Agricultural origins and the isotopic identity of domestication in northern China

Stable isotope biochemistry (δ 13C and δ 15N) and radiocarbon dating of ancient human and animal bone document 2 distinct phases of plant and animal domestication at the Dadiwan site in northwest China. The first was brief and nonintensive: at various times between 7900 and 7200 calendar years before present (calBP) people harvested and stored enough broomcorn millet (Panicum miliaceum) to provision themselves and their hunting dogs (Canis sp.) throughout the year. The second, much more intensive phase was in place by 5900 calBP: during this time both broomcorn and foxtail (Setaria viridis spp. italica) millets were cultivated and made significant contributions to the diets of people, dogs, and pigs (Sus sp.). The systems represented in both phases developed elsewhere: the earlier, low-intensity domestic relationship emerged with hunter-gatherers in the arid north, while the more intensive, later one evolved further east and arrived at Dadiwan with the Yangshao Neolithic. The stable isotope methodology used here is probably the best means of detecting the symbiotic human-plantanimal linkages that develop during the very earliest phases of domestication and is thus applicable to the areas where these connections first emerged and are critical to explaining how and why agriculture began in East Asia

Disease burden and economic impact of diagnosed non-alcoholic steatohepatitis (NASH) in the United Kingdom (UK) in 2018

BACKGROUNDS AND AIMS: Non-alcoholic steatohepatitis (NASH) – a progressive subset of non-alcoholic fatty liver disease (NAFLD) – is a chronic liver disease that can progress to advanced fibrosis, cirrhosis, and end-stage liver disease (ESLD) if left untreated. Early-stage NASH is usually asymptomatic, meaning a large proportion of the prevalent population are undiagnosed. Receiving a NASH diagnosis increases the probability that a patient will receive interventions for the purpose of managing their condition. The purpose of this study was to estimate the disease burden and economic impact of diagnosed NASH in the United Kingdom (UK) adult population in 2018. METHODS: The socioeconomic burden of diagnosed NASH from a societal perspective was estimated using cost-of-illness methodology applying a prevalence approach. This involved estimating the number of adults with diagnosed NASH in the UK in a base period (2018) and the economic and wellbeing costs attributable to diagnosed NASH in that period. The analysis was based on a targeted review of the scientific literature, existing databases and consultation with clinical experts, health economists and patient groups. RESULTS: Of the prevalent NASH population in the UK in 2018, an estimated 79.8% were not diagnosed. In particular, of the prevalent population in disease stages F0 to F2, only 2.0% (F0), 2.0% (F1) and 16.5% (F2), respectively, were diagnosed. Total economic costs of diagnosed NASH in the UK ranged from £2.3 billion (lower prevalence scenario, base probability of diagnosis scenario) to £4.2 billion (higher prevalence scenario, base probability of diagnosis scenario). In 2018, people with NASH in the UK were estimated to experience 94,094 to 174,564 disability-adjusted life years (DALYs) overall. Total wellbeing costs associated with NASH in 2018 were estimated to range between £5.6 to £10.5 billion. CONCLUSIONS: The prevention and appropriate management of adult NASH patients could result in reduced economic costs and improvements in wellbeing

UK experience of liver transplantation for erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is characterised by excess production of free protoporphyrin from the bone marrow, most commonly due to deficiency of the enzyme ferrochelatase. Excess protoporphyrin gives rise to the cutaneous photosensitivity characteristic of the disease, and in a minority of patients leads to end-stage liver disease necessitating liver transplantation (LT). There is limited information regarding the timing, impact and long-term outcome of LT in such patients, thus we aimed to identify the indications and outcomes of all transplants performed for EPP in the UK using data from the UK Transplant Registry. Between 1987 and 2009, five patients underwent LT for EPP liver disease. Median follow-up was 60 months, and there were two deaths at 44 and 95 months from causes unrelated to liver disease. The remaining recipients are alive at 22.4 years, 61 months and 55 months after transplant. A high rate of postoperative biliary stricturing requiring multiple biliary interventions was observed. Recurrent EPP-liver disease occurred in 4/5 (80%) of patients but graft failure has not been observed. Given the role of biliary obstruction in inducing EPP-mediated liver damage, we suggest that consideration should be given for construction of a Roux loop at the time of transplant. Thus we demonstrate that although EPP liver transplant recipients have a good long-term survival, comparable to patients undergoing LT for other indications, biliary complications and disease recurrence are almost universal, and bone marrow transplantation should be considered where possible

