bluuebunny/crossref_metadata_2025 huggingface dataset:
Extracellular vesicles from retinal pigment epithelial cells expressing R345W‐Fibulin‐3 induce epithelial‐mesenchymal transition in recipient cells
Authors: Zhou Mi , Zhao Yuanjun , Weber Sarah R. , Gates Christopher , Carruthers Nicholas J. , Chen Han , Liu Xiaoming , Wang Hong‐Gang , Ford Michael , Swulius Matthew T. , Barber Alistair J. , Grillo Stephanie L. , Sundstrom Jeffrey M.
Published: October 2023

We have shown previously that expression of R345W‐Fibulin‐3 induces epithelial‐mesenchymal transition (EMT) in retinal pigment epithelial (RPE) cells. The purpose of the current study was to determine if extracellular vesicles (EVs) derived from RPE cells expressing R345W‐Fibulin‐3 mutation are sufficient to induce EMT in recipient cells. ARPE‐19 cells were infected with luciferase‐tagged wild‐type (WT)‐ Fibulin‐3 or luciferase‐tagged R345W‐Fibulin‐3 (R345W) using lentiviruses. EVs were isolated from the media by ultracentrifugation or density gradient ultracentrifugation. Transmission electron microscopy and cryogenic electron microscopy were performed to study the morphology of the EVs. The size distribution of EVs were determined by nanoparticle tracking analysis (NTA). EV cargo was analysed using LC‐MS/MS based proteomics. EV‐associated transforming growth factor beta 1 (TGFβ1) protein was measured by enzyme‐linked immunosorbent assay. The capacity of EVs to stimulate RPE migration was evaluated by treating recipient cells with WT‐ or R345W‐EVs. The role of EV‐bound TGFβ was determined by pre‐incubation of EVs with a pan‐TGFβ blocking antibody or IgG control. EM imaging revealed spherical vesicles with two subpopulations of EVs: a group with diameters around 30 nm and a group with diameters over 100 nm, confirmed by NTA analysis. Pathway analysis revealed that members of the sonic hedgehog pathway were less abundant in R345W‐ EVs, while EMT drivers were enriched. Additionally, R345W‐EVs had higher concentrations of TGFβ1 compared to control. Critically, treatment with R345W‐EVs was sufficient to increase EMT marker expression, as well as cell migration in recipient cells. This EV‐increased cell migration was significantly inhibited by pre‐incubation of EVs with pan‐TGFβ‐neutralising antibody. In conclusion, the expression of R345W‐Fibulin‐3 alters the size and cargo of EVs, which are sufficient to enhance the rate of cell migration in a TGFβ dependent manner. These results suggest that EV‐bound TGFβ plays a critical role in the induction of EMT in RPE cells.
Radial polarity in the first cranial neuromast of selected teleost fishes
Authors: Otsuka Machiko , Sugita Shoei , Shimizu Daisuke , Aoyama Masato , Matsuda Masaru
Published: October 2023

The neuromast is a sensory structure of the lateral line system in aquatic vertebrates, which consists of hair cells and supporting cells. Hair cells are mechanosensory cells, generally arranged with bidirectional polarity. Here, we describe a neuromast with hair cells arranged radially instead of bidirectionally in the first cranial neuromast of four teleost species: red seabream (Pagrus major), spotted halibut (Verasper variegatus), brown sole (Pseudopleuronectes herzensteini), and marbled sole (Pseudopleuronectes yokohamae). In these four species, this polarity was identified only in the first cranial neuromast, where it appeared at the rostral edge of the otic vesicle before hatching. We investigated the initial appearance and fate of this unique neuromast using scanning electron microscopy. We also assessed characteristics of radial neuromast pertaining to morphogenesis, development, and innervation using a vital fluorescent marker and immunohistochemistry in V. variegatus. The kinocilium initially appears at the center of each hair cell, then moves to its outer perimeter to form radial polarity by around 7 days postfertilization. However, hair cells arranged radially disappear about 15 days after hatching. This is followed by the appearance of bidirectionally arranged hair cells, indicating that polarity replacement from radial to bidirectional has occurred. In P. herzensteini, both afferent and efferent synapses between the nerve fibers and hair cells were observed by transmission electron microscopy, suggesting that radial neuromast is functional. Our discovery suggests that neuromasts with radial polarity could enable larval fish to assimilate multiaxial stimuli during this life stage, potentially assisting them in detecting small water vibrations or water pressure changes.
In Vivo Measurement of Rat Brain Water Content at 9.4 T MR Using Super‐Resolution Reconstruction: Validation With Ex Vivo Experiments
Authors: Thomas Dennis C. , Oros‐Peusquens Ana‐Maria , Schöneck Michael , Willuweit Antje , Abbas Zaheer , Zimmermann Markus , Felder Jörg , Celik Avdo , Shah Nadim Joni
Published: October 2023

Background

Given that changes in brain water content are often correlated with disease, investigating water content non‐invasively and in vivo could lead to a better understanding of the pathogenesis of several neurologic diseases.

