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Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
Optimal stroke care requires access to resources such as neuroimaging, acute revascularization, rehabilitation, and stroke prevention services, which may not be available in rural areas. We aimed to determine geographic access to stroke care for residents of rural communities in the province of Ontario, Canada.
We used the Ontario Road Network File database linked with the 2016 Ontario Acute Stroke Care Resource Inventory to estimate the proportion of people in rural communities, defined as those with a population size <10,000, who were within 30, 60, and 240 minutes of travel time by car from stroke care services, including brain imaging, thrombolysis treatment centers, stroke units, stroke prevention clinics, inpatient rehabilitation facilities, and endovascular treatment centers.
Of the 1,496,262 people residing in rural communities, the majority resided within 60 minutes of driving time to a center with computed tomography (85%), thrombolysis (81%), a stroke unit (68%), a stroke prevention clinic (74%), or inpatient rehabilitation (77.0%), but a much lower proportion (32%) were within 60 minutes of driving time to a center capable of providing endovascular thrombectomy (EVT).
Most rural Ontario residents have appropriate geographic access to stroke services, with the exception of EVT. This information may be useful for jurisdictions seeking to optimize the regional organization of stroke care services.
Progesterone (P4) plays a key role in pregnancy establishment and maintenance; during early pregnancy, P4 stimulates the production and release of uterine secretions necessary for conceptus growth prior to implantation; therefore, exogenous P4 supplementation may improve embryo development. This study evaluated the effects of supplementation during early pregnancy with long-acting injectable progesterone or altrenogest on embryonic characteristics of sows and gilts. Thus, a total of 32 sows and 16 gilts were used. On day 6 of pregnancy sows and gilts were allocated to one of the following groups: non-supplemented; supplemented with 20 mg of altrenogest, orally, from days 6 to 12 of pregnancy; supplemented with 2.15 mg/kg of long-acting injectable progesterone on day 6 of pregnancy. Animals were killed on day 28 of pregnancy, and ovulation rate, embryo survival, embryo weight, crown-to-rump length, uterine glandular epithelium and endometrial vascularization were assessed. Treatments had no effect on pregnancy rate, embryo survival or endometrial vascular density (P > 0.05). Non-supplemented gilts presented larger and heavier embryos compared to gilts from supplemented groups (P < 0.05). Sows in the altrenogest group presented larger and heavier embryos compared to non-supplemented sows and sows supplemented with long-acting injectable progesterone. In conclusion, supplementation of sows and gilts with progestagen from day 6 of pregnancy can be used as a means to improve embryo survival without deleterious effects.
The detection of fireballs streaks in astronomical imagery can be carried out by a variety of methods. The Desert Fireball Network uses a network of cameras to track and triangulate incoming fireballs to recover meteorites with orbits and to build a fireball orbital dataset. Fireball detection is done on-board camera, but due to the design constraints imposed by remote deployment, the cameras are limited in processing power and time. We describe the processing software used for fireball detection under these constrained circumstances. Two different approaches were compared: (1) A single-layer neural network with 10 hidden units that were trained using manually selected fireballs and (2) a more traditional computational approach based on cascading steps of increasing complexity, whereby computationally simple filters are used to discard uninteresting portions of the images, allowing for more computationally expensive analysis of the remainder. Both approaches allowed a full night’s worth of data (over a thousand 36-megapixel images) to be processed each day using a low-power single-board computer. We distinguish between large (likely meteorite-dropping) fireballs and smaller fainter ones (typical ‘shooting stars’). Traditional processing and neural network algorithms both performed well on large fireballs within an approximately 30 000-image dataset, with a true positive detection rate of 96% and 100%, respectively, but the neural network was significantly more successful at smaller fireballs, with rates of 67% and 82%, respectively. However, this improved success came at a cost of significantly more false positives for the neural network results, and additionally the neural network does not produce precise fireball coordinates within an image (as it classifies). Simple consideration of the network geometry indicates that overall detection rate for triangulated large fireballs is calculated to be better than 99.7% and 99.9%, by ensuring that there are multiple double-station opportunities to detect any one fireball. As such, both algorithms are considered sufficient for meteor-dropping fireball event detection, with some consideration of the acceptable number of false positives compared to sensitivity.
