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Typical enteropathogenic Escherichia coli (tEPEC) infection is a major cause of diarrhoea and contributor to mortality in children <5 years old in developing countries. Data were analysed from the Global Enteric Multicenter Study examining children <5 years old seeking care for moderate-to-severe diarrhoea (MSD) in Kenya. Stool specimens were tested for enteric pathogens, including by multiplex polymerase chain reaction for gene targets of tEPEC. Demographic, clinical and anthropometric data were collected at enrolment and ~60-days later; multivariable logistic regressions were constructed. Of 1778 MSD cases enrolled from 2008 to 2012, 135 (7.6%) children tested positive for tEPEC. In a case-to-case comparison among MSD cases, tEPEC was independently associated with presentation at enrolment with a loss of skin turgor (adjusted odds ratio (aOR) 2.08, 95% confidence interval (CI) 1.37–3.17), and convulsions (aOR 2.83, 95% CI 1.12–7.14). At follow-up, infants with tEPEC compared to those without were associated with being underweight (OR 2.2, 95% CI 1.3–3.6) and wasted (OR 2.5, 95% CI 1.3–4.6). Among MSD cases, tEPEC was associated with mortality (aOR 2.85, 95% CI 1.47–5.55). This study suggests that tEPEC contributes to morbidity and mortality in children. Interventions aimed at defining and reducing the burden of tEPEC and its sequelae should be urgently investigated, prioritised and implemented.
Gravitational waves from coalescing neutron stars encode information about nuclear matter at extreme densities, inaccessible by laboratory experiments. The late inspiral is influenced by the presence of tides, which depend on the neutron star equation of state. Neutron star mergers are expected to often produce rapidly rotating remnant neutron stars that emit gravitational waves. These will provide clues to the extremely hot post-merger environment. This signature of nuclear matter in gravitational waves contains most information in the 2–4 kHz frequency band, which is outside of the most sensitive band of current detectors. We present the design concept and science case for a Neutron Star Extreme Matter Observatory (NEMO): a gravitational-wave interferometer optimised to study nuclear physics with merging neutron stars. The concept uses high-circulating laser power, quantum squeezing, and a detector topology specifically designed to achieve the high-frequency sensitivity necessary to probe nuclear matter using gravitational waves. Above 1 kHz, the proposed strain sensitivity is comparable to full third-generation detectors at a fraction of the cost. Such sensitivity changes expected event rates for detection of post-merger remnants from approximately one per few decades with two A+ detectors to a few per year and potentially allow for the first gravitational-wave observations of supernovae, isolated neutron stars, and other exotica.
The radiocarbon (14C) calibration curve so far contains annually resolved data only for a short period of time. With accelerator mass spectrometry (AMS) matching the precision of decay counting, it is now possible to efficiently produce large datasets of annual resolution for calibration purposes using small amounts of wood. The radiocarbon intercomparison on single-year tree-ring samples presented here is the first to investigate specifically possible offsets between AMS laboratories at high precision. The results show that AMS laboratories are capable of measuring samples of Holocene age with an accuracy and precision that is comparable or even goes beyond what is possible with decay counting, even though they require a thousand times less wood. It also shows that not all AMS laboratories always produce results that are consistent with their stated uncertainties. The long-term benefits of studies of this kind are more accurate radiocarbon measurements with, in the future, better quantified uncertainties.
Presently, evidence guiding clinicians on the optimal approach to safely screen patients for coronavirus disease 2019 (COVID-19) to a nonemergent hospital procedure is scarce. In this report, we describe our experience in screening for SARS-CoV-2 prior to semiurgent and urgent hospital procedures.
Retrospective case series.
A single tertiary-care medical center.
Our study cohort included patients ≥18 years of age who had semiurgent or urgent hospital procedures or surgeries.
Overall, 625 patients were screened for SARS-CoV-2 using a combination of phone questionnaire (7 days prior to the anticipated procedure), RT-PCR and chest computed tomography (CT) between March 1, 2020, and April 30, 2020.
