bluuebunny/crossref_metadata_2025 huggingface dataset:
A national retrospective cohort study of mechanical ventilator availability and its association with mortality risk in intensive care patients with COVID-19
Authors: Wilde Harrison , Mellan Thomas A , Hawryluk Iwona , Dennis John , Denaxas Spiros , Pagel Christina , Duncan Andrew , Bhatt Samir , Flaxman Seth , Mateen Bilal A , Vollmer Sebastian
Published: January 2021

Objectives: To determine if there is an association between survival rates in intensive care units (ICU) and occupancy of the unit on the day of admission.

Design: National retrospective observational cohort study during the COVID-19 pandemic.

Setting: 90 English hospital trusts (i.e. groups of hospitals functioning as single operational units).

Participants: 6,686 adults admitted to an ICU in England between 2nd April and 1st December, 2020 (inclusive), with presumed or confirmed COVID-19, for whom data was submitted to the national surveillance programme and met study inclusion criteria.

Interventions: N/A

Main Outcomes and Measures: A Bayesian hierarchical approach was used to model the association between hospital trust level (mechanical ventilation compatible) bed occupancy, and in-hospital all-cause mortality. Results were adjusted for unit characteristics (pre-pandemic size), individual patient-level demographic characteristics (age, sex, ethnicity, time-to-ICU admission), and recorded chronic comorbidities (obesity, diabetes, respiratory disease, liver disease, heart disease, hypertension, immunosuppression, neurological disease, renal disease).

Results: 121,151 patient-days were observed, with a mortality rate of 20.8 per 1,000 patient days. Adjusting for patient-level factors, mortality was higher for admissions during periods of high occupancy (>85% occupancy versus the baseline of 45 to 85%) [OR 1.18 (95% posterior credible interval (PCI): 1.00 to 1.38)]. In contrast, mortality was decreased for admissions during periods of low occupancy (<45% relative to the baseline) [OR 0.79 (95% PCI: 0.69 to 0.90)].

Conclusion and Relevance: Increasing occupancy of beds compatible with mechanical ventilation, a proxy for operational strain, is associated with a higher mortality risk for individuals admitted to ICU. Public health interventions (such as expeditious vaccination programmes and non-pharmaceutical interventions) to control both incidence and prevalence of COVID-19, and therefore keep ICU occupancy low in the context of the pandemic, are necessary to mitigate the impact of this type of resource saturation.

Trial Registration: N/A
Rates and predictors of uptake of formal and informal mental health support during the COVID-19 pandemic: an analysis of 26,740 adults in the UK in lockdown
Authors: Bu Feifei , Mak Hei Wan , Fancourt Daisy
Published: January 2021

Purpose

The coronavirus disease 2019 (COVID-19) pandemic has put a great strain on people’s mental health. A growing number of studies have shown worsening mental health measures globally during the pandemic. However, there is a lack of empirical study on how people support their mental health during the COVID-19 pandemic. This study aimed to examine a number of formal and informal mental health supports. Further, it explored factors that might be associated with the use of different types mental health support.

Method

Data from 26,740 adults in the UCL COVID -19 Social Study were analysed between 13thApril, 2020 and 3rdJuly, 2020. Data were analysed using logistic and Poisson regression models.

Results

About 45% of people reported talking to friends or family members to support their mental health, 43% engaging in self-care activities, 20% taking medication, 9% speaking to mental health professionals, 8% talking to a GP or other health professional, and another 8% using helpline or online services. Gender, education, living status, loneliness, pre-existing mental health conditions, general depression and anxiety, coping and personality were found to be associated with the use of mental health support.

Conclusion

While the negative impacts caused by the COVID-19 pandemic are inevitable, people can play an active role in managing their mental health. Understanding the patterns and predictors of various kinds of mental health support during the pandemic is crucial for future service planning and delivery through recognising potential barriers to mental health care faced by certain groups.
Proton magnetic resonance spectroscopy in frontotemporal lobar degeneration-related syndromes
Authors: Murley Alexander G , Tsvetanov Kamen A , Rouse Matthew A , Jones P Simon , Sværke Katrine , Li Win , Carpenter T Adrian , Rowe James B
Published: January 2021

Objective

To measure cortical metabolite deficitsin vivoin syndromes associated with frontotemporal lobar degeneration, in relation to cognitive and behavioral change.

Methods

Sixty patients were recruited with a clinical syndrome associated with frontotemporal lobar degeneration (behavioral variant frontotemporal dementia n=11, progressive supranuclear palsy n=26, corticobasal syndrome n=11, primary progressive aphasias n=12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex using 3T semi-laser magnetic resonance spectroscopy. Metabolite concentrations were corrected for age, sex, and partial volume. We related corrected metabolite concentrations to cognitive and behavioral measures using canonical correlation analysis.

Results

Metabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64)=1.73, p<0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioral variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioral impairment (canonical correlation analysis R=0.95, p<0.001).

