and Leptolyngbyaceae cyanobacterium MP9P1.79 in 498,942 unassembled metagenomes from the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA). The Microcoleus sp. MP8IB2.171 MAG was found in a wide variety of environments, the P. pseudopriestleyi MAG was found in environments with challenging conditions, the Leptolyngbyaceae cyanobacterium MP9P1.79 MAG was only found in Antarctica, and the Leptolyngbya sp. BulkMat.35 and Pseudanabaenaceae cyanobacterium MP8IB2.15 MAGs were found in Antarctic and other cold environments. The findings based on metagenome matches and global comparisons suggest that these Antarctic cyanobacteria have distinct distribution patterns ranging from locally restricted to global distribution across the cold biosphere and other climatic zones

The Impact of Dementia on Women Internationally: an Integrative Review

Women are disproportionately affected by dementia, both in terms of developing dementia and becoming caregivers. We conducted an integrative review of English language literature of the issues affecting women in relation to dementia from an international perspective. The majority of relevant studies were conducted in high income countries, and none were from low-income countries. The effects of caregiving on health, wellbeing and finances are greater for women; issues facing women, particularly in low and middle-income countries need to be better understood. Research should focus on building resilience to help people adjust and cope long term

Competing Tradeoff between Increasing Marine Mammal Predation and Fisheries Harvest of Chinook Salmon

Many marine mammal predators, particularly pinnipeds, have increased in abundance in recent decades, generating new challenges for balancing human uses with recovery goals via ecosystem-based management. We used a spatio-temporal bioenergetics model of the Northeast Pacific Ocean to quantify how predation by three species of pinnipeds and killer whales (Orcinus orca) on Chinook salmon (Oncorhynchus tshawytscha) has changed since the 1970s along the west coast of North America, and compare these estimates to salmon fisheries. We find that from 1975 to 2015, biomass of Chinook salmon consumed by pinnipeds and killer whales increased from 6,100 to 15,200 metric tons (from 5 to 31.5 million individual salmon). Though there is variation across the regions in our model, overall, killer whales consume the largest biomass of Chinook salmon, but harbor seals (Phoca vitulina) consume the largest number of individuals. The decrease in adult Chinook salmon harvest from 1975–2015 was 16,400 to 9,600 metric tons. Thus, Chinook salmon removals (harvest + consumption) increased in the past 40 years despite catch reductions by fisheries, due to consumption by recovering pinnipeds and endangered killer whales. Long-term management strategies for Chinook salmon will need to consider potential conflicts between rebounding predators or endangered predators and prey

Estimates of Chinook salmon consumption in Washington State inland waters by four marine mammal predators from 1970 to 2015

Conflicts can arise when the recovery of one protected species limits the recovery of another through competition or predation. The recovery of many marine mammal populations on the west coast of the United States has been viewed as a success; however, within Puget Sound in Washington State, the increased abundance of three protected pinniped species may be adversely affecting the recovery of threatened Chinook salmon (Oncorhynchus tshawytscha) and endangered killer whales (Orcinus orca) within the region. Between 1970 and 2015, we estimate that the annual biomass of Chinook salmon consumed by pinnipeds has increased from 68 to 625 metric tons. Converting juvenile Chinook salmon into adult equivalents, we found that by 2015, pinnipeds consumed double that of resident killer whales and six times greater than the combined commercial and recreational catches. We demonstrate the importance of interspecific interactions when evaluating species recovery. As more protected species respond positively to recovery efforts, managers should attempt to evaluate tradeoffs between these recovery efforts and the unintended ecosystem consequences of predation and competition on other protected species

Competing tradeoffs between increasing marine mammal predation and fisheries harvest of Chinook salmon

