bluuebunny/crossref_metadata_2025 huggingface dataset:
140 Killed in Action (KIA): an analysis of military personnel who died of their injuries before reaching a definitive medical treatment facility in Afghanistan (2004–2014)
Authors: Webster Stacey , Barnard Ed , Smith Jason , Marsden Max , Wright Chris
Published: January 2021

Aims/Objectives/Background

Most fatalities from trauma, in civilian and military settings, die before reaching a hospital. However, no previous studies have comprehensively examined this phase of care. The aim of this study was to define the time interval between injury and death in UK military personnel who died pre-hospital from enemy action (Killed in Action, KIA).

Methods/Design

The UK Joint Trauma Theatre Registry (JTTR) was used to identify all UK military personnel who died in Afghanistan (2004–2014). Through novel linkage of medical and tactical databases, an accurate timeline of events was obtained. Cause of death was determined from post mortem review. The primary objective was to report time between injury and death. Secondary objectives: mortality at key timepoints, the temporal lethality of different anatomical injuries, and trends in the case fatality rate (CFR, defined as deaths/injuries x100). Data are reported as n(%), and median [inter-quartile range]. Proportions compared with a Fisher’s exact test, and survival was with a Gehan-Breslow-Wilcoxon test; level of significance was corrected by Bonferroni.

Results/Conclusions

2413 UK personnel were injured in Afghanistan from 2004–2014; 448 died, a CFR of 18.6%. 390 (87.1%) of total deaths (KIA + Killed Non-Enemy Action) were prehospital. Complete timeline data were available for n=303 (87.1%) KIA – this cohort had a median injury severity score of 75.0 [55.5–75.0]. The median time between injury and death in KIA was 0.0 [0.0–21.8] minutes; 173 (57.1%) died immediately, and by 10 min more than two-thirds had died. Primary injury to the head had a significantly shorter time to death compared to the abdomen and lower extremity (both p<0.01). Significant improvement in survival over the decade was due to a reduction in pre-hospital CFR without an increase in in-hospital CFR.

Over two-thirds of KIA deaths occurred within 10 min of injury. Improvement in the CFR in Afghanistan was predominantly in the prehospital phase.
145 Point of care lung ultrasound in patient triage: integration of ultrasound into a streaming pathway for COVID-19
Authors: Craver Dominic , Ahmad Aminah , Colclough Anna
Published: January 2021

Aims/Objectives/Background

Rapid risk stratification of patients is vital for Emergency Department (ED) streaming during the COVID-19 pandemic. Ideally, patients should be split into red (suspected/confirmed COVID-19) and green (non COVID-19) zones in order to minimise the risk of patient-to-patient and patient-to-staff transmission. A robust yet rapid streaming system combining clinician impression with point-of-care diagnostics is therefore necessary.

Point of care ultrasound (POCUS) findings in COVID-19 have been shown to correlate well with computed tomography (CT) findings, and it therefore has value as a front-door diagnostic tool. At University Hospital Lewisham (a district general hospital in south London), we recognised the value of early POCUS and its potential for use in patient streaming.

Methods/Design

We developed a training programme, ‘POCUS for COVID’ and subsequently integrated POCUS into streaming of our ED patients. The training involved Zoom lectures, a face to face practical, a 10 scan sign off process followed by a final triggered assessment. Patient outcomes were reviewed in conjunction with their scan reports.

Results/Conclusions

Currently, we have 21 ED junior doctors performing ultrasound scans independently, and all patients presenting to our department are scanned either in triage or in the ambulance. A combination of clinical judgement and scan findings are used to stream the patient to an appropriate area.

Service evaluation with analysis of audit data has found our streaming to be 94% sensitive and 79% specific as an indicator of COVID 19. Further analysis is ongoing.

