bluuebunny/crossref_metadata_2025 huggingface dataset:
Experimental and Numerical Investigations of Intermittence for Electronic Connectors Subjected to Mechanical Shocks
Authors: Huang T.-C. , Liao K.-C.
Published: June 2022

A phenomenon of intermittence is a critical issue for electronic joints of components installed in such as a mobile carrier. In this study, a finite element analysis of the DDR4 connector is utilized to assess the dynamic responses of terminal pairs embedded in the polymeric housing subjected to various mechanical shock conditions. Two approaches, respectively, based on the contact normal force and relative displacement between the contacting terminal and the associated gold finger, are proposed to investigate the presence of intermittence. The intermittence of the critical terminal pair under various shock conditions along the normal and longitudinal direction of the terminal is found to be strongly related to contact loss. Under the shock conditions along the transverse direction of the terminal, a threshold of the relative displacement between two reference points is set to effectively and accurately assess the occurrence of intermittence. The elastic/elastic-plastic multiscale rough surface (MSRS) model adopted to directly estimate the contact resistance history of the terminal pair is further attempted. The relatively low contact resistance of the terminal pair under the condition denoting pass can be observed. On the other hand, a sudden rise of the contact resistance of the terminal pair under the condition referring to fail is demonstrated based on the MSRS model although dramatic underestimations of the contact resistance are given when the contact normal force is rather low.
Effect of Gypsum Waste Inclusion on Gasification of Municipal Solid Waste
Authors: Burra Kiran Raj Goud , Fernández Hernández Inés , Castaldi Marco J. , Goff Stephen , Gupta Ashwani K.
Published: June 2022

Sustainable disposal techniques of municipal solid wastes (MSW) are essential for effective materials recovery and energy management. Synergistic incorporation of gypsum waste from the construction and demolition (C&D) sector is explored here for the low techno-economic viability of MSW in waste-to-energy facilities. Co-processing of MSW with this low-value gypsum can potentially provide improved product recovery and simultaneously furnish economic viability. To understand the impact of gypsum incorporation into MSW conversion, we tested synthetic MSW and a 1:1 mixture of MSW with gypsum from drywall wastes and compared their micro-scale mass loss kinetics along with macro-scale syngas evolution and conversion at different temperatures, and in pyrolytic and oxidizing environments. Gypsum incorporation led to increased syngas production and decreased char yields as the char was oxidized by CaSO4. Thermogravimetric analysis (TGA) revealed two different temperature zones of gypsum interaction with MSW depending on the oxidation concentration in the environment. Adding 50% gypsum only changed the final ash yield by 10% in pyrolysis conditions suggesting the viability of gypsum incorporation. While the addition of gypsum led to delayed evolution of H2 and CO, the cumulative yields of H2 and CO2 increased significantly and the yield of CO changed minimally. Additionally, hydrocarbon by-products such as CH4 decreased by gypsum addition. The results showed improved syngas yield and uniformity, as well as operational conditions from the gypsum interaction with MSW which can help in the further development of gypsum waste incorporation.
A coherence-based phase and amplitude gradient estimator method for calculating active acoustic intensity
Authors: Cook Mylan R. , Gee Kent L. , Sommerfeldt Scott D.
Published: June 2022

The phase and amplitude gradient estimator (PAGE) method [Thomas, Christensen, and Gee, J. Acoust. Soc. Am. 137, 3366–3376 (2015)] has been developed as an alternative to the traditional p-p method for calculating energy-based acoustic measures such as active acoustic intensity. While this method shows many marked improvements over the traditional method, such as a wider valid frequency bandwidth for broadband sources, contaminating noise can lead to inaccurate results. Contaminating noise degrades performance for both the traditional and PAGE methods and causes probe microphone pairs to exhibit low coherence. When coherence is low, better estimates of the pressure magnitude and gradient can be obtained by using a coherence-based approach, which yields a more accurate intensity estimate. This coherence-based approach to the PAGE method, known as the CPAGE method, employs two main coherence-based adjustments. The pressure magnitude adjustment mitigates the negative impact of uncorrelated contaminating noise and improves intensity magnitude calculation. The phase gradient adjustment uses coherence as a weighting to calculate the phase gradient for the probe and improves primarily the calculation of intensity direction. Though requiring a greater computation time than the PAGE method, the CPAGE method is shown to improve intensity calculations, both in magnitude and direction.
Structure of the mammalian ribosome as it decodes the selenocysteine UGA codon
Authors: Hilal Tarek , Killam Benjamin Y. , Grozdanović Milica , Dobosz-Bartoszek Malgorzata , Loerke Justus , Bürger Jörg , Mielke Thorsten , Copeland Paul R. , Simonović Miljan , Spahn Christian M. T.
Published: June 2022

The elongation of eukaryotic selenoproteins relies on a poorly understood process of interpreting in-frame UGA stop codons as selenocysteine (Sec). We used cryo-electron microscopy to visualize Sec UGA recoding in mammals. A complex between the noncoding Sec-insertion sequence (SECIS), SECIS-binding protein 2 (SBP2), and 40
S
ribosomal subunit enables Sec-specific elongation factor eEFSec to deliver Sec. eEFSec and SBP2 do not interact directly but rather deploy their carboxyl-terminal domains to engage with the opposite ends of the SECIS. By using its Lys-rich and carboxyl-terminal segments, the ribosomal protein eS31 simultaneously interacts with Sec-specific transfer RNA (tRNA
Sec
) and SBP2, which further stabilizes the assembly. eEFSec is indiscriminate toward
l
-serine and facilitates its misincorporation at Sec UGA codons. Our results support a fundamentally distinct mechanism of Sec UGA recoding in eukaryotes from that in bacteria.
Interleukin-17 governs hypoxic adaptation of injured epithelium
Authors: Konieczny Piotr , Xing Yue , Sidhu Ikjot , Subudhi Ipsita , Mansfield Kody P. , Hsieh Brandon , Biancur Douglas E. , Larsen Samantha B. , Cammer Michael , Li Dongqing , Landén Ning Xu , Loomis Cynthia , Heguy Adriana , Tikhonova Anastasia N. , Tsirigos Aristotelis , Naik Shruti
Published: June 2022

