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Whole-genome sequencing (WGS) shotgun metagenomics (metagenomics) attempts to sequence the entire genetic content straight from the sample. Diagnostic advantages lie in the ability to detect unsuspected, uncultivatable, or very slow-growing organisms.
To evaluate the clinical and economic effects of using WGS and metagenomics for outbreak management in a large metropolitan hospital.
Intensive care unit and burn unit of large metropolitan hospital.
Simulated intensive care unit and burn unit patients.
We built a complex simulation model to estimate pathogen transmission, associated hospital costs, and quality-adjusted life years (QALYs) during a 32-month outbreak of carbapenem-resistant Acinetobacter baumannii (CRAB). Model parameters were determined using microbiology surveillance data, genome sequencing results, hospital admission databases, and local clinical knowledge. The model was calibrated to the actual pathogen spread within the intensive care unit and burn unit (scenario 1) and compared with early use of WGS (scenario 2) and early use of WGS and metagenomics (scenario 3) to determine their respective cost-effectiveness. Sensitivity analyses were performed to address model uncertainty.
On average compared with scenario 1, scenario 2 resulted in 14 fewer patients with CRAB, 59 additional QALYs, and $75,099 cost savings. Scenario 3, compared with scenario 1, resulted in 18 fewer patients with CRAB, 74 additional QALYs, and $93,822 in hospital cost savings. The likelihoods that scenario 2 and scenario 3 were cost-effective were 57% and 60%, respectively.
The use of WGS and metagenomics in infection control processes were predicted to produce favorable economic and clinical outcomes.
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.
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.
The Neotoma Paleoecology Database is a community-curated data resource that supports interdisciplinary global change research by enabling broad-scale studies of taxon and community diversity, distributions, and dynamics during the large environmental changes of the past. By consolidating many kinds of data into a common repository, Neotoma lowers costs of paleodata management, makes paleoecological data openly available, and offers a high-quality, curated resource. Neotoma’s distributed scientific governance model is flexible and scalable, with many open pathways for participation by new members, data contributors, stewards, and research communities. The Neotoma data model supports, or can be extended to support, any kind of paleoecological or paleoenvironmental data from sedimentary archives. Data additions to Neotoma are growing and now include >3.8 million observations, >17,000 datasets, and >9200 sites. Dataset types currently include fossil pollen, vertebrates, diatoms, ostracodes, macroinvertebrates, plant macrofossils, insects, testate amoebae, geochronological data, and the recently added organic biomarkers, stable isotopes, and specimen-level data. Multiple avenues exist to obtain Neotoma data, including the Explorer map-based interface, an application programming interface, the neotoma R package, and digital object identifiers. As the volume and variety of scientific data grow, community-curated data resources such as Neotoma have become foundational infrastructure for big data science.
This paper describes the planning, designing, constructing, and initial operating phases of a state-of-the-art agricultural pesticide facility (APF). The APF on the University of Minnesota, St. Paul Campus is located within a major metropolitan area, causing environmental and human safety to be priority considerations. The building site was located adjacent to a greenhouse complex and field plots to provide access for all users of pesticides on the St. Paul Campus for storing, measuring, packaging for off campus use, applying, and disposing of pesticides. This central facility eliminated the need for about 25 generally inadequate locations on campus where pesticides were previously stored and handled. Changing state and federal pesticide regulations and in-house operating requirements may require future modification and retrofitting of the APF. However, the APF is a valuable research and education addition to the St. Paul Campus, and it has provided greater safety for personnel, students, visitors, the community, and the environment.
Oregon's Fort Rock Cave is iconic in respect to both the archaeology of the northern Great Basin and the history of debate about when the Great Basin was colonized. In 1938, Luther Cressman recovered dozens of sagebrush bark sandals from beneath Mt. Mazama ash that were later radiocarbon dated to between 10,500 and 9350 cal B.P. In 1970, Stephen Bedwell reported finding lithic tools associated with a date of more than 15,000 cal B.P., a date dismissed as unreasonably old by most researchers. Now, with evidence of a nearly 15,000-year-old occupation at the nearby Paisley Five Mile Point Caves, we returned to Fort Rock Cave to evaluate the validity of Bedwell's claim, assess the stratigraphic integrity of remaining deposits, and determine the potential for future work at the site. Here, we report the results of additional fieldwork at Fort Rock Cave undertaken in 2015 and 2016, which supports the early Holocene occupation, but does not confirm a pre–10,500 cal B.P. human presence.