Longitudinal studies of first episode of psychosis (FEP) patients are critical to understanding the dynamic clinical factors influencing functional outcomes; negative symptoms and verbal memory (VM) deficits are two such factors that remain a therapeutic challenge. This study uses white-gray matter contrast at the inner edge of the cortex, in addition to cortical thickness, to probe changes in microstructure and their relation with negative symptoms and possible intersections with verbal memory.
T1-weighted images and clinical data were collected longitudinally for patients (N = 88) over a two-year period. Cognitive data were also collected at baseline. Relationships between baseline VM (immediate/delayed recall) and rate of change in two negative symptom dimensions, amotivation and expressivity, were assessed at the behavioral level, as well as at the level of brain structure.
VM, particularly immediate recall, was significantly and positively associated with a steeper rate of expressivity symptom decline (r = 0.32, q = 0.012). Significant interaction effects between baseline delayed recall and change in expressivity were uncovered in somatomotor regions bilaterally for both white-gray matter contrast and cortical thickness. Furthermore, interaction effects between immediate recall and change in expressivity on cortical thickness rates were uncovered across higher-order regions of the language processing network.
This study shows common neural correlates of language-related brain areas underlying expressivity and VM in FEP, suggesting deficits in these domains may be more linked to speech production rather than general cognitive capacity. Together, white-gray matter contrast and cortical thickness may optimally inform clinical investigations aiming to capture peri-cortical microstructural changes.
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.
The use of additives such as ractopamine (Rac) in pregnant sows during early-mid pregnancy is an alternative to increase foetal and progeny growth and development. However, Rac supplementation in finishing pigs can lead to behavioural and physiological changes similar to the typical stress responses. The objective of this study was to evaluate the effects of dietary supplementation with Rac in pregnant sows from day 25 to 50 of gestation (pre-hyperplastic stage) on piglet’s vitality, blood parameters, number, diameter and perimeter of muscle fibres in semitendinosus muscle and developmental characteristics of piglets at birth to weaning. Forty-one hybrid sows were divided into three dietary treatments: (1) control diet without Rac (control), (2) addition of 10 mg/kg of Rac (Rac10) and (3) addition of 20 mg/kg of Rac (Rac20). Higher numbers of low-vitality piglets (P<0.05) were observed in Rac-fed sows, regardless of dose, compared with the control group. Very low-density lipoprotein levels were lower in the Rac10 group when compared with the Rac20 group at day 21. Haematocrit was greater, and the mean corpuscular haemoglobin concentration was lower in piglets from Rac-fed sows. No significant statistical differences were detected regarding piglets body weight, average daily gain, blood gasometry, complete blood count and muscle fibre measurements in semitendinosus muscle. The use of Rac in pregnant sows reduced the vitality parameters of piglets but did not improve the performance from birth until weaning and did not negatively influence the haematological parameter and lipid metabolism.