Of the 625 patients, 520 scans (83.2%) were interpreted as normal; 1 (0.16%) had typical features of COVID-19; 18 scans (2.88%) had indeterminate features of COVID-19; and 86 (13.76%) had atypical features of COVID-19. In total, 640 RT-PCRs were performed, with 1 positive result (0.15%) in a patient with a CT scan that yielded an atypical finding. Of the 18 patients with chest CTs categorized as indeterminate, 5 underwent repeat negative RT-PCR nasopharyngeal swab 1 week after their initial swab. Also, 1 patient with a chest CT categorized as typical had a follow-up repeat negative RT-PCR, indicating that the chest CT was likely a false positive. After surgery, none of the patients developed signs or symptoms suspicious of COVID-19 that would indicate the need for a repeated RT-PCR or CT scan.
In our experience, chest CT scanning did not prove provide valuable information in detecting asymptomatic cases of SARS-CoV-2 (COVID-19) in our low-prevalence population.
Introduction: For rhythm control of acute atrial flutter (AAFL) in the emergency department (ED), choices include initial drug therapy or initial electrical cardioversion (ECV). We compared the strategies of pharmacological cardioversion followed by ECV if necessary (Drug-Shock), and ECV alone (Shock Only). Methods: We conducted a randomized, blinded, placebo-controlled trial (1:1 allocation) comparing two rhythm control strategies at 11 academic EDs. We included stable adult patients with AAFL, where onset of symptoms was <48 hours. Patients underwent central web-based randomization stratified by site. The Drug-Shock group received an infusion of procainamide (15mg/kg over 30 minutes) followed 30 minutes later, if necessary, by ECV at 200 joules x 3 shocks. The Shock Only group received an infusion of saline followed, if necessary, by ECV x 3 shocks. The primary outcome was conversion to sinus rhythm for ≥30 minutes at any time following onset of infusion. Patients were followed for 14 days. The primary outcome was evaluated on an intention-to-treat basis. Statistical significance was assessed using chi-squared tests and multivariable logistic regression. Results: We randomized 76 patients, and none was lost to follow-up. The Drug-Shock (N = 33) and Shock Only (N = 43) groups were similar for all characteristics including mean age (66.3 vs 63.4 yrs), duration of AAFL (30.1 vs 24.5 hrs), previous AAFL (72.7% vs 69.8%), median CHADS2 score (1 vs 1), and mean initial heart rate (128.9 vs 126.0 bpm). The Drug-Shock and Shock only groups were similar for the primary outcome of conversion (100% vs 93%; absolute difference 7.0%, 95% CI -0.6;14.6; P = 0.25). The multivariable analyses confirmed the similarity of the two strategies (P = 0.19). In the Drug-Shock group 21.2% of patients converted with the infusion. There were no statistically significant differences for time to conversion (84.2 vs 97.6 minutes), total ED length of stay (9.4 vs 7.5 hours), disposition home (100% vs 95.3%), and stroke within 14 days (0 vs 0). Premature discontinuation of infusion (usually for transient hypotension) was more common in the Drug-Shock group (9.1% vs 0.0%) but there were no serious adverse events. Conclusion: Both the Drug-Shock and Shock Only strategies were highly effective and safe in allowing AAFL patients to go home in sinus rhythm. IV procainamide alone was effective in only one fifth of patients, much less than for acute AF.
