bluuebunny/crossref_metadata_2025 huggingface dataset:
The Meteoritical Bulletin, No. 109
Authors: Gattacceca Jérôme , McCubbin Francis M. , Grossman Jeffrey , Bouvier Audrey , Bullock Emma , Chennaoui Aoudjehane Hasnaa , Debaille Vinciane , D’Orazio Massimo , Komatsu Mutsumi , Miao Bingkui , Schrader Devin L.
Published: July 2021

Meteoritical Bulletin 109 contains the 2790 meteorites approved by the Nomenclature Committee of the Meteoritical Society in 2020. It includes 17 falls (Al Farciya, Auckland, Cavezzo, Flensburg, Gatuto, Kolang, Mahadeva, Matarka, Narashino, Novo Mesto, Oslo, Saint‐Ouen‐en‐Champagne, Santa Filomena, Tarda, Tiros, Wad Lahteyba, Zhob), with 2336 ordinary chondrites, 131 carbonaceous chondrites (including 8 ungrouped ones), 123 HED achondrites, 41 Martian meteorites, 35 lunar meteorites, 23 iron meteorites, 21 ureilites, 17 primitive achondrites, 13 ungrouped achondrites, 12 mesosiderites, 12 Rumuruti chondrites, 9 enstatite chondrites, 8 pallasites, 4 unclassified meteorites (identified at the surface of Mars), 3 enstatite achondrites, 1 angrite, and 1 ungrouped chondrite. One thousand five hundred and forty‐one are from Antarctica, 763 from Africa, 297 from South America, 127 from Asia, 31 from North America, 11 from Europe, 10 from Oceania, 9 from Mars, and 1 from an unknown location.
Coordinated activity of amoebic formin and profilin are essential for phagocytosis
Authors: Bharadwaj Ravi , Bhattacharya Alok , Somlata
Published: July 2021

For the protist parasite Entamoeba histolytica, endocytic processes, such as phagocytosis, are essential for its survival in the human gut. The actin cytoskeleton is involved in the formation of pseudopods and phagosomal vesicles by incorporating a number of actin‐binding and modulating proteins along with actin in a temporal manner. The actin dynamics, which comprises polymerization, branching, and depolymerization is very tightly regulated and takes place directionally at the sites of initiation of phagocytosis. Formin and profilin are two actin‐binding proteins that are known to regulate actin cytoskeleton dynamics and thereby, endocytic processes. In this article, we report the participation of formin and profilin in E. histolytica phagocytosis and propose that these two proteins interact with each other and their sequential recruitment at the site is required for the successful completion of phagocytosis. The evidence is based on detailed microscopic, live imaging, interaction studies, and expression downregulation. The cells downregulated for expression of formin show absence of profilin at the site of phagocytosis, whereas downregulation of profilin does not affect formin localization.
finFindR: Automated recognition and identification of marine mammal dorsal fins using residual convolutional neural networks
Authors: Thompson Jaime W. , Zero Victoria H. , Schwacke Lori H. , Speakman Todd R. , Quigley Brian M. , Morey Jeanine S. , McDonald Trent L.
Published: July 2021

Photographic identification is an essential research and management tool for marine mammal scientists. However, manual identification of individuals is time‐consuming. To shorten processing times, we developed finFindR, an open‐source application that uses a series of neural networks to autonomously locate dorsal fins in unedited field images, quantify an individual's unique fin characteristics, and match them to an existing photograph catalog. During a blind test comparing manual searching to finFindR for common bottlenose dolphin (Tursiops Tursiops truncatus) photographs, experienced photo‐identification technicians achieved similar match rates but examined an order of magnitude fewer photographs using finFindR (an average of 10 required with finFindR versus 124 with manual search). In those tests, the correct identity was ranked in the first position in 88% of cases and was within the top 50 ranked positions in 97% of cases. Our observations suggest that finFindR's matching capabilities are robust to moderate variation in image quality and fin distinctiveness. Importantly, finFindR allows users to build a catalog of known individuals through time and match an unlimited number of individuals instead of being restricted to a predefined set. finFindR's convolutional neural networks could be re‐trained to identify members of many marine mammal species without altering finFindR's inherent structure.
Examining the association between adiposity and DNA methylation: A systematic review and meta‐analysis
Authors: Do Whitney L. , Gohar Jazib , McCullough Lauren E. , Galaviz Karla I. , Conneely Karen N. , Narayan K. M. Venkat
Published: July 2021

Obesity is associated with widespread differential DNA methylation (DNAm) patterns, though there have been limited overlap in the obesity‐associated cytosine–guanine nucleotide pair (CpG) sites that have been identified in the literature. We systematically searched four databases for studies published until January 2020. Eligible studies included cross‐sectional, longitudinal, or intervention studies examining adiposity and genome‐wide DNAm in non‐pregnant adults aged 18–75 in all tissue types. Study design and results were extracted in the descriptive review. Blood‐based DNAm results in body mass index (BMI) and waist circumference (WC) were meta‐analyzed using weighted sum of Z‐score meta‐analysis. Of the 10,548 studies identified, 46 studies were included in the systematic review with 18 and nine studies included in the meta‐analysis of BMI and WC, respectively. In the blood, 77 and four CpG sites were significant in three or more studies of BMI and WC, respectively. Using a genome‐wide threshold for significance, 52 blood‐based CpG sites were significantly associated with BMI. These sites have previously been associated with many obesity‐related diseases including type 2 diabetes, cardiovascular disease, Crohn's disease, and depression. Our study shows that DNAm at 52 CpG sites represent potential mediators of obesity‐associated chronic diseases and may be novel intervention or therapeutic targets to protect against obesity‐associated chronic diseases.
One million years of diversity shifts in amphibians and reptiles in a Mediterranean landscape: resilience rules the Quaternary
Authors: Martínez‐Monzón Almudena , Cuenca‐Bescós Gloria , Bisbal‐Chinesta Josep‐Francesc , Blain Hugues‐Alexandre
Published: July 2021