Background: Previous post-hoc analysis of three 12-week, double-blind, placebo-controlled trials of adjunctive brivaracetam (BRV) in patients with focal seizures demonstrated similar efficacy over placebo regardless of previous carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or topiramate (TPM) failure. This analysis explored long-term retention of adjunctive BRV in patients with previous CBZ/LTG/LEV/TPM. Methods: Post-hoc analysis of double-blind, placebo-controlled trial (N01358 [NCT01261325]) and open-label extension (N01379 [NCT01339559]; cut-off 15-March-2017) of adjunctive BRV in patients (≥16 years) with focal seizures. Outcomes were assessed in patients randomized to BRV (100 or 200 mg/day) who had previous CBZ/LTG/LEV/TPM (stopped ≥90 days before BRV initiation). Results: 503 patients were analyzed. Baseline characteristics were generally similar in subgroups with previous CBZ/LTG/LEV/TPM (n=209/162/256/182). Overall, Kaplan-Meier-estimated BRV retention at 1-, 3-, and 5-years was 71.0%, 50.9%, and 32.4%. Across previous antiepileptic drug (AED) subgroups, Kaplan-Meier-estimated BRV retention (1-year: 64.8%–73.2%; 3-year: 41.9%–49.9%; 5-year: 31.5%–35.7%), BRV discontinuations (58.4%–63.0%), and most common reasons for discontinuation (lack of efficacy: 23.0%–25.3%; adverse event: 16.7%–22.2%) were generally similar. Conclusions: Post-hoc analysis demonstrated similar long-term retention rates and discontinuation reasons with adjunctive BRV in adults previously treated with CBZ/LTG/LEV/TPM. Adjunctive BRV provides long-term effectiveness in patients who failed common AED treatments, including LEV.
Introduction: September 2017 saw the launch of the British Columbia (BC) Emergency Medicine Network (EM Network), an innovative clinical network established to improve emergency care across the province. The intent of the EM Network is to support the delivery of evidence-informed, patient-centered care in all 108 Emergency Departments and Diagnostic & Treatment Centres in BC. After one year, the Network undertook a formative evaluation to guide its growth. Our objective is to describe the evaluation approach and early findings. Methods: The EM Network was evaluated on three levels: member demographics, online engagement and member perceptions of value and progress. For member demographics and online engagement, data were captured from member registration information on the Network's website, Google Analytics and Twitter Analytics. Membership feedback was sought through an online survey using a social network analysis tool, PARTNER (Program to Analyze, Record, and Track Networks to Enhance Relationships), and semi-structured individual interviews. This framework was developed based on literature recommendations in collaboration with Network members, including patient representatives. Results: There are currently 622 EM Network members from an eligible denominator of approximately 1400 physicians (44%). Seventy-three percent of the Emergency Departments and Diagnostic and Treatment Centres in BC currently have Network members, and since launch, the EM Network website has been accessed by 11,154 unique IP addresses. Online discussion forum use is low but growing, and Twitter following is high. There are currently 550 Twitter followers and an average of 27 ‘mentions’ of the Network by Twitter users per month. Member feedback through the survey and individual interviews indicates that the Network is respected and credible, but many remain unaware of its purpose and offerings. Conclusion: Our findings underscore that early evaluation is useful to identify development needs, and for the Network this includes increasing awareness and online dialogue. However, our results must be interpreted cautiously in such a young Network, and thus, we intend to re-evaluate regularly. Specific action recommendations from this baseline evaluation include: increasing face-to-face visits of targeted communities; maintaining or accelerating communication strategies to increase engagement; and providing new techniques that encourage member contributions in order to grow and improve content.
The increased use of insecticide seed treatments in rice has raised many questions about the potential benefits of these products. In 2014 and 2015, a field experiment was conducted near Stuttgart and Lonoke, AR, to evaluate whether an insecticide seed treatment could possibly lessen injury from acetolactate synthase (ALS)–inhibiting herbicides in imidazolinone-resistant (IR) rice. Two IR cultivars were tested (a hybrid, ‘CLXL745’, and an inbred, ‘CL152’), with and without an insecticide seed treatment (thiamethoxam). Four different herbicide combinations were evaluated: a nontreated control, two applications of bispyribac-sodium (hereafter bispyribac), two applications of imazethapyr, and two applications of imazethapyr plus bispyribac. The first herbicide application was to two- to three-leaf rice, and the second immediately prior to flooding (one- to two-tiller). At both 2 and 4 wk after final treatment (WAFT), the sequential applications of imazethapyr or bispyribac plus imazethapyr were more injurious to CLXL745 than CL152. This increased injury led to decreased groundcover 3 WAFT. Rice treated with thiamethoxam was less injured than nontreated rice and had improved groundcover and greater canopy heights. Even with up to 32% injury, the rice plants recovered by the end of the growing season, and yields within a cultivar were similar with and without a thiamethoxam seed treatment across all herbicide treatments. Based on these results, thiamethoxam can partially protect rice from injury caused by ALS-inhibiting herbicides as well as increase groundcover and canopy height; that is, the injury to rice never negatively affected yield.