Mammalian cells autonomously activate hypoxia-inducible transcription factors (HIFs) to ensure survival in low-oxygen environments. We report here that injury-induced hypoxia is insufficient to trigger HIF1α in damaged epithelium. Instead, multimodal single-cell and spatial transcriptomics analyses and functional studies reveal that retinoic acid–related orphan receptor γt
+
(RORγt
+
) γδ T cell–derived interleukin-17A (IL-17A) is necessary and sufficient to activate HIF1α. Protein kinase B (AKT) and extracellular signal–regulated kinase 1/2 (ERK1/2) signaling proximal of IL-17 receptor C (IL-17RC) activates mammalian target of rapamycin (mTOR) and consequently HIF1α. The IL-17A–HIF1α axis drives glycolysis in wound front epithelia. Epithelial-specific loss of IL-17RC, HIF1α, or blockade of glycolysis derails repair. Our findings underscore the coupling of inflammatory, metabolic, and migratory programs to expedite epithelial healing and illuminate the immune cell–derived inputs in cellular adaptation to hypoxic stress during repair.
Accelerated aging of all-inorganic, interface-stabilized perovskite solar cells
Authors: Zhao Xiaoming , Liu Tianran , Burlingame Quinn C. , Liu Tianjun , Holley Rudolph , Cheng Guangming , Yao Nan , Gao Feng , Loo Yueh-Lin
Published: June 2022

To understand degradation routes and improve the stability of perovskite solar cells (PSCs), accelerated aging tests are needed. Here, we use elevated temperatures (up to 110°C) to quantify the accelerated degradation of encapsulated CsPbI
3
PSCs under constant illumination. Incorporating a two-dimensional (2D) Cs
2
PbI
2
Cl
2
capping layer between the perovskite active layer and hole-transport layer stabilizes the interface while increasing power conversion efficiency of the all-inorganic PSCs from 14.9 to 17.4%. Devices with this 2D capping layer did not degrade at 35°C and required >2100 hours at 110°C under constant illumination to degrade by 20% of their initial efficiency. Degradation acceleration factors based on the observed Arrhenius temperature dependence predict intrinsic lifetimes of 51,000 ± 7000 hours (>5 years) operating continuously at 35°C.
A photonic integrated circuit–based erbium-doped amplifier
Authors: Liu Yang , Qiu Zheru , Ji Xinru , Lukashchuk Anton , He Jijun , Riemensberger Johann , Hafermann Martin , Wang Rui Ning , Liu Junqiu , Ronning Carsten , Kippenberg Tobias J.
Published: June 2022

Erbium-doped fiber amplifiers revolutionized long-haul optical communications and laser technology. Erbium ions could provide a basis for efficient optical amplification in photonic integrated circuits but their use remains impractical as a result of insufficient output power. We demonstrate a photonic integrated circuit–based erbium amplifier reaching 145 milliwatts of output power and more than 30 decibels of small-signal gain—on par with commercial fiber amplifiers and surpassing state-of-the-art III-V heterogeneously integrated semiconductor amplifiers. We apply ion implantation to ultralow–loss silicon nitride (Si
3
N
4
) photonic integrated circuits, which are able to increase the soliton microcomb output power by 100 times, achieving power requirements for low-noise photonic microwave generation and wavelength-division multiplexing optical communications. Endowing Si
3
N
4
photonic integrated circuits with gain enables the miniaturization of various fiber-based devices such as high–pulse-energy femtosecond mode-locked lasers.
A genetic module at one locus in rice protects chloroplasts to enhance thermotolerance
Authors: Zhang Hai , Zhou Ji-Fu , Kan Yi , Shan Jun-Xiang , Ye Wang-Wei , Dong Nai-Qian , Guo Tao , Xiang You-Huang , Yang Yi-Bing , Li Ya-Chao , Zhao Huai-Yu , Yu Hong-Xiao , Lu Zi-Qi , Guo Shuang-Qin , Lei Jie-Jie , Liao Ben , Mu Xiao-Rui , Cao Ying-Jie , Yu Jia-Jun , Lin Youshun , Lin Hong-Xuan
Published: June 2022

How the plasma membrane senses external heat-stress signals to communicate with chloroplasts to orchestrate thermotolerance remains elusive. We identified a quantitative trait locus,
Thermo-tolerance 3
(
TT3
), consisting of two genes,
TT3.1
and
TT3.2
, that interact together to enhance rice thermotolerance and reduce grain-yield losses caused by heat stress. Upon heat stress, plasma membrane–localized E3 ligase TT3.1 translocates to the endosomes, on which TT3.1 ubiquitinates chloroplast precursor protein TT3.2 for vacuolar degradation, implying that TT3.1 might serve as a potential thermosensor. Lesser accumulated, mature TT3.2 proteins in chloroplasts are essential for protecting thylakoids from heat stress. Our findings not only reveal a
TT3.1-TT3.2
genetic module at one locus that transduces heat signals from plasma membrane to chloroplasts but also provide the strategy for breeding highly thermotolerant crops.
Oil at sea—how much is too much?
Authors: Leifer Ira
Published: June 2022