In contrast with the well documented strain on extant amphibian and reptile populations today, the Quaternary fossil record of these groups is very conservative showing few changes over long periods of time. In order to establish the non‐human‐induced effect of climate change on herpetofaunal diversity, we collected data from Pleistocene sites in the Sierra de Atapuerca complex (Burgos, Spain), which records the last few million years of changes. Diversity was measured in terms of richness and evenness indices and its relationship to the climatic parameters was analysed with OLS regression models. The highest diversity (richness and evenness; 1‐D) occurred in periods considered to be analogues of the current interglacial, whereas minimum diversity values were reached during periods when conditions were harsher (cooler or glacial stage). In all cases, the diversity values were always restored subsequently, pointing to great resilience. Temperature proves to be the most influential climatic factor. Accordingly, amphibians and reptiles have been able to overcome previous climatic changes successfully. In contrast, the effects of anthropization have generated an uncommon loss of diversity, the like of which has not been seen in the last few million years. The data presented here demonstrate that the current amphibian loss seems to be driven by anthropogenic influence, with climate a factor of a secondary importance.
Chemoselective Photoreaction of Enamides: Divergent Reactivity towards [3+2]‐Photocycloaddition vs Paternò–Büchi Reaction†
Authors: Kandappa Sunil Kumar , Kumarasamy Elango , Singathi Ravichandranath , Valloli Lakshmy Kannadi , Ugrinov Angel , Sivaguru Jayaraman
Published: July 2021

Photoreaction of enamides tethered to a phenyl ketone leads to either [3+2]‐photocycloaddition or Paternò–Büchi reaction. This divergence in chemical reactivity originating from the same excited state was dependent on the reaction temperature. At low temperatures the Paternò–Büchi reaction was preferred, whereas at higher temperatures there was preference toward formation of [3+2]‐photoproduct.
Inventory Policies for Pharmaceutical Distribution in Zambia: Improving Availability and Access Equity
Authors: Gallien Jérémie , Leung Ngai‐Hang Z. , Yadav Prashant
Published: July 2021

In many low‐ and middle‐income countries, including Zambia, stockouts of life‐saving medicines threaten the advancement of the Sustainable Development Goals (SDGs); it is therefore vital to reduce stockouts through the use of improved inventory control policies. The associated medicine distribution problem is challenging because it involves seasonality and uncertainty in both demand and lead times, heterogeneous delivery locations, and lost demand. Besides service level and inventory costs, equity across delivery locations must also be considered. This empirical study is based on an independently validated simulation model constructed from extensive field data, and addresses the lack of rigorous recommendations of inventory policies in this context. It compares the current base‐stock and other policies proposed in the practitioner's literature with an optimization‐based policy adapted from research on industrial settings. Although the optimization‐based policy may need more implementation efforts, it generally outperforms the other evaluated policies. Our results also suggest that the prevalent proportional inventory rationing rules may lead to substantial service level discrepancies between facilities. Finally, the performance metrics of service level and distribution equity can be at odds, prompting non‐trivial design trade‐offs and considerations. This work motivated the development of a digital distribution information system involving smartphones with barcode scanners deployed in 60 health centers, posts, and district hospitals in Zambia until 2018.
Spatially varying multifeedback for robust signaling
Authors: Wan Frederic Y.M.
Published: July 2021

Elaborate regulatory feedback processes are thought to make biological development robust, that is, resistant to changes induced by sustained genetic or environmental perturbations. How this might be accomplished is still not completely understood, especially when models of some known feedback processes have been shown, some analytically and others by numerical simulations, to be ineffective in promoting robust signaling. By working with nonlocal feedback processes, combinations of two of these ineffective feedback processes were found to ensure robustness as measured by a well‐defined robustness index for the Dpp–Tkv (decapentaplegic–thickvein) signaling in the wing imaginal disc of Drosophila fruit flies. In this paper, we show that there are also spatially varying multifeedback combinations of individually ineffective components that are similarly successful. The analysis of these Hill function type multifeedback models are found to be much more challenging mathematically as the relevant boundary‐value problem remains nonlinear even for systems in a steady state of low receptor occupancy.
Structural Injustice and Labour Migration – From Individual Responsibility to Collective Action
Authors: Egan Magnus Skytterholm
Published: July 2021

This paper argues that the vast inequalities in access to migration opportunities and treatment of migrants constitute a structural injustice, and that although states are clearly the most powerful agents in migration injustices, individuals also bear a personal responsibility to ameliorate these injustices. The argument builds on Young's theory of structural injustice and critically applies it to labour migration. The paper argues that wealthy migrants and citizens who benefit from migrant labour have a responsibility to contribute towards ameliorating migration injustice on account of their position of privilege, whereas disadvantaged migrants have a responsibility due to their interest in changing their situation. It then considers how people might discharge such an obligation through collective political action, pointing in particular to non‐governmental organizations, labour unions, and local government. Finally, the paper addresses the objections that positing personal responsibility for labour migration is overly demanding and that the current labour migration regime is meritocratic and fair. The article concludes by showing how this sort of stance can be seen as interest‐driven by privileged groups and argues for the role of disruptive politics in overcoming it.
High‐risk transmission clusters of leprosy in an endemic area in the Northeastern Brazil: A retrospective spatiotemporal modelling (2001–2019)
Authors: Damasceno Dayanne Maria , da Paz Wandklebson Silva , de Souza Carlos Dornels Freire , dos Santos Allan Dantas , Bezerra‐Santos Márcio
Published: July 2021

OBJECTIVES

To analyse and map the leprosy risk areas in the state of Alagoas, an endemic region in the Northeastern Brazil, between 2001 and 2019.

