bluuebunny/crossref_metadata_2025 huggingface dataset:
Silicon amendment improves wheat defence against Fusarium graminearum and complements the control by fungicide of Fusarium head blight
Authors: Pazdiora Paulo Cesar , Crizel Rosane Lopes , da Rosa Dorneles Keilor , da Silva Sabrina Monks , Morello Thomas Natali , Chaves Fabio Clasen , Dallagnol Leandro José
Published: September 2022

A three‐year field experiment with two wheat cultivars evaluated the effect of soil‐applied silicon (Si), with and without fungicide spraying, on Fusarium head blight (FHB) control. Silicon treatment alone reduced FHB severity and the percentage of damaged wheat kernels, regardless of the cultivar. The best disease control was obtained for the cultivar with moderate disease resistance (MR), supplied with silicon and treated with fungicide during flowering. Silicon treatment alone promoted an increase in deoxynivalenol (DON) concentration in the disease‐susceptible cultivar; however, in the MR cultivar, silicon amendment associated with fungicide treatment led to a reduction in DON concentration. Greenhouse experiments evaluated the effect of silicon combined with different timings of fungicide application on wheat defences against Fusarium graminearum. Plants supplied with silicon had a longer pathogen incubation period, lower FHB severity and lower DON concentration when compared to plants without silicon. In addition, silicon‐supplied plants had higher soluble phenolic content and altered antioxidant enzyme activities (SOD, CAT, POX and PPO) that favoured early accumulation of hydrogen peroxide when compared to plants without silicon. Greater control of FHB and lower DON concentration in plants treated with silicon and fungicide before inoculation and up to 1 day after inoculation was associated with increased levels of defence‐associated metabolites. Silicon contributed to the reduction of FHB and DON concentration in wheat, especially for the MR cultivar and, when combined with fungicide spraying, both MR and disease‐susceptible cultivars had enhanced performances upon silicon amendment.
Perspectives of Agroforestry Practitioners on Agroforestry Adoption: Case Study of Selected SARE Participants☆
Authors: Romanova Olga , Gold Michael A. , Hall Damon M. , Hendrickson Mary K.
Published: September 2022

Agroforestry practices offer a compelling addition to conventional agriculture as they provide a broad range of economic, ecological, and social benefits. Despite its recognized potential, broad on‐the‐ground adoption of U.S. agroforestry remains limited. Factors influencing agroforestry adoption and dissemination bottlenecks by actual practitioners are underexplored. While previous studies have focused mostly on landowner and farmer interests in agroforestry, without them necessarily being practitioners, this research details the perspective of those who have actively implemented some agroforestry practices. Early adopters of agroforestry represent an essential catalyst for future agroforestry diffusion. Better understanding of the factors influencing their decisions and reasons behind agroforestry practice adoption will help to support and promote wider adoption. This research study documents the what and why questions of early‐stage agroforestry adoption and the intrinsic and extrinsic factors that influence both adoption and discontinuation decisions. Recommendations are offered to target and attract more agroforestry practitioners.
Inferring a Cognitive Architecture from Multitask Neuroimaging Data: A Data‐Driven Test of the Common Model of Cognition Using Granger Causality
Authors: Hake Holly Sue , Sibert Catherine , Stocco Andrea
Published: September 2022

Cognitive architectures (i.e., theorized blueprints on the structure of the mind) can be used to make predictions about the effect of multiregion brain activity on the systems level. Recent work has connected one high‐level cognitive architecture, known as the “Common Model of Cognition,” to task‐based functional MRI data with great success. That approach, however, was limited in that it was intrinsically top‐down, and could thus only be compared with alternate architectures that the experimenter could contrive. In this paper, we propose a bottom‐up method to infer a cognitive architecture directly from brain imaging data itself, overcoming this limitation. Specifically, Granger causality modeling was applied to the same task‐based fMRI data to infer a network of causal connections between brain regions based on their functional connectivity. The resulting network shares many connections with those proposed by the Common Model of Cognition but also suggests important additions likely related to the role of episodic memory. This combined top‐down and bottom‐up modeling approach can be used to help formalize the computational instantiation of cognitive architectures and further refine a comprehensive theory of cognition.
Factor eight inhibiting bypass activity for refractory bleeding in acute type A aortic dissection repair: A propensity‐matched analysis
Authors: Pupovac Stevan S. , Levine Randy , Giammarino Ashley T. , Scheinerman Samuel Jacob , Hartman Alan R. , Brinster Derek R. , Hemli Jonathan M.
Published: September 2022

Background

Perioperative bleeding and transfusion have been associated with adverse outcomes after cardiac surgery. The use of factor eight inhibiting bypass activity (FEIBA) in managing bleeding after repair of acute Stanford type A aortic dissection (ATAAD) has not previously been evaluated. We report our experience in utilizing FEIBA in ATAAD repair.

Study Design and Methods

A retrospective review was undertaken of all consecutive patients who underwent repair of ATAAD between July 2014 and December 2019. Patients were divided into two groups, dependent upon whether or not they received FEIBA intraoperatively: “FEIBA” (n = 112) versus “no FEIBA” (n = 119). From this, 53 propensity‐matched pairs of patients were analyzed with respect to transfusion requirements and short‐term clinical outcomes.