The anthropogenic share of marine oil discharge is much larger than previously thought
Turning materials into robots
Authors: Rafsanjani Ahmad
Published: June 2022

Researchers showcase a 3D-printed millirobot made out of multifunctional metamaterials
In Vitro
Selection of Remdesivir-Resistant SARS-CoV-2 Demonstrates High Barrier to Resistance
Authors: Checkmahomed Liva , Carbonneau Julie , Du Pont Venice , Riola Nicholas C. , Perry Jason K. , Li Jiani , Paré Bastien , Simpson Shawn M. , Smith Martin A. , Porter Danielle P. , Boivin Guy
Published: June 2022

In vitro
selection of remdesivir-resistant severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) revealed the emergence of a V166L substitution, located outside of the polymerase active site of the Nsp12 protein, after 9 passages of a single lineage. V166L remained the only Nsp12 substitution after 17 passages (10 μM remdesivir), conferring a 2.3-fold increase in 50% effective concentration (EC
50
).
Antibiotic Exposure Leads to Reduced Phage Susceptibility in Vancomycin Intermediate Staphylococcus aureus (VISA)
Authors: McCallin Shawna , Menzi Carmen , Lassen Swenja , Daraspe Jean , Oechslin Frank , Moreillon Philippe
Published: June 2022

In the time of antimicrobial resistance, phage therapy is frequently suggested as a possible solution for such difficult-to-treat infections. Vancomycin-intermediate
Staphylococcus aureus
(VISA) remains a relatively rare yet increasing occurrence in the clinic for which phage therapy may be an option.
Draft Genome Sequence of
Trichomonas tenax
Strain Hs-4:NIH
Authors: Yang Nawu , Christie Jevan , Keen Henry L. , Matthew Maurice A. , Yao Chaoqun
Published: June 2022

Trichomonas tenax
is a flagellated parasite that plays an important role in periodontal disease, with high prevalence worldwide. Its pathogenesis remains largely unknown, and there is very little information on its genome. Here, we present the whole-genome shotgun sequence of
T. tenax
strain Hs-4:NIH.
Metagenome-Assembled Genomes of Bacterial Symbionts Associated with Insecticide-Resistant and -Susceptible Individuals of the Glassy-Winged Sharpshooter (Homalodisca vitripennis)
Authors: Ettinger Cassandra L. , Byrne Frank J. , Redak Richard A. , Stajich Jason E.
Published: June 2022

The role of microbes in insecticide resistance is an emerging question. Here, we describe six metagenome-assembled genomes (MAGs) associated with the glassy-winged sharpshooter (
Homalodisca vitripennis
[Germar, 1821]) (Hemiptera, Cicadellidae).
Incidence and aetiology of infant Gram-negative bacteraemia and meningitis: systematic review and meta-analysis
Authors: Hallmaier-Wacker Luisa K , Andrews Amelia , Nsonwu Olisaeloka , Demirjian Alicia , Hope Russell J , Lamagni Theresa , Collin Simon M
Published: June 2022

Background

One in six infant deaths worldwide are caused by invasive bacterial infections, of which a substantial but unquantified proportion are caused by Gram-negative bacteria.

Methods

We conducted a systematic review of studies published from 31 May 2010 to 1 June 2020 indexed in MEDLINE, Embase and Global Health databases. We performed meta-analyses of the incidence of Gram-negative bacteraemia and of individual Gram-negative species as proportions of all infant bacteraemia, stratified by onset (early vs late) and country income (low/middle vs high).

Results

152 studies from 54 countries were included, 60 in high-income countries (HIC) and 92 in low-income/middle-income countries (LMIC). Gram-negatives represented a higher proportion (53%, 95% CI 49% to 57%) of all infant bacteraemia in LMIC compared with HIC (28%, 95% CI 25% to 32%). Incidence of infant Gram-negative bacteraemia was 2.01 (95% CI 1.15 to 3.51) per 1000 live births; it was five times higher in LMIC (4.35, 95% CI 2.94 to 6.43) compared with HIC (0.73, 95% CI 0.39 to 7.5). In HIC,Escherichia coliwas the leading Gram-negative pathogen, representing 19.2% (95% CI 15.6% to 23.4%) of early and 7.3% (95% CI 5.3% to 10.1%) of all late-onset bacteraemia;Klebsiellaspp were the next most common cause (5.3%) of late-onset bacteraemia. In LMIC,Klebsiellaspp caused 16.4% (95% CI 11.5% to 22.7%) of early and 15.0% (95% CI 10.1% to 21.8%) of late-onset bacteraemia, followed byE. coli(early-onset 7.50%, 95% CI 4.98% to 11.1%; late-onset 6.53%, 95% CI 4.50% to 9.39%) andPseudomonasspp (early-onset 3.93%, 95% CI 2.04% to 7.44%; late-onset 2.81%, 95% CI 1.99% to 3.95%).

Conclusion

E. coli,KlebsiellaandPseudomonasspp cause 20%–28% of early-onset infant bacteraemia and 14% cases of infant meningitis worldwide. Implementation of preventive measures could reduce the high incidence of Gram-negative bacteraemia in LMIC.

