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Recent technological advances have led to a novel class of microfluidic devices which can be rapidly fabricated by printing a fluid onto a solid substrate with flows generated passively via surface tension. The nonlinear dependence between flow and the heights of the conduits, however, prevent straightforward calculation of the resulting dynamics. In this paper we use matched asymptotic expansions to predict how flow through these devices can be tuned by changing their geometry. We begin with the simple ‘dumbbell’ configuration in which two fluid drops with different sizes are connected by a long, thin and narrow conduit. We calculate the time scale required for one drop to drain into the other and how this depends both on the geometry of the pinned contact line and volume of fluid deposited into the drops. Our model therefore provides the mechanistic basis to design conduits with a particular fluid flux and/or shear stress, which are often key experimental constraints. Our asymptotic predictions are shown to be in excellent agreement with numerical simulations even for moderate aspect ratios (the ratio of conduit width to length). Next, we show how our results for the simple dumbbell configuration can be extended to predict the flow through networks of conduits with multiple drops and nodes, and hence may assist in their design and implementation. This new mathematical framework has the potential to increase the use of surface tension driven microfluidics across a wide range of disciplines as it allows alternate designs to be rapidly assessed.
Over the past 15 years, there has been substantial growth in web-based psychological interventions. We summarize evidence regarding the efficacy of web-based self-directed psychological interventions on depressive, anxiety and distress symptoms in people living with a chronic health condition.
We searched Medline, PsycINFO, CINAHL, EMBASE databases and Cochrane Database from 1990 to 1 May 2019. English language papers of randomized controlled trials (usual care or waitlist control) of web-based psychological interventions with a primary or secondary aim to reduce anxiety, depression or distress in adults with a chronic health condition were eligible. Results were assessed using narrative synthases and random-effects meta-analyses.
In total 70 eligible studies across 17 health conditions [most commonly: cancer (k = 20), chronic pain (k = 9), arthritis (k = 6) and multiple sclerosis (k = 5), diabetes (k = 4), fibromyalgia (k = 4)] were identified. Interventions were based on CBT principles in 46 (66%) studies and 42 (60%) included a facilitator. When combining all chronic health conditions, web-based interventions were more efficacious than control conditions in reducing symptoms of depression g = 0.30 (95% CI 0.22–0.39), anxiety g = 0.19 (95% CI 0.12–0.27), and distress g = 0.36 (95% CI 0.23–0.49).
Evidence regarding effectiveness for specific chronic health conditions was inconsistent. While self-guided online psychological interventions may help to reduce symptoms of anxiety, depression and distress in people with chronic health conditions in general, it is unclear if these interventions are effective for specific health conditions. More high-quality evidence is needed before definite conclusions can be made.
Approximately, 1.7 million individuals in the United States have been infected with SARS-CoV-2, the virus responsible for the novel coronavirus disease-2019 (COVID-19). This has disproportionately impacted adults, but many children have been infected and hospitalised as well. To date, there is not much information published addressing the cardiac workup and monitoring of children with COVID-19. Here, we share the approach to the cardiac workup and monitoring utilised at a large congenital heart centre in New York City, the epicentre of the COVID-19 pandemic in the United States.
From 1971 to 2012, in New York State, years with human Eastern equine encephalitis (EEE) were more strongly associated with the presence of Aedes canadensis, Coquillettidia perturbans and Culiseta melanura mosquitoes infected with the EEE virus (Fisher's exact test, one-sided P = 0.005, 0.03, 0.03) than with Culiseta morsitans, Aedes vexans, Culex pipiens-restuans, Anopheles quadrimaculatus or Anopheles punctipennis (P = 0.05, 0.40, 0.33, 1.00, 1.00). The estimated relative risk of a case in a year in which the virus was detected vs. not detected was 14.67 for Ae. canadensis, 6.38 for Cq. perturbans and 5.50 for Cs. morsitans. In all 5 years with a case, Cs. melanura with the virus was detected. In no year was there a case in the absence of Cs. melanura with the virus. There were 18 years with no case in the presence of Cs. melanura with the virus. Such observations may identify the time of increased risk, and when the methods may be used to prevent or reduce exposure to vector mosquito species in this geographic region.
