USING ISOTONIC REGRESSION TO IMPROVE ESTIMATION IN FACTORIAL EXPERIMENTS WITH ORDERED FACTOR LEVELS

In many designed experiments in agriculture and the life sciences, a researcher can anticipate the direction that responses will take when treatments are varied. For example, in a 2-way factorial, a researcher may know that increasing the levels of nitrogen and phosphorus will increase yields of a crop. Classical analysis of variance does not take into account a known ordering among population means. However, it can be shown that by restricting the estimates of means to have the same ordering as the anticipated ordering of population means, a reduction in mean-squared errors of estimators will likely occur, often by more than 50%. A procedure used to create such estimates is called isotonic regression. In this article, a recently proposed method of isotonic regression for lattice-ordered means will be presented after first reviewing well-established methods. The newer method will be illustrated using data from an entomology experiment. In addition, standard errors of the estimators will be approximated using a bootstrap procedure

Lessons learned : the first in-situ laboratory fault injection test

The CSIRO In-Situ Laboratory has been a world first injection of CO2 into a large faulted zone at depth. A total of 38 tonnes of CO2 was injected into the F10 fault zone at approximately 330 m depth and the process monitored in detail. The site uses a well, Harvey-2, in SW Western Australia (the South West Hub CCS Project area). The top 400 m section of Harvey-2 was available for injection and instrumentation. An observation well, ISL OB-1 (400 m depth) was drilled 7 m to the north east of Harvey-2. ISL OB-1 well was cased with fibreglass to provide greater monitoring options. The CSIRO In-Situ Laboratory was designed to integrate existing facilities and infrastructure from the South West Hub CCS Project managed by the West Australian Department of Mines, Industry Regulation and Safety. While new equipment was deployed for this specific project, the site facilities were complemented by a range of mobile deployable equipment from the National Geosequestration Laboratory (NGL). The geology of the area investigated poses interesting challenges: a large fault (F10) is estimated to have up to 1000 m throw overall, the presence of packages of paleosols rather than a contiguous mudstone seal, and a 1500 m vertical thickness of Triassic sandstone as the potential commercial storage interval. This unique site provides abundant opportunities for testing more challenging geological environments for carbon storage than at other sites. While details of this first project are described elsewhere, lessons were learned during the development and execution of the project. A rigorous risk register was developed to manage project risk, but not all events encountered were foreseen. This paper describes some of the challenges encountered and the team's response. Relocation of the project site due to changes in landholder ownership) and other sensitivities resulted in the need for rapid replanning of activities at short notice resulting in the development of the site at Harvey-2. The relocation allowed other research questions to be addressed through new activities, such as the ability to consider a shallow/controlled release experiment in an extensive fault zone, but this replanning did cause some timing stress. The first test at the In-Situ Laboratory was reconfigured to address some of those knowledge gaps that shallow/controlled release experiments had yet to address. Novel approaches to drilling and completing the monitoring well also threw up unanticipated difficulties. Loss of containment from the wellbore also posed significant challenges, and the team's response to this unintended release of gas and water from the monitoring well at the conclusion of the field experiment will be discussed. Other challenges that we encountered, their impacts, and our response are also catalogued here (Table 1 and below) to enable broad knowledge exchange

A controlled CO2 release experiment in a fault zone at the in-situ laboratory in Western Australia

A controlled-release test at the In-Situ Laboratory Project in Western Australia injected 38 tonnes of gaseous CO2 between 336-342 m depth in a fault zone, and the gas was monitored by a wide range of downhole and surface monitoring technologies. Injection of CO2 at this depth fills the gap between shallow release (600 m) field trials. The main objectives of the controlled-release test were to assess the monitorability of shallow CO2 accumulations, and to investigate the impacts of a fault zone on CO2 migration. CO2 arrival was detected by distributed temperature sensing at the monitoring well (7 m away) after approximately 1.5 days and an injection volume of 5 tonnes. The CO2 plume was detected also by borehole seismic and electric resistivity imaging. The early detection of significantly less than 38 tonnes of CO2 in the shallow subsurface demonstrates rapid and sensitive monitorability of potential leaks in the overburden of a commercial-scale storage project, prior to reaching shallow groundwater, soil zones or the atmosphere. Observations suggest that the fault zone did not alter the CO2 migration along bedding at the scale and depth of the test. Contrary to model predictions, no vertical CO2 migration was detected beyond the perforated injection interval. CO2 and formation water escaped to the surface through the monitoring well at the end of the experiment due to unexpected damage to the well’s fibreglass casing. The well was successfully remediated without impact to the environment and the site is ready for future experiments

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure

Publisher Copyright: © 2023 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.Background: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. Methods: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. Results: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. Conclusions: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.Peer reviewe

