An early modern human presence in Sumatra 73,000-63,000 years ago.

Genetic evidence for anatomically modern humans (AMH) out of Africa before 75 thousand years ago (ka) and in island southeast Asia (ISEA) before 60 ka (93-61 ka) predates accepted archaeological records of occupation in the region. Claims that AMH arrived in ISEA before 60 ka (ref. 4) have been supported only by equivocal or non-skeletal evidence. AMH evidence from this period is rare and lacks robust chronologies owing to a lack of direct dating applications, poor preservation and/or excavation strategies and questionable taxonomic identifications. Lida Ajer is a Sumatran Pleistocene cave with a rich rainforest fauna associated with fossil human teeth. The importance of the site is unclear owing to unsupported taxonomic identification of these fossils and uncertainties regarding the age of the deposit, therefore it is rarely considered in models of human dispersal. Here we reinvestigate Lida Ajer to identify the teeth confidently and establish a robust chronology using an integrated dating approach. Using enamel-dentine junction morphology, enamel thickness and comparative morphology, we show that the teeth are unequivocally AMH. Luminescence and uranium-series techniques applied to bone-bearing sediments and speleothems, and coupled uranium-series and electron spin resonance dating of mammalian teeth, place modern humans in Sumatra between 73 and 63 ka. This age is consistent with biostratigraphic estimations, palaeoclimate and sea-level reconstructions, and genetic evidence for a pre-60 ka arrival of AMH into ISEA. Lida Ajer represents, to our knowledge, the earliest evidence of rainforest occupation by AMH, and underscores the importance of reassessing the timing and environmental context of the dispersal of modern humans out of Africa.

Human induced pluripotent stem cells: A disruptive innovation.

This year (2016) will mark the 10th anniversary of the discovery of induced pluripotent stem cells (iPSCs). The finding that the transient expression of four transcription factors can radically remodel the epigenome, transcriptome and metabolome of differentiated cells and reprogram them into pluripotent stem cells has been a major and groundbreaking technological innovation. In this review, we discuss the major applications of this technology that we have grouped in nine categories: a model to study cell fate control; a model to study pluripotency; a model to study human development; a model to study human tissue and organ physiology; a model to study genetic diseases in a dish; a tool for cell rejuvenation; a source of cells for drug screening; a source of cells for regenerative medicine; a tool for the production of human organs in animals.

Assessment of N and P status at the landscape scale using environmental models and measurements.

We assessed the compliance of a Dutch landscape, dominated by dairy farming, with environmental quality standards using a combination of model calculations and measurements. The total ammonia emission of 2.4 kton NH(3) yr(-1) does not exceed the environmental quality standard (2.6 kton NH(3) yr(-1)). Nevertheless, the total N deposition (on average 24.4 kg N ha(-1) yr(-1)) is such that critical N loads are exceeded at 53% of the nature areas. The deposited N mainly results from non-agricultural sources and agricultural sources outside the area (72%). The calculated average NO(3)(-) concentration in the upper groundwater does not exceed the 50 mg l(-1) threshold. Calculated annual average N-total and P-total concentrations in discharge water are relatively high but these cannot be directly compared with thresholds for surface water. The results suggest that compliance monitoring at the landscape scale needs to include source indicators and cannot be based on state indicators alone.

Impact of inspiratory muscle training in patients with COPD: what is the evidence?

A meta-analysis including 32 randomised controlled trials on the effects of inspiratory muscle training (IMT) in chronic obstructive pulmonary disease (COPD) patients was performed. Overall and subgroup analyses with respect to training modality (strength or endurance training, added to general exercise training) and patient characteristics were performed. Significant improvements were found in maximal inspiratory muscle strength (P(I,max); +13 cmH2O), endurance time (+261 s), 6- or 12-min walking distance (+32 and +85 m respectively) and quality of life (+3.8 units). Dyspnoea was significantly reduced (Borg score -0.9 point; Transitional Dyspnoea Index +2.8 units). Endurance exercise capacity tended to improve, while no effects on maximal exercise capacity were found. Respiratory muscle endurance training revealed no significant effect on P(I,max), functional exercise capacity and dyspnoea. IMT added to a general exercise programme improved P(I,max) significantly, while functional exercise capacity tended to increase in patients with inspiratory muscle weakness (P(I,max) <60 cmH2O). IMT improves inspiratory muscle strength and endurance, functional exercise capacity, dyspnoea and quality of life. Inspiratory muscle endurance training was shown to be less effective than respiratory muscle strength training. In patients with inspiratory muscle weakness, the addition of IMT to a general exercise training program improved P(I,max) and tended to improve exercise performance.

A whole-farm strategy to reduce environmental impacts of nitrogen.

Dutch regulations for ammonia emission require farmers to inject slurry into the soil (shallow) or to apply it in narrow bands at the surface. For one commercial dairy farm in the Netherlands it was hypothesized that its alternative farming strategy, including low-protein feeding and surface spreading, could be an equally effective tool for ammonia emission abatement. The overall objective of the research was to investigate how management at this farm is related to nitrogen (N) losses to the environment, including groundwater and surface water. Gaseous emission of ammonia and greenhouse gasses from the naturally ventilated stables were 8.1 and 3.1 kg yr(-1) AU(-1) on average using the internal tracer (SF(6))-ratio method. Measurements on volatilization of ammonia from slurry application to the field using an integrated horizontal flux method and the micrometeorological mass balance method yielded relatively low values of ammonia emissions per ha (3.5-10.9 kg NH(3)-N ha(-1)). The mean nitrate concentration in the upper ground water was 6.7 mg L(-1) for 2004 and 3.0 mg L(-1) for 2005, and the half-year summer means of N in surface water were 2.3 mg N L(-1) and 3.4 mg N L(-1) for 2004 and 2005, respectively. Using a nutrient budget model for this farm, partly based on these findings, it was found that the calculated ammonia loss per ton milk (range 5.3-7.5 kg N Mg(-1)) is comparable with the estimated ammonia loss of a conventional farm that applies animal slurry using prescribed technologies.

Polyunsaturated fatty acids of the n-3 class in chronic dialysis.

N-3 PUFAs are believed to 1) reduce serum lipids, 2) modify the complement activating system, 3) increase red blood cell elasticity, and 4) decrease thrombotic events. These four parameters were investigated in 19 chronic stabilized dialysis patients assessed by 1) the control of the serum lipids, 2) the degree of leukopenia 10 minutes after the start of dialysis, 3) the degree of red cell fragmentation (RCF) during dialysis, and 4) the reusability of the dialyzer. The patients were their own controls during four periods: 1) no PUFAs for longer than 6 months, 2) 4 x 425 mg of PUFAs/day for 6 weeks, 3) 6 x 425 mg PUFAs/day for 6 weeks, and 4) no PUFAs during at least 6 weeks. Previous diets and medications remained unchanged. It was concluded that there was no significant effect on serum lipids in the given dosages, and no effect on the degree of leukopenia, red blood cell elasticity or bleeding, and/or antithrombotic activity. No change was seen in insulinemia, fibrinogenemia, or arterial pressure. No serious side effects were noted other than a "fishy aftertaste."