We consider the dynamics of an Boussinesq approximation Benard convection uid evolving in a three-dimensional domain bounded below by a xed atten boundary and above by a free moving surface. The domain is horizontally periodic and the eect of the surface tension is neglected on the free surface. By developing a priori estimates for the model, we prove the global existence and almost exponential decay of solutions in the framework of high regularity.

A fetus harboring a duplication of SMAD2 exons 1-6 presented with dextrocardia and pulmonary hypoplasia. Mate-pair sequencing revealed the duplication to be in inverted tandem orientation to the wild-type SMAD2 allele, disrupting its sequence and decreasing expression. These observations suggest SMAD2 to be responsible for the fetal dextrocardia.

In this paper, motivated by Kamran et al. [Mathematics, 5(19), (2017), 7 pages] we introduce the notion of parametric $(b, \theta)$-metric space as an extended form of parametric $b$-metric space, which was introduced by Hussain et al.[J. Nonlinear Sci. Appl., 8 (2015), 719–739] and improve the results of Alsulami et al.[Abstract and Applied Analysis, (2014), Article ID 187031, 10 pages] and others in such space. We also apply our result to establish an existence of solution of integral equation.

Based on a data-driven selection of an estimator from a fixed family of kernel estimators, Goldenshluger \& Lepski (2014) considered the problem of adaptive minimax un-compactly supported density estimation on $\mathbb{R}^{d}$ with $L^{p}$ risk over Nikol’skii classes. This paper shows the same convergence rates by using a data-driven wavelet estimator over Besov spaces, because the wavelet estimations provide more local information and fast algorithm. Moreover, we provide better convergence rates under the independence hypothesis, which reduces the dimension disaster effectively.