Field experiments were conducted in 1999, 2000, and 2001 to investigate PRE and POST applications of halosulfuron-methyl in combination with clomazone plus ethalfluralin for control of sedge and smooth pigweed in summer squash. Halosulfuron was applied PRE or POST to summer squash at 9, 18, or 27 g ai/ha in combination with a PRE application of clomazone at 175 g ai/ha plus ethalfluralin at 630 g ai/ha. Smooth pigweed control by addition of halosulfuron at 18 and 27 g/ha in combination with clomazone plus ethalfluralin PRE was greater than 89% independent of application method. Yellow nutsedge control was greater than 83% with POST applications of halosulfuron at 18 and 27 g/ha in combination with clomazone plus ethalfluralin PRE. Yellow nutsedge control was greater than 60% from all POST halosulfuron applications at 9, 18, or 27 g/ha in the greenhouse. In a separate field study without ethalfluralin PRE, rice flatsedge control was more than 85% from halosulfuron applied POST at 18 and 27 g/ha. Yellow summer squash and zucchini squash were injured as much as 52 and 47%, respectively, from inclusion of halosulfuron PRE or POST at 27 g/ha in treatments. Summer squash yields were generally not affected by halosulfuron rate, and were comparable to or higher than summer squash treated by only the mixture of clomazone plus ethalfluralin. In these studies, summer squash were injured by halosulfuron applied at 9 to 27 g/ha PRE or POST, yet rapidly recovered, making this herbicide acceptable for use in combination with clomazone and ethalfluralin for controlling several common weed species.
Greenhouse experiments were conducted to evaluate the response to halosulfuron of several smooth pigweed populations that had been shown to be resistant to acetolactate synthase (ALS, EC 184.108.40.206)-inihibiting herbicides. Five ALS-resistant smooth pigweed populations (R1, R2, R3, R4, and R5) and one susceptible (S) population were treated with halosulfuron POST at 0.27, 2.7, 27, 270, and 2,700 g ai/ha. Percentage injury and dry weight were used to determine resistance of smooth pigweed populations to halosulfuron. Populations of smooth pigweed with previous reports of resistance to ALS-inhibiting herbicides showed varying degrees of resistance to halosulfuron compared with the susceptible population. Concentrations of halosulfuron required to reduce ALS-resistant smooth pigweed dry weights 50% were 2 to 12-fold higher than that of the susceptible population. One population, designated R2, had increased resistance to halosulfuron applications, requiring 97 g/ha halosulfuron to reduce shoot dry weight 50% compared with only 8 g/ha for S. Our results show that populations of smooth pigweed with a history of ALS-inhibiting resistance can have differing degrees of resistance to halosulfuron.
Field experiments were conducted in 1999, 2000, and 2001 to investigate PRE and POST applications of halosulfuron-methyl in combination with clomazone plus ethalfluralin for control of several broadleaf weeds in cucumber and pumpkin. Halosulfuron was applied PRE or POST to cucumber and pumpkin at 9, 18, and 27 g ai/ha in combination with a PRE application of clomazone at 175 g ai/ha plus ethalfluralin at 630 g ai/ha. Halosulfuron applied POST at 27 g/ha in combination with clomazone plus ethalfluralin controlled weed species greater than 62%. Smooth pigweed control by addition of halosulfuron at 27 g/ha PRE or POST was greater than 88%, and common ragweed control was greater than 78% PRE and 88% POST, but control of ivyleaf morningglory and tall morningglory was 43 to 67% PRE and 62 to 76% POST. Cucumber injury with addition of halosulfuron did not exceed 13% PRE or POST, but pumpkin was injured as much as 43% with addition of halosulfuron PRE and 27% by POST applications. In a separate study without clomazone plus ethalfluralin PRE, smooth pigweed up to 13 cm tall was controlled 83% by halosulfuron at 27 g/ha in 2000, but rapidly growing smooth pigweed 15 to 40 cm tall was controlled only 58% in 2001. Cucumber and pumpkin yields were not affected by halosulfuron rate but were higher than yields produced by cucumber and pumpkin treated with only the mixture of clomazone plus ethalfluralin. In these studies, cucumber and pumpkin were tolerant to halosulfuron at 9 to 27 g/ha PRE or POST, making this herbicide acceptable for use in combination with clomazone and ethalfluralin for controlling several common weed species.
