bluuebunny/crossref_metadata_2025 huggingface dataset:
Applying the Model of the European Foundation for Quality Management to evaluate quality of care alongside the merger of mental health care institutes in Amsterdam: a five year pre–post study
Authors: Nabitz Udo , Klazinga Niek , Muller Jeroen , Schramade Mark , Lans Marijke , Osseman Dick
Published: July 2023

Background

Health care reforms over the past decades in the Netherlands enforced institutions to enhance quality and to contain costs. To cope with the policy context, a majority of mental health care institutes applied a merger strategy and hence large mental health care organizations were created. This study assesses the impact of a merger and the related quality management approach on the quality of care of three large Dutch mental health care institutes in Amsterdam. The nine criteria of the Model of the European Foundation for Quality Management (EFQM Model) with 32 criteria parts for total quality management were used.

Method

A case study with a pre–post design was applied, with the EFQM baseline (pre) and follow-up (post) assessments using the standardized EFQM protocol with a 0%–100% scoring system. The baseline status of 2007–2008 was scored and validated by seven independent certified assessors. During a period of 5 years, the merge was conducted, enhancing the quality management and effectuating the findings of the advice of the feedback report. An EFQM post-assessment of the status of 2012–2013 was carried out by five independent certified assessors applying the strict EFQM assessment protocol. The statistics of pre–post differences were evaluated. The study can be seen as a before–after assessment of a naturalistic experiment.

Results

The comparison of the nine EFQM criteria before and after the merger on the bases of the scores of the assessors shows an overall improvement from 358 to 425 points on the EFQM scale 0–1000. There is one slight deterioration concerning criterion 8: Society Results, five criteria show positive changes. The top three criteria with the highest improvement are 1: Leadership (15% improvement), 5: Processes, Products, and Services (12%), 6: Customer Results (15%). The overall statement of the audit team of 2013 is ‘The merged organisation strives for effectiveness, which leads to better results in most of the areas.’ Learning from the results is one recommendation of the assessors for the future.

Conclusion

The conduced merge of three Dutch mental health care institutions in Amsterdam showed an improvement of quality based on the criteria of the EFQM Model over a period of 5 years. This naturalistic experiment can stimulate further studies about mergers. The systematic and transparent approach and documentation can facilitate mutual learning.
Method for the Determination of 2′-Fucosyllactose (2′-FL), 3-Fucosyllactose (3-FL), 6′-Sialyllactose (6′-SL), 3′-Sialyllactose (3′-SL), Lacto-N-Tetraose (LNT), and Lacto-N-neoTetraose (LNnT) by High-Performance Anion-Exchange Chromatography With Pulsed Amperometric Detection (HPAEC-PAD): First Action 2022.04
Authors: Haselberger Philip , Tian Fang , Erney Renée , Liu Shuang , Wang Shuo , Lin Qi , Ding Yi
Published: July 2023

Background

A method for simultaneous determination of six human milk oligosaccharides (HMOs) is described. The HMOs include 2′-fucosyllactose (2′-FL, CAS number 41263-94-9), 3-fucosyllactose (3-FL, CAS number 41312-47-4), 6′-sialyllactose (6′-SL, CAS number 35890-39-2), 3′-sialyllactose (3′-SL, CAS number 35890-38-1), lacto-N-tetraose (LNT, CAS number 14116-68-8), and lacto-N-neotetraose (LNnT, CAS number 13007-32-4). The method was designed to comply with the respective Standard Method Performance Requirements (SMPR®; seeTable 1), respectively.

Objective

The method is valid for six HMOs in infant formula and adult nutritional matrixes, including samples with intact protein, protein hydrolysates, elemental formulations free of intact protein, and rice flour over the ranges defined in the SMPR (seeTable 2). The method is not valid for determination of difucosyllactose (DFL/DiFL).

Method

For most samples, reconstitution with water followed by filtration. For products containing interferences (fructans and maltodextrins), hydrolysis with enzymes is used. After preparation, samples are analyzed using high-performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD). The method provides for separation of six HMOs and other carbohydrates commonly found in infant formula and adult nutritional products (e.g., lactose, sucrose, and GOS).

Results

This study includes data from multiple matrixes evaluated by multiple laboratories globally. RSDr ranged from 0.0068 to 4.8% RSDr, and spike recovery results ranged from 89.4 to 109%. Calibration fit optimal with a quadratic curve; alternately linear fit showed no statistically significant impact to data (when correlation passes).

Conclusions

This method was reviewed by the AOAC SPIFAN Expert Review Panel (ERP) and determined to meet the SMPRs for the six noted HMOs.

Highlights

The method was granted First Action Official MethodsSM status.
Conversion of water-soluble CBD to ∆9-THC in synthetic gastric fluid—An unlikely cause of positive drug tests
Authors: Hart E. Dale , Mullen Lawrance , Vikingsson Svante , Cone Edward J , Winecker Ruth E , Hayes Eugene D , Flegel Ronald R
Published: July 2023

