The range of potential applications of compact laser-plasma ion sources motivates the development of new acceleration schemes to increase achievable ion energies and conversion efficiencies. Whilst ...the evolving nature of laser-plasma interactions can limit the effectiveness of individual acceleration mechanisms, it can also enable the development of hybrid schemes, allowing additional degrees of control on the properties of the resulting ion beam. Here we report on an experimental demonstration of efficient proton acceleration to energies exceeding 94 MeV via a hybrid scheme of radiation pressure-sheath acceleration in an ultrathin foil irradiated by a linearly polarised laser pulse. This occurs via a double-peaked electrostatic field structure, which, at an optimum foil thickness, is significantly enhanced by relativistic transparency and an associated jet of super-thermal electrons. The range of parameters over which this hybrid scenario occurs is discussed and implications for ion acceleration driven by next-generation, multi-petawatt laser facilities are explored.
Adeno-associated viral vector 9 (AAV9) has recently been shown to penetrate the blood-brain barrier via intravascular administration, making it a good candidate for diffuse gene delivery. However, ...the potential side effects of systemic delivery are unknown. Intrathecal viral vector administration may be more invasive than intravenous injections, but it requires far less vector and it can be performed on an outpatient basis, making it an ideal route of delivery for clinical translation. A total of 12 domestic farm pigs (<20 kg) underwent a single-level lumbar laminectomy with intrathecal catheter placement for AAV9 delivery. Animals were perfused and the tissue was harvested 30 days after treatment. Gene expression was assessed by anti-green fluorescent protein immunohistochemistry. Although a single lumbar injection resulted in gene expression limited to the lumbar segment of the spinal cord, three consecutive boluses via a temporary catheter resulted in diffuse transduction of motor neurons (MNs) throughout the cervical, thoracic and lumbar spinal cords. We now present the first successful robust transduction of MNs in the spinal cord of a large animal via intrathecal gene delivery using a self-complementary AAV9. These promising results can be translated to many MN diseases requiring diffuse gene delivery.
Aims/hypothesis
Sedentary (sitting) behaviours are ubiquitous in modern society. We conducted a systematic review and meta-analysis to examine the association of sedentary time with diabetes, ...cardiovascular disease and cardiovascular and all-cause mortality.
Methods
Medline, Embase and the Cochrane Library databases were searched for terms related to sedentary time and health outcomes. Cross-sectional and prospective studies were included. RR/HR and 95% CIs were extracted by two independent reviewers. Data were adjusted for baseline event rate and pooled using a random-effects model. Bayesian predictive effects and intervals were calculated to indicate the variance in outcomes that would be expected if new studies were conducted in the future.
Results
Eighteen studies (16 prospective, two cross-sectional) were included, with 794,577 participants. Fifteen of these studies were moderate to high quality. The greatest sedentary time compared with the lowest was associated with a 112% increase in the RR of diabetes (RR 2.12; 95% credible interval CrI 1.61, 2.78), a 147% increase in the RR of cardiovascular events (RR 2.47; 95% CI 1.44, 4.24), a 90% increase in the risk of cardiovascular mortality (HR 1.90; 95% CrI 1.36, 2.66) and a 49% increase in the risk of all-cause mortality (HR 1.49; 95% CrI 1.14, 2.03). The predictive effects and intervals were only significant for diabetes.
Conclusions/interpretation
Sedentary time is associated with an increased risk of diabetes, cardiovascular disease and cardiovascular and all-cause mortality; the strength of the association is most consistent for diabetes.
Debates about human prehistory often center on the role that population expansions play in shaping biological and cultural diversity. Hypotheses on the origin of the Austronesian settlers of the ...Pacific are divided between a recent "pulse-pause" expansion from Taiwan and an older "slow-boat" diffusion from Wallacea. We used lexical data and Bayesian phylogenetic methods to construct a phylogeny of 400 languages. In agreement with the pulse-pause scenario, the language trees place the Austronesian origin in Taiwan approximately 5230 years ago and reveal a series of settlement pauses and expansion pulses linked to technological and social innovations. These results are robust to assumptions about the rooting and calibration of the trees and demonstrate the combined power of linguistic scholarship, database technologies, and computational phylogenetic methods for resolving questions about human prehistory.