Here we present both the structure of our training programme and our integrated streaming pathway along with preliminary analysis results.
188 Senior clinical and business managers’perspectives on how different mechanisms and models of employing general practitioners in or alongside Emergency Departments influence wider system outcomes
Authors: Choudrhey Mazhar , Edwards Michelle , Cooper Alison , Anderson Pippa , Hughes Thomas , Carson-Stevens Andrew , Porter Alison , Adrian Edwards
Published: January 2021

Aims/Objectives/Background

We aim to examine senior managers’ perspectives on funding mechanisms used to implement the policy and experiences of success or challenges in introducing models of using GPs in or alongside emergency departments. Health policy in England has advocated the use of primary care clinicians at emergency departments to address pressures from rising attendances. However, implementing large systemic changes such as placing GPs in or alongside emergency departments requires significant funding, consideration of the opportunity costs of the alternative uses of such funding, an available workforce and evidence of how it should be used. Our findings will inform policy adaptation and service development to improve the healthcare provided to patients by providing new evidence of the reported experiences of adopting models of using GPs in or alongside emergency departments.

Methods/Design

The perspectives of senior clinical, business and finance managers with responsibility for emergency department services and on-site primary care service implementation were investigated in semi-structured interviews with 31 managers at 12 type-1 emergency departments in England and Wales. Emergency departments operated one of three GP models or had prior experience of implementing a GP model. Interviews were thematically analysed.

Results/Conclusions

Successful GPs models in emergency departments were perceived to be reliant on well-organised and unified funding mechanisms, appropriate staffing and governance, and consideration of population demands and needs. Funding mechanisms and the flow of funds were reported as complex, the most efficient mechanisms were described at departments where funding was unified, in collaboration with health and community care services. Staffing with local, experienced GPs was important. There were also cautions from experiences with private locum providers. Our findings contribute to debates about implementing policy on how primary care clinicians are effectively and safely deployed in emergency departments and how local context should be considered.
303 What goes bump in the night? A literature review and noise exposure experiment in a UK paediatric emergency department
Authors: Hall Lucy , Dando Sophie , Hanks Anthony
Published: January 2021

Aims/Objectives/Background

In the Emergency department (ED), noise is a frequent and often unavoidable consequence of work undertaken and levels can often be raised during the day and night. Raised ambient noise levels have potential implications for the workforce, patients and relatives.

Investigation into the problem of noise levels in the ED follows feedback from a young patient who couldn’t sleep during a prolonged stay. His complaint focused on loud, irregular banging noises such as those from closing bins that kept him awake.

The team felt work should be done to see if it was a wider spread problem or just isolated to his case. A simple sound recording experiment and literature search was conducted.

Methods/Design

The literature search was conducted using electronic/online databases (Medline; Cochrane library) with a fixed date range and specific inclusion criteria.

The noise exposure experiment was conducted using a verified phone app to record the sound levels. They were measured at 3 times, during a night shift, in the paediatric emergency department of UHW. All measurements were at a fixed distance and were averaged and compared with WHO recommendations.

Results/Conclusions

There are many sources of noise pollution in the ED, some are unavoidable for safety and clinical reasons.

The literature review produced a small number of papers all of which found that sound levels were raised above recommended levels. Similarly, all the sounds measured in the ED also exceeded the recommendations.

The most consistent finding across the papers, matched by findings from recordings, was that human behavioural modification is an easy and effective way to reduce noise levels.

There are simple steps that can be taken to reduce and eliminate sounds

Raising awareness regarding this problem is of great importance and focussing future work on assessing the impact in younger patients within the Emergency Department is paramount.
217 The end-tidal and arterial carbon dioxide gradient in serious traumatic brain injury after pre-hospital emergency anaesthesia: a retrospective observational study
Authors: Price James , Sandbach Daniel , Ercole Ari , Wilson Alastair , Barnard Ed
Published: January 2021

Aims/Objectives/Background

In the United Kingdom (UK), 20% of patients with severe traumatic brain injury (TBI) receive pre-hospital emergency anaesthesia (PHEA). Current guidance recommends an end-tidal carbon dioxide (ETCO2) of 4.0–4.5kPa to achieve a low-normal arterial partial pressure of CO2 (PaCO2), and reduce secondary brain injury. This recommendation assumes a 0.5kPa ETCO2-PaCO2 gradient. However, the gradient in the acute phase of TBI is unknown. Our primary aim was to report the ETCO2-PaCO2 gradient of TBI patients at hospital arrival.

