Non-invasive prenatal testing for aneuploidy: a systematic review of Internet advertising to potential users by commercial companies and private health providers.

BACKGROUND: The development of non-invasive prenatal testing has increased accessibility of fetal testing. Companies are now advertising prenatal testing for aneuploidy via the Internet. OBJECTIVES: The aim of this systematic review of websites advertising non-invasive prenatal testing for aneuploidy was to explore the nature of the information being provided to potential users. METHODS: We systematically searched two Internet search engines for relevant websites using the following terms: 'prenatal test', 'antenatal test', 'non-invasive test', 'noninvasive test', 'cell-free fetal DNA', 'cffDNA', 'Down syndrome test' or 'trisomy test'. We examined the first 200 websites identified through each search. Relevant web-based text was examined, and key topics were identified, tabulated and counted. To analyse the text further, we used thematic analysis. MAIN RESULTS: Forty websites were identified. Whilst a number of sites provided balanced, accurate information, in the majority supporting evidence was not provided to underpin the information and there was inadequate information on the need for an invasive test to definitely diagnose aneuploidy. CONCLUSIONS: The information provided on many websites does not comply with professional recommendations. Guidelines are needed to ensure that companies offering prenatal testing via the Internet provide accurate and comprehensible information

Effects of Explicit Convection on Future Projections of Mesoscale Circulations, Rainfall, and Rainfall Extremes over Eastern Africa

Eastern Africa’s fast-growing population is vulnerable to changing rainfall and extremes. Using the first pan-African climate change simulations that explicitly model the rainfall-generating convection, we investigate both the climate change response of key mesoscale drivers of eastern African rainfall, such as sea and lake breezes, and the spatial heterogeneity of rainfall responses. The explicit model shows widespread increases at the end of the century in mean (~40%) and extreme (~50%) rain rates, whereas the sign of changes in rainfall frequency has large spatial heterogeneity (from −50% to over +90%). In comparison, an equivalent parameterized simulation has greater moisture convergence and total rainfall increase over the eastern Congo and less over eastern Africa. The parameterized model also does not capture 1) the large heterogeneity of changes in rain frequency; 2) the widespread and large increases in extreme rainfall, which result from increased rainfall per humidity change; and 3) the response of rainfall to the changing sea breeze, even though the sea-breeze change is captured. Consequently, previous rainfall projections are likely inadequate for informing many climate-sensitive decisions—for example, for infrastructure in coastal cities. We consider the physics revealed here and its implications to be relevant for many other vulnerable tropical regions, especially those with coastal convection

Regional differences in the response of rainfall to convectively coupled Kelvin waves over tropical Africa

The representation of convection remains one of the most important sources of bias in global models and evaluation methods are needed that show that models provide the correct mean state and variability; both for the correct reasons. Here we develop a novel approach for evaluating rainfall variability due to CCKWs in this region. A phase cycle was defined for the CCKW cycle in OLR and used to composite rainfall anomalies. We characterize the observed (TRMM) rainfall response to CCKWs over tropical Africa in April and evaluate the performance of regional climate model (RCM) simulations: a parameterized convection simulation (P25) and the first pan-Africa convection permitting simulation (CP4). TRMM mean rainfall is enhanced and suppressed by CCKW activity and the occurrence of extreme rainfall and dry days is coupled with CCKW activity. Focusing on regional differences, we show for the first time that: there is a dipole between West Africa and the Gulf of Guinea involving onshore/offshore shifts in rainfall; and the transition to enhanced rainfall over west equatorial Africa occurs one phase before the transition over east equatorial Africa. The global model used to drive the RCMs simulated CCKWs with mean amplitudes of 75%-82% of observations. The RCMs simulated coherent responses to the CCKWs and captured the large-scale spatial patterns and phase relationships in rainfall although the simulated rainfall response is weaker than observations and there are regional biases which are bigger away from the equator. P25 produced a closer match to TRMM mean rainfall anomalies than CP4 although the response in dry days was more closely simulated by CP4

The effect of westerlies on East African rainfall and the associated role of tropical cyclones and the Madden–Julian Oscillation