Results

Thirty‐day mortality for the entire cohort was 11.7% (27 deaths), not significantly different between patient groups. Those patients who received FEIBA demonstrated reduced transfusion requirements for all types of blood products in the first 48 h after surgery as compared with the “no FEIBA” cases, including red blood cells, platelets, plasma, and cryoprecipitate (p < .0001). There was no significant difference in major postoperative morbidity between the two groups. The FEIBA cohort did not demonstrate an increased incidence of thrombotic complications (stroke, deep venous thrombosis, pulmonary thromboembolism).

Discussion

When used as rescue therapy for refractory bleeding following repair of ATAAD, FEIBA appears to be effective in decreasing postoperative transfusion requirements whilst not negatively impacting clinical outcomes. These findings should prompt further investigation and validation via larger, multi‐center, randomized trials.
A Non-Intrusive Particle Temperature Extraction Methodology Using Infrared and Visible-Image Sequences for High-Temperature Particle Plumes
Authors: Ortega Jesus D. , Ho Clifford K. , Anaya Guillermo , Vorobieff Peter , Mohan Gowtham
Published: September 2022

The direct measurement of particle temperatures in particle-laden flows presents a unique challenge to thermometry due to the flow's transient and stochastic nature. Previous attempts to measure the bulk particle temperature of a dilute particle plume or particle curtain using intrusive and non-intrusive methods have been mildly successful. In this work, a non-intrusive method using a high-speed infrared (IR) camera and a visible-light camera to yield an indirect particle temperature measurement technique is developed and tested. The image sequences obtained from the IR camera allow for the calculation of the apparent particle temperature, while the visible-light image sets allow for the calculation of the plume opacity as a function of flow discharge position. To extract the true particle temperature, a post-processing algorithm based on Planck's radiation theory was developed. The results were validated through a series of lab-scale tests at the University of New Mexico using a test rig capable of generating particle curtains at various temperatures. The temperature profiles extracted from the methodology presented were compared to the temperature data measured during experimental measurements yielding agreement of the bulk particle temperature of the plume within 10% error. The methods described here will be developed further to estimate the heat losses from the falling particle receiver at Sandia National Laboratories.
Structural Integrity Management of Ageing Offshore Structures: A Regulatory Perspective
Authors: Stacey Alexander , Ersdal Gerhard
Published: September 2022

The North Sea offshore industry is now over 50 years old with the installation of the first platform in the North Sea in 1966. The majority of platforms have now exceeded their design lives and are considered to be ageing structures in the life-extension phase. Safe operation requires the implementation of structural integrity management systems that recognise the potential issues associated with damage, deterioration and obsolescence.

The UK Health and Safety Executive (HSE) Energy Division and Norway’s Petroleum Safety Authority(PSA)have been very active in the development and promotion of good practice in the integrity management of ageing offshore installations from the outset. In the UK, with the transfer of responsibilities from the UK Department of Energy to the HSE following the Piper Alpha disaster of 1988, the HSE has funded a substantial research programme on ageing and life extension (ALE) issues. This has supported the development of codes, standards and guidance on structural integrity management and ageing / life extension. The HSE has under taken major industry-wide inspection programmes and led significant stakeholder engagement activities to promote awareness of ALE within the offshore industry. A particularly successful initiative was the creation of the Energy Institute Ageing and Life Extension Work Group which supports the development of guidance on ALE issues and continues to be very active. Most recently, the HSE has extended its activity to the assessment of extreme weather loading, characterised by the 10,000-year event, which was not a design requirement for ageing installations and now presents a challenge to these.

Similarly, PSA in Norway has placed an increasing focus on ageing facilities since the late 1990s. By then, a few fixed offshore platforms had exceeded their original design life but, more significantly, a number of drilling rigs showed signs of ageing and had exceeded their design life. A joint letter to the industry about managing ageing drilling rigs was issued by the HSE in the UK and PSA in Norway in 2003. From 2005 to 2010, PSA undertook a key programme on ageing and life extension of oil and gas facilities. This key programme initiated several technology-development projects with the aim of increasing knowledge in the industry on life extension assessment.

This paper outlines the work of the offshore regulatory authorities on the issue of ageing and life extension and concludes that, with the focus on energy transition, ALE will present further challenges to the safe operation of offshore structures for the foreseeable future. The management of ALE in the evolving offshore environment also highlights the importance of suitable integrity management practices and the role of regulation in ensuring workforce safety.
Implications of the Loads Jip on Extreme Wave Conditions in the North Sea
Authors: Feld Graham , Randell David , Jonathan Phillip
Published: September 2022

Extreme value analysis is used to assess the impact of the new approaches described in the LOADS JIP on the development of metocean wave criteria in the Central North Sea. The use of the Forristall distributions for determining crest and wave heights is well established but this paper compares inferences using those short-term probability distributions with those from the new approaches in LOADS which better reflect wave non-linearity and the effects of wave breaking in intermediate and deep waters. The new distributions also indicate some sensitivity to wave spreading and JONSWAP peakedness and the sensitivity of extreme wave conditions to these sea-state descriptors is examined. For crest heights, the analysis covered both point and area statistics for nominal deck sizes up to 50m x 50m.

