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This report is on the synthesis by electrospinning of multiferroic core-shell nanofibers of strontium hexaferrite and lead zirconate titanate or barium titanate and studies on magneto-electric (ME) coupling. Fibers with well-defined core–shell structures showed the order parameters in agreement with values for nanostructures. The strength of ME coupling measured by the magnetic field-induced polarization showed the fractional change in the remnant polarization as high as 21%. The ME voltage coefficient in H-assembled films showed the strong ME response for the zero magnetic bias field. Follow-up studies and potential avenues for enhancing the strength of ME coupling in the core–shell nanofibers are discussed.
Reconstructions of prehistoric vegetation composition help establish natural baselines, variability, and trajectories of forest dynamics before and during the emergence of intensive anthropogenic land use. Pollen–vegetation models (PVMs) enable such reconstructions from fossil pollen assemblages using process-based representations of taxon-specific pollen production and dispersal. However, several PVMs and variants now exist, and the sensitivity of vegetation inferences to PVM selection, variant, and calibration domain is poorly understood. Here, we compare the reconstructions, parameter estimates, and structure of a Bayesian hierarchical PVM, STEPPS, both to observations and to REVEALS, a widely used PVM, for the pre–Euro-American settlement-era vegetation in the northeastern United States (NEUS). We also compare NEUS-based STEPPS parameter estimates to those for the upper midwestern United States (UMW). Both PVMs predict the observed macroscale patterns of vegetation composition in the NEUS; however, reconstructions of minor taxa are less accurate and predictions for some taxa differ between PVMs. These differences can be attributed to intermodel differences in structure and parameter estimates. Estimates of pollen productivity from STEPPS broadly agree with estimates produced for use in REVEALS, while comparison between pollen dispersal parameter estimates shows no significant relationship. STEPPS parameter estimates are similar between the UMW and NEUS, suggesting that STEPPS parameter estimates are transferable between floristically similar regions and scales.
The Genomics Used to Improve DEpresssion Decisions (GUIDED) trial assessed outcomes associated with combinatorial pharmacogenomic (PGx) testing in patients with major depressive disorder (MDD). Analyses used the 17-item Hamilton Depression (HAM-D17) rating scale; however, studies demonstrate that the abbreviated, core depression symptom-focused, HAM-D6 rating scale may have greater sensitivity toward detecting differences between treatment and placebo. However, the sensitivity of HAM-D6 has not been tested for two active treatment arms. Here, we evaluated the sensitivity of the HAM-D6 scale, relative to the HAM-D17 scale, when assessing outcomes for actively treated patients in the GUIDED trial.
Outpatients (N=1,298) diagnosed with MDD and an inadequate treatment response to >1 psychotropic medication were randomized into treatment as usual (TAU) or combinatorial PGx-guided (guided-care) arms. Combinatorial PGx testing was performed on all patients, though test reports were only available to the guided-care arm. All patients and raters were blinded to study arm until after week 8. Medications on the combinatorial PGx test report were categorized based on the level of predicted gene-drug interactions: ‘use as directed’, ‘moderate gene-drug interactions’, or ‘significant gene-drug interactions.’ Patient outcomes were assessed by arm at week 8 using HAM-D6 and HAM-D17 rating scales, including symptom improvement (percent change in scale), response (≥50% decrease in scale), and remission (HAM-D6 ≤4 and HAM-D17 ≤7).
At week 8, the guided-care arm demonstrated statistically significant symptom improvement over TAU using HAM-D6 scale (Δ=4.4%, p=0.023), but not using the HAM-D17 scale (Δ=3.2%, p=0.069). The response rate increased significantly for guided-care compared with TAU using both HAM-D6 (Δ=7.0%, p=0.004) and HAM-D17 (Δ=6.3%, p=0.007). Remission rates were also significantly greater for guided-care versus TAU using both scales (HAM-D6 Δ=4.6%, p=0.031; HAM-D17 Δ=5.5%, p=0.005). Patients taking medication(s) predicted to have gene-drug interactions at baseline showed further increased benefit over TAU at week 8 using HAM-D6 for symptom improvement (Δ=7.3%, p=0.004) response (Δ=10.0%, p=0.001) and remission (Δ=7.9%, p=0.005). Comparatively, the magnitude of the differences in outcomes between arms at week 8 was lower using HAM-D17 (symptom improvement Δ=5.0%, p=0.029; response Δ=8.0%, p=0.008; remission Δ=7.5%, p=0.003).