Cannabidiol (CBD) has been shown to convert to ∆9-tetrahydrocannabinol (∆9-THC) in acidic environments, raising a concern of conversion when exposed to gastric fluid after consumption. Using synthetic gastric fluid (SGF), it has been demonstrated that the conversion requires surfactants, such as sodium dodecyl sulfate (SDS), due to limited solubility of CBD. Recently, water-compatible nanoemulsions of CBD have been prepared as a means of fortifying beverages and water-based foods with CBD. Since these emulsions contain surfactants as part of their formulation, it is possible that these preparations might enhance the production of ∆9-THC even in the absence of added surfactants. Three THC-free CBD products, an oil, an anhydrous powder and a water-soluble formulation, were incubated for 3 h in SGF without SDS. The water-soluble CBD product produced a dispersion, while the powder and the oil did not mix with the SGF. No THC was detected with the CBD oil (<0.0006% conversion), and up to 0.063% and 0.0045% conversion to ∆9-THC was observed with the water-soluble CBD and the CBD powder, respectively. No formation of ∆8-THC was observed. In comparison, when the nano-formulated CBD was incubated in SGF with 1% SDS, 33–36% conversion to ∆9-THC was observed. Even though the rate of conversion with the water-soluble CBD was at least 100-fold higher compared to the CBD oil, it was still smaller than ∆9-THC levels reported in CBD products labeled “THC-free” or “<0.3% THC” based on the Agricultural Improvement Act of 2018 (the Farm Bill). Assuming a daily CBD dose of around 30 mg/day, it is unlikely that conversion of CBD to ∆9-THC could produce a positive urinary drug test for 11-Nor-9-carboxy-∆9-THC (15 ng/mL cut-off).
Different responses of macro- and microelement contents of 41 subtropical plants to environmental changes in the wet and dry seasons
Authors: Yu Zheng-Chao , Zheng Xiao-Ting , He Wei , Lin Wei , Yan Guan-Zhao , Zhu Hui , Peng Chang-Lian
Published: July 2023

Differences in plant leaf elemental contents due to seasonal climate change reflect potential plant growth strategies. However, the distribution patterns of elements mediated by seasonal climate change remain unclear. This limits assessment of plant growth status and prediction of plant growth dynamics under global climate change. We collected 41 subtropical evergreen broadleaf plant leaves (31 tree species and 10 shrub species) during the wet and dry seasons, and determined foliar contents of macro- and microelements by inductively coupled plasma mass spectrometer. Our results showed that 41 plant leaves had significantly greater macroelement contents and significantly lower microelement contents in wet season than dry season. The highest macroelement content was in tree layer plants in wet season, followed by tree layer plants in dry season and shrub layer plants in wet season, the lowest was in shrub layer plants in dry season. The highest microelement content was in tree and shrub layer plants in dry season, followed by shrub layer plants in wet season, the lowest was in tree layer plants in wet season. Our results show that macro- and microelement contents of plant leaves with different vertical structures are affected by seasonal climate change. The transition from wet to dry season was detrimental to tree layer plants growth, but had less impact on shrub layer plants growth. These findings provide valuable evidence for predicting how different vertically structured subtropical evergreen broadleaf plants can adapt to changes in wet and dry season environments and to future global climate change.
Capturing the Border in Refugee Solidarity Camp Visits and City Tours in Germany: Theorizing Relationality through the Border as Horizon in Refugee/Migrant Solidarity Activism as Citizenship Politics
Authors: Rygiel Kim
Published: July 2023

This article explores the idea of the border as a connective space using the concepts of ‘border’s capture’, ‘borderizations’, and ‘border as horizon’ to highlight ‘practices of relationality’ where borders ‘run the risk of themselves being captured’. This article discusses refugee/migrant solidarity activism as citizenship politics through two examples from Germany across different snapshots in time, illustrating bordering through the camp and the dispersal of borders throughout the city. This article shows why ‘border’s capture’ is central to solidarity mobilizing as citizenship politics, exploring how borders, while integral to violent orderings, are also productive of relations across them in ways that transgress physical and ontological borders of status and belonging. This article argues for conceptualizing the border as horizon to highlight relationality and shows through the two examples why doing so matters politically in terms of how we relate to those identified as ‘outsiders’.
Infrared spectroscopy of nearby radio active early-type galaxies - II: spectral atlas
Authors: Durré Mark , Mould Jeremy , Brown Michael , Reynolds Tristan
Published: July 2023

We present a near-infrared spectroscopic atlas of nearby, bright early-type galaxies with radio emission, containing 163 galaxies observed by the Palomar 200″ TripleSpec instrument, measuring the emission line fluxes for H, He, [Fe ii], and H2 and determined the nuclear excitation mechanisms. By stacking spectra, we deduced the H2 excitation temperature (1957 ± 182 K) and dominant excitation mechanism (thermal and shock heating combined) from the K-band emission line sequence. Stacking also produces an ‘average’ spectrum of absorption features and spectral indices from the literature; the CO12 absorption line index versus J − K colour shows a trend of stronger nuclear activity producing a weaker CO12 index and a redder (flatter) continuum. The correlations between the radio and the emission-line luminosities finds a trend with radio power; however, the large scatter in the upper limits shows that the two are not directly coupled and the duty cycles of SF and AGN activity are not synchronized.
Acceleration of cosmic rays in presence of magnetohydrodynamic fluctuations at small scales
Authors: Kundu Sayan , Singh Nishant K , Vaidya Bhargav
Published: July 2023

