bluuebunny/crossref_metadata_2025 huggingface dataset:
Using hybrid consistent fuzzy preference relations–importance‐performance analysis model to improve shared decision‐making quality based on orthopaedic nurses' perceptions
Authors: Chuang Yen‐Ching , Zhu Zhong , Jin Yanjun , Chien Ching‐Wen , Tung Tao‐Hsin
Published: July 2022

Purpose

To understand key factors for shared decision‐making (SDM) and the quality improvement of nursing decisions in the orthopaedic clinical environment.

Method

This study applied the consistent consistent fuzzy preference relations (CFPRs) and importance‐performance analysis (IPA) methods to explore the attribute weights and SDM performance, respectively. The dataset was collected from 16 orthopaedic clinical nurses' experiences in a third‐grade and first‐level general hospital in Taizhou, China. This study was performed according to the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) guidelines.

Results

The results showed that “I made clear to my patient or patient's family that a nursing care decision needs to be made”, “I explained the advantages and disadvantages of the nursing care options to my patient or patient's family” and “I told my patient or patient's family that there are different nursing care options for caring his/her medical condition” were key factors for affecting SDM. The statistical significance confidence and difference error of weight results were 98.321% and 1.679%, respectively. In addition, “I asked my patient or patient's family which nursing care option he/she prefers” was the key factor for improving orthopaedic clinical nursing in the case hospital.

Conclusion

The hybrid CFPRs‐IPA model can help hospital managers effectively understand the key factors of SDM quality and improve the orthopaedic clinical nursing performance from nurses' perspectives.

Relevance to Clinical Practice

A quantitative decision‐making model can help nurses understand the key factors affecting the quality of SDM in nursing decision‐making and promote nursing decision‐making and patient‐centred nursing service quality. A series of corresponding SDM training courses (i.e. concepts, knowledge and skills) can be provided for hospital and nursing department managers to maximise the potentially available resources.

Patient or Public Contribution

The clinical care process should be committed to involving patients in their care decisions and also provide an opportunity for patients to gain a comprehensive understanding of the care decision‐making process in order to inform future patient contributions to care decisions.
Treatment of intracranial neoplasia in dogs using higher doses: A randomized controlled trial comparing a boosted to a conventional radiation protocol
Authors: Staudinger Chris , Meier Valeria , Beckmann Katrin , Körner Maximilian , Rohrer Bley Carla
Published: July 2022

Background

Local progression of intracranial tumors can be the consequence of insufficient radiation dose delivered. Dose increases in the brain must be made carefully so as not to risk debilitating adverse effects such as radiation necrosis.

Hypothesis

A new protocol with 10 × 4 Gy + 11% physical dose increase limited to the macroscopic tumor volume results in a clinically better outcome compared to a 10 × 4 Gy protocol.

Animals

Fifty‐seven client‐owned dogs with primary intracranial neoplasia.

Methods

Randomized controlled trial. Twenty‐eight dogs were assigned to the control protocol (10 × 4 Gy) and 29 to the simultaneous integrated boost (SIB) protocol with 4.45 Gy dose increase. Treatment groups were compared for outcome and signs of toxicity.

Results

Mild, transient acute or early‐delayed adverse radiation effects were observed in 5 dogs. Severe late adverse effects were not seen. Between the protocols, no significant differences were found for outcome (intention‐to‐treat analysis): overall time to progression (TTP) was 708 days (95% confidence interval (95% CI) [545,872]), in the control group it was 828 days (95% CI [401,1256]), and in the SIB group 627 days (95% CI [282,973]; P = .07). Median overall survival (OS) was 684 days (95% CI [516,853]), in the control group it was 724 days (95% CI [623,826]), and in the SIB group 557 days (95% CI [95,1020]; P = .47). None of the tested variables was prognostic in terms of outcome.

Conclusion and Clinical Importance

The dose escalation used with an 11% physical dose increase did not result in better outcome.
Applications of molecular barcode sequencing for the detection of low‐frequency variants in circulating tumour DNA from hepatocellular carcinoma
Authors: Lee Hye Won , Kim Esl , Cho Kyung Joo , Park Hye Jung , Seo Jieun , Lee Hyeonah , Baek Eunha , Choi Jong Rak , Han Kwang‐Hyub , Lee Seung‐Tae , Park Jun Yong
Published: July 2022

Purpose

Liquid biopsy has emerged as a promising tool for minimally invasive and accurate detection of various malignancies. We aimed to apply molecular barcode sequencing to circulating tumour DNA (ctDNA) from liquid biopsies of hepatocellular carcinoma (HCC).

Study Design

Patients with HCC or benign liver disease were enrolled between 2017 and 2018. Matched tissue and serum samples were obtained from these patients. Plasma cell‐free DNA was extracted and subjected to targeted sequencing with ultra‐high coverage and molecular barcoding.

Results

The study included 143 patients: 102 with HCC, 7 with benign liver tumours and 34 with chronic liver disease. No tier 1/2 or oncogenic mutations were detected in patients with benign liver disease. Among the HCC patients, 49 (48%) had tier 1/2 mutations in at least one gene; detection rates were higher in advanced stages (75%) than in early stages (26%–33%). TERT was the most frequently mutated gene (30%), followed by TP53 (16%), CTNNB1 (14%), ARID2 (5%), ARID1A (4%), NFE2L2 (4%), AXIN1 (3%) and KRAS (1%). Survival among patients with TP53 mutations was significantly worse (p = 0.007) than among patients without these mutations, whereas CTNNB1 and TERT mutations did not affect survival. ctDNA testing combined with α‐fetoprotein and prothrombin induced by vitamin K absence‐II analyses improved HCC detection, even in early stages.

