bluuebunny/crossref_metadata_2025 huggingface dataset:
Koselleck and conceptual history
Authors: Whatmore Richard
Published: November 2021

‘Koselleck and conceptual history’ reviews how the study of the history of political thought ended up as the site of the Third Reich and the Holocaust. The question to ask is what had gone wrong with the German traditions of philology and lexicography that is associated with studies of the classical past? Systematic knowledge can be defined through foundational concepts. The disaster of modern history and the failure of historical sensibility in Germany can be used as new techniques to investigate how the past explained the sense of national and cultural failure. The project of ‘conceptual history’ was formulated in the 1950s by Otto Brunner, Werner Conze, and Reinhart Koselleck.
Michel Foucault and governmentality
Authors: Whatmore Richard
Published: November 2021

‘Michel Foucault and governmentality’ talks about Michel Foucault, who is often associated with the poststructuralist and postmodernist ideas of Jacques Derrida, Gilles Deleuze, and Jean-François Lyotard. Lyotard’s famous La condition postmoderne in 1979 gave common currency to the term postmodern. Texts that contributed to mental climates in diverse ways are being adapted to the passage of time and alteration of circumstance. Derrida’s 'arche-writing' is an innovative approach to the study of texts. Derrida claimed that the author’s intentions are constrained by language and logic that relied upon the expression of ideas, as the text could go beyond the limits imagined by the author.
Globality, morality, and the future
Authors: Whatmore Richard
Published: November 2021

‘Globality, morality, and the future’ recounts the 1960s research in the history of political thought, which was inspired by the writings of Leo Strauss, Michel Foucault, Reinhart Koselleck, and the Cambridge School authors. The reconstruction of the meaning of texts can be seen through the scholars’ ideological contexts and perspectives. Despite the rejection of Marxist categories for interrogating history and proletarian revolution, the world created by capitalism continues to be attacked for its endemic war and fanatical politics. Aspects of the history of political thought trained scholars to see the problems of contemporary society. The history of political thought allowed political actions to be charted and evaluated for success.
Minimum Alcohol Pricing and Motor Vehicle Collisions in Scotland
Authors: Vandoros Sotiris , Kawachi Ichiro
Published: November 2021

On May 1, 2018, Scotland introduced a minimum price of 50 pence per unit of alcohol, which led to a reduction in alcohol consumption. As drink-driving is an important risk factor for motor vehicle collisions, we examined whether the minimum alcohol pricing was followed by a decrease in collisions. We took advantage of a case where the minimum price was introduced to 1 population during the study period (Scotland) and another population that served as the control group did not experience this intervention (England and Wales). We used data on the daily number of motor vehicle collisions resulting in death or injury in 2018 and used a differences-in-differences econometric approach, comparing trends before and after the introduction of the minimum price. Controlling for seasonality, we found a small relative decrease in collisions in Scotland compared with England and Wales (difference-in-difference interaction coefficient, −0.35; 95% confidence interval: −0.65, −0.04; P = 0.03). Our results suggest that there was a relative decrease in motor vehicle collisions in Scotland of between 1.52 and 1.90, on average, in the first months after the introduction of the policy. More research is needed to understand any long-term impacts of minimum alcohol pricing.
CellVGAE: an unsupervised scRNA-seq analysis workflow with graph attention networks
Authors: Buterez David , Bica Ioana , Tariq Ifrah , Andrés-Terré Helena , Liò Pietro
Published: November 2021

Motivation

Single-cell RNA sequencing allows high-resolution views of individual cells for libraries of up to millions of samples, thus motivating the use of deep learning for analysis. In this study, we introduce the use of graph neural networks for the unsupervised exploration of scRNA-seq data by developing a variational graph autoencoder architecture with graph attention layers that operates directly on the connectivity between cells, focusing on dimensionality reduction and clustering. With the help of several case studies, we show that our model, named CellVGAE, can be effectively used for exploratory analysis even on challenging datasets, by extracting meaningful features from the data and providing the means to visualize and interpret different aspects of the model.

Results

We show that CellVGAE is more interpretable than existing scRNA-seq variational architectures by analysing the graph attention coefficients. By drawing parallels with other scRNA-seq studies on interpretability, we assess the validity of the relationships modelled by attention, and furthermore, we show that CellVGAE can intrinsically capture information such as pseudotime and NF-ĸB activation dynamics, the latter being a property that is not generally shared by existing neural alternatives. We then evaluate the dimensionality reduction and clustering performance on 9 difficult and well-annotated datasets by comparing with three leading neural and non-neural techniques, concluding that CellVGAE outperforms competing methods. Finally, we report a decrease in training times of up to × 20 on a dataset of 1.3 million cells compared to existing deep learning architectures.

Availabilityand implementation

The CellVGAE code is available at https://github.com/davidbuterez/CellVGAE.

Supplementary information

Supplementary data are available at Bioinformatics online.
Comparing outcomes of robotic versus open mesorectal excision for rectal cancer
Authors: Jimenez-Rodriguez Rosa M , Flynn Jessica , Patil Sujata , Widmar Maria , Quezada-Diaz Felipe , Lynn Patricio , Strombom Paul , Temple Larissa , Smith J. Joshua , Wei Iris H , Pappou Emmanouil P , Guillem Jose G , Paty Philip B. , Nash Garrett M , Weiser Martin R , Garcia-Aguilar Julio
Published: November 2021

Background

The outcomes of robot-assisted mesorectal excision for rectal cancer, compared with open resection, have not been fully characterized.