Long-term species, sexual and individual variations in foraging strategies of fur seals revealed by stable isotopes in whiskers

Background: Individual variations in the use of the species niche are an important component of diversity in trophic interactions. A challenge in testing consistency of individual foraging strategy is the repeated collection of information on the same individuals. Methodology/Principal Findings: The foraging strategies of sympatric fur seals (Arctocephalus gazella and A. tropicalis) were examined using the stable isotope signature of serially sampled whiskers. Most whiskers exhibited synchronous delta C-13 and delta N-15 oscillations that correspond to the seal annual movements over the long term (up to 8 years). delta C-13 and delta N-15 values were spread over large ranges, with differences between species, sexes and individuals. The main segregating mechanism operates at the spatial scale. Most seals favored foraging in subantarctic waters (where the Crozet Islands are located) where they fed on myctophids. However, A. gazella dispersed in the Antarctic Zone and A. tropicalis more in the subtropics. Gender differences in annual time budget shape the seal movements. Males that do not perform any parental care exhibited large isotopic oscillations reflecting broad annual migrations, while isotopic values of females confined to a limited foraging range during lactation exhibited smaller changes. Limited inter-individual isotopic variations occurred in female seals and in male A. tropicalis. In contrast, male A. gazella showed large inter-individual variations, with some males migrating repeatedly to high-Antarctic waters where they fed on krill, thus meaning that individual specialization occurred over years. Conclusions/Significance: Whisker isotopic signature yields unique long-term information on individual behaviour that integrates the spatial, trophic and temporal dimensions of the ecological niche. The method allows depicting the entire realized niche of the species, including some of its less well-known components such as age-, sex-, individual- and migration-related changes. It highlights intrapopulation heterogeneity in foraging strategies that could have important implications for likely demographic responses to environmental variability

Stable isotope analysis provides new information on winter habitat use of declining avian migrants that is relevant to their conservation

Winter habitat use and the magnitude of migratory connectivity are important parameters when assessing drivers of the marked declines in avian migrants. Such information is unavailable for most species. We use a stable isotope approach to assess these factors for three declining African-Eurasian migrants whose winter ecology is poorly known: wood warbler Phylloscopus sibilatrix, house martin Delichon urbicum and common swift Apus apus. Spatially segregated breeding wood warbler populations (sampled across a 800 km transect), house martins and common swifts (sampled across a 3,500 km transect) exhibited statistically identical intra-specific carbon and nitrogen isotope ratios in winter grown feathers. Such patterns are compatible with a high degree of migratory connectivity, but could arise if species use isotopically similar resources at different locations. Wood warbler carbon isotope ratios are more depleted than typical for African-Eurasian migrants and are compatible with use of moist lowland forest. The very limited variance in these ratios indicates specialisation on isotopically restricted resources, which may drive the similarity in wood warbler populations' stable isotope ratios and increase susceptibility to environmental change within its wintering grounds. House martins were previously considered to primarily use moist montane forest during the winter, but this seems unlikely given the enriched nature of their carbon isotope ratios. House martins use a narrower isotopic range of resources than the common swift, indicative of increased specialisation or a relatively limited wintering range; both factors could increase house martins' vulnerability to environmental change. The marked variance in isotope ratios within each common swift population contributes to the lack of population specific signatures and indicates that the species is less vulnerable to environmental change in sub-Saharan Africa than our other focal species. Our findings demonstrate how stable isotope research can contribute to understanding avian migrants' winter ecology and conservation status