Introduction: Acute heart failure (AHF) is a common emergency department (ED) presentation and may be associated with poor outcomes. Conversely, many patients rapidly improve with ED treatment and may not need hospital admission. Because there is little evidence to guide disposition decisions by ED and admitting physicians, we sought to create a risk score for predicting short-term serious outcomes (SSO) in patients with AHF. Methods: We conducted prospective cohort studies at 9 tertiary care hospital EDs from 2007 to 2019, and enrolled adult patients who required treatment for AHF. Each patient was assessed for standardized real-time clinical and laboratory variables, as well as for SSO (defined as death within 30 days or intubation, non-invasive ventilation (NIV), myocardial infarction, coronary bypass surgery, or new hemodialysis after admission). The fully pre-specified, logistic regression model with 13 predictors (age, pCO2, and SaO2 were modeled using spline functions with 3 knots and heart rate and creatinine with 5 knots) was fitted to the 10 multiple imputation datasets. Harrell's fast stepdown procedure reduced the number of variables. We calculated the potential impact on sensitivity (95% CI) for SSO and hospital admissions and estimated a sample size of 170 SSOs. Results: The 2,246 patients had mean age 77.4 years, male sex 54.5%, EMS arrival 41.1%, IV NTG 3.1%, ED NIV 5.2%, admission on initial visit 48.6%. Overall there were 174 (7.8%) SSOs including 70 deaths (3.1%). The final risk scale is comprised of five variables (points) and had c-statistic of 0.76 (95% CI: 0.73-0.80): 1.Valvular heart disease (1) 2.ED non-invasive ventilation (2) 3.Creatinine 150-300 (1) ≥300 (2) 4.Troponin 2x-4x URL (1) ≥5x URL (2) 5.Walk test failed (2) The probability of SSO ranged from 2.0% for a total score of 0 to 90.2% for a score of 10, showing good calibration. The model was stable over 1,000 bootstrap samples. Choosing a risk model total point admission threshold of >2 would yield a sensitivity of 80.5% (95% CI 73.9-86.1) for SSO with no change in admissions from current practice (48.6% vs 48.7%). Conclusion: Using a large prospectively collected dataset, we created a concise and sensitive risk scale to assist with admission decisions for patients with AHF in the ED. Implementation of this risk scoring scale should lead to safer and more efficient disposition decisions, with more high-risk patients being admitted and more low-risk patients being discharged.
Introduction: An important challenge physicians face when treating acute heart failure (AHF) patients in the emergency department (ED) is deciding whether to admit or discharge, with or without early follow-up. The overall goal of our project was to improve care for AHF patients seen in the ED while avoiding unnecessary hospital admissions. The specific goal was to introduce hospital rapid referral clinics to ensure AHF patients were seen within 7 days of ED discharge. Methods: This prospective before-after study was conducted at two campuses of a large tertiary care hospital, including the EDs and specialty outpatient clinics. We enrolled AHF patients ≥50 years who presented to the ED with shortness of breath (<7 days). The 12-month before (control) period was separated from the 12-month after (intervention) period by a 3-month implementation period. Implementation included creation of rapid access AHF clinics staffed by cardiology and internal medicine, and development of referral procedures. There was extensive in-servicing of all ED staff. The primary outcome measure was hospital admission at the index visit or within 30 days. Secondary outcomes included mortality and actual access to rapid follow-up. We used segmented autoregression analysis of the monthly proportions to determine whether there was a change in admissions coinciding with the introduction of the intervention and estimated a sample size of 700 patients. Results: The patients in the before period (N = 355) and the after period (N = 374) were similar for age (77.8 vs. 78.1 years), arrival by ambulance (48.7% vs 51.1%), comorbidities, current medications, and need for non-invasive ventilation (10.4% vs. 6.7%). Comparing the before to the after periods, we observed a decrease in hospital admissions on index visit (from 57.7% to 42.0%; P <0.01), as well as all admissions within 30 days (from 65.1% to 53.5% (P < 0.01). The autoregression analysis, however, demonstrated a pre-existing trend to fewer admissions and could not attribute this to the intervention (P = 0.91). Attendance at a specialty clinic, amongst those discharged increased from 17.8% to 42.1% (P < 0.01) and the median days to clinic decreased from 13 to 6 days (P < 0.01). 30-day mortality did not change (4.5% vs. 4.0%; P = 0.76). Conclusion: Implementation of rapid-access dedicated AHF clinics led to considerably increased access to specialist care, much reduced follow-up times, and possible reduction in hospital admissions. Widespread use of this approach can improve AHF care in Canada.