Methods

A retrospective analysis of pathologic, short-term, and long-term outcomes in patients with rectal adenocarcinoma who underwent total or tumour-specific mesorectal excision at a high-volume cancer centre between 2008 and 2017 was conducted. Outcomes after robotic and open surgery were compared on an intention-to-treat basis.

Results

Out of 1048 resections performed, 1018 patients were reviewed, with 638 who underwent robotic surgery and 380 open surgery. Robotic surgery was converted to the open approach in 17 (2.7 per cent) patients. Patients who underwent robotic surgery were younger (median 54 (range 22–91) years versus median 58 (range 18–97) years; P < 0.001), had higher tumours (median 80 (range 0–150) mm from the anal verge versus median 70 (0–150) mm; P = 0.001), and were less likely to have received neoadjuvant therapy (64 per cent versus 73 per cent; P = 0.003). For patients who underwent a robotic total mesorectal excision, the operating time was longer (median 283.5 (range 117–712) min versus median 249 (range 70–661) min; P < 0.001). However, the rate of complications was lower (29 per cent versus 45 per cent; P < 0.001) and length of hospital stay was shorter (median 5 (range 1–32) days versus median 7 (range 0–137) days; P < 0.001). Median follow-up of survivors was 2.9 years. The proportion of patients with a positive circumferential resection margin did not differ between the groups, nor did the rate of local recurrence (robotic versus open: 3.7 per cent, 95 per cent c.i. 1.9 to 5.6 versus 2.8 per cent, 95 per cent c.i. 1.0 to 4.6; P = 0.400), systemic recurrence (robotic versus open: 11.7 per cent, 95 per cent c.i. 8.5 to 14.8 versus 13.0 per cent, 95 per cent c.i. 9.2 to 16.5; P = 0.300), or overall survival (robotic versus open: 97.8 per cent, 95 per cent c.i. 96.3 to 99.3 versus 93.5 per cent, 95 per cent c.i. 90.8 to 96.2; P = 0.050). The same results were documented in a subanalysis of 370 matched patients, including 185 who underwent robotic surgery and 185 open surgery, for the overall incidence of any postoperative complications, overall survival, disease-free survival, local recurrence, and systemic recurrence.

Conclusion

In patients with rectal cancer who are candidates for curative resection, robotic mesorectal excision is associated with lower complication rates, shorter length of stay, and equivalent oncologic outcomes, compared with open mesorectal excision.
Optimal Urine Culture Diagnostic Stewardship Practice—Results from an Expert Modified-Delphi Procedure
Authors: Claeys Kimberly C , Trautner Barbara W , Leekha Surbhi , Coffey K C , Crnich Christopher J , Diekema Dan J , Fakih Mohamad G , Goetz Matthew Bidwell , Gupta Kalpana , Jones Makoto M , Leykum Luci , Liang Stephen Y , Pineles Lisa , Pleiss Ashley , Spivak Emily S , Suda Katie J , Taylor Jennifer M , Rhee Chanu , Morgan Daniel J
Published: November 2021

Background

Urine cultures are nonspecific and often lead to misdiagnosis of urinary tract infection and unnecessary antibiotics. Diagnostic stewardship is a set of procedures that modifies test ordering, processing, and reporting in order to optimize diagnosis and downstream treatment. In this study, we aimed to develop expert guidance on best practices for urine culture diagnostic stewardship.

Methods

A RAND-modified Delphi approach with a multidisciplinary expert panel was used to ascertain diagnostic stewardship best practices. Clinical questions to guide recommendations were grouped into three thematic areas (ordering, processing, reporting) in practice settings of emergency department, inpatient, ambulatory, and long-term care. Fifteen experts ranked recommendations on a 9-point Likert scale. Recommendations on which the panel did not reach agreement were discussed during a virtual meeting, then a second round of ranking by email was completed. After secondary review of results and panel discussion, a series of guidance statements was developed.

Results

One hundred and sixty-five questions were reviewed. The panel reaching agreement on 104, leading to 18 overarching guidance statements. The following strategies were recommended to optimize ordering urine cultures: requiring documentation of symptoms, sending alerts to discourage ordering in the absence of symptoms, and cancelling repeat cultures. For urine culture processing, conditional urine cultures and urine white blood cell count as criteria were supported. For urine culture reporting, appropriate practices included nudges to discourage treatment under specific conditions and selective reporting of antibiotics to guide therapy decisions.

Conclusions

These 18 guidance statements can optimize use of urine cultures for better patient outcomes.
Lessons learnt when accounting for competing events in the external validation of time-to-event prognostic models
Authors: Ramspek Chava L , Teece Lucy , Snell Kym I E , Evans Marie , Riley Richard D , van Smeden Maarten , van Geloven Nan , van Diepen Merel
Published: November 2021

Background

External validation of prognostic models is necessary to assess the accuracy and generalizability of the model to new patients. If models are validated in a setting in which competing events occur, these competing risks should be accounted for when comparing predicted risks to observed outcomes.

Methods

We discuss existing measures of calibration and discrimination that incorporate competing events for time-to-event models. These methods are illustrated using a clinical-data example concerning the prediction of kidney failure in a population with advanced chronic kidney disease (CKD), using the guideline-recommended Kidney Failure Risk Equation (KFRE). The KFRE was developed using Cox regression in a diverse population of CKD patients and has been proposed for use in patients with advanced CKD in whom death is a frequent competing event.