METHODS

Ecological and time series study, using spatial analysis techniques. First, we analyse the epidemiological aspects of leprosy cases, using the data available in the Notifiable Diseases Information System; then, we used the segmented log‐linear regression model to assess time trends. Spatial distribution was analysed by the Local Empirical Bayesian Estimator and by calculating the Global and Local Moran Index. Finally, spatiotemporal clusters were identified through scanning statistics, using the Kulldorf method of retrospective analysis.

RESULTS

We observed that Alagoas showed an average new case detection rate of 14.43/100,000 inhabitants between 2001 and 2019, being classified as highly endemic. The area of highest risk was the 9th health region (state hinterland), with increasing time trend (Annual Percentage Change/APC = 7.2; p‐value < 0.05). Several clusters of high risk of leprosy transmission were verified in Alagoas, including the state capital and hinterland municipalities.

CONCLUSIONS

Our data indicate that active M. leprae transmission persists in Alagoas; that diagnosis is delayed and that there are high‐risk areas, especially in inland municipalities.
Irritable Bowel Syndrome Therapeutic Has Broad-Spectrum Antimicrobial Activity
Authors: Cunningham Ashley L. , Esarte Palomero Orhi , Voss Bradley J. , Trent M. Stephen , Davies Bryan W.
Published: July 2021

Otilonium bromide is a poorly absorbed oral medication used to control irritable bowel syndrome. It is thought to act as a muscle relaxant in the intestine. Here, we show that otilonium bromide has broad-spectrum antibacterial and antifungal activity, including against multidrug-resistant strains. Our results suggest otilonium bromide acts on enteric pathogens and may offer a new scaffold for poorly absorbed intestinal antimicrobial therapy.
Sterilizing Effects of Novel Regimens Containing TB47, Clofazimine, and Linezolid in a Murine Model of Tuberculosis
Authors: Yu Wei , Yusuf Buhari , Wang Shuai , Tian Xirong , Hameed H. M. Adnan , Lu Zhili , Chiwala Gift , Alam Md Shah , Cook Gregory M. , Maslov Dmitry A. , Zhong Nanshan , Zhang Tianyu
Published: July 2021

TB47, a new drug candidate targeting QcrB in the electron transport chain, has shown a unique synergistic activity with clofazimine and forms a highly sterilizing combination. Here, we investigated the sterilizing effects of several all-oral regimens containing TB47 plus clofazimine and linezolid as a block and the roles of fluoroquinolones and pyrazinamide in them.
Characterization of Proteobacterial Plasmid Integron-Encoded
qac
Efflux Pump Sequence Diversity and Quaternary Ammonium Compound Antiseptic Selection in Escherichia coli Grown Planktonically and as Biofilms
Authors: Slipski Carmine J. , Jamieson-Datzkiw Taylor R. , Zhanel George G. , Bay Denice C.
Published: July 2021

Qac efflux pumps from proteobacterial multidrug-resistant plasmids are integron encoded and confer resistance to quaternary ammonium compound (QAC) antiseptics; however, many are uncharacterized and misannotated. A survey of >2,000 plasmid-carried
qac
genes identified 37 unique
qac
sequences that correspond to one of five representative motifs: QacE, QacEΔ1, QacF/L, QacH/I, and QacG.
Dissecting
psa
Locus Regulation in Yersinia pestis
Authors: Li Peng , Wang Xiuran , Smith Carol , Shi Yixin , Wade Joseph T. , Sun Wei
Published: July 2021

Y. pestis
, the etiologic agent of plague, has been responsible for high mortality in several epidemics throughout human history. The plague bacillus has been used as a biological weapon during human history and is currently one of the most likely biological threats. PsaA and PsaE appear to play important roles during
Y. pestis
infection. Understanding their regulation by environmental cues would facilitate a solution to impede
Y. pestis
infection.
Genetic and Biochemical Characterization of the Na
+
/H
+
Antiporters of Pseudomonas aeruginosa
Authors: Foreman Sara , Ferrara Kristina , Hreha Teri N. , Duran-Pinedo Ana E. , Frias-Lopez Jorge , Barquera Blanca
Published: July 2021

Pseudomonas aeruginosa
has four Na
+
/H
+
antiporters that connect and interconvert its Na
+
and H
+
gradients. We have constructed four deletion mutants, each of which has only one of the four Na
+
/H
+
antiporters.
A new dysferlin gene mutation in a Portuguese family with Miyoshi myopathy
Authors: Ganchinho Lucas Sandra , Vieira Santos Inês , Pencas Alfaiate Filipe Jorge , Lino Ireneia
Published: July 2021