This work investigates the evolution of the distribution of charged particles (cosmic rays) due to the mechanism of stochastic turbulent acceleration (STA) in presence of small-scale turbulence with a mean magnetic field. STA is usually modelled as a biased random walk process in the momentum space of the non-thermal particles. This results in an advection-diffusion type transport equation for the non-thermal particle distribution function. Under quasi-linear approximation, and by assuming turbulent spectra with power being available only in the sub-gyroscale range, we find that the Fokker–Planck diffusion coefficients Dγγ and Dμμ scale with the Lorentz factor γ as Dγγ ∝ γ−2/3 and Dμμ ∝ γ−8/3. We consider Alfvèn and fast waves in our calculations, and find a universal trend for the momentum diffusion coefficient irrespective of the properties of the small-scale turbulence. Such universality has already been reported regarding the spatial diffusion of the cosmic rays, and, here too, we observe a universality in the momentum diffusion coefficient. Furthermore, with the calculated transport coefficients, we numerically solve the advection-diffusion-type transport equation for the non-thermal particles. We demonstrate the interplay of various mircophysical processes such as STA, synchrotron loss, and particle escape on the particle distribution by systematically varying the parameters of the problem. We observe that the effect of the small-scale turbulence is more impactful for the high-energy protons as compared to the electrons and such turbulence is capable of sustaining the energy of the protons from catastrophic radiative loss processes. Such a finding is novel and helps us to enhance our understanding about the hadronic emission processes that are typically considered as a competitor for the leptonic emission for certain astrophysical systems.
Multiwavelength afterglow emission from bursts associated with magnetar flares and fast radio bursts
Authors: Wei Yujia , Zhang B Theodore , Murase Kohta
Published: July 2023

Magnetars have been considered as progenitors of magnetar giant flares (MGFs) and fast radio bursts (FRBs). We present detailed studies on afterglow emissions caused by bursts that occur in their wind nebulae and surrounding baryonic ejecta. In particular, following the bursts-in-bubble model, we analytically and numerically calculate spectra and light curves of such afterglow emission. We scan parameter space for the detectability of radio signals, and find that a burst with ∼1045 erg is detectable with the Very Large Array or other next-generation radio facilities. The detection of multiwavelength afterglow emission from MGFs and/or FRBs is of great significance for their localization and revealing their progenitors, and we estimate the number of detectable afterglow events.
Internal transcription termination widely regulates differential expression of operon-organized genes including ribosomal protein and RNA polymerase genes in an archaeon
Authors: Zhang Wenting , Ren Derong , Li Zhihua , Yue Lei , Whitman William B , Dong Xiuzhu , Li Jie
Published: July 2023

Genes organized within operons in prokaryotes benefit from coordinated expression. However, within many operons, genes are expressed at different levels, and the mechanisms for this remain obscure. By integrating PacBio-seq, dRNA-seq, Term-seq and Illumina-seq data of a representative archaeon Methanococcus maripaludis, internal transcription termination sites (ioTTSs) were identified within 38% of operons. Higher transcript and protein abundances were found for genes upstream than downstream of ioTTSs. For representative operons, these differences were confirmed by northern blotting, qRT-PCR and western blotting, demonstrating that these ioTTS terminations were functional. Of special interest, mutation of ioTTSs in ribosomal protein (RP)-RNA polymerase (RNAP) operons not only elevated expression of the downstream RNAP genes but also decreased production of the assembled RNAP complex, slowed whole cell transcription and translation, and inhibited growth. Overexpression of the RNAP subunits with a shuttle vector generated the similar physiological effects. Therefore, ioTTS termination is a general and physiologically significant regulatory mechanism of the operon gene expression. Because the RP-RNAP operons are found to be widely distributed in archaeal species, this regulatory mechanism could be commonly employed in archaea.
Science—an important lever to tackle sustainability in the specialty chemical industry
Authors: Zhou Wen-Juan , Metivier Pascal
Published: July 2023

Achieving carbon neutrality in the chemical industry necessitates a green and efficient transformation. Working together, industry and academia hold the key to developing clean chemical processes, which is crucial.
Phosphorylation of ADAPTOR PROTEIN-2 μ-adaptin by ADAPTOR-ASSOCIATED KINASE1 regulates the tropic growth of Arabidopsis roots
Authors: Siao Wei , Wang Peng , Zhao Xiuyang , Vu Lam Dai , De Smet Ive , Russinova Eugenia
Published: July 2023

ADAPTOR-ASSOCIATED PROTEIN KINASE1 (AAK1) is a known regulator of clathrin-mediated endocytosis in mammals. Human AAK1 phosphorylates the μ2 subunit of the ADAPTOR PROTEIN-2 (AP-2) complex (AP2M) and plays important roles in cell differentiation and development. Previous interactome studies discovered the association of AAK1 with AP-2 in Arabidopsis (Arabidopsis thaliana), but its function was unclear. Here, genetic analysis revealed that the Arabidopsis aak1 and ap2m mutants both displayed altered root tropic growth, including impaired touch- and gravity-sensing responses. In Arabidopsis, AAK1-phosphorylated AP2M on Thr-163, and expression of the phospho-null version of AP2M in the ap2m mutant led to an aak1-like phenotype, whereas the phospho-mimic forms of AP2M rescued the aak1 mutant. In addition, we found that the AAK1-dependent phosphorylation state of AP2M modulates the frequency distribution of endocytosis. Our data indicate that the phosphorylation of AP2M on Thr-163 by AAK1 fine-tunes endocytosis in the Arabidopsis root to control its tropic growth.
Comparison of red raspberry and wild strawberry fruits reveals mechanisms of fruit type specification
Authors: Zhou Junhui , Li Muzi , Li Yongping , Xiao Yuwei , Luo Xi , Gao Shenglan , Ma Zhimin , Sadowski Norah , Timp Winston , Dardick Chris , Callahan Ann , Mount Stephen M , Liu Zhongchi
Published: July 2023

