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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.
The Square Kilometre Array (SKA) is a planned large radio interferometer designed to operate over a wide range of frequencies, and with an order of magnitude greater sensitivity and survey speed than any current radio telescope. The SKA will address many important topics in astronomy, ranging from planet formation to distant galaxies. However, in this work, we consider the perspective of the SKA as a facility for studying physics. We review four areas in which the SKA is expected to make major contributions to our understanding of fundamental physics: cosmic dawn and reionisation; gravity and gravitational radiation; cosmology and dark energy; and dark matter and astroparticle physics. These discussions demonstrate that the SKA will be a spectacular physics machine, which will provide many new breakthroughs and novel insights on matter, energy, and spacetime.
This chapter discusses and reviews research on the relationship between two closely aligned concepts: intelligence and reasoning. We begin by defining reasoning in a general sense. Next, we review prominent theories and models of intelligence and reasoning in both the psychometric and cognitive psychological traditions, highlighting how the two constructs are both intertwined yet nonetheless conceptually discriminable. We follow by discussing issues involved in validly measuring reasoning, touching on considerations, concerns, and evidence informed by the cognitive and psychometric perspectives. Then, we review the relationship between reasoning and allied constructs and domains, including expertise, practical outcomes (e.g., educational and workplace achievement), working memory, and critical thinking. We conclude by sketching multiple avenues for future research.
Technological advances have led to better patient outcomes and the expansion of clinical services in paediatric cardiology. This expansion creates an ever-growing workload for clinicians, which has led to workflow and staffing issues that need to be addressed. The objective of this study was the development of a novel tool to measure the clinical workload of a paediatric cardiology service in Cape Town, South Africa: The patient encounter index is a tool designed to quantify clinical workload. It is defined as a ratio of the measured duration of clinical work to the total time available for such work. This index was implemented as part of a prospective cross-sectional study design. Clinical workload data were collected over a 10-day period using time-and-motion sampling. Clinicians were contractually expected to spend 50% of their daily workload on patient care. The median patient encounter index for the Western Cape Paediatric Cardiac Service was 0.81 (range 0.19–1.09), reflecting that 81% of total contractual working time was spent on clinical activities. This study describes the development and implementation of a novel tool for clinical workload quantification and describes its application to a busy paediatric cardiology service in Cape Town, South Africa. This tool prospectively quantifies clinical workload which may directly influence patient outcomes. Implementation of this novel tool in the described setting clearly demonstrated the excessive workload of the clinical service and facilitated effective motivation for improved allocation of resources.
Rapeseed is a popular cover crop choice due to its deep-growing taproot, which creates soil macropores and increases water infiltration. Brassicaceae spp. that are mature or at later growth stages can be troublesome to control. Experiments were conducted in Delaware and Virginia to evaluate herbicides for terminating rapeseed cover crops. Two separate experiments, adjacent to each other, were established to evaluate rapeseed termination by 14 herbicide treatments at two timings. Termination timings included an early and late termination to simulate rapeseed termination prior to planting corn and soybean, respectively, for the region. At three locations where rapeseed height averaged 12 cm at early termination and 52 cm at late termination, glyphosate + 2,4-D was most effective, controlling rapeseed 96% 28 d after early termination (DAET). Paraquat + atrazine + mesotrione (92%), glyphosate + saflufenacil (91%), glyphosate + dicamba (91%), and glyphosate (86%) all provided at least 80% control 28 DAET. Rapeseed biomass followed a similar trend. Paraquat + 2,4-D (85%), glyphosate + 2,4-D (82%), and paraquat + atrazine + mesotrione (81%) were the only treatments that provided at least 80% control 28 d after late termination (DALT). Herbicide efficacy was less at Painter in 2017, where rapeseed height was 41 cm at early termination, and 107 cm at late termination. No herbicide treatments controlled rapeseed >80% 28 DAET or 28 DALT at this location. Herbicide termination of rapeseed is best when the plant is small; termination of large rapeseed plants may require mechanical of other methods beyond herbicides.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Residual herbicides are routinely applied to control troublesome weeds in pumpkin production. Fluridone and acetochlor, Groups 12 and 15 herbicides, respectively, provide broad-spectrum PRE weed control. Field research was conducted in Virginia and New Jersey to evaluate pumpkin tolerance and weed control to PRE herbicides. Treatments consisted of fomesafen at two rates, ethalfluralin, clomazone, halosulfuron, fluridone, S-metolachlor, acetochlor emulsifiable concentrate (EC), acetochlor microencapsulated (ME), and no herbicide. At one site, fluridone, acetochlor EC, acetochlor ME, and halosulfuron injured pumpkin 81%, 39%, 34%, and 35%, respectively, at 14 d after planting (DAP); crop injury at the second site was 40%, 8%, 19%, and 33%, respectively. Differences in injury between the two sites may have been due to the amount and timing of rainfall after herbicides were applied. Fluridone provided 91% control of ivyleaf morningglory and 100% control of common ragweed at 28 DAP. Acetochlor EC controlled redroot pigweed 100%. Pumpkin treated with S-metolachlor produced the most yield (10,764 fruits ha–1) despite broadcasting over the planted row; labeling requires a directed application to row-middles. A separate study specifically evaluated fluridone applied PRE at 42, 84, 126, 168, 252, 336, and 672 g ai ha–1. Fluridone resulted in pumpkin injury ≥95% when applied at rates of ≥168 g ai ha–1; significant yield loss was noted when the herbicide was applied at rates >42 g ai ha–1. We concluded that fluridone and acetochlor formulations are unacceptable candidates for pumpkin production.