In the presence of uncertainty, there is also potential ambiguity surrounding the precise definition of return value. The quantitative effect of uncertainty is dependent upon the definition used and the impact of three different definitions is compared with the traditional approach of effectively ignoring uncertainty in the extrapolation process.

The analysis was carried out using the NORA10 WAM hindcast developed by the Norwegian Met Office which covered approximately 60 years of historical atmospheric and sea-state conditions. The paper presents quantitative comparisons between return values derived using the different approaches concentrating on return periods of 100 and 10,000 years.
Establishing Unmanning Criteria for a Jacket Structure on the NCS
Authors: Lian Gunnar , Hagen Øistein , Haver Sverre K.
Published: September 2022

The shut-down and unmanning procedure shall be implemented to ensure that the structural reliability of the facility with personnel on-board are not less than for permanently manned platforms. A permanently manned installation shall withstand the abnormal metocean actions (ALS) with an annual probability of exceedance equal to 10−4. According to NORSOK N-006 it can be assumed that the same safety level is achieved by unmanning the installation for a metocean action of 5 x 10−4 exceedance probability per year. NORSOK also recommends to have a criterium related to the probability of exceeding the structural capacity in the forecasted extreme storm. Further, NORSOK N-006 requires that the uncertainty and/or bias in weather forecasts shall be accounted for.

A consistent way of estimating the extreme response is by utilizing a long-term analysis. Two long term approaches will be considered in this paper: all sea states approach and random storm approach. Unmanning criteria according to N-006 will be established for both methods. The example case is unmanning due to possible wave-in-deck impact of a jacket structure in water depth of 110m.

The paper will discuss unmanning by considering the annual target constraint and by considering constraint in terms of forecasted storm event. Further, the effect of forecasted uncertainty will be discussed.
ISO 19901-1 Petroleum and Natural Gas Industries — Specific Requirements for Offshore Structures — Part 1: Metocean Design and Operating Considerations
Authors: Smith Donald
Published: September 2022

ISO 19901-1, the metocean design and operating considerations standard, has been providing the international oil and gas industry with requirements, guidance and region-specific data since it was first issued in 2005. It addresses the sourcing of metocean data, their analyses and extrapolation to long return periods, wave kinematics, joint probability considerations, metocean data (real time) collection and a range of other considerations.

Over the past few years, through a series of Joint Industry Projects and company led initiatives, the industry’s understanding of a range of specific metocean issues has advanced considerably, in particular in relation to crest height determination, wave kinematics, breaking waves, response based analyses and, most recently, how to address epistemic uncertainty within long term metocean extrapolations.

The introduction of these changes within the design and assessment of new and existing structures is likely to require some operators to revisit the basis on which they previously demonstrated that their structures deliver the required level of reliability.

This paper outlines the latest revisions to ISO 19901-1 which address the improvement in knowledge listed above. In addition, it presents new and revised guidance on the validation of Metocean forecasts for weather sensitive operations and region specific information.
Overvview of Underwater Inspection and Repair for Ageing Offshore Structures
Authors: Sharp John V , Ersdal Gerhard
Published: September 2022

Underwater inspection, monitoring and repair (IMR) are increasingly important for offshore structures, particularly in the life extension phase. In many cases, such ageing structures are experiencing an increasing amount of damage and degradation and it is vital for the integrity of these structures that these are detected, located, sized and repaired if required. Techniques for these have been developed over many years with growing experience. Monitoring may become an essential part of continuous managing the safety of such structures.

A significant amount of work has been undertaken in the area of IMR over the years since the start-up of the offshore oil and gas industry. This paper aims to give a brief review of the history and techniques of underwater inspection, monitoring and repair of offshore structures. The following topics will be described:

Life extension assessment should be based on a thorough understanding of the condition and configuration of a structure, established through inspection and monitoring. Hence, the above-mentioned topics are highly relevant for ageing and life extension. Experience has shown that a proper inspection and repair regime can contribute to avoiding structural accidents. For ageing structure an increased number of interventions and repairs place more demands on the technology and personnel available.
Inspection-Based Life Extension of Offshore Jacket Fleets
Authors: Younan Adel , Angevine Doug
Published: September 2022

Over the years, underwater inspections of analytically “fatigued” tubular joints have mostly concluded with lack of weld cracks or indication thereof. Life extension of platforms, however, continues to honor fatigue results by considering all “fatigued” joints as severed in the end-of-life models. With many severed joints, linear design assessments seldom work, typically triggering nonlinear pushovers, with fewer qualified contractors and software, higher running times, leading to risk assessments, fit-for-risk conclusions, and mitigation measures such as downgrading platform manning and additional underwater inspections. All these struggles continue today while underwater inspections continue to negate analytical fatigue results. This paper proposes two approaches to reconcile this conflict. The first is based on use of underwater inspections of “fatigued” joints to reset their lives, and also to regress an update for similar uninspected yet “fatigued” joints. The second approach is based on leveraging the statistics of the underlying S-N curves to suggest scenarios of severed joints. In the first approach, only one end-of-life extension model is retained albeit with fewer “fatigued” joints. In the second approach, several end-of-life extension models are developed albeit each has fewer severed joints consistent with S-N statistics. In both cases, the conflict between end-of-life models and underwater inspections is addressed, linear design checks become more successful, nonlinear pushovers are mostly avoided as are the ensuing risk assessments and mitigation measures. The two approaches were developed internally in ExxonMobil and successfully applied to its offshore fleets worldwide. The two methods with example applications are presented in this paper for industry consideration.
UK Regulatory Initiative on the Extreme Environmental Loading of Fixed Offshore Installations in the North Sea
Authors: Stacey A.
Published: September 2022