Belonging to Rosaceae, red raspberry (Rubus idaeus) and wild strawberry (Fragaria vesca) are closely related species with distinct fruit types. While the numerous ovaries become the juicy drupelet fruits in raspberry, their strawberry counterparts become dry and tasteless achenes. In contrast, while the strawberry receptacle, the stem tip, enlarges to become a red fruit, the raspberry receptacle shrinks and dries. The distinct fruit-forming ability of homologous organs in these 2 species allows us to investigate fruit type determination. We assembled and annotated the genome of red raspberry (R. idaeus) and characterized its fruit development morphologically and physiologically. Subsequently, transcriptomes of dissected and staged raspberry fruit tissues were compared to those of strawberry from a prior study. Class B MADS box gene expression was negatively associated with fruit-forming ability, which suggested a conserved inhibitory role of class B heterodimers, PISTILLATA/TM6 or PISTILLATA/APETALA3, for fruit formation. Additionally, the inability of strawberry ovaries to develop into fruit flesh was associated with highly expressed lignification genes and extensive lignification of the ovary pericarp. Finally, coexpressed gene clusters preferentially expressed in the dry strawberry achenes were enriched in “cell wall biosynthesis” and “ABA signaling,” while coexpressed clusters preferentially expressed in the fleshy raspberry drupelets were enriched in “protein translation.” Our work provides extensive genomic resources as well as several potential mechanisms underlying fruit type specification. These findings provide the framework for understanding the evolution of different fruit types, a defining feature of angiosperms.
Empowerment and capacity of external police oversight: The paradox of the Control Yuan in Taiwan
Authors: Ho Lawrence Ka-ki , Li Angus Siu-cheong , Chan Jason Kwun-hong
Published: July 2023

Prevailing scholarly literature generally suggested the significance of an externally empowered oversight agency to ensure the public accountability of the police. As an electoral democratic regime, Taiwan’s model of police oversight is characterized by the parallel existence of both internal and external investigative bodies. The Control Yuan is a constitutionally empowered ‘super ombudsman’ to monitor the integrity management of civil servants including the police. This thematic research studies the reflection of ‘insiders’—the Control Yuan members who have taken part in police misconduct hearings, on this mechanism that is uncommon in western democracies. Paradoxically, the respondents generally questioned the effectiveness of this powerful establishment with both abundant human resources and legal authorization. The technical competence among investigators and party politics in agenda setting are also perceived as structural limitations of the current mechanism.
The Democratic Mission of Higher Education: A Review Essay
Authors: Levine Peter
Published: July 2023

Controversies about speech on college campuses attract intense popular attention. Three recent books analyze campus speech as one of the ways that academia affects American democracy. In The Channels of Student Activism, Amy J. Binder and Jeffrey L. Kidder argue that college-student activists respond to incentives. Progressive students have opportunities to engage closely with their universities but often end up frustrated, while conservative students get support from national organizations to work off-campus and endorse conservative visiting speakers as a way of influencing their own institutions. Among other recommendations, Binder and Kidder suggest that universities should promote democratic values by adopting more persuasive positions about controversial speech. In Cancel Wars, Sigal-Ben Porath defends one such position: universities should avoid censorship and punitive responses to speech while actively ensuring that all members of their community are valued. In What Universities Owe Democracy, Johns Hopkins University President Ronald J. Daniels argues that higher education affects democracy in many ways beyond explicit political speech, and he presents recommendations that involve admissions, curricular reform, and research. Levine finds many helpful insights and suggestions in these books but adds reasons to doubt the democratic potential of prestigious colleges and universities. He advocates serious public investment in democratic education for children and for adults who are not students.
Influences of Financial and Workplace Factors on Physical Therapist Job Satisfaction
Authors: Mulligan Edward P , Hegedus Eric J , Foucrier Jeffrey , Dickson Tara
Published: July 2023

Objective

The physical therapist labor market has recently noted higher rates of turnover and job vacancies. An understudied factor contributing to these trends in the profession is job satisfaction. The profession continues to experience relatively low wages compared with other health professions, and graduates of Doctor of Physical Therapy programs face increasingly high student debt. This study used the labor-search model as a conceptual framework to understand associations between job satisfaction, income, and educational debt. The purpose of this study is to observe the financial and workplace factors that are associated with higher levels of physical therapist job satisfaction.

Methods

Data from 4764 physical therapists in 1 state were captured retrospectively through the state’s licensure renewal process from 2014 to 2020. A random effects panel analysis, with job satisfaction as the dependent variable, was used to evaluate the relationships between job satisfaction and income, educational debt, and a variety of work-related factors.

Results

Job satisfaction was negatively correlated with educational debt, number of hours worked per week, and some practice settings. Conversely, job satisfaction was positively correlated with the expected age of retirement. The percentage of time spent in research and administration was also positively correlated with job satisfaction, though additional research in this area is needed to draw meaningful conclusions on this association.

Conclusion

The results support the conceptual framework, which suggests that early career physical therapists, motivated by high amounts of educational debt, may choose more financially advantageous practice settings and increased working hours to the detriment of job satisfaction.

