On what scale can we predict the agronomic onset of the West African Monsoon?

Accurate prediction of the commencement of local rainfall over West Africa can provide vital information for local stakeholders and regional planners. However, in comparison with analysis of the regional onset of the West African Monsoon, the spatial variability of the local monsoon onset has not been extensively explored. One of the main reasons behind the lack of local onset forecast analysis is the spatial noisiness of local rainfall. A new method that evaluates the spatial scale at which local onsets are coherent across West Africa is presented. This new method can be thought of as analogous to a regional signal against local noise analysis of onset. This method highlights regions where local onsets exhibit a quantifiable degree of spatial consistency (denoted local onset regions or LORs). It is found that local onsets exhibit a useful amount of spatial agreement, with LORs apparent across the entire studied domain; this is in contrast to previously found results. Identifying local onset regions and understanding their variability can provide important insight into the spatial limit of monsoon predictability. Whilst local onset regions can be found over West Africa, their size is much smaller than the scale found for seasonal rainfall homogeneity. A potential use of local onset regions is presented that shows the link between the annual Inter-Tropical Front progression and local agronomic onset

What Drives the Intensification of Mesoscale Convective Systems over the West African Sahel under Climate Change?

Extreme rainfall is expected to increase under climate change, carrying potential socioeconomic risks. However, the magnitude of increase is uncertain. Over recent decades, extreme storms over the West African Sahel have increased in frequency, with increased vertical wind shear shown to be a cause. Drier midlevels, stronger cold pools, and increased storm organization have also been observed. Global models do not capture the potential effects of lower- to midtropospheric wind shear or cold pools on storm organization since they parameterize convection. Here we use the first convection-permitting simulations of African climate change to understand how changes in thermodynamics and storm dynamics affect future extreme Sahelian rainfall. The model, which simulates warming associated with representative concentration pathway 8.5 (RCP8.5) until the end of the twenty-first century, projects a 28% increase of the extreme rain rate of MCSs. The Sahel moisture change on average follows Clausius–Clapeyron scaling, but has regional heterogeneity. Rain rates scale with the product of time-of-storm total column water (TCW) and in-storm vertical velocity. Additionally, prestorm wind shear and convective available potential energy both modulate in-storm vertical velocity. Although wind shear affects cloud-top temperatures within our model, it has no direct correlation with precipitation rates. In our model, projected future increase in TCW is the primary explanation for increased rain rates. Finally, although colder cold pools are modeled in the future climate, we see no significant change in near-surface winds, highlighting avenues for future research on convection-permitting modeling of storm dynamics

Neo-Aristotelian Naturalism and the Evolutionary Objection: Rethinking the Relevance of Empirical Science

Neo-Aristotelian metaethical naturalism is a modern attempt at naturalizing ethics using ideas from Aristotle’s teleological metaphysics. Proponents of this view argue that moral virtue in human beings is an instance of natural goodness, a kind of goodness supposedly also found in the realm of non-human living things. Many critics question whether neo-Aristotelian naturalism is tenable in light of modern evolutionary biology. Two influential lines of objection have appealed to an evolutionary understanding of human nature and natural teleology to argue against this view. In this paper, I offer a reconstruction of these two seemingly different lines of objection as raising instances of the same dilemma, giving neo-Aristotelians a choice between contradicting our considered moral judgment and abandoning metaethical naturalism. I argue that resolving the dilemma requires showing a particular kind of continuity between the norms of moral virtue and norms that are necessary for understanding non-human living things. I also argue that in order to show such a continuity, neo-Aristotelians need to revise the relationship they adopt with empirical science and acknowledge that the latter is relevant to assessing their central commitments regarding living things. Finally, I argue that to move this debate forward, both neo-Aristotelians and their critics should pay attention to recent work on the concept of organism in evolutionary and developmental biology

Total versus partial knee replacement in patients with medial compartment knee osteoarthritis : the TOPKAT RCT