Dysferlinopathies are autosomal recessive muscular dystrophies caused by mutations in the dysferlin gene (DYSF). A 33-year-old man was born to a non-consanguineous couple. At the age of 25 he stared to feel weakness of the distal lower limbs and also experienced episodes of rhabdomyolysis. Electromyography showed a myopathic pattern, and muscle biopsy revealed dystrophic changes with absence of dysferlin. Genetic analysis was positive for a mutation in the c3367_3368del DYSF gene (p.Lys1123GLUFS*2). After 8 years of disease evolution the symptomatology worsened. This is the first report of this mutation of the DYSF gene identified in a non-consanguineous Portuguese family, studied over 8 years. We believe the mutation is responsible for the Miyoshi myopathy. Disease progression cannot be predicted in either the patient or carrier family because there are no similar cases previously described in the literature.
Hypomagnesaemia causing functional hypoparathyroidism in rheumatic mitral stenosis leading to sudden cardiac arrest in a young woman
Authors: Jacob Jeny , Raghothama Srivatsa , Subramanyam Kodangala , Johny Dilip
Published: July 2021

A 23-year-old young woman with a known history of valvular heart disease of rheumatic origin, post balloon mitral valvotomy 5 years ago, presented with fever, palpitations and breathlessness. ECG showed atrial fibrillation with fast ventricular rate. A 2D transthoracic echocardiography showed severe restenosis of mitral valve and moderate left ventricular dysfunction. She was admitted for evaluation of fever and control of the ventricular rate. She sustained cardiac arrest due to unknown cause and was resuscitated. When the patient sustained another cardiac arrest, torsades de pointes was detected on the monitor. Blood parameters showed hypomagnesaemia, hypocalcaemia and hypokalaemia, causing functional hypoparathyroidism which was treated with intravenous magnesium, oral calcium and vitamin D supplements. Timely detection of a tachyarrhythmia due to a ventricular origin was life saving, which is rarely seen in patients with rheumatic heart disease and mitral stenosis.
Telemammography for breast cancer screening: a cost-effective approach in Argentina
Authors: Malek Pascha Victoria Alba , Sun Li , Gilardino Ramiro , Legood Rosa
Published: July 2021

Objectives

Argentina is a low and middle-income country (LMIC) with a highly fragmented healthcare system that conflicts with access to healthcare stated by the country’s Universal Health Coverage plan. A tele-mammography network could improve access to breast cancer screening decreasing its mortality. This research aims to conduct an economic evaluation of the implementation of a tele-mammography program to improve access to healthcare.

Methods

A cost-utility analysis was performed to explore the incremental benefit of annual tele-mammography screening for at-risk Argentinian women over 40 years old. A Markov model was developed to simulate annual mammography or tele-mammography screening in two hypothetical population-based cohorts of asymptomatic women. Parameter uncertainty was evaluated through deterministic and probabilistic sensitivity analysis. Model structure uncertainty was also explored to test the robustness of the results.

Results

It was estimated that 31 out of 100 new cases of breast cancer would be detected by mammography and 39/100 by tele-mammography. The model returned an incremental cost-effectiveness ratio (ICER) of £26 051/quality-adjusted life-year (QALY) which is lower than the WHO-recommended threshold of £26 288/QALY for Argentina. Deterministic sensitivity analysis showed the ICER is most sensitive to the uptake and sensitivity of the screening tests. Probabilistic sensitivity analysis showed tele-mammography is cost-effective in 59% of simulations.

Discussion

Tele-mammography should be considered for adoption as it could improve access to expertise in underserved areas where adherence to screening protocols is poor. Disaggregated data by province is needed for a better- informed policy decision. Telemedicine could also be beneficial in ensuring the continuity of care when health systems are under stress like in the current COVID-19 pandemic.

Conclusion

There is a 59% chance that tele-mammography is cost-effective compared to mammography for at-risk Argentinian women over 40- years old, and should be adopted to improve access to healthcare in underserved areas of the country.
Relationship between management and resilience in healthcare: a study protocol for a systematic review
Authors: Petersen Erika E , Lyng Hilda Bø , Ree Eline , Wiig Siri
Published: July 2021

Introduction

Management has been identified as a critical component of organisational resilience when responding to adverse events and crises, as managers must ensure an effective operational response and provide direction and guidance to teams. While there are many management approaches, strategies and interventions that have been applied and studied in healthcare, the impact of them in relation to resilience in healthcare has not been explored, particularly at the organisational level. Understanding the impact of management approaches, strategies and interventions on resilience has the potential to inform healthcare organisations on how to better use management to prepare and respond to organisational adverse events. The objective of this mixed-methods systematic review is to understand the relationship between management and organisational resilience in healthcare, including management approaches and strategies that promote resilience in healthcare.

Methods and analysis

A search through MEDLINE, Cumulative Index to Nursing and Allied Health Literature, PubMed and EMBASE will be conducted between 1 August 2021 and 31 December 21. This review will consider empirical quantitative, qualitative and mixed-methods studies published in English from 2010 to the present that meet the inclusion and exclusion criteria. Selected studies will be assessed in detail and extracted data will be reviewed by two independent reviewers. Results of the search will be reported in full in the final systematic review and presented in a Preferred Reporting Items for Systematic Reviews and Meta-Analysis flow diagram. This review will follow a convergent integrated approach to data synthesis and integration.

Ethics and dissemination

This systematic literature review includes no collection of primary data; hence ethical approval will not be sought. The outcomes from this review will be disseminated in a peer-reviewed journal, as conference presentation, and as condensed summary for managers in healthcare and policy-makers.