A significant number of offshore installations on the United Kingdom Continental Shelf are considered to be ageing installations which have exceeded their original design lives and were designed to less stringent criteria than those required of modern installations using current standards. As a result, they have not been designed to survive the 10,000-year environmental event, which is now a requirement for UK waters. A study was recently completed on behalf of the HSE’s Energy Division to develop guidance providing recommendations for the development of industry practice on the assessment of extreme loading acting on fixed offshore structures and the evaluation and management of the risk of structural failure associated with extreme environmental loading.

It was concluded that current procedures may underestimate the capacity of some offshore structures to withstand the 10,000-year event and that further work is required to develop industry practice on the assessment of the extreme weather capacity of offshore structures and mitigation measures to ensure their continued safe operation. It was further concluded that a programme of stakeholder engagement is required to raise awareness of the issue. This paper outlines the work undertaken, the general findings and recommendations and the latest offshore industry initiatives to take these forward.
Learnings from the Performance of Fixed Steel Structures in Gulf of Mexico Hurricanes
Authors: Puskar Frank J.
Published: September 2022

Starting in 1992 with Hurricane Andrew, thousands of fixed steel structures located in the Gulf of Mexico were subjected to seven major hurricanes ending with Hurricane Ike in 2008. While most structures survived with little or no damage, hundreds of structures were severely damaged and over 250 structures were destroyed. Since all of the manned structures were evacuated in advance of the hurricanes and operations shut-in, there were no lives lost and no major environmental issues. The offshore structures industry responded with multiple comprehensive studies and updated guidance documents addressing everything from metocean conditions, jacket structures, topsides structures, drilling rigs and masts, pre- and post-hurricane planning and other associated issues. The efforts involved API, government regulators, academia as well as individual operator initiatives.

This paper discusses these hurricanes and structures, looking at the types of damage and destruction, including issues such as wave-in-deck (WID), and then what went right and what went wrong. Several types of above and below water repairs related to integrity management are discussed including how some repairs installed after the first few hurricanes performed in subsequent hurricanes. Comparisons between hindcast hurricane wave conditions are described including global metocean loading compared to structure performance (survived, damaged, destroyed). Associated updates to API guidance are discussed including ongoing efforts to update the code calibration work performed at that time to some of the latest findings on metocean loading.
Life Extension of Mooring Chains - Including Effects of Mean Load and Corrosion Condition to Fatigue Capacity
Authors: Gabrielsen Øystein , Voie Per Erlend , Lone Erling , Reinholdtsen Svein-Arne
Published: September 2022

The mooring systems on floating offshore installations are typically designed for a life of 25 years. Life extension of installations beyond the original design life thus requires either mooring system replacement or assessment to document life extension of the mooring system components. Mooring chains are normally the components with the shortest design life, where the design codes define how break strength and fatigue capacity reduce with time, due to an annual expected corrosion loss.

Equinor has replaced many mooring chains, and these have been thoroughly inspected, where some have been tested to document actual break capacity and fatigue capacity. The effect of corrosion on breaking strength is found to be low, while the effect of corrosion on fatigue capacity is found to be significantly larger than specified in design codes. Another key finding is that the fatigue capacity is dependent on mean load. For mooring systems with low pretension or mean load, the mooring lines may have better fatigue capacity than initially calculated in design. By analyzing full scale fatigue test data from both new and used chain, it is now possible to establish formulas for mooring chain fatigue capacity which also account for the effects of mean load and corrosion condition.

The total number of chain replacements has, together with installation specific chain replacements, made it possible to estimate corrosion condition and forecast future corrosion development. It has thus been possible to perform fatigue reassessment including fatigue capacity with the effect of chain degeneration.

This paper presents the fatigue life reassessment of the mooring chains for an FPSO on the Norwegian Continental Shelf (NCS), utilizing the new knowledge. The reassessment documents a significant increase of the service life for certain mooring line segments, while some are confirmed due for replacement. As a result, the initially planned chain replacement scope has been reduced, with large cost savings. The paper presents and discusses the assumptions and data used in the analysis, including comparison with standard fatigue analysis for the same mooring system.
Lifetime Extension of Mooring Anchors
Authors: Gabrielsen Øystein , Liengen Turid , Molid Solfrid , Skåum Gro
Published: September 2022

The mooring systems for floating offshore installations are typically designed for a life of 25 years. Life extension of the installations beyond original design life require either replacement of components or life extension of the existing, where keeping components in the systems as is require assessments knowing the condition of the components. Some of the components are difficult or impossible to inspect in operation, such as chain in the seabed and the anchors. On the NCS typically suction anchors have been used, where all the load bearing parts, including connection to mooring lines, are buried in the soil.