Conclusion

Magnetic resonance spectroscopy confirms behaviourally relevant metabolite deficits including glutamate, in syndromes associated with frontotemporal lobar degeneration. Magnetic resonance spectroscopy may be a useful index of neurodegeneration, and highlight candidates for pharmacological treatment.
Integrative Omics Reveal Novel Protein Targets For Chronic Obstructive Pulmonary Disease Biomarker Discovery
Authors: Cordero Ana I Hernandez , Milne Stephen , Yang Chen Xi , Li Xuan , Shi Henry , Sin Don D. , Obeidat Ma’en
Published: January 2021

Background

Large genome-wide association studies (GWAS) and other genetic studies have revealed genetic loci that are associated with chronic obstructive pulmonary disease (COPD). However, the proteins responsible for COPD pathogenesis remain elusive. We used integrative-omics by combining genetics of lung function and COPD with genetics of proteome to identify proteins underlying lung function variation and COPD risk.

Methods

We used summary statistics from the GWAS of human plasma proteome from the INTERVAL cohort (n=3,301) and integrated these data with lung function GWAS results from the UK Biobank cohorts (n=400,102) and COPD GWAS results from the ICGC cohort (35,735 cases and 222,076 controls). We performed in parallel: a proteome-wide Bayesian colocalization, and a proteome-wide Mendelian Randomization (MR) analyses. Next, we selected proteins that colocalized with lung function and/or COPD risk and explored their causal association with lung function and/or COPD using MR analysis (P<0.05).

Results

We found 537, 607, and 250 proteins that colocalized with force expiratory volume in one second (FEV1), FEV1/forced vital capacity (FVC), or COPD risk, respectively. Of these, 1,051 were unique proteins. The sRAGE protein demonstrated the strongest colocalization with FEV1/FVC and COPD risk, while QSOX2, FAM3D and F177A proteins had the strongest associations with FEV1. Of these, 37 proteins that colocalized with lung function and/or COPD, also had a significant causal association. These included proteins such as PDE4D, QSOX2 and RGAP1, amongst others.

Conclusion

Integrative-omics reveals new proteins related to lung function. These proteins may play important roles in the pathogenesis of COPD.
A heritable androgenic mechanism of female intrasexual competition in cooperatively breeding meerkats
Authors: Drea Christine M. , Davies Charli S. , Greene Lydia K. , Mitchell Jessica , Blondel Dimitri V. , Shearer Caroline L. , Feldblum Joseph T. , Dimac-Stohl Kristin A. , Smyth-Kabay Kendra N. , Clutton-Brock Tim H.
Published: January 2021

Female intrasexual competition can be intense in cooperatively breeding species, with the dominant breeder or matriarch limiting reproduction in subordinates via aggression, eviction or infanticide. In males, these tendencies bidirectionally link to testosterone, but in females, there has been no systematic investigation of androgen-mediated behaviour within and across generations. In 22 wild meerkat (Suricata suricatta) clans, we show that matriarchs 1) express peak androgen concentrations during late gestation, 2) when displaying peak feeding competition, dominance, and evictions, and 3) relative to subordinates, produce offspring that are more aggressive in early development. Late-gestation, antiandrogen treatment of matriarchs 4) reduced their dominance behaviour, was associated with infrequent evictions, decreased social centrality within the clan, 5) increased aggression in cohabiting subordinate dams, and 6) reduced their offspring’s aggression. These effects implicate androgen-mediated aggression in the operation of female sexual selection, and intergenerational transmission of ‘masculinised’ phenotypes in the evolution of meerkat cooperative breeding.
An insight into neurotoxic and toxicity of spike fragments SARS-CoV-2 by exposure environment: A threat to aquatic health?
Authors: Charlie-Silva Ives , Araújo Amanda P. C. , Guimarães Abraão T. B. , Veras Flávio P , Braz Helyson L. B. , de Pontes Letícia G. , Jorge Roberta J. B. , Belo Marco A. A. , Fernandes Bianca H V. , Nóbrega Rafael H. , Galdino Giovane , Condino-Neto Antônio , Galindo-Villegas Jorge , Machado-Santelli Glaucia M. , Sanches Paulo R. S. , Rezende Rafael M. , Cilli Eduardo M. , Malafaia Guilherme
Published: January 2021

The Spike protein (S protein) is a critical component in the infection of the new coronavirus (SARS-CoV-2). The objective of this work was to evaluate whether peptides from S protein could cause negative impact in the aquatic animals. The aquatic toxicity of SARS-CoV-2 spike protein peptides derivatives has been evaluated in tadpoles (n = 50 tadpoles / 5 replicates of 10 animals) from species Physalaemus cuvieri (Leptodactylidae). After synthesis, purification, and characterization of peptides (PSDP2001, PSDP2002, PSDP2003) an aquatic contamination has been simulatedwith these peptides during 24 hours of exposure in two concentrations (100 and 500 ng/mL). The control group (“C”) was composed of tadpoles kept in polyethylene containers containing de-chlorinated water. Oxidative stress, antioxidant biomarkers and neurotoxicity activity were assessed. In both concentrations, PSPD2002 and PSPD2003 increased catalase and superoxide dismutase antioxidants enzymes activities, as well as oxidative stress (nitrite levels, hydrogen peroxide and reactive oxygen species). All three peptides also increased acetylcholinesterase activity in the highest concentration. These peptides showed molecular interactions in silico with acetylcholinesterase and antioxidant enzymes. Aquatic particle contamination of SARS-CoV-2 has neurotoxics effects in P. cuvieri tadpoles. These findings indicate that the COVID-19 can constitute environmental impact or biological damage potential.