PROSPERO registration number

CRD42020223362.
Challenges facing essential workers: a cross-sectional survey of the subjective mental health and well-being of New Zealand healthcare and ‘other’ essential workers during the COVID-19 lockdown
Authors: Bell Caroline , Williman Jonathan , Beaglehole Ben , Stanley James , Jenkins Matthew , Gendall Philip , Rapsey Charlene , Every-Palmer Susanna
Published: July 2021

Objectives

To compare psychological outcomes, experiences and sources of stress over the COVID-19 lockdown in New Zealand in essential workers (healthcare and ‘other’ essential workers) with that of workers in nonessential work roles.

Design

Online cross-sectional survey.

Setting

Conducted in New Zealand over level 4 lockdown in April/May 2020.

Participants

Findings from employed participants (2495) are included in this report; 381 healthcare workers, 649 ‘other’ essential workers and 1465 nonessential workers.

Primary and secondary outcome measures

Measures included psychological distress (Kessler Psychological Distress Scale (K10)), anxiety (Generalised Anxiety Disorder (GAD-7)), well-being (WHO-5), alcohol use, subjective experiences and sources of stress. Differences between work categories were quantified as risk ratios or χ2tests.

Results

After controlling for confounders that differed between groups of essential and nonessential workers, those in healthcare and those in ‘other’ essential work were at 71% (95% CI 1.29 to 2.27) and 59% (95% CI 1.25 to 2.02) greater risk respectively, of moderate levels of anxiety (GAD-7 ≥10), than those in nonessential work. Those in healthcare were at 19% (95% CI 1.02 to 1.39) greater risk of poor well-being (WHO-5 <13). There was no evidence of differences across work roles in risk for psychological distress (K10 ≥12) or increased alcohol use. Healthcare and ‘other’ essential workers reported increased workload (p<0.001) and less uncertainty about finances and employment than those in nonessential work (p<0.001). Healthcare and nonessential workers reported decreased social contact. No difference by work category in health concerns was reported; 15% had concerns about participants’ own health and 33% about other people’s health.

Conclusions

During the pandemic lockdown, essential workers (those in healthcare and those providing ‘other’ essential work) were at increased risk of anxiety compared with those in nonessential work, with those in healthcare also being at increased risk of poor well-being. This highlights the need to recognise the challenges this vital workforce face in pandemics.
Thinking green: modelling respirator reuse strategies to reduce cost and waste
Authors: Chu Jacqueline , Ghenand Omkar , Collins Joy , Byrne James , Wentworth Adam , Chai Peter R. , Dadabhoy Farah , Hur Chin , Traverso Giovanni
Published: July 2021

Objectives

To compare the impact of respirator extended use and reuse strategies with regard to cost and sustainability during the COVID-19 pandemic.

Design

Cost analysis.

Setting

USA.

Participants

All healthcare workers within the USA.

Interventions

Not applicable.

Main outcome measures

A model was developed to estimate usage, costs and waste incurred by several respirator usage strategies over the first 6 months of the pandemic in the USA. This model assumed universal masking of all healthcare workers. Estimates were taken from the literature, government databases and commercially available data from approved vendors.

Results

A new N95 respirator per patient encounter would require 7.41 billion respirators, cost $6.38 billion and generate 84.0 million kg of waste in the USA over 6 months. One respirator per day per healthcare worker would require 3.29 billion respirators, cost $2.83 billion and generate 37.22 million kg of waste. Decontamination by ultraviolet germicidal irradiation would require 1.64 billion respirators, cost $1.41 billion and accumulate 18.61 million kg of waste. H2O2vapour decontamination would require 1.15 billion respirators, cost $1.65 billion and produce 13.03 million kg of waste. One reusable respirator with daily disposable filters would require 18 million respirators, cost $1.24 billion and generate 15.73 million kg of waste. Pairing a reusable respirator with H2O2vapour-decontaminated filters would reduce cost to $831 million and generate 1.58 million kg of waste. The use of one surgical mask per healthcare worker per day would require 3.29 billion masks, cost $460 million and generate 27.92 million kg of waste.

Conclusions

Decontamination and reusable respirator-based strategies decreased the number of respirators used, costs and waste generated compared with single-use or daily extended-use of disposable respirators. Future development of low-cost,simple technologies to enable respirator and/or filter decontamination is needed to further minimise the economic and environmental costs of masks.
Health workers’ perspectives of a mobile health tool to improve diagnosis and management of paediatric acute respiratory illnesses in Uganda: a qualitative study
Authors: Ellington Laura Elizabeth , Najjingo Irene , Rosenfeld Margaret , Stout James W , Farquhar Stephanie A , Vashistha Aditya , Nekesa Bridget , Namiya Zaituni , Kruse Agatha J , Anderson Richard , Nantanda Rebecca
Published: July 2021

Objectives

Mobile health tools have potential to improve the diagnosis and management of acute lower respiratory illnesses (ALRI), a leading cause of paediatric mortality worldwide. The objectives were to evaluate health workers’ perceptions of acceptability, usability and feasibility of Acute Lower Respiratory Illness Treatment and Evaluation (ALRITE), a novel mobile health tool to help frontline health workers diagnose, treat and provide education about ALRI in children <5 years.

Design

A qualitative study including semistructured interviews with health facility administrators and focus groups with primary care health workers.

Setting

Two federally funded Ugandan primary care health facilities, one peri-urban and one rural.

Participants

We enrolled 3 health administrators and 28 health workers (clinical officers and nurses).