Aims/hypothesis
The study aimed to examine the associations between objectively measured sedentary time, breaks in sedentary time, moderate-to-vigorous physical activity (MVPA) and total physical ...activity with markers of cardiometabolic health in a population with known risk factors for type 2 diabetes mellitus.
Methods
This study reports data from two ongoing diabetes prevention programmes. Participants with known risk factors were recruited from primary care practices located within the East Midlands, UK, over the period 2010–2011. ActiGraph GT3X accelerometers (15 s epochs) were used to assess sedentary time (<25 counts per 15 s), MVPA (≥488 counts per 15 s) and total physical activity (total counts). A break was considered as any interruption in sedentary time (≥25 counts per 15 s). Linear regression examined the independent association of sedentary time, breaks in sedentary time, MVPA and total physical activity with markers of cardiometabolic health.
Results
The sample comprised 878 participants; 153 from Project STAND (Sedentary Time And Diabetes) (age 32.9 ± 5.6 years, 28.8% male) and 725 from Walking Away from Diabetes (age 63.7 ± 7.8 years, 64.8% male). Following adjustment for various covariates, including MVPA and BMI, there were detrimental linear associations of sedentary time with 2 h plasma glucose (standardised beta coefficient) (β = 0.220,
p
< 0.001), triacylglycerol (β = 0.206,
p
= 0.001) and HDL-cholesterol (β = −0.123,
p
= 0.029). Breaks in sedentary time, total physical activity and MVPA were significantly inversely associated with measures of adiposity, but not with any other cardiometabolic variables after adjustment for sedentary time and BMI.
Conclusions/interpretation
In adults at high risk of type 2 diabetes mellitus, time spent sedentary is strongly and adversely associated with cardiometabolic health and may be a more important indicator of poor health than MVPA.
The measurement of minuscule forces and displacements with ever greater precision is inhibited by the Heisenberg uncertainty principle, which imposes a limit to the precision with which the position ...of an object can be measured continuously, known as the standard quantum limit
. When light is used as the probe, the standard quantum limit arises from the balance between the uncertainties of the photon radiation pressure applied to the object and of the photon number in the photoelectric detection. The only way to surpass the standard quantum limit is by introducing correlations between the position/momentum uncertainty of the object and the photon number/phase uncertainty of the light that it reflects
. Here we confirm experimentally the theoretical prediction
that this type of quantum correlation is naturally produced in the Laser Interferometer Gravitational-wave Observatory (LIGO). We characterize and compare noise spectra taken without squeezing and with squeezed vacuum states injected at varying quadrature angles. After subtracting classical noise, our measurements show that the quantum mechanical uncertainties in the phases of the 200-kilowatt laser beams and in the positions of the 40-kilogram mirrors of the Advanced LIGO detectors yield a joint quantum uncertainty that is a factor of 1.4 (3 decibels) below the standard quantum limit. We anticipate that the use of quantum correlations will improve not only the observation of gravitational waves, but also more broadly future quantum noise-limited measurements.
Overview of the SPARC tokamak Creely, A. J.; Greenwald, M. J.; Ballinger, S. B. ...
Journal of plasma physics,
10/2020, Letnik:
86, Številka:
5
Journal Article
Recenzirano
Odprti dostop
The SPARC tokamak is a critical next step towards commercial fusion energy. SPARC is designed as a high-field ($B_0 = 12.2$ T), compact ($R_0 = 1.85$ m, $a = 0.57$ m), superconducting, D-T tokamak ...with the goal of producing fusion gain $Q>2$ from a magnetically confined fusion plasma for the first time. Currently under design, SPARC will continue the high-field path of the Alcator series of tokamaks, utilizing new magnets based on rare earth barium copper oxide high-temperature superconductors to achieve high performance in a compact device. The goal of $Q>2$ is achievable with conservative physics assumptions ($H_{98,y2} = 0.7$) and, with the nominal assumption of $H_{98,y2} = 1$, SPARC is projected to attain $Q \approx 11$ and $P_{\textrm {fusion}} \approx 140$ MW. SPARC will therefore constitute a unique platform for burning plasma physics research with high density ($\langle n_{e} \rangle \approx 3 \times 10^{20}\ \textrm {m}^{-3}$), high temperature ($\langle T_e \rangle \approx 7$ keV) and high power density ($P_{\textrm {fusion}}/V_{\textrm {plasma}} \approx 7\ \textrm {MW}\,\textrm {m}^{-3}$) relevant to fusion power plants. SPARC's place in the path to commercial fusion energy, its parameters and the current status of SPARC design work are presented. This work also describes the basis for global performance projections and summarizes some of the physics analysis that is presented in greater detail in the companion articles of this collection.