Impact

High levels of job satisfaction among physical therapists are correlated with low levels of educational debt, working 45 hours or less per week, a longer time horizon until retirement, and practice settings other than home health and skilled nursing facilities.
Lunar far-side radio arrays: a preliminary site survey
Authors: Le Conte Zoe A , Elvis Martin , Gläser Philipp A
Published: July 2023

The origin and evolution of structure in the Universe could be studied in the Dark Ages. The highly redshifted H i signal between 30 < z < 80 is the only observable signal from this era. Human radio interference and ionospheric effects limit Earth-based radio astronomy to frequencies >30 MHz. To observe the low-frequency window with research from compact steep spectrum sources, pulsars, and solar activity, a 200 km baseline lunar far-side radio interferometer has been much discussed. This paper conducts a preliminary site survey of potential far-side craters, which are few in number on the mountainous lunar far-side. Based on LRO LOLA data, 200 m resolution topographic maps of eight far-side sites were produced, and slope and roughness maps were derived from them. A figure of merit was created to determine the optimum site. Three sites are identified as promising. There is a need to protect these sites for astronomy.
The Nature of the Familial Risk for Psychosis in Bipolar Disorder
Authors: Kendler Kenneth S , Abrahamsson Linda , Sundquist Jan , Sundquist Kristina
Published: July 2023

Background and Hypothesis

To clarify whether the familial liability to psychosis associated with bipolar disorder (BD) is nonspecific or has a greater effect on risk for psychosis in cases with prominent mood symptoms and/or a remitting course.

Study Design

We examined, in 984 809 offspring raised in intact families in Sweden, born 1980–1996 and followed-up through 2018, by multivariable Cox proportional hazards regression, risk in offspring of parents with BD for 7 psychotic disorders: Psychotic MD (PMD), psychotic BD (PBD), schizoaffective disorder (SAD), acute psychoses, psychosis NOS, delusional disorder (DD) and schizophrenia (SZ). Diagnoses were obtained from national registers.

Study Results

In the offspring of BD parents, the hazard ratios (HR) for these 7 disorders formed an inverted U-shaped curve, rising from 2.98 for PMD, to peak at 4.49 for PBD and 5.25 for SAD, and then declining to a HR of 3.48 for acute psychoses and 3.22 for psychosis NOS, to a low of 2.19 for DD and 2.33 for SZ. A similar pattern of risks was seen in offspring of mothers and fathers affected with BD and in offspring predicted from age at onset in their BD parent.

Conclusions

The BD-associated risk for psychosis impacts most strongly on mood disorders, moderately on episodic psychotic syndromes, and least on chronic psychotic disorders. These results support prior clinical studies suggesting a qualitative difference in the familial substrate for psychosis occurring in BD and SZ.
Long-term efficacy and safety of tonic motor activation for treatment of medication-refractory restless legs syndrome: A 24-Week Open-Label Extension Study
Authors: Roy Asim , Ojile Joseph , Kram Jerrold , Olin Jonathan , Rosenberg Russell , Hudson J Douglas , Bogan Richard K , Charlesworth Jonathan D
Published: July 2023

Study Objectives

To evaluate long-term efficacy and safety of tonic motor activation (TOMAC) for treatment of medication-refractory moderate-to-severe primary restless legs syndrome (RLS).

Methods

In the parent study (RESTFUL), adults with refractory RLS were randomized to active TOMAC or sham for 4 weeks followed by 4 weeks of open-label active TOMAC. In the extension study, earlier RESTFUL completers comprised the control group (n = 59), which was followed for 24 weeks with no TOMAC intervention, and later RESTFUL completers compromised the treatment group (n = 44), which received 24 additional weeks of open-label active TOMAC followed by no intervention for 8 weeks. The primary endpoint was Clinician Global Impressions-Improvement (CGI-I) responder rate at week 24 compared to RESTFUL entry.

Results

CGI-I responder rate improved from 63.6% (95% CI, 49.4 to 77.9%) at RESTFUL completion to 72.7% (95% CI, 58.2 to 83.7%) at week 24 for the treatment group versus 13.6% (95% CI, 7.0 to 24.5%) at week 24 for the control group (p < 0.0001). Mean change in International RLS Rating Scale (IRLS) score improved from −7.4 (95% CI, −5.6 to −9.2) at RESTFUL completion to -11.3 points (95% CI, −8.8 to −13.9) at week 24 for the treatment group versus −5.4 (95% CI, −3.7 to −7.2) at week 24 for control group (p = 0.0001). All efficacy endpoints partially reverted during cessation of treatment. There were no grade 2 or higher device-related adverse events.

Conclusions

TOMAC remained safe and efficacious for >24 total weeks of treatment with partial reversion of benefits upon cessation.

Clinical Trial

Extension Study Evaluating NTX100 Neuromodulation System for Medication-Refractory Primary RLS; clinicaltrials.gov/ct2/show/NCT05196828; Registered at ClinicalTrials.gov with the identifier number NCT05196828.
IEnglish Language
Authors: Kostadinova Viktorija , Wiemann Marco , Dreschler Gea , Bouso Tamara , Gyuris Beáta , Zhong Ai , Scott Maggie , Anderwald Lieselotte , Ahlers Wiebke , Vida-Mannl Manuela , Al-Thubaiti Kholoud A , Ting Shawnea Sum Pok , Parise Ida , Cogo Alessia , Reber Elisabeth
Published: July 2023

This chapter has thirteen sections: 1. General; 2. History of English Linguistics; 3. Phonetics and Phonology; 4. Morphology; 5. Syntax; 6. Semantics; 7. Lexicography, Lexicology, and Lexical Semantics; 8. Onomastics; 9. Dialectology and Sociolinguistics; 10. New Englishes and Creolistics; 11. Second Language Acquisition; 12. English as a Lingua Franca; 13. Pragmatics and Discourse Analysis. Sections 1 and 2 are by Viktorija Kostadinova; section 3 is by Marco Wiemann; sections 4 and 5 are by Gea Dreschler and Tamara Bouso; section 6 is by Beáta Gyuris; section 7 is by Ai Zhong; section 8 is by Maggie Scott; section 9 is by Lieselotte Anderwald; section 10 is by Wiebke Ahlers and Manuela Vida-Mannl; section 11 is by Kholoud A. Al-Thubaiti; section 12 is by Shawnea Sum Pok Ting, Ida Parise, and Alessia Cogo; section 13 is by Elisabeth Reber.
Aberrant activation of estrogen receptor‐α signaling in Mettl14‐deficient uteri impairs embryo implantation
Authors: Kobayashi Ryosuke , Kawabata‐Iwakawa Reika , Terakawa Jumpei , Sugiyama Makoto , Morita Sumiyo , Horii Takuro , Hatada Izuho
Published: July 2023