Methods/Design

A retrospective cohort study of adult patients with serious TBI, who received a PHEA by a pre-hospital critical care team in the East of England between 1st April 2015 to 31st December 2017. Linear regression was performed to test for correlation and reported as R-squared (R2). A Bland-Altman plot was used to test for paired ETCO2 and PaCO2 agreement and reported with 95% confidence intervals (95%CI). ETCO2-PaCO2 gradient data were compared with a two-tailed, unpaired, t-test.

Results/Conclusions

107 patients were eligible for inclusion. Sixty-seven patients did not receive a PaCO2 sample within 30 minutes of hospital arrival and were therefore excluded. Forty patients had complete data and were included in the final analysis; per protocol.

The mean ETCO2-PaCO2 gradient was 1.7 (±1.0) kPa, with only moderate correlation of ETCO2 and PaCO2 at hospital arrival (R2=0.23, p=0.002). The Bland-Altman bias was 1.7 (95%CI 1.4–2.0) kPa with upper and lower limits of agreement of 3.6 (95%CI 3.0–4.1) kPa and -0.2 (95%CI -0.8–0.3) kPa respectively. There was no significant gradient correlation in patients with a co-existing serious thoracic injury (R2=0.13, p=0.10), and this cohort had a larger ETCO2-PaCO2 gradient, 2.0 (±1.1) kPa, p=0.01. Patients who underwent pre-hospital arterial blood sampling had an arrival PaCO2 of 4.7 (±0.2) kPa.

Lower ETCO2 targets than previously recommended may be safe and appropriate. The use of pre-hospital PaCO2 measurement is advocated.
451 Children’s emergency department review clinic: what we have learnt in the covid-19 pandemic
Authors: Munday Charlotte , Jain Neha , Harrington Seamus , Darvill Benjamin , Perry Sophie , Irwin Alice , Deibel Francesca , Turck Richard , Barber Clarissa
Published: January 2021

Aims/Objectives/Background

The Children’s Emergency Department (CED) in the Bristol Royal Hospital for Children (BRHC) runs ‘Review Clinics’ by a Paediatric Emergency Consultant. These were suspended in March 2020 due to the Covid-19 pandemic and new patient pathways were put in place. Our aim was to assess the effectiveness of these pathways and to evaluate if they should continue once the pressures of Covid-19 have eased.

Methods/Design

We reviewed all the attendances to the ED Review Clinic over a six-week period in 2019 and identified common conditions that are seen in this clinic – abscesses, cellulitis, scaphoid fracture, toddler fracture, limp, headache, peri-orbital cellulitis, torticollis, and neck lumps (accounting for 66% of all attendances).

We then identified all of the ED attendances with these conditions over the same six-week period during the Covid-19 pandemic and performed a service review using medical notes.

Results/Conclusions

All children presenting with a limp during the Covid-19 pandemic were discharged with a leaflet and advised to return in one week if the limp persisted. None of them re-attended.

Scaphoid and toddler fractures that presented during the Covid-19 pandemic were followed-up by Orthopaedics with a combination of telephone and face-to-face reviews. The toddler fractures were put into soft casts to be removed at home - 93% of parents were happy to do this. Orthopaedic review was quicker than the previous ED Review Clinic (an average of 63 hours compared to 216 for scaphoid fractures and 67 hours compared to 235 for toddler fractures).