Results

When validating the 5-year KFRE with methods that account for competing events, it becomes apparent that the 5-year KFRE considerably overestimates the real-world risk of kidney failure. The absolute overestimation was 10%age points on average and 29%age points in older high-risk patients.

Conclusions

It is crucial that competing events are accounted for during external validation to provide a more reliable assessment the performance of a model in clinical settings in which competing risks occur.
Medicine acceptability for older people in hospital and care home: the influence of setting
Authors: Jani Yogini H , Liu Fang , Orlu Mine , Desai Neel , du Chayla Florence , Ruiz Fabrice , Vallet Thibault
Published: November 2021

Objective

Medicines acceptability is likely to have a significant impact on older people’s adherence and, consequently, treatment effectiveness. The objective was to explore the influence of setting on medicines acceptability in older people.

Methods

A multi-centre, prospective, cross-sectional, observational study was conducted in one care home and one elderly care hospital ward in London, UK, involving individuals on ≥1 medicine(s) and aged ≥65 years. Data-driven approach was applied using multiple observer-reported outcomes analysis tool to distinguish between positively and negatively accepted medicines.

Key findings

263 observer reports from the care home (n = 97) and hospital ward (n = 166) involving 155 distinct medicinal products were assessed. Collectively, medicines appeared better accepted by patients at the hospital. Differences appeared to be driven by variations in solid oral dosage form (SODF) acceptability. Patients with dysphagia poorly accepted medicines in both settings, as expected. SODFs were unexpectedly better accepted in the hospital than in the care home in patients without dysphagia.

Conclusions

Medicines acceptability was affected by patient’s characteristics, dosage form type and setting. Changes in care practices between care home and hospital may affect medicine administration and lead to variations in the ability and willingness of patients and carers to use the product as intended.
Cubic and Quartic Points on Modular Curves Using Generalised Symmetric Chabauty
Authors: Box Josha , Gajović Stevan , Goodman Pip
Published: November 2021

Answering a question of Zureick-Brown, we determine the cubic points on the modular curves $X_0(N)$ for $N \in \{53,57,61,65,67,73\}$ as well as the quartic points on $X_0(65)$. To do so, we develop a “partially relative” symmetric Chabauty method. Our results generalise current symmetric Chabauty theorems and improve upon them by lowering the involved prime bound. For our curves a number of novelties occur. We prove a “higher-order” Chabauty theorem to deal with these cases. Finally, to study the isolated quartic points on $X_0(65)$, we rigorously compute the full rational Mordell–Weil group of its Jacobian.
A Gonococcal Vaccine Has the Potential to Rapidly Reduce the Incidence of Neisseria gonorrhoeae Infection Among Urban Men Who Have Sex With Men
Authors: Hui Ben B , Padeniya Thilini N , Rebuli Nic , Gray Richard T , Wood James G , Donovan Basil , Duan Qibin , Guy Rebecca , Hocking Jane S , Lahra Monica M , Lewis David A , Whiley David M , Regan David G , Seib Kate L
Published: November 2021

Background

A gonococcal vaccine is urgently needed due to increasing gonorrhea incidence and emerging multidrug-resistant gonococcal strains worldwide. Men who have sex with men (MSM) have among the highest incidences of gonorrhea and may be a key target population for vaccination when available.

Methods

An individual-based, anatomical site-specific mathematical model was used to simulate Neisseria gonorrhoeae transmission in a population of 10 000 MSM. The impact of vaccination on gonorrhea prevalence was assessed.

Results

With a gonococcal vaccine of 100% or 50% protective efficacy, gonorrhea prevalence could be reduced by 94% or 62%, respectively, within 2 years if 30% of MSM are vaccinated on presentation for sexually transmitted infection (STI) testing. Elimination of gonorrhea is possible within 8 years with vaccines of ≥ 50% efficacy lasting 2 years, providing a booster vaccination is available every 3 years on average. A vaccine’s impact may be reduced if it is not effective at all anatomical sites.

Conclusions

Our study indicates that with a vaccine of modest efficacy and an immunization strategy that targets MSM presenting for STI screening, the prevalence of gonorrhea in this population could be rapidly and substantially reduced.
Evolutionary conservative analysis revealed novel functional sites in the efflux pump NorA of Staphylococcus aureus
Authors: Shang Yan , Lv Peiwen , Su Dandan , Li Yaru , Liang Yu , Ma Cuiqing , Yang Chunyu
Published: November 2021

Objectives

The NorA antiporter of Staphylococcus aureus belongs to the major facilitator superfamily (MFS) and extrudes various kinds of drugs. With no structure available for this drug efflux pump, the aim of this study was to explore its important structural elements that contribute to substrate binding and drug transport.

Methods

Evolutionary conservative analyses were conducted on different compilations of NorA homologues to identify conservative motifs and residues. Site-directed mutations were constructed to verify the functional changes in NorA efflux capacities and the conformational changes were further measured by fluorescence resonance energy transfer (FRET) and microscale thermophoresis (MST) analysis.

Results

Besides Motif-A, Motif-B and Motif-C that were reported previously in MFS proteins, two other motifs, Motif-1 and Motif-2, were identified in NorA. Site-directed mutations of Motif-1 and Motif-2 as well as 11 predicted binding sites all caused remarkable reductions in drug resistance and efflux activity. Among these, mutant F16A/E222A/F303A/D307A showed an altered binding affinity for tetraphenylphosphonium chloride when measured by MST and Motif-1 mutant G114D/A117E/D118G/V119I and Motif-2 mutant Q325E/G326E/A328E/G330E displayed obvious conformational alterations when compared with the wild-type NorA in the FRET signal spectra.