Auxin herbicides are used in combinations to control glyphosate-resistant horseweed preplant burndown. Herbicide labels for 2,4-D–containing products require a 30-d rotation interval for planting cotton cultivars not resistant to 2,4-D. Dicamba labels require an accumulation of 2.5 cm of rain plus 21 d per 280 g ae ha–1 rotation interval for planting cotton cultivars not resistant to dicamba. Previous research has shown that cotton injury caused by dicamba applied 14 d before planting was transient with little effect on cotton yield, whereas 2,4-D has little effect on cotton when applied 7 d prior to planting. Injury caused by dicamba and 2,4-D is inversely related to rainfall received between herbicide application and cotton planting. Experiments were conducted to evaluate cotton tolerance to halauxifen-methyl, a new Group 4 herbicide, applied at intervals shorter than labeled requirements. Experiments were established near Painter and Suffolk, VA, and Belvidere, Clayton, Eure, Lewiston, and Rocky Mount, NC, during the 2017 and 2018 growing seasons. Herbicide treatments included halauxifen, dicamba, and 2,4-D applied 4, 3, 2, 1, and 0 wk before planting (WBP). Visible estimates of cotton growth reduction and total injury were collected 1, 2, and 4 wk after cotton emergence (WAE). Cotton stand and percentage of plants with distorted leaves were recorded 2 and 4 WAE. Cotton plant heights were recorded 4 and 8 WAE. Halauxifen was less injurious (9%) than dicamba (26%) or 2,4-D (21%) 2 WAE when herbicides were applied 0 WBP. Cotton stand reduction 2 WAE by halauxifen was less than 2,4-D and dicamba when applied 0 WBP. Injury observed from herbicides applied 1, 2, 3, and 4 WBP was minor, and no significant differences in cotton stand were observed. Early-season cotton injury was transient, and seed cotton yield was unaffected by any treatment.
We reappraise the psychiatric potential of calcium channel blockers (CCBs). First, voltage-gated calcium channels are risk genes for several disorders. Second, use of CCBs is associated with altered psychiatric risks and outcomes. Third, research shows there is an opportunity for brain-selective CCBs, which are better suited to psychiatric indications.
Declaration of interest
E.M.T. and P.J.H. hold an unrestricted educational grant from Johnson & Johnson to work on the molecular neurobiology of calcium channels.