The results suggest that ED Review Clinics can and should change. Children with a limp can be sent home safely with clear advice. There is a greater role for telephone reviews, in particular, for injuries such as toddler fractures. This would be quicker, less time-consuming for patients, parents and physicians and more cost effective for the department.
131 Rapid and sustained increase in #FOAMed based education during COVID-19 on the St Emlyn’s blog and podcast
Authors: Carley Simon , Jafar Anisa , Reynard Charlie , Beardsell Iain , Horner Dan , Liebig Ashley Voss , Body Richard
Published: January 2021

Aims/Objectives/Background

COVID 19 has resulted in a rapid and unplanned change in the way that education is delivered and consumed. The St Emlyn’s team published a range of webinars, blogs, podcasts and critical appraisal articles specifically focused on COVID-19 during the pandemic. Some webinar content was published in conjunction with the Royal College of Emergency Medicine and the University of Manchester.

We reviewed how engagement with the free and open access medical education (FOAMed) St Emlyn’s blog and podcast changed as a result of the pandemic

Methods/Design

We compared the number of visits for the last 12 months against the previous 12 months. We obtained data from Wordpress and Podbean platforms for the blog and podcast respectively. We did not add data from other social media platforms such as Twitter and Facebook. Differences are expressed as a ratio to indicate an increase or decrease in the number of engagements from the previous year.

Abstract 131 Figure 1

Results/Conclusions

The data shows similar levels of between year activity from July 2018 through to February 2019. It then shows a rapid and profound increase in activity from March 2019, coinciding with the rapid spread of the pandemic in Europe and an early blog/podcast with colleagues from Northern Italy. Since then activity has fallen but still remains roughly 1.5 times higher than in previous years. Combined visits to the blog and podcast peaked at 162,019 engagements, representing a near 6.9 fold increase in podcast engagement and a 2.7 increase in blog activity during May 2019.

The COVID-19 pandemic resulted in a rapid and sustained engagement with the St Emlyn’s platform. The reasons for this are unclear from the data presented here, but we believe reflect the superior agility of modern educational tools such as blogs and podcasts to share and disseminate information as compared to traditional academic publishing methods.
Differences in calculated percentage improvement versus patient-reported percentage improvement in pain scores: a review of spinal cord stimulation trials
Authors: Hagedorn Jonathan M , Deer Timothy R , Canzanello Nicholas C , Covington Stephen M , Schroeder Darrell R , Bendel Markus A , Moeschler Susan M , Hooten W Michael
Published: January 2021

Introduction

Spinal cord stimulation is frequently used for the treatment of intractable chronic pain conditions. Trialing of the spinal cord stimulator device is recommended to assess the patient’s response to neurostimulation before permanent implantation. The trial response is often assessed by Numeric Rating Scale changes and patient-reported percentage pain improvement. Using number rating scale changes between prespinal and postspinal cord stimulation trial, a calculated percentage pain improvement can be obtained. The aim of this study was to assess the difference between calculated and patient-reported percentage improvement in pain scale during spinal cord stimulation trials.

Methods

This study was a retrospective single center review of all spinal cord stimulation trials from January 1 2017 to July 1 2019. A total of 174 patients were included. The paired t-test was used to compare numeric pain scores obtained prestimulation versus poststimulation. The mean difference between methods (patient-reported minus calculated) was compared with zero using the 1-sample t-test. Lin’s concordance correlation coefficient was computed with a 95% CI, calculated using Fisher z-transformation; and a bootstrapping approach was used to compare the concordance correlation coefficient between groups. In all cases, two-tailed tests were used with p<0.05 considered statistically significant.

Results

Based on prestimulation and poststimulation numeric rating scale scores, the mean±SD calculated percentage improvement in pain scale was 54±28. The mean±SD patient-reported percentage improvement in pain scale was 59±25. The overall 95% limits of agreement for the two methods are −30% to +41%. The overall concordance correlation coefficient was 0.76 (95% CI 0.69 to 0.81).

