bluuebunny/crossref_metadata_2025 huggingface dataset:
Computed angiographic variations in hepatic venous vasculature in dogs
Authors: Takagi Satoshi , Nishino Ayano , Hanazono Kiwamu , Hosoya Kenji
Published: February 2022

Objective

To identify the number of hepatic veins draining directly or indirectly into the caudal vena cava Thank you (CVC) using computed tomography angiography (CTA) in dogs.

Study design

Retrospective clinical study.

Animals

Client‐owned dogs (n = 77).

Methods

Abdominal CTA images were analyzed. Retrospective convenience sampling was performed using archived clinical cases to determine the number of hepatic veins in each liver lobe.

Results

A median of 2 vessels from the right lateral lobe (range: 1‐4) and the caudate process of the caudate lobe (range: 1‐5) drained directly into the CVC. In the quadrate lobe, most common patterns consisted of 1 vessel directly draining to the CVC or indirectly via the left hepatic vein (LHV), and a vessel from quadrate lobe and right medial lobe merging into 1 vessel draining into the CVC or the LHV. A median of 3 vessels in the left lateral lobe (range: 2‐8) and a median of 1 vessel in the left medial lobe (range: 1‐3) drained into the LHV. In the papillary process of the caudate lobe, a median of 1 (range: 1‐2) vessel drained directly into the CVC or the LHV.

Conclusion

The draining pattern of hepatic veins varied widely in all liver lobes, especially the left lateral liver lobe.

Clinical significance

Veterinary surgeons should consider the potential presence of multiple hepatic veins and their draining pattern when performing hilar liver lobe resection. Attentive evaluation of a preoperative CTA is recommended for surgical planning.
The physics of knocking over LEGO minifigures with time reversal focused vibrations for use in a museum exhibit
Authors: Barnes Lucas A. , Anderson Brian E. , Le Bas Pierre-Yves , Kingsley Adam D. , Brown Aaron C. , Thomsen Henrik R.
Published: February 2022

Time reversal (TR) is a method of focusing wave energy at a point in space. The optimization of a TR demonstration is described, which knocks over one selected LEGO minifigure among other minifigures by focusing the vibrations within an aluminum plate at the target minifigure. The aim is to achieve a high repeatability of the demonstration along with reduced costs to create a museum exhibit. By comparing the minifigure's motion to the plate's motion directly beneath its feet, it is determined that a major factor inhibiting the repeatability is that the smaller vibrations before the focal event cause the minifigure to bounce repeatedly and it ends up being in the air during the main vibrational focal event, which was intended to launch the minifigure. The deconvolution TR technique is determined to be optimal in providing the demonstration repeatability. The amplitude, frequency, and plate thickness are optimized in a laboratory setting. An eddy current sensor is then used to reduce the costs, and the impact on the repeatability is determined. A description is given of the implementation of the demonstration for a museum exhibit. This demonstration illustrates the power of the focusing acoustic waves, and the principles learned by optimizing this demonstration can be applied to other real-world applications.
A point-wise artifact rejection method for estimating transient-evoked otoacoustic emissions and their group delay
Authors: Fang Chieh-Hsi , Liu Yi-Wen
Published: February 2022

Due to its low intensity, measurement of transient-evoked otoacoustic emission (TEOAE) requires repeated stimulation. When any acoustic artifact occurs, an entire click interval is typically abandoned. Here, a point-wise artifact rejection strategy is proposed, and it partially preserves the data when artifacts occur in an interval. At the noisiest setting (−46 dB signal-to-noise ratio) the proposed strategy retains four times more data and thereby reduces the root mean square signal estimation error by over 60%. Consequently, the group delay can be calculated more accurately. These findings might facilitate TEOAE measurement at home or in other noisy environments in the future.
Establishment of mouse stem cells that can recapitulate the developmental potential of primitive endoderm
Authors: Ohinata Yasuhide , Endo Takaho A. , Sugishita Hiroki , Watanabe Takashi , Iizuka Yusuke , Kawamoto Yurie , Saraya Atsunori , Kumon Mami , Koseki Yoko , Kondo Takashi , Ohara Osamu , Koseki Haruhiko
Published: February 2022

The mammalian blastocyst consists of three distinct cell types: epiblast, trophoblast (TB), and primitive endoderm (PrE). Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) retain the functional properties of epiblast and TB, respectively, stem cells that fully recapitulate the developmental potential of PrE have not been established. Here, we report derivation of primitive endoderm stem cells (PrESCs) in mice. PrESCs recapitulate properties of embryonic day 4.5 founder PrE, are efficiently incorporated into PrE upon blastocyst injection, generate functionally competent PrE-derived tissues, and support fetal development of PrE-depleted blastocysts in chimeras. Furthermore, PrESCs can establish interactions with ESCs and TSCs and generate descendants with yolk sac–like structures in utero. Establishment of PrESCs will enable the elucidation of the mechanisms for PrE specification and subsequent pre- and postimplantation development.
Nocturnal survival of isoprene linked to formation of upper tropospheric organic aerosol
Authors: Palmer Paul I. , Marvin Margaret R. , Siddans Richard , Kerridge Brian J. , Moore David P.
Published: February 2022