Combinatorial PGx-guided care achieved significantly better patient outcomes compared with TAU when assessed using the HAM-D6 scale. These findings suggest that the HAM-D6 scale is better suited than is the HAM-D17 for evaluating change in randomized, controlled trials comparing active treatment arms.
Until recently, beef carcass payment grids were predominantly based on weight and fatness categories with some adjustment for age, defined as number of adult teeth, to determine the price received by Australian beef producers for slaughter cattle. With the introduction of the Meat Standards Australia (MSA) grading system, the beef industry has moved towards payments that account for intramuscular fat (IMF) content (marble score (MarbSc)) and MSA grades. The possibility of a payment system based on lean meat yield (LMY, %) has also been raised. The BeefSpecs suite of tools has been developed to assist producers to meet current market specifications, specifically P8-rump fat and hot standard carcass weight (HCW). A series of equations have now been developed to partition empty body fat and fat-free weight into carcass fat-free mass (FFM) and fat mass (FM) and then into flesh FFM (FleshFFM) and flesh FM (FleshFM) to predict carcass components from live cattle assessments. These components then predict denuded lean (kg) and finally LMY (%) that contribute to emerging market specifications. The equations, along with the MarbSc equation, are described and then evaluated using two independent datasets. The decomposition of evaluation datasets demonstrates that error in prediction of HCW (kg), bone weight (BoneWt, kg), FleshFFM (kg), FleshFM (kg), MarbSc and chemical IMF percentage (ChemIMF%) is shown to be largely random error (%) in evaluation dataset 1, though error for ChemIMF% was primarily slope bias (%) in evaluation dataset 1, and BoneWt had substantial mean bias (%) in evaluation dataset 2. High modelling efficiencies of 0.97 and 0.95 for predicting HCW for evaluation datasets 1 and 2, respectively, suggest a high level of accuracy and precision in the prediction of HCW. The new outputs of the model are then described as to their role in estimating MSA index scores. The modelling system to partition chemical components of the empty body into carcass components is not dependent on the base modelling system used to derive empty body FFM and FM. This can be considered a general process that could be used with any appropriate model of body composition.
Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Decades of research show that people with schizophrenia have an increased risk of death from cancer; however, the relationship between schizophrenia and cancer incidence remains less clear. This population-based study investigates the incidence of seven common types of cancer among people with a hospital diagnosis of schizophrenia and accounting for the effects of age, sex and calendar time.
This population-based study used 1990–2013 data from three nationwide Swedish registries to calculate the incidence (in total, by age group and by sex) of any cancer and of lung, oesophageal, pancreatic, stomach, colon, (in men) prostate and (in women) breast cancer in 111 306 people with a hospital diagnosis of schizophrenia. The incidence in people with diagnosed schizophrenia was compared with the incidence in the general population. Risk estimates accounted for the effects of calendar time.
In 1 424 829 person-years of follow-up, schizophrenia did not confer an overall higher cancer risk (IRR 1.02, 95% CI 0.91–1.13) but was associated with a higher risk for female breast (IRR 1.19, 95% CI 1.12–1.26), lung (IRR 1.42, 95% CI 1.28–1.58), oesophageal (IRR 1.25, 95% CI 1.07–1.46) and pancreatic (IRR 1.10, 95% CI 1.01–1.21) and a lower risk of prostate (IRR 0.66, 95% CI 0.55–0.79) cancer. Some age- and sex-specific differences in risk were observed.
People with schizophrenia do not have a higher overall incidence of cancer than people in the general population. However, there are significant differences in the risk of specific cancer types overall and by sex calling for efforts to develop disease-specific prevention programmes. In people with schizophrenia, higher risk generally occurs in those <75 years.
Topical nasal decongestants are frequently used as part of the medical management of symptoms related to Eustachian tube dysfunction.
This study aimed to assess the effect of topical xylometazoline hydrochloride sprayed in the anterior part of the nose on Eustachian tube active and passive opening in healthy ears.
Active and passive Eustachian tube function was assessed in healthy subjects before and after intranasal administration of xylometazoline spray, using tympanometry, video otoscopy, sonotubometry, tubo-tympano-aerodynamic-graphy and tubomanometry.
Resting middle-ear pressures were not significantly different following decongestant application. Eustachian tube opening rate was not significantly different following the intervention, as measured by all function tests used. Sonotubometry data showed a significant increase in the duration of Eustachian tube opening following decongestant application.
There remains little or no evidence that topical nasal decongestants improve Eustachian tube function. Sonotubometry findings do suggest that further investigation with an obstructive Eustachian tube dysfunction patient cohort is warranted.