Conclusions

The NorA structure agrees well with the typical structures of MFS proteins, with two newly identified motifs (Motif-1 and Motif-2) that are critical to the structural stability of NorA, and sites F16, E222, F303 and D307 are involved in substrate binding.
Genotypic, proteomic, and phenotypic approaches to decipher the response to caspofungin and calcineurin inhibitors in clinical isolates of echinocandin-resistantCandida glabrata
Authors: Ceballos-Garzon Andres , Monteoliva Lucia , Gil Concha , Alvarez-Moreno Carlos , Vega-Vela Nelson E , Engelthaler David M , Bowers Jolene , Le Pape Patrice , Parra-Giraldo Claudia M
Published: November 2021

Background

Echinocandin resistance represents a great concern, as these drugs are recommended as first-line therapy for invasive candidiasis. Echinocandin resistance is conferred by mutations in FKS genes. Nevertheless, pathways are crucial for enabling tolerance, evolution, and maintenance of resistance. Therefore, understanding the biological processes and proteins involved in the response to caspofungin may provide clues indicating new therapeutic targets.

Objectives

We determined the resistance mechanism and assessed the proteome response to caspofungin exposure. We then evaluated the phenotypic impact of calcineurin inhibition by FK506 and cephalosporine A (CsA) on caspofungin-resistant Candida glabrata isolates.

Methods

Twenty-five genes associated with caspofungin resistance were analysed by NGS, followed by studies of the quantitative proteomic response to caspofungin exposure. Then, susceptibility testing of caspofungin in presence of FK506 and CsA was performed. The effects of calcineurin inhibitor/caspofungin combinations on heat stress (40°C), oxidative stress (0.2 and 0.4 mM menadione) and on biofilm formation (polyurethane catheter) were analysed. Finally, a Galleria mellonella model using blastospores (1 × 109 cfu/mL) was developed to evaluate the impact of the combinations on larval survival.

Results

F659-del was found in the FKS2 gene of resistant strains. Proteomics data showed some up-regulated proteins are involved in cell-wall biosynthesis, response to stress and pathogenesis, some of them being members of calmodulin–calcineurin pathway. Therefore, the impact of calmodulin inhibition was explored. Calmodulin inhibition restored caspofungin susceptibility, decreased capacity to respond to stress conditions, and reduced biofilm formation and in vivo pathogenicity.

Conclusions

Our findings confirm that calmodulin-calcineurin-Crz1 could provide a relevant target in life-threatening invasive candidiasis.
Cesarean scar pregnancy with devastating profuse vaginal bleeding
Authors: Tjokroprawiro Brahmana Askandar , Akbar Muhammad Ilham Aldika
Published: November 2021

A cesarean scar pregnancy (CSP) is a rare type of ectopic pregnancy that does not have any obvious signs or symptoms. However, the gestational sac in CSP is often embedded in the myometrial scar from the previous cesarean section. We report two cases of CSP in women with a history of cesarean sections who experienced profuse vaginal bleeding. The patients underwent hysterectomy at their own request due to devastating bleeding. CSP is one of the complications of cesarean sections. The patient may present with devastating bleeding, and immediate management is necessary. In a woman who is early into her pregnancy and has a history of cesarean section with profuse vaginal bleeding, CSP is one of the possible diagnoses.
Biomechanics of the parasite–host interaction of the European mistletoe
Authors: Mylo Max D , Hofmann Mara , Balle Frank , Beisel Samuel , Speck Thomas , Speck Olga
Published: November 2021

The European mistletoe (Viscum album) is an epiphytic hemiparasite that attaches to its host by an endophytic system. Two aspects are essential for its survival: the structural integrity of the host–parasite interface must be maintained during host growth and the functional integrity of the interface must be maintained during ontogeny and under mechanical stress. We investigated the mechanical properties of the mistletoe–host interaction. Intact and sliced mistletoe–host samples, with host wood as reference, were subjected to tensile tests up to failure. We quantified the rough fractured surface by digital microscopy and analysed local surface strains by digital image correlation. Tensile strength and deformation energy were independent of mistletoe age but exhibited markedly lower values than host wood samples. Cracks initiated at sites with a major strain of about 30%, especially along the mistletoe–host interface. The risk of sudden failure was counteracted by various sinkers and a lignification gradient that smooths the differences in the mechanical properties between the two species. Our results improve the understanding of the key mechanical characteristics of the host–mistletoe interface and show that the mechanical connection between the mistletoe and its host is age-independent. Thus, functional and structural integrity is ensured over the lifetime of the mistletoe.
X-ray spectra of circumgalactic medium around star-forming galaxies: connecting simulations to observations
Authors: Vijayan Aditi , Li Miao
Published: November 2021