Purpose

To adapt a super‐resolution‐based technique, previously developed for humans, to the rat brain and report in vivo high‐resolution (HR) water content maps in comparison with ex vivo wet/dry methods.

Study Type

Prospective.

Animal Model

Eight healthy male Wistar rats.

Field Strength/Sequence

9.4‐T, multi‐echo gradient‐echo (mGRE) sequence.

Assessment

Using super‐resolution reconstruction (SRR), a HR mGRE image (200 μm isotropic) was reconstructed from three low‐resolution (LR) orthogonal whole‐brain images in each animal, which was followed by water content mapping in vivo. The animals were subsequently sacrificed, the brains excised and divided into five regions (front left, front right, middle left, middle right, and cerebellum–brainstem regions), and the water content was measured ex vivo using wet/dry measurements as the reference standard. The water content values of the in vivo and ex vivo methods were then compared for the whole brain and also for the different regions separately.

Statistical Tests

Friedman's non‐parametric test was used to test difference between the five regions, and Pearson's correlation coefficient was used for correlation between in vivo and ex vivo measurements. A P‐value <0.05 was considered statistically significant.

Results

Water content values derived from in vivo MR measurements showed strong correlations with water content measured ex vivo at a regional level (r = 0.902). Different brain regions showed significantly different water content values. Water content values were highest in the frontal brain, followed by the midbrain, and lowest in the cerebellum and brainstem regions.

Data Conclusion

An in vivo technique to achieve HR isotropic water content maps in the rat brain using SRR was adopted in this study. The MRI‐derived water content values obtained using the technique showed strong correlations with water content values obtained using ex vivo wet/dry methods.

Level of Evidence

1

Technical Efficacy

Stage 1
Comparative changes in seasonal marine heatwaves and cold spells over the Tropical Indian Ocean during recent decades and disentangling the drivers of highly intense events
Authors: Dinesh Anand Singh , Mishra Alok Kumar , Dubey Aditya Kumar , Kumari Suruchi , Anand Akash
Published: October 2023

The unprecedented increase in the Sea Surface Temperature (SST) in the warming climate yield stress to the system and pose severe threats to the marine ecosystem. Marine Heatwaves (MHWs) and Marine Cold Spells (MCSs) are two extreme events related to SST variability. For better management of ocean productivity, marine ecosystem, marine services, and fisheries, the understanding of seasonal discrepancies rather than annual documentation of MHWs and MCSs metrics is more utilitarian. This study documents the decadal changes in the MHWs and MCSs over the Tropical Indian Ocean (TIO) for all seasons. Additionally, highly intense events (based on intensity and duration) are identified and demonstrate the associated drivers. During the past two decades (1982–1990, 1991–2000), the MCSs were more frequent than MHWs in every season. However, in the recent two decades (2001–2010, 2011–2020), TIO become more prone to MHWs with considerably more frequent and prolonged events in JJAS months. Moreover, MCSs are disappearing from the TIO. It was noted that the choice of baseline period has an impact on the magnitude of MHWs and MCSs changes, but the spatial pattern (regions with high/low magnitude MHWs and MCSs) stays fairly constant in all baseline period sensitivity checks. The investigation of highly intense events reveals that MHWs and MCSs are produced and sustained by the same drivers when they are at their opposing edges. In general, the coherence effort from winds, net heat fluxes (shortwave radiation, longwave radiation, latent heat flux, and sensible heat flux), mixed level depth, and mean sea level pressure contribute to the genesis of seasonal MHWs or MCSs events. Additionally, in some cases, a single driver (e.g., wind) may also play a crucial role in these extreme events. The remote climate modes of variability, such as El Niño–Southern Oscillation, also contribute significantly to the MHWs and MCSs. El Niño (La Niña) events not only increase the spatial coverage of MHWs (MCSs) but also increases the intensity.
The effect of homogenization when constructing long‐term gridded monthly precipitation and temperature data
Authors: Tveito Ole Einar
Published: October 2023

When assessing long‐term climate trends and variability, it is important to analyse data that are not disturbed by external factors that might lead to misleading trends. It is also urgent to analyse consistent series that cover the entire time period. Since observation networks are continuously changing not too many complete series are available for a centennial long analysis. In this paper an approach to construct long‐term homogenized climate series to be used to derive a long‐term gridded dataset is presented. A gridded dataset of monthly climate anomalies based on all available observations was used to construct 165 raw temperature series and 323 raw precipitation series covering the entire period 1901–2020. These series are homogenized by using the automatic procedure in the R‐package climatol. The gridded data based on the homogenized data show the same regional trends and variability as the data derived from non‐homogenized data. The local spatial variance is smaller in the gridded data based on homogenized series than those based on the raw data series. Both the construction and homogenization of data series to provide spatial and temporal consistent data for gridding lead to better and more reliable gridded datasets for analysing climate trends and variability.
Development of nanofibers functionalized with Cyanex 272 for selective recovery of gold from printed circuit board
Authors: Bernardo Heliano Clemente , Martins Thiago Rodrigues , Bertuol Daniel Assumpção , Tanabe Eduardo Hiromitsu
Published: October 2023