PROSPERO registration number

CRD42020191618.
National Institutes of Health Stroke Scale scores obtained using a mobile application compared to the conventional paper form: a randomised controlled validation study
Authors: Bugge Helge Fagerheim , Guterud Mona Marie , Røislien Jo , Larsen Karianne , Ihle-Hansen Hege , Toft Mathias , Hov Maren Ranhoff , Sandset Else Charlotte
Published: June 2022

Background

Prehospital delay contributes to treatment delay in acute stroke. Numerous prehospital stroke scales exist for stroke identification, but they lack the diagnostic accuracy of the in-hospital National Institutes of Health Stroke Scale (NIHSS). We have developed a mobile application to aid paramedics assessing prehospital NIHSS. This study explores agreement between NIHSS scores obtained using the Paramedic Norwegian Acute Stroke Prehospital Project (ParaNASPP) application compared with conventional assessment.

Methods

25 physicians working with stroke were randomised to an application group or control. 20 unique videos portraying acute stroke symptoms were scored by both groups. 95% limits of agreement (LoA) were calculated using Bland-Altman’s method, comparing the groups to predefined scores, and each other. LoAs within ±3 NIHSS points were considered acceptable. Cohen’s kappa was calculated on dichotomised NIHSS scores.

Results

The ParaNASPP application group had 95% LoA of −2.33 to 2.71. The control group had LoA of −2.60 to 2.55. Direct comparison between the groups gave LoA of −3.12 to 3.55. When compared with the dichotomised predefined scores kappa was 0.93 in the application group and 0.89 in the control group. Kappa was 0.84 for direct comparison between the groups.

Discussion

There was very good agreement between the application and both the predefined score and the control group. Scores from the ParaNASPP application differ slightly more than our predefined goal when compared with the control group, but is well within when compared with the predefined NIHSS scores. We consider this acceptable and the ParaNASPP application validated for further clinical studies.
Safety of ezetimibe in lipid-lowering treatment: systematic review and meta-analysis of randomised controlled trials and cohort studies
Authors: Wang Yang , Zhan Shipeng , Du Heyue , Li Jing , Khan Safi U , Aertgeerts Bert , Guyatt Gordon , Hao Qiukui , Bekkering Geertruida , Li Ling , Delvaux Nicolas , Su Na , Riaz Irbaz , Vandvik Per Olav , Tian Haoming , Li Sheyu
Published: June 2022

Objective

To determine the harms of ezetimibe in people who need lipid-lowering treatment.

Design

Systematic review and meta-analysis.

Data sources

Randomised controlled trials and cohort studies.

Eligibility criteria for selecting studies

Studies comparing ezetimibe with placebo, standard care, or other lipid-lowering agents in people who need lipid-lowering treatment with a follow-up duration of at least six months (or 24 weeks). The relative effects for potential harms of ezetimibe were pooled by use of random effect pairwise meta-analyses for randomised controlled trials and the evidence from observational studies was narratively summarised. The certainty of evidence was assessed using the Grading of Recommendation Assessment, Development, and Evaluation.

Results

48 randomised controlled trials with 28 444 participants (median follow-up 34 weeks, range 24-312 weeks) and four observational studies with 1667 participants (median follow-up 282 weeks, range 72-400 weeks) were included. The meta-analyses of randomised trials showed moderate to high certainty that ezetimibe was not associated with cancer (relative risk 1.01; 95% confidence interval 0.92 to 1.11), fractures (0.90; 0.74 to 1.10), discontinuation due to any adverse event (0.87; 0.74 to 1.03), gastrointestinal adverse events leading to discontinuation (1.34; 0.58 to 3.08), myalgia or muscular pain leading to discontinuation (0.82; 0.51 to 1.33), neurocognitive events (1.48; 0.58 to 3.81), or new-onset diabetes (0.88; 0.61 to 1.28). The narrative analysis of observational studies provided consistent findings. No credible subgroup effects were identified for the harm outcomes, including shorter versus longer follow-up duration of trials.

Conclusions

Ezetimibe results in little to no difference in adverse events or other undesirable effects compared with placebo, usual care or other lipid-lowering agents.

Review registration

PROSPERO CRD42020187437.
Digital cognitive training in children with attention-deficit/hyperactivity disorder: a study protocol of a randomised controlled trial
Authors: Richmond Sally , Kirk Hannah , Gaunson Tori , Bennett Meg , Bellgrove Mark A , Cornish Kim
Published: June 2022

Introduction

Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent neurodevelopmental disorders and is a persistent pattern of inattention and/or hyperactivity-impulsivity that interferes with daily functioning. Children with ADHD are developmentally vulnerable, with the disorder linked to emotional regulation difficulties, behavioural disturbances, as well as academic challenges. Emerging evidence suggests that children with ADHD may benefit from cognitive training interventions, including those focused on attention. This study aims to assess the immediate and long-term efficacy of an attention training intervention in children with ADHD.

Methods and analysis

This study is a preregistered, parallel, double blind, randomised controlled trial. Participants will comprise 104 children with a diagnosis of ADHD aged 5–8 years 11 months. Participants will be randomly allocated to either an adaptive, digital game-based (1) attention training programme (intervention) or (2) a numeracy programme (control). Both programmes will be delivered on a touchscreen tablet, and children will complete five 20 min sessions per week for a 5-week period at home (25 sessions in total). Assessments of the primary outcome (ie, attention and inhibitory control) and secondary outcomes (ie, selective attention, interference control, sustained attention, inhibition, behavioural attention, impairment in everyday functioning, working memory and executive functioning) will occur at preintervention, immediately postintervention and at 3-month follow-up. Multivariate linear regression will be employed to examine primary and secondary outcomes. The data analyst will be blinded to group membership.

