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On 30 December 2019, the Program for Monitoring Emerging Diseases notified the world about a pneumonia of unknown cause in Wuhan, China. Since then, scientists have made remarkable progress in understanding the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its transmission, pathogenesis, and mitigation by vaccines, therapeutics, and non-pharmaceutical interventions. Yet more investigation is still needed to determine the origin of the pandemic. Theories of accidental release from a lab and zoonotic spillover both remain viable. Knowing how COVID-19 emerged is critical for informing global strategies to mitigate the risk of future outbreaks.

Present-day people from England and Wales harbour more ancestry derived from Early European Farmers (EEF) than people of the Early Bronze Age. To understand this, we generated genome-wide data from 793 individuals, increasing data from the Middle to Late Bronze and Iron Age in Britain by 12-fold, and Western and Central Europe by 3.5-fold. Between 1000 and 875 BC, EEF ancestry increased in southern Britain (England and Wales) but not northern Britain (Scotland) due to incorporation of migrants who arrived at this time and over previous centuries, and who were genetically most similar to ancient individuals from France. These migrants contributed about half the ancestry of Iron Age people of England and Wales, thereby creating a plausible vector for the spread of early Celtic languages into Britain. These patterns are part of a broader trend of EEF ancestry becoming more similar across central and western Europe in the Middle to Late Bronze Age, coincident with archaeological evidence of intensified cultural exchange2–6. There was comparatively less gene flow from continental Europe during the Iron Age, and Britain’s independent genetic trajectory is also reflected in the rise of the allele conferring lactase persistence to ~50% by this time compared to ~7% in central Europe where it rose rapidly in frequency only a millennium later. This suggests that dairy products were used in qualitatively different ways in Britain and in central Europe over this period.

Objectives: To estimate the economic efficiency of tight blood pressure control, with angiotensin converting enzyme inhibitors or beta blockers, compared with less tight control in hypertensive patients with type 2 diabetes. Design: Cost effectiveness analysis incorporating within trial analysis and estimation of impact on life expectancy through use of the within trial hazards of reaching a defined clinical end point. Use of resources driven by trial protocol and use of resources in standard clinical practice were both considered. Setting: 20 hospital based clinics in England, Scotland, and Northern Ireland. Subjects: 1148 hypertensive patients with type 2 diabetes from UK prospective diabetes study randomised to tight control of blood pressure (n=758) or less tight control (n=390). Main outcome measure: Cost effectiveness ratios based on (a) use of healthcare resources associated with tight control and less tight control and treatment of complications and (b) within trial time free from diabetes related end points, and life years gained. Results: Based on use of resources driven by trial protocol, the incremental cost effectiveness of tight control compared with less tight control was cost saving. Based on use of resources in standard clinical practice, incremental cost per extra year free from end points amounted to £1049 (costs and effects discounted at 6% per year) and £434 (costs discounted at 6% per year and effects not discounted). The incremental cost per life year gained was £720 (costs and effects discounted at 6% per year) and £291 (costs discounted at 6% per year and effects not discounted). Conclusions: Tight control of blood pressure in hypertensive patients with type 2 diabetes substantially reduced the cost of complications, increased the interval without complications and survival, and had a cost effectiveness ratio that compares favourably with many accepted healthcare programmes.

Nocturnal sleep was recorded prior to daytime testing that included the Multiple Sleep Latency Test, profile of mood states, card sorting, and Stanford Sleepiness Scale in 138 volunteers with the complaint of chronic insomnia and 89 noncomplaining sleepers ("normals"). In both groups daytime sleep tendency had no significant linear correlation either with any Minnesota Multiphasic Personality Inventory scale or with tension/anxiety and other moods assessed in the morning. In normals, speed of card sorting but not subjective sleepiness tended to correlate with sleep tendency. Given that physiological sleepiness is the most predictable consequence of sleep deprivation in normals, it is particularly interesting that 14% of the insomniac group are chronic insomniacs with no measurable daytime sleep tendency. Despite this lack of sleep tendency during the day, their nocturnal sleep was just as poor as insomniacs with greater daytime sleep tendency. The lack of daytime sleepiness seen in this subgroup may reflect a basic pathophysiological aspect of their insomnia.

Fluorescent labeling was seen in rat brain after injections of 10 μ1 of 10% bisbenzimide into the posterior chamber of the eye. Small and spindle shaped fluorescent nuclei were seen in the ipsilateral optic nerve, chiasm and contralateral optic tract, while larger apparently neuronal nuclei were seen in regions such as the lateral geniculate and superior colliculus where the retinal projection terminates. These experiments suggest that, like radioactive compounds, fluorescent dyes undergo anterograde and transcellular transport following large injections. Although limited by sensitivity and the large injection volumes required, this anterograde transport and transcellular transfer of bisbenzimide may be useful in identifying cell populations near the terminal projections of specific neuronal pathways.

Although it has previously been shown that Neanderthals contributed DNA to modern humans(1,2), not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA(3) and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA(3–5). Here we use hypochlorite treatment(6) of as little as 9 mg of bone or tooth powder to generate between 1- and 2.7-fold genomic coverage of five Neanderthals who lived around 39,000 to 47,000 years ago (that is, late Neanderthals), thereby doubling the number of Neanderthals for which genome sequences are available. Genetic similarity among late Neanderthals is well predicted by their geographical location, and comparison to the genome of an older Neanderthal from the Caucasus(2,7) indicates that a population turnover is likely to have occurred, either in the Caucasus or throughout Europe, towards the end of Neanderthal history. We find that the bulk of Neanderthal gene flow into early modern humans originated from one or more source populations that diverged from the Neanderthals that were studied here at least 70,000 years ago, but after they split from a previously sequenced Neanderthal from Siberia(2) around 150,000 years ago. Although four of the Neanderthals studied here post-date the putative arrival of early modern humans into Europe, we do not detect any recent gene flow from early modern humans in their ancestry.

8 páginas, 4 figuras, 1 tabla.-- Artículo Open Access.-- et al., Using DNA extracted from a finger bone found in Denisova Cave in southern Siberia, we have sequenced the genome of an archaic hominin to about 1.9-fold coverage. This individual is from a group that shares a common origin with Neanderthals. This population was not involved in the putative gene flow from Neanderthals into Eurasians; however, the data suggest that it contributed 4–6% of its genetic material to the genomes of present-day Melanesians. We designate this hominin population ‘Denisovans’ and suggest that it may have been widespread in Asia during the Late Pleistocene epoch. A tooth found in Denisova Cave carries a mitochondrial genome highly similar to that of the finger bone. This tooth shares no derived morphological features with Neanderthals or modern humans, further indicating that Denisovans have an evolutionary history distinct from Neanderthals and modern humans., The Presidential Innovation Fund of the Max Planck Society and the Krekeler Foundation provided financial support. M.S. was supported by a US National Institutes of Health grant (R01-GM40282). The National Science Foundation provided an International Postdoctoral Fellowship (OISE-0754461) to J.M.G., a Fellowship in Biological Informatics to P.L.F.J. and a HOMINID grant (1032255) to D.R.