Advances in technological development mean that the recovery of rare and strategic metals from secondary sources has become essential, due to the high demand for these metals in the production of electronic equipment. Contributing to this goal, the main purpose of this work was to develop Nylon 6 nanofibers modified with the Cyanex 272 organic extractant, for use in the selective recovery of gold present in printed circuit boards from armored vehicles. The nanofibers were produced by the centrifugation technique, employing the Forcespinning® system. The best extraction conditions for the separation and concentration of gold were 10% Cyanex 272, fixed pH of 1.5, contact time of 15 min, and solid:liquid ratio (S/L) of 1/700. Gold extraction efficiencies above 77% were achieved in this step. In the stripping step, efficiencies exceeding 85% were obtained using 1 M HCl, 1 M thiourea, S/L of 1/50, and contact time of 3 min. The nanofibers were evaluated in terms of their adsorption capacity, stability, and capacity for reuse in successive cycles. The results showed that the Nylon 6/Cyanex 272 nanofibers could be used in several extraction and stripping cycles. These nanofibers provided high selectivity in the recovery of gold when applied using real leachate solutions, in the presence of other metals (lead, tin, zinc, and copper). The use of nanofibers modified with Cyanex 272 was shown to be an effective option for gold recovery, with lower environmental impacts, compared to conventional liquid–liquid extraction methods that require the use of organic solvents.
Long‐term application of core spun fabric strain sensor manufactured via dip coating for large deformation monitoring
Authors: Han Lei , Zhang Taochuan , Lin Cheng , Gao Qun , Liu Yanlin , Tang Jilong
Published: October 2023

In this study, we fabricated strain sensors using a dip‐coating method on spandex fabric utilizing a mixed solvent of tetrahydrofuran/N,N‐dimethylformamide and carbon black. Scanning electron microscopy images demonstrated a positive correlation between the amount of adhered Carbon black (CB) particles and coating time. Thermogravimetric analysis revealed the thermodynamic behavior of the sensor as gradually heated up to 650°. Mechanical analysis indicated that the reported sensors exhibited a higher elongation at break compared to the original spandex fabric, but with a slight decrease in strength. Moreover, the dissipated energy of each fabric shows a stabilizing tendency after 10 cycles during a 300% stretching‐releasing cyclic tests, where no significant changes observed until the 50th cycle, demonstrating an excellent mechanical repeatability of the fabric sensors. In terms of sensing performance, the sensor exhibited a high sensing range of up to 300%, with the maximum sensitivity reaching 16. Furthermore, we conducted cyclic stretching tests up to 200% strain to characterize the long‐term stability of the fabric's sensing ability. The results demonstrated that our reported method enables a low‐cost and efficient fabrication of sensors with excellent performance.
Lack of benefit from premedication for pegylated asparaginase during pediatric acute lymphoblastic leukemia/lymphoma therapy: A side‐by‐side comparison
Authors: Menig Sarah , Dinh Andrew , Angus Jonathan , Tucker Sarah , Leger Kasey J. , Rushing Teresa , Orgel Etan
Published: October 2023

Background

Pegylated l‐asparaginase (PEG) is integral to treatment regimens for acute lymphoblastic leukemia (ALL) and lymphoma. Hypersensitivity reactions (HSRs) to PEG are common and can preclude continued administration. Data supporting recommendations for universal premedication (UPM) prior to PEG infusion to reduce incidence of HSRs are limited; UPM has become common practice.

Procedures

Two free‐standing children's hospitals independently implemented UPM prior to PEG infusions in 2016 and 2019, respectively. In a side‐by‐side retrospective analysis, incidence and severity of HSRs were analyzed pre‐ and postimplementation of UPM in youth ≥1 years old treated with frontline PEG‐containing ALL regimens (2015–2018, 2016–2020). All HSRs were centrally reviewed within each institution to confirm and grade the HSR (Common Terminology Criteria for Adverse Events, v5). Planned analyses of subsets at potentially greater risk for HSRs included intensive PEG regimens (≥5 doses), adolescent and young adults (AYA), Hispanic/Latinx ethnicity, and obesity.

Results

In 410 patients (by institution, n = 282 and n = 128), the overall incidence of Grade ≥ 3 HSRs was 20% (56 out of 282) and 18% (23 out of 128), respectively. No difference in incidence of Grade ≥ 3 HSRs in patients with versus without UPM was found at either institution (23 vs. 19%, p = .487 and 19 vs. 17%, p = .845). UPM also did not reduce the severity of HSRs, nor influence HSR risk within any patient subset.

Conclusions

UPM prior to PEG infusion did not alter incidence or severity of HSRs at either institution. HSR remains a common complication of PEG therapy, impacting the patient experience. Alternative strategies to reduce HSRs are urgently required.
Optimal timing of delivery for growth restricted fetuses with gastroschisis: A decision analysis
Authors: Packer Claire H. , Pilliod Rachel A. , Caughey Aaron B. , Sparks Teresa N.
Published: October 2023

Objective

Our objective was to determine the optimal timing of delivery of growth restricted fetuses with gastroschisis in the setting of normal umbilical artery (UA) Dopplers.