HIGHLIGHTS

SARS-CoV-2 spike protein peptides (PSDP) were synthesized, purified, and characterized by solid phase peptide synthesis.

PSDP peptides promoted REDOX imbalance and acute neurotoxicity in tadpoles (Physalaemus cuvieri)

In silico studies have shown interactionsbetween peptides and acetylcholinesterase and antioxidant enzymes

Aquatic particle contamination of SARS-CoV-2 can constitute additional environmental damage

GRAPHICAL ABSTRACT
Slowing down an analyte in a nanopore
Authors: Sampath G.
Published: January 2021

An unresolved problem in nanopore sensing is the high translocation speed (∼10-100 monomers/μs) of an analyte (nucleotide, DNA, amino acid (AA), peptide) through the pore. Here a method based on reversing the pore voltage and changing the solution pH is described. A simplified Fokker-Planck model shows mean translocation times of 1-10 ms in a nanopore of length 10 nm. Simulations show that a positive-negative voltage profile can trap an analyte for ∼1 ms. This method can be used for free nucleotides, single AAs, oligonucleotides, and oligopeptides. Its applicability to existing nanopore sensing and sequencing techniques and implementation issues are discussed.
Paradoxes and synergies: optimizing management of a deadly virus in an endangered carnivore
Authors: Gilbertson Marie L.J. , Onorato Dave , Cunningham Mark , VandeWoude Sue , Craft Meggan E.
Published: January 2021

Pathogen management strategies in wildlife are typically accompanied by an array of uncertainties such as the efficacy of vaccines or potential unintended consequences of interventions. In the context of such uncertainties, models of disease transmission can provide critical insight for optimizing pathogen management, especially for species of conservation concern. The endangered Florida panther experienced an outbreak of feline leukemia virus (FeLV) in 2002-04, and continues to be affected by this deadly virus. Ongoing management efforts aim to mitigate the effects of FeLV on panthers, but with limited information about which strategies may be most effective and efficient.

We used a simulation-based approach to determine optimal FeLV management strategies in panthers. We simulated use of proactive FeLV management strategies (i.e., proactive vaccination) and several reactive strategies, including reactive vaccination and test-and-removal. Vaccination strategies accounted for imperfect vaccine-induced immunity, specifically partial immunity in which all vaccinates achieve partial pathogen protection. We compared the effectiveness of these different strategies in mitigating the number of FeLV mortalities and the duration of outbreaks.

Results showed that inadequate proactive vaccination can paradoxically increase the number of disease-induced mortalities in FeLV outbreaks. These effects were most likely due to imperfect vaccine immunity causing vaccinates to serve as a semi-susceptible population, thereby allowing outbreaks to persist in circumstances otherwise conducive to fadeout. Combinations of proactive vaccination with reactive test-and-removal or vaccination, however, had a synergistic effect in reducing impacts of FeLV outbreaks, highlighting the importance of using mixed strategies in pathogen management.

Synthesis and applications:Management-informed disease simulations are an important tool for identifying unexpected negative consequences and synergies among pathogen management strategies. In particular, we find that imperfect vaccine-induced immunity necessitates further consideration to avoid unintentionally worsening epidemics in some conditions. However, mixing proactive and reactive interventions can improve pathogen control while mitigating uncertainties associated with imperfect interventions.
Anomalous brain energy in old age by wavelet analysis of ERP during a Stroop task
Authors: Sánchez-Moguel Sergio M. , Baravalle Roman , González-Salinas Sofía , Rosso Osvaldo A. , Fernández Thalía , Montani Fernando
Published: January 2021

By event-related potentials (ERP) during a counting Stroop task it was shown that the elderly with excess in theta activity in their electroencephalogram (EEG) are at risk of cognitive decline and have a higher neuronal activity during stimulus categorization than the elderly with a normal EEG. It was suggested that this increased neuronal activity could have a compensatory function. However, the quantification of energy associated with the enhanced neuronal activity was not investigated in this group. By wavelet analysis, we measured total and relative energy in ERP during the execution of a counting Stroop task in two groups of elderly: one with excess in theta activity (Theta-EEG, n = 23) and the other with normal EEG (Normal-EEG, n = 23). In delta, theta, and alpha bands, the Theta-EEG group used a higher amount of total energy as compared to the Normal-EEG group for both types of stimuli, interference and no interference. In theta and alpha bands, the total energy was higher in the Theta-EEG group, specifically in the window of 258-516 ms, coinciding with stimulus categorization. Given that no major behavioral differences were observed between EEG groups, we suggest that a higher energy in delta, theta, and alpha bands is one of the neurobiological mechanisms that allows the Theta-EEG group to cope with the cognitive demands of the task. However, this increased energy might not be an effective mechanism in the long term as it could promote a metabolic and cellular dysregulation that would trigger the transition to cognitive impairment.