Conclusions

ctDNA detection using molecular barcoding technology offers dynamic and personalized information concerning tumour biology, such information can guide clinical diagnosis and management. This detection also has the potential as a minimally invasive approach for prognostic stratification and post‐therapeutic monitoring.
Threshold concepts in medical education: A scoping review
Authors: Jones Helen , Hammond Lucy
Published: July 2022

Introduction

The threshold concept framework (TCF) was first described nearly 20 years ago, but its application in the field of medical education has recently seen a significant growth of interest with a diverse range of literature published on the subject. The transformative nature of threshold concepts (TCs) offers potential for the design of learning experiences and curricula across the medical education continuum. A scoping review was conducted to map the extent of the current literature regarding TCs in medical education—to describe the types of available evidence and its focus—and identify research gaps.

Methods

The review followed the JBI Manual for Evidence Synthesis approach for scoping reviews. Four databases and two additional websites were searched for articles exploring TCs in medical education. Data were analysed using quantitative and qualitative thematic approaches. A framework of conceptual change was used to synthesise the TCs identified.

Results

Thirty‐six papers, spanning undergraduate, postgraduate and continuing medical education, were included in the final analysis. The most frequent application of the TCF was in the identification of TCs, which related to basic scientific knowledge, ways of thinking and ways of practising in medicine. Uncertainty, patient care, clinical reasoning and professional identify formation were themes that emerged at multiple stages of training. Several papers evaluated the use of the TCF in teaching.

Conclusion

The understanding and embodiment of TCs increases in complexity across the medical education continuum, with TCs recurring with changes in clinical environment and responsibilities. This lends support to a holistic approach to curriculum design spanning all stages of training. Further research is needed to develop a consistent approach for describing and applying the TCF in medical education and to address how the TCF can be used in teaching and how threshold crossing can be measured.
A trilemma for naturalized metaphysics
Authors: Jaksland Rasmus
Published: July 2022

Radical naturalized metaphysics wants to argue (1) that metaphysics without sufficient epistemic warrant should not be pursued, (2) that the traditional methods of metaphysics cannot provide epistemic warrant, (3) that metaphysics using these methods must therefore be discontinued, and (4) that naturalized metaphysics should be pursued instead since (5) such science‐based metaphysics succeeds in establishing justified conclusions about ultimate reality. This paper argues that to defend (5), naturalized metaphysics must rely on methods similar to those criticized in (2). If naturalized metaphysics instead opts for the weaker claim that science‐based metaphysics is only superior to other metaphysics, then this is insufficient to establish (4). In this case, (4) might therefore be defeated by (1). An alternative is to replace (1) with the view that we should just approach metaphysical questions with the best means available. While this would recommend a science‐based approach whenever possible, it would also allow for the continuation of science‐independent metaphysics in domains that science has no bearing on and thus reject (3). The paper concludes that none of these alternatives is entirely satisfactory for naturalized metaphysics.
Sensitization of colonic nociceptors by TNFα is dependent on TNFR1 expression and p38 MAPK activity
Authors: Barker Katie H. , Higham James P. , Pattison Luke A. , Taylor Toni S. , Chessell Iain P. , Welsh Fraser , Smith Ewan St. J. , Bulmer David C.
Published: July 2022

Visceral pain is a leading cause of morbidity in gastrointestinal diseases, which is exacerbated by the gut‐related side‐effects of many analgesics. New treatments are needed and further understanding of the mediators and mechanisms underpinning visceral nociception in disease states is required to facilitate this. The pro‐inflammatory cytokine TNFα is linked to pain in both patients with inflammatory bowel disease and irritable bowel syndrome, and has been shown to sensitize colonic sensory neurons. Somatic, TNFα‐triggered thermal and mechanical hypersensitivity is mediated by TRPV1 signalling and p38 MAPK activity respectively, downstream of TNFR1 receptor activation. We therefore hypothesized that TNFR1‐evoked p38 MAPK activity may also be responsible for TNFα sensitization of colonic afferent responses to the TRPV1 agonist capsaicin, and noxious distension of the bowel. Using Ca2+ imaging of dorsal root ganglion sensory neurons, we observed TNFα‐mediated increases in intracellular [Ca2+] and sensitization of capsaicin responses. The sensitizing effects of TNFα were dependent on TNFR1 expression and attenuated by p38 MAPK inhibition. Consistent with these findings, ex vivo colonic afferent fibre recordings demonstrated an enhanced response to noxious ramp distention of the bowel and bath application of capsaicin following TNFα pre‐treatment. Responses were reversed by p38 MAPK inhibition and absent in tissue from TNFR1 knockout mice. Our findings demonstrate a contribution of TNFR1, p38 MAPK and TRPV1 to TNFα‐induced sensitization of colonic afferents, highlighting the potential utility of these drug targets for the treatment of visceral pain in gastrointestinal disease.

image

Key points

The pro‐inflammatory cytokine TNFα is elevated in gastrointestinal disease and sensitizes colonic afferents via modulation of TRPA1 and NaV1.8 activity. We further develop this understanding by demonstrating a role for p38 MAPK and TRPV1 in TNFα‐mediated colonic afferent sensitization. Specifically, we show that:

TNFα sensitizes sensory neurons and colonic afferents to the TRPV1 agonist capsaicin.