We recently reported an association of offspring educational attainment with polygenic risk scores (PRS) computed on parent’s non-transmitted alleles for educational attainment using the second GWAS meta-analysis article on educational attainment published by the Social Science Genetic Association Consortium. Here we test the replication of these findings using a more powerful PRS from the third GWAS meta-analysis article by the Consortium. Each of the key findings of our previous paper is replicated using this improved PRS (N = 2335 adolescent twins and their genotyped parents). The association of children’s attainment with their own PRS increased substantially with the standardized effect size, moving from β = 0.134, 95% CI = 0.079, 0.188 for EA2, to β = 0.223, 95% CI = 0.169, 0.278, p < .001, for EA3. Parent’s PRS again predicted the socioeconomic status (SES) they provided to their offspring and increased from β = 0.201, 95% CI = 0.147, 0.256 to β = 0.286, 95% CI = 0.239, 0.333. Importantly, the PRS for alleles not transmitted to their offspring — therefore acting via the parenting environment — was increased in effect size from β = 0.058, 95% CI = 0.003, 0.114 to β = 0.067, 95% CI = 0.012, 0.122, p = .016. As previously found, this non-transmitted genetic effect was fully accounted for by parental SES. The findings reinforce the conclusion that genetic effects of parenting are substantial, explain approximately one-third the magnitude of an individual’s own genetic inheritance and are mediated by parental socioeconomic competence.
We evaluated the effects of cattle manure and inoculation with arbuscular mycorrhizal fungi (AMF) in maize plants growing in a semiarid area of Brazilian north-east in 2012 and 2013. Three isolates of AMF (Acaulosporalongula URM-FMA 07 and URM-FMA 03, Claroideoglomusetunicatum UNIVASF 06A) were used, with or without the application of cattle manure, during two growing cycles. In the first year, significant effects of inoculation were detected for straw yield only when the manure was applied. In the second year, there was an interaction between fertilisation and inoculation for plant height and grain yield, with the highest values in the fertilised treatments. Inoculation with A. longula demonstrated that mycorrhizal inoculation in field-grown plants could be an alternative management for improving plant growth and grain yield, reducing the use of cattle manure. The AMF sporulation and mycorrhizal colonisation were improved after inoculation, and A. longula URM-FMA 07 increased sporulation by more than 15 times while inoculation with C. etunicatum increased sporulation by more than 3 times. The mycorrhizal inoculation is a management practice that can be useful for recovering or maintaining AMF infective propagules in soil, showing potential to be used in large-scale field conditions in Brazilian semiarid. Although mycorrhisation presents high agricultural relevance due to benefits promoted to the soil and plants, the knowledge about the factors influencing the interactions among microorganisms, soil and plants need to be broadened aiming to achieve successful crop management in semiarid regions.
A wealth of clinical studies have identified objective biomarkers, which separate schizophrenia patients from healthy controls on a group level, but current diagnostic systems solely include clinical symptoms. In this study, we investigate if machine learning algorithms on multimodal data can serve as a framework for clinical translation.
Forty-six antipsychotic-naïve, first-episode schizophrenia patients and 58 controls underwent neurocognitive tests, electrophysiology, and magnetic resonance imaging (MRI). Patients underwent clinical assessments before and after 6 weeks of antipsychotic monotherapy with amisulpride. Nine configurations of different supervised machine learning algorithms were applied to first estimate the unimodal diagnostic accuracy, and next to estimate the multimodal diagnostic accuracy. Finally, we explored the predictability of symptom remission.