A. R. MacKenzie1,2,*, S. Krause1,2, K. M. Hart1, R. M. Thomas1,3, P. J. Blaen1,4, R.L. Hamilton1,2, G. Curioni1,2, S. E. Quick1,2, A. Kourmouli1,2, D. M. Hannah1,2, S. A. Comer-Warner1,2, N. Brekenfeld1,2, S. Ullah1,2 and M. C. Press1,51. Birmingham Institute of Forest Research, University of Birmingham, Birmingham B15 2TT, UK2. School of Geography, Earth and Environmental Science, University of Birmingham, Birmingham B15 2TT, UK3. Now at Big Sky Science Ltd, Sutton Coldfield, West Midlands, B72 1SY, UK4. Now at Yorkshire Water, Chadwick Street, Leeds, LS10 1LJ, UK5. Now at Manchester Metropolitan University, Manchester, M15 6BH, UK* Corresponding author:a.r.mackenzie@bham.ac.ukKeywordsSoil moisture; stream metabolism; climate change; long-term monitoringSummary Paragraph The ecosystem services provided by forests modulate runoff generation processes, nutrient cycling and water and energy exchange between soils, vegetation and atmosphere. Increasing atmospheric CO2affects many linked aspects of forest and catchment function in ways we do not adequately understand. Most significantly, global levels of atmospheric CO2 will be around 40% higher in 2050 than current levels, yet estimates of how water and solute fluxes in forested catchments will respond to increased CO2 are highly uncertain. The Free Air Carbon Enrichment (FACE) facility of the University of Birmingham’s Institute of Forest Research (BIFoR) is an intensively monitored forest site specialising in fundamental studies of the response of whole ecosystem patches of mature, deciduous, temperate woodland to elevated CO2. Here, we introduce the facility, situated in a mixed land-use headwater catchment, with a particular focus on its environmental setting and the experimental infrastructure. The facility offers a significant opportunity to advance multi- and interdisciplinary understanding at the interfaces of soil, vegetation, hydrosphere and atmosphere under changed atmospheric composition.Site Description and MethodsThis summary complements online introductory videos (https://tinyurl.com/y3a2hkkx) and draws on the facility ‘White Book’, which is a live web-document containing extensive details of all the projects undertaken at the facility and details of instrument placement (heights, depths, spatial separation).The Wood Brook catchment and FACE facilityThe BIFoR FACE facility is situated in a mainly agricultural headwater catchment in the UK drained by the Wood Brook, and consists of the main elevated CO2 (eCO2) facility and a number of spatially nested satellite study sites including various forest plantations of different age and management (Figure 1). The facility is in lowland, rural, central England (52o48’ 3.6” N, 2o 18’ 0” W, 106 m above mean sea level (amsl)), within a patchy landscape typical of most temperate forest settings (Haddad et al., 2015). Wood Brook is a second-order stream with a 3.1 km² catchment ranging in elevation from 90 to 150 m amsl (Blaen et al., 2017) and subsequently draining into the River Severn catchment (the most voluminous river in England and Wales). The entire catchment is experiencing drastic land-use changes, having been converted to organic farming since 2019 and herbal lays in replacement of what was previously grass monoculture or arable, in addition to the new forest plantations.[Figure 1 here]The BIFoR FACE forest at the bottom of the Wood Brook catchment is a mature deciduous woodland, with dominant (25-m tall) English oak (Quercus robur ) planted around 1850. Sub-dominant (ca. 10 m tall) species consist of common hazel (Corylus avellana ), common hawthorn (Crataegus monogyna ), sycamore maple (Acer pseudoplatanus ) and other native species (Hart et al., 2019). Each stem with diameter-at-breast-height greater than 10 cm has been geolocated and tagged. Centimetre-scale forest structure was measured by a lidar overflight in August 2014 and by terrestrial laser scanning (private communication, Eric Casella, Forest Research, Surrey, UK); this structure establishes the basis for penetration of air, light, and water into the forest canopy.The central, eCO2 component of BIFoR FACE consists of nine experimental patches of 15 m radius (Hart et al., 2019). Three ‘undisturbed’ (or ‘ghost’) patches have no CO2-dosing infrastructure; three ‘control’ patches are exposed to ambient CO2 concentrations delivered via the same infrastructure used in the three ‘treatment’ patches to maintain +150 ppmv above ambient CO2 at all levels of the canopy. Elevated CO2 is maintained during daylight hours from oak bud burst (ca. 1st April) to last leaf fall (ca. 31st October). The CO2-dosing system works well; one-minute running means are within 15% of target in the treatment plots, with less than 1% of the time showing deviation above 10% of the baseline value in the control plots (Hart et al., 2019). The first season with eCO2 was 2017 and the treatment will continue until at least 2026. A parallel study of the effect of nitrogen and phosphorus addition began in 2020 in the forest away from the FACE patches.Surrounding the BIFoR FACE, the Wood Brook catchment hosts several long-term forest hydrological observatories. In partnership with the estate owners, young mixed-deciduous plantations are subjected to different manipulation treatment including irrigation and fertilisation experiments.The environmental contextThe climate at the Wood Brook catchment is that of the temperate maritime zone of north-west Europe (Barry and Chorley, 2010). The site-mean annual temperature (MAT) measured between 2016 and 2019 was 10.6 ± 0.8 oC and its mean annual precipitation (MAP) was 676 ± 66 mm. This situates BIFoR FACE well inside the MAT-MAP climate space for temperate forests (Sommerfeld et al., 2018). The catchment is within the area covered by the Central England Temperature record, which provides a time series back to 1772 (Parker et al., 1992).The Wood Brook catchment is situated in a Nitrate Vulnerable Zone (European Union Directive 91/676/EEC) with mean nitrate concentrations in the Wood Brook ranging from 5 to 7 mg N l-1 (Blaen et al., 2017). The contemporary reactive nitrogen deposition from the atmosphere in the catchment is ~22 kg N ha-1 y-1 with an ammonium to nitrate deposition ratio of 7:3 (private communication, S. Tomlinson, UK Centre for Ecology & Hydrology). Deposition of this scale represents less than about 15% of the total nitrogen nutrition of temperate deciduous forest trees (Rennenberg and Dannenmann, 2015).Site infrastructureThe Wood Brook is equipped with two continuous water quality monitoring stations comprising in-stream sensors measuring stage, water temperature, and electrical conductivity continuously (up to every 10 seconds). Sensors to measure further parameters (UV-VIS absorbance, DO, pH, and turbidity) are housed in an insulated kiosk located on the streambank (Blaen et al., 2017a). An ISCO peristaltic pump (Lincoln, NE, USA) passes 1 L of stream water through these sensors every hour. Continuous stream monitoring is supplemented with campaign-based sampling facilitated by networks of surface water ISCO autosamplers, for instance during tracer tests (Blaen et al., 2017a,b), as well as spatially nested multi-level mini-piezometers installed in the streambed to investigate streambed biogeochemical processes and groundwater-surface water interactions (Comer-Warner et al., 2019, Comer-Warner et al., 2020).Soil moisture in the main BIFoR FACE facility is monitored by 12 cm long frequency domain sensors (CS655 by Campbell Scientific, claimed accuracy ± 3 % v/v for ‘typical’ soils) installed diagonally from the surface in groups of three spaced 1 m apart, with two groups in the ’control’ and ’treatment’ patches and one group in the ’ghost’ patches, and monitoring at 15 to 30 min resolution.In addition, one of the juvenile plantations close to the catchment outlet has been instrumented since 2016 with active fibre-optic distributed temperature sensing (FO-DTS) for measuring soil temperature and soil moisture at a submeter spatial resolution, resulting in 1850 soil temperature and soil moisture sampling locations across the site, ranging from 10-40 cm depths (Ciocca et al., 2020). The retrieval from the FO-DTS has a maximum at 38%v/v, a value empirically determined from a soil-specific field calibration against point soil moisture sensors installed adjacent to the fibre-optic cable. The variability shown for the FO-DTS is that for 4 quasi-independent measurements per day at 25 cm intervals along the fibre-optic cable. Uncertainties of ca. 3-5% v/v have been reported for soil moisture measurements with the DTS technique (Gamage et al. 2018).Each treatment (eCO2) and control experimental patch is ringed by 16 free‐standing, climbable, lattice towers that reach 2-3 m above the local oak canopy; a 17th tower is sited in the centre of each patch. The lattice towers are secured by screw piles; the experimental site contains no concrete foundations or guy wires. Access to the experimental patches is via low-level walkways raised approximately 30 cm above ground level to prevent compaction. Canopy access above 5 m is contracted to climbing arborists or achieved using a bespoke canopy access system (CAS) installed from the 17th central tower of each infrastructure array. The CAS is operated by trained staff so that rope access training is not required for researchers. Welfare and simple laboratory facilities are provided. Elevated CO2 dosing, canopy access, and routine monitoring is operated by a team of six technical staff permanently stationed at BIFoR FACE.Four meteorological masts are located at the periphery of the woodland and a 40 m ‘flux tower’ stands towards the downwind end of the wooded area so that its flux ‘footprint’ is within the forest for the prevailing south-westerly winds. During dosing, true biogeochemical CO2 fluxes are, of course, obscured by the gas released to provide the eCO2 treatment effect but sensible and latent heat fluxes are recorded.Figure 2 illustrates the flow of data and tissue samples into their permanent repositories. Other equipment (not shown) is deployed ad hoc within specific projects.