Flagellar dyneins are the molecular motors responsible for producing the propagating bending motions of cilia and flagella. They are located within a densely packed and highly organised super-macromolecular cytoskeletal structure known as the axoneme. Using the mesoscale simulation technique Fluctuating Finite Element Analysis (FFEA), which represents proteins as viscoelastic continuum objects subject to explicit thermal noise, we have quantified the constraints on the range of molecular conformations that can be explored by dynein-c within the crowded architecture of the axoneme. We subsequently assess the influence of crowding on the 3D exploration of microtubule-binding sites, and specifically on the axial step length. Our calculations combine experimental information on the shape, flexibility and environment of dynein-c from three distinct sources; negative stain electron microscopy, cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET). Our FFEA simulations show that the super-macromolecular organisation of multiple protein complexes into higher-order structures can have a significant influence on the effective flexibility of the individual molecular components, and may, therefore, play an important role in the physical mechanisms underlying their biological function.
Positive symptoms are a useful predictor of aggression in schizophrenia. Although a similar pattern of abnormal brain structures related to both positive symptoms and aggression has been reported, this observation has not yet been confirmed in a single sample.
To study the association between positive symptoms and aggression in schizophrenia on a neurobiological level, a prospective meta-analytic approach was employed to analyze harmonized structural neuroimaging data from 10 research centers worldwide. We analyzed brain MRI scans from 902 individuals with a primary diagnosis of schizophrenia and 952 healthy controls.
The result identified a widespread cortical thickness reduction in schizophrenia compared to their controls. Two separate meta-regression analyses revealed that a common pattern of reduced cortical gray matter thickness within the left lateral temporal lobe and right midcingulate cortex was significantly associated with both positive symptoms and aggression.
These findings suggested that positive symptoms such as formal thought disorder and auditory misperception, combined with cognitive impairments reflecting difficulties in deploying an adaptive control toward perceived threats, could escalate the likelihood of aggression in schizophrenia.
The Children of the Twins Early Development Study (CoTEDS) is a new prospective children-of-twins study in the UK, designed to investigate intergenerational associations across child developmental stages. CoTEDS will enable research on genetic and environmental factors that underpin parent–child associations, with a focus on mental health and cognitive-related traits. Through CoTEDS, we will have a new lens to examine the roles that parents play in influencing child development, as well as the genetic and environmental factors that shape parenting behavior and experiences. Recruitment is ongoing from the sample of approximately 20,000 contactable adult twins who have been enrolled in the Twins Early Development Study (TEDS) since infancy. TEDS twins are invited to register all offspring to CoTEDS at birth, with 554 children registered as of May 2019. By recruiting the second generation of TEDS participants, CoTEDS will include information on adult twins and their offspring from infancy. Parent questionnaire-based data collection is now underway for 1- and 2-year-old CoTEDS infants, with further waves of data collection planned. Current data collection includes the following primary constructs: child mental health, temperament, language and cognitive development; parent mental health and social relationships; parenting behaviors and feelings; and other socioecological factors. Measurement tools have been selected with reference to existing genetically informative cohort studies to ensure overlap in phenotypes measured at corresponding stages of development. This built-in study overlap is intended to enable replication and triangulation of future analyses across samples and research designs. Here, we summarize study protocols and measurement procedures and describe future plans.