The precise control of endometrial receptivity is crucial for successful embryo implantation, which is strictly regulated by the ovarian steroid hormones estrogen and progesterone. Despite our improved understanding of the genetic regulation of implantation downstream of the action of hormones, we do not know much about the epigenetic regulation that occurs during early pregnancy. To investigate the role of the N6‐methyladenosine (m6A) RNA modification in embryo implantation, we generated mice with conditional deletion of Mettl14, a core component of the m6A writer complex, in the uterus. These mice were infertile due to implantation failure. We showed that Mettl14‐deficient uteri had aberrant upregulation of estrogen receptor α (ERα) signaling and ERα phosphorylation, but progesterone receptor (PGR) signaling was largely unaffected. Additionally, Mettl14 deletion led to abnormal activation of the innate immune pathway in Mettl14‐deficient uteri. This effect was accompanied by the infiltration of immune cells, such as macrophages and dendritic cells, into the basal region of the endometrial epithelium. Methylated RNA immunoprecipitation sequencing (MeRIP‐seq) showed that genes involved in the innate immune response had decreased m6A peaks in Mettl14‐deficient mice. These results suggest that Mettl14 plays a crucial role in successful implantation by precisely regulating both ERα signaling and innate immunity in the uterus.
Cost-utility Analysis of Evoke closed-loop Spinal Cord Stimulation for Chronic Back and Leg Pain
Authors: Duarte Rui V. , Bentley Anthony , Soliday Nicole , Leitner Angela , Gulve Ashish , Staats Peter S. , Sayed Dawood , Falowski Steven M. , Hunter Corey W. , Taylor Rod S.
Published: July 2023

Objectives:

The effectiveness of Evoke closed-loop spinal cord stimulation (CL-SCS), a novel modality of neurostimulation, has been demonstrated in a randomised controlled trial (RCT). The objective of this cost-utility analysis was to develop a de novo economic model to estimate the cost-effectiveness Evoke CL-SCS when compared to open-loop SCS (OL-SCS) for the management of chronic back and leg pain.

Methods:

A decision tree followed by a Markov model were used to estimate costs and outcomes of Evoke CL-SCS versus OL-SCS over a 15-year time horizon from the UK National Health Service perspective. A ‘high-responder’ health state was included to reflect improved levels of SCS pain reduction recently reported. Results are expressed as incremental cost per quality adjusted life year (QALY). Deterministic and probabilistic sensitivity analysis (PSA) were conducted to assess uncertainty in the model inputs.

Results:

Evoke CL-SCS was estimated to be the dominant treatment strategy at approximately 5 years post-implant (i.e., generates more QALYs while cost-saving compared to OL-SCS). PSA showed that Evoke CL-SCS has a 92% likelihood of being cost-effective at a willingness to pay threshold of £20,000/QALY. Results were robust across a wide range of scenario and sensitivity analyses.

Discussion:

The results indicate a strong economic case for the use of Evoke CL-SCS in the management of chronic back and leg pain with or without prior spinal surgery with dominance observed at approximately 5 years.
Risk Factors for the Development of Multisite Pain in Children
Authors: Kaplan Chelsea M. , Schrepf Andrew , Boehnke Kevin F. , He Ying , Smith Tristin , Williams David A. , Bergmans Rachel , Voepel-Lewis Terri , Hassett Afton L. , Harris Richard E. , Clauw Daniel J. , Beltz Adriene M. , Harte Steven E.
Published: July 2023

Objective:

Chronic pain has economic costs on par with cardiovascular disease, diabetes, and cancer. Despite this impact on the health care system and an increasing awareness of the relationship between pain and mortality, efforts to identify simple symptom-based risk factors for the development of pain, particularly in children, have fallen short. This is critically important as pain that manifests during childhood often persists into adulthood. To date no longitudinal studies have examined symptoms in pain-free children that presage a new, multisite manifestation of pain in the future. We hypothesized that female sex, sleep problems and heightened somatic complaints at baseline would be associated with the risk of developing new multisite pain one year later.

Methods:

Symptom assessments were completed by parents of youth (ages 9-10) enrolled in the Adolescent Brain Cognitive Development study. Multivariate logistic regression models focused on children who developed multisite pain one year later (n=331) and children who remained pain-free (n=3335) .

Results:

Female sex (OR=1.35; 95% CI=1.07, 1.71; P=0.01) , elevated non-painful somatic complaints (OR=1.17; 95% CI=1.06, 1.29; P<0.01) , total sleep problems (OR=1.20; 95% CI=1.07, 1.34; P< 0.01) , and attentional issues (OR=1.22; 95% CI=1.10, 1.35; P<0.001) at baseline were associated with new multisite pain one year later. Baseline negative affect was not associated with new multisite pain.