[Figure 2 here.]To complement the experimental infrastructure in the Wood Brook catchment and BIFoR FACE facility, an integrated groundwater-surface water model has been developed and validated by a combination of flow signatures and applied to investigate stream and subsurface water and energy balance in response to forest shading (Qiu et al., 2019).Example ResultsSoil moisture dynamics, stream discharge, and water quality in mature forest and young plantationExample core data (precipitation and FACE soil water content, discharge and DO) and project-specific data (field-scale soil moisture measured by FO-DTS at 10 cm) demonstrate the value of long-term integrated monitoring in ecohydrological observatories such as the Wood Brook catchment (Figure 3).The variability of the temperate maritime climate is evident: prolonged wetting and drying events with occasional, shorter, high-intensity rainfall events. Signals can take a long time to emerge within such variability, which is a key argument for a long-term experimental platform such as BIFoR FACE. The time series at this relatively early stage suggests that: (i) the plantation is systematically wetter than the neighbouring FACE forest even though the plantation slopes downwards towards FACE; (ii) there is significant spatial variability in the plantation and FACE forest; and (iii) the eCO2 patches are drier than the aCO2 and undisturbed patches. Point (iii) is a result of spatial variability in the forest; the strength of soil moistening due to eCO2, if any is present (cf. Ellsworth, 1999; Drake et al., 2016), remains to be quantified.Corresponding water levels at the Wood Brook catchment outlet highlight the general “flashiness” of the flow regime with relatively fast responses to precipitation events for a permeable catchment as well as fast recession of flow (Figure 3 bottom). This example time series of one of our monitoring stations also indicates some of the challenges in maintaining consistent quality control throughout long-term observation networks. In addition to data losses induced by power supply failures in Spring 2019, observed values up to early 2019 were an order of magnitude lower than from summer 2019 onwards due to repeated sedimentation of the water level sensor and recurring changes to the channel cross sectional profile that finally led to a relocation of the sensor as indicated in Figure 3. The additional value of continuously monitored water level and water quality data (as highlighted by the example of dissolved oxygen in Fig 3 bottom) extends beyond the ability to observe long-term trends in catchment behaviour in response to land-use changes but also provides opportunity to enhance mechanistic process understanding of in stream metabolism and biogeochemical processing as well as event-based activation of pollution sources (Blaen et al., 2017a).[Figure 3 here.]Data protocol and availabilityAll projects form part of the overall collaborative effort to understand catchment behaviour and forest form and function, and all facility users sign a data protocol to that effect. The BIFoR FACE science community believe and advocate transparency in science, assured through open data after an agreed period of privileged use.The facility is supported by a full-time data manager (author GC), responsible for tracking all data and tissue samples. The data is available upon request; an open data repository for a subset of core data is under construction.The continuous streams of data are handled by a suite of dataloggers and a local LAN network which allows data to be saved on the BIFoR FACE facility server (Figure 2). A back-up server located on site in a separate building stores a daily image of the primary server. Data is transferred daily to the University of Birmingham servers and the raw and processed data (i.e. organised in a consistent format and cleared of evident issues) are stored separately to improve resilience. Non-continuous data collected by researchers is stored in the University of Birmingham servers and handled directly between researchers and the data manager.All tissue is recorded when sampled and a chain-of-custody initiated using Pro-curo. Quenching of biological samples to -70oC is accomplished on-site using a dry shipper (BioTrex-10, Statebourne Cryogenics, Tyne & Wear, UK), avoiding the need for transporting liquid nitrogen. Short-term tissue storage at 5oC and -20 oC can be accommodated on-site, but the permanent tissue bank resides at the University of Birmingham Edgbaston campus.In summary, BIFoR FACE is an ambitious field facility designed primarily to measure the whole-system response of mature temperate forest to elevated CO2, but suitable for a wide range of complementary catchment studies. The facility is highly collaborative in nature and welcomes partners11https://www.birmingham.ac.uk/research/bifor/get-involved/index.aspx who wish to contribute as part of a multidisciplinary Community of Practice.AcknowledgmentsWe very gratefully acknowledge support from the JABBS Trust, Norbury Park Estate, The John Horseman Trust, Ecological Continuity Trust, NERC (grants NE/S015833/1, NE/P003486/1, NE/N020502/1; NE/T000449/1; NE/T012323/1), and the University of Birmingham. The soil moisture FO-DTS system installation was led by Francesco Ciocca while holding joint positions at the University of Birmingham and at Silixa Ltd. (London, UK).The BIFoR FACE facility cannot run without the dedicated support of its operations team (currently; Nicholas Harper, Peter Miles, Thomas Downes, Gael Denny and Robert Grzesik, formerly; Gary McClean and Anna Gardner). Foundational contributions to the design and implementation of the facility were made by Michael Tausz and Sabine Tausz-Posch. The FACE facility eCO2 treatment uses the system designed by John Nagy and installed by Keith Lewin, both of Brookhaven National Lab, USA. We acknowledge the considerable scientific input of visiting fellows (David Ellsworth, Kristine Crous, Debbie Hemming, Rich Norby, Theresa Blume and Mantha Phanikumar) and former researchers (Will Allwood, Alex Poynter, Elizabeth Hamilton). We gratefully acknowledge strategic guidance from BIFoR Directors (Rob Jackson, Jerry Pritchard, and Nicola Spence) and the Science Committee (Christine Foyer, Vincent Gauci, Francis Pope, and Estrella Luna Diez).ReferencesBarry, R. G., and Chorley, R. J. (2010) Atmosphere, Weather and Climate, 9th ed., Routledge, London.Blaen, P., K. Khamis, C. Lloyd, S. Comer-Warner, F. Ciocca, R. M. Thomas, A. R. MacKenzie, Stefan Krause (2017a), High-frequency monitoring of catchment nutrient exports reveals highly variable storm-event responses and dynamic source zone activation, J. Geophys. Res-Biogeosciences, 10.1002/2017JG003904Blaen P., Brekenfeld N., Comer-Warner S., Krause S. (2017b). Multitracer Field Fluorometry: Accounting for Temperature and Turbidity Variability during Stream Tracer Tests. Water Resources Research, 53,https://doi.org/10.1002/2017WR020815.Ciocca F., Abesser C., Findlay J., Chalari A., Mondanos M., Hannah D.M., Blaen P., Krause S. 2020. A Distributed Heat Pulse Sensor Network for Thermo-Hydraulic Monitoring of the Soil Subsurface. Quarterly Journal of Engineering Geology and Hydrogeology. 53. 352-365,https://doi.org/10.1144/qjegh2018-147Comer-Warner S., Ullah S., Kettridge N., Gooddy D., Krause S. (2019). Seasonal variability of sediment controls on carbon cycling in an agricultural stream. Science of the Total Environment. 688, 732-741,https://doi.org/10.1016/j.scitotenv.2019.06.317Comer-Warner, S.A., Gooddy, D.C., Ullah, S., Glover L., Kettridge N., Wrexler S.K., Kaiser J., Krause S. 2020. Seasonal variability of sediment controls of nitrogen cycling in an agricultural stream. Biogeochemistry. 148, 31–48 (2020). https://doi.org/10.1007/s10533-020-00644-zDrake, J.E., Macdonald, C.A., Tjoelker, M.G., Crous, K.Y., Gimeno, T.E., Singh, B.K., Reich, P.B., Anderson, I.C. and Ellsworth, D.S. (2016), Short‐term carbon cycling responses of a mature eucalypt woodland to gradual stepwise enrichment of atmospheric CO2concentration. Glob Change Biol, 22: 380-390. doi:10.1111/gcb.13109Ellsworth, D.S. (1999), CO2 enrichment in a maturing pine forest: are CO2 exchange and water status in the canopy affected?. Plant, Cell & Environment, 22: 461-472. doi:10.1046/j.1365-3040.1999.00433.xGalloway, J.N., Dentener, F.J., Capone, D.G. et al. (2004) Nitrogen Cycles: Past, Present, and Future. Biogeochemistry 70, 153–226. https://doi.org/10.1007/s10533-004-0370-0Gamage, D.N.V., Biswas, A., Strachan, I.B., Adamchuk, V.I. 2018. Soil Water Measurement Using Actively Heated Fiber Optics at Field Scale. Sensors 18 (4): 1116 DOI: 10.3390/s18041116Haddad, N.M., Brudvig, L.A., Clobert, J., Davies, K.F., Gonzalez, A., Holt, R.D., Lovejoy, T.E., Sexton, J.O., Austin, M.P., Collins, C.D., Cook, W.M., Damschen, E.I., Ewers, R.M., Foster, B.L., Jenkins, C.N., King, A.J., Laurance, W.F., Levey, D.J., Margules, C.R., Melbourne, B.A., Nicholls, A.O., Orrock, J.L., Song, D.X., Townshend, J.R., 2015. Habitat fragmentation and its lasting impact on Earth’s ecosystems. Sci. Adv. 1.https://doi.org/10.1126/sciadv.1500052Hart, Kris; Curioni, Giulio; Blaen, Philip; Thomas, Rick; Harper, Nicholas; Miles, Peter; Lewin, Keith; Nagy, John; Bannister, Edward; Cai, Xiaoming ; Krause, Stefan; Tausz, Michael; MacKenzie, A. Robert (2019) Characteristics of Free Air Carbon Dioxide Enrichment of a Northern Temperate Mature Forest. Glob Change Biol. doi:10.1111/gcb.14786Norby, R. J., M. G. De Kauwe, T. F. Domingues, R. A. Duursma, D. S. Ellsworth, D. S. Goll, D. M. Lapola, K. A. Luus, A. R. MacKenzie, B. E. Medlyn, R. Pavlick, A Rammig, B Smith, R Thomas, K Thonicke, A. P. Walker, Xiaojuan Yang, and Sönke Zaehle, Model-data synthesis for the next generation of forest FACE experiments, New Phytologist, 2015, DOI: 10.1111/nph.13593.Parker, D.E., T.P. Legg, and C.K. Folland. 1992. A new daily Central England Temperature Series, 1772-1991. Int. J. Clim., Vol 12, pp. 317-342.Payne, Richard John, Dise, Nancy B., Field, Christopher D et al. (3 more authors) (2017) Nitrogen deposition and plant biodiversity : past, present and future. Frontiers in Ecology and the Environment.https://doi.org/10.1002/fee.1528Qiu, H., Blaen, P., Comer‐Warner, S., Hannah, D. M., Krause, S., & Phanikumar, M. S. 2019. Evaluating a coupled phenology – surface energy balance model to understand stream – subsurface temperature dynamics in a mixed‐use farmland catchment. Water Resources Research, 55.https://doi.org/10.1029/2018WR023644Rennenberg, H., Dannenmann, M. (2015) Nitrogen nutrition of trees and temperate forests – the significance of nitrogen availability in pedosphere and atmosphere. Forests 6, 2820-2835.Sommerfeld, A., Senf, C., Buma, B. et al. (2018) Patterns and drivers of recent disturbances across the temperate forest biome. Nat Commun 9, 4355. https://doi.org/10.1038/s41467-018-06788-9Figure CaptionsFigure 1. (a) BIFoR FACE is located in Mill Haft (white dashed line; lighter patches show locations of the FACE arrays and control patches) in a patchwork of old-growth forest, new forest plantation on arable land, and arable fields. (b) Wood Brook catchment (white dashed line) with the stream running along the northern edge of Mill Haft. (c) Central England location of Mill Haft.Figure 2. A schematic view of the sensor deployment and tissue and data flow through BIFoR FACE and Wood Brook. The main experimental infrastructure elements are shown (left); replicates are indicated by “n = “. Data from electronic sensors are recorded in networked field dataloggers and relayed to the facility server. Back-up is carried out on-site and by daily data download to the main University of Birmingham servers with Retrospect software (Retrospect Inc. USA). Initial quality assurance is under the control of the BIFoR Data Manager (author GC) before data is released to the BIFoR FACE community. A parallel system operates for physical samples, the metadata from which enters the BIFoR FACE database via chain-of-custody software (Pro-curo Software Ltd, West Sussex, UK).Figure 3. a) time series of daily top-of-forest precipitation and soil moisture from distributed temperature sensing (DTS) by fibre-optic cable embedded at 10 cm depth between rows on new broadleaf forest plantation immediately south of the FACE forest (see Figure 1). b) Time series of shallow soil water content from an array of sensors in the FACE forest. The numbers of sensors at each part of the time series are reported in the top of the panel. c) Water level (in blue) and dissolved oxygen (in green) measured on the Wood Brook stream (see Figure 1).