Isoprene is emitted mainly by terrestrial vegetation and is the dominant volatile organic compound (VOC) in Earth’s atmosphere. It plays key roles in determining the oxidizing capacity of the troposphere and the formation of organic aerosol. Daytime infrared satellite observations of isoprene reported here broadly agree with emission inventories, but we found substantial differences in the locations and magnitudes of isoprene hotspots, consistent with a recent study. The corresponding nighttime infrared observations reveal unexpected hotspots over tropical South America, the Congo basin, and Southeast Asia. We used an atmospheric chemistry model to link these nighttime isoprene measurements to low-NO

x

regions with high biogenic VOC emissions; at sunrise the remaining isoprene can lead to the production of epoxydiols and subsequently to the widespread seasonal production of organic aerosol in the tropical upper troposphere.
Per- and polyfluoroalkyl substances in the environment
Authors: Evich Marina G. , Davis Mary J. B. , McCord James P. , Acrey Brad , Awkerman Jill A. , Knappe Detlef R. U. , Lindstrom Andrew B. , Speth Thomas F. , Tebes-Stevens Caroline , Strynar Mark J. , Wang Zhanyun , Weber Eric J. , Henderson W. Matthew , Washington John W.
Published: February 2022

Over the past several years, the term PFAS (per- and polyfluoroalkyl substances) has grown to be emblematic of environmental contamination, garnering public, scientific, and regulatory concern. PFAS are synthesized by two processes, direct fluorination (e.g., electrochemical fluorination) and oligomerization (e.g., fluorotelomerization). More than a megatonne of PFAS is produced yearly, and thousands of PFAS wind up in end-use products. Atmospheric and aqueous fugitive releases during manufacturing, use, and disposal have resulted in the global distribution of these compounds. Volatile PFAS facilitate long-range transport, commonly followed by complex transformation schemes to recalcitrant terminal PFAS, which do not degrade under environmental conditions and thus migrate through the environment and accumulate in biota through multiple pathways. Efforts to remediate PFAS-contaminated matrices still are in their infancy, with much current research targeting drinking water.
Genome organization controls transcriptional dynamics during development
Authors: Batut Philippe J. , Bing Xin Yang , Sisco Zachary , Raimundo João , Levo Michal , Levine Michael S.
Published: February 2022

Past studies offer contradictory claims for the role of genome organization in the regulation of gene activity. Here, we show through high-resolution chromosome conformation analysis that the
Drosophila
genome is organized by two independent classes of regulatory sequences, tethering elements and insulators. Quantitative live imaging and targeted genome editing demonstrate that this two-tiered organization is critical for the precise temporal dynamics of Hox gene transcription during development. Tethering elements mediate long-range enhancer-promoter interactions and foster fast activation kinetics. Conversely, the boundaries of topologically associating domains (TADs) prevent spurious interactions with enhancers and silencers located in neighboring TADs. These two levels of genome organization operate independently of one another to ensure precision of transcriptional dynamics and the reliability of complex patterning processes.
CRISPR activation and interference screens decode stimulation responses in primary human T cells
Authors: Schmidt Ralf , Steinhart Zachary , Layeghi Madeline , Freimer Jacob W. , Bueno Raymund , Nguyen Vinh Q. , Blaeschke Franziska , Ye Chun Jimmie , Marson Alexander
Published: February 2022

Regulation of cytokine production in stimulated T cells can be disrupted in autoimmunity, immunodeficiencies, and cancer. Systematic discovery of stimulation-dependent cytokine regulators requires both loss-of-function and gain-of-function studies, which have been challenging in primary human cells. We now report genome-wide CRISPR activation (CRISPRa) and interference (CRISPRi) screens in primary human T cells to identify gene networks controlling interleukin-2 (IL-2) and interferon-γ (IFN-γ) production. Arrayed CRISPRa confirmed key hits and enabled multiplexed secretome characterization, revealing reshaped cytokine responses. Coupling CRISPRa screening with single-cell RNA sequencing enabled deep molecular characterization of screen hits, revealing how perturbations tuned T cell activation and promoted cell states characterized by distinct cytokine expression profiles. These screens reveal genes that reprogram critical immune cell functions, which could inform the design of immunotherapies.
The adenine methylation debate
Authors: Boulias Konstantinos , Greer Eric Lieberman
Published: February 2022

N
6
-methyl-2′-deoxyadenosine (6mA) is less prevalent in metazoan DNA than thought
Science needs affirmative action
Authors: Thorp H. Holden
Published: February 2022

As science struggles to correct systemic racism in the laboratory and throughout academia in the United States, external forces press on, making it even more difficult to achieve equity on all fronts—including among scientists. The latest example is the decision by the US Supreme Court to hear cases brought against Harvard University and the University of North Carolina (UNC) at Chapel Hill challenging their right to use race as a factor in undergraduate admissions. It is sometimes easy for scientists to let colleagues in other disciplines engage in a debate like this, but the dismantling of race-conscious admissions would deal another blow to equity in science. The Supreme Court has protected affirmative action in the past, but the Court’s current majority of conservative justices could mean the end of the program. This is no time for the scientific community to stay silent. It is a crucial moment for science to mobilize against this latest assault on diversity.
Draft Genome Sequences of Two Lactobacillus johnsonii and Three Ligilactobacillus salivarius Strains Isolated from Intestinal Microbiomes of Chickens
Authors: Reed Alyxandra , Olszewska Magdalena A. , Mann Amy , Novoa Rama Estefanía , Thippareddi Harshavardhan , Singh Manpreet , den Bakker Henk C.
Published: February 2022