Assumptions with respect of degradation were established in design of the anchors. However, actual degradation of the parts buried in the soil has been uncertain, and in situ inspection of the anchors has been impossible. Equinor has retrieved several anchors to shore which has enabled degradation investigation. Two suction anchors have been retrieved as mooring lines were taken out of service, while a third anchor has been retrieved and substituted from a mooring system in operation. By bringing the anchors to shore, thorough inspection followed by life extension evaluation for remaining anchors has been possible.

This paper presents the work done on retrieving used mooring anchors, including description of condition and degradation mechanisms. The paper presents our conclusions for life extension of mooring anchors on the NCS.
Ageing and Life Extention of Pipelines
Authors: Salama Mamdouh M.
Published: September 2022

This section addresses issues associated with degradation, life extension and reuse of pipelines. In addition, one paper in the section addresses an issue related to leak potential of an LNG flare header due to temperature gradient and another paper addresses integrity assessment of pressure vessels. Regarding pipelines, there three main aspects that affect their ageing assessment and life extension studies. These are: 1) time dependent materials degradation such as corrosion and fatigue, 2) changes in operational conditions particularly fluid composition, and 3) accidental damage such as drop object impact. Maintaining safe operating condition of pipelines, particularly those handling corrosive fluids requires implementation of proper corrosion control strategy that includes inspection and maintenance programs to avoid uneconomical decisions if inspection and maintenance are scheduled too early, and to ensure against increasing the probability of failure leading to unacceptable risk if the inspection and maintenance is scheduled too late. The papers in this section highlight the importance of in-line inspection as well as requalification in case of change of operating conditions.
Inspection and Repair
Authors: Ersdal Gerhard
Published: September 2022

All structures and pipelines deteriorate and experience damage during operation, even if they are properly designed for a given design life. Inspection activities are as a result needed to find and characterize these damages and deteriorations and repair activities may be needed if significant damage or deterioration are found to avoid unsafe conditions. Although the design of these structures and pipelines are intended to provide a safe operation life, experience has shown that inspection and repair is needed during the design life. The likelihood of damages and deteriorations often increases with age and inspection and repair, as a result, becomes even more important for such ageing infrastructure.
PD-1/PD-L1 blockade abrogates a dysfunctional innate-adaptive immune axis in critical β-coronavirus disease
Authors: Duhalde Vega Maite , Olivera Daniela , Gastão Davanzo Gustavo , Bertullo Mauricio , Noya Verónica , Fabiano de Souza Gabriela , Primon Muraro Stéfanie , Castro Icaro , Arévalo Ana Paula , Crispo Martina , Galliussi Germán , Russo Sofía , Charbonnier David , Rammauro Florencia , Jeldres Mathías , Alamón Catalina , Varela Valentina , Batthyany Carlos , Bollati-Fogolín Mariela , Oppezzo Pablo , Pritsch Otto , Proença-Módena José Luiz , Nakaya Helder I. , Trias Emiliano , Barbeito Luis , Anegon Ignacio , Cuturi María Cristina , Moraes-Vieira Pedro , Segovia Mercedes , Hill Marcelo
Published: September 2022

Severe COVID-19 is associated with hyperinflammation and weak T cell responses against SARS-CoV-2. However, the links between those processes remain partially characterized. Moreover, whether and how therapeutically manipulating T cells may benefit patients are unknown. Our genetic and pharmacological evidence demonstrates that the ion channel TMEM176B inhibited inflammasome activation triggered by SARS-CoV-2 and SARS-CoV-2–related murine β-coronavirus.

Tmem176b
−/−

mice infected with murine β-coronavirus developed inflammasome-dependent T cell dysfunction and critical disease, which was controlled by modulating dysfunctional T cells with PD-1 blockers. In critical COVID-19, inflammasome activation correlated with dysfunctional T cells and low monocytic TMEM176B expression, whereas PD-L1 blockade rescued T cell functionality. Here, we mechanistically link T cell dysfunction and inflammation, supporting a cancer immunotherapy to reinforce T cell immunity in critical β-coronavirus disease.
PKM2 promotes pulmonary fibrosis by stabilizing TGF-β1 receptor I and enhancing TGF-β1 signaling
Authors: Gao Shaoyan , Li Xiaohe , Jiang Qiuyan , Liang Qing , Zhang Fangxia , Li Shuangling , Zhang Ruiqin , Luan Jiaoyan , Zhu Jingyan , Gu Xiaoting , Xiao Ting , Huang Hui , Chen Shanshan , Ning Wen , Yang Guang , Yang Cheng , Zhou Honggang
Published: September 2022