Optical parametric chirped-pulse amplification (OPCPA) [Dubietis et al., Opt. Commun. 88, 437 (1992)] implemented by multikilojoule Nd:glass pump lasers is a promising approach to produce ultraintense pulses (
). Technologies are being developed to upgrade the OMEGA EP Laser System with the goal to pump an optical parametric amplifier line (EP OPAL) with two of the OMEGA EP beamlines. The resulting ultraintense pulses (1.5 kJ, 20 fs,
) would be used jointly with picosecond and nanosecond pulses produced by the other two beamlines. A midscale OPAL pumped by the Multi-Terawatt (MTW) laser is being constructed to produce 7.5-J, 15-fs pulses and demonstrate scalable technologies suitable for the upgrade. MTW OPAL will share a target area with the MTW laser (50 J, 1 to 100 ps), enabling several joint-shot configurations. We report on the status of the MTW OPAL system, and the technology development required for this class of all-OPCPA laser system for ultraintense pulses.
This paper describes a model of electron energization and cyclotron-maser emission applicable to astrophysical magnetized collisionless shocks. It is motivated by the work of Begelman, Ergun and Rees [Astrophys. J. 625, 51 (2005)] who argued that the cyclotron-maser instability occurs in localized magnetized collisionless shocks such as those expected in blazar jets. We report on recent research carried out to investigate electron acceleration at collisionless shocks and maser radiation associated with the accelerated electrons. We describe how electrons accelerated by lower-hybrid waves at collisionless shocks generate cyclotron-maser radiation when the accelerated electrons move into regions of stronger magnetic fields. The electrons are accelerated along the magnetic field and magnetically compressed leading to the formation of an electron velocity distribution having a horseshoe shape due to conservation of the electron magnetic moment. Under certain conditions the horseshoe electron velocity distribution function is unstable to the cyclotron-maser instability [Bingham and Cairns, Phys. Plasmas 7, 3089 (2000); Melrose, Rev. Mod. Plasma Phys. 1, 5 (2017)].
In this paper we report high voltage MOS and Schottky Diode CV techniques for silicon and SiC power devices. 4H Silicon carbide is a wide bandgap semiconductor suitable for high voltage power electronics and RF applications due to high avalanche breakdown critical electric field, and thermal conductivity. The performance of various power devices, which may include MOSFET and Static Induction Transistor (SIT), can be affected by the deep level traps in the substrate and the oxide interfacial defects. We have characterized deep level trap (High Voltage Schottky Diode HF CV) and oxide interface trap densities (High Voltage HF MOS CV), measured the device channel doping profile for both 4H SiC and silicon, gate metal workfunction, and simulated the effects on DC/AC performance.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
Oldowan sites in primary geological context are rare in the archaeological record. Here we describe the depositional environment of Oldowan occurrences at Kanjera South, Kenya, based on field descriptions and granulometric analysis. Excavations have recovered a large Oldowan artefact sample as well as the oldest substantial sample of archaeological fauna. The deposits at Kanjera South consist of 30 m of fluvial, colluvial and lacustrine sediments. Magneto- and biostratigraphy indicate the Kanjera South Member of the Kanjera Formation was deposited during 2.3–1.92 Ma, with 2.0 Ma being a likely age for the archaeological occurrences. Oldowan artefacts and associated fauna were deposited in the colluvial and alluvial silts and sands of beds KS1–3, in the margins of a lake basin. Field descriptions and granulometric analysis of the sediment fine fraction indicate that sediments from within the main archaeological horizon were emplaced as a combination of tractional and hyperconcentrated flows with limited evidence of debris-flow deposition. This style of deposition is unlikely to significantly erode or disturb the underlying surface, and therefore promotes preservation of surface archaeological accumulations. Hominins were repeatedly attracted to the site locale, and rapid sedimentation, minimal bone weathering and an absence of bone or artefact rounding further indicate that fossils and artefacts were quickly buried.
Background: Continuous video-EEG (cvEEG) monitoring is the standard of care for diagnosis and management of neonatal seizures. However, it is labour-intensive. We aimed to establish consistency in monitoring of newborns utilising NICU nurses. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues. Guidelines, checklists and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. We compared 100 infants with moderate to severe HIE before and after the training program. Results: 192 cvEEGs were performed. Of the 100 infants compared; time to initiate brain monitoring decreased by average of 31.5 hours, in electrographic seizure detection increased(20% compared to 34% a), seizure clinical misdiagnosis decreased (65% compared to 36% ), and Anti-Seizure burden decreased. Conclusions: Training experienced NICU nurses to set-up, start and monitor cvEEG can decrease the time to initiate cvEEG which may lead to better seizure diagnosis and management.