Cockayne syndrome is an ultra-rare autosomal recessive disorder characterized by growth failure and multisystemic degeneration. Excision repair cross-complementation group 6 (ERCC6) mutations account for most cases. We report a child with pre- and post-natal growth failure and progressive neurologic deterioration with multi-system involvement who has bi-allelic ERCC6 variants, that were discovered by whole genome sequencing, including a previously unreported intronic variant. Pathogenicity of these variants was established by demonstrating reduced levels of ERCC6 mRNA and protein expression, normal unscheduled DNA synthesis and impaired recovery of RNA synthesis in patient fibroblasts following UV-irradiation. The study confirms the pathogenicity of a previously undescribed upstream intronic variant, highlighting the power of genome sequencing to identify non-coding variants. In addition, this report provides evidence for the utility of a combination approach of genome sequencing plus functional studies to provide diagnosis in a child for whom a lengthy diagnostic odyssey, including exome sequencing, was previously unrevealing.

The development of computational methods to assess pathogenicity of pre-messenger RNA splicing variants is critical for diagnosis of human disease. We assessed the capability of eight algorithms, and a consensus approach, to prioritize 250 variants of uncertain significance (VUS) that underwent splicing functional analyses. It is the capability of algorithms to differentiate VUSs away from the immediate splice site as ‘pathogenic’ or ‘benign’ that is likely to have the most substantial impact on diagnostic testing. We show that SpliceAI is the best single strategy in this regard, but that combined usage of tools using a weighted approach can increase accuracy further. We incorporated prioritization strategies alongside diagnostic testing for rare disorders. We show that 15% of 2783 referred individuals carry rare variants expected to impact splicing that were not initially identified as ‘pathogenic’ or ‘likely pathogenic’; 1 in 5 of these cases could lead to new or refined diagnoses.