Ethics and dissemination

Ethics approval has been obtained from the Monash University HREC (20495). Results will be disseminated through peer-reviewed journals, conference presentations, media outlets, the internet and various community/stakeholder activities.

Trial registration number

ACTRN12620000964910, UTN U1111-1250-2620.
Optimising Xpert-Ultra and culture testing to reliably measure tuberculosis prevalence in the community: findings from surveys in Zambia and South Africa
Authors: Floyd Sian , Klinkenberg Eveline , de Haas Petra , Kosloff Barry , Gachie Thomas , Dodd Pete J , Ruperez Maria , Wapamesa Chali , Burnett Michael J , Kalisvaart Nico , Vermaak Redwaan , Mainga Tila , Schaap Albertus , Fidler Sarah , Mureithi Linda , Shanaube Kwame , Hayes Richard , Ayles Helen
Published: June 2022

Objectives

Prevalence surveys remain the best way to assess the national tuberculosis (TB) burden in many countries. Challenges with using culture (the reference standard) for TB diagnosis in prevalence surveys have led to increasing use of molecular tests (Xpert assays), but discordance between these two tests has created problems for deciding which individuals have TB. We aimed to design an accurate diagnostic algorithm for TB prevalence surveys (TBPS) that limits the use of culture.

Design

TBPS in four communities, conducted during 2019.

Setting

Three Zambian communities and one South-African community included in the TBPS of the Tuberculosis Reduction through Expanded Anti-retroviral Treatment and Screening study.

Participants

Randomly sampled individuals aged ≥15 years. Among those who screened positive on chest X-ray or symptoms, two sputum samples were collected for field Xpert-Ultra testing and a third for laboratory liquid-culture testing. Clinicians reviewed screening and test results; in Zambia, participants with Mycobacterium tuberculosis-positive results were followed up 6–13 months later. Among 10 984 participants, 2092 screened positive, 1852 provided two samples for Xpert-Ultra testing, and 1009 had valid culture results.

Outcomes

Culture and Xpert-Ultra test results.

Results

Among 946 culture-negative individuals, 917 were Xpert-negative, 12 Xpert-trace-positive and 17 Xpert-positive (grade very low, low, medium or high), with Xpert categorised as the highest grade of the two sample results. Among 63 culture-positive individuals, 8 were Xpert-negative, 9 Xpert-trace-positive and 46 Xpert-positive. Counting trace-positive results as positive, the sensitivity of Xpert-Ultra compared with culture was 87% (95% CI 76% to 94%) using two samples compared with 76% (95% CI 64% to 86%) using one. Specificity was 97% when trace-positive results were counted as positive and 98% when trace-positive results were counted as negative. Most Xpert-Ultra-positive/culture-negative discordance was among individuals whose Xpert-positive results were trace-positive or very low grade or they reported previous TB treatment. Among individuals with both Xpert-Ultra results grade low or above, the positive-predictive-value was 90% (27/30); 3/30 were plausibly false-negative culture results.

Conclusion

Using Xpert-Ultra as the primary diagnostic test in TBPS, with culture only for confirmatory testing, would identify a high proportion of TB cases while massively reducing survey culture requirements.

Trial registration number

NCT03739736.
Mixed methods evaluation of the Getting it Right First Time programme in elective orthopaedic surgery in England: an analysis from the National Joint Registry and Hospital Episode Statistics
Authors: Barratt Helen , Hutchings Andrew , Pizzo Elena , Aspinal Fiona , Jasim Sarah , Gafoor Rafael , Ledger Jean , Mehta Raj , Mason James , Martin Peter , Fulop Naomi J , Morris Stephen , Raine Rosalind
Published: June 2022

Objective

To evaluate the impact of the ‘Getting it Right First Time’ (GIRFT) national improvement programme in orthopaedics, which started in 2012.

Design

Mixed-methods study comprising statistical analysis of linked national datasets (National Joint Registry; Hospital Episode Statistics; Patient-Reported Outcomes); economic analysis and qualitative case studies in six National Health Service (NHS) Trusts.

Setting

NHS elective orthopaedic surgery in England.

Participants

736 088 patients who underwent primary hip or knee replacement at 126 NHS Trusts between 1 April 2009 and 31 March 2018, plus 50 NHS staff.

Intervention

Improvement bundle including ‘deep dive’ visits by senior clinician to NHS Trusts, informed by bespoke set of routine performance data, to discuss how improvements could be made locally.

Main outcome measures

Number of procedures conducted by low volume surgeons; use of uncemented hip implants in patients >65; arthroscopy in year prior to knee replacement; hospital length of stay; emergency readmissions within 30 days; revision surgery within 1 year; health-related quality of life and functional status.

Results

National trends demonstrated substantial improvements beginning prior to GIRFT. Between 2012 and 2018, there were reductions in procedures by low volume surgeons (ORs (95% CI) hips 0.58 (0.53 to 0.63), knees 0.77 (0.72 to 0.83)); uncemented hip prostheses in >65 s (OR 0.56 (0.51 to 0.61)); knee arthroscopies before surgery (OR 0.48 (0.41 to 0.56)) and mean length of stay (hips −0.90 (−1.00 to -0.81), knees −0.74 days (−0.82 to −0.66)). The additional impact of visits was mixed and comprised an overall economic saving of £431 848 between 2012 and 2018, but this was offset by the costs of the visits. Staff reported that GIRFT’s influence ranged from procurement changes to improved regional collaboration.