SIGNIFICANCE STATEMENT

By using wavelet transform analysis we report that the elderly with excess in theta activity show a higher energy in delta, theta, and alpha bands during the categorization of stimuli in a counting Stroop task. Our findings imply that this increase neuronal activity might be related to a dysregulated energy metabolism in the elderly with theta excess that could explain the progress to cognitive impairment in this group. The analysis of energy by wavelet transform in data obtained by ERP complements other techniques that evaluate the risk of cognitive impairment.
Predictors of COVID-19 Vaccine Hesitancy: Socio-demographics, Co-Morbidity and Past Experience of Racial Discrimination
Authors: Savoia E. , Piltch-Loeb R. , Goldberg B. , Miller-Idriss C. , Hughes B. , Montrond AM. , Kayyem JN. , Testa MA.
Published: January 2021

Importance

Immunization programs are only successful when there are high rates of acceptance and coverage. While delivering billions of COVID 19 doses globally addressing vaccine hesitancy will be one of the most significant public health communication efforts ever undertaken.

Objective

The goal of this study is to explore predictors of COVID 19 vaccine hesitancy, including sociodemographic factors, comorbidity, risk perception, and experience of discrimination, in a sample of the U.S. population.

Design

We used a cross sectional online survey study design. The survey was implemented between Dec 13 and 23, 2020.

Setting

The survey was limited to respondents over 18 years of age residing in the USA.

Participants

Respondents were individuals belonging to priority groups for vaccine distribution.

Main Outcome(s) and Measure(s)

Respondents were asked how likely they would be to take a COVID 19 vaccine if offered at no cost within two months. Vaccine hesitancy was measured using a scale ranging from 1 (low hesitancy) to 6 (high hesitancy).

Results

Responses were received from 2,650 respondents (response rate 84%) from all 50 states and Puerto Rico, American Samoa, and Guam. The majority were in the age category between 25 and 44 years (66%), male (53%), and working in the healthcare sector (61%). Most were White and non-Hispanic (66%) respondents followed by Black non-Hispanic (14%) and Hispanic (8%) respondents. Experience with racial discrimination was a predictor of vaccine hesitancy. Those reporting racial discrimination having 21% increased odds of being at a higher level of hesitancy compared to those who did not report such experience (OR=1.21, 95% C.I. 1.01-1.45).

Conclusions and Relevance

Communication and logistical aspects during the COVID 19 vaccination campaign need to be sensitive to individuals past-experience of discrimination by identifying appropriate channels of communication and sites for vaccine distribution to reach those who may have sentiments of mistrust in the vaccination campaign.
Arm-hand boost therapy during inpatient stroke rehabilitation: a pilot randomized controlled trial
Authors: Meyer Sarah , Verheyden Geert , Kempeneers Kristof , Michielsen Marc
Published: January 2021

Objective

It was the aim to assess feasibility, safety and potential efficacy of a new intensive, focused arm-hand BOOST program and to investigate whether there is a difference between early versus late delivery of the program in the sub-acute phase post stroke.

Methods

In this pilot RCT, patients with stroke were randomized to the immediate group (IG): 4 weeks (4w) BOOST +4w CONTROL or the delayed group (DG): 4w CONTROL +4w BOOST, on top of their usual inpatient care program. The focused arm-hand BOOST program (1 hour/day, 5x/week, 4 weeks) consisted of group exercises with focus on scapula-setting, core-stability, manipulation and complex ADL tasks. Additionally, one hour per week the Armeo®Power (Hocoma AG, Switzerland) was used. The CONTROL intervention comprised a dose-matched program (24 one-hour sessions in 4w) of lower limb strengthening exercises and general reconditioning. At baseline, after 4 and 8 weeks of training, the Fugl-Meyer assessment upper extremity (FMA-UE), action research arm test (ARAT) and stroke upper limb capacity scale (SULCS) were administered.

Results

Eighteen participants (IG: n=10, DG: n=8) were included, with a median (IQR) time post stroke of 8.6 weeks (5-12). No adverse events were experienced. After 4 weeks of training, significant between-group differences were found for FMA-UE (p=0.003) and SULCS (p=0.033) and a trend for ARAT (p=0.075) with median (IQR) change scores for the IG of 9 (7-16), 2 (1-3) and 12.5 (1-18) respectively, and for the DG of 0.5 (−3-3), 1 (0-1) and 1.5 (−1-9), respectively. In the IG, 80% of patients improved beyond the minimal clinical important difference of FMA-UE after 4 weeks, compared to none of the DG patients. Between 4 and 8 weeks of training, patients in the DG tend to show larger improvements when compared to the IG, however, between-group comparisons did not reach significance.

Conclusions

Results of this pilot RCT showed that an intensive, specific arm-hand BOOST program, on top of usual care, is feasible and safe in the sub-acute phase post stroke and suggests positive, clinical meaningful effects on upper limb function, especially when delivered in the early sub-acute phase post stroke.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT04584177
Isolation of SARS-CoV-2 from the air in a car driven by a COVID patient with mild illness
Authors: Lednicky John A. , Lauzardo Michael , Alam Md. M. , Elbadry Maha A. , Stephenson Caroline J. , C.Gibson Julia , Morris J. Glenn
Published: January 2021

We used a Sioutas personal cascade impactor sampler (PCIS) to screen for SARS-CoV-2 in a car driven by a COVID-19 patient. SARS-CoV-2 was detectable at all PCIS stages by PCR and was cultured from the section of the sampler collecting particles in the 0.25 to 0.50 □μm size range.
Socioeconomic status determines COVID-19 incidence and related mortality in Santiago, Chile
Authors: Mena Gonzalo , Martinez Pamela P. , Mahmud Ayesha S. , Marquet Pablo A. , Buckee Caroline O. , Santillana Mauricio
Published: January 2021