This report describes the genome sequences of two
Lactobacillus johnsonii
strains (AER105 and AER25) and three
Ligilactobacillus salivarius
strains (AER35, AER36, and AER04) recovered from broiler chicken gastrointestinal tracts in the southeastern United States. These genome sequences will enhance our understanding of the ecology of lactobacilli in the chicken gut microbiome.
Whole-Genome Sequences of
Vibrio
Species from Warm-Water Shrimps Imported into Canada: Detection of Genetic Elements Associated with Antimicrobial Resistance and Potential Mobilizing Capacities
Authors: Teixeira Januana S. , Weedmark Kelly , Dussault Forest , Banerjee Swapan
Published: February 2022

We present draft genome sequences of
Vibrio
species (
Vibrio alginolyticus
,
Vibrio cholerae
, and two
Vibrio parahaemolyticus
strains) that were isolated from warm-water shrimps imported into Canada. All four isolates harbor genetic elements associated with antimicrobial resistance (AMR), including mobile genetic elements that can promote horizontal transfer of AMR genes.
Genome of Bovine Viral Diarrhea Virus (BVDV) Contaminating a Continuous LFBK-α
V
β
6
Cell Line
Authors: Holinka-Patterson Lauren G. , Fish Ian H. , Bertram Miranda R. , Hartwig Ethan J. , Smoliga George R. , Stenfeldt Carolina , Rodriguez Luis L. , Arzt Jonathan
Published: February 2022

Here, we report the genome of bovine viral diarrhea virus 1 (BVDV-1) contaminating a continuous fetal bovine kidney cell line. The cell line (LFBK-α
V
β
6
) is used for the rapid isolation and serotyping of foot-and-mouth disease virus (FMDV). The sequence contains the full polyprotein-coding sequence and partial untranslated regions (UTRs).
SARS-CoV-2 Genome Sequence Obtained from Ethiopia
Authors: Bitew Molalegne , Hailu Getnet , Gebregziabher Tsegay Yakob , Tuki Keyru , Asmamaw Kominist , Tesfaye Kassahun , Dadi Hailu , Orsini Emanuele , Dal Monego Simeone , Licastro Danilo , Marcello Alessandro
Published: February 2022

The coding-complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from 15 nasopharyngeal swabs collected in Addis Ababa, Ethiopia, during the period from December 2020 to March 2021 were determined using Illumina MiSeq technology. A sequence analysis identified that the B.1 SARS-CoV-2 lineage was most prevalent with the worrying emergence of B.1.1.7 in June 2021.
Paleozoic–Mesozoic dispersal of Gondwana: Insights from detrital zircon geochronology of Lesser Himalaya strata, eastern Nepal
Authors: Baral Upendra , Ding Lin , Dhital Megh Raj , Kumar KC , Li Shun
Published: February 2022

Detrital zircon geochronology has rapidly evolved into a powerful tool for reconstructing the assembly and dispersal processes of supercontinents. Currently, the dispersal history of Gondwanaland remains highly controversial. Here we focus on detrital zircon geochronology of the Gondwana (Carboniferous–Permian Kokaha Diamictite and Jurassic–Cretaceous Sapt Koshi Formation) and post-Gondwana (Miocene Tamrang Formation) sequences of the Lesser Himalaya in eastern Nepal. Detrital zircon U-Pb dating results show that the Carboniferous–Permian sequence peaks at 544 Ma, 890 Ma, 1178 Ma, and 1752 Ma. Likewise, the Jurassic–Cretaceous sequence peaks at 531 Ma, 947 Ma, 1176 Ma and 1806 Ma along with a much younger peak at 123 Ma. Similarly, the Miocene sequence peaks at 526 Ma, 987 Ma, and 1740 Ma. Comparing these newly obtained ages with those of surrounding regions, we confirm that during the Carboniferous–Permian, the Indian continent was still connected to Gondwana. The U-Pb age distribution of the Kokaha Diamictite coincides with that of the Tethys Himalaya, which further suggests the possibility that this unit either shared the same provenance with or was recycled from the Tethys Himalaya. During the early Mesozoic, the Indian plate rifted from Gondwana and drifted northward, as evidenced by Triassic–Jurassic, rift-related magmatism along the Indian continental margin. Remarkably, there were significant inputs from the Rajmahal Basalt during deposition of the Jurassic–Cretaceous sequence. Besides, the Miocene sequence records a large number of zircons that closely resemble those of the Greater Himalaya, which implies that the Greater Himalaya may have already been uplifted and eroded by then.
Non-steady-state slip rates emerge along evolving restraining bends under constant loading
Authors: Elston Hanna , Cooke Michele , Hatem Alex
Published: February 2022