Conclusion

Although the two methods are highly correlated, there is substantial lack of agreement between patient-reported and calculated percentage improvement in pain scale, suggesting that these measures should not be used interchangeably for spinal cord stimulator trial outcome assessment. This emphasizes the need for improved metrics to better measure patient response to neuromodulation therapies. Additionally, patient-reported percentage improvement in pain was found to be higher than calculated percentage improvement in pain, potentially highlighting the multidimensional experience of pain and the unpredictability of solely using Numeric Rating Scale scores to assess patient outcomes.
Organophosphate and carbamate insecticide exposure is related to lung function change among smallholder farmers: a prospective study
Authors: Hansen Martin Rune Hassan , Jørs Erik , Sandbæk Annelli , Sekabojja Daniel , Ssempebwa John C , Mubeezi Ruth , Staudacher Philipp , Fuhrimann Samuel , Sigsgaard Torben , Burdorf Alex , Bibby Bo Martin , Schlünssen Vivi
Published: January 2021

Introduction and aim

Exposure to some insecticides may cause airway obstruction, but existing evidence is limited by cross-sectional designs and inadequate confounder control. We investigated the relation between organophosphate and carbamate insecticides and pulmonary function in a prospective study accounting for important confounders.

Methods

In a cohort of 364 smallholder farmers in Uganda (69% women), participants underwent pre-bronchodilator spirometry at baseline (September/October 2018) and at two follow-up visits (November/December 2018 and January/February 2019). Exposure to carbamate and organophosphate insecticides was assessed using haemoglobin-adjusted erythrocyte acetylcholinesterase (AChE/Hb). Less than 3% of participants were lost to follow-up. We calculated Z-scores for FEV1, FVC and FEV1/FVC using the Global Lung Function Initiative equations. Data were analysed in linear mixed and fixed effect models accounting for family relationships and repeated measures of exposure and outcome.

Results

Low AChE/Hb was significantly associated with low FEV1Z-score in both unadjusted and adjusted analyses. Compared with individuals with AChE/Hb 25.90 U/g (50thpercentile, reference), those with lower AChE/Hb 24.50 U/g (35thpercentile) had mean FEV1Z-score 0.045 (0.003 to 0.087) lower, and persons with higher AChE/Hb 27.30 U/g (65thpercentile) had a mean FEV1Z-score 0.043 (−0.002 to 0.087) higher compared with the reference. Similar, but numerically smaller and statistically non-significant effects were seen for Z-scores of FVC and FEV1/FVC.

Conclusion

Exposure to organophosphate and carbamate insecticides may lead to lung function decline. Our results add to the growing evidence of health effects in relation to exposure to organophosphate and carbamate insecticides, underlining the importance of minimising exposure.
Academic criteria for promotion and tenure in faculties of medicine: a cross-sectional study of the Canadian U15 universities
Authors: Rice Danielle B. , Raffoul Hana , Ioannidis John P.A. , Moher David
Published: January 2021

Background: The objective of this study was to determine the presence of a set of prespecified criteria used to assess scientists for promotion and tenure within faculties of medicine among the U15 Group of Canadian Research Universities.

Methods: Each faculty guideline for assessing promotion and tenure was reviewed and the presence of five traditional (peer-reviewed publications, authorship order, journal impact factor, grant funding, and national/international reputation) and seven nontraditional (citations, data sharing, publishing in open access mediums, accommodating leaves, alternative ways for sharing research, registering research, using reporting guidelines) criteria were collected by two reviewers.

Results: Among the U15 institutions, four of five traditional criteria (80.0%) were present in at least one promotion guideline, whereas only three of seven nontraditional incentives (42.9%) were present in any promotion guidelines. When assessing full professors, there were a median of three traditional criteria listed, versus one nontraditional criterion.