Background: Despite advances in neonatal care, neonates with moderate to severe HIE are at high risk of mortality and morbidity. we report the impact of a dedicated NNCC team on short term mortality and morbidities. Methods: A retrospective cohort study on neonates with moderate to serve HIE between July 1st 2008 and December 31st 2017. primary outcome : a composite of death and/or brain injury on MRI. Secondary outcomes: rate of cooling, length of hospital stay, anti-seizure medication burden, and use of inotropes. A regression analysis was done adjusting for gestational age, birth weight, gender, out-born status, Apgar score at 10 minutes, cord blood pH, and HIE clinical staging Results: 216 neonates were included, 109 before NNCC implementation, and 107 thereafter. NNCC program resulted in reduction in the primary outcome (AOR: 0.28, CI: 0.14-0.54, p<0.001) and brain injury (AOR: 0.28, CI: 0.14-0.55, p<0.001). It decreased average length of stay/infants by 5 days (p=0.03), improved cooling rate (73% compared to 93% , p <0.001), reduced: seizure misdiagnosis (71% compared to 23%, P <0.001), anti-seizure medication burden (P = 0.001), and inotrope use (34% compared to 53%, p=0.004) Conclusions: NNCC program decreased mortality and brain injury , shortened the length of hospital stay and improved care of neonates with significant HIE.
Subjects at ultra high-risk (UHR) for psychosis have an enhanced vulnerability to develop the disorder but the risk factors accounting for this accrued risk are undetermined.
Systematic review of associations between genetic or environmental risk factors for psychosis that are widely established in the literature and UHR state, based on comparisons to controls.
Forty-four studies encompassing 170 independent datasets and 54 risk factors were included. There were no studies on association between genetic or epigenetic risk factors and the UHR state that met the inclusion criteria. UHR subjects were more likely to show obstetric complications, tobacco use, physical inactivity, childhood trauma/emotional abuse/physical neglect, high perceived stress, childhood and adolescent low functioning, affective comorbidities, male gender, single status, unemployment and low educational level as compared to controls.
The increased vulnerability of UHR subjects can be related to environmental risk factors like childhood trauma, adverse life events and affective dysfunction. The role of genetic and epigenetic risk factors awaits clarification.
Nutrient deficiencies during childhood have adverse effects on child growth and health. In a single-arm 48-week long-term intervention, we previously reported the efficacy of oral nutritional supplementation (ONS) and dietary counselling on catch-up growth and growth maintenance in nutritionally at-risk Filipino children. The present analysis was done to assess the contributing effects of ONS to nutritional adequacy, dietary diversity, food intake and longitudinal growth. ONS (450 ml) was consumed daily providing 450 kcal (1880 kJ) and at least 50 % of micronutrient requirements among 200 children aged 3–4 years with weight-for-height percentiles between 5th and 25th (WHO Growth Standards). Weight, height and dietary intakes using 24-h food recalls were measured at baseline, and at weeks 4, 8, 16, 24, 32, 40 and 48. Nutrient adequacy and dietary diversity score (DDS) were calculated. Generalised estimating equations were used to assess the effects of total nutrient intakes, DDS, ONS compliance and sociodemographic factors on longitudinal growth. The percentages of children with adequate intake of energy, protein, Fe, Ca and some vitamins at each post-baseline visit were improved from baseline, reaching 100 % for most nutrients. DDS was also increased from baseline and reached significance from week 16 onwards (P < 0·01). Male children, total energy intake and parental employment status were associated with weight-for-height percentile gain (P < 0·05), whereas higher parental education level and ONS compliance were significantly associated with height-for-age percentile gain over time (P < 0·05). Long-term ONS intervention did not interfere with normal food intake and helped promote nutritional adequacy and growth of Filipino children.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.