Introduction: In Nova Scotia, under the Paramedics Providing Palliative Care program, paramedics can now manage symptom crises in patients with palliative care goals and often at home without the need to transport to hospital. Growing recognition that non-cancer conditions benefit from a palliative approach is expanding the program. Our team previously found treatment of pain and breathlessness is not optimized, pain scores are underutilized, and paramedics were more comfortable (pre-launch) with a palliative approach in cancer versus non-cancer conditions. Our objective was to compare symptom management in cancer versus non-cancer subgroup. Methods: We conducted a retrospective cohort study. The Electronic Patient Care Record and Special Patient Program were queried for patients with palliative goals from July 1, 2015 to July 1, 2016. Descriptive analysis was conducted and results were compared with a t-test and Bonferroni correction (alpha = p < 0.007). Results: 1909 unique patients; 765/1909 (40.1%) cancer and 1144/1909 (59.9%) non-cancer. Female sex: cancer 357/765 (46.7%), non-cancer 538/1144 (47.0%). Mean age cancer: 73.3 (11.65), non-cancer 77.7 (12.80). Top non-cancer conditions: COPD (495/1144, 43.3%), CHF (322/1144, 28.1%), stroke (172/1144, 15.0%) and dementia (149/1144, 13.0%). Comorbidities for cancer patients (range): 0 to 3; non-cancer 0 to 5. Most common chief complaint (CC) for cancer and non-cancer: respiratory distress, 10.8% vs 21.5%. Overall, no difference in proportion treated cancer vs non-cancer, 11.5% vs 10.1%, p = 0.35. Some difference in individual therapies: morphine 83/765 (10.8%) vs 55/1144 (4.8%), p < 0.001, hydromorphone 9/765 (1.2%) vs 2/1144 (0.2%), p = 0.014, salbutamol 38/765 (5.0%) vs 5/1144 (0.4%), p < 0.001 and ipratropium 27/765 (3.5%) vs 134/1144 (11.7%), p < 0.001, in addition to any support with home medication which is not queriable. Pre-treatment pain scores were documented more often than post-treatment in both groups (58.7% vs 25.6% (p < 0.001), 57.4% vs 26.9% (p < 0.001)). Conclusion: Non-cancer patients represent an important proportion of palliative care calls for paramedics. Cancer and non-cancer patients had very similar CC and received similar treatment, although low proportions, despite pre-launch findings that non-cancer conditions were likely to be undertreated. Pain scores remain underutilized. Further research into the underlying reason(s) is required to improve the support of non-cancer patients by paramedics.
Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.
We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.
Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.
Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.
Legionnaires’ disease (LD) incidence in the USA has quadrupled since 2000. Health departments must detect LD outbreaks quickly to identify and remediate sources. We tested the performance of a system to prospectively detect simulated LD outbreaks in Allegheny County, Pennsylvania, USA. We generated three simulated LD outbreaks based on published outbreaks. After verifying no significant clusters existed in surveillance data during 2014–2016, we embedded simulated outbreak-associated cases into 2016, assigning simulated residences and report dates. We mimicked daily analyses in 2016 using the prospective space-time permutation scan statistic to detect clusters of ⩽30 and ⩽180 days using 365-day and 730-day baseline periods, respectively. We used recurrence interval (RI) thresholds of ⩾20, ⩾100 and ⩾365 days to define significant signals. We calculated sensitivity, specificity and positive and negative predictive values for daily analyses, separately for each embedded outbreak. Two large, simulated cooling tower-associated outbreaks were detected. As the RI threshold was increased, sensitivity and negative predictive value decreased, while positive predictive value and specificity increased. A small, simulated potable water-associated outbreak was not detected. Use of a RI threshold of ⩾100 days minimised time-to-detection while maximizing positive predictive value. Health departments should consider using this system to detect community-acquired LD outbreaks.
C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.
To explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.
Declaration of interest
S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.
To study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals.
In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging.
Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety–threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC.
Poor vmPFC safety–threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Invasive rodents detrimentally affect native bird species on many islands worldwide, and rodent eradication is a useful tool to safeguard endemic and threatened species. However, especially on tropical islands, rodent eradications can fail for various reasons, and it is unclear whether the temporary reduction of a rodent population during an unsuccessful eradication operation has beneficial effects on native birds. Here we examine the response of four endemic land bird species on subtropical Henderson Island in the Pitcairn Island Group, South Pacific Ocean, following an unsuccessful rodent eradication in 2011. We conducted point counts at 25 sampling locations in 14 survey periods between 2011 and 2015, and modelled the abundance trends of all species using binomial mixture models accounting for observer and environmental variation in detection probability. Henderson Reed Warbler Acrocephalus taiti more than doubled in abundance (2015 population estimate: 7,194-28,776), and Henderson Fruit Dove Ptilinopus insularis increased slightly between 2011 and 2015 (2015 population estimate: 4,476–10,072), while we detected no change in abundance of the Henderson Lorikeet Vini stepheni (2015 population estimate: 554–3014). Henderson Crake Zapornia atra increased to pre-eradication levels following anticipated mortality during the operation (2015 population estimate: 4,960–20,783). A temporary reduction of rat predation pressure and rat competition for fruit may have benefitted the reed warbler and the fruit dove, respectively. However, a long drought may have naturally suppressed bird populations prior to the rat eradication operation in 2011, potentially confounding the effects of temporary rat reduction and natural recovery. We therefore cannot unequivocally ascribe the population recovery to the temporary reduction of the rat population. We encourage robust monitoring of island biodiversity both before and after any management operation to better understand responses of endemic species to failed or successful operations.