Background: To examine associations between phenotypes of short sleep duration and clinically-assessed health conditions in long-term survivors of childhood cancer. Methods: Survivors recruited from the St. Jude Lifetime Cohort (n=911; 52% female; mean age 34 years; 26 years post-diagnosis) completed behavioral health surveys and underwent comprehensive physical examinations. Sleep was assessed with the Pittsburgh Sleep Quality Index. Short sleep was defined as <7 hours per night with phenotypes of short sleep including poor sleep efficiency (<85%), prolonged sleep onset latency (≥30 minutes), and wake after sleep onset (≥3 times per week). Covariates included childhood cancer treatment exposures, demographics, body mass index, and physical inactivity. Separate modified Poisson regression models were computed for each health category to estimate relative risks (RR) and 95% confidence intervals (CI). Multinomial logistic regression models examined associations between sleep and an aggregated burden of chronic health conditions. Results: Short sleep duration was reported among 44% (95% CI 41%-47%) of survivors. In multivariable models, short sleep duration alone was associated with pulmonary (RR=1.35, 95% CI 1.08-1.69), endocrine (RR=1.22, 95% CI 1.06-1.39) and gastrointestinal/hepatic conditions (RR=1.46, 95% CI 1.18-1.79), and anxiety (RR 3.24, 95% CI 1.64-6.41) and depression (RR=2.33, 95% CI 1.27-4.27). Short sleep with prolonged SOL was associated with a high/severe burden of health conditions (OR=2.35, 95% CI 1.12-4.94). Conclusions: Short sleep duration was associated with multiple clinically-ascertained adverse health conditions. Although the temporality of these associations cannot be determined in this cross-sectional study, sleep is modifiable, and improving sleep may improve long-term health in survivors.

Thermal rate coefficients for the hydrogen abstraction reactions of 3-butenal by hydrogen atom were obtained, for the first time, with the application of the multipath canonical variational theory with small-curvature tunneling (MP-CVT/SCT). Torsional anharmonicity due to the hindered rotors was taken into account with the calculation of the rovibrational partition function using the extended two-dimensional torsional method (E2DT). In contrast with the (E)-2-butenal reactions, the abstraction reactions of 3-butenal proceed via five reaction channels, (R1)–(R5). In the conformational search, 48 distinguishable structures of transition states were found, including enantiomers, and separated into six conformational reaction channels (CRC). The individual reactive paths were constructed, variational and recrossing coefficients estimated, and the multipath rate constants obtained. The torsional anharmonicity is responsible for increased the rate constants for (R2). In the case of (R1), (R3), (R4), and (R5), this effect decreased the velocity of reactions. Compared to the overall (E)-2-butenal + H reaction, the thermal rate constants of this study are faster in a wide range of temperatures. The analysis of the contributions of each conformer of the transition state shows an important contribution of the high energy rotamers in the total flux of (R1)–(R5). After fitting of rate constants in a four-parameters equation, the activation energy estimation shown strong temperature dependence.