Conclusion: This study demonstrates that faculties of medicine among the U15 Group of Canadian Research Universities base assessments for promotion and tenure on traditional criteria. Some of these metrics may reinforce problematic practices in medical research. These faculties should consider incentivizing criteria that can enhance the quality of medical research.
Stability and improved physical characteristics of relativistic compact objects arising from the quadratic term in $$p_r = \alpha \rho ^2 + \beta \rho - \gamma $$
Authors: Thirukkanesh S. , Bogadi Robert S. , Govender Megandhren , Moyo Sibusiso
Published: January 2021

We investigate the stability and enhancement of the physical characteristics of compact, relativistic objects which follow a quadratic equation of state. To achieve this, we make use of the Vaidya–Tikekar metric potential. This gravitational potential has been shown to be suitable for describing superdense stellar objects. Pressure anisotropy is also a key feature of our model and is shown to play an important role in maintaining stability. Our results show that the combination of the Vaidya–Tikekar gravitational potential used together with the quadratic equation of state provide models which are favourable. In comparison with other equations of state, we have shown that the quadratic equation of state mimics the colour-flavour-locked equation of state more closely than the linear equation of state.
The challenges and possibilities of earthquake predictions using non-seismic precursors
Authors: Bhardwaj A. , Sam L. , Martin-Torres F. J.
Published: January 2021

The catastrophic magnitude of life and monetary losses associated with earthquakes deserve serious attention and mitigation measures. However, in addition to the pre-earthquake and post-earthquake alleviation actions, the scientific community indeed needs to reconsider the possibilities of earthquake predictions using non-seismic precursors. A significant number of studies in the recent decades have reported several possible earthquake precursors such as anomalies in electric field, magnetic field, gas/aerosol emissions, ionospheric signals, ground water level, land surface temperature, surface deformations, animal behaviour, thermal infrared signals, atmospheric gravity waves, and lightning. Such substantial number of scientific articles and reported anomalous signals cannot be overlooked without a thoughtful appraisal. Here, we provide an opinion on the way forward for earthquake prediction in terms of challenges and possibilities while using non-seismic precursors. A general point of concern is the widely varying arrival times and the amplitudes of the anomalies, putting a question mark on their universal applicability as earthquake markers. However, a unifying concept which does not only define the physical basis of either all or most of these anomalies but which also streamlines their characterisation procedure must be the focus of future earthquake precursory research. Advancements in developing the adaptable instrumentation for in-situ observations of the claimed non-seismic precursors must be the next step and the satellite observations should not be taken as a replacement for field-based research. We support the need to standardise the precursor detection techniques and to employ a global-scale monitoring system for making any possible earthquake predictions reliable.
Critical zone of the branching crack model for earthquakes: Inherent randomness, earthquake predictability, and precursor modelling
Authors: Zhuang Jiancang , Matsu’ura Mitsuhiro , Han Peng
Published: January 2021

The branching crack model for earthquakes was developed by Vere-Jones and Kagan in the 1970s and the 1980s, respectively. With some simple and rational assumptions, its simulation results explain the Gutenberg-Richter magnitude-frequency relationship and the Omori-Utsu aftershock decay formula. By introducing the concept of the critical zone, this model can be connected with the asperity model, the barrier model, and the nucleation model through a parameter – criticality. Particularly, the size of the critical zone determines the maximum magnitude of potential earthquakes and the source of their anomalies. The key to earthquake forecasting is to determine whether the concerned area is in a critical state and how large the critical zone is. We discuss what kinds of anomalies are meaningful as candidates of earthquake precursors. Finally, we outline modelling strategies for earthquake precursors with low probability gains that are due to the inherent randomness of earthquake source processes.
Regression based fast multi-trait genome-wide QTL analysis
Authors: Alam Md. Jahangir , Hossain Md. Ripter , Islam S. M. Shahinul , Mollah Md. Nurul Haque
Published: January 2021