Article history The research reported in this issue of the journal was funded by the HTA programme as project number 08/14/08. The contractual start date was in January 2010. The draft report began editorial review in February 2019 and was accepted for publication in October 2019. The authors have been wholly responsible for all data collection, analysis and interpretation, and for writing up their work. The HTA editors and publisher have tried to ensure the accuracy of the authors’ report and would like to thank the reviewers for their constructive comments on the draft document. However, they do not accept liability for damages or losses arising from material published in this report. Acknowledgements TOPKAT study group Chief investigator David Beard. Trial co-investigators Nigel Arden (Oxford), Helen Campbell (Oxford), Marion Campbell (Aberdeen), Andrew Carr (Oxford), Jonathan Cook (Aberdeen then Oxford), Helen Doll (Oxford), Ray Fitzpatrick (Oxford), David Murray (Oxford) and Andrew Price (Oxford). Trial management Mayret Castillo (until 2011), Cushla Cooper, Loretta Davies, Anne Duncan (until 2017), Gordon Fernie, Sophie Halpin (until 2015) and Alison McDonald. Trial administration Katie Chegwin, Jiyang Li (until 2018), Elena Rabaiotti (until 2013), Sandra Regan (until 2012) and Victoria Stalker (until 2014). Data management Diana Collins (until 2013), Janice Cruden, Akiko Greshon, Kay Holland and Beverley Smith (until 2017). Database/programming management Gladys McPherson. Trial statisticians Charles Boachie (until 2013), Jemma Hudson and Graeme MacLennan. Health economists Helen Campbell (until 2015), Francesco Fusco (until 2018), Seamus Kent and Jose Leal. We would also like to thank Hannah Wilson (DPhil student, University of Oxford) for her help with the update to the literature search. Research teams We are grateful to the participants and research teams at collaborating hospital sites: Aneurin Bevan University Health Board, Royal Gwent Hospital Ruth Jenkins, Mark Lewis [principal investigator (PI)] and Witek Mintowt-Czyz. Belfast Health and Social Care Trust, Musgrove Park Hospital, Belfast David Beverland (PI), Leeann Bryce, Julie Catney, Ian Dobie, Emer Doran and Seamus O’Brien. Chesterfield Royal Hospital NHS Foundation Trust Fazal Ali, Heather Cripps, Amanda Whileman, Phil Williams (PI) and Julie Toms. County Durham and Darlington NHS Foundation Trust Ellen Brown, Gillian Horner, Andrew Jennings (PI) and Glynis Rose. East Lancashire Hospitals NHS Trust, Royal Blackburn Hospital Frances Bamford, Wendy Goddard, Hans Marynissen (PI), Haleh Peel and Lyndsey Richards. Great Western Hospitals NHS Foundation Trust, Swindon Amanda Bell, Sunny Deo, Sarah Grayland, David Hollinghurst, Suzannah Pegler, Venkat Satish (PI) and Claire Woodruffe. Harrogate and District NHS Foundation Trust, Harrogate Nick London (PI), David Duffy, Caroline Bennett and James Featherstone. Hull and East Yorkshire Hospitals NHS Trust Joss Cook, Kim Dearnley, Nagarajan Muthukumar (PI), Laura Onuoha and Sarah Wilson. Maidstone and Tunbridge Wells NHS Trust, Medway Sandhu Banher, Eunice Emeakaroha, Jamie Horohan, Sunil Jain (PI) and Susan Thompson. Mid Yorkshire Hospitals NHS Trust Sarah Buckley, Aaron Ng (PI), Ajit Shetty and Karen Simeson. Milton Keynes University Hospital NHS Foundation Trust Julian Flynn, Meryl Newsom, Cheryl Padilla-Harris