Conclusion

Nationally, we found substantial improvements in care, but the specific contribution of GIRFT cannot be reliably estimated due to other concurrent initiatives. Our approach enabled additional analysis of the discrete impact of GIRFT visits.
Integrating Indigenous healing practices within collaborative care models in primary healthcare in Canada: a rapid scoping review
Authors: Corso Melissa , DeSouza Astrid , Brunton Ginny , Yu Hainan , Cancelliere Carolina , Mior Silvano , Taylor-Vaisey Anne , MacLeod-Beaver Kathy , Côté Pierre
Published: June 2022

Objectives

In November 2020, a series of reports, In Plain Sight, described widespread Indigenous-specific stereotyping, racism and discrimination limiting access to medical treatment and negatively impacting the health and wellness of Indigenous Peoples in British Columbia, Canada. To address the health inequalities experienced by Indigenous peoples, Indigenous healing practices must be integrated within the delivery of care. This rapid scoping review aimed to identify and synthesise strategies used to integrate Indigenous healing practices within collaborative care models available in community-based primary healthcare, delivered by regulated health professionals in Canada.

Eligibility criteria

We included quantitative, qualitative and mixed-methods studies conducted in community-based primary healthcare practices that used strategies to integrate Indigenous healing practices within collaborative care models.

Sources of evidence

We searched MEDLINE, Embase, Indigenous Studies Portal, Informit Indigenous Collection and Native Health Database for studies published from 2015 to 2021.

Charting methods

Our data extraction used three frameworks to categorise the findings. These frameworks defined elements of integrated healthcare (ie, functional, organisational, normative and professional), culturally appropriate primary healthcare and the extent of community engagement. We narratively summarised the included study characteristics.

Results

We identified 2573 citations and included 31 in our review. Thirty-nine per cent of reported strategies used functional integration (n=12), 26% organisational (n=8), 19% normative (n=6) and 16% professional (n=5). Eighteen studies (58%) integrated all characteristics of culturally appropriate Indigenous healing practices into primary healthcare. Twenty-four studies (77%) involved Indigenous leadership or collaboration at each phase of the study and, seven (23%) included consultation only or the level of engagement was unclear.

Conclusions

We found that collaborative and Indigenous-led strategies were more likely to facilitate and implement the integration of Indigenous healing practices. Commonalities across strategies included community engagement, elder support or Indigenous ceremony or traditions. However, we did not evaluate the effectiveness of these strategies.
Effect of beetroot or beetroot plus vitamin C supplementation on cardiovascular function in patients with coronary artery disease: protocol for a double-blind, placebo-controlled, randomised trial
Authors: Bahrami Leila Sadat , Mohebaty Mohsen , Arabi Seyyed Mostafa , Tabesh Hamed , Nematy Mohsen , Rezvani Reza
Published: June 2022

Introduction

Coronary artery disease (CAD), classified into the atherosclerosis category, is a prevalent cardiovascular disease worldwide that is associated with serious comorbidities and death. The purpose of this study was to evaluate the effect of beetroot/beetroot plus vitamin C on cardiovascular health status and function in patients with CAD.

Method and analysis

A randomised, placebo-controlled, double-blind clinical trial to recruit 90 patients with CAD at the cardiac outpatient clinic and Imam Reza Hospital, Mashhad, Iran. Participants will be divided into three groups: (1) Those who receive 500 mg three times a day of beetroot capsules, (2) Those who receive 500 mg three times a day of beetroot plus vitamin C capsules, and (3) Those who receive placebo capsules three times a day for 4 weeks. Pulse wave velocity, Augmentation Index, heart rate, volume of oxygen (VO2) max/VO2 peak, peak heart rate, blood pressure, interleukin 6 (IL-6), high sensitivity C reactive protein, intercellular adhesion molecule, vascular cell adhesion molecule, lipid profile and anthropometry will be measured at the beginning and end of the intervention.

Ethics and dissemination

This study was approved by the Ethics Committee of Mashhad University of Medical Sciences (IR.MUMS.MEDICAL.REC.1399.717). All participants will be asked to complete the consent form at the beginning of the study. The results will be actively disseminated through peer-reviewed journals and conference presentations.

Trial registration number

Iranian Registry of Clinical Trials, IRCT20210217050393N1 (registered 16 May 2021).
Spiritual conversation model for patients and loved ones in palliative care: a validation study
Authors: Haufe Marc , Leget Carlo , Glasner Tina , Teunissen Saskia , Potma Marieke
Published: June 2022

Objectives

In palliative care, validated tools for professionals that facilitate day-to-day spiritual conversations with patients and loved ones are scarce. The objective of this study was to validate the Diamond spiritual conversation model across different palliative care settings as well as professional and educational levels.

Methods

An online survey was filled in by 387 professionals providing palliative care for patients in hospice, home care, hospital and nursing home settings. The five polarities of the Diamond model: holding on–letting go, doing–undergoing, remembering–forgetting, me–the other and believing–knowing were operationalised and evaluated on reported occurrence.

Results

In conversations with patients, palliative care professionals reported
letting go of loved ones
(81.8%)
, dealing with pain and suffering
(88.1%)
, dealing with issues from the past
(67.2%)
, dealing with own versus loved one’s wishes
(69.4%) and
giving meaning to death
(66.7%) as themes occurring regularly to very often. In conversations with loved ones, this was 70.8%, 78.5%, 55.4%, 68,8% and 62%, respectively. Respondents working in hospices reported these themes significantly more than those working in home care settings, nursing homes or hospitals. Nurse assistant respondents reported the themes significantly less than nurses or chaplains.