Multivariate simple interval mapping (SIM) is one of the most popular approaches for multiple quantitative trait locus (QTL) analysis. Both maximum likelihood (ML) and least squares (LS) multivariate regression (MVR) are widely used methods for multi-trait SIM. ML-based MVR (MVR-ML) is an expectation maximization (EM) algorithm based iterative and complex time-consuming approach. Although the LS-based MVR (MVR-LS) approach is not an iterative process, the calculation of likelihood ratio (LR) statistic in MVR-LS is also a time-consuming complex process. We have introduced a new approach (called FastMtQTL) for multi-trait QTL analysis based on the assumption of multivariate normal distribution of phenotypic observations. Our proposed method can identify almost the same QTL positions as those identified by the existing methods. Moreover, the proposed method takes comparatively less computation time because of the simplicity in the calculation of LR statistic by this method. In the proposed method, LR statistic is calculated only using the sample variance–covariance matrix of phenotypes and the conditional probability of QTL genotype given the marker genotypes. This improvement in computation time is advantageous when the numbers of phenotypes and individuals are larger, and the markers are very dense resulting in a QTL mapping with a bigger dataset.
One Size Does Not Fit All
Authors: Botacin Marcus , Aghakhani Hojjat , Ortolani Stefano , Kruegel Christopher , Vigna Giovanni , Oliveira Daniela , Geus Paulo Lício De , Grégio André
Published: January 2021

Malware analysis is an essential task to understand infection campaigns, the behavior of malicious codes, and possible ways to mitigate threats. Malware analysis also allows better assessment of attackers’ capabilities, techniques, and processes. Although a substantial amount of previous work provided a comprehensive analysis of the international malware ecosystem, research on regionalized, country-, and population-specific malware campaigns have been scarce. Moving towards addressing this gap, we conducted a longitudinal (2012-2020) and comprehensive (encompassing an entire population of online banking users) study of MS Windows desktop malware that actually infected Brazilian banks’ users. We found that the Brazilian financial desktop malware has been evolving quickly: it started to make use of a variety of file formats instead of typical PE binaries, relied on native system resources, and abused obfuscation techniques to bypass detection mechanisms. Our study on the threats targeting a significant population on the ecosystem of the largest and most populous country in Latin America can provide invaluable insights that may be applied to other countries’ user populations, especially those in the developing world that might face cultural peculiarities similar to Brazil’s. With this evaluation, we expect to motivate the security community/industry to seriously consider a deeper level of customization during the development of next-generation anti-malware solutions, as well as to raise awareness towards regionalized and targeted Internet threats.
Lower Bounding the AND-OR Tree via Symmetrization
Authors: Kretschmer William
Published: January 2021

We prove a simple, nearly tight lower bound on the approximate degree of the two-level AND-OR tree using symmetrization arguments. Specifically, we show that
˜
deg(AND

m

ˆ OR

n

) =
˜
Ω(√
mn
). We prove this lower bound via reduction to the OR function through a series of symmetrization steps, in contrast to most other proofs that involve formulating approximate degree as a linear program [6, 10, 21]. Our proof also demonstrates the power of a symmetrization technique involving Laurent polynomials (polynomials with negative exponents) that was previously introduced by Aaronson et al. [2].
Fine-Grained Time Complexity of Constraint Satisfaction Problems
Authors: Jonsson Peter , Lagerkvist Victor , Roy Biman
Published: January 2021

We study the constraint satisfaction problem (CSP) parameterized by a constraint language Γ (CSPΓ) and how the choice of Γ affects its worst-case time complexity. Under the exponential-time hypothesis (ETH), we rule out the existence of subexponential algorithms for finite-domain NP-complete CSPΓ problems. This extends to certain infinite-domain CSPs and structurally restricted problems. For CSPs with finite domain
D
and where all unary relations are available, we identify a relation
S

D

such that the time complexity of the NP-complete problem CSP({

S
D

}) is a lower bound for all NP-complete CSPs of this kind. We also prove that the time complexity of CSP({