TNFα‐mediated sensitization of sensory neurons and colonic nociceptors is dependent on TNFR1 expression.

TNFα sensitization of sensory neurons and colonic afferents to capsaicin and noxious ramp distension is abolished by inhibition of p38 MAPK.

Collectively these data support the utility of targeting TNFα, TNFR1 and their downstream signalling via p38 MAPK for the treatment of visceral pain in gastrointestinal disease.
Heat Transfer From Spheres to a Rarefied Gas in Subsonic Flow
Authors: Kavanau L. L.
Published: July 2022

Experimental over-all average heat-transfer coefficients for spheres in a subsonic air stream are presented for the slip-flow region in the range of Mach number M, and Reynolds number Re (based on diameter), 0.1 ⩽ M1 ⩽ 0.69 and 1.75 ⩽ Re1 ⩽ 124. A simplified analysis is presented which yields the convective heat-transfer coefficient for a rarefied gas by means of a correction to the continuum coefficient at the same Reynolds number. Comparison of this analysis is made with an existing theory for cylinders. An expression for the nondimensional over-all average heat-transfer coefficient for spheres in a rarefied subsonic flow is given as Nuavg=Nu°avg1+3.42M1Re1PrNu°avg
The Determination of Residual Stresses in Hardened, Ground Steel
Authors: Colwell L. V. , Sinnott M. J. , Tobin J. C.
Published: July 2022

The residual surface stresses induced by grinding a hardened SAE 4340 steel have been investigated by means of x-ray diffraction and by optical interferometric methods. The depth of penetration of the residual stresses increases as the severity of grinding is increased. The higher the hardness level of the steel, the greater is the absolute value of the residual stress. The magnitude of the residual stresses varies from 100,000 psi in tension to 135,000 psi in compression depending on the hardness level of the steel and the severity of grinding. Light grinding produces residual compressive stresses while heavy grinding produces tensile stresses.
Numerical Solutions for Laminar-Flow Heat Transfer in Circular Tubes
Authors: Kays W. M.
Published: July 2022

The existing solutions for laminar-flow heat transfer in a circular tube are generally based on the assumption of a fully established velocity profile at the point in the tube where heating begins. For high Prandtl number fluids, such as the viscous liquids, this idealization does not seriously restrict the usefulness of the solutions because the velocity profile is established much more rapidly than the temperature profile. However, for the Prandtl number range near 1.00, which includes the gas range, the velocity and temperature profiles develop at similar rates along the tube, and the assumption of a fully established velocity profile at the tube entrance can, for many applications, lead to a considerable error in predicted performance. In this paper, numerical solutions are presented for a number of heating conditions for the case of a fluid of NPr = 0.7 with both velocity and temperature uniform at the tube entrance. The solution of Langhaar (1) is employed to provide the velocity profiles which are introduced into the energy equation. Experimental data for laminar air flow in circular tubes are presented for two heating conditions, constant wall temperature and constant heat input per unit of tube length. These data correspond closely to the numerical solutions based on the Langhaar velocity profiles, while differing considerably from solutions based on a parabolic profile throughout the tube. All of the solutions and experimental data are presented in the form of either a local or mean Nusselt number as a function of a modified Graetz number, NRNPr/(x/D).
Analysis of Regulating Systems With Particular Reference to Speed Control
Authors: Macmillan R. H.
Published: July 2022

The design of speed-regulating systems is discussed in relation to that of other closed-loop control systems. Frequency-response methods are found to form a common basis suitable for the analysis of all such systems. The derivation of transfer functions for linear and quasi-linear elements, together with their application to the analysis of regulating systems, is described, and a simplified gas-turbine governor is studied in greater detail. A summary of the latest work likely to be of importance to control engineers is given, together with extensive references, but it is argued that they can make the best use of the work of others in the field only when a common approach is adopted universally. It is therefore concluded that an elementary study of these methods should be included in the training of every engineering graduate.
Closure to “Discussion: Selective-Compliance-Based Lagrange Model and Multilevel Noncollocated Feedback Control of a Humanoid Robot” (Spyrakos-Papastavridis, E., Dai, J. S., Childs, P. R. N., and Tsagarakis, N. G., 2018, ASME J. Mech. Rob., 10(3), p. 031009)
Authors: Spyrakos-Papastavridis Emmanouil , Dai Jian S. , Childs Peter R. N. , Tsagarakis Nikos G.
Published: July 2022