Recent field studies provide evidence of fault slip-rate variability over time periods of 10–100 k.y., yet researchers do not know how processes internal to the fault system (e.g., fault reorganization) impact records of fault slip rates. In this study, we directly observed fault-system evolution and measured slip-rate histories within a scaled physical experiment of a dextral strike-slip 15° restraining bend representative of a gentle crustal restraining bend. To assess the degree of slip-rate variability at particular sites along the experimental faults, such as would be revealed in a field study, we tracked fault slip rates at specific locations that advected throughout the experiment with accrued fault slip. Slip rates increased or decreased (5%–25% of the applied velocity) both during fault reorganization (e.g., fault growth and abandonment) and as sites migrated to new structural positions. Sites that advected into the restraining bend showed decreased slip rate. While we expect new fault growth to reduce slip rates along nearby fault segments, we document that the growth of new oblique-slip faults can increase strike-slip rates on nearby fault segments. New oblique-slip thrust faults within the experiment accommodated off-fault convergence and unclamped nearby strike-slip segments. The experimental results show that even under a constant loading rate, slip rates at sites located on stable fault segments can vary due to either reorganization elsewhere in the fault system or site advection.
Candida glabratachorioamnionitis in a twin pregnancy following in vitro fertilisation: a rare cause of septic miscarriage
Authors: Yusoff Muhammad Ashraf , Wee Ian Liang En , Sim Jean Xiang Ying , Yang Liying
Published: February 2022

Candida glabratachorioamnionitis is uncommon and associated with poor fetal outcomes. We present a case ofC. glabratachorioamnionitis of a dichorionic diamniotic pregnancy conceived by fresh embryo transfer. Despite antifungal therapy with amphotericin B, spontaneous miscarriage of both twins occurred. The mother otherwise recovered uneventfully. Our case highlights the high fetal mortality associated withC. glabratachorioamnionitis and the challenges of antifungal treatment in pregnancy. We recommend a low threshold of suspicion forCandidainfection in pregnancy, notably those involving transvaginal uterine instrumentation such as in vitro fertilisation.
Ketamine for the acute treatment of severe suicidal ideation: double blind, randomised placebo controlled trial
Authors: Abbar Mocrane , Demattei Christophe , El-Hage Wissam , Llorca Pierre-Michel , Samalin Ludovic , Demaricourt Pierre , Gaillard Raphael , Courtet Philippe , Vaiva Guillaume , Gorwood Philip , Fabbro Pascale , Jollant Fabrice
Published: February 2022

Objective

To confirm the rapid onset anti-suicidal benefits of ketamine in the short term and at six weeks, overall and according to diagnostic group.

Design

Prospective, double blind, superiority, randomised placebo controlled trial.

Setting

Seven French teaching hospitals between 13 April 2015 and 12 March 2019.

Eligibility criteria for participants

Aged 18 or older with current suicidal ideation, admitted to hospital voluntarily. Exclusion criteria included a history of schizophrenia or other psychotic disorders, substance dependence, and contraindications for ketamine.

Participants

156 participants were recruited and randomised to placebo (n=83) or ketamine (n=73), stratified by centre and diagnosis: bipolar, depressive, or other disorders.

Intervention

Two 40 minute intravenous infusions of ketamine (0.5 mg/kg) or placebo (saline) were administered at baseline and 24 hours, in addition to usual treatment.

Main outcome measures

The primary outcome was the rate of patients in full suicidal remission at day 3, according to the scale for suicidal ideation total score ≤3. Analyses were conducted on an intention-to-treat basis.

Results

More participants receiving ketamine reached full remission of suicidal ideas at day 3 than those receiving placebo: 46 (63.0%) of 83 participants in the ketamine arm and 25 (31.6%) of 73 in the placebo arm (odds ratio 3.7 (95% confidence interval 1.9 to 7.3), P<0.001). This effect differed according to the diagnosis (treatment: P<0.001; interaction: P=0.02): bipolar (odds ratio 14.1 (95% confidence interval 3.0 to 92.2), P<0.001), depressive (1.3 (0.3 to 5.2), P=0.6), or other disorders (3.7 (0.9 to 17.3, P=0.07)). Side effects were limited. No manic or psychotic symptom was seen. Moreover, a mediating effect of mental pain was found. At week 6, remission in the ketamine arm remained high, although non-significantly versus placebo (69.5%v56.3%; odds ratio 0.8 (95% confidence interval 0.3 to 2.5), P=0.7).

Conclusions

The findings indicate that ketamine is rapid, safe in the short term, and has persistent benefits for acute care in suicidal patients. Comorbid mental disorders appear to be important moderators. An analgesic effect on mental pain might explain the anti-suicidal effects of ketamine.

Trial registration

ClinicalTrials.govNCT02299440.
Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study
Authors: Ben Hassen Céline , Fayosse Aurore , Landré Benjamin , Raggi Martina , Bloomberg Mikaela , Sabia Séverine , Singh-Manoux Archana
Published: February 2022

Objective

To examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia.

Design

Prospective cohort study.

Setting

Civil service departments in London (Whitehall II study, study inception in 1985-88).

Participants

10 095 participants, aged 35 to 55 at baseline.

Main outcome measure

Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death.

Results

The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18).