Conclusion

From the perspective of professionals providing palliative care in different palliative care settings, the Diamond model offers a validated framework for addressing relevant spiritual themes for patients and loved ones.
Telemedicine for outpatient palliative care during COVID-19 pandemics: a longitudinal study
Authors: Caraceni Augusto , Pellegrini Chiara , Shkodra Morena , Zecca Ernesto , Bracchi Paola , Lo Dico Silvia , Caputo Mariangela , Zappata Simonetta , Zito Emanuela , Brunelli Cinzia
Published: June 2022

Objectives

During the COVID-19 pandemic, telemedicine (TM) emerged as an important mean to reduce risks of transmission, yet delivering the necessary care to patients. Our aim was to evaluate feasibility, characteristics and satisfaction for a TM service based on phone/video consultations for patients with cancer attending an outpatient palliative care clinic during COVID-19 pandemics.

Methods

A longitudinal observational study was conducted from April to December 2020. Consecutive patients were screened for video consultations feasibility. Either patients or their caregivers received video/phone consultations registering reason and intervention performed. Those contacted at least twice were eligible for experience of care assessment.

Results

Video consultations were feasible in 282 of 572 screened patients (49%, 95% CI 45% to 52%); 112 patients among the 572 had at least two phone/video consultations and 12 of them had one or more video consultations. Consultations were carried out with patients (56%), caregivers (30%) or both (14%). 63% of the consultations were requested by the patients/caregivers. Reasons for consultation included uncontrolled (66%) or new symptom onset (20%), therapy clarifications (37%) and updates on diagnostic tests (28%). Most interventions were therapy modifications (70%) and appointments’ rescheduling (51%). 49 patients and 19 caregivers were interviewed, reporting good care experience (average of 1–5 satisfaction score of 3.9 and 4.2, respectively). The majority (83% and 84%) declared they would use TM after the pandemics.

Conclusions

Although feasibility is still limited for some patients, TM can be a satisfactory alternative to in-person visits for palliative care patients in need of limiting access to the hospital.
Short-term effect of deprescribing antihypertensives in older people
Authors: Morselli Franca , Khong Teck K
Published: June 2022

Commentary on:Sheppard JP, Burt J, Lown M,et al. Effect of antihypertensive medication reduction vs usual care on short-term blood pressure control in patients with hypertension aged 80 years and older: The OPTIMISE randomized clinical trial.JAMA. 2020;323:2039–51.

Series co-ordinator:Dr Teck Khong, DTB Associate Editor, Clinical Pharmacology, St George’s, University of London, UK
IBD therapeutics: what is in the pipeline?
Authors: Toskas Alexandros , Akbar Ayesha
Published: June 2022

Inflammatory bowel disease (IBD) is an idiopathic long-term relapsing and remitting disorder including ulcerative colitis and Crohn’s disease. The aim of therapy is to induce and maintain remission. Anti-TNF therapies dramatically improved clinical outcomes but primary failure or secondary loss is a common problem as well as potential side effects potentially limiting efficacy and long-term use. The advent of new targeted agents with the potential for greater safety is welcomed in IBD and offers the potential for different agents as the disease becomes refractory or even combination therapies to maximise effectiveness without compromising safety in the future. More data are required to understand the best positioning in pathways and longer-term safety effects.
Detection of microsatellite instability-high (MSI-H) by liquid biopsy predicts robust and durable response to immunotherapy in patients with pancreatic cancer
Authors: Chakrabarti Sakti , Bucheit Leslie , Starr Jason Scott , Innis-Shelton Racquel , Shergill Ardaman , Dada Hiba , Resta Regina , Wagner Stephanie , Fei Naomi , Kasi Pashtoon Murtaza
Published: June 2022

Clinical trials reporting the robust antitumor activity of immune checkpoint inhibitors (ICIs) in microsatellite instability-high (MSI-H) solid tumors have used tissue-based testing to determine the MSI-H status. This study assessed if MSI-H detected by a plasma-based circulating tumor DNA liquid biopsy test predicts robust response to ICI in patients with pancreatic ductal adenocarcinoma (PDAC). Retrospective analysis of patients with PDAC and MSI-H identified on Guardant360 from October 2018 to April 2021 was performed; clinical outcomes were submitted by treating providers. From 52 patients with PDAC +MSI-H, outcomes were available for 10 (19%) with a median age of 68 years (range: 56–82 years); the majority were male (80%) and had metastatic disease (80%). Nine of 10 patients were treated with ICI. Eight out of nine patients received single-agent pembrolizumab (8/9), while one received ipilimumab plus nivolumab. The overall response rate by Response Evaluation Criteria in Solid Tumors was 77% (7/9). The median progression-free survival and overall survival were not reached in this cohort. The median duration of treatment with ICI was 8 months (range: 1–24), and six out of seven responders continued to show response at the time of data cut-off after a median follow-up of 21 months (range: 11–33). Tissue-based MSI results were concordant with plasma-based G360 results in five of six patients (83%) who had tissue-based test results available, with G360 identifying one more patient with MSI-H than tissue testing. These results suggest that detecting MSI-H by a well-validated liquid biopsy test could predict a robust response to ICI in patients with PDAC. The use of liquid biopsy may expand the identification of PDAC patients with MSI-H tumors and enable treatment with ICI resulting in improved outcomes.
Detection of cryptic balanced chromosomal rearrangements using high-resolution optical genome mapping
Authors: Zhang Shuo , Pei Zhenle , Lei Caixia , Zhu Saijuan , Deng Ke , Zhou Jing , Yang Jingmin , Lu Daru , Sun Xiaoxi , Xu Chenming , Xu Congjian
Published: June 2022

Background

Chromosomal rearrangements have profound consequences in diverse human genetic diseases. Currently, the detection of balanced chromosomal rearrangements (BCRs) mainly relies on routine cytogenetic G-banded karyotyping. However, cryptic BCRs are hard to detect by karyotyping, and the risk of miscarriage or delivering abnormal offspring with congenital malformations in carrier couples is significantly increased. In the present study, we aimed to investigate the potential of single-molecule optical genome mapping (OGM) in unravelling cryptic chromosomal rearrangements.