Many marine mammal predators, particularly pinnipeds, have increased in abundance in recent decades, generating new challenges for balancing human uses with recovery goals via ecosystem-based management. We used a spatio-temporal bioenergetics model of the Northeast Pacific Ocean to quantify how predation by three species of pinnipeds and killer whales (Orcinus orca) on Chinook salmon (Oncorhynchus tshawytscha) has changed since the 1970s along the west coast of North America, and compare these estimates to salmon fisheries. We find that from 1975 to 2015, biomass of Chinook salmon consumed by pinnipeds and killer whales increased from 6,100 to 15,200 metric tons (from 5 to 31.5 million individual salmon). Though there is variation across the regions in our model, overall, killer whales consume the largest biomass of Chinook salmon, but harbor seals (Phoca vitulina) consume the largest number of individuals. The decrease in adult Chinook salmon harvest from 1975–2015 was 16,400 to 9,600 metric tons. Thus, Chinook salmon removals (harvest + consumption) increased in the past 40 years despite catch reductions by fisheries, due to consumption by recovering pinnipeds and endangered killer whales. Long-term management strategies for Chinook salmon will need to consider potential conflicts between rebounding predators or endangered predators and prey

Competing tradeoffs between increasing marine mammal predation and fisheries harvest of Chinook salmon

Many marine mammal predators, particularly pinnipeds, have increased in abundance in recent decades, generating new challenges for balancing human uses with recovery goals via ecosystem-based management. We used a spatio-temporal bioenergetics model of the Northeast Pacific Ocean to quantify how predation by three species of pinnipeds and killer whales (Orcinus orca) on Chinook salmon (Oncorhynchus tshawytscha) has changed since the 1970s along the west coast of North America, and compare these estimates to salmon fisheries. We find that from 1975 to 2015, biomass of Chinook salmon consumed by pinnipeds and killer whales increased from 6,100 to 15,200 metric tons (from 5 to 31.5 million individual salmon). Though there is variation across the regions in our model, overall, killer whales consume the largest biomass of Chinook salmon, but harbor seals (Phoca vitulina) consume the largest number of individuals. The decrease in adult Chinook salmon harvest from 1975–2015 was 16,400 to 9,600 metric tons. Thus, Chinook salmon removals (harvest + consumption) increased in the past 40 years despite catch reductions by fisheries, due to consumption by recovering pinnipeds and endangered killer whales. Long-term management strategies for Chinook salmon will need to consider potential conflicts between rebounding predators or endangered predators and prey

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The influence of hydrological regimes on sex ratios and spatial segregation of the sexes in two dioecious riparian shrub species in northern Sweden

River management practices have altered the hydrological regimes of many rivers and also altered the availability of regeneration niches for riparian species. We investigated the impact of changed hydrological regimes on the sex ratios and the Spatial Segregation of the Sexes (SSS) in the dioecious species Salix myrsinifolia Salisb.–phylicifolia L. and S. lapponum L. by studying the free-flowing Vindel River and the regulated Ume River in northern Sweden. We surveyed sex ratios of these species in 12 river reaches on the Vindel River and in 17 reaches on the Ume River. In addition, we surveyed the sex and location above mean river stage of 1,002 individuals across both river systems to investigate the SSS of both species. Cuttings were collected from male and female individuals of S. myrsinifolia–phylicifolia from both rivers and subjected to four different water table regimes in a greenhouse experiment to investigate growth response between the sexes. We found an M/F sex ratio in both river systems similar to the regional norm of 0.62 for S. myrsinifolia–phylicifolia and of 0.42 for S. lapponum. We found no evidence of SSS in either the free-flowing Vindel River or the regulated Ume River. In the greenhouse experiment, hydrological regime had a significant effect on shoot and root dry weight and on root length. Significantly higher shoot dry weights were found in females than in males and significantly different shoot and root dry weights were found between cuttings taken from the two rivers. We concluded that changed hydrological regimes are likely to alter dimensions of the regeneration niche and therefore to influence sex ratios and SSS at an early successional stage, making it difficult to find clear spatial patterns once these species reach maturity and can be sexed