This closure exposes the technical inconsistencies, erroneous comments, and misconceptions contained in the Discussion Article (Medrano-Cerda, 2020, “Discussion: ‘Selective Compliance-Based Lagrange Model and Multilevel Noncollocated Feedback Control of a Humanoid Robot’,” ASME J. Mech. Rob., 10.1115/1.4049005 [1]). The majority of incorrect comments relating to stability are not based on mathematical rigor and equations, but on the reproduction of more generic statements made in some textbooks published in the early 1990s. The comments in the Discussion Article fail to demonstrate how any of these generic statements could be applied to the specific cases presented in the Paper (Spyrakos-Papastavridis et al., 2018, “Selective-Compliance-Based Lagrange Model and Multilevel Noncollocated Feedback Control of a Humanoid Robot,” ASME J. Mech. Rob., 10(3). 10.1115/1.4039394 [2]) criticized by the Discussion Article. Further, the only equation that appears in the Discussion Article is incorrect, as will be demonstrated in this closure. Apart from being expressed incorrectly, the text accompanying this equation reveals the fundamentally incorrect mathematical assumption that a diagonal matrix is not equal to its transpose. Moreover, a significant proportion of the comments in the Discussion Article relies upon misconceptions about flexible-joint robot control and humanoid robotics, in terms of their theory and practice, standing in contrast to results reported in these research fields over the last decades.
Impact of interfacial thickness on Raman intensity profiles and phonon anisotropy in short-period (AlSb)n/(GaSb)m superlattices
Authors: Talwar Devki N.
Published: July 2022

Comprehensive simulations of phonon dispersions ωj(q→SL) and atomic displacements are reported for short-period (AlSb)n/(GaSb)m superlattices (SLs) using a modified linear-chain model. A bond-polarizability methodology is employed for exploring the impact of meticulously included interfacial thickness Δ (≡1–3 monolayers) on the Raman intensity profiles of graded SLs in the optical phonon region. Results of ωj(q→SL) are also presented by exploiting a realistic rigid-ion-model (RIM) and considering short-range, long-range Coulomb interactions and SL symmetry. Besides the anisotropic behavior of optical phonons, the RIM provided evidence of the acoustic-mode anticrossing, minigap formation, confinement, and interface modes. Controlling the vibrational traits by altering a number of monolayers (n, m) in SLs can provide excellent opportunities for improving the electrical and thermal properties of Sb-based materials for engineering various electronic device structures.
Depth-dependent apodization window based on Chebyshev polynomial for ultrasound imaging
Authors: Wang Ping , Liang Jiaqi , Li Xitao
Published: July 2022

To improve the image resolution of a portable real-time ultrasound imaging device, this paper proposes a beamformer with composite apodization windows based on Chebyshev polynomial. By introducing the Chebyshev window, the level of sidelobe can be flexibly controlled. The value of weighting changes according to the detection depth and ultrasound attenuation such that it can attain better image resolution than traditional beamformers. The simulations and experiments indicate that the proposed method can flexibly narrow the mainlobe width while keeping the performance of the suppressing artifacts. The full width at half-maximum of this method is 14.1%–27.8% and 4.2%–25.0% narrower than those of traditional apodization methods in the field II simulations and Geabr_0 experiment, respectively.
Speech recognition as a function of the number of channels for Mid-Scala electrode array recipients
Authors: Berg Katelyn A. , Noble Jack H. , Dawant Benoit M. , Dwyer Robert T. , Labadie Robert F. , Gifford René H.
Published: July 2022

This study investigated the number of channels needed for maximum speech understanding and sound quality in 15 adult cochlear implant (CI) recipients with Advanced Bionics (AB) Mid-Scala electrode arrays completely within scala tympani. In experiment I, CI programs used a continuous interleaved sampling (CIS)-based strategy and 4–16 active electrodes. In experiment II, CI programs used an n-of-m strategy featuring 16 active electrodes with either 8- or 12-maxima. Speech understanding and sound quality measures were assessed. For CIS programs, participants demonstrated performance gains using up to 4–10 electrodes on speech measures and sound quality ratings. For n-of-m programs, there was no significant effect of maxima, suggesting 8-maxima is sufficient for this sample's maximum performance and sound quality. These results are largely consistent with previous studies using straight electrode arrays [e.g., Fishman, Shannon, and Slattery (1997). J. Speech Lang. Hear. Res. 40, 1201–1215; Friesen, Shannon, Baskent, and Wang (2001). J. Acoust. Soc. Am. 110, 1150–1163; Shannon, Cruz, and Galvin (2011). Audiol. Neurotol. 16, 113–123; Berg, Noble, Dawant, Dwyer, Labadie, and Gifford (2020). J. Acoust. Soc. Am. 147, 3646–3656] and in contrast with recent studies looking at cochlear precurved electrode arrays [e.g., Croghan, Duran, and Smith (2017). J. Acoust. Soc. Am. 142, EL537–EL543; Berg, Noble, Dawant, Dwuer, Labadie, and Gifford (2019b). J. Acoust. Soc. Am. 145, 1556-1564], which found continuous improvements up to 16 independent channels. These findings suggest that Mid-Scala electrode array recipients demonstrate similar channel independence to straight electrode arrays rather than other manufacturer's precurved electrode arrays.
Semi-empirical wall pressure spectral modeling for zero and favorable pressure gradient flows
Authors: Thomson Nicholas , Rocha Joana
Published: July 2022