Methods

We designed a decision analytic model using TreeAge software for a hypothetical cohort of 2000 fetuses with isolated gastroschisis, fetal growth restriction (FGR), and normal UA Dopplers across 34–39 weeks of gestation. This model accounted for costs and quality adjusted life years (QALYs) for the pregnant individual and the neonate. Model outcomes included stillbirth, respiratory distress syndrome (RDS), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), short gut syndrome (SGS), neonatal sepsis, neonatal death, and neurodevelopmental disability (NDD).

Results

We found 38 weeks to be the optimal timing of delivery for minimizing overall perinatal mortality and leading to the highest total QALYs. Compared to 37 weeks, delivery at 38 weeks resulted in 367.98 more QALYs, 2.22 more cases of stillbirth, 2.41 fewer cases of RDS, 0.02 fewer cases of NEC, 1.65 fewer cases of IVH, 0.5 fewer cases of SGS, 2.04 fewer cases of sepsis, 11.8 fewer neonatal deaths and 3.37 fewer cases of NDD. However, 39 weeks were the most cost‐effective strategy with a savings of $1,053,471 compared to 38 weeks. Monte Carlo analysis demonstrated that 38 weeks was the optimal gestational age for delivery 51.70% of the time, 39 weeks were optimal 47.40% of the time, and 37 weeks was optimal 0.90% of the time.

Conclusion

Taking into consideration a range of adverse perinatal outcomes and cost effectiveness, 38–39 weeks gestation is ideal for the delivery of fetuses with gastroschisis, FGR, and normal UA Dopplers. However, there are unique details to consider for each case, and the timing of delivery should be individualized using shared multidisciplinary decision making.
The case for health professional student communication skills training for persons with aphasia
Authors: Mattar Kevin , Eickmeyer Sarah M. , Babbitt Edna , Rydberg Leslie
Published: October 2023

Communication challenges in persons with aphasia may negatively affect their health care. Building effective communication skills is critical for health professional student education, yet communication skills for interacting with persons with aphasia are often not taught or practiced within health care education. A review of the literature found that research is limited but does demonstrate evidence‐based training can improve skills for health professional students. Through utilization of workshops, seminars, and standardized patients, medical students and other health professional students can build confidence and skills in successful communication for future encounters with persons with aphasia.
Automated performance metrics, learning curve and robotic colorectal surgery
Authors: Wong Shing Wai , Crowe Philip
Published: October 2023

Background

The aim of this study was to evaluate the usefulness of Automated Performance Metrics (APMs) in assessing the learning curve.

Methods

A retrospective review of 85 consecutive patients who underwent total robotic colorectal surgery at a single institution between August 2020 and October 2022 was performed. Patient demographics, operation type, and APMs were collected and analysed. Cumulative summation technique (CUSUM) was used to construct learning curves of surgeon console time (SCT), use of the fourth arm, clutch activation, instrument off screen (number and duration), and cut electrocautery activation.

Results

Two phases with 50 and 35 cases were identified from the CUSUM graph for SCT. The SCT was significantly different between the two phases (176 and 251 min, p < 0.002). After adjustment for SCT, the APMs were not significantly different between the two phases.

Conclusions

Most APMs do not offer additional learning curve information when compared with SCT analysis alone.
Copper‐Catalyzed (3+2) Annulation of 5‐Ethynyloxazolidine‐2,4‐diones with Benzoylacetonitriles: Synthesis of Dihydrofuran Derivatives
Authors: Du Juan , Qu Siting , Yu Zhiyuan , Duan Zeqing , Yu Songcheng , Wu Yongjun , Zheng Bing , Guo Hongchao
Published: October 2023

The copper‐catalyzed (3+2) annulation of 5‐ethynyloxazolidine‐2,4‐diones with acylacetonitriles worked well under mild reaction conditions to afford biologically important 2,3‐dihydrofuran derivatives having an amide moiety in moderate to high yields. A wide scope of easily accessible 5‐ethynyloxazolidine‐2,4‐diones and acylacetonitriles were tolerated. The successful scale‐up reaction demonstrated that the reaction is a useful method for the synthesis of 2,3‐dihydrofuran derivatives.
Elevated parent and child hair cortisol moderated the efficacy of a mindful eating intervention
Authors: Ling Jiying , Miller Alison L. , Robbins Lorraine B. , Zhang Nanhua
Published: October 2023