Conclusion

Multimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.
EPOS trial: the effect of air filtration through a plasma chamber on the incidence of surgical site infection in orthopaedic surgery: a study protocol of a randomised, double-blind, placebo-controlled trial
Authors: Persson Anders , Atroshi Isam , Tyszkiewicz Thomas , Hailer Nils , Lazarinis Stergios , Eisler Thomas , Brismar Harald , Mukka Sebastian , Kernell Per-Juan , Mohaddes Maziar , Sköldenberg Olof , Gordon Max
Published: February 2022

Introduction

There is controversy regarding the importance of air-transmitted infections for surgical site infections (SSIs) after orthopaedic surgery. Research has been hindered by both the inability in blinding the exposure, and by the need for recruiting large enough cohorts. The aim of this study is to investigate whether using a new form of air purifier using plasma air purification (PAP) in operating rooms (ORs) lowers the SSI rate or not.

Methods and analysis

Multicentre, double-blind, cluster-randomised, placebo-controlled trial conducted at seven hospitals in 2017–2022. All patients that undergo orthopaedic surgery for minimum 30 min are included. Intervention group: patients operated in OR with PAP devices turned on. Control group: patients operated in OR with PAP devices turned off. Randomisation: each OR will be randomised in periods of 4 weeks, 6 weeks or 8 weeks to either have the devices on or off. Primary outcome: any SSI postoperatively defined as a composite endpoint of any of the following: use of isoxazolylpenicillin, clindamycin or rifampicin for 2 days or more, International Classification of Diseases codes or Nordic Medico-Statistical Committee codes indicating postoperative infection. In a second step, we will perform a chart review on those patients with positive indicators of SSI to further validate the outcome. Secondary outcomes are described in the Methods section. Power: we assume an SSI rate of 2%, an SSI reduction rate of 25% and we need approximately 45 000 patients to attain a power of 80% at a significance level of 0.05.

Ethics and dissemination

The study is approved by the Swedish Ethical Review Authority. The interim analysis results from the study will be presented only to the researchers involved unless the study thereafter is interrupted for whatever reason. Publication in a medical journal will be presented after inclusion of the last patient.

Trial registration number

NCT02695368.
Study protocol of the ACCESS trial: a randomised trial to evaluate the effectiveness of human papillomavirus testing by self-sampling in cervical cancer screening uptake and precancer detection
Authors: Fujita Misuzu , Shimazu Minobu , Nagashima Kengo , Suzuki Misae , Tauchi Ichiro , Sakuma Miwa , Yamamoto Setsuko , Shozu Makio , Hanaoka Hideki , Tsuruoka Nobuhide , Kasai Tokuzo , Hata Akira
Published: February 2022

Introduction

Recently, the incidence of cervical cancer has increased in Japan, probably because of an interruption in human papillomavirus (HPV) vaccination and a low cervical cancer screening rate. There is a lack of evidence for self-sampling HPV testing as a cervical cancer screening tool in Japan. The Accelerating Cervical Cancer Elimination by Self-Sampling test trial aims to compare the effectiveness of screening using the self-sampling HPV test with that of routine screening concerning screening uptake and precancer detection.

Methods and analysis

This trial has a single-municipality, open-label, parallel, superiority and randomised design. Approximately 20 000 women who have not undergone cervical cancer screening for at least 3 years will be assigned randomly to the self-sampling arm and the control arm using a 1:1 ratio. Participants assigned to the control arm will undergo routine cervical cancer screening (cytology test) provided by Ichihara City, while those assigned to the self-sampling arm will choose the routine screening or self-sampling HPV test. HPV tests will be performed using the cobas 8800 system (Roche Diagnostics, Rotkreuz, Switzerland). Participants who will undergo the self-sampling HPV testing will be recommended to undergo routine screening. The results of the cytology test and further tests, such as colposcopy and biopsy, will be collected and used for this trial. The risk ratio and risk difference in the proportion of participants with cervical intraepithelial neoplasia two or worse between the two arms will be calculated. The test for the null hypothesis (the detection rates are equal between the two arms) will be performed using Pearson’s χ2 test.

Ethics and dissemination

This trial was approved by the Research Ethics Committees of the Chiba Foundation for Health Promotion and Disease Prevention and the collaborating research institutes. The results will be disseminated through peer-reviewed journals and conference presentations.

Trial registration number

jRCT1030200276. Pre-results.
Factors associated with recruitment success in the phase 2a study of aztreonam–avibactam development programme: a descriptive qualitative analysis among sites in Spain
Authors: Jimenez-Rodriguez Rosa M , Martín-Gutiérrez Guillermo , Jiménez-Jorge Silvia , Rosso-Fernández Clara M , Tallón-Aguilar Luis , Roca-Oporto Cristina , Padillo Javier , Luckey Alison , Cano Angela , López-Ruiz José , Gómez-Zorrilla Silvia , Bonnín-Pascual Jaime , Boix-Palop Lucía , Montejo José Miguel , Torre-Cisneros Julian , Cisneros José Miguel
Published: February 2022

Objective

Successful clinical trials are subject to recruitment. Recently, the REJUVENATE trial, a prospective phase 2a open-label, single-arm interventional clinical trial conducted within the Innovative Medicines Initiative-supported Combatting Bacterial Resistance in Europe-Carbapenem Resistance project, was published, with 85% of the recruitment performed in Spain. We analysed the recruitment success in this trial by establishing a model of recruitment practice.