Semi-empirical models are used to predict the power spectral density of wall pressure fluctuations in the turbulent boundary layer. Current advancements in power spectral density wall pressure fluctuation prediction have focused on expanding the range of experiments that can be predicted to include adverse pressure gradient flows; however, favorable pressure gradient flows have not received much attention. An experiment was performed to capture the effects of the favorable pressure gradient on the power spectral density. A model was then created to improve upon some of the limitations of existing models. The proposed model improves upon the prediction of the high-frequency roll-off location, incorporates improvements made by past models, and captures the effects of favorable pressure gradients.
Cas9/Nickase-induced allelic conversion by homologous chromosome-templated repair in
Drosophila
somatic cells
Authors: Roy Sitara , Juste Sara Sanz , Sneider Marketta , Auradkar Ankush , Klanseck Carissa , Li Zhiqian , Julio Alison Henrique Ferreira , del Amo Victor Lopez , Bier Ethan , Guichard Annabel
Published: July 2022

Repair of double-strand breaks (DSBs) in somatic cells is primarily accomplished by error-prone nonhomologous end joining and less frequently by precise homology-directed repair preferentially using the sister chromatid as a template. Here, a
Drosophila
system performs efficient somatic repair of both DSBs and single-strand breaks (SSBs) using intact sequences from the homologous chromosome in a process we refer to as homologous chromosome-templated repair (HTR). Unexpectedly, HTR-mediated allelic conversion at the
white
locus was more efficient (40 to 65%) in response to SSBs induced by Cas9-derived nickases D10A or H840A than to DSBs induced by fully active Cas9 (20 to 30%). Repair phenotypes elicited by Nickase versus Cas9 differ in both developmental timing (late versus early stages, respectively) and the production of undesired mutagenic events (rare versus frequent). Nickase-mediated HTR represents an efficient and unanticipated mechanism for allelic correction, with far-reaching potential applications in the field of gene editing.
A systematic review of newborn health interventions in humanitarian settings
Authors: Rodo Mariana , Duclos Diane , DeJong Jocelyn , Akik Chaza , Singh Neha S
Published: July 2022

Background

Almost half of the under-5 deaths occur in the neonatal period and most can be prevented with quality newborn care. The already vulnerable state of newborns is exacerbated in humanitarian settings. This review aims to assess the current evidence of the interventions being provided in these contexts, identify strategies that increase their utilisation and their effects on health outcomes in order to inform involved actors in the field and to guide future research.

Methods

Searched for peer-reviewed and grey literature in four databases and in relevant websites, for published studies between 1990 and 15 November 2021. Search terms were related to newborns, humanitarian settings, low-income and middle-income countries and newborn health interventions. Quality assessment using critical appraisal tools appropriate to the study design was conducted. Data were extracted and analysed using a narrative synthesis approach.

Results

A total of 35 articles were included in this review, 33 peer-reviewed and 2 grey literature publications. The essential newborn care (ENC) interventions reported varied across the studies and only three used the Newborn Health in Humanitarian Settings: Field Guide as a guideline document. The ENC interventions most commonly reported were thermal care and feeding support whereas delaying of cord clamping and administration of vitamin K were the least. Training of healthcare workers was the most frequent strategy reported to increase utilisation. Community interventions, financial incentives and the provision of supplies and equipment were also reported.

Conclusion

There is insufficient evidence documenting the reality of newborn care in humanitarian settings in low-income and middle-income countries. There is a need to improve the reporting of these interventions, including when there are gaps in service provision. More evidence is needed on the strategies used to increase their utilisation and the effect on health outcomes.

PROSPERO registration number

CRD42020199639.
Application of a data-driven XGBoost model for the prediction of COVID-19 in the USA: a time-series study
Authors: Fang Zheng-gang , Yang Shu-qin , Lv Cai-xia , An Shu-yi , Wu Wei
Published: July 2022

Objective

The COVID-19 outbreak was first reported in Wuhan, China, and has been acknowledged as a pandemic due to its rapid spread worldwide. Predicting the trend of COVID-19 is of great significance for its prevention. A comparison between the autoregressive integrated moving average (ARIMA) model and the eXtreme Gradient Boosting (XGBoost) model was conducted to determine which was more accurate for anticipating the occurrence of COVID-19 in the USA.

Design

Time-series study.

Setting

The USA was the setting for this study.

Main outcome measures

Three accuracy metrics, mean absolute error (MAE), root mean square error (RMSE) and mean absolute percentage error (MAPE), were applied to evaluate the performance of the two models.

Results

In our study, for the training set and the validation set, the MAE, RMSE and MAPE of the XGBoost model were less than those of the ARIMA model.

Conclusions

The XGBoost model can help improve prediction of COVID-19 cases in the USA over the ARIMA model.
Differences in emergency nurse triage between a simulated setting and the real world, post hoc analysis of a cluster randomised trial
Authors: Morreel Stefan , Verhoeven Veronique , Philips Hilde , Meysman Jasmine , Homburg Ines , De Graeve Diana , Monsieurs KG
Published: July 2022

Objectives

In the TRIAGE trial, a cluster randomised trial about diverting emergency department (ED) patients to a general practice cooperative (GPC) using a new extension to the Manchester Triage System, the difference in the proportion of patients assigned to the GPC was striking: 13.3% in the intervention group (patients were encouraged to comply to an ED or GPC assignment, real-world setting) and 24.7% in the control group (the assignment was not communicated, all remained at the ED, simulated setting). In this secondary analysis, we assess the differences in the use of the triage tool between intervention and control group and differences in costs and hospitalisations for patients assigned to the GPC.

Setting

ED of a general hospital and the adjacent GPC.

Participants

8038 patients (6294 intervention and 1744 control).