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease, and the molecular mechanisms remain poorly understood. Our findings demonstrated that pyruvate kinase M2 (PKM2) promoted fibrosis progression by directly interacting with Smad7 and reinforcing transforming growth factor–β1 (TGF-β1) signaling. Total PKM2 expression and the portion of the tetrameric form elevated in lungs and fibroblasts were derived from mice with bleomycin (BLM)–induced pulmonary fibrosis.
Pkm2
deletion markedly alleviated BLM-induced fibrosis progression, myofibroblast differentiation, and TGF-β1 signaling activation. Further study showed that PKM2 tetramer enhanced TGF-β1 signaling by directly binding with Smad7 on its MH2 domain, and thus interfered with the interaction between Smad7 and TGF-β type I receptor (TβR1), decreased TβR1 ubiquitination, and stabilized TβR1. Pharmacologically enhanced PKM2 tetramer by TEPP-46 promoted BLM-induced pulmonary fibrosis, while tetramer disruption by compound 3k alleviated fibrosis progression. Our results demonstrate how PKM2 regulates TGF-β1 signaling and is a key factor in fibrosis progression.
Gastric dysfunction in patients with chronic nausea and vomiting syndromes defined by a noninvasive gastric mapping device
Authors: Gharibans Armen A. , Calder Stefan , Varghese Chris , Waite Stephen , Schamberg Gabriel , Daker Charlotte , Du Peng , Alighaleh Saeed , Carson Daniel , Woodhead Jonathan , Farrugia Gianrico , Windsor John A. , Andrews Christopher N. , O’Grady Greg
Published: September 2022

Chronic nausea and vomiting syndromes (NVSs) are prevalent and debilitating disorders. Putative mechanisms include gastric neuromuscular disease and dysregulation of brain-gut interaction, but clinical tests for objectively defining gastric motor function are lacking. A medical device enabling noninvasive body surface gastric mapping (BSGM) was developed and applied to evaluate NVS pathophysiology. BSGM was performed in 43 patients with NVS and 43 matched controls using Gastric Alimetry (Alimetry), a conformable high-resolution array (8 × 8 electrodes; 20-mm interelectrode spacing), wearable reader, and validated symptom-logging app. Continuous measurement encompassed a fasting baseline (30 minutes), 482-kilocalorie meal, and 4-hour postprandial recording, followed by spectral and spatial biomarker analyses. Meal responses were impaired in NVS, with reduced amplitudes compared to controls (median, 23.3 microvolts versus 38.0 microvolts,
P
< 0.001), impaired fed-fasting power ratios (1.1 versus 1.6,
P
= 0.02), and disorganized slow waves (spatial frequency stability, 13.6 versus 49.5;
P
< 0.001). Two distinct NVS subgroups were evident with indistinguishable symptoms (all
P
> 0.05). Most patients (62%) had normal BSGM studies with increased psychological comorbidities (43.5% versus 7.7%;
P
= 0.03) and anxiety scores (median, 16.5 versus 13.0;
P
= 0.035). A smaller subgroup (31%) had markedly abnormal BSGM, with biomarkers correlating with symptoms (nausea, pain, excessive fullness, early satiety, and bloating; all
r
> 0.35,
P
< 0.05). Patients with NVS share overlapping symptoms but comprise distinct underlying phenotypes as revealed by a BSGM device. These phenotypes correlate with symptoms, which should inform clinical management and therapeutic trial design.
Passenger donor lymphocytes: To affinity and beyond
Authors: Manook Miriam , Motallebzadeh Reza , Pettigrew Gavin J
Published: September 2022

Graft-versus-host recognition by passenger donor lymphocytes within organ transplants can trigger host alloantibody production (Charmetant
et al
.)
.
Supplemental Material: Location and shape of the Lhasa terrane prior to India-Asia collision
Authors: Bian Weiwei , al. et
Published: September 2022

The supplemental material contains further illustrations of hysteresis loops (Fig. S1), k-T curves (Fig. S2), equal-area projections of the specimen-mean directions of the low-temperature component (Fig. S3), equal-area projections of the site-mean directions of the intermediate-temperature component (Fig. S4), hysteresis parameter for individual specimens at room temperature (Table S1), intermediate-temperature component directions for the Duoni Formation red beds (Table S2), high-temperature component directions for the Duoni Formation red beds (Table S3), and summary of the available Cretaceous paleomagnetic results from the Shiquanhe, Gerze, Cuoqin, Maxiang, Linzhou, and Naqu areas in the Lhasa terrane (Table S4).
Stability of the Boundary Layer with Internal Heat Release and Gas Injection through a Porous Wall
Authors: Gaponov S. A.
Published: September 2022

The problem of stability of a subsonic boundary layer is solved under the conditions of heat supply inside the boundary layer with injection of a homogeneous gas through a porous plate that partially simulates the problem of stability of a boundary layer with diffuse combustion. Two-dimensional waves are the most growing waves over the entire range of investigated parameters. It is found that in the case of a fixed norm of heat supply the maximum temperature in the boundary layer increases with the Reynolds number, i.e., with increase in the distance from the leading plate edge. This is in agreement with available experiments and calculations of parameters of the boundary layer with diffuse combustion. In this case the dependence of the degrees of amplification on the Reynolds number, which are maximum in the frequency, is nonmonotonic. It is shown that gas injection with heat supply destabilizes the boundary layer, as it occurs without heat supply. On the other hand, the stabilizing role of heat supply is also shown under the conditions of gas injection through a porous wall. As the frequency of growing wave increases, the phase velocity tends to the velocity at the generalized inflection point. Despite fairly large degrees of growing, the Gaster relation is valid. In accordance with this relation the spatial degree of amplification is equal to the temporal degree of amplification divided by the group velocity.
Primary resection of oligometastatic recurrent prostatic carcinoma in the urethra
Authors: Foo Malia Alexandra , Lim Ee Jean , Cheng Christopher Wai Sam , Ng Lay Guat
Published: September 2022