Association between mid-wall late gadolinium enhancement and sudden cardiac death in patients with dilated cardiomyopathy and mild and moderate left ventricular systolic dysfunction

Background—Current guidelines only recommend the use of an implantable cardioverter defibrillator (ICD) in patients with dilated cardiomyopathy (DCM) for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF)35%. Patients with a LVEF>35% also have low competing risks of death from non-sudden causes. Therefore, those at high-risk of SCD may gain longevity from successful ICD therapy. We investigated whether late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) identified patients with DCM without severe LV systolic dysfunction at high-risk of SCD. Methods—We prospectively investigated the association between mid-wall late gadolinium enhancement (LGE) and the pre-specified primary composite outcome of SCD or aborted SCD amongst consecutive referrals with DCM and a LVEF≥40% to our center between January 2000 and December 2011, who did not have a pre-existing indication for ICD implantation. Results—Of 399 patients (145 women, median age 50 years, median LVEF 50%, 25.3% with LGE) followed for a median of 4.6 years, 18 of 101 (17.8%) patients with LGE reached the pre-specified end-point, compared to 7 of 298 (2.3%) without (HR 9.2; 95% CI 3.9-21.8; p5% compared to those without LGE were 10.6 (95%CI 3.9-29.4), 4.9 (95% CI 1.3-18.9) and 11.8 (95% CI 4.3-32.3) respectively. Conclusions—Mid-wall LGE identifies a group of patients with DCM and LVEF≥40% at increased risk of SCD and low-risk of non-sudden death who may benefit from ICD implantation

Leveraging visual outcome measures to advance therapy development in neuroimmunologic disorders

The visual system offers unparalleled precision in the assessment of neuroaxonal damage. With the majority of patients with multiple sclerosis (MS) experiencing afferent and efferent visual dysfunction, outcome measures capturing these deficits provide insight into neuroaxonal injury, even in those with minimal disability. Ideal for use in clinical trials, visual measures are generally inexpensive, accessible, and reproducible. Quantification of visual acuity, visual fields, visual quality of life, and electrophysiologic parameters allows assessment of function, whereas optical coherence tomography (OCT) provides reliable measures of the structural integrity of the anterior afferent visual pathway. The technology of oculomotor biometrics continues to advance, and discrete measures of fixation, smooth pursuit, and saccadic eye movement abnormalities are ready for inclusion in future trials of MS progression. Visual outcomes allow tracking of neuroaxonal injury and aid in distinguishing MS from diseases such as neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated diseases (MOGAD). OCT has also provided unique insights into pathophysiology, including the identification of foveal pitting in NMOSD, possibly from damage to Müller cells, which carry an abundance of aquaporin-4 channels. For some study designs, the cost-benefit ratio favors visual outcomes over more expensive MRI outcomes. With the next frontier of therapeutics focused on remyelination and neuroprotection, visual outcomes are likely to take center stage. As an international community of collaborative, committed, vision scientists, this review by the International MS Visual System Consortium (IMSVISUAL) outlines the quality standards, informatics, and framework needed to routinely incorporate vision outcomes into MS and NMOSD trials

Pre-Whaling Genetic Diversity and Population Ecology in Eastern Pacific Gray Whales: Insights from Ancient DNA and Stable Isotopes