Primary and secondary outcome measures proportion of patients with triage parameters (reason for encounter, discriminator and urgency category) leading to an assignment to the ED, proportion of patients for which the computer-generated GPC assignment was overruled, motivations for choosing certain parameters, costs (invoices) and hospitalisations.

Results

An additional 3.1% (p<0.01) of the patients in the intervention group were classified as urgent. Discriminators leading to the ED were registered for an additional 16.2% (p<0.01), mainly because of a perceived need for imaging. Nurses equally chose flow charts leading to the ED (p=0.41) and equally overruled the protocol (p=0.91). In the intervention group, the mean cost for patients assigned to the GPC was €23 (p<0.01) lower and less patients with an assignment to the GPC were hospitalised (1.0% vs 1.6%, p<0.01).

Conclusion

Nurses used a triage tool more risk averse when it was used to divert patients to primary care as compared with a theoretical assignment to primary care. Outcomes from a simulated setting should not be extrapolated to real patients.

Trial registration number

NCT03793972.
Identifying the top research priorities in medically not yet explained symptoms (MNYES): a James Lind Alliance priority setting partnership
Authors: van der Feltz-Cornelis Christina Maria , Sweetman Jennifer , Edwards Mark , Gall Nicholas , Gilligan Jennifer , Hayle Stephanie , Kaul Arvind , Moriarty Andrew Stephen , Perros Petros , Sampford James , Smith Natalie , Elfeddali Iman , Varley Danielle , Gower Jonathan
Published: July 2022

Objectives

This study establishes research priorities for medically not yet explained symptoms (MNYES), also known as persistent physical symptoms or medically unexplained symptoms, from the perspective of patients, caregivers and clinicians, in a priority setting partnership (PSP) following the James Lind Alliance (JLA) approach. Research into such symptoms in general has been poorly funded over the years and so far has been primarily researcher-led with minimal input from patients, caregivers and clinicians; and sometimes has been controversial.

Design

JLA PSP method. The PSP termed these symptoms MNYES.

Methods

The study was conducted according to the JLA’s detailed methodology for conducting priority setting exercises. It involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology.

Results

Over 700 responses from UK patients, caregivers and clinicians were identified in the two surveys and charities contributed from a broad range of medical specialties and primary care. The final top 10 unanswered research questions cover, among others: treatment strategies, personalisation of treatment, collaborative care pathways, training for clinicians and outcomes that matter to patients.

Interpretation

The top 10 unanswered research questions are expected to generate much needed, relevant and impactful research into MNYES.
Effectiveness of the Med Safety mobile application in improving adverse drug reaction reporting by healthcare professionals in Uganda: a protocol for a pragmatic cluster-randomised controlled trial
Authors: Kiguba Ronald , Mwebaza Norah , Ssenyonga Ronald , Ndagije Helen Byomire , Nambasa Victoria , Katureebe Cordelia , Katumba Kenneth , Tregunno Phil , Harrison Kendal , Karamagi Charles , Scott Kathryn A , Pirmohamed Munir
Published: July 2022

Introduction

Combination antiretroviral therapy (cART) has massively reduced HIV mortality. However, long-term cART increases the risk of adverse drug reactions (ADRs), which can lead to higher morbidity, mortality and healthcare costs for people living with HIV (PLHIV).

Pharmacovigilance—monitoring the effects of medicines—is essential for understanding real-world drug safety. In Uganda, pharmacovigilance systems have only recently been developed, and rates of ADR reporting for cART are very low. Thus, the safety profile of medicines currently used to treat HIV and tuberculosis in our population is poorly understood.

The Med Safety mobile application has been developed through the European Union’s Innovative Medicines Initiative WEB-Recognising Adverse Drug Reactions project to promote digital pharmacovigilance. This mobile application has been approved for ADR-reporting by Uganda’s National Drug Authority. However, the barriers and facilitators to Med Safety uptake, and its effectiveness in improving pharmacovigilance, are as yet unknown.

Methods and analysis

A pragmatic cluster-randomised controlled trial will be implemented over 30 months at 191 intervention and 191 comparison cART sites to evaluate Med Safety. Using a randomisation sequence generated by the sealed envelope software, we shall randomly assign the 382 prescreened cART sites to the intervention and comparison arms. Each cART site is a cluster that consists of healthcare professionals and PLHIV receiving dolutegravir-based cART and/or isoniazid preventive therapy. Healthcare professionals enrolled in the intervention arm will be trained in the use of mobile-based, paper-based and web-based reporting, while those in the comparison arm will be trained in paper-based and web-based reporting only.

Ethics and dissemination

Ethical approval was given by the School of Biomedical Sciences Research and Ethics Committee at Makerere University (SBS-REC-720), and administrative clearance was obtained from Uganda National Council for Science and Technology (HS1366ES). Study results will be shared with healthcare professionals, policymakers, the public and academia.