A man in his 70s presented to the emergency department with acute urinary retention following a 2-day history of gross haematuria with blood clots. He had a significant medical history of intermediate-risk prostate adenocarcinoma (grade group 2, prostate-specific antigen (PSA) 14.9 ng/mL) for which he underwent a robotic-assisted laparoscopic radical prostatectomy (RARP) 13 years ago. PSA nadir was achieved (<0.03 ng/mL). Three years after RARP, he had biochemical recurrence with PSA rising to 0.06 ng/mL. Salvage radiotherapy was performed with good PSA response back to nadir. Workup for gross haematuria included a flexible cystoscopy which revealed a lobulated fleshy lesion occupying the mid-penile urethra. Staging imaging showed no local recurrence at prostatectomy site or lymphadenopathy. PSA was 4.2 ng/mL. Surgical resection with primary repair of the urethra was performed. Postoperative recovery was good with PSA achieving nadir. Histology revealed an upgraded metastatic prostate adenocarcinoma, grade group 5.
Effects of short-term exposure to air pollution on hospital admissions for autism spectrum disorder in Korean school-aged children: a nationwide time-series study
Authors: Kim Kyoung-Nam , Sohn Ji Hoon , Cho Sung Joon , Seo Hwo Yeon , Kim Soontae , Hong Yun-Chul
Published: September 2022

Objectives

This study explored the effects of short-term exposure to air pollution on hospital admissions for autism spectrum disorder (ASD), a proxy for symptom aggravation, among Korean children aged 5–14 years.

Design

Time-series study.

Setting, participants and outcome measures

We used data from the National Health Insurance Service (2011–2015). Daily concentrations of fine particulate matter (PM2.5), nitrogen dioxide (NO2) and ozone (O3) levels in each region were used as exposures. ASD cases were defined based on a principal admission diagnosis of the claims data. We applied distributed lag non-linear models and a generalised difference-in-differences method to the quasi-Poisson models to estimate the causal effects of air pollution for up to 6 days. We also performed weighted quantile sum regression analyses to assess the combined effects of air pollution mixtures.

Results

PM2.5levels at lag day 1, NO2levels at lag day 5 and O3levels at lag day 4 increased the risks of hospital admissions for ASD (relative risk (RR)=1.17, 95% CI 1.10 to 1.25 for PM2.5; RR=1.09, 95% CI 1.01 to 1.18 for NO2and RR=1.03, 95% CI 1.00 to 1.06 for O3). The mean daily count of hospital admissions for ASD was 8.5, and it would be 7.3, 7.8 and 8.3 when the PM2.5levels would be decreased by 10.0 µg/m3, NO2by 10 ppb and O3by 10 ppb, respectively. The weighted quantile sum index, constructed from PM2.5, NO2and O3levels, was associated with a higher risk of hospital admissions for ASD (RR 1.29, 95% CI 1.14 to 1.46), where NO2was found to contribute to the effects most (the weight of 0.80).

Conclusions

These results emphasise that reduction of air pollution exposure should be considered for ASD symptom management, with important implications for the quality of life and economic costs.
Impact of the COVID-19 pandemic upon self-reported physician burnout in Ontario, Canada: evidence from a repeated cross-sectional survey
Authors: Gajjar Jainita , Pullen Naomi , Li Yin , Weir Sharada , Wright James G
Published: September 2022

Objectives

To estimate the impact of the SARS-CoV-2 (COVID-19) pandemic on levels of burnout among physicians in Ontario, Canada, and to understand physician perceptions of the contributors and solutions to burnout.

Design

Repeated cross-sectional survey.

Setting

Active and retired physicians, residents and medical students in Canada’s largest province were invited to participate in an online survey via an email newsletter.

Participants

In the first survey wave (March 2020), 1400 members responded (representing 76.3% of those who could be confirmed to have received the survey and 3.1% of total membership). In the second wave (March 2021), 2638 responded (75.9% of confirmed survey recipients and 5.8% of membership).

Key outcome measure

Level of burnout was assessed using a validated, single-item, self-defined burnout measure where options ranged from 1 (no symptoms of burnout) to 5 (completely burned out).

Results

The overall rate of high levels of burnout (self-reported levels 4–5) increased from 28.0% in 2020 (99% CI: 24.3% to 31.7%) to 34.7% in 2021 (99% CI: 31.8% to 37.7%), a 1-year increase of 6.8 percentage points (p<0.01). After a full year of practising during the COVID-19 pandemic, respondents ranked ‘patient expectations/patient accountability’, ‘reporting and administrative obligations’ and ‘practice environment’ as the three factors that contributed most to burnout. Respondents ranked ‘streamline and reduce required documentation/administrative work’, ‘provide fair compensation’ and ‘improve work–life balance’ as the three most important solutions.