The current coronavirus disease 2019 (COVID-19) pandemic has impacted dense urban populations particularly hard. Here, we provide an in-depth characterization of disease incidence and mortality patterns, and their dependence on demographic and socioeconomic strata in Santiago, a highly segregated city and the capital of Chile. We find that among all age groups, there is a strong association between socioeconomic status and both mortality –measured either by direct COVID-19 attributed deaths or excess deaths– and public health capacity. Specifically, we show that behavioral factors like human mobility, as well as health system factors such as testing volumes, testing delays, and test positivity rates are associated with disease outcomes. These robust patterns suggest multiple possibly interacting pathways that can explain the observed disease burden and mortality differentials: (i) in lower socioeconomic status municipalities, human mobility was not reduced as much as in more affluent municipalities; (ii) testing volumes in these locations were insufficient early in the pandemic and public health interventions were applied too late to be effective; (iii) test positivity and testing delays were much higher in less affluent municipalities, indicating an impaired capacity of the health-care system to contain the spread of the epidemic; and (iv) infection fatality rates appear much higher in the lower end of the socioeconomic spectrum. Together, these findings highlight the exacerbated consequences of health-care inequalities in a large city of the developing world, and provide practical methodological approaches useful for characterizing COVID-19 burden and mortality in other segregated urban centers.
Mortality of Diabetes-related Acute Metabolic Emergencies in COVID-19 patients: a systematic review and meta-analysis
Authors: Papadopoulos Vasileios P. , Avramidou Peny , Bakola Stefania-Aspasia , Zikoudi Dimitra-Geogia , Touzlatzi Ntilara , Koutroulos Marios-Vasileios , Filippou Dimitrios K.
Published: January 2021

Purpose

Little is known on the mortality rate in COVID-19 related acute metabolic emergencies, namely diabetic ketoacidosis (DKA), hyperglycaemic hyperosmolar state (HHS), combined DKA/HHS, and euglycaemic diabetic ketoacidosis (EDKA).

Methods

A systematic literature review was conducted using EMBASE, PubMed/Medline, and Google Scholar from January 1, 2020 to January 9, 2021 to identify all case report series, cross-sectional studies, and meta-analyses of case reports describing mortality rate in DKA, HHS, and EDKA, in COVID-19 patients. The Joanna Briggs Institute critical appraisal checklist for case reports was used for quality assessment.

Results

From 313 identified publications, 4 fulfilled the inclusion criteria and analyzed qualitatively and quantitatively. A systematic review and meta-analysis with subgroup analyses examined mortality rate in a total of 152 COVID-19 patients who had developed DKA, HHS, combined DKA/HHS, or EDKA. Combined mortality rate and confidence intervals (CI) were estimated using random effects model. The study was registered to PROSPERO database (ID: 230737).

Results

Combined mortality rate was found to be 27.1% [95% CI: 11.2-46.9%]. Heterogeneity was considerable (I2=83%; 95% CI: 56-93%), corrected to 67% according to Von Hippel adjustment for small meta-analyses. Funnel plot presented no apparent asymmetry; Egger’s and Begg’s test yielded in P=0.44 and P=0.50, respectively. Sensitivity analysis failed to explain heterogeneity.

Conclusion

COVID-19 related acute metabolic emergencies (DKA, HHS, and EDKA) are characterized by considerable mortality; thus, clinicians should be aware of timely detection and immediate treatment commencing.
What delirium detection tools are used in routine clinical practice in the United Kingdom? Survey results from 91% of acute healthcare organisations
Authors: Tieges Zoë , Lowrey Jacqueline , MacLullich Alasdair M. J.
Published: January 2021

Purpose

Our aim was to collect information on delirium assessment processes and pathways in non-intensive care settings in the United Kingdom (UK).

Methods

We sent a Freedom of Information request to 169 UK National Health Service (NHS) hospitals, trusts and health boards (units) in July 2020 to obtain data on usage of delirium assessment tools in clinical practice and delirium pathways or guidelines.

Results

We received responses from 154/169 units (91% response rate). Of these, 146/154 (95%) units reported use of formal delirium assessment processes and 131/154 (85%) units had guidelines or pathways in place. The 4 ‘A’s Test (4AT) was the most widely used tool, with 117/146 (80%) units reporting use. The Confusion Assessment Method was used in 65/146 (45%) units, and the Single Question to identify Delirium (SQiD) in 52/146 (36%) units.

Conclusions

Our findings show that the 4AT is the most commonly used tool in the UK, with 80% of units reporting use. This study adds to our knowledge of real-world uptake of delirium detection methods at scale. Future studies should evaluate real-world implementation of delirium assessment tools further via (i) tool completion rates and (ii) rates of positive scores against the expected prevalence delirium in the clinical population concerned.

KEY SUMMARY POINTS

Aim

To seek information on delirium assessment processes and pathways in non-intensive clinical care settings in the United Kingdom (UK), and to assess usage of specific delirium assessment tools: the 4 ‘A’s Test (4AT), Confusion Assessment Method and Single Question to identify Delirium (SQiD).