Trial registration number

PACTR202009822379650.
Human MAIT cells are devoid of alloreactive potential: prompting their use as universal cells for adoptive immune therapy
Authors: Tourret Marie , Talvard-Balland Nana , Lambert Marion , Ben Youssef Ghada , Chevalier Mathieu F , Bohineust Armelle , Yvorra Thomas , Morin Florence , Azarnoush Saba , Lantz Olivier , Dalle Jean-Hugues , Caillat-Zucman Sophie
Published: July 2022

Background

Mucosal-associated invariant T (MAIT) cells are semi-invariant T cells that recognize microbial antigens presented by the highly conserved MR1 molecule. MAIT cells are predominantly localized in the liver and barrier tissues and are potent effectors of antimicrobial defense. MAIT cells are very few at birth and accumulate gradually over a period of about 6 years during the infancy. The cytotoxic potential of MAIT cells, as well as their newly described regulatory and tissue repair functions, open the possibility of exploiting their properties in adoptive therapy. A prerequisite for their use as ‘universal’ cells would be a lack of alloreactive potential, which remains to be demonstrated.

Methods

We used ex vivo, in vitro and in vivo models to determine if human MAIT cells contribute to allogeneic responses.

Results

We show that recovery of MAIT cells after allogeneic hematopoietic stem cell transplantation recapitulates their slow physiological expansion in early childhood, independent of recovery of non-MAIT T cells. In vitro, signals provided by allogeneic cells and cytokines do not induce sustained MAIT cell proliferation. In vivo, human MAIT cells do not expand nor accumulate in tissues in a model of T-cell-mediated xenogeneic graft-versus-host disease in immunodeficient mice.

Conclusions

Altogether, these results provide evidence that MAIT cells are devoid of alloreactive potential and pave the way for harnessing their translational potential in universal adoptive therapy overcoming barriers of HLA disparity.

Trial registration number

ClinicalTrials.gov numberNCT02403089.
Staffing crisis capacity: a different approach to healthcare resource allocation for a different type of scarce resource
Authors: Butler Catherine R , Webster Laura B , Diekema Douglas S
Published: July 2022

Severe staffing shortages have emerged as a prominent threat to maintaining usual standards of care during the COVID-2019 pandemic. In dire settings of crisis capacity, healthcare systems assume the ethical duty to maximise aggregate population-level benefit of existing resources. To this end, existing plans for rationing mechanical ventilators and intensive care unit beds in crisis capacity focus on selecting individual patients who are most likely to survive and prioritising these patients to receive scarce resources. However, staffing capacity is conceptually different from availability of these types of discrete resources, and the existing strategy of identifying and prioritising patients with the best prognosis cannot be readily adapted to fit this real-world scenario. We propose that two alternative approaches to staffing resource allocation offer a better conceptual fit: (1)prioritise the worst off: restrict access to acute care services and hospital admission for patients at relatively low clinical risk and (2)prioritise staff interventions with high near-term value: universally restrict selected interventions and treatments that require substantial staff time and/or energy but offer minimal near-term patient benefit. These strategies—while potentially resulting in care that deviates from usual standards–support the goal of maximising the aggregate benefit of scarce resources in crisis capacity settings triggered by staffing shortages. This ethical framework offers a foundation to support institutional leaders in developing operationalisable crisis capacity policies that promote fairness and support healthcare workers.
The Patient preference predictor and the objection from higher-order preferences
Authors: Mainz Jakob Thrane
Published: July 2022

Recently, Jardaset alhave convincingly defended the patient preference predictor (PPP) against a range of autonomy-based objections. In this response, I propose a new autonomy-based objection to the PPP that is not explicitly discussed by Jardaset al. I call it the ‘objection from higher-order preferences’. Even if this objection is not sufficient reason to reject the PPP, the objection constitutes a pro tanto reason that is at least as powerful as the ones discussed by Jardaset al.
Disorders of gut-brain interaction in post-acute COVID-19 syndrome
Authors: Golla Rithvik , Vuyyuru Sudheer Kumar , Kante Bhaskar , Kedia Saurabh , Ahuja Vineet
Published: July 2022

The novel coronavirus SARS-CoV-2 is responsible for the devastating pandemic which has caused more than 5 million deaths across the world until today. Apart from causing acute respiratory illness and multiorgan dysfunction, there can be long-term multiorgan sequalae after recovery, which is termed ‘long COVID-19’ or ‘post-acute COVID-19 syndrome’. Little is known about long-term gastrointestinal (GI) consequences, occurrence of post-infection functional gastrointestinal disorders and impact the virus may have on overall intestinal health. In this review, we put forth the various mechanisms which may lead to this entity and possible ways to diagnose and manage this disorder. Hence, making physicians aware of this spectrum of disease is of utmost importance in the present pandemic and this review will help clinicians understand and suspect the occurrence of functional GI disease post recovery from COVID-19 and manage it accordingly, avoiding unnecessary misconceptions and delay in treatment.
The relationship between interstitial lung abnormalities, mortality, and multimorbidity: a cohort study
Authors: Sanders Jason Leigh , Axelsson Gisli , Putman Rachel , Menon Aravind , Dupuis Josée , Xu Hanfei , Wang Shuai , Murabito Joanne , Vasan Ramachandran , Araki Tetsuro , Nishino Mizuki , Washko George R , Hatabu Hiroto , O'Connor George , Gudmundsson Gunnar , Gudnason Vilmundur , Hunninghake Gary M
Published: July 2022

Background

Interstitial lung abnormalities (ILAs) are associated with increased mortality. It is unclear whether multimorbidity accounts for the mortality association or how strongly ILA is associated with mortality relative to other common age-associated diseases. We determined the association of ILA with all-cause mortality adjusted for multimorbidity, compared mortality associated with ILA and prevalent cardiovascular disease (CVD), diabetes mellitus, chronic kidney disease, chronic obstructive pulmonary disease and cancer and also determined the association between ILA and these diseases.