To explore whether elevated baseline hair cortisol moderated effects of a mindful eating intervention on anthropometrics, blood pressure (BP), household food insecurity, eating behaviour, and various psychosocial outcomes. The 14‐week intervention included a parent Facebook‐based programme, 3 parent meetings, preschooler letters connecting school learning to home practices, and a preschool‐based mindful eating programme. Among 107 parent‐preschooler dyads, mean age was 47.32 months for preschoolers and 30.12 years for parents. Among preschoolers, 54.2% were female, 8.4% were Hispanic, and 19.6% were Black. Among parents, 95.3% were female, 6.5% were Hispanic, 15.0% were Black, 39.4% were single, and 43.4% were unemployed. Preschoolers' elevated hair cortisol was related to a smaller reduction in preschoolers' % body fat (r =.31) and smaller increases in parents' perceived responsibility for child feeding (r = −.37). Parents' elevated hair cortisol was associated with smaller decreases in preschoolers' emotional eating (r = .39) and household food insecurity (r = .44). Relationships between baseline hair cortisol and post‐intervention outcomes (BP, emotional eating, fruit/vegetable intake, food insecurity, and coping) varied by baseline values of outcome variables. Given that stress may attenuate intervention effects, a stress management component may be necessary to foster positive behavioural changes. Moreover, interventions should be tailored according to participants' characteristics to achieve optimal effects.
Smart Physical‐Based Transdermal Drug Delivery System:Towards Intelligence and Controlled Release
Authors: Zhang Haojie , Pan Yinping , Hou Yao , Li Minghui , Deng Jia , Wang Bochu , Hao Shilei
Published: October 2023

Transdermal drug delivery systems based on physical principles have provided a stable, efficient, and safe strategy for disease therapy. However, the intelligent device with real‐time control and precise drug release is required to enhance treatment efficacy and improve patient compliance. This review summarizes the recent developments, application scenarios, and drug release characteristics of smart transdermal drug delivery systems fabricated with physical principle. Special attention is paid to the progress of intelligent design and concepts in of physical‐based transdermal drug delivery technologies for real‐time monitoring and precise drug release. In addition, facing with the needs of clinical treatment and personalized medicine, the recent progress and trend of physical enhancement are further highlighted for transdermal drug delivery systems in combination with pharmaceutical dosage forms to achieve better transdermal effects and facilitate the development of smart medical devices. Finally, the next generation and future application scenarios of smart physical‐based transdermal drug delivery systems are discussed, a particular focus in vaccine delivery and tumor treatment.
The use of non‐invasive stool tests for verification of Helicobacter pylori eradication and clarithromycin resistance
Authors: Mommersteeg Michiel C. , Nieuwenburg Stella A. V. , Wolters Leonieke M. M. , Roovers Buddy H. C. M. , van Vuuren Hanneke A. J. , Verhaar Auke P. , Bruno Marco J. , Kuipers Ernst J. , Peppelenbosch Maikel P. , Spaander Manon C. W. , Fuhler Gwenny M.
Published: October 2023

Background

Clarithromycin resistance of Helicobacter pylori (H. pylori) represents a major challenge in eradication therapy. In this study, we assessed if non‐invasive stool tests can be used to verify successful H. pylori eradication and determine clarithromycin resistance.

Materials and methods

In this prospective study, patients undergoing urea breath testing (UBT) for confirmation of H. pylori eradication were asked to collect the stool as both a dry fecal sample and fecal immunochemical test (FIT). Stool H. pylori antigen testing (SAT) was performed on these samples and assessed for its accuracy in eradication verification. Type and duration of antibiotic treatment were retrospectively collected from patient records and compared with clarithromycin resistance determined by PCR of stool samples.

Results

H. pylori eradication information was available for a total of 145 patients (42.7% male, median age: 51.2). Successful eradication was achieved in 68.1% of patients. SAT on FIT samples had similar accuracy for eradication assessment compared to dry fecal samples, 72.1% [95% CI 61.4–81.2] versus 72.2% [95% CI 60.9–81.7]. Clarithromycin resistance rate was 13.4%.

Conclusion

H. pylori antigen testing on FIT stool samples to verify H. pylori eradication is feasible and has similar accuracy as H. pylori antigen testing on dry stool samples. Dry stool, but not FIT, was suitable for non‐invasive identification of H. pylori clarithromycin resistance by rt‐PCR personalizing antibiotic treatment strategies without the need for invasive diagnostics is desirable, as the cure rate of first‐line empirical H. pylori treatment remains low.
Insights into tension‐mediated and antecedent water effects on soil water isotopic composition
Authors: Deseano Diaz Paulina , Nong Thai , Brüggemann Nicolas , Dubbert Maren , Javaux Mathieu , Orlowski Natalie , Vereecken Harry , Rothfuss Youri
Published: October 2023

Using isotopic spike experiments, we investigated the existence and magnitude of soil‐mediated isotopic effects and of the interaction between isotopically distinct soil water pools, both associated in isotopic mismatches between water extracted from soil and soil water taken up by the roots. For this, we applied and compared four established techniques commonly used for the extraction of water (vapor) from soil, three of them relying on destructive soil sampling (cryogenic vacuum distillation, centrifugation, and direct water vapor equilibration), and one being a nondestructive in situ online technique. We observed an almost complete mixing of sequentially added, isotopically distinct water samples to a pure quartz sand (memory effect). The isotopic composition of water held at high soil tension in the pure quartz sand (pF = 2) as well as in a sandy soil (pF = 1.8 and 3) deviated considerably from that of the added water (tension effect). However, we could attribute this deviation not exclusively to a soil‐mediated effect but also to methodological shortcomings during our experiments. Finally, we found the following decreasing trend in precision as well as in accuracy of the used water extraction methods: in situ online > centrifugation > direct water vapor equilibration > cryogenic vacuum distillation. The investigation of isotopic fractionation of soil water due to physicochemical processes in soil can be facilitated if the experimental techniques used do not involve isotopic fractionation. In addition, methodological uncertainties and inaccuracies can be minimized by method standardization, increasing the potential of water stable isotopic monitoring in ecohydrological studies.
Subcontracting Safety (Cases)
Authors: Le Coze Jean-Christophe
Published: October 2023