Methods

A descriptive qualitative study was performed from May 2016 to October 2017 at 10 participating Spanish centres. Data were extracted from: (1) feasibility questionnaires to assess the centre’s potential for patient enrolment; (2) delegation of responsibility records; (3) pre-screening records including an anonymised list of potentially eligible and (4) screening and enrolment records. A descriptive analysis of the features was performed by the participating centre. Pearson’s and Spearman’s correlation coefficients were calculated to determine factors of recruitment success.

Results

The highest recruitment rate was observed in Hospitals 3 and 6 (58.8 and 47.0 patients per month, respectively). All the study teams were multidisciplinary with a median of 15 members (range: 7–22). Only Hospitals 3, 5 and 6 had dedicated nursing staff appointed exclusively to this study. Moreover, in those three hospitals and in Hospital 9, the study coordinator performed exclusive functions as a research planner, and did not assume these functions for the other hospitals. The univariate analysis showed a significant association between recruitment success and months of recruitment (p=0.024), number of staff (p<0.001), higher number of pharmacists (p=0.005), infectious disease specialists (p<0.001), the presence of microbiologist in the research team (p=0.018) and specifically dedicated nursing staff (p=0.036).

Conclusions

The existence of broad multidisciplinary teams with staff dedicated exclusively to the study as well as the implementation of a well-designed local patient assessment strategy were the essential optimisation factors for recruitment success in Spain.

Trial registration number

NCT02655419; EudraCT 2015-002726-39; analysis of pre-screened patients.
Causes of death and characteristics of non-survivors rescued during recreational mountain activities in Japan between 2011 and 2015: a retrospective analysis
Authors: Oshiro Kazue , Murakami Tomikazu
Published: February 2022

Objectives

This study aimed to describe the cause of death and characteristics at the prehospital setting associated with care and rescue processes of non-survivors rescued in the mountain of Japan.

Design

Retrospective analysis.

Setting

Prehospital setting of mountain searches and rescues in Japan. A total of 10 prefectural police headquarters with >10 cases of mountain death from 2011 to 2015.

Participants

Data were generated from the existing records. Of the total 6159 rescued subjects, 548 mountain deaths were caused by recreational activities.

Results

Among the 548 mountain deaths, 83% were men, and major causes of death were trauma (49.1%), hypothermia (14.8%), cardiac death (13.1%) and avalanche-related death (6.6%). The alive rate at rescue team arrival in all non-survivors was 3.5%, with 1, 4 and 14 cases of cardiac, hypothermia and trauma, respectively. Cardiac deaths occurred in 93.1% (67/72) of men and individuals aged >41 years, and 88.7% (63/71) were found on mountain trails. In hypothermia, callouts were made between 17:00 and 6:00 at 49% (40/81) and by persons not on-site in 59.7% (46/77). People with >6 hours in trauma or >1 hour in cardiac death already died on rescue team arrival, but some with hypothermia after 6 hours were alive.

Conclusion

This study is one of the first large-scale retrospective analyses of prehospital non-survivors in mountain emergencies. The alive rate at rescue arrival in all mountain deaths was only 3.5%. These data showed that the circumstances related to onset and the process until the rescue team arrives have different characteristics, depending on the cause of death. Survival may be enhanced by targeting better use of the time before rescue team arrival and by providing further education, particularly mountain rescue-related medical problems to rescuers including bystanders.
Subjective experiences of the first response to mental health crises in the community: a qualitative systematic review
Authors: Xanthopoulou Penny , Thomas Ciara , Dooley Jemima
Published: February 2022

Objective

To review and synthesise qualitative studies that have explored subjective experiences of people with lived experience of mental health-related illness/crisis (MHC), their families and first responders.

Design

A systematic review of qualitative evidence was conducted. English-language articles exploring the content of interactions and participants’ experiences were included.

Data sources

MEDLINE, PsycINFO, EMBASE, CINAHL; Google Scholar, SAGE journals, Science Direct and PubMed.

Data extraction and synthesis

Two reviewers read and systematically extracted data from the included papers. Papers were appraised for methodological rigour using the Critical Appraisal Skills Programme Qualitative Checklist. Data were thematically analysed.

Results

We identified 3483 unique records, 404 full-texts were assessed against the inclusion criteria and 79 studies were included in the qualitative synthesis. First responders (FRs) identified in studies were police and ambulance staff. Main factors influencing response are persistent stigmatised attitudes among FRs, arbitrary training and the triadic interactions between FRs, people with mental illness and third parties present at the crisis. In addition, FR personal experience of mental illness and focused training can help create a more empathetic response, however lack of resources in mental health services continues to be a barrier where ‘frequent attenders’ are repeatedly let down by mental health services.