Discussion:

Identifying symptom-based risk factors for multisite pain in children is critical for early prevention. Somatic awareness, sleep and attention problems represent actionable targets for early detection, treatment, and possible prevention of multisite pain in youth.
Socioeconomic Characteristics Associated With Development of Chronic Pain After Pain Interference Experienced in Early Adulthood
Authors: Peace Jordan , Pooleri Anand , Frech Adrianne , Tumin Dmitry
Published: July 2023

Objective:

Predictors of pain persistence have been identified among patients undergoing treatment for chronic pain or related conditions, but correlates of pain persistence in the general population remain underexplored. We identify socioeconomic variables associated with pain onset or persistence over a 6-10 year period in a nationally representative cohort.

Methods:

Using panel data from the National Longitudinal Survey of Youth-1997, we examined the presence of pain interference at age 29 and chronic pain at ages 35-39. Persistent pain was defined as pain present at both interview timepoints; new onset pain was defined as pain not reported at age 29, but present at ages 35-39; and transient pain was defined as experiencing pain interference at age 29 with no report of chronic pain at ages 35-39.

Results:

Based on a sample of 6,188 participants, we estimated that 4% experienced persistent pain, 11% experienced transient pain, and 7% experienced new-onset pain. Pain persistence was less likely among non-Hispanic Black respondents but more likely among formerly married respondents and those with poor health, health-related work limitation, or greater pain interference at the age 29 baseline. New onset pain was most likely among female respondents, respondents with some college education, and respondents with poor self-rated health or obesity at baseline.

Discussion:

Development of chronic pain by mid-late 30s was common among young adults experiencing pain interference at age 29. Race/ethnicity, gender, and educational attainment exhibited different associations with persistence as compared to new onset of pain problems.
No Evidence of Short-Term Changes in Muscle Activity Elicited by Dry Needling in Chronic Unilateral Shoulder Pain Patients
Authors: Intelangelo Leonardo , Mendoza Cristian , Lassaga Ignacio , Barbosa Alexandre Carvalho , Manresa José Biurrun , Mista Christian
Published: July 2023

Objectives:

The aim of the study was to assess short-term changes in shoulder muscle activity elicited by dry needling in chronic unilateral shoulder pain patients.

Methods:

A double-blind, placebo-controlled clinical trial was conducted, in which 30 volunteers with unilateral shoulder pain (USP) were recruited and randomly assigned to either real or sham dry needling conditions. Pain intensity scores, pressure pain threshold (PPT), glenohumeral internal rotation angles, and electromyographic activity during isotonic shoulder tasks (shoulder flexion and extension) were assessed before, immediately and 72 h after the intervention in the infraspinatus and deltoid muscles.

Results:

A single application of real dry needling resulted in lower pain intensity scores and a larger range in glenohumeral internal rotation 72 h after the intervention in comparison with sham dry needling. No differences in PPT or muscle activity were observed due to the intervention.

Discussion:

A single application of real dry needling resulted in clinically significant changes in the short-term. No differences were detected in muscle activation in the infraspinatus or deltoid muscles. Complementary interventions and longer follow-up times may be required to observe changes in muscle activity.
Individualized Positive End-expiratory Pressure on Postoperative Atelectasis in Patients with Obesity: A Randomized Controlled Clinical Trial
Authors: Li Xiang , Liu He , Wang Jun , Ni Zhi-Lin , Liu Zhong-Xiao , Jiao Jia-Li , Han Yuan , Cao Jun-Li
Published: July 2023

Background

Individualized positive end-expiratory pressure (PEEP) guided by dynamic compliance improves oxygenation and reduces postoperative atelectasis in nonobese patients. The authors hypothesized that dynamic compliance–guided PEEP could also reduce postoperative atelectasis in patients undergoing bariatric surgery.

Methods

Patients scheduled to undergo laparoscopic bariatric surgery were eligible. Dynamic compliance–guided PEEP titration was conducted in all patients using a downward approach. A recruitment maneuver (PEEP from 10 to 25 cm H2O at 5–cm H2O step every 30 s, with 15–cm H2O driving pressure) was conducted both before and after the titration. Patients were then randomized (1:1) to undergo surgery under dynamic compliance–guided PEEP (PEEP with highest dynamic compliance plus 2 cm H2O) or PEEP of 8 cm H2O. The primary outcome was postoperative atelectasis, as assessed with computed tomography at 60 to 90 min after extubation, and expressed as percentage to total lung tissue volume. Secondary outcomes included Pao
2/inspiratory oxygen fraction (Fio
2) and postoperative pulmonary complications.

Results

Forty patients (mean ± SD; 28 ± 7 yr of age; 25 females; average body mass index, 41.0 ± 4.7 kg/m2) were enrolled. Median PEEP with highest dynamic compliance during titration was 15 cm H2O (interquartile range, 13 to 17; range, 8 to 19) in the entire sample of 40 patients. The primary outcome of postoperative atelectasis (available in 19 patients in each group) was 13.1 ± 5.3% and 9.5 ± 4.3% in the PEEP of 8 cm H2O and dynamic compliance–guided PEEP groups, respectively (intergroup difference, 3.7%; 95% CI, 0.5 to 6.8%; P = 0.025). Pao
2/Fio
2 at 1 h after pneumoperitoneum was higher in the dynamic compliance–guided PEEP group (397 vs. 337 mmHg; group difference, 60; 95% CI, 9 to 111; P = 0.017) but did not differ between the two groups 30 min after extubation (359 vs. 375 mmHg; group difference, –17; 95% CI, –53 to 21; P = 0.183). The incidence of postoperative pulmonary complications was 4 of 20 in both groups.

Conclusions

Postoperative atelectasis was lower in patients undergoing laparoscopic bariatric surgery under dynamic compliance–guided PEEP versus PEEP of 8 cm H2O. Postoperative Pao
2/Fio
2 did not differ between the two groups.