Companies operating high-hazard installations in the process industry call upon consultants to provide safety-related expertise. They do so voluntarily but also in specific regulatory contexts which require operating companies to assess risks and establish a safety case, a structured evidence-based demonstration that the facility will not generate unacceptable risks for society. Consulting companies have different strategies and compete to gain access to contracts, which are selected according to criteria such as costs, technical propositions, trust or reputation. This creates a specific market. National regulators play a key role in setting the level of expectation regarding safety cases, by among other things, requiring the use of a third-party expert. These preliminary outcomes show the importance of situating and understanding the contribution of these private actors in process safety regulation and governance as another facet of subcontracting in relation to safety.
Complementarity: Ensuring that Contracts Are Compatible with Collaborative Relationships
Authors: Pinnington Bruce
Published: October 2023

Contracts, with their focus on safeguarding a firm’s interests, traditionally, have been considered to be incompatible with collaborative relationships. This chapter explains the basis for this incompatibility and considers how it may be resolved. The key to ensuring that contracts complement collaboration is in the way the coordination function of contracts is aligned with mutuality and consequent trust development. Even dysfunctional relationships may then be repaired.
Boundaries: Their Influence on Managing Safety in Outsourcing
Authors: Pilbeam Colin
Published: October 2023

Boundaries are an essential feature of an organization and integral to the on-going process of organizing. Outsourcing not only disrupts the configuration of organizational boundaries but also compounds the safety management challenges faced by an organization. This chapter connects these two observations through an examination of the composite nature of the organizational boundary. Misalignment between organizations in one or more of the three clusters of processes (physical, mental or social) that comprise the boundary create differences which may contribute to the safety management challenges commonly experienced in outsourcing. Boundary spanning skills that manage these processes are vital for successful working relationships between organizations but are rarely taught in safety training.
Sfumato as a Metaphor for Creating a Common Understanding in Complex Projects
Authors: Gotcheva Nadezhda
Published: October 2023

Sfumato painting technique is proposed as an artistic metaphor for creating a shared understanding about safety and risk in complex safety-critical multi-stakeholder projects. The aim is to illuminate a mindset and suggest approaches for softening potentially detrimental effect of sharp dysfunctional boundaries between and within different project parties, which might impair quality of communication, coordination, and collaboration and impact safety.
State of the Evidence on Climate (Im)mobilities and Well-Being
Authors: Bergmann Jonas
Published: October 2023

In this chapter, I assess the existing evidence with relevance to the research questions. Based on the review of the empirical knowledge on climate-immobility linkages as well as of the objective and subjective well-being impacts of (climate) (im)mobilities, I draw implications for this study. The review yielded a breadth of evidence on migration, but implications on immobility are uncertain. First, the evidence suggests that internal migration can have mixed effects on people’s OWB. Key determinants include how voluntarily and how prepared migrants can leave; under what conditions they move and into which contexts of reception they arrive; the time passed since settling; and how intersectional factors shape (dis-)advantages throughout the process. Some gains seem possible under positive conditions of moving but even then, high costs will likely accompany these gains. Finally, the effects on sending communities depend on the strength of translocal ties; remittances are one central effect but should not detract from others, including those on social relationships. Second, SWB effects greatly depend on context. As in other poor countries, most involuntary migrants and rural-to-urban migrants may be bound to lose present SWB. Only a few, specific groups of migrants might lose SWB shortly before migrating, but then make gains beyond the prior set range. It is possible that climate migrants’ SWB will remain worse than that of stayers and locals. Additionally, negative feelings are likely for stayers, but may be accompanied by positive feelings and gains in satisfaction, especially for poorer recipients of remittances in areas where migration is common. Strong stressors, including those related to climate change, could negatively shape outlooks to the future, but personal-level factors may create buffering effects. More positive views of the future are possible where migrants perceive opportunities, agency, and pathways to desired futures, including for next generations. Critically, if the affected people end up holding more hope or fear could have feedback effects on OWB. Third, the review shows that migrants’ OWB and SWB may converge or diverge, stressing the need to analyze both jointly. Finally, present SWB and views of the future can also converge to varying degrees depending on external and personal-level factors. This study intends to add insights into the array of possible outcomes.
Comparative Analysis and Overarching Propositions
Authors: Bergmann Jonas
Published: October 2023