Findings

In total, 95% of National Health Service (NHS) units (hospitals, trusts and health boards) reported use of formal delirium assessment processes and 85% of units had guidelines or pathways in place. The 4AT was the most widely used tool, with 80% of units reporting use; the Confusion Assessment Method was reportedly used in 45% of units and the SQiD in 36% of units.

Message

This study shows real-world, large-scale uptake of delirium detection methods and delirium guidelines in UK hospitals, which contributes to ongoing efforts to improve delirium care.
Modelling the impact of household size distribution on the transmission dynamics of COVID-19
Authors: Liu Pengyu , McQuarrie Lisa , Song Yexuan , Colijn Caroline
Published: January 2021

Under the implementation of non-pharmaceutical interventions such as social distancing and lockdowns, household transmission has been shown to be significant for COVID-19, posing challenges for reducing incidence in settings where people are asked to self-isolate at home and to spend increasing amounts of time at home due to distancing measures. Accordingly, characteristics of households in a region have been shown to relate to transmission heterogeneity of the virus. We introduce a stochastic epidemiological model to examine the impact of the household size distribution in a region on the transmission dynamics. We choose parameters to reflect incidence in two health regions of the Greater Vancouver area in British Columbia and simulate the impact of distancing measures on transmission, with household size distribution the only different parameter between simulations for the two regions. Our result suggests that the dissimilarity in household size distribution alone can cause significant differences in incidence of the two regions, and the distributions drive distinct dynamics that match reported cases. Furthermore, our model suggests that offering individuals a place to isolate outside their household can speed the decline in cases, and does so more effectively where there are more larger households.
Impact of COVID-19 shelter-in-place order on transmission of gastrointestinal pathogens in Northern California
Authors: Bulterys Philip L. , Leung Nicole Y. , Saleem Atif , Budvytiene Indre , Banaei Niaz
Published: January 2021

Society-wide cessation of human interaction outside the household due to the COVID-19 shelter-in-place created a unique opportunity in modern history to reexamine the transmission of communicable gastrointestinal pathogens. We conducted a quasi-experimental study from January 1, 2018 to Sept 30, 2020 to investigate the effect of California’s COVID-19 shelter-in-place order on the community transmission of viral, bacterial, and parasitic gastrointestinal pathogens detected with the FilmArray GI Panel (BioFire Diagnostics, Salt Lake City, UT). The incidence of viral causes of gastroenteritis, enteroaggregative/enteropathogenic/enterotoxigenic Escherichia coli, Shigella, and Cyclospora cayetanensis decreased sharply after shelter-in place took effsect, whilst Salmonella, Campylobacter, shiga toxin-producing E. coli (O157 and non-O157) and other bacterial and parasitic causes of gastroenteritis were largely unaffected. Findings suggest community spread of viral gastroenteritis, pathogenic E. coli (except for shiga toxin-producing E. coli), Shigella, and Cyclospora is more susceptible to changes associated with shelter-in-place than other gastrointestinal pathogens.
Individual Molecular Motors use Low Forces to bypass Roadblocks during Collective Cargo Transport
Authors: Shukla Saurabh , Troitskaia Alice , Swarna Nikhila , Maity Barun Kumar , Tjioe Marco , Bookwalter Carol S , Chrin Lynn , Berger Christopher L , Trybus Kathleen M , Chemla Yann R , Selvin Paul R
Published: January 2021

A cargo encounters many obstacles during its transport by molecular motors as it moves throughout the cell. Multiple motors on the cargo exert forces to steer the cargo to its destination. Measuring these forces is essential for understanding intracellular transport. Using kinesin as an example, we measured the force exerted by multiple stationary kinesinsin vitro, driving a common microtubule. We find that individual kinesins generally exert less than a piconewton (pN) of force, even while bypassing obstacles, whether these are artificially placed 20-100 nm particles or tau, a Microtubule Associated Protein. We demonstrate that when a kinesin encounters an obstacle, the kinesin either becomes dislodged and then re-engages or switches protofilaments while the other kinesins continue to apply their (sub-)pN forces. By designing a high-throughput assay involving nanometer-resolved multicolor-fluorescence and a force-sensor able to measure picoNewtons of force, our technique is expected to be generally useful for many different types of molecular motors.
Exposure to fruit-flavoring during adolescence increases nicotine consumption and promotes dose escalation
Authors: Patten Theresa , Dreier Allison , Herman Rae J. , Kimball Bruce A. , De Biasi Mariella
Published: January 2021

The rise of e-cigarette popularity has sparked interest in the role of palatable flavors on nicotine use. Despite growing evidence that sweet flavorants enhance nicotine reward, their influence on nicotine consumption has not been studied extensively. In addition, the impact that flavored nicotine use in adolescence could have on nicotine reward and dependence in adulthood remains unclear. This study examined the role of flavored nicotine access on nicotine preference and consumption longitudinally, from adolescence to adulthood. Male and female adolescent mice preferred a fruit-flavored nicotine solution. However, only adolescent female mice with access to flavored nicotine consumed higher doses. Furthermore, while adolescent male mice escalated consumption of both flavored and unflavored nicotine, female mice only escalated when given access to flavored nicotine. As mice matured into adulthood, there was no evidence that a history of flavored-nicotine access altered preference for unflavored nicotine. However, when the nicotine concentration was reduced, mice that had consumed strawberry-flavored nicotine in adolescence maintained baseline nicotine consumption levels longer than mice that initiated nicotine use without flavor in adolescence. Finally, addition of fruit-flavorants into the nicotine solution during adulthood led to increased levels of nicotine consumption, regardless of previous flavored-nicotine access or of familiarity with the selected flavorant. These results indicate that flavorants increase nicotine consumption independent of life stage, possibly posing a disproportionate risk to adolescent females. Our results also point to an effect of adolescent flavored-nicotine use on nicotine dose maintenance in adulthood, which could have implications for the success of future quit attempts.
Does the punishment fit the crime? Consequences and diagnosis of misspecified detection functions in Bayesian spatial capture-recapture modelling
Authors: Dey Soumen , Bischof Richard , Dupont Pierre P. A. , Milleret Cyril
Published: January 2021