Intervention

The ALRITE smartphone application was developed to help frontline health workers adhere to ALRI guidelines and differentiate wheezing illnesses from pneumonia in children under 5 years of age. ALRITE contains a simple decision tree, a partially automated respiratory rate counter, educational videos and an adapted respiratory assessment score to determine bronchodilator responsiveness. We performed a demonstration of ALRITE for participants at the beginning of interviews and focus groups. No participant had used ALRITE prior.

Results

Themes impacting the potential implementation of ALRITE were organised using individual-level, clinic-level and health-system level determinants. Individual-level determinants were acceptability and perceived benefit, usability, provider needs and provider–patient relationship. Clinic-level determinants were limited resources and integration within the health centre. Systems-level determinants included medication shortages and stakeholder engagement.

Conclusions

Incorporation of these themes will ready ALRITE for field testing. Early engagement of end users provides insights critical to the development of tailored mHealth decision support tools.
Effect of power Doppler and digital subtraction techniques on the comparison of myocardial contrast echocardiography with SPECT
Authors: Haluska B , Case C , Short L , Anderson J , Marwick T H
Published: July 2021

OBJECTIVE

To compare the accuracy and feasibility of harmonic power Doppler and digitally subtracted colour coded grey scale imaging for the assessment of perfusion defect severity by single photon emission computed tomography (SPECT) in an unselected group of patients.

DESIGN

Cohort study.

SETTING

Regional cardiothoracic unit.

PATIENTS

49 patients (mean (SD) age 61 (11) years; 27 women, 22 men) with known or suspected coronary artery disease were studied with simultaneous myocardial contrast echo (MCE) and SPECT after standard dipyridamole stress.

MAIN OUTCOME MEASURES

Regional myocardial perfusion by SPECT, performed with 99mTc tetrafosmin, scored qualitatively and also quantitated as per cent maximum activity.

RESULTS

Normal perfusion was identified by SPECT in 225 of 270 segments (83%). Contrast echo images were interpretable in 92% of patients. The proportion of normal MCE by grey scale, subtracted, and power Doppler techniques were respectively 76%, 74%, and 88% (p < 0.05) at > 80% of maximum counts, compared with 65%, 69%, and 61% at < 60% of maximum counts. For each technique, specificity was lowest in the lateral wall, although power Doppler was the least affected. Grey scale and subtraction techniques were least accurate in the septal wall, but power Doppler showed particular problems in the apex. On a per patient analysis, the sensitivity was 67%, 75%, and 83% for detection of coronary artery disease using grey scale, colour coded, and power Doppler, respectively, with a significant difference between power Doppler and grey scale only (p < 0.05). Specificity was also the highest for power Doppler, at 55%, but not significantly different from subtracted colour coded images.

CONCLUSIONS

Myocardial contrast echo using harmonic power Doppler has greater accuracy than with grey scale imaging and digital subtraction. However, power Doppler appears to be less sensitive for mild perfusion defects.
Unusual localisation of a ventricular septal defect following blunt chest trauma
Authors: Pierli C , Iadanza A , Del Pasqua A , Sinicropi G
Published: July 2021

A 64 year old man presented with a traumatic ventricular septal defect following blunt chest trauma 40 years before. Echocardiography and left ventriculography were helpful in locating the unusual septal defect, which was subpulmonary. The shunt was small, but the anomalous chronic overload led to right ventricular failure. The surgical correction was thus too late to improve right ventricular function.
Incremental shuttle walk test in the assessment of patients for heart transplantation
Authors: Lewis M E , Newall C , Townend J N , Hill S L , Bonser R S
Published: July 2021

OBJECTIVE

To compare the incremental shuttle walk test (ISWT) with treadmill exercise testing (TT) derived measurement of peak oxygen consumption (peak Vo2) in patients undergoing assessment for cardiac transplantation.

DESIGN

Prospective comparison. All investigations occurred during a single period of admission for transplant assessment.

SETTING

Single UK cardiothoracic transplantation unit.

PATIENTS

25 patients recruited (21 men). Mean age was 53 years.

INTERVENTIONS

Patients underwent two TT of peak Vo2 using the modified Naughton protocol and three (one practice) ISWT. Investigations were performed on consecutive days.

MAIN OUTCOME MEASURES

Main outcome measures were repeatability of TT and ISWT assessments; relation between peak Vo2 and distance walked in the ISWT; and receiver operating characteristic (ROC) analysis to establish a distance walked in the ISWT that predicted which patients would have a peak Vo2 greater than 14 ml/min/kg.

RESULTS

Both the ISWT and the TT were highly reproducible. Following the first practice walk, mean (SD) ISWT distances were 400.0 (146) m (ISWT2) and 401.3 (129) m (ISWT3),r = 0.90, p < 0.0001. Mean peak Vo2 by TT was 15.2 (4.4) ml/kg/min (TT1) and 15.0 (4.4) ml/kg/min (TT2), r = 0.83, p < 0.0001. The results revealed a strong correlation between distance covered in the ISWT and peak Vo2obtained during TT (r = 0.73, p = 0.0001). ROC analysis showed that a distance walked of 450 m allowed the selection of patients with a peak Vo2 of over 14 ml/min/kg.

CONCLUSIONS

This work confirms the utility of the ISWT in the assessment of exercise capacity in patients with severe heart failure undergoing assessment for cardiac transplantation. ISWT may provide a widely applicable surrogate measure for peak Vo2 estimation in this population. Shuttle distance walked may therefore allow the convenient, serial assessment of patients with heart failure before referral for transplantation.
Abnormalities of right ventricular long axis function after atrial repair of transposition of the great arteries
Authors: Derrick G P , Josen M , Vogel M , Henein M Y , Shinebourne E A , Redington A N
Published: July 2021

BACKGROUND

While volume derived global indices of right ventricle (RV) function are frequently abnormal after the Mustard procedure, the mechanism for these abnormalities is poorly understood. RV muscle fibres are predominantly arranged longitudinally and thus indices derived in the long axis may better describe RV function.