The hot component of the circumgalactic medium (CGM) around star-forming galaxies is detected as diffuse X-ray emission. The X-ray spectra from the CGM depend on the temperature and metallicity of the emitting plasma, providing important information about the feeding and feedback of the galaxy. The observed spectra are commonly fitted using simple one-temperature (1-T) or two-temperature (2-T) models. However, the actual temperature distribution of the gas can be complex because of the interaction between galactic outflows and halo gas. Here, we demonstrate this by analysing 3D hydrodynamical simulations of the CGM with a realistic outflow model. We investigate the physical properties of the simulated hot CGM, which shows a broad distribution in density, temperature, and metallicity. By constructing and fitting the simulated spectra, we show that, while the 1-T and 2-T models are able to fit the synthesized spectra reasonably well, the inferred temperature(s) does not bear much physical meaning. Instead, we propose a lognormal distribution as a more physical model. The lognormal model better fits the simulated spectra while reproducing the gas temperature distribution. We also show that when the star formation rate is high, the spectra inside the biconical outflows are distinct from those outside, as outflows are generally hotter and more metal enriched. Finally, we produce mock spectra for future missions with the eV-level spectral resolution, such as Athena, Lynx, the Hot Universe Baryon Surveyor, and theX-ray Imaging and Spectroscopy Mission.
A low-frequency pilot survey of southern H ii regions in the vela constellation
Authors: Tremblay Chenoa D , Bourke Tyler L , Green James A , Dickey John M , Wong O Ivy , Galvin Tim J
Published: November 2021

Atomic ionized regions with strong continuum emission are often associated with regions of high-mass star formation and low-frequency (<2 GHz) observations of these regions are needed to help build star formation models. The region toward the Vela Supernova Remnant is particularly interesting as it is a complex structure of recent supernova explosions and molecular clouds containing a number of H ii regions that are not well characterized. We searched publicly available catalogues for H ii regions, both candidate and identified, which also have low-frequency emission. In the area of ∼400 square degrees toward the Vela Supernova remnant, we found 10 such H ii regions, some of which have multiple components in catalogues. In this work we use data from the Australian Square Kilometre Array Pathfinder and previously unpublished data from the Murchison Widefield Array and the Australian Telescope Compact Array to analyse these sources. The high-mass star forming region RCW 38, with observations specifically targeted on the source, is used as a pilot study to demonstrate how low-frequency, wide-field continuum observations can identify and study H ii regions in our Galaxy. For the nine other H ii regions, we discuss their properties; including information about which clouds are interacting, their ages, whether they are dominated by infrared or optical H α lines, distances, ionizing photon flux, and upper limits on the infrared luminosity. In future work, these nine regions will be analysed in more detail, similar to the result for RCW 38 presented here.
New photometry of 12 ultrashort-period late-type binary stars
Authors: Koen C
Published: November 2021

Candidate late-type binary stars were selected on the basis of their red g − i and r − z colours, and short (0.1159–0.2059 d) published periods. At least one cycle of variation of each star was observed in the RC and IC bands. For the five brightest stars, observations were also obtained in V. Typically ∼17 standardized photometric measurements of each of the stars, ranging over the optical and infrared, are available from various surveys. These were used to accurately determine the reddenings and effective temperatures. In all but one case Gaia parallaxes are available, so that the luminosities of the binaries could also be estimated. Deduced spectral types are in the range M2–M4.5. Preliminary modelling suggests that half the stars may be in contact configurations.
Impact of gas spin and Lyman–Werner flux on black hole seed formation in cosmological simulations: implications for direct collapse
Authors: Bhowmick Aklant K , Blecha Laura , Torrey Paul , Kelley Luke Zoltan , Vogelsberger Mark , Nelson Dylan , Weinberger Rainer , Hernquist Lars
Published: November 2021

Direct collapse black holes (BHs) are promising candidates for producing massive z ≳ 6 quasars, but their formation requires fine-tuned conditions. In this work, we use cosmological zoom simulations to study systematically the impact of requiring: (1) low gas angular momentum (spin), and (2) a minimum incident Lyman–Werner (LW) flux in order to form BH seeds. We probe the formation of seeds (with initial masses of $M_{\rm seed} \sim 10^4\!-\!10^6\, \mathrm{M}_{\odot }\, h^{-1})$ in haloes with a total mass >3000 × Mseed and a dense, metal-poor gas mass >5 × Mseed. Within this framework, we find that the seed-forming haloes have a prior history of star formation and metal enrichment, but they also contain pockets of dense, metal-poor gas. When seeding is further restricted to haloes with low gas spins, the number of seeds formed is suppressed by factors of ∼6 compared to the baseline model, regardless of the seed mass. Seed formation is much more strongly impacted if the dense, metal-poor gas is required to have a critical LW flux (Jcrit). Even for Jcrit values as low as 50J21, no $8\times 10^{5}~\mathrm{M}_{\odot }\, h^{-1}$ seeds are formed. While lower mass ($1.25\times 10^{4},1\times 10^{5}~\mathrm{M}_{\odot }\, h^{-1}$) seeds do form, they are strongly suppressed (by factors of ∼10–100) compared to the baseline model at gas mass resolutions of $\sim 10^4~\mathrm{M}_{\odot }\, h^{-1}$ (with even stronger suppression at higher resolutions). As a result, BH merger rates are also similarly suppressed. Since early BH growth is dominated by mergers in our models, none of the seeds are able to grow to the supermassive regime ($\gtrsim 10^6~\mathrm{M}_{\odot }\, h^{-1}$) by z = 7. Our results hint that producing the bulk of the z ≳ 6 supermassive BH population may require alternate seeding scenarios that do not depend on the LW flux, early BH growth dominated by rapid or super-Eddington accretion, or a combination of these possibilities.
Type I CRISPR-Cas provides robust immunity but incomplete attenuation of phage-induced cellular stress
Authors: Malone Lucia M , Hampton Hannah G , Morgan Xochitl C , Fineran Peter C
Published: November 2021