Cognitive data significantly classified patients from controls (accuracies = 60–69%; p values = 0.0001–0.009). Accuracies of electrophysiology, structural MRI, and diffusion tensor imaging did not exceed chance level. Multimodal analyses with cognition plus any combination of one or more of the remaining three modalities did not outperform cognition alone. None of the modalities predicted symptom remission.
In this multivariate and multimodal study in antipsychotic-naïve patients, only cognition significantly discriminated patients from controls, and no modality appeared to predict short-term symptom remission. Overall, these findings add to the increasing call for cognition to be included in the definition of schizophrenia. To bring about the full potential of machine learning algorithms in first-episode, antipsychotic-naïve schizophrenia patients, careful a priori variable selection based on independent data as well as inclusion of other modalities may be required.
Each year there are multiple reports of drift occurrences, and the majority of drift complaints in rice are from imazethapyr or glyphosate. In 2014 and 2015, multiple field experiments were conducted near Stuttgart, AR, and near Lonoke, AR, to evaluate whether insecticide seed treatments would reduce injury from glyphosate or imazethapyr drift or decrease the recovery time following exposure to a low rate of these herbicides. Study I was referred to as the “seed treatment study,” and Study II was the “drift timing study.” In the seed treatment study the conventional rice cultivar ‘Roy J’ was planted, and herbicide treatments included imazethapyr at 10.5 g ai ha–1, glyphosate at 126 g ae ha–1, or no herbicide. Each plot had either a seed treatment of thiamethoxam, clothianidin, chlorantraniliprole, or no insecticide seed treatment. The herbicides were applied at the two- to three-leaf growth stage. Crop injury was assessed 1, 3, and 5 wk after application. Averaged over site-years, thiamethoxam-treated rice had less injury than rice with no insecticide seed treatment at each rating, along with an increased yield. Clothianidin-treated rice had an increased yield over no insecticide seed treatment, but the reduction in injury for both herbicides was less pronounced than in the thiamethoxam-treated plots. Overall, chlorantraniliprole was generally the least effective of the three insecticides in reducing injury from either herbicide and in protecting rice yield potential. A second experiment conducted at Stuttgart, AR, was meant to determine whether damage to rice from glyphosate and imazethapyr was influenced by the timing (15, 30, and 45 d after planting) of exposure to herbicides for thiamethoxam-treated and nontreated rice. There was an overall reduction in injury with the use of thiamethoxam, but the reduction in injury was not dependent on the timing of the drift event. Reduction in damage from physical drift of glyphosate and imazethapyr as well as increased yields over the absence of an insecticide seed treatment appear to be an added benefit.
A Last affiliation changed 3 to 4 against MS. Please check and confirm if it is fine. small number of the sample of 184 carbon stars in the Magellanic Clouds show signs that they are in the act of evolving off of the asymptotic giant branch. Most carbon stars grow progressively redder in all infrared colors and develop stronger pulsation amplitudes as their circumstellar dust shells become optically thicker. The reddest sources, however, have unexpectedly low pulsation amplitudes, and some even show blue excesses that could point to deviations from spherical symmetry as they eject the last of their envelopes. Previously, all dusty carbon-rich AGB stars have been labeled “extreme,” but that term should be reserved for the truly extreme carbon stars. These objects may well hold the clues needed to disentangle what actually happens when a star ejects the last of its envelope and evolves off of the AGB.
We present ALMA band 7 data of the extreme OH/IR star, OH 26.5+0.6. In addition to lines of CO and its isotopologues, the circumstellar envelope also exhibits a number of emission lines due to metal-containing molecules, e.g., NaCl and KCl. A lack of C18O is expected, but a non-detection of C17O is puzzling given the strengths of H217O in Herschel spectra of the star. However, a line associated with Si17O is detected. We also report a tentative detection of a gas-phase emission line of MgS. The ALMA spectrum of this object reveals intriguing features which may be used to investigate chemical processes and dust formation during a high mass-loss phase.