METHODS

20 survivors of the Mustard operation were studied (age 7.8–37.3 years, median 14.2 years). Long axis recordings from the apical four chamber view were obtained with the M mode cursor positioned through the lateral angle of the tricuspid valve annulus. M mode traces were recorded on paper and later digitised to derive total atrioventricular ring excursion, peak lengthening rate, and peak shortening rate. These data were averaged and compared with control data for the normal RV and left ventricle (LV).

RESULTS

RV total atrioventricular ring excursion was lower than that for the RV (p < 0.0001) or LV (p < 0.005) of controls. Peak lengthening rate was lower than the normal RV (p < 0.0001) and LV (p < 0.0001) rates. Furthermore, peak shortening rate was less than that of normal RV (p < 0.0001) and normal LV (p < 0.005) controls.

CONCLUSION

Systemic RV long axis function is notably reduced compared with that of either the normal subpulmonary RV or the systemic LV. This presumably reflects the response of the predominantly longitudinally arranged myocardial fibres to increased afterload. However, such measurements may provide a more sensitive marker for progressive changes in global function during long term follow up.
Magnesium causes nitric oxide independent coronary artery vasodilation in humans
Authors: Teragawa H , Kato M , Yamagata T , Matsuura H , Kajiyama G
Published: July 2021

OBJECTIVE

To determine how magnesium affects human coronary arteries and whether endothelium derived nitric oxide (EDNO) is involved in the coronary arterial response to magnesium.

DESIGN

Quantitative coronary angiography and Doppler flow velocity measurements were used to determine the effects of the nitric oxide synthase inhibitorNG-monomethyl-L-arginine (L-NMMA) on magnesium induced dilation of the epicardial and resistance coronary arteries.

SETTING

Hiroshima University Hospital a tertiary cardiology centre.

PATIENTS

17 patients with angiographically normal coronary arteries.

INTERVENTIONS

Magnesium sulfate (MgSO4) (0.02 mmol/min and 0.2 mmol/min) was infused for two minutes into the left coronary ostium before and after intracoronary infusion of L-NMMA.

MAIN OUTCOME MEASURES

Diameter of the proximal and distal segments of the epicardial coronary arteries and coronary blood flow.

RESULTS

At a dose of 0.02 mmol/min, MgSO4 did not affect the coronary arteries. At a dose of 0.2 mmol/min, MgSO4 caused coronary artery dilation (mean (SEM) proximal diameter 3.00 (0.09) to 3.11 (0.09) mm; distal 1.64 (0.06) to 1.77 (0.07) mm) and increased coronary blood flow (79.3 (7.5) to 101.4 (9.9) ml/min, p < 0.001 vbaseline for all). MgSO4 increased the changes in these parameters after the infusion of L-NMMA (p < 0.001v baseline).

CONCLUSIONS

Magnesium dilates both the epicardial and resistance coronary arteries in humans. Furthermore, the coronary arterial response to magnesium is dose dependent and independent of EDNO.
GCH1 induces immunosuppression through metabolic reprogramming and IDO1 upregulation in triple-negative breast cancer
Authors: Wei Jin-Li , Wu Si-Yu , Yang Yun-Song , Xiao Yi , Jin Xi , Xu Xiao-En , Hu Xin , Li Da-Qiang , Jiang Yi-Zhou , Shao Zhi-Ming
Published: July 2021

Purpose

Regulatory T cells (Tregs) heavily infiltrate triple-negative breast cancer (TNBC), and their accumulation is affected by the metabolic reprogramming in cancer cells. In the present study, we sought to identify cancer cell-intrinsic metabolic modulators correlating with Tregs infiltration in TNBC.

Experimental design

Using the RNA-sequencing data from our institute (n=360) and the Molecular Taxonomy of Breast Cancer International Consortium TNBC cohort (n=320), we calculated the abundance of Tregs in each sample and evaluated the correlation between gene expression levels and Tregs infiltration. Then, in vivo and in vitro experiments were performed to verify the correlation and explore the underlying mechanism.

Results

We revealed that GTP cyclohydrolase 1 (GCH1) expression was positively correlated with Tregs infiltration and high GCH1 expression was associated with reduced overall survival in TNBC. In vivo and in vitro experiments showed that GCH1 increased Tregs infiltration, decreased apoptosis, and elevated the programmed cell death-1 (PD-1)-positive fraction. Metabolomics analysis indicated that GCH1 overexpression reprogrammed tryptophan metabolism, resulting in L-5-hydroxytryptophan (5-HTP) accumulation in the cytoplasm accompanied by kynurenine accumulation and tryptophan reduction in the supernatant. Subsequently, aryl hydrocarbon receptor, activated by 5-HTP, bound to the promoter of indoleamine 2,3-dioxygenase 1 (IDO1) and thus enhanced the transcription of IDO1. Furthermore, the inhibition of GCH1 by 2,4-diamino-6-hydroxypyrimidine (DAHP) decreased IDO1 expression, attenuated tumor growth, and enhanced the tumor response to PD-1 blockade immunotherapy.