We present a detailed overview of the cosmological surveys that we aim to carry out with Phase 1 of the Square Kilometre Array (SKA1) and the science that they will enable. We highlight three main surveys: a medium-deep continuum weak lensing and low-redshift spectroscopic HI galaxy survey over 5 000 deg2; a wide and deep continuum galaxy and HI intensity mapping (IM) survey over 20 000 deg2 from
$z = 0.35$
to 3; and a deep, high-redshift HI IM survey over 100 deg2 from
$z = 3$
to 6. Taken together, these surveys will achieve an array of important scientific goals: measuring the equation of state of dark energy out to
$z \sim 3$
with percent-level precision measurements of the cosmic expansion rate; constraining possible deviations from General Relativity on cosmological scales by measuring the growth rate of structure through multiple independent methods; mapping the structure of the Universe on the largest accessible scales, thus constraining fundamental properties such as isotropy, homogeneity, and non-Gaussianity; and measuring the HI density and bias out to
$z = 6$
. These surveys will also provide highly complementary clustering and weak lensing measurements that have independent systematic uncertainties to those of optical and near-infrared (NIR) surveys like Euclid, LSST, and WFIRST leading to a multitude of synergies that can improve constraints significantly beyond what optical or radio surveys can achieve on their own. This document, the 2018 Red Book, provides reference technical specifications, cosmological parameter forecasts, and an overview of relevant systematic effects for the three key surveys and will be regularly updated by the Cosmology Science Working Group in the run up to start of operations and the Key Science Programme of SKA1.
Patients diagnosed with glioblastoma (GBM) are treated with surgery followed by fractionated radiotherapy with concurrent and adjuvant temozolomide. Patients are monitored with serial magnetic resonance imaging (MRI). However, treatment-related changes frequently mimic disease progression. We reviewed a series of patients undergoing surgery for presumed first-recurrence GBM, where pathology reports were available for tissue diagnosis, in order to better understand factors associated with a diagnosis of treatment-related changes on final pathology.
Patient records at a single institution between 2005 and 2015 were retrospectively reviewed. Pathology reports were reviewed to determine diagnosis of recurrent GBM or treatment effect. Survival analysis was performed interrogating overall survival (OS) and progression-free survival (PFS). Correlation with radiation treatment plans was also examined.
One-hundred-twenty-three patients were identified. One-hundred-sixteen patients (94%) underwent resection and seven underwent biopsy. Treatment-related changes were reported in 20 cases (16%). These patients had longer median OS and PFS from the time of recurrence than patients with true disease progression. However, there was no significant difference in OS from the time of initial diagnosis. Treatment effect was associated with surgery within 90 days of completing radiation. In patients receiving radiation at our institution (n = 53), larger radiation target volume and a higher maximum dose were associated with treatment effect.
Treatment effect was associated with surgery nearer to completion of radiation, a larger radiation target volume, and a higher maximum point dose. Treatment effect was associated with longer PFS and OS from the time of recurrence, but not from the time of initial diagnosis.
To further understand the contribution of feedstuff ingredients to gut health in swine, gut histology and intestinal bacterial profiles associated with the use of two high-quality protein sources, microbially enhanced soybean meal (MSBM) and Menhaden fishmeal (FM) were assessed. Weaned pigs were fed one of three experimental diets: (1) basic diet containing corn and soybean meal (Negative Control (NEG)), (2) basic diet + fishmeal (FM; Positive Control (POS)) and (3) basic diet + MSBM (MSBM). Phase I POS and MSBM diets (d 0 to d 7 post-wean) included FM or MSBM at 7.5%, while Phase II POS and MSBM diets (d 8 to d 21) included FM or MSBM at 5.0%. Gastrointestinal tissue and ileal digesta were collected from euthanised pigs at d 21 (eight pigs/diet) to assess gut histology and intestinal bacterial profiles, respectively. Data were analysed using Proc Mixed in SAS, with pig as the experimental unit and pig (treatment) as the random effect. Histological and immunohistochemical analyses of stomach and small intestinal tissue using haematoxylin–eosin, Periodic Acid Schiff/Alcian blue and inflammatory cell staining did not reveal detectable differences in host response to dietary treatment. Ileal bacterial composition profiles were obtained from next-generation sequencing of PCR generated amplicons targeting the V1 to V3 regions of the 16S rRNA gene. Lactobacillus-affiliated sequences were found to be the most highly represented across treatments, with an average relative abundance of 64.0%, 59.9% and 41.80% in samples from pigs fed the NEG, POS and MSBM diets, respectively. Accordingly, the three most abundant Operational Taxonomic Units (OTUs) were affiliated to Lactobacillus, showing a distinct abundance pattern relative to dietary treatment. One OTU (SD_Ssd_00001), most closely related to Lactobacillus amylovorus, was found to be more abundant in NEG and POS samples compared to MSBM (23.5% and 35.0% v. 9.2%). Another OTU (SD_Ssd_00002), closely related to Lactobacillus johnsonii, was more highly represented in POS and MSBM samples compared to NEG (14.0% and 15.8% v. 0.1%). Finally, OTU Sd_Ssd-00011, highest sequence identity to Lactobacillus delbrueckii, was found in highest abundance in ileal samples from MSBM-fed pigs (1.9% and 3.3% v. 11.3, in POS, NEG and MSBM, respectively). There was no effect of protein source on bacterial taxa to the genus level or diversity based on principal component analysis. Dietary protein source may provide opportunity to enhance presence of specific members of Lactobacillus genus that are associated with immune-modulating properties without altering overall intestinal bacterial diversity.