and Oliver Pearce (PI). NHS Grampian, Woodend Hospital, Aberdeen James Bidwell (PI), Alison Innes, Winifred Culley and Bill Ledingham and Janis Stephen. North Bristol NHS Trust Rachel Bray, Hywel Davies, Debbie Delgado, Jonathan Eldridge, Leigh Morrison, James Murray (PI), Andrew Porteous and James Robinson. North Cumbria University Hospitals NHS Trust, Carlisle Matt Dawson (PI), Raj Dharmarajan, David Elson, Will Hage, Nicci Kelsall and Mike Orr. North Tees and Hartlepool NHS Foundation Trust, Stockton-On-Tees Jackie Grosvenor, SS Maheswaran (PI), Claire McCue, Hemanth Venkatesh, Michelle Wild and Deborah Wilson. Oxford University Hospitals NHS Trust, Nuffield Orthopaedic Centre Chris Dodd, William Jackson (PI), Pam Lovegrove, David Murray, Jennifer Piper and Andrew Price. Royal United Hospitals Bath NHS Foundation Trust, Bath Neil Bradbury, Lucy Clark, Stefanie Duncan, Genevieve Simpson and Allister Trezies (PI). Sherwood Forest Hospitals NHS Foundation Trust, Kings Mill Hospital, Sutton in Ashfield Vikram Desai (PI), Cheryl Heeley, Kramer Guy and Rosalyn Jackson. South Devon Healthcare NHS Foundation Trust, Torbay Alan Hall, Gordon Higgins (PI), Michael Hockings, David Isaac and Pauline Mercer. Stockport NHS Foundation Trust, Stockport Lindsey Barber, Helen Cochrane, Janette Curtis, Julie Grindey, David Johnson (PI), and Phil Turner. The Hillingdon Hospitals NHS Trust David Houlihan-Burne (PI), Briony Hill, Ron Langstaff and Mariam Nasseri. The Ipswich Hospital NHS Trust, Ipswich Mark Bowditch, Chris Martin, Steven Pryke, Bally Purewal, Chris Servant (PI), Sheeba Suresh and Claire Tricker. University Hospitals of Leicester NHS Trust, Leicester Robert Ashford, Manjit Attwal, Jeanette Bunga, Urjit Chatterji, Susan Cockburn, Colin Esler (PI), Steven Godsiff, Tim Green, Christina Haines and Subash Tandon. University Hospitals of North Midlands NHS Trust, Stoke on Trent Racquel Carpio, Sarah Griffiths, Natalie Grocott and Ian dos Remedios (PI). University Hospital Southampton NHS Foundation Trust David Barrett, Phil Chapman-Sheath, Caroline Grabau, Jane Moghul, William Tice (PI) and Catherine Trevithick. United Lincolnshire Hospitals NHS Trust, Boston Rajiv Deshmukh, Mandy Howes, Kimberley Netherton, Dipak Raj (PI) and Nikki Travis. United Lincolnshire Hospitals NHS Trust, Lincoln Mohammad Maqsood, Rebecca Norton, Farzana Rashid, Alison Raynor, Mark Rowsell and Karen Warner. We would like to thank the external members of the TSC and DMC for their advice and support for the project. Trial Steering Committee Donna Dodwell as our patient representative, Simon Donell (chairperson) (University of East Anglia), Shawn Tavares (Royal Berkshire Hospital) and Jonathan Waite (South Warwickshire NHS Foundation Trust). Data Monitoring Committee Karen Barker (Oxford University Hospitals NHS Foundation Trust), Gordon Murray (chairperson) (University of Edinburgh) and Hamish Simpson (University of Edinburgh). Independent review and interpretation of results Professor David Torgerson (University of York). Professor Chris Maher (University of Sydney). Mr Peter Brownson (The Royal Liverpool and Broadgreen University Hospitals NHS Trust). Professor Simon Donell (University of East Anglia, Norwich). Mr Mark Mullins (Abertawe Bro Morgannwg University Health Board). Professor Jane Blazeby (Bristol University).Peer reviewedPublisher PD