Conclusions

Tumor-cell-intrinsic GCH1 induced immunosuppression through metabolic reprogramming and IDO1 upregulation in TNBC. Inhibition of GCH1 by DAHP serves as a potential immunometabolic strategy in TNBC.
Home dampness, current allergic diseases, and respiratory infections among young adults
Authors: Kilpeläinen M , Terho E O , Helenius H , Koskenvuo M
Published: July 2021

BACKGROUND

The relation between home dampness and respiratory symptoms among adults is well confirmed, but data on specific allergic diseases and respiratory infections is more limited. Individual factors that may enhance susceptibility to the effects of home dampness are mainly unknown.

METHODS

The association between home dampness and current physician diagnosed asthma, allergic rhinitis, allergic conjunctivitis, atopic dermatitis, common colds, and bacterial respiratory infections was studied in a questionnaire survey of 10 667 Finnish first year university students aged 18–25 years. The dampness categories analysed were visible mould and visible mould or damp stains or water damage during the last year. In multivariate analyses adjustment was made for parental education, active and passive smoking, type and place of residence, pets, and wall to wall carpets. The interaction effect of atopic heredity and dampness was investigated.

RESULTS

Visible mould or damp stains or water damage was reported by 15.0% of the respondents. In multivariate models there was a positive association between home dampness and current asthma, allergic rhinitis, and atopic dermatitis, as well as common colds ⩾4 times per year and other respiratory infections, but not between home dampness and allergic conjunctivitis. The strongest association was found between exposure to visible mould and asthma (OR 2.21, 95% CI 1.48 to 3.28) and common colds (OR 1.49, 95% CI 1.18 to 1.87). The risk of current asthma in damp homes was highest among subjects with atopic heredity.

CONCLUSIONS

The risk of current asthma, allergic rhinitis, and atopic dermatitis was higher in damp homes. Of the respiratory infections, the risk of common colds was most clearly increased.
Enhanced survival of lung granulocytes in an animal model of asthma: evidence for a role of GM-CSF activated STAT5 signalling pathway
Authors: Turlej R K , Fiévez L , Sandersen C F , Dogné S , Kirschvink N , Lekeux P , Bureau F
Published: July 2021

BACKGROUND

As granulocyte/macrophage colony stimulating factor (GM-CSF) mediated delay of granulocyte apoptosis contributes to the accumulation of inflammatory cells at the site of inflammation in many diseases, we sought to determine whether asthma is also associated with a GM-CSF dependent increase in lung granulocyte survival. Moreover, because GM-CSF mediates its effects through activation of signal transducer and activator of transcription 5 (STAT5), we also investigated the potential role of STAT5 in allergic inflammation.

METHODS

Blood granulocytes were recovered from six healthy and six heaves affected horses, a model of asthma. Lung granulocytes were obtained by bronchoalveolar lavage (BAL) from the same horses. Granulocytes were cultured in the presence or absence of anti-GM-CSF receptor antibodies for different times and apoptosis was determined using the Annexin-V/propidium iodide detection method. Nuclear protein extracts from cultured granulocytes were analysed for STAT5 binding activity by electrophoretic mobility shift assay.

RESULTS

BAL fluid granulocytes from heaves affected horses demonstrated a significant delay in apoptosis compared with blood granulocytes from the same horses and blood and BAL fluid granulocytes from healthy horses. Conversely, the rate of apoptosis in blood granulocytes from healthy and heaves affected horses was comparable. The enhanced survival of BAL fluid granulocytes from affected horses was suppressed in the presence of antibodies directed against GM-CSF receptors. Increased levels of active STAT5 were found in BAL fluid granulocytes from heaves affected horses and were markedly reduced after treatment with anti-GM-CSF receptor antibodies.

CONCLUSIONS

These data indicate that granulocyte survival is enhanced in the lung of heaves affected horses and suggest a role for a GM-CSF activated STAT5 pathway in delaying apoptosis of lung granulocytes in this model of asthma.
Aerosolised iloprost improves pulmonary haemodynamics in patients with primary pulmonary hypertension receiving continuous epoprostenol treatment
Authors: Petkov V , Ziesche R , Mosgoeller W , Schenk P , Vonbank K , Stiebellehner L , Raderer M , Brunner Ch , Kneussl M , Block L H
Published: July 2021

BACKGROUND

Continuous intravenous treatment with epoprostenol significantly improves pulmonary haemodynamics and survival in patients with primary pulmonary hypertension (PPH). Its beneficial effect, however, may be blunted due to adverse effects such as catheter sepsis and systemic hypotension. Recent investigations have shown that inhaled iloprost is effective in the treatment of PPH. Based on their different pharmacokinetics, we hypothesised that the combination of intravenous epoprostenol and inhaled iloprost would be more efficacious than epoprostenol alone during acute testing in patients with PPH.

METHODS

The effect of a single dose of inhaled iloprost (30 μg total over 15 minutes) on pulmonary haemodynamics was examined in eight patients with PPH (initial non-responders to nitric oxide) who had considerable adverse effects during treatment with epoprostenol.

RESULTS

The combination of inhaled iloprost and intravenous epoprostenol significantly improved mean pulmonary artery pressure (MPAP), cardiac index (CI), mixed venous oxygen saturation (Svo2), and systemic arterial oxygen pressure (Pao2) compared with epoprostenol treatment alone. Mean systemic arterial pressure (MSAP) and pulmonary capillary wedge pressure (PCWP) remained unchanged.

CONCLUSIONS

The pulmonary vasoreactivity shown by additional iloprost inhalation during effective epoprostenol treatment suggests that an improvement of treatment for pulmonary hypertension may be possible by combining vasoactive substances.