Reduced occupational energy expenditure and increased energy intake are important contributors to the increasing prevalence of obesity. The aim of this study was to examine whether sedentary occupations, and specific indicators of energy intake and expenditure are associated with obesity risk in Australian women. Data were from 3,444 participants in the Australian Longitudinal Study on Women's Health, who reported their weight, dietary intake, physical activity and occupation in 2009 (at age 31–36), and weight in 2012. Participants were categorised as having a ‘less sedentary’ or ‘sedentary work’, based on occupation and activity patterns at work. Multivariate models were conducted to examine the odds of being obese (> 30 body-mass index) and risk of obesity in the two occupational groups based on energy balance factors (diet and physical activity). Models were adjusted for major confounders (smoking, education, income, number of children).There was no significant difference in the prevalence of obesity between groups (20.3% less sedentary vs 22.7% sedentary work, p = 0.11) at baseline. Being in the highest total energy intake tertile, saturated fat intake > 35g/d and drinking 3 or more sugar-sweetened beverages per week increased the odds of being obese in both groups. But to a higher extent in ‘less sedentary work’ (OR 2.11 95%CI 1.41–3.19; OR 3.04 95%CI 2.09–4.45; 2.07 95%CI 1.45–2.97, respectively). High physical activity (> 1000MET.min/week) was consistently associated with lower odds of being obese (OR 0.64 95%CI 0.43–0.97 ‘less sedentary’; OR 0.58 95%CI 0.36–0.93 ‘sedentary work’) but lower incidence of obesity only in ‘less sedentary work’ group (IRR 0.52 95%CI 0.30–0.88, absolute risk 14%). High sugar-sweetened beverages increased the incidence of obesity only in this group (IRR 1.72 95%CI 1.08–2.73, absolute risk 23%). Having a sedentary work per se did not play a major role in obesity prevalence and risk in women. Instead, high saturated fat and SSB intake, and physical inactivity remained the major contributors to obesity prevalence and risk, particularly for those in less sedentary jobs.