In this chapter, I comparative and assess the full empirical evidence from three case studies on the highlands, rainforest, and coastal zone of Peru. By doing so, I identify resemblances and divergences regarding the well-being impacts of climate (im)mobilities and mechanisms of action. Findings show that the studied (im)mobilities led to a range of total well-being outcomes, with more net-negative than net-positive results on average. More often than not, significant structural constraints set hard limits on people’s well-being pathways. Foremost, weak governance as well as development and climate inequalities, together with other structures of neglect and marginalization, created an uneven distribution of opportunities to migrate in the first place, to move or stay under tolerable conditions, and to subsequently preserve or enhance well-being. Simultaneously, people’s well-being trajectories also depended on the varying nature and impacts of hazards, which shaped their baseline resources to different extents. Severe abrupt or late-stage gradual climate impacts created particularly heavy well-being burdens for subsequent (im)mobilities. Moreover, the analysis demonstrates that most farmers had very limited agency to address climate impacts or circumvent state failures and other structural hurdles, which further lowered their chances of maintaining or enhancing their well-being. Few affected people managed to use their limited agency to achieve small advances within their constrained room to maneuver. Using the full empirical evidence base generated in this book, I conclude by distilling nine key propositions regarding the well-being impacts of climate (im)mobilities that can be applied beyond the contexts studied here and tested in future research.
Venlafaxine’s therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis
Authors: Lense X.M. , Hiemke C. , Funk C.S.M. , Havemann-Reinecke U. , Hefner G. , Menke A. , Mössner R. , Riemer T.G. , Scherf-Clavel M. , Schoretsanitis G. , Gründer G. , Hart X.M.
Published: October 2023

Introduction

The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.

Objectives

We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.

Methods

Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.

Results

High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75–225 mg/day). The population-based concentration ranges (25–75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225–450 ng/ml for the AM and (ii) 144–302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140–600 ng/ml.

Conclusion

VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN’s dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Interventions to Improve Patient Care on Surgical Ward Rounds: A Systematic Review
Authors: He Reuben , Bhat Sameer , Varghese Chris , Rossaak Jeremy , Keane Celia , Baraza Wal , Wells Cameron I.
Published: October 2023

Background

Ward rounds are an essential component of surgical and perioperative care. However, the relative effectiveness of different interventions to improve the quality of surgical ward rounds remains uncertain. The aim of this systematic review was to evaluate the efficacy of various ward round interventions among surgical patients.

Methods

A systematic literature search of the MEDLINE (OVID), EMBASE (OVID), Scopus, Cumulative Index of Nursing and Allied Health (CINAHL), and PsycInfo databases was performed on 7 October 2022 in accordance with PRISMA guidelines. All studies investigating surgical ward round quality improvement strategies with measurable outcomes were included. Data were analysed via narrative synthesis based on commonly reported themes.

Results

A total of 28 studies were included. Most were cohort studies (n = 25), followed by randomised controlled trials (n = 3). Checklists/proformas were utilised most commonly (n = 22), followed by technological (n = 3), personnel (n = 2), and well‐being (n = 1) quality improvement strategies. The majority of checklist interventions (n = 21, 95%) showed significant improvements in documentation compliance, staff understanding, or patient satisfaction. Other less frequently reported ward round interventions demonstrated improvements in communication, patient safety, and reductions in patient stress levels.

Conclusions

Use of checklists, technology, personnel, and well‐being improvement strategies have been associated with improvements in ward round documentation, communication, as well as staff and patient satisfaction. Future studies should investigate the ease of implementation and long‐term durability of these interventions, in addition to their impact on clinically relevant outcomes such as patient morbidity and mortality.
Thulium fiber laser vs Ho:YAG in RIRS: a prospective randomized clinical trial assessing the efficacy of lasers and different fiber diameters (150 µm and 200 µm)
Authors: Taratkin Mark , Azilgareeva Camilla , Petov Vladislav , Morozov Andrey , Ali Stanislav , Babaevskaya Diana , De Coninck Vincent , Korolev Dmitry , Akopyan Gagik , Scoffone Cesare Marco , Chinenov Denis , Androsov Alexander , Fajkovic Harun , Lifshitz David , Traxer Olivier , Enikeev Dmitry
Published: October 2023

Introduction

The aims of the study: (1) to compare the Super Pulse Thulium Fiber Laser (SP TFL) and the holmium: yttrium–aluminium-garnet (Ho:YAG) lasers in retrograde intrarenal surgery (RIRS); (2) to compare the efficacy of SP TFL laser fibers of different diameters (150 μm and 200 μm).

Methods

A prospective randomized single-blinded trial was conducted. Patients with stones from 10 to 20 mm were randomly assigned RIRS in three groups: (1) SP TFL (NTO IRE-Polus, Russia) with fiber diameter of 150 μm; (2) SP TFL with 200-μm fiber; and (3) Ho:YAG (Lumenis, USA) with 200-μm fiber.

Results

Ninety-six patients with kidney stones were randomized to undergo RIRS with SP TFL using a 150-μm fiber (34 patients) and a 200-μm fiber (32 patients) and RIRS with Ho:YAG (30 patients). The median laser on time (LOT) in the 200-μm SP TFL group was 9.2 (6.2–14.6) min, in 150-μm SP TFL—11.4 (7.7–14.9) min (p = 0.390), in Ho:YAG—14.1 (10.8–18.1) min (p = 0.021). The total energy consumed in 200-μm SP TFL was 8.4 (5.8–15.2) kJ; 150-μm SP TFL − 10.8 (7.3–13.5) kJ (p = 0.626) and in Ho:YAG—15.2 (11.1–25.3) kJ (p = 0.005).