Light Detection and Ranging (LiDAR) is a primary sensor for autonomous vehicles to recognize surroundings. It detects near-infrared (NIR) light pulses, typically at 905nm, which is emitted and reflected by surrounding objects. Here, the fact of the matter is that conventional black or dark-tone cars with extremely low NIR reflection are hard to be detected by LiDAR and endanger the future highway. In this work, we propose to use platelet-shaped effect pigments with visible absorption and NIR reflectivity. Copper(Ⅱ) oxide and Silicon dioxide multilayer are theoretically investigated with different numbers of layers and thicknesses. The optimized structures appear various dark-tone colors with high NIR-reflectivity over 90%.
The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Iraq and Afghanistan Veterans with posttraumatic stress disorder (PTSD) and traumatic brain injury (TBI) history have high rates of performance validity test (PVT) failure. The study aimed to determine whether those with scores in the invalid versus valid range on PVTs show similar benefit from psychotherapy and if psychotherapy improves PVT performance.
Veterans (N = 100) with PTSD, mild-to-moderate TBI history, and cognitive complaints underwent neuropsychological testing at baseline, post-treatment, and 3-month post-treatment. Veterans were randomly assigned to cognitive processing therapy (CPT) or a novel hybrid intervention integrating CPT with TBI psychoeducation and cognitive rehabilitation strategies from Cognitive Symptom Management and Rehabilitation Therapy (CogSMART). Performance below standard cutoffs on any PVT trial across three different PVT measures was considered invalid (PVT-Fail), whereas performance above cutoffs on all measures was considered valid (PVT-Pass).
Although both PVT groups exhibited clinically significant improvement in PTSD symptoms, the PVT-Pass group demonstrated greater symptom reduction than the PVT-Fail group. Measures of post-concussive and depressive symptoms improved to a similar degree across groups. Treatment condition did not moderate these results. Rate of valid test performance increased from baseline to follow-up across conditions, with a stronger effect in the SMART-CPT compared to CPT condition.
Both PVT groups experienced improved psychological symptoms following treatment. Veterans who failed PVTs at baseline demonstrated better test engagement following treatment, resulting in higher rates of valid PVTs at follow-up. Veterans with invalid PVTs should be enrolled in trauma-focused treatment and may benefit from neuropsychological assessment after, rather than before, treatment.
The science of studying diamond inclusions for understanding Earth history has developed significantly over the past decades, with new instrumentation and techniques applied to diamond sample archives revealing the stories contained within diamond inclusions. This chapter reviews what diamonds can tell us about the deep carbon cycle over the course of Earth’s history. It reviews how the geochemistry of diamonds and their inclusions inform us about the deep carbon cycle, the origin of the diamonds in Earth’s mantle, and the evolution of diamonds through time.
Early in a foodborne disease outbreak investigation, illness incubation periods can help focus case interviews, case definitions, clinical and environmental evaluations and predict an aetiology. Data describing incubation periods are limited. We examined foodborne disease outbreaks from laboratory-confirmed, single aetiology, enteric bacterial and viral pathogens reported to United States foodborne disease outbreak surveillance from 1998–2013. We grouped pathogens by clinical presentation and analysed the reported median incubation period among all illnesses from the implicated pathogen for each outbreak as the outbreak incubation period. Outbreaks from preformed bacterial toxins (Staphylococcus aureus, Bacillus cereus and Clostridium perfringens) had the shortest outbreak incubation periods (4–10 h medians), distinct from that of Vibrio parahaemolyticus (17 h median). Norovirus, salmonella and shigella had longer but similar outbreak incubation periods (32–45 h medians); campylobacter and Shiga toxin-producing Escherichia coli had the longest among bacteria (62–87 h medians); hepatitis A had the longest overall (672 h median). Our results can help guide diagnostic and investigative strategies early in an outbreak investigation to suggest or rule out specific etiologies or, when the pathogen is known, the likely timeframe for exposure. They also point to possible differences in pathogenesis among pathogens causing broadly similar syndromes.
Patients with major depressive disorder (MDD) display cognitive deficits in acutely depressed and remitted states. Childhood maltreatment is associated with cognitive dysfunction in adults, but its impact on cognition and treatment related cognitive outcomes in adult MDD has received little consideration. We investigate whether, compared to patients without maltreatment and healthy participants, adult MDD patients with childhood maltreatment display greater cognitive deficits in acute depression, lower treatment-associated cognitive improvements, and lower cognitive performance in remission.