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Objective: To assess if maternal hemodynamics assessment in healthy women, at the end of pregnancy, before the labor onset, could predict the development of complications during labor. Design: Prospective observational study. Settings: Department of Obstetrics and Gynecology of Casilino Hospital in Rome, University of Tor Vergata. (September 2016 - December 2017) Population: 395 healthy women not in labor at term of pregnancy. Methods: Univariate and multivariate binary logistic regression analysis of association between hemodynamic variables and delivery complications, adjusted for significant prenatal variables. Main Outcome Measures: ORs for hemodynamic parameters and identification of independent risk factors in the prediction of adverse outcome. Results: we observed adverse outcomes in 45 patients (11.39%). Women who developed maternal or fetal complications during delivery were mainly nulliparous (93.33% vs 72.29%, p<0.01), showed higher values of systemic vascular resistances (SVR) (1368.32±228.50. vs 1260.34±271.94 d.s.cm-5, p=0.01) and lower values of cardiac output (CO) (5.38±0.77 vs 5.80±1.20 L/min, p=0.02), compared with women who did not develop complications. ROC curve analysis identified the best cut-offs to predict complicated delivery: SVR > 1135 d.s.cm-5 (OR 7.87, CI 95% 2.39-25.92, p<0.01), CO ≤5.6 L/min (OR 2.38; CI 95% 1.21-4.68, p<0.01), diastolic blood pressure > 79 mmHg (OR 1.89, CI 95%.1.01-3.54, p=0.04), Potential-Kinetic energy Ratio >22 (OR 2.32, 0.95-5.64, p=0.04). The multivariate logistic regression analysis identified as independent predictors of complication the SVR, Flow Time corrected and parity. Conclusion: the assessment of maternal hemodynamics at term of pregnancy could increase the capacity to predict patients at risk during labor.

Objective: Increasing evidences suggest that oxidative stress is closely related to the pathogenesis of hepatitis C virus (HCV) infection. The purpose of this study was to examine the dynamic thiol/disulfide homeostasis (DTDH) and total oxidant/antioxidant status in patients with HCV infection. Methods: Levels of serum total thiol (TT), native thiol (NT), disulfide (DS), total oxidant status (TOS), total antioxidant status (TAS), and oxidative stress index (OSI; TOS/TAS ratio) as oxidative stress markers were determined in 162 individuals, including 74 patients with HCV infection and 88 non-HCV controls. Results: The NT, TT levels and NT/TT ratio were significantly lower and DS level, DS/NT and DS/TT ratios were significantly higher in HCV group compared to the control group. The TOS and OSI values were significantly higher and the TAS level was significantly lower in the HCV group than in the control group. No significant correlations were found between oxidative stress markers and albumin, alanine aminotransferase, aspartate aminotransferase and bilirubin levels in patients with HCV infection. A negative correlation was found only between OSI and albumin. Conclusion: These results indicate that patients with HCV infection are vulnerable to oxidative stress and have disturbed status of oxidant and antioxidant.

Background: The ongoing acute respiratory disease pandemic termed COVID-19 caused by a newly emerged coronavirus has jeopardized the world’s health and economic sectors. As of July 20, 2020, the virus now known as SARS-CoV-2 has already infected more than 14 million individuals and killed 612,815 patients with a mortality rate of 4.12% around the world regardless of age, gender and race. Main body: Bangladesh has become one of its worst sufferers, with 207,453 infected people and 2,668 related deaths with a mortality rate of 1.29% until July 20, 2020. More than 50% of COVID-19 patients in Bangladesh are aged between 21 and 40 but elderly people aged more than 60 have the highest mortality rate (44.7%). Male individuals are also more susceptible to the virus than females and consist of 71% and 79% among the infected and deceased patients respectively. The most prevalent clinical features following the virus incubation period are fever, fatigue and dry cough. A phylogenetic analysis study elucidated that the virus strain found in the country has 9 single-nucleotide variants, mostly in the ORF1ab gene, and a sequence containing 3 successive variants in the N protein, which reflects a weaker strain of SARS-CoV-2, implicating a possibility of its lower mortality rate. Another investigation of 184 genome samples of SARS-CoV-2 across the country implicated a close homology with a European haplotype of SARS-CoV-2. The country has also joined the race of vaccine development and started phase-III clinical trials of a candidate vaccine developed by Sinovac Research and Development Co Ltd, China. Conclusion: Bangladesh, as a developing country, still struggles with the pandemic and needs to scale up its response operation and improve health care facilities such as testing capacity, institutional quarantine and isolation centers and promote awareness. Preventive measures such as strict lockdown, social distancing and boosting the existing immune system are thus considered the only contrivances.

COVID-19 pandemic continues to spread across the world in late September 2020. To date, total cases of COVID-19 exceed 33 million including 996.342 deaths according to the WHO data. Although hydroxychloroquine, oseltamivir, remdesivir, favipiravir have been reported as an anti-SARS-CoV-2 effect, it is still unclear the fully effective protective drug and treatment. Herein, we report a woman under Tenofovir diphosphate who live and close contact with his COVID-19 positive husband. Although she had close contact with his husband without measure in the home she did not show any symptoms and signs of COVID-19 and her PCR test along with antibody test negative. Given the high reproduction number of SARS-CoV-2 and long-term close contact of the case, it can be speculated that Tenofovir could interfere with the transmission of COVID-19.