Spatial capture-recapture (SCR) is now used widely to estimate wildlife densities. At the core of SCR models lies the detection function, linking individual detection probability to the distance from its latent activity center. The most common function (half-normal) assumes a bivariate normal space use and consequently detection pattern. This is likely an oversimplification and misrepresentation of real-life animal space use patterns, but studies have reported that density estimates are relatively robust to misspecified detection functions. However, information about consequences of such misspecification on space use parameters (e.g. home range area), as well as diagnostic tools to reveal it are lacking.

We simulated SCR data under six different detection functions, including the half-normal, to represent a wide range of space use patterns. We then fit three different SCR models, with the three simplest detection functions (half-normal, exponential and half-normal plateau) to each simulated data set. We evaluated the consequences of misspecification in terms of bias, precision and coverage probability of density and home range area estimates. We also calculated Bayesian p-values with respect to different discrepancy metrics to assess whether these can help identify misspecifications of the detection function.

We corroborate previous findings that density estimates are robust to misspecifications of the detection function. However, estimates of home range area are prone to bias when the detection function is misspecified. When fitted with the half-normal model, average relative bias of 95% kernel home range area estimates ranged between −25% and 26% depending on the misspecification. In contrast, the half-normal plateau model (an extension of the half-normal) returned average relative bias that ranged between −26% and −4%. Additionally, we found useful heuristic patterns in Bayesianp-values to diagnose the misspecification in detection function.

Our analytical framework and diagnostic tools may help users select a detection function when analyzing empirical data, especially when space use parameters (such as home range area) are of interest. We urge development of additional custom goodness of fit diagnostics for Bayesian SCR models to help practitioners identify a wider range of model misspecifications.
High-throughput Identification of Eukaryotic Parasites and Arboviruses in Mosquitoes
Authors: Cannon Matthew V. , Bogale Haikel N. , Bhalerao Devika , Keita Kalil , Camara Denka , Barry Yaya , Keita Moussa , Coulibaly Drissa , Kone Abdoulaye K. , Doumbo Ogobara K. , Thera Mahamadou A. , Plowe Christopher V. , Travassos Mark A. , Irish Seth R. , Yeroshefsky Joshua , Dorothy Jeannine , Prendergast Brian , Laurent Brandyce St. , Fritz Megan L. , Serre David
Published: January 2021

Vector-borne pathogens cause many human infectious diseases and are responsible for high mortality and morbidity throughout the world. They can also cause livestock epidemics with dramatic social and economic consequences. Due to the high costs, vector-borne disease surveillance is often limited to current threats, and the investigation of emerging pathogens typically occur after the reports of clinical cases. Here, we use high-throughput sequencing to detect and identify a wide range of parasites and viruses carried by mosquitoes from Cambodia, Guinea, Mali and Maryland. We apply this approach to individualAnophelesmosquitoes as well as pools of mosquitoes captured in traps; and compare the outcomes of this assay when applied to DNA or RNA. We identified known human and animal pathogens and mosquito parasites belonging to a wide range of taxa, insect Flaviviruses, and novel DNA sequences from previously uncharacterized organisms. Our results also revealed that analysis of the content of an entire trap is an efficient approach to monitor and identify potential vector-borne pathogens in large surveillance studies, and that analyses of RNA extracted from mosquitoes is preferable, when possible, over DNA-based analyses. Overall, we describe a flexible and easy-to-customize assay that can provide important information for vector-borne disease surveillance and research studies to efficiently complement current approaches.
Hydration-induced structural transitions in biomimetic tandem repeat proteins
Authors: Dubini Romeo C. A. , Jung Huihun , Demirel Melik C. , Rovó Petra
Published: January 2021

A major challenge in developing biomimetic, high-performance, and sustainable products is the accurate replication of the biological materials’ striking properties, such as high strength, self-repair, and stimuli-responsiveness. The rationalization of such features on the microscopic scale, together with the rational design of synthetic materials, is currently hindered by our limited understanding of the sequence-structure-property relationship. Here, employing state-of-the-art nuclear magnetic resonance (NMR) spectroscopy, we link the atomistic structural and dynamic properties of an artificial bioinspired tandem repeat protein TR(1,11) to its stunning macroscopic properties including high elasticity, self-healing capabilities, and recordholding proton conductivity amongst biological materials. We show that the hydration-induced structural rearrangement of the amorphous Gly-rich soft segment and the ordered Ala-rich hard segment is the key to the material’s outstanding physical properties. We found that in the hydrated state both the Ala-rich ordered and Gly-rich disordered parts contribute to the formation of the nanoconfinedβ-sheets, thereby enhancing the strength and toughness of the material. This restructuring is accompanied by fast proline ring puckering and backbonecis-transisomerization at the water-protein interface, which in turn enhances the elasticity and the thermal conductivity of the hydrated films. Our in-depth characterization provides a solid ground for the development of next-generation materials with improved properties.
Reticulate Evolutionary History in a Recent Radiation of Montane Grasshoppers Revealed by Genomic Data
Authors: Tonzo Vanina , Bellvert AdriÀ , Ortego Joaquín
Published: January 2021