Methods

Eleven couples with normal karyotypes that had abortions/affected offspring with unbalanced rearrangements were enrolled. Ultra-high-molecular-weight DNA was isolated from peripheral blood cells and processed via OGM. The genome assembly was performed followed by variant calling and annotation. Meanwhile, multiple detection strategies, including FISH, long-range-PCR amplicon-based next-generation sequencing and Sanger sequencing were implemented to confirm the results obtained from OGM.

Results

High-resolution OGM successfully detected cryptic reciprocal translocation in all recruited couples, which was consistent with the results of FISH and sequencing. All high-confidence cryptic chromosomal translocations detected by OGM were confirmed by sequencing analysis of rearrangement breakpoints. Moreover, OGM revealed additional complex rearrangement events such as inverted aberrations, further refining potential genetic interpretation.

Conclusion

To the best of our knowledge, this is the first study wherein OGM facilitate the rapid and robust detection of cryptic chromosomal reciprocal translocations in clinical practice. With the excellent performance, our findings suggest that OGM is well qualified as an accurate, comprehensive and first-line method for detecting cryptic BCRs in routine clinical testing.
Should institutions fund the feedback of individual findings in genomic research?
Authors: Ewuoso Cornelius , Berkman Benjamin , Wonkam Ambroise , de Vries Jantina
Published: June 2022

The article argues the thesis that institutions have aprima facieobligation to fund the feedback of individual findings in genomic research conducted on the African continent by drawing arguments from an underexplored Afro-communitarian view of distributive justice and rights of researchers to be aided. Whilst some studies have explored how institutions have a duty to support return as a form of ancillary care or additional foreseeable service in research by mostly appealing to dominant principles and theories in the Global North, this mostlynormative studyexplores this question by appealing to underexplored African philosophy. This is a new way of thinking about institutional responsibility to fund feedback and responds to the call to decolonise health research in Africa. Further studies are required to study how thisprima facieobligation will interact with social contexts and an institution’s extant relationships to find an actual duty. The research community should also work out procedures, policies and governance structures to facilitate feedback. In our opinion, though the impacts of feeding back can inform how institutions think about their actual duty, these do not obliterate the binding duty to fund feedback.
Association between implantable loop recorder use and secondary stroke prevention: a meta-analysis
Authors: Huang Wen-Yi , Ovbiagele Bruce , Hsieh Cheng-Yang , Lee Meng
Published: June 2022

Objective

To conduct a meta-analysis of randomised controlled trials (RCTs) to evaluate the impact of ILR use on occurrence of recurrent stroke.

Methods

PubMed, EMBASE, CENTRAL and ClinicalTrials.gov were searched from 1966 to November 2021 to identify RCTs comparing ILR versus non-ILR in patients with ischaemic stroke. Relative risk (RR) with 95% CI was used as a measure of the effect of ILR versus non-ILR on recurrent stroke, recurrent ischaemic stroke, AF detection and oral anticoagulant (OAC) initiation. A fixed-effect estimate based on the Mantel-Haenszel method was computed.

Results

We identified three RCTs with 1233 patients with ischaemic stroke. Among three included RCTs, 54 recurrent stroke events were reported in two RCTs and 84 recurrent ischaemic stroke events were reported in three RCTs. Pooled results showed that patients who received ILR versus no ILR was not associated with a significantly reduced risk of recurrent stroke (5.6% vs 8.0%; RR 0.70; 95% CI 0.42 to 1.19) or recurrent ischaemic stroke (5.7% vs 7.9%; RR 0.72; 95% CI 0.48 to 1.10). Compared to non-ILR patients, ILR patients had higher rates of AF detection (12.9% vs 2.4%; RR 5.31; 95% CI, 3.10 to 9.11) and OAC initiation (15.2% vs 5.5%; RR 2.77; 95% CI 1.90 to 4.03).

Conclusions

Patients assigned to ILR vs non-ILR did not have a significantly reduced risk of recurrent stroke or recurrent ischaemic stroke despite higher rates of AF detection and OAC initiation. Sufficiently powered RCTs of ILR to assess the risk of recurrent stroke are warranted.
Primary progressive aphasia: ReADing the clinical GRANularity
Authors: Chokesuwattanaskul Anthipa , Marshall Charles R , van Harskamp Natasja , Houlden Henry , Rohrer Jonathan D , Hardy Chris JD , Warren Jason D
Published: June 2022

Primary progressive aphasia remains a diagnostic challenge despite (or even because of) the increasing availability of ancillary tests and biomarkers. We present a 67-year-old man with apparently sporadic logopenic aphasia and positive Alzheimer biomarkers who was subsequently found also to have a pathogenic mutation in the progranulin gene. This was signalled by early atypical features (mild expressive agrammatism and behavioural change, rapid clinical deterioration) around the core logopenic aphasia syndrome. Each of the canonical progressive aphasia syndromes has a ‘halo’ of less typical variants that may herald alternative or additional pathologies. The accurate diagnosis of primary progressive aphasia depends on careful clinical analysis to direct investigations appropriately.