Editor’s Perspective

What We Already Know about This Topic

What This Article Tells Us That Is New
Barriers to a Timely Diagnosis of Endometriosis
Authors: Davenport Sophie , Smith Diane , Green Dan J.
Published: July 2023

OBJECTIVE:

The diagnosis of endometriosis, a common gynecologic condition, is characterized by delays of up to 11 years. During this time, women may experience persistent symptoms that affect their quality of life, productivity, and relationships, and the disease may progress. It is therefore a priority to understand the factors that contribute to this delay to help improve the diagnostic pathway. Our objective was to describe the diagnosis barriers of endometriosis from the patient and health care professional perspectives using a qualitative evidence synthesis.

DATA SOURCES:

We searched MEDLINE, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature using combinations of the synonyms of endometriosis, diagnosis, and qualitative research. The search was restricted to English-language articles from database creation until May 2022.

METHODS OF STUDY SELECTION:

The initial search yielded 899 articles. Studies were included if they explored the experiences or views of affected women or health care professionals on the diagnosis of endometriosis and used qualitative methods for data collection and data analysis. Risk of bias was assessed with the Critical Appraisal Skills Programme checklist.

TABULATION, INTEGRATION, AND RESULTS:

Thirty-seven articles were considered for full review, with 13 eligible articles identified for inclusion. Thematic synthesis was used to identify four key themes: 1) individual factors (n=6), 2) interpersonal influences (n=6), 3) health system factors (n=13), and 4) factors specific to endometriosis (n=13). These encompassed 12 subthemes that represented barriers to the diagnosis of endometriosis: 1) difficulty establishing pathologic symptoms from normal menstruation and the use of self-care techniques; 2) menstrual stigma and the normalization of menstrual pain; 3) attitudes and lack of training for health care professionals, delayed referrals to specialist services, and poor explanation of oral contraceptive pill use in the diagnostic process; and 4) variability in presenting symptoms, overlap with other conditions, lack of a noninvasive method of diagnosis, and concerns about the value of a diagnosis.

CONCLUSION:

This review identified barriers to the timely diagnosis of endometriosis from the perspective of affected individuals and health care professionals. It highlights areas for improvement along the diagnostic pathway, which may guide future strategies to reduce delays.
Reassessing Preterm Birth Prevention After the Withdrawal of 17-α Hydroxyprogesterone Caproate
Authors: Heyborne Kent
Published: July 2023

The U.S. Food and Drug Administration has recently withdrawn approval for 17-α hydroxyprogesterone caproate for prevention of recurrent preterm birth, and recent studies have called into question benefits of the pessary in the setting of a short cervix. Obstetric health care professionals are once again left with limited remaining options for preterm birth prevention. This narrative review summarizes the best current evidence on the use of vaginal progesterone, low-dose aspirin, and cerclage for the prevention of preterm birth; attempts to distill possible lessons learned from studies of progesterone and pessary, as well as their implementation into practice; and highlights areas where inroads into preterm birth prevention may be possible outside of the progesterone–aspirin–cerclage paradigm.
Development and Validation of an ICU Delirium Playbook for Provider Education
Authors: Makhija Hirsh , Fine Janelle M. , Pollack Daniel , Novelli Francesca , Davidson Judy E. , Cotton Shannon A. , Diaz De Leon Bianca , Reyes Paola Alicea , Montoya Jessica L. , Arroyo-Novoa Carmen Mabel , Figueroa-Ramos Milagros I. , Song Yeonsu , Fuentes Ana Lucia , LaBuzetta Jamie Nicole , Moore Alison A. , Ely E. Wesley , Malhotra Atul , Needham Dale M. , Martin Jennifer L. , Kamdar Biren B.
Published: July 2023

OBJECTIVES:

Although delirium detection and prevention practices are recommended in critical care guidelines, there remains a persistent lack of effective delirium education for ICU providers. To address this knowledge-practice gap, we developed an “ICU Delirium Playbook” to educate providers on delirium detection (using the Confusion Assessment Method for the ICU) and prevention.

DESIGN:

Building on our previous ICU Delirium Video Series, our interdisciplinary team developed a corresponding quiz to form a digital “ICU Delirium Playbook.” Playbook content validity was evaluated by delirium experts, and face validity by an ICU nurse focus group. Additionally, focus group participants completed the quiz before and after video viewing. Remaining focus group concerns were evaluated in semi-structured follow-up interviews.

SETTING:

Online validation survey, virtual focus group, and virtual interviews.

SUBJECTS:

The validation group included six delirium experts in the fields of critical care, geriatrics, nursing, and ICU education. The face validation group included nine ICU nurses, three of whom participated in the semi-structured feedback interviews.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

The 44-question quiz had excellent content validity (average scale-level content validity index [S-CVI] of individual items = 0.99, universal agreement S-CVI = 0.93, agreement κ ≥ 0.75, and clarity p ≥ 0.8). The focus group participants completed the Playbook in an average (sd) time of 53 (14) minutes, demonstrating significant improvements in pre-post quiz scores (74% vs 86%; p = 0.0009). Verbal feedback highlighted the conciseness, utility, and relevance of the Playbook, with all participants agreeing to deploy the digital education module in their ICUs.

CONCLUSIONS:

The ICU Delirium Playbook is a novel, first-of-its-kind asynchronous digital education tool aimed to standardize delirium detection and prevention practices. After a rigorous content and face validation process, the Playbook is now available for widespread use.