Inferring the ecological and evolutionary processes underlying lineage and phenotypic diversification is of paramount importance to shed light on the origin of contemporary patterns of biological diversity. However, reconstructing phylogenetic relationships in recent evolutionary radiations represents a major challenge due to the frequent co-occurrence of incomplete lineage sorting and introgression. In this study, we combined high throughput sequence data (ddRADseq), geometric morphometric information, and novel phylogenetic inference methods that explicitly account for gene flow to infer the evolutionary relationships and the timing and mode of diversification in a complex of Ibero-Maghrebian montane grasshoppers of the subgenusDreuxius(genusOmocestus). Our analyses supported the phenotypic distinctiveness of most sister taxa, two events of historical introgression involving lineages at different stages of the diversification continuum, and the recent Pleistocene origin (< 1 Ma) of the complex. Phylogenetic analyses did not recover the reciprocal monophyly of taxa from Iberia and northwestern Africa, supporting overseas migration between the two continents during the Pleistocene. Collectively, these results indicate that periods of isolation and secondary contact linked to Pleistocene glacial cycles likely contributed to both allopatric speciation and post divergence gene flow in the complex. This study exemplifies how the integration of multiple lines of evidence can help to reconstruct complex histories of reticulated evolution and highlights the important role of Quaternary climatic oscillations as a diversification engine in the Ibero-Maghrebian biodiversity hotspot.
The long-term dynamics of the CA1 spatial code preserve the relative structure of contextual representation
Authors: Keinath Alexandra T. , Mosser Coralie-Anne , Brandon Mark P.
Published: January 2021

The hippocampus is thought to mediate episodic memory through the instantiation and reinstatement of context-specific cognitive maps. However, recent longitudinal experiments have challenged this view, reporting that most hippocampal cells change their tuning properties over days even in the same environment. Often referred to asrepresentational drift, these dynamics raise multiple questions about the representational capacity and content of the hippocampal code. One such question is whether and how these dynamics impact the contextual code. To address this, here we imaged large CA1 populations over more than a month of daily experience as freely behaving mice participated in an extended geometric morph paradigm. We find that long-timescale changes in population activity occurred orthogonally to the representation of context in network space, allowing for consistent readout of contextual information across weeks. Together, these results demonstrate that long-timescale changes to the CA1 spatial code preserve the relative structure of contextual representation.
Protein-Free ribosomal RNA scaffolds can assemble poly-lysine oligos from charged tRNA fragments
Authors: Xu Doris , Wang Yuhong
Published: January 2021

Ribosomal protein synthesis is a central process of the modern biological world. Because the ribosome contains proteins itself, it is very important to understand its precursor and evolution. Small ribozymes have demonstrated the principle of “RNA world” hypothesis, but protein free peptide ligase remains elusive. In this report, we have identified two fragments in the peptidyl transfer center that can synthesize a 9-mer poly-lysine in a solution contains Mg2+. This result is deduced from isotope-shifting in high resolution MS. To our best knowledge, this is the longest peptide oligo that can be synthesized by a pure ribozyme. Via single molecule FRET experiments, we have demonstrated the ligase mechanism was probably by substrate proximity via dimerization. We prospect that these RNA fragments can be useful to synthesize template free natural and non-natural peptides, to be model system for peptidyl transfer reaction mechanism and can shed light to the evolution of ribosome.

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The landscape of transcriptional and translational changes over 22 years of bacterial adaptation
Authors: Favate John S. , Liang Shun , Yadavalli Srujana S. , Shah Premal
Published: January 2021

Organisms can adapt to an environment by taking multiple mutational paths. This redundancy at the genetic level, where many mutations have similar phenotypic and fitness effects, can make untangling the molecular mechanisms of complex adaptations difficult. Here we use theE. colilong-term evolution experiment (LTEE) as a model to address this challenge. To bridge the gap between disparate genomic changes and parallel fitness gains, we characterize the landscape of transcriptional and translational changes across 11 replicate populations evolving in parallel for 50,000 generations. By quantifying absolute changes in mRNA abundances, we show that not only do all evolved lines have more mRNAs but that this increase in mRNA abundance scales with cell size. We also find that despite few shared mutations at the genetic level, clones from replicate populations in the LTEE are remarkably similar to each other in their gene expression patterns at both the transcriptional and translational levels. Furthermore, we show that the bulk of the expression changes are due to changes at the transcriptional level with very few translational changes. Finally, we show how mutations in transcriptional regulators lead to consistent and parallel changes in the expression levels of downstream genes, thereby linking genomic changes to parallel fitness gains in the LTEE. These results deepen our understanding of the molecular mechanisms underlying complex adaptations and provide insights into the repeatability of evolution.