Commercial whaling decimated many whale populations, including the eastern Pacific gray whale, but little is known about how population dynamics or ecology differed prior to these removals. Of particular interest is the possibility of a large population decline prior to whaling, as such a decline could explain the ∼5-fold difference between genetic estimates of prior abundance and estimates based on historical records. We analyzed genetic (mitochondrial control region) and isotopic information from modern and prehistoric gray whales using serial coalescent simulations and Bayesian skyline analyses to test for a pre-whaling decline and to examine prehistoric genetic diversity, population dynamics and ecology. Simulations demonstrate that significant genetic differences observed between ancient and modern samples could be caused by a large, recent population bottleneck, roughly concurrent with commercial whaling. Stable isotopes show minimal differences between modern and ancient gray whale foraging ecology. Using rejection-based Approximate Bayesian Computation, we estimate the size of the population bottleneck at its minimum abundance and the pre-bottleneck abundance. Our results agree with previous genetic studies suggesting the historical size of the eastern gray whale population was roughly three to five times its current size

Isotopic Investigation of Contemporary and Historic Changes in Penguin Trophic Niches and Carrying Capacity of the Southern Indian Ocean

A temperature-defined regime shift occurred in the 1970s in the southern Indian Ocean, with simultaneous severe decreases in many predator populations. We tested a possible biological link between the regime shift and predator declines by measuring historic and contemporary feather isotopic signatures of seven penguin species with contrasted foraging strategies and inhabiting a large latitudinal range. We first showed that contemporary penguin isotopic variations and chlorophyll a concentration were positively correlated, suggesting the usefulness of predator δ13C values to track temporal changes in the ecosystem carrying capacity and its associated coupling to consumers. Having controlled for the Suess effect and for increase CO2 in seawater, δ13C values of Antarctic penguins and of king penguins did not change over time, while δ13C of other subantarctic and subtropical species were lower in the 1970s. The data therefore suggest a decrease in ecosystem carrying capacity of the southern Indian Ocean during the temperature regime-shift in subtropical and subantarctic waters but not in the vicinity of the Polar Front and in southward high-Antarctic waters. The resulting lower secondary productivity could be the main driving force explaining the decline of subtropical and subantarctic (but not Antarctic) penguins that occurred in the 1970s. Feather δ15N values did not show a consistent temporal trend among species, suggesting no major change in penguins’ diet. This study highlights the usefulness of developing long-term tissue sampling and data bases on isotopic signature of key marine organisms to track potential changes in their isotopic niches and in the carrying capacity of the environment

A retrospective study of PBDEs and PCBs in human milk from the Faroe Islands

BACKGROUND: Persistent organic pollutants (POPs) in wildlife and humans remain a cause of global concern, both in regard to traditional POPs, such as the polychlorinated biphenyls (PCBs), and emerging POPs, such as the polybrominated diphenyl ethers (PBDEs). To determine the time related concentrations, we analyzed human milk for these substances at three time points between 1987 and 1999. Polychlorobiphenylols (OH-PCBs), the dominating class of PCB metabolites, some of which are known to be strongly retained in human blood, were also included in the assessment. METHODS: We obtained milk from the Faroe Islands, where the population is exposed to POPs from their traditional diet (which may include pilot whale blubber). In addition to three pools, nine individual samples from the last time point were also analyzed. After cleanup, partitioning of neutral and acidic compounds, and separation of chemical classes, the analyses were carried out by gas chromatography and/or gas chromatography/mass spectrometry. RESULTS: Compared to other European populations, the human milk had high PCB concentrations, with pool concentrations of 2300 ng/g fat 1987, 1600 ng/g fat in 1994, and 1800 ng/g fat in 1999 (based on the sum of eleven major PCB congeners). The nine individual samples showed great variation in PCB concentrations. The OH-PCBs were present in trace amounts only, at levels of approximately 1% of the PCB concentrations. The PBDE concentrations showed a clear increase over time, and their concentrations in human milk from 1999 are among the highest reported so far from Europe, with results of individual samples ranging from 4.7 to 13 ng/g fat CONCLUSION: Although remote from pollution sources, the Faroe Islands show high concentrations of POPs in human milk, particularly PCBs, but also PBDEs. The PBDEs show increasing concentrations over time. The OH-PCB metabolites are poorly transferred to human milk, which likely is related to their acidic character