The coastline along the southern Arabian Gulf between Al Jubail, Kingdom of Saudi Arabia, and Dubai, UAE, appears to have risen at least 125 m in the last 18,000 years. Dating and topographic surveying of paleo-dunes (43–53 ka), paleo-marine terraces (17–30 ka), and paleo-marine shorelines (3.3–5.5 ka) document a rapid, > 1 mm/a subsidence, followed by a 6 mm/a uplift that is decreasing with time. The mechanism causing this movement remains elusive but may be related to the translation of the coastal area through the backbasin to forebulge hinge line movement of the Arabian plate or, alternatively, by movement of the underlying Infracambrian-age Hormuz salt in response to sea-level changes associated with continental glaciation. Independent of the mechanism, rapid and episodic uplift may impact the design of engineering projects such as nuclear power plants, airports, and artificial islands as well as the interpretation of sedimentation and archeology of the area.
The evolution of septal complexity in fossil ammonoids has been widely regarded as an adaptive response to mechanical stresses imposed on the shell by hydrostatic pressure. Thus, septal (and hence sutural) complexity has been used as a proxy for depth: for a given amount of septal material greater complexity permitted greater habitat depth. We show that the ultimate septum is the weakest part of the chambered shell. Additionally, finite element stress analyses of a variety of septal geometries exposed to pressure stresses show that any departure from a hemispherical shape actually yields higher, not lower, stresses in the septal surface. Further analyses show, however, that an increase in complexity is consistent with selective pressures of predation and buoyancy control. Regardless of the mechanisms that drove the evolution of septal complexity, our results clearly reject the assertion that complexly sutured ammonoids were able to inhabit deeper water than did ammonoids with simpler septa. We suggest that while more complexly sutured ammonoids were limited to shallower habitats, the accompanying more complex septal topograhies enhanced buoyancy regulation (chamber emptying and refilling), through increased surface tension effects.
A World Health Organization Expert Committee has concluded that symptoms of methylmercury poisoning may appear at blood concentrations of 200-500 ng Hg/ml. Blood levels in this range have been found in several Indian and Inuit communities in Canada. The syndrome of severe methylmercury poisoning (Hunter-Russell syndrome) is well described. However, diagnosis of less severe cases is difficult. This paper reviews the present situation in Canada. The problems of diagnosis currently being encountered are discussed and are illustrated by the case of an individual who had one of the highest blood concentrations (551 ng Hg/ml) ever described in fish-eating populations outside of the outbreaks in Minamata and Niigata in Japan. Although mercury concentrations in brain were estimated to have been in the “symptomatic” range at least once in the two years prior to his death, neurohisiological examination was normal. Detailed examination by two teams of neurologists revealed effects that may be associated with methylmercury poisoning but a definitive diagnosis remained elusive.
An ancestral paragastrioceratid, Svetlanoceras irwinense (Teichert and Glenister, 1952), and a specifically indeterminate gonioloboceratid, cf. Mescalites sp., from the basal Callytharra Formation are described as the oldest ammonoids recovered from the Permian of the Carnarvon Basin, Western Australia. Identity of these taxa strengthens correlation with the Holmwood Shale (Sakmarian) of the adjacent Perth Basin. Svetlanoceras moylei Mikesh, n. sp., from the Lenox Hills Formation of West Texas, is described for comparison with other simple paragastrioceratids.
There is comparatively little empirical evidence regarding the accuracy of regional housing sector forecasts. Much of the recent analysis conducted for this topic is developed for housing starts and indicates a relatively poor track record. This study examines residential real estate forecasts previously published for El Paso, TX using a structural econometric model. Model coverage is much broader than just starts. Similar to earlier studies, the previously published econometric predictions frequently do not fare very well against the selected random walk benchmarks utilized for the various series under consideration.