While mutations in the KRAS oncogene are among the most prevalent in human cancer, there are few successful treatments to target these tumors. It is also likely that heterogeneity in KRAS-mutant ...tumor biology significantly contributes to the response to therapy. We hypothesized that the presence of commonly co-occurring mutations in STK11 and TP53 tumor suppressors may represent a significant source of heterogeneity in KRAS-mutant tumors. To address this, we utilized a large cohort of resected tumors from 442 lung adenocarcinoma patients with data including annotation of prevalent driver mutations (KRAS and EGFR) and tumor suppressor mutations (STK11 and TP53), microarray-based gene expression and clinical covariates, including overall survival (OS). Specifically, we determined impact of STK11 and TP53 mutations on a new KRAS mutation-associated gene expression signature as well as previously defined signatures of tumor cell proliferation and immune surveillance responses. Interestingly, STK11, but not TP53 mutations, were associated with highly elevated expression of KRAS mutation-associated genes. Mutations in TP53 and STK11 also impacted tumor biology regardless of KRAS status, with TP53 strongly associated with enhanced proliferation and STK11 with suppression of immune surveillance. These findings illustrate the remarkably distinct ways through which tumor suppressor mutations may contribute to heterogeneity in KRAS-mutant tumor biology. In addition, these studies point to novel associations between gene mutations and immune surveillance that could impact the response to immunotherapy.
Although best known as an animal disease, human babesiosis is attracting increasing attention as a worldwide emerging zoonosis. Humans are commonly infected by the bite of ixodid ticks. Rare ways of ...transmission are transplacental, perinatal and transfusion-associated. Infection of the human host can cause a very severe host-mediated pathology including fever, and hemolysis leading to anemia, hyperbilirubinuria, hemoglobinuria and possible organ failure. In recent years, apparently owing to increased medical awareness and better diagnostic methods, the number of reported cases in humans is rising steadily worldwide. Hitherto unknown zoonotic
Babesia
spp. are now being reported from geographic areas where babesiosis was not previously known to occur and the growing numbers of travelers and immunocompromised individuals suggest that the frequency of cases in Europe will also continue to rise. Our review is intended to provide clinicians with practical information on the clinical management of this rare, but potentially life-threatening zoonotic disease. It covers epidemiology, phylogeny, diagnostics and treatment of human babesiosis and the potential risk of transfusion-transmitted disease with a special focus on the European situation.
BackgroundNo previous team–based multi–disciplinary Quality Improvement (QI) training package in child health in regionHuge appetite for change across city/trust – bid made to Health Education ...EnglandAimTo deliver a 1-year QI programme to groups of multi-disciplinary professionals working across child health in city and facilitate group project work-streams (minimum of 8) utilising these QI skills to deliver specific, measurable, achievable, realistic improvements within the year.ProcessAll groups working with children invited across hospital trust & primary care15 Team EQUIP sessions organised with standardised structureFirst part: Introduction to QI and methodologySecond part: Interactive project planning (brainstorming areas for improvement, dot voting & Pareto charting to decide on project(s) followed by driver diagram, process mapping, generating SMART aim & initial stage planning)Outcome MeasuresPre– and post–course questionnaire relating to knowledge, interest and involvement in QIVariable measures for different work–streamsResults64 attended sessions with improvement in knowledge, interest and likelihood to get involved19 work–streams in progress spanning a wide array of improvement areas relating to child healthLearning PointsRunning a programme like this single–handedly is massively time consuming but good for quality controlNHS work pressures are over–whelming (2 sessions cancelled last minute by day surgery and one of the GP teams)Incentives (free lunch, prizes, conference funding) workFacilitating self–directed projects works wonders for engagement & motivation for the vast majority (but not all!)Next StepsSupporting ongoing projects & dissemination via poster production, conference presentations & publicationSpread learning & experience to other specialties through trust–wide QI steering group & for child health regionally via regional QI network, Q network & nationally through RCPCH conference & RCPCH QI Central
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