Perinatal depression is a depressive illness that affects 10–15% of women in the UK with an estimated cost of £1.8 billion/year. Zinc deficiency is associated with the development of mood disorders and zinc supplementation has been shown to help reduce the symptoms of depression. Women who are pregnant and breastfeeding are at risk of lower levels of zinc because of the high demand from the developing and feeding baby. However, studies in the perinatal period are limited. With a long-term aim of designing a randomised controlled trial (RCT) to examine if zinc supplementation reduces depressive symptoms in pregnant and lactating women;the objective of this review was to systematically evaluate previous RCTs assessing zinc supplementation and depressive symptoms, in order to establish a zinc dosing regimen with regards to Galenic formulation, unit dose and frequency. The review was conducted by independent reviewers in accordance with PRISMA guidelines and is registered at Prospero (CRD42017059205). The Allied and Complimentary Medicine, CINAHL, Embase, MEDLINE, PsycINFO, PubMed, and Cochrane databases were searched since records began, with no restrictions, for intervention trials assessing Galenic formulation, unit dose and frequency of zinc supplementation to reduce the symptoms of depression. From a total of 66 identified records, 7 articles met the inclusion and exclusion criteria; all assessed the effect of zinc supplementation on mood. Risk of bias was independently assessed using the standard ‘Cochrane risk of bias tool’. Overall, 5 of the 7 papers were rated as high-quality trials; of the other two, one was rated poor and the other fair but both had a number of learning points. Preliminary findings indicate at the end of supplementing zinc, depression scores were reduced significantly. In one study, the Beck score decreased in the placebo group, but this reduction was not significant compared to the baseline. In two of the studies there was a significant correlation between serum zinc and self-reported mood questionnaires. Results also suggest that 25 mg zinc supplementation combined with antidepressant drugs can be effective in the treatment of major depression in women. This supports other work where researchers supplemented 25 mg of elemental zinc for 12 weeks or longer and found a reduction of symptoms in both pregnant and non-pregnant women. Thus, an early conclusion is that 25 mg of elemental zinc is an effective dose for improving low mood and is achievable in a trial setting.
Research on psychotic illness is loosening emphasis on diagnostic stringency in favour of including a more dimensionally based conceptualization of psychopathology and pathobiology. However, to clarify these notions requires investigation of the full scope of psychotic diagnoses.
The Cavan–Monaghan First Episode Psychosis Study ascertained cases of first episode psychosis across all 12 DSM-IV psychotic diagnoses via all routes to care: public, private or forensic; home-based, outpatient or inpatient. There was no arbitrary upper age cut-off and minimal impact of factors associated with variations in social milieu, ethnicity or urbanicity. Cases were evaluated epidemiologically and assessed for psychopathology, neuropsychology, neurology, antecedent factors, insight and quality of life.
Among 432 cases, the annual incidence of any DSM-IV psychotic diagnosis was 34.1/100 000 of population and encompassed functional psychotic diagnoses, substance-induced psychopathology and psychopathology due to general medical conditions, through to psychotic illness that defied contemporary diagnostic algorithms. These 12 DSM-IV diagnostic categories, including psychotic disorder not otherwise specified, showed clinical profiles that were consistently more similar than distinct.
There are considerable similarities and overlaps across a broad range of diagnostic categories in the absence of robust discontinuities between them. Thus, psychotic illness may be of such continuity that it cannot be fully captured by operational diagnostic algorithms that, at least in part, assume discontinuities. This may reflect the impact of diverse factors each of which acts on one or more overlapping components of a common, dysfunctional neuronal network implicated in the pathobiology of psychotic illness.
Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom.
We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians.
Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window.
Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice.
We have observed the G23 field of the Galaxy AndMass Assembly (GAMA) survey using the Australian Square Kilometre Array Pathfinder (ASKAP) in its commissioning phase to validate the performance of the telescope and to characterise the detected galaxy populations. This observation covers ~48 deg2 with synthesised beam of 32.7 arcsec by 17.8 arcsec at 936MHz, and ~39 deg2 with synthesised beam of 15.8 arcsec by 12.0 arcsec at 1320MHz. At both frequencies, the root-mean-square (r.m.s.) noise is ~0.1 mJy/beam. We combine these radio observations with the GAMA galaxy data, which includes spectroscopy of galaxies that are i-band selected with a magnitude limit of 19.2. Wide-field Infrared Survey Explorer (WISE) infrared (IR) photometry is used to determine which galaxies host an active galactic nucleus (AGN). In properties including source counts, mass distributions, and IR versus radio luminosity relation, the ASKAP-detected radio sources behave as expected. Radio galaxies have higher stellar mass and luminosity in IR, optical, and UV than other galaxies. We apply optical and IR AGN diagnostics and find that they disagree for ~30% of the galaxies in our sample. We suggest possible causes for the disagreement. Some cases can be explained by optical extinction of the AGN, but for more than half of the cases we do not find a clear explanation. Radio sources aremore likely (~6%) to have an AGN than radio quiet galaxies (~1%), but the majority of AGN are not detected in radio at this sensitivity.