Variability of rainfall in East Africa has major impacts on lives and livelihoods. From floods to droughts, this variability is important on short daily time‐scales to longer decadal time‐scales, as is apparent from the devastating effects of droughts in East Africa over recent decades. Past studies have highlighted the Congo airmass in enhancing East African rainfall. Our detailed analysis of the feature shows that days with a westerly moisture flow, bringing the Congo airmass, enhance rainfall by up to 100% above the daily mean, depending on the time of year. Conversely, there is a suppression of rainfall on days with a strong easterly flow. Days with a westerly moisture flux are in a minority in all seasons but we show that long rains with more westerly days are wetter, and that during the most‐recent decade which has had more frequent droughts (associated with the “Eastern African climate paradox”), there has been few days with such westerlies. We also investigate the influence of the Madden–Julian Oscillation (MJO) and tropical cyclones, and their interaction with the westerly flow. We show that days of westerly moisture flux are more likely during phases 3 and 4 of the MJO and when there are one or more tropical cyclones present. In addition, tropical cyclones are more likely to form during these phases of the MJO, and more likely to be coincident with westerlies when forming to the east of Madagascar. Overall, our analysis brings together many different processes that have been discussed in the literature but not yet considered in complete combination. The results demonstrate the importance of the Congo airmass on daily to climate time‐scales, and in doing so offers useful angles of investigation for future studies into prediction of East African rainfall

A comparison of temperature and precipitation responses to different Earth radiation management geoengineering schemes

Earth radiation management has been suggested as a way to rapidly counteract global warming in the face of a lack of mitigation efforts, buying time and avoiding potentially catastrophic warming. We compare six different radiation management schemes that use surface, troposphere, and stratosphere interventions in a single climate model in which we projected future climate from 2020 to 2099 based on RCP4.5. We analyze the surface air temperature responses to determine how effective the schemes are at returning temperature to its 1986–2005 climatology and analyze precipitation responses to compare side effects. We find crop albedo enhancement is largely ineffective at returning temperature to its 1986–2005 climatology. Desert albedo enhancement causes excessive cooling in the deserts and severe shifts in tropical precipitation. Ocean albedo enhancement, sea-spray geoengineering, cirrus cloud thinning, and stratospheric SO2 injection have the potential to cool more uniformly, but cirrus cloud thinning may not be able to cool by much more than 1 K globally. We find that of the schemes potentially able to return surface air temperature to 1986–2005 climatology under future greenhouse gas warming, none has significantly less severe precipitation side effects than other schemes. Despite different forcing patterns, ocean albedo enhancement, sea-spray geoengineering, cirrus cloud thinning, and stratospheric SO2 injection all result in large scale tropical precipitation responses caused by Hadley cell changes and land precipitation changes largely driven by thermodynamic changes. Widespread regional scale changes in precipitation over land are significantly different from the 1986–2005 climatology and would likely necessitate significant adaptation despite geoengineering

Understanding Intermodel Variability in Future Projections of a Sahelian Storm Proxy and Southern Saharan Warming

Projected changes in the intensity of severe rain events over the North African Sahel—falling from large mesoscale convective systems—cannot be directly assessed from global climate models due to their inadequate resolution and parameterization of convection. Instead, the large-scale atmospheric drivers of these storms must be analyzed. Here we study changes in meridional lower-tropospheric temperature gradient across the Sahel (ΔTGrad), which affect storm development via zonal vertical wind shear and Saharan air layer characteristics. Projected changes in ΔTGrad vary substantially among models, adversely affecting planning decisions that need to be resilient to adverse risks, such as increased flooding. This study seeks to understand the causes of these projection uncertainties and finds three key drivers. The first is intermodel variability in remote warming, which has strongest impact on the eastern Sahel, decaying toward the west. Second, and most important, a warming–advection–circulation feedback in a narrow band along the southern Sahara varies in strength between models. Third, variations in southern Saharan evaporative anomalies weakly affect ΔTGrad, although for an outlier model these are sufficiently substantive to reduce warming here to below that of the global mean. Together these uncertain mechanisms lead to uncertain southern Saharan/northern Sahelian warming, causing the bulk of large intermodel variations in ΔTGrad. In the southern Sahel, a local negative feedback limits the contribution to uncertainties in ΔTGrad. This new knowledge of ΔTGrad projection uncertainties provides understanding that can be used, in combination with further research, to constrain projections of severe Sahelian storm activity