Objectives We aimed to summarize the clinical presentation, therapeutic approaches, and outcomes of type B intramural hematoma (IMHB) patients with and without type 2 diabetes mellitus (DM). Methods Patients with uncomplicated IMHBs were included between January 2016 and January 2018 and divided into two groups according to whether they had DM or not. Cox proportional hazard analysis was utilized to investigate the risk factors of aortic-related mortality. Kaplan-Meier survival analysis with the log-rank test was used to estimate the cumulative mortality and aortic-related mortality. Results 149 patients were included and were divided into to two groups (DM group [n=60] and non-DM group [n=89]). Patients in the non-DM group underwent thoracic endovascular aortic repair (TEVAR) treatment more frequently (12% vs 2%, P=0.028) and had a higher reintervention rate during the follow-up (9 in 81 cases, 11% vs 2%, P=0.043). There were significant differences between the two groups regarding the aorta-related mortality rate during the acute phase (9% vs 0%, P=0.042) and the all-cause mortality rate (22% vs 7%, P=0.011). Ulcer-like projection (ULP) development (during the acute phase) (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.01-1.31, P=0.008), C-reactive protein (CRP) level (HR, 1.92; 95% CI, 1.51-2.49, P<0.001) and MMP-9 level (HR, 16.82; 95% CI, 7.52-28.71, P<0.001) were associated with an elevated risk for aorta-related mortality. Conclusions IMHBs without DM are not benign and have a considerably high aortic-related mortality rate. ULP development (during the acute phase), CRP levels and maximum MMP-9 are associated with an elevated risk for aorta-related mortality.

Animal tuberculosis (TB) is a widespread infectious disease caused by the Mycobacterium tuberculosis bacteria belonging to the Mycobacterium tuberculosis complex (MTC) that can persist in reservoir wildlife hosts. Wild boar (sus scrofa) are a key reservoir for MTC and an increasing trend in wild boar density is expected to lead to an increase in TB prevalence with spill-over to livestock. MTC infection is presently controlled through a variety of strategies, including culling. African swine fever (ASF) is a virulent, viral infection which affects wild boar and is spreading across Eurasia and Oceania. ASF infection leads to near 100% mortality at the individual level, can cause a dramatic decrease in population density and may therefore lead to TB control. In this study we develop a mathematical model to examine the impact of ASF introduction into a wild boar population that supports endemic TB. Our model results indicate that an ASF infection will reduce wild boar population density and lead to a decrease in the prevalence of TB. If ASF persists in the local host population the model predicts the long-term decline of TB prevalence in wild boar. If ASF is eradicated, or fades-out in the local host population, the model predicts a slower recovery of TB prevalence in comparison to wild boar density after an ASF epidemic. This may open a window of opportunity to apply TB management to maintain low TB prevalence.

Objective COVID-19 mortality and outcomes differ significantly across the globe. Limited data exists from low-middle income countries (LMICs) on risk-factors for COVID-19 severity and mortality. We describe the clinical spectrum and predictors of mortality and severity of illness in COVID-19 from a single center in Karachi, Pakistan. Methods Retrospective cohort study of adults admitted with COVID-19 between February-June 2020 were reviewed and logistic regression applied on admission related risk-factors for severity and mortality. Results A total of 445 patients [66.97% males, mean age 51.6 (18-91) years] were admitted with PCR confirmed COVID-19 during the study period. Asymptomatic and severe/critical disease occurred in 55 (12.36%) and 137 (30.79%) patients, respectively. The proportion of severe disease increased with time and most (268, 60.22%) had ≥ 1 co-morbid. Disease severity was associated with age ≥ 60 (OR:1.92), shortness of breath (OR:4.43) , CRP ≥150mg/L (OR:1.77), LDH ≥ 500 I.U/L (OR:1.98), Neutrophil to Lymphocyte ratio (NLR) ≥5 (OR:2.80) and unit increase in serum creatinine (OR:1.32). All-cause mortality was 13%. Mortality was associated with septic shock (AOR= 13.2), age ≥ 60 (AOR: 3.25), Ferritin ≥ 1500ng/ml (AOR: 3.78) and NLR ≥ 5 (AOR: 4.04). Conclusion We describe the experience with COVID-19 from a tertiary-care hospital in a LMIC. Our study found a comparatively low inpatient mortality, high proportion of diabetics, and neutrophil to lymphocyte ratio of greater than 5 as a predictor of both severity of illness and as poor prognostic marker in COVID-19.

We analyze the role of the processing atmosphere and influence of long term ageing (up to 30 days) in ambient air on the wettability of the laser-processed stainless steel meshes. The effect of low-pressure and vacuum ageing transform the initial superhydrophilic characteristics of freshly laser structured mesh to near superhydrophobic state. Laser texturing of meshes was carried out in the presence of different gas environmental conditions: N 2 , O 2 , CO 2 , Ar, SF 6 , ambient atmospheric air and under different vacuum conditions. The influence of each gas on the time evolution of the wettability properties after ageing in ambient air is analyzed.

Large mammal herbivores are important drivers of plant evolution and vegetation patterns, but whether current plant traits and ecosystem geography reflect the historical distribution of extinct megafauna is unknown. We address this question for Southern America (Neotropical biogeographic realm) by relating plant defense trait information at the ecoregion scale to climate, soil, fire, and the historical distribution of megafauna. Here we show that megafauna history explains substantial trait variability and detected three distinct regions (called “Antiherbiomes”) characterized by convergent plant defense strategies, environmental and megafauna patterns. We also identified ecoregions that experienced biome shift, from grassy- to forest- dominated, following the Pleistocene megafauna extinction. These results suggest that extinct megafauna left a significant imprint in the current plant trait and ecosystems biogeography of Southern America.

Herbivorous fishes play integral roles in preventing macroalgae from displacing corals, yet appear to decline with depth despite the presence of coral-dominated habitats to >80 m. We investigated the relationship between herbivorous fish and a suite of bottom-up and top-down parameters (algal turf, macroalgal and coral cover, nutritional quality and palatability, temperature, light, and predator density) along a depth gradient from 3-50 m. Fishes were not food-limited as upper mesophotic algae had similar nutritional content, assemblages, and appeared highly palatable from algal choice experiments. In-situ temperature recordings suggest temperature was not a limiting factor. Multivariate redundancy analyses reveal the combination of increased habitat patchiness and reduced light levels best explain distributions with depth. These results suggest reductions in herbivorous fish populations across shallow to upper mesophotic depths are likely the result of non-consumptive predator effects and behavioral choices rather than abiotic constraints or resource limitation.