Methods

We measured ILA (none, indeterminant, definite) using blinded reads of CT images, prevalent chronic diseases and potential confounders in two observational cohorts, the Framingham Heart Study (FHS) (n=2449) and Age, Gene/Environment Susceptibility - Reykjavik Study (AGES-Reykjavik) (n=5180). We determined associations with mortality using Cox proportional hazards models and between ILA and diseases with multinomial logistic regression.

Results

Over a median (IQR) follow-up of 8.8 (1.4) years in FHS and 12.0 (7.7) years in AGES-Reykjavik, in adjusted models, ILAs were significantly associated with increased mortality (HR, 95% CI 1.95, 1.23 to 3.08, p=0.0042, in FHS; HR 1.60, 1.41 to 1.82, p<0.0001, in AGES-Reykjavik) adjusted for multimorbidity. In both cohorts, the association of ILA with mortality was of similar magnitude to the association of most other diseases. In adjusted models, ILAs were associated only with prevalent kidney disease (OR, 95% CI 1.90, 1.01 to 3.57, p=0.0452) in FHS and with prevalent CVD (OR 1.42, 1.12 to 1.81, p=0.0040) in AGES-Reykjavik.

Conclusions

ILAs were associated with mortality adjusted for multimorbidity and were similarly associated with increased mortality compared with several common chronic diseases. ILAs were not consistently associated with the prevalence of these diseases themselves.
Genome organization of major tandem repeats and their specificity for heterochromatin of macro- and microchromosomes in Japanese quail
Authors: Kulak Maria , Komissarov Aleksey , Fillon Valerie , Tsukanova Kseniya , Saifitdinova Alsu , Galkina Svetlana
Published: July 2022

Tandemly repeated DNAs form heterochromatic regions of chromosomes, including the vital centromeric chromatin. Despite the progress in new genomic technologies, tandem repeats remain poorly deciphered and need targeted analysis in the species of interest. The Japanese quail is one of the highest-producing poultry species as well as a model organism. Its genome differs by a noticeable accumulation of heterochromatin, which led to an increase by 1/7 compared to the chicken genome size. Prominent heterochromatin blocks occupy the short arms of acrocentric macrochromosomes and of microchromosomes. We have applied de novo repeat finder approach to unassembled raw reads of the Japanese quail genome. We identified the 20 most common tandem repeats with the abundance >1 Mb, which represent about 4.8% of the genome. We found that tandem repeat CjapSAT primarily contributes to the centromeric regions of the macrochromosomes CJA1–8. Cjap31B together with previously characterized BglII makes up centromere regions of microchromosomes and W chromosome. Other repeats populate heterochromatin of microchromosomal short arms in unequal proportions, as revealed by fluorescence in situ hybridization. The Cjap84A, Cjap408A, and CjapSAT repeat sequences show similarities to retrotransposon motifs. This suggests that retroelements may have played a crucial role in the distribution of repeats throughout the Japanese quail genome.
Mechanism to control the internal structure of thick brane
Authors: Bazeia D. , Lobão A. S.
Published: July 2022

In this work we study braneworlds generated by several scalar fields. The investigation describes the necessary formalism to examine models and evaluate the conditions for the stability of the gravitational sector under linear perturbations. In particular, we develop a mechanism that help us investigate distinct situations controlled by two and by three fields, focusing on how the fields can be used to modify the internal structure of the brane.
Uncovering Brain Differences in Preschoolers and Young Adolescents with Autism Spectrum Disorder Using Deep Learning
Authors: Li Shijun , Tang Ziyang , Jin Nanxin , Yang Qiansu , Liu Gang , Liu Tiefang , Hu Jianxing , Liu Sijun , Wang Ping , Hao Jingru , Zhang Zhiqiang , Zhang Xiaojing , Li Jinfeng , Wang Xin , Li Zhenzhen , Wang Yi , Yang Baijian , Ma Lin
Published: July 2022

Identifying brain abnormalities in autism spectrum disorder (ASD) is critical for early diagnosis and intervention. To explore brain differences in ASD and typical development (TD) individuals by detecting structural features using T1-weighted magnetic resonance imaging (MRI), we developed a deep learning-based approach, three-dimensional (3D)-ResNet with inception (I-ResNet), to identify participants with ASD and TD and propose a gradient-based backtracking method to pinpoint image areas that I-ResNet uses more heavily for classification. The proposed method was implemented in a preschool dataset with 110 participants and a public autism brain imaging data exchange (ABIDE) dataset with 1099 participants. An extra epilepsy dataset with 200 participants with clear degeneration in the parahippocampal area was applied as a verification and an extension. Among the datasets, we detected nine brain areas that differed significantly between ASD and TD. From the ROC in PASD and ABIDE, the sensitivity was 0.88 and 0.86, specificity was 0.75 and 0.62, and area under the curve was 0.787 and 0.856. In a word, I-ResNet with gradient-based backtracking could identify brain differences between ASD and TD. This study provides an alternative computer-aided technique for helping physicians to diagnose and screen children with an potential risk of ASD with deep learning model.