Neuroprotection in a Novel Mouse Model of Multiple Sclerosis

The authors acknowledge the support of the Barts and the London Charity, the Multiple Sclerosis Society of Great Britain and Northern Ireland, the National Multiple Sclerosis Society, USA, notably the National Centre for the Replacement, Refinement & Reduction of Animals in Research, and the Wellcome Trust (grant no. 092539 to ZA). The siRNA was provided by Quark Pharmaceuticals. The funders and Quark Pharmaceuticals had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript

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

The implausibility of ‘usual care’ in an open system: sedation and weaning practices in Paediatric Intensive Care Units (PICUs) in the United Kingdom (UK)

Background: The power of the randomised controlled trial depends upon its capacity to operate in a closed system whereby the intervention is the only causal force acting upon the experimental group and absent in the control group, permitting a valid assessment of intervention efficacy. Conversely, clinical arenas are open systems where factors relating to context, resources, interpretation and actions of individuals will affect implementation and effectiveness of interventions. Consequently, the comparator (usual care) can be difficult to define and variable in multi-centre trials. Hence outcomes cannot be understood without considering usual care and factors that may affect implementation and impact on the intervention. Methods: Using a fieldwork approach, we describe PICU context, ‘usual’ practice in sedation and weaning from mechanical ventilation, and factors affecting implementation prior to designing a trial involving a sedation and ventilation weaning intervention. We collected data from 23 UK PICUs between June and November 2014 using observation, individual and multi-disciplinary group interviews with staff. Results: Pain and sedation practices were broadly similar in terms of drug usage and assessment tools. Sedation protocols linking assessment to appropriate titration of sedatives and sedation holds were rarely used (9 % and 4 % of PICUs respectively). Ventilator weaning was primarily a medical-led process with 39 % of PICUs engaging senior nurses in the process: weaning protocols were rarely used (9 % of PICUs). Weaning methods were variably based on clinician preference. No formal criteria or use of spontaneous breathing trials were used to test weaning readiness. Seventeen PICUs (74 %) had prior engagement in multi-centre trials, but limited research nurse availability. Barriers to previous trial implementation were intervention complexity, lack of belief in the evidence and inadequate training. Facilitating factors were senior staff buy-in and dedicated research nurse provision. Conclusions: We examined and identified contextual and organisational factors that may impact on the implementation of our intervention. We found usual practice relating to sedation, analgesia and ventilator weaning broadly similar, yet distinctively different from our proposed intervention, providing assurance in our ability to evaluate intervention effects. The data will enable us to develop an implementation plan; considering these factors we can more fully understand their impact on study outcomes

General Form of the Color Potential Produced by Color Charges of the Quark

Constant electric charge $e$ satisfies the continuity equation $\partial_\mu j^{\mu}(x)= 0$ where $j^\mu(x)$ is the current density of the electron. However, the Yang-Mills color current density $j^{\mu a}(x)$ of the quark satisfies the equation $D_\mu[A] j^{\mu a}(x)= 0$ which is not a continuity equation ($\partial_\mu j^{\mu a}(x)\neq 0$) which implies that a color charge $q^a(t)$ of the quark is not constant but it is time dependent where $a=1,2,...8$ are color indices. In this paper we derive general form of color potential produced by color charges of the quark. We find that the general form of the color potential produced by the color charges of the quark at rest is given by \Phi^a(x) =A_0^a(t,{\bf x}) =\frac{q^b(t-\frac{r}{c})}{r}\[\frac{{\rm exp}[g\int dr \frac{Q(t-\frac{r}{c})}{r}] -1}{g \int dr \frac{Q(t-\frac{r}{c})}{r}}\]_{ab} where $dr$ integration is an indefinite integration, ~~ $Q_{ab}(\tau_0)=f^{abd}q^d(\tau_0)$, ~~$r=|{\vec x}-{\vec X}(\tau_0)|$, ~~$\tau_0=t-\frac{r}{c}$ is the retarded time, ~~$c$ is the speed of light, ~~${\vec X}(\tau_0)$ is the position of the quark at the retarded time and the repeated color indices $b,d$(=1,2,...8) are summed. For constant color charge $q^a$ we reproduce the Coulomb-like potential $\Phi^a(x)=\frac{q^a}{r}$ which is consistent with the Maxwell theory where constant electric charge $e$ produces the Coulomb potential $\Phi(x)=\frac{e}{r}$.Comment: Final version, two more sections added, 45 pages latex, accepted for publication in JHE