Conclusions

Irrespective of the density, RIRS with SP TFL laser has proven to be both a safe and effective procedure. Whilst the introduction of smaller fibers may have the potential to reduce the duration of surgery, SP TFL results in a reduction in the LOT and total energy for stone ablation in RIRS compared with Ho:YAG.
Greater adherence to the Healthy Nordic Food Index is associated with lower all-cause mortality in a population-based sample from northern Germany
Authors: Stürmer Paula , Ratjen Ilka , Weber Katharina Susanne , Övermöhle Cara , Liedtke Tatjana Patricia , Waniek Sabina , Strathmann Eike Andreas , Lieb Wolfgang
Published: October 2023

Purpose

Dietary pattern scores reflecting a high intake of beneficial food groups were associated with reduced mortality risk. Data on associations of such dietary pattern scores in population-based samples from northern Germany are lacking. Therefore, we examined the association of three dietary pattern scores with all-cause mortality in a moderate-sized prospective sample from northern Germany.

Methods

The study sample comprised 836 participants (43.8% females, median age 62.4 years). Based on a validated, self-administered Food Frequency Questionnaire, the dietary scores Dietary Approaches to Stop Hypertension (DASH), Modified Mediterranean Diet Score (MMDS), and Healthy Nordic Food Index (HNFI) were calculated. Cox proportional hazard regression models, adjusted for age, sex, body mass index, waist to hip ratio, education, smoking status, total energy intake, and physical activity, were used to separately relate DASH, MMDS, and HNFI to all-cause mortality.

Results

During a median follow-up period of 11 years, 93 individuals died. While DASH and MMDS scores were not associated with all-cause mortality, greater adherence to HNFI was associated with lower mortality hazards (HR: 0.47 [95% CI 0.25–0.89] when comparing the highest score quartile to the lowest; HR: 0.79 [95% CI 0.64–0.98] for HNFI modeled as a 1-Standard Deviation increment). Among different HNFI components, higher intake of oats and cereals displayed the most conclusive association with all-cause mortality (HR: 0.59 [95% CI 0.38–0.91] when comparing high and low intake).

Conclusion

In an elderly general population sample from northern Germany, we observed greater adherence to HNFI to be associated with lower all-cause mortality.
The effect of age on outpatient pediatric procedural sedation with intranasal dexmedetomidine and oral midazolam
Authors: Zhou Xiaqing , Zhao Jialian , Tu Haiya , Chen Kunwei , Hu Yaoqin , Jin Yue
Published: October 2023

Procedural sedation for diagnostic examination is a common practice in children. The study aims to analyze the sedative effect and safety of intranasal dexmedetomidine combined with oral midazolam in outpatient pediatric procedural sedation across different age groups and to assess the incidence of sedation failure. From February 2021 to September 2021, children who underwent procedural sedation were retrospectively enrolled. The children were divided into 4 groups based on age: the infant group (0 to 1 year old), toddler group (1 to 3 years old), preschool group (3 to 6 years old), and school-age group (6 to 12 years old). Two-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam were used for sedation. The sedation success rate after rescue, sedation success rate, onset time of sedation, and the sedation time were recorded. The incidence of adverse events and the risk factors for sedation failure were also analyzed. A total of 4758 patients were identified. After exclusion, 3149 patients were ultimately enrolled. The combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam resulted in a total success rate of 99.7% and a sedation success rate of 91.4%. The sedation success rate varied among the four groups: 90.2% in the infant group, 93.1% in the toddler group, 92.7% in the preschool group, and 78.4% in the school-age group. The sedation success rate was significantly lower in the school-age group compared to the other three groups (P < 0.001). The onset time of sedation was shorter in infant (22 min, IQR: 18–28 min, P < 0.001) and longer in the school-age group (30 min, IQR: 25–35 min, P < 0.05). Additionally, the infants had a longer sedation time (110 min, IQR: 90–135 min, P < 0.001) and a higher rate of delayed recovery (27.5%, all P < 0.001). The incidence of adverse events was low (4.70%), which bradycardia (2.03%) being the most common. Age (0–1 year and > 6 years), weight, ASA class II, and history of failed sedation were identified as risk factors of sedation failure.

  Conclusion: Intranasal administration of 2-mcg/kg dexmedetomidine combined with oral administration of 0.5-mg/kg midazolam was found to be efficient and safety for pediatric procedural sedation. Different age groups of children exhibited distinct sedation characteristics, and age was identified as a risk factor affecting the efficacy of sedation.

What is Known:• Procedural sedation for diagnostic examination is a common practice in children.• The combination of dexmedetomidine with midazolam can improve sedative effects.

What is New:• The success rate of sedation using a combination of 2-mcg/kg intranasal dexmedetomidine and 0.5-mg/kg oral midazolam was significantly lower in school-age children as compared to infants, toddlers, and preschoolers.• The onset time of sedation increased with age, and the sedation time was found to be longer in infant patients.