During infection, phages manipulate bacteria to redirect metabolism towards viral proliferation. To counteract phages, some bacteria employ CRISPR-Cas systems that provide adaptive immunity. While CRISPR-Cas mechanisms have been studied extensively, their effects on both the phage and the host during phage infection remains poorly understood. Here, we analysed the infection of Serratia by a siphovirus (JS26) and the transcriptomic response with, or without type I-E or I-F CRISPR-Cas immunity. In non-immune Serratia, phage infection altered bacterial metabolism by upregulating anaerobic respiration and amino acid biosynthesis genes, while flagella production was suppressed. Furthermore, phage proliferation required a late-expressed viral Cas4 homologue, which did not influence CRISPR adaptation. While type I-E and I-F immunity provided robust defence against phage infection, phage development still impacted the bacterial host. Moreover, DNA repair and SOS response pathways were upregulated during type I immunity. We also discovered that the type I-F system is controlled by a positive autoregulatory feedback loop that is activated upon phage targeting during type I-F immunity, leading to a controlled anti-phage response. Overall, our results provide new insight into phage-host dynamics and the impact of CRISPR immunity within the infected cell.
An Analytic Framework for Interpreting Investment Regressions in the Presence of Financial Constraints
Authors: Abel Andrew B , Panageas Stavros
Published: November 2021

We derive analytic solutions for the valuation, optimal investment, and optimal payout of a financially constrained firm. While marginal $q$ and average $q$ would be identically equal in the absence of financial constraints, they differ when financial constraints bind. We use analytic solutions to characterize the properties of regressions of investment on average $q$ and cash flow. The coefficient on cash flow is positive, but does not isolate the impact of the financial constraint, since it also partially reflects the impact of persistent profitability. The coefficient on average $q$ understates the impact of persistent profitability.
Intragenerational Social Mobility and Well-being in Great Britain: A Biomarker Approach
Authors: Präg Patrick , Fritsch Nina-Sophie , Richards Lindsay
Published: November 2021

Social theory has long predicted that social mobility, in particular downward social mobility, is detrimental to the well-being of individuals. Dissociative and “falling from grace” theories suggest that mobility is stressful due to the weakening of social ties, feelings of alienation, and loss of status. In light of these theories, it is a puzzle that the majority of quantitative studies in this area have shown null results. Our approach to resolve the puzzle is two-fold. First, we argue for a broader conception of the mobility process than is often used and thus focus on intragenerational occupational class mobility rather than restricting ourselves to the more commonly studied intergenerational mobility. Second, we argue that self-reported measures may be biased by habituation (or “entrenched deprivation”). Using nurse-collected health and biomarker data from the UK Household Longitudinal Study (2010–2012, N = 4,123), we derive a measure of allostatic load as an objective gauge of physiological “wear and tear” and compare patterns of mobility effects with self-reports of health using diagonal reference models. Our findings indicate a strong class gradient in both allostatic load and self-rated health, and that both first and current job matter for current well-being outcomes. However, in terms of the effects of mobility itself, we find that intragenerational social mobility is consequential for allostatic load, but not for self-rated health. Downward mobility is detrimental and upward mobility beneficial for well-being as assessed by allostatic load. Thus, these findings do not support the idea of generalized stress from dissociation, but they do support the “falling from grace” hypothesis of negative downward mobility effects. Our findings have a further implication, namely that the differences in mobility effects between the objective and subjective outcome infer the presence of entrenched deprivation. Null results in studies of self-rated outcomes may therefore be a methodological artifact, rather than an outright rejection of decades-old social theory.
The Performance and Trajectory of Medical Students With Disabilities: Results From a Multisite, Multicohort Study
Authors: Meeks Lisa M. , Plegue Melissa , Swenor Bonnielin K. , Moreland Christopher J. , Jain Sharad , Grabowski Christina J. , Westervelt Marjorie , Case Ben , Eidtson William H. , Patwari Rahul , Angoff Nancy R. , LeConche Jack , Temple Bliss M. , Poullos Peter , Sanchez-Guzman Mijiza , Coates Caitlyn , Low Christine , Henderson Mark C. , Purkiss Joel , Kim Michael H.
Published: November 2021

Purpose

To conduct a post–Americans with Disabilities Act Amendments Act of 2008 multisite, multicohort study called the Pathways Project to assess the performance and trajectory of medical students with disabilities (SWDs).

Method

From June to December 2020, the authors conducted a matched cohort study of SWDs and nondisabled controls from 2 graduating cohorts (2018 and 2019) across 11 U.S. MD-granting medical schools. Each SWD was matched with 2 controls, one from their institution and, whenever possible, one from their cohort for Medical College Admission Test score and self-reported gender. Outcome measures included final attempt Step 1 and Step 2 Clinical Knowledge scores, time to graduation, leave of absence, matching on first attempt, and matching to primary care.