Conclusion

Lack of resources in mental healthcare and rise in mental illness suggest that FR response to MHC is inevitable. Inconsistent training, complexity of procedures and persistent stigmatisation make this a very challenging task. Improving communication with family carers and colleagues could make a difference. Broader issues of legitimacy and procedural barriers should be considered in order to reduce criminalisation and ensure an empathetic response.
Older adults with pre-existing noncommunicable conditions and their healthcare access amid COVID-19 pandemic: a cross-sectional study in eastern Nepal
Authors: Ghimire Saruna , Shrestha Aman , Yadav Uday Narayan , Mistry Sabuj Kanti , Chapadia Bunsi , Yadav Om Prakash , Ali ARM Mehrab , Rawal Lal B , Yadav Priyanka , Mehata Suresh , Harris Mark
Published: February 2022

Background

COVID-19 has greatly impacted older adults with pre-existing noncommunicable conditions (hereafter called pre-existing conditions) in terms of their access to essential healthcare services. Based on the theory of vertical health equity, this study investigated access to healthcare by Nepali older adults with pre-existing conditions during the COVID-19 pandemic.

Methods

A cross-sectional study surveyed 847 randomly selected older adults (≥60 years) in three districts of eastern Nepal. Survey questionnaires, administered by trained community health workers, collected information on participants reported difficulty obtaining routine care and medications during the pandemic, in addition to questions on demographics, socioeconomic factors and pre-existing conditions. Cumulative scores for pre-existing conditions were recoded as no pre-existing condition, single condition and multimorbidity for the analyses. χ2 tests and binary logistic regressions determined inferences.

Results

Nearly two-thirds of the participants had a pre-existing condition (43.8% single condition and 22.8% multimorbid) and reported experiencing difficulty obtaining routine care (52.8%) and medications (13.5%). Participants with single (OR 3.06, 95% CI 2.17 to 4.32) and multimorbid (OR 5.62, 95% CI 3.63 to 8.71) conditions had threefold and fivefold increased odds of experiencing difficulty accessing routine care. Findings were similar for difficulty obtaining medication (OR single: 3.12, 95% CI 1.71 to 5.69; OR multimorbid: 3.98, 95% CI 2.01 to 7.87) where odds were greater than threefolds.

Conclusions

Older adults with pre-existing conditions in Nepal, who require routine medical care and medication, faced significant difficulties obtaining them during the pandemic, which may lead to deterioration in their pre-existing conditions. Public health emergency preparedness should incorporate plans for both managing the emergency and providing continuing care.
Type 2 diabetes in Scottish military veterans: a retrospective cohort study
Authors: Bergman Beverly P , Mackay Daniel , Pell J P
Published: February 2022

Objectives

Type 2 diabetes is an important public health problem but the risk in UK military veterans is unknown. We used data from the Trends in Scottish Veterans' Health study to investigate the risk in comparison with people with no record of service.

Design

Retrospective cohort study of a large national sample in Scotland, with up to 37 years follow-up.

Setting

Pseudoanonymised extract of computerised Scottish National Health Service records, including a disease register and national vital records.

Participants

78 000 veterans and 253 000 people with no record of service matched for age, sex and area of residence.

Outcome measures

Cox proportional HRs for first record of type 2 diabetes in veterans compared with non-veterans, overall and by sex and birth cohort. Long-term trend, comorbidity with specific mental health outcomes and risk of limb loss.

Results

Overall, 7.2% of veterans were diagnosed with type 2 diabetes, and were at slightly increased risk compared with non-veterans, Cox proportional HR 1.08, 95%CIs 1.04 to 1.11, p<0.001. The increased risk was confined to men, and to veterans born prior to 1960. There has been no change in HR over the last 25 years. Among veterans with post-traumatic stress disorder (PTSD), 12.1% had been diagnosed with type 2 diabetes, compared with 9.4% of non-veterans with PTSD. The difference was statistically significant, OR 1.29, 95% CI 1.04 to 1.59, p=0.021. Risk of limb loss was increased among the oldest veterans.

Conclusions

Older veterans in Scotland have an increased risk of type 2 diabetes in comparison with non-veterans, but there is no difference in respect of younger veterans, and the pattern of risk shows no evidence that it is changing. There is a positive association between type 2 diabetes and PTSD, especially in the presence of comorbid mood disorder, an important finding which should be noted by care providers.
Development of machine learning prediction models to explore nutrients predictive of cardiovascular disease using Canadian linked population-based data
Authors: Morgenstern Jason D. , Rosella Laura C. , Costa Andrew P. , Anderson Laura N.
Published: February 2022

Machine learning may improve use of observational data to understand the nutritional epidemiology of cardiovascular disease (CVD) through better modelling of non-linearity, non-additivity, and dietary complexity. Our objective was to develop machine learning prediction models for exploring how nutrients are related to CVD risk and to evaluate their predictive performance. We established a population-based cohort from the Canadian Community Health Survey and measured CVD incidence and mortality from 2004 to 2018 using administrative databases of national hospital discharges and deaths. Predictors included 61 nutrition variables and fourteen socioeconomic, demographic, psychological, and behavioural variables. Conditional inference forest models were interpreted and evaluated by permutation feature importance, accumulated local effects, and predictive discrimination and calibration. A total of 12 130 individuals were included in the study. Use of supplements, caffeine, and alcohol were the most important nutrition variables for prediction of CVD. Supplement use was associated with decreased risk, caffeine was associated with increasing risk, and alcohol had a u-shaped association with risk. The model had an out-of-sample c-statistic of 0.821 (95% confidence interval = 0.801–0.842). Exploratory findings included both known and novel associations and predictive performance was competitive, suggesting that further application of machine learning to nutritional epidemiology may help elucidate risks and improve predictive models.