We present very detailed images of the photosphere of an AGB star obtained with the PIONIER instrument, installed at the Very Large Telescope Interferometer (VLTI). The images show a well defined stellar disc populated by a few convective patterns. Thanks to the high precision of the observations we are able to derive the contrast and granulation horizontal scale of the convective pattern for the first time in a direct way. Such quantities are then compared with scaling relations between granule size, effective temperature, and surface gravity that are predicted by simulations of stellar surface convection.
Silicon carbide together with amorphous carbon are the main components of dust grains in the atmospheres of C-rich AGB stars. Small gaseous Si-C bearing molecules (such as SiC, SiCSi, and SiC2) are efficiently formed close to the stellar photosphere. They likely condense onto dust seeds owing to their highly refractory nature at the lower temperatures (i.e., below about 2500 K) in the dust growth zone which extends a few stellar radii from the photosphere. Beyond this region, the abundances of Si-C bearing molecules are expected to decrease until they are eventually reformed in the outer shells of the circumstellar envelope, owing to the interaction between the gas and the interstellar UV radiation field. Our goal is to understand the time-dependent chemical evolution of Si-C bond carriers probed by molecular spectral line emission in the circumstellar envelope of IRC+10216 at millimeter wavelengths.
Our objective was to identify predictors of severe acute respiratory infection in hospitalised patients and understand the impact of vaccination and neuraminidase inhibitor administration on severe influenza. We analysed data from a study evaluating influenza vaccine effectiveness in two Michigan hospitals during the 2014–2015 and 2015–2016 influenza seasons. Adults admitted to the hospital with an acute respiratory infection were eligible. Through patient interview and medical record review, we evaluated potential risk factors for severe disease, defined as ICU admission, 30-day readmission, and hospital length of stay (LOS). Two hundred sixteen of 1119 participants had PCR-confirmed influenza. Frailty score, Charlson score and tertile of prior-year healthcare visits were associated with LOS. Charlson score >2 (OR 1.5 (1.0–2.3)) was associated with ICU admission. Highest tertile of prior-year visits (OR 0.3 (0.2–0.7)) was associated with decreased ICU admission. Increasing tertile of visits (OR 1.5 (1.2–1.8)) was associated with 30-day readmission. Frailty and prior-year healthcare visits were associated with 30-day readmission among influenza-positive participants. Neuraminidase inhibitors were associated with decreased LOS among vaccinated participants with influenza A (HR 1.6 (1.0–2.4)). Overall, frailty and lack of prior-year healthcare visits were predictors of disease severity. Neuraminidase inhibitors were associated with reduced severity among vaccine recipients.
Karlsruhe Institute of Technology (KIT) is doing research and development in the field of megawatt-class radio frequency (RF) sources (gyrotrons) for the Electron Cyclotron Resonance Heating (ECRH) systems of the International Thermonuclear Experimental Reactor (ITER) and the DEMOnstration Fusion Power Plant that will follow ITER. In the focus is the development and verification of the European coaxial-cavity gyrotron technology which shall lead to gyrotrons operating at an RF output power significantly larger than 1 MW CW and at an operating frequency above 200 GHz. A major step into that direction is the final verification of the European 170 GHz 2 MW coaxial-cavity pre-prototype at longer pulses up to 1 s. It bases on the upgrade of an already existing highly modular short-pulse (ms-range) pre-prototype. That pre-prototype has shown a world record output power of 2.2 MW already. This paper summarizes briefly the already achieved experimental results using the short-pulse pre-prototype and discusses in detail the design and manufacturing process of the upgrade of the pre-prototype toward longer pulses up to 1 s.