In the round: supporting teachers' authentic professional learning

2013 Fall.Includes bibliographical references.This is a study of teachers' authentic professional learning at a public school in Poudre School District in northern Colorado. At Polaris Expeditionary Learning School, teachers and administrators have developed a form of school-based instructional rounds referred to herein as PLC rounds (professional learning community rounds). In PLC rounds, Polaris teachers visit their colleagues' classrooms in teams to observe and interact with the host teacher and students. Afterwards, observing teachers reflect on their observations and interactions and engage in professional dialogue about how the experience might inform their practice. These dialogues become part of a larger conversation across all rounds teams in service of school improvement. Despite increased interest in school-based instructional rounds as a professional learning approach, a theory-research gap persists. This study draws upon teachers' lived experiences by encouraging them to reflect on their participation in PLC rounds. Through interviews and analysis, a theoretical framework is constructed to explain this dynamic phenomenon. The study distinguishes the PLC rounds approach from other forms of instructional rounds, outlines its key components, articulates teachers' professional learning experiences, explores this learning in relation to the strengthening of the professional learning community, and identifies practices that support and hinder their professional learning. In addition, it contributes insights for local practice at Polaris, considerations for interested schools and/or school districts, and recommendations for future research

Heavy mineral assemblages of the De Long Trough and southern Lomonosov Ridge glacigenic deposits:implications for the East Siberian Ice Sheet extent

Abstract The Arctic’s glacial history has classically been interpreted from marine records in terms of the fluctuations of the Eurasian and North American ice sheets. However, the extent and timing of the East Siberian Ice Sheet (ESIS) have remained uncertain. A recently discovered glacially scoured cross-shelf trough extending to the edge of the continental shelf north of the De Long Islands has provided additional evidence that glacial ice existed on parts of the East Siberian Sea (ESS) during previous glacial periods MIS 6 and 4. This study concentrates on defining the heavy mineral signature of glacigenic deposits from the East Siberian continental margin which were collected during the 2014 SWERUS-C3 expedition. The cores studied are 20-GC1 from the East Siberian shelf, 23-GC1 and 24-GC1 from the De Long Trough (DLT), and 29-GC1 from the southern Lomonosov Ridge (LR). Heavy mineral assemblages were used to identify prominent parent rocks in hinterland and other sediment source areas. The parent rock areas include major eastern Siberian geological provinces such as the Omolon massif, the Chukotka fold belt, the Verkhoyansk fold belt, and possibly the Okhotsk–Chukotka volcanic belt. The primary riverine sources for the ESS sediments are the Indigirka and Kolyma rivers, the material of which was glacially eroded and re-deposited in the DLT. The higher abundances of amphiboles in the heavy mineral assemblages may indicate ESS paleovalley of the Indigirka River as a major pathway of sediments, while the Kolyma River paleovalley pathway relates to a higher share of pyroxenes and epidote. The mineralogical signature in the DLT diamicts, consisting predominantly of amphiboles and pyroxenes with a minor content of garnet and epidote, shows clear delivery from the eastern part of the ESIS. Although the physical properties of the DLT glacial diamict closely resemble a pervasive diamict unit recovered from the southern LR, their source material is slightly different. The assemblages with elevated amphibole and garnet content, along with higher titanite and ilmenite content of the southern LR ice-rafted diamict, emphasise the Verkhoyansk fold belt as a possible primary source. The presence of glacial sediments and the recovered glacial–tectonic features on the East Siberian continental shelf and slope, along with the results from this heavy mineral analysis, imply that glacial ice not only grew out of the East Siberian shelf but also from the De Long Islands, and that there was also ice rafting related sediment transportation to the southern LR from westerly sources, such as the Laptev Sea

Identification and characterization of amphiphysin II as a novel cellular interaction partner of the hepatitis C virus NS5A protein

The hepatitis C virus (HCV) NS5A protein is highly phosphorylated by cellular protein kinases. To study how NS5A might be integrated in cellular kinase signalling, we isolated phosphoproteins from HuH-7 hepatoma cells that specifically interacted with recombinant NS5A protein. Subsequent mass spectrometry identified the adaptor protein amphiphysin II as a novel interaction partner of NS5A. Mutational analysis revealed that complex formation is primarily mediated by a proline-rich region in the C-terminal part of NS5A, which interacts with the amphiphysin II Src homology 3 domain. Importantly, we could further demonstrate specific co-precipitation and cellular co-localization of endogenous amphiphysin II with NS5A in HuH-7 cells carrying a persistently replicating subgenomic HCV replicon. Although the NS5A–amphiphysin II interaction appeared to be dispensable for replication of these HCV RNAs in cell culture, our results indicate that NS5A–amphiphysin II complex formation might be of physiological relevance for the HCV life cycle