Healthy and acutely depressed MDD participants were enrolled in a multi-center MDD predictive marker discovery trial. MDD participants received 16 weeks of standardized antidepressant treatment. Maltreatment and cognition were assessed with the Childhood Experience of Care and Abuse interview and the CNS Vital Signs battery, respectively. Cognitive scores and change from baseline to week 16 were compared amongst MDD participants with (DM+, n = 93) and without maltreatment (DM−, n = 90), and healthy participants with (HM+, n = 22) and without maltreatment (HM−, n = 80). Separate analyses in MDD participants who remitted were conducted.
DM+ had lower baseline global cognition, processing speed, and memory v. HM−, with no significant baseline differences amongst DM−, HM+, and HM− groups. There were no significant between-group differences in cognitive change over 16 weeks. Post-treatment remitted DM+, but not remitted DM−, scored significantly lower than HM− in working memory and processing speed.
Childhood maltreatment was associated with cognitive deficits in depressed and remitted adults with MDD. Maltreatment may be a risk factor for more severe and persistent cognitive deficits in adult MDD.
Machine learning algorithms could potentially be used to classify patients referred on the two-week wait pathway for suspected head and neck cancer. Patients could be classified into ‘predicted cancer’ or ‘predicted non-cancer’ groups.
A variety of machine learning algorithms were assessed using the clinical data of 5082 patients. These patients had previously been referred via the two-week wait pathway for suspected head and neck cancer to two separate tertiary referral centres in the UK. Outcomes from machine learning classification were analysed in comparison to known clinical diagnoses.
Variational logistic regression was the most clinically useful technique of those chosen to perform the analysis and patient classification; the proportion of patients correctly classified as having ‘non-cancer’ was 25.8 per cent, with a false negative rate of 1 out of 1000.
Machine learning algorithms can accurately and effectively classify patients referred with suspected head and neck cancer symptoms.
Evidence suggests that low birth weight and fetal exposure to extreme maternal undernutrition is associated with cardiovascular disease in adulthood. Hyperemesis gravidarum, a clinical entity characterized by severe nausea and excess vomiting leading to a suboptimal maternal nutritional status during early pregnancy, is associated with an increased risk of adverse pregnancy outcomes. Several studies also showed that different measures related to hyperemesis gravidarum, such as maternal daily vomiting or severe weight loss, are associated with increased risks of adverse fetal pregnancy outcomes. Not much is known about long-term offspring consequences of maternal hyperemesis gravidarum and related measures during pregnancy. We examined the associations of maternal daily vomiting during early pregnancy, as a measure related to hyperemesis gravidarum, with childhood cardiovascular risk factors.
In a population-based prospective cohort study from early pregnancy onwards among 4,769 mothers and their children in Rotterdam, the Netherlands, we measured childhood body mass index, total fat mass percentage, android/gynoid fat mass ratio, preperitoneal fat mass area, blood pressure, lipids, and insulin levels. We used multiple regression analyses to assess the associations of maternal vomiting during early pregnancy with childhood cardiovascular outcomes.
Compared with the children of mothers without daily vomiting during early pregnancy, the children of mothers with daily vomiting during early pregnancy had a higher childhood total body fat mass (difference 0.12 standard deviation score [SDS]; 95% confidence interval [CI] 0.03–0.20), android/gynoid fat mass ratio (difference 0.13 SDS; 95% CI 0.04–0.23), and preperitoneal fat mass area (difference 0.10 SDS; 95% CI 0–0.20). These associations were not explained by birth characteristics but partly explained by higher infant growth. Maternal daily vomiting during early pregnancy was not associated with childhood blood pressure, lipids, and insulin levels.
Maternal daily vomiting during early pregnancy is associated with higher childhood total body fat mass and abdominal fat mass levels, but not with other cardiovascular risk factors. Further studies are needed to replicate these findings, to explore the underlying mechanisms and to assess the long-term consequences.
We describe the design and deployment of GREENBURST, a commensal Fast Radio Burst (FRB) search system at the Green Bank Telescope. GREENBURST uses the dedicated L-band receiver tap to search over the 960–1 920 MHz frequency range for pulses with dispersion measures out to
. Due to its unique design, GREENBURST is capable of conducting searches for FRBs when the L-band receiver is not being used for scheduled observing. This makes it a sensitive single pixel detector capable of reaching deeper in the radio sky. While single pulses from Galactic pulsars and rotating radio transients will be detectable in our observations, and will form part of the database we archive, the primary goal is to detect and study FRBs. Based on recent determinations of the all-sky rate, we predict that the system will detect approximately one FRB for every 2–3 months of continuous operation. The high sensitivity of GREENBURST means that it will also be able to probe the slope of the FRB fluence distribution, which is currently uncertain in this observing band.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.