How a typical West African day in the future-climate compares with current-climate conditions in a convection-permitting and parameterised convection climate model

Current-climate precipitation and temperature extremes have been identified by decision makers in West Africa as among the more impactful weather events causing lasting socioeconomic damage. In this article, we use a plausible future-climate scenario (RCP8.5) for the end of the twenty-first century to explore the relative commonness of such extremes under global warming. The analysis presented considers what a typical day in the future climate will feel like relative to current extrema. Across much of West Africa, we see that the typical future-climate day has maximum and minimum temperatures greater than 99.5% of currently experienced values. This finding exists for most months but is particularly pronounced during the Boreal spring and summer. The typical future precipitation event has a daily rainfall rate greater than 95% of current storms. These findings exist in both a future scenario model run with and without parameterised convection, and for many of the Coupled Model Inter-comparison Project version 5 ensemble members. Additionally, agronomic monsoon onset is projected to occur later and have greater inter-annual variability in the future. Our findings suggest far more extreme conditions in future climate over West Africa. The projected changes in temperature and precipitation could have serious socioeconomic implications, stressing the need for effective mitigation given the potential lack of adaptation pathways available to decision makers

Dysfunction of NaV1.4, a skeletal muscle voltage-gated sodium channel, in sudden infant death syndrome: a case-control study.

BACKGROUND: Sudden infant death syndrome (SIDS) is the leading cause of post-neonatal infant death in high-income countries. Central respiratory system dysfunction seems to contribute to these deaths. Excitation that drives contraction of skeletal respiratory muscles is controlled by the sodium channel NaV1.4, which is encoded by the gene SCN4A. Variants in NaV1.4 that directly alter skeletal muscle excitability can cause myotonia, periodic paralysis, congenital myopathy, and myasthenic syndrome. SCN4A variants have also been found in infants with life-threatening apnoea and laryngospasm. We therefore hypothesised that rare, functionally disruptive SCN4A variants might be over-represented in infants who died from SIDS. METHODS: We did a case-control study, including two consecutive cohorts that included 278 SIDS cases of European ancestry and 729 ethnically matched controls without a history of cardiovascular, respiratory, or neurological disease. We compared the frequency of rare variants in SCN4A between groups (minor allele frequency <0·00005 in the Exome Aggregation Consortium). We assessed biophysical characterisation of the variant channels using a heterologous expression system. FINDINGS: Four (1·4%) of the 278 infants in the SIDS cohort had a rare functionally disruptive SCN4A variant compared with none (0%) of 729 ethnically matched controls (p=0·0057). INTERPRETATION: Rare SCN4A variants that directly alter NaV1.4 function occur in infants who had died from SIDS. These variants are predicted to significantly alter muscle membrane excitability and compromise respiratory and laryngeal function. These findings indicate that dysfunction of muscle sodium channels is a potentially modifiable risk factor in a subset of infant sudden deaths. FUNDING: UK Medical Research Council, the Wellcome Trust, National Institute for Health Research, the British Heart Foundation, Biotronik, Cardiac Risk in the Young, Higher Education Funding Council for England, Dravet Syndrome UK, the Epilepsy Society, the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health, and the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program

Experimental evolution of sperm competitiveness in a mammal

<p>Abstract</p> <p>Background</p> <p>When females mate with multiple partners, sperm from rival males compete to fertilise the ova. Studies of experimental evolution have proven the selective action of sperm competition on male reproductive traits. However, while reproductive traits may evolve in response to sperm competition, this does not necessarily provide evidence that sperm competitive ability responds to selection. Indeed, a study of <it>Drosophila </it>failed to observe divergence in sperm competitive ability of males in lines selected for enhanced sperm offence and defence.</p> <p>Results</p> <p>Adopting the naturally polygamous house mouse (<it>Mus domesticus</it>) as our vertebrate model, we performed an experimental evolution study and observed genetic divergence in sperm quality; males from the polygamous selection lines produced ejaculates with increased sperm numbers and greater sperm motility compared to males from the monogamous lines. Here, after 12 generations of experimental evolution, we conducted competitive matings between males from lineages evolving under sperm competition and males from lineages subject to relaxed selection. We reduced variation in paternity arising from embryo mortality by genotyping embryos <it>in utero </it>at 14 days gestation. Our microsatellite data revealed a significant paternity bias toward males that evolved under the selective regime of sperm competition.</p> <p>Conclusion</p> <p>We provide evidence that the sperm competitiveness phenotype can respond to selection, and show that improved sperm quality translates to greater competitive fertilisation success in house mice.</p