Results

A total of 171 SWDs and 341 controls were included; the majority of SWDs had cognitive/learning disabilities (118/171, 69.0%). Compared with controls, SWDs with physical/sensory disabilities had similar times to graduation (88.6%, 95% confidence interval [CI]: 77.0, 100.0 vs 95.1%, 95% CI: 90.3, 99.8; P = .20), Step 1 scores (229.6 vs 233.4; P = .118), and match on first attempt (93.9%, 95% CI: 86.9, 100.0 vs 94.6%, 95% CI: 91.8, 97.4; P = .842), while SWDs with cognitive/learning disabilities had lower Step 1 scores (219.4; P < .001) and were less likely to graduate on time (81.2%, 95% CI: 69.2, 93.2; P = .003) and match on first attempt (85.3%, 95% CI: 78.0, 92.7; P = .009). Accommodated SWDs had Step 1 scores that were 5.9 points higher than nonaccommodated SWDs (95% CI: –0.7, 12.5; P = .08).

Conclusions

Structural barriers remain for SWDs with cognitive/learning disabilities, which could be partially mitigated by accommodations on high-stakes exams.
Innovative Teaching Strategies Using Simulation for Pediatric Nursing Clinical Education During the Pandemic: A Case Study
Authors: Cook Tamara C. , Camp-Spivey Logan J.
Published: November 2021

Existing challenges associated with pediatric clinical placements for prelicensure nursing students were heightened when clinical agencies halted nursing student entry in response to the COVID-19 pandemic. At the same time, the pandemic created opportunities for innovative teaching strategies for pediatric clinical rotations in nursing education. The purpose of this project was to design, develop, and implement meaningful, interactive, and intentional clinical experiences for nursing students that enhanced their pediatric assessment skills, reduced their anxiety about pediatric inpatient care, and advanced their proficiency in the nursing process. Two simulated clinical experiences were created: (1) a virtual pediatric physical assessment checkoff and (2) a pediatric escape room. The pediatric physical assessment checkoff was performed in a remote, virtual setting while students used personal resources to demonstrate their assessment skills. For the escape room, students worked in small, in-person groups using the nursing process to unlock clues to improve their client’s health condition. Students reported gaining meaningful clinical experiences through simulation that allowed them to apply their nursing knowledge and increased their confidence in pediatric assessment skills, dosage calculation competency, communications and interactions with the pediatric population, and teamwork abilities. The virtual pediatric physical assessment checkoff and the pediatric escape room were enjoyable and beneficial educational events that facilitated student learning.
Student-Run Free Clinics Stand at a Critical Junction Between Undergraduate Medical Education, Clinical Care, and Advocacy
Authors: Rupert Deborah D. , Alvarez George V. , Burdge Eric J. , Nahvi Roxanna J. , Schell Spencer M. , Faustino Francis L.
Published: November 2021

Student-run free clinics (SRFCs) act as primary care providers that bring health care to populations in need and are an important source of undergraduate medical education (UME), guiding trainees through the art of history taking and physical examination. However, they are also social justice and advocacy initiatives—addressing disparity in access to care and educating medical trainees with firsthand exposure to socioeconomic determinants of health as well as language and medical illiteracy barriers. Here, the authors review academic literature examining the impact of SRFCs in their 3 roles: as medical care providers, as components of medical education, and as advocacy organizations. Based on the evidence of that literature and decades of direct SRFC leadership experience, the authors make the case that SRFCs are an undersupported means by which UME institutions contribute to correcting health care disparities and to serving social justice reform.
Indication of Proximal Gastrectomy for Advanced Proximal Gastric Cancer Based on Lymph Node Metastasis at the Distal Part of the Stomach
Authors: Lee Sejin , Son Won Jeong , Roh Yun Ho , Song Jeong Ho , Park Sung Hyun , Cho Minah , Kim Yoo Min , Hyung Woo Jin , Kim Hyoung-Il
Published: November 2021

Objective:

To suggest the possible indication of proximal gastrectomy for advanced gastric cancer located at the upper third of the stomach.

Background:

Proximal gastrectomy has been an alternative surgical procedure for early proximal gastric cancer due to its benefits for quality of life while maintaining oncological outcomes. However, the oncological safety of proximal gastrectomy for advanced tumors remains unclear.

Methods:

We retrospectively reviewed data from 878 patients who underwent radical total gastrectomy from 2003 to 2018 for pathologic T2–T4 gastric cancer in the upper third of the stomach. We identified risk factors for lymph node metastasis at the distal part of the stomach, which was not dissected in proximal gastrectomy. Subsequently, we evaluated the metastasis rate and therapeutic value index of lymph nodes at the distal part of the stomach in patients with none of these risk factors.

Results:

Multivariable analysis revealed that esophagogastric junction (EGJ)-tumor epicenter distance >30 mm, tumor size >70 mm, macroscopic type IV tumor, and serosal invasion were risk factors for lymph node metastasis at the distal stomach. In patients without risk factors, the therapeutic value index for any lymph nodes at the distal stomach was 0.8, suggesting that lymph node dissection could be omitted in these patients.

Conclusions:

EGJ-tumor epicenter distance ≤ 30 mm, tumor size ≤ 70 mm, not a macroscopic type IV tumor, and no serosal invasion could be an indication of proximal gastrectomy for advanced gastric cancer located at the upper third of the stomach.
Improvement and International Validation of the Predictive Probability of the Patient Demographics, Radiographic Index, and Surgical Invasiveness for Mechanical Failure (PRISM) Model for Preventive Procedures in Adult Spinal Deformity Surgery
Authors: Yagi Mitsuru , Hosogane Naobumi , Ames Christopher P. , Smith Justin S. , Shaffrey Christopher I. , Schwab Frank J. , Lafage Virginie , Bess Shay , Suzuki Satoshi , Satoshi Nori , Takahashi Yohei , Tsuji Osahiko , Nagoshi Narihito , Nakamura Masaya , Matsumoto Morio , Watanabe Kota
Published: November 2021

Study Design.