Conclusions

During the first 12 months of the COVID-19 pandemic in Ontario, prevalence of high levels of burnout had significantly increased. The contributors and solutions ranked highest by physicians were system-level or organisational in nature.
Are better existing WASH practices in urban slums associated with a lower long-term risk of severe cholera? A prospective cohort study with 4 years of follow-up in Mirpur, Bangladesh
Authors: Kang Sophie , Chowdhury Fahima , Park Juyeon , Ahmed Tasnuva , Tadesse Birkneh Tilahun , Islam Md. Taufiqul , Kim Deok Ryun , Im Justin , Aziz Asma Binte , Hoque Masuma , Pak Gideok , Khanam Farhana , Ahmmed Faisal , Liu Xinxue , Zaman K , Khan Ashraful Islam , Kim Jerome H , Marks Florian , Qadri Firdausi , Clemens John D
Published: September 2022

Objective

To investigate the association between existing household water quality, sanitation and hygiene (WASH) practices and severe cholera risk in a dense urban slum where cholera is highly endemic.

Design, setting and participants

We assembled a large prospective cohort within a cluster randomised trial evaluating the effectiveness of oral cholera vaccine. Our dynamic cohort population (n=193 576) comprised individuals living in the ‘non-intervention’ clusters of the trial, and were followed over 4 years. This study was conducted in a dense urban slum community of Dhaka, Bangladesh and cholera surveillance was undertaken in 12 hospitals serving the study area.

Primary outcome measure

First severe cholera episode detected during follow-up period.

Methods

We applied a machine learning algorithm on a training subpopulation (n=96 943) to develop a binary (‘better’, ‘not better’) composite WASH variable predictive of severe cholera. The WASH rule was evaluated for performance in a separate validation subpopulation (n=96 633). Afterwards, we used Cox regression models to evaluate the association between ‘better’ WASH households and severe cholera risk over 4 years in the entire study population.

Results

The ‘better’ WASH rule found that water quality and access were the most significant factors associated with severe cholera risk. Members of ‘better’ WASH households, constituting one-third of the population, had a 47% reduced risk of severe cholera (95% CI: 29 to 69; p<0.001), after adjusting for covariates. The protective association between living in a ‘better’ WASH household and severe cholera persisted in all age groups.

Conclusions

Salutary existing household WASH practices were associated with a significantly reduced long-term risk of severe cholera in an urban slum of Dhaka. These findings suggest that WASH adaptations already practised in the community may be important for developing and implementing effective and sustainable cholera control programmes in similar settings.

Trial registration number

This article is a re-analysis of data from a cluster randomized trial; can be found on ClinicalTrials.govNCT01339845
Effects of healthcare system transformations spurred by the COVID-19 pandemic on management of stroke and STEMI: a registry-based cohort study in France
Authors: Lesaine Emilie , Francis-Oliviero Florence , Domecq Sandrine , Bijon Marine , Cetran Laura , Coste Pierre , Lhuaire Quentin , Miganeh-Hadi Sahal , Pradeau Catherine , Rouanet François , Sevin Floriane , Sibon Igor , Saillour-Glenisson Florence
Published: September 2022

Objective

To assess the impact of changes in use of care and implementation of hospital reorganisations spurred by the COVID-19 pandemic (first wave) on the acute management times of patients who had a stroke and ST-segment elevation myocardial infarction (STEMI).

Design

Two cohorts of patients who had an STEMI and stroke in the Aquitaine Cardio-Neuro-Vascular (CNV) registry.

Setting

6 emergency medical services, 30 emergency units (EUs), 14 hospitalisation units and 11 cathlabs in the Aquitaine region.

Participants

This study involved 9218 patients (6436 patients who had a stroke and 2782 patients who had an STEMI) in the CNV Registry from January 2019 to August 2020.

Method

Hospital reorganisations, retrieved in a scoping review, were collected from heads of hospital departments. Other data were from the CNV Registry. Associations between reorganisations, use of care and care management times were analysed using multivariate linear regression mixed models. Interaction terms between use-of-care variables and period (pre-wave, per-wave and post-wave) were introduced.

Main outcome measures

STEMI cohort, first medical contact-to-procedure time; stroke cohort, EU admission-to-imaging time.

Results

Per-wave period management times deteriorated for stroke but were maintained for STEMI. Per-wave changes in use of care did not affect STEMI management. No association was found between reorganisations and stroke management times. In the STEMI cohort, the implementation of systematic testing at admission was associated with a 41% increase in care management time (exp=1.409, 95% CI 1.075 to 1.848, p=0.013). Implementation of plan blanc, which concentrated resources in emergency activities, was associated with a 19% decrease in management time (exp=0.801, 95% CI 0.639 to 1.023, p=0.077).

Conclusions

The pandemic did not markedly alter the functioning of the emergency network. Although stroke patient management deteriorated, the resilience of the STEMI pathway was linked to its stronger structuring. Transversal reorganisations, aiming at concentrating resources on emergency care, contributed to maintenance of the quality of care.

Trial registration number

NCT04979208.