Background: The Coronavirus Disease 2019 (COVID-19) is causing of the new global pandemic and is responsible for millions of infections and thousands of deaths in the world. The lung ultrasound is a non-invasive and easily repeatable tool and can be carried out by the pediatrician at the bedside of children with a consequent reduction in the risk of transmission of the virus. Objective: To determine whether the lung ultrasound is a useful tool in identifying the signs of lung involvement in children with COVID-19 and whether can monitor the course of the disease. Methods: The study was made in the emergency department in a tertiary level pediatric hospital. All patients with swab-confirmed COVID-19 infection were subjected a lung ultrasound within 6 hours from admission and after 96 hours. Results: Among a total of 30 children, 18 (60%) were males, 4 reported exertional dyspnea and only 1 chest pain. The mean oxygen saturation was 98.8 ± 1.0 % in ambient air in emergency department and no patient needed oxygen therapy during hospitalization. After 96 hours we had observed ultrasound abnormality al the lung ultrasound only in 20% of the children. We found a statistically significant reduction in pleural irregularities (30% vs 16.7; p: .001) and in B lines (50% vs 20%; p: .008). Conclusions: lung ultrasound is safe and useful tool in detecting lung involvement in children with COVID-19 and in monitoring these patients during the course of disease.

Background: This systematic review and meta-analysis was performed to assess the prognostic role of left atrial peak systolic longitudinal strain (LA-PLSsys) as a predictor of atrial fibrillation (AF) recurrence after catheter ablation. Methods We systematically searched major electronic databases and grey literature for studies assessing the role of preablation LA-PLSsys, measured in at least 2 segments, in post-ablation AF recurrence, after a follow up period of at least 6 months. Results: 17 eligible studies were included, resulting in 1704 patients (68.6% men) with a pooled mean age of 59.9±10.6 years, 65.9% with paroxysmal AF. Recurrence occurred in 32.7% of patients. Those without recurrence had significantly higher LA-PLSsys (pooled mean±SD: 22.22%±10.64%, weighted mean difference: 5.43%, 95%CI: 4.03-6.84%, I2: 82.7%). Subgroup analysis revealed that methodology used (echocardiographic view and segments assessed) was a significant source of heterogeneity (p=0.02), while meta-regression analysis demonstrated that the effect size was inversely related to the baseline LA volume index (p=0.004). Conclusions: Pre-ablation LA-PLSsys seems to be a useful predictor of post-ablation AF recurrence. However, data for patients with persistent AF and severe LA dilation are still lacking, thus no safe conclusion can be made for this challenging subgroup. Moreover, use of different methodology seems to introduce bias in the effort to obtain a universal cutoff value. Whether LA strain may be of clinical use, which would require better methodological definition and deriving a reference range - with adequate positive and negative predictive value for recurrence - is subject to further investigation.

Circadian clocks have evolved to resonate with external day and night cycles. However, these entrainment signals are not consistent everywhere and vary with latitude, climate and seasonality. This leads to divergent selection for clocks which are locally adapted. To investigate the genetic basis for this circadian variation, we used a Delayed Fluorescence (DF) imaging assay to screen 191 naturally occurring Swedish Arabidopsis accessions for their circadian phenotypes. We demonstrate that period length co-varies with both geography and population sub-structure. Several candidate loci linked to period, phase and Relative Amplitude Error (RAE) were revealed by genome-wide association mapping and candidate genes were investigated using TDNA mutants. We show that natural variation in a single non-synonymous substitution within COR28 is associated with a long-period and late-flowering phenotype similar to that seen in TDNA knock-out mutants. COR28 is a known coordinator of flowering time, freezing tolerance and the circadian clock; all of which may form selective pressure gradients across Sweden. We demonstrate the effect of the COR28-58S SNP in increasing period length through a co-segregation analysis. Finally, we show that period phenotypic tails remain diverged under lower temperatures and follow a distinctive ‘arrow-shaped’ trend indicative of selection for a cold-biased temperature compensation response.

The U.S. Department of Energy’s (DOE) East River community observatory (ER) in the Upper Colorado River Basin was established in 2015 as a representative mountainous, snow-dominated watershed to study hydrobiogeochemical responses to hydrological perturbations in headwater systems. Led by the Watershed Function Science Focus Area (SFA), the ER has both long-term and spatially-extensive observations paired with experimental campaigns. The Watershed Function SFA, led by Berkeley Laboratory, includes researchers from over 30 organizations who conduct cross-disciplinary process-based investigations and mechanistic modeling of watershed behavior in the ER. The data generated at the ER are extremely heterogeneous, and include hydrological, biogeochemical, climate, vegetation, geological, remote sensing, and model data that together comprise an unprecedented collection of data and value-added products within a mountainous watershed, across multiple spatiotemporal scales, compartments, and life zones. Within 5 years of data collection, these datasets have already revealed insights into numerous aspects of watershed function such as factors influencing snow accumulation and melt timing, water balance partitioning, and impacts of floodplain biogeochemistry and hillslope ecohydrology on riverine geochemical exports. Data generated by the SFA are managed and curated through its Data Management Framework. The SFA has an open data policy, and over sixty ER datasets are publicly available through relevant data repositories. A public interactive map of data collection sites run by the SFA is available to inform the broader community about SFA field activities. Here, we describe the ER and the SFA measurement network, present the public data collection generated by the SFA and partner institutions, and highlight the value of collecting multidisciplinary multiscale measurements in representative catchment observatories.