Novelty: Machine learning prediction models were developed for CVD using dietary data. Models were interpreted with interpretable machine learning techniques, revealing diverse associations between diet and CVD. Models achieved comparable or superior predictive performance to existing CVD risk prediction models.
Responsive feeding values and practices among families across the Canadian Maritime provinces
Authors: Rossiter Melissa D. , Richard Brenna , Whitfield Kyly C. , Mann Linda , McIsaac Jessie-Lee D.
Published: February 2022

Children benefit from responsive feeding practices where their internal signals of hunger and satiety are valued and met with prompt, emotionally supportive, and developmentally appropriate responses. Using an online survey, this study describes responsive feeding values and practices among parents of young children (0–5 years) (n = 1039) across 3 Canadian Maritime provinces. Independent-samples t-tests and 1-way ANOVA were performed to determine the differences in survey questions related to the responsive feeding practices and values. First-time parents and parents with younger children report implementing more consistently some of the challenging responsive feeding practices, such as avoiding pressuring their children to eat, compared with parents with multiple children and parents with children ages 3–5 years. Parents often have well-intended reasons to encourage their children to eat; however, these can coincide with non-responsive practices with food such as pressuring, rewarding, and restriction. These coercive practices may be ineffective and counterproductive as they reinforce reasons to eat unrelated to appetite and self-regulation. Preschool and early feeding interventions that support parents in understanding normal child development, including typical eating behaviours and self-regulation, could help to equip them for challenging feeding experiences and encourage long-term responsive feeding practices.

Novelty: First-time parents and parents with younger children report more consistently avoiding pressuring their children to eat, compared with parents with multiple children and parents with children ages 3–5 years. Parents often have well-intended reasons to encourage their children to eat; however, these can coincide with non-responsive practices such as pressuring, rewarding, and restriction.
Teaching phronesis in a research integrity course
Authors: Goddiksen Mads Paludan , Gjerris Mickey
Published: February 2022

More and more research institutions are implementing courses in research integrity (RI). Recent studies indicate that teachers of RI courses are increasingly adopting a “phronetic” approach to their teaching, where the focus is on nurturing values and practical wisdom—what Aristotle called phronesis. When adopting a phronetic approach, it is important to understand what phronesis in relation to RI entails and how and to what extent an RI course can contribute to the development of research phronesis. This paper contains a practice-based discussion of the realistic aims of RI courses and a first step towards a specification of the skill set necessary for developing research phronesis drawing on experiences from the PhD courses on Responsible Conduct of Research at the University of Copenhagen. We discuss the limited extent to which research phronesis can be taught in short courses and examine the broader implications of this for the role of RI courses in the training of good researchers.
Gauge invariance and localization of vector Kaluza–Klein modes
Authors: Fu Chun-E. , Zhao Zhen-hua , Sun Ming-Hui
Published: February 2022

We investigate the gauge invariance and localization of vector KK modes for a bulk U(1) gauge field under three kinds of localization mechanism on a brane with one extra dimension. By a general KK decomposition for the bulk U(1) gauge field, there are both vector and scalar KK modes on the brane, which couple with each other. We demonstrate that for a localization mechanism with a gauge invariant bulk action of the U(1) gauge field, the effective action of the KK modes on the brane can be formalized to gauge invariant form. However, only the massive vector KK modes and their accompanying scalar ones can be both localized on the brane, which depends on the solution of the brane, the gauge invariance of the massive vector field is finally preserved. For a localization mechanism with a broken gauge invariant bulk action of the field, it is impossible to rebuild the gauge invariance on the brane.
OSIRIS: a new code for ray tracing around compact objects
Authors: Velásquez-Cadavid J. M. , Arrieta-Villamizar J. A. , Lora-Clavijo F. D. , Pimentel O. M. , Osorio-Vargas J. E.
Published: February 2022

The radiation observed in quasars and active galactic nuclei is mainly produced by a relativistic plasma orbiting close to the black hole event horizon, where strong gravitational effects are relevant. The observational data of such systems can be compared with theoretical models to infer the black hole and plasma properties. In the comparison process, ray-tracing algorithms are essential to computing the trajectories followed by the photons from the source to our telescopes. In this paper, we present : a new stable FORTRAN code capable of efficiently computing null-geodesics around compact objects, including general relativistic effects such as gravitational lensing, redshift, and relativistic boosting. The algorithm is based on the Hamiltonian formulation and uses different integration schemes to evolve null-geodesics while tracking the error in the Hamiltonian constrain to ensure physical results. We found from an error analysis that the integration schemes are all stable, and the best one maintains an error below $$10^{-11}$$

10

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. Particularly, to test the robustness and ability of the code to evolve geodesics in curved space-time, we compute the shadow and Einstein rings of a Kerr black hole with different rotation parameters and obtain the image of a thin Keplerian accretion disk around a Schwarzschild black hole. Although is parallelized neither with MPI nor with CUDA, the computation times are of the same order as those reported by other codes with these types of parallel computing platforms.