This is an international multicenter retrospective review of 219 surgically treated consecutive adult spinal deformity (ASD) patients who had a minimum of five fused segments, completed a 2-year follow-up.

Objective.

The purpose of this study was to add the indices of preventive procedures to improve and to validate the predictive probability of the PRISM (patient demographics, radiographic index, and surgical invasiveness for mechanical failure) for mechanical failure (MF) following ASD surgery.

Summary of Background Data.

The PRISM was developed from the data of 321 ASD patients, which stratified the risk of MF from six types of risk.

Methods.

Data from 136 Japanese ASD patients (age 49 ± 21 yr, 88% female) were used to develop PRISM2, and data from 83 US ASD patients (age 58 ± 12 yr, 86% female) were used for the external validation. We analyzed the associations between three preventive procedures (UIV+1 tethering [TH], teriparatide [TP], and multirod [MR]) and MF by multivariate logistic regression analysis (MRA). The values for the nearest integer of the β of the procedures were added to the six indices of the original PRISM to establish the PRISM2. The discriminative ability of the PRISM/ PRISM2 for MF was evaluated using the area under the receiver operating characteristic curve (AUC) and the precision-recall (PR) curve. The Cochran-Armitage test was used to analyze the trend between PRISM/PRISM2 scores and MF.

Results.

MF developed in 25% (34 cases). The β values for the preventive procedures calculated by MRA were TH: –2.5, TP: –3.0, and MR: –2.1. The Cochran-Armitage test showed an excellent trend between MF and PRISM/2. The diagnostic ability was superior for the PRISM2 compared with the PRISM (PRISM2; AUC = 0.94 [0.90–0.98], PRISM; AUC = 0.87 [0.81–0.93], difference = –0.07 [–0.11 to –0.03], P 
< 0.01). The AUC of the PRISM2 was 0.70 [0.59–0.81, P < 0.01] in the US patient cohort.

Conclusion.

We refined the PRISM by adding preventive procedures to the risk indices. Further validation and adjustment in a large different patient cohorts may improve the predictive probability of PRISM2.

Level of Evidence: 3
Rare Case of Double-Positive CD4/CD8 Immunophenotype in Lennert Lymphoma With Cutaneous Involvement: A Case Report
Authors: Kim Joong Ho , Lee Soo Kyung , Kim Ho Young , Uh Ji An , Lee Jae Ho , Kim Myoung Shin , Lee Un Ha
Published: November 2021

Lennert lymphoma is a lymphoepithelioid variant of peripheral T-cell lymphoma (not otherwise specified) with characteristics that do not fit into other peripheral T-cell lymphoma categories. Lennert lymphoma is primarily a nodal disease, and skin involvement may be exhibited. Cutaneous manifestations in Lennert lymphoma are nonspecific and include erythematous papules, nodules, and small plaques. Histological examination of cutaneous involvement characteristically presents epithelioid histiocytes and atypical small lymphocytes around vessels or appendages. A lymph node (LN) biopsy is essential for Lennert lymphoma diagnosis. In Lennert lymphoma, immunohistochemistry of both LNs and the involved skin reveals T-cell marker positivity. Although most Lennert lymphoma cases present with a single-positive CD4/CD8 immunophenotype, few cases present with a double-positive CD4/CD8 immunophenotype. We report a case of a 54-year-old woman presenting with fever, chills, general weakness, and a skin rash of erythematous patches on the trunk, extremities, and buttocks. A skin biopsy of the buttocks revealed atypical lymphocytes around the dermal vessels. In immunohistochemistry, these atypical lymphocytes stained positive for CD3, CD4, CD8, and CD68 but negative for CD20, CD30, and granzyme B. Similarly, a biopsy of the axillary LN revealed numerous epithelioid cells with atypical lymphocytes, exhibiting positivity for CD3, CD4, CD8, and CD68 but negativity for CD20, CD30, and S-100. Ki-67 was overexpressed in both the skin and LN. The final diagnosis of the patient was Lennert lymphoma with cutaneous involvement and a rare double-positive CD4/CD8 immunophenotype. The patient was transferred to another hospital for chemotherapy as per her request.
The Impact of Changes in Work Arrangements During COVID-19 Pandemic on the Lifestyle of Qatar's Working Population
Authors: Abed Alah Muna , Abdeen Sami , Kehyayan Vahe , Bougmiza Iheb
Published: November 2021

Objectives:

To explore the impact of changing work arrangements during COVID-19 on diet, physical activity, body weight, and sleep of Qatar's working population.

Methods:

A web-based survey targeting working adults who were residing in Qatar during the period of home confinement was conducted.

Results:

About 47% of 1061 participants reported weight gain. Higher proportions of participants reported consuming more fatty foods (P = 0.007), more sugary foods (P = 0.001), and greater increase in screen and sitting/reclining times (P < 0.001) among the work from home (WFH) group. Participants with higher adverse dietary changes score were more likely to report weight gain in both the WFH (adjusted OR 1.38, 95% CI 1.28 to 1.49), and working regularly groups (adjusted OR, 1.31, 95% CI 1.20 to 1.43) with P < 0.001.

Conclusion:

Qatar's working population experienced adverse lifestyle changes which were more prominent among those who shifted to WFH.