S
D

}) strictly decreases when |D| increases (unless the ETH is false) and provide stronger complexity results in the special case when |D|=3.
Child Sexual Abuse as a Unique Risk Factor for the Development of Psychopathology: The Compounded Convergence of Mechanisms
Authors: Noll Jennie G.
Published: January 2021

Meta-analytic, population cohort, prospective, and clinical studies provide systematic evidence that child sexual abuse accounts for unique variation in several deleterious outcomes. There is strong evidence for psychiatric disorders, including posttraumatic stress disorder and mood, anxiety, and substance use disorders, and mixed evidence for personality disorders. Evaluation of sex-specific outcomes shows strong evidence for teenage childbearing, sexual revictimization, and sexual dysfunction and mixed evidence for heightened sexual behaviors and sexual offending. This review further demonstrates not only that survivors suffer the noxious impact of traumatic sexualization but that additional transdiagnostic mechanisms, including the biological embedding of stress, emotion dysregulation, avoidance, and insecure attachment, converge to compound risk for deleterious outcomes. A road map to enhance the rigor of future research is outlined, and specific recommendations for evidence-based policy making to boost prevention efforts and increase access to treatment are discussed.
Dry Deposition of Atmospheric Aerosols: Approaches, Observations, and Mechanisms
Authors: Farmer Delphine K. , Boedicker Erin K. , DeBolt Holly M.
Published: January 2021

Aerosols are liquid or solid particles suspended in the atmosphere, typically with diameters on the order of nanometers to microns. These particles impact air quality and the radiative balance of the planet. Dry deposition is a key process for the removal of aerosols from the atmosphere and plays an important role in controlling the lifetime of atmospheric aerosols. Dry deposition is driven by turbulence and shows a strong dependence on particle size. This review summarizes the mechanisms behind aerosol dry deposition, including measurement approaches, field observations, and modeling studies. We identify several gaps in the literature, including deposition over the cryosphere (i.e., snow and ice surfaces) and the ocean; in addition, we highlight new techniques to measure black carbon fluxes. While recent advances in aerosol instrumentation have enhanced our understanding of aerosol sources and chemistry, dry deposition and other loss processes remain poorly investigated.
Roles of Phase Purity and Crystallinity on Chloramphenicol Sensing Performance of CuCo2O4/CuFe2O4-based Electrochemical Nanosensors
Authors: Pham Tuyet Nhung , Van Cuong Nguyen , Dinh Ngo Xuan , Van Tuan Hoang , Phan Vu Ngoc , Thi Lan Nguyen , Nam Man Hoai , Thanh Tran Dang , Lam Vu Dinh , Van Quy Nguyen , Huy Tran Quang , Phan Manh-Huong , Le Anh-Tuan
Published: January 2021

For the first time, the influences of phase purity and crystallinity on the electrochemical and electrocatalytic properties of CuCo2O4 (CCO) and CuFe2O4 (CFO)-based electrochemical sensors for the detection of chloramphenicol (CAP) are reported. A series of CCO and CFO nanoparticles were prepared by a modified coprecipitation method and then annealed at different temperatures under air (400 °C, 600 °C, 800 °C, and 1000 °C). Surface morphology, the evolution of the crystallite size, and crystalline phase transition, as well as phase purity of CCO and CFO at each annealing temperature, were characterized via different techniques. Their electrochemical properties were analyzed using cyclic voltammetry and differential pulse voltammetry measurements conducted with a PalmSens3 workstation. Results obtained show that the phase purity and crystallinity have decisive effects on their electrocatalytic activity, conductivity, and adsorption efficiency. Under an optimized condition (more namely, annealed 600 °C), both CCO and CFO samples offer high phase purity with low percent of CuO side phase (below 38%), small enough size with a large number of defects and available active sites; particularly, the cubic CFO nanoparticles are present due to its tetragonal phase transition. The modified electrodes with CCO-600 and CFO-600 exhibit a better voltammetric response, a higher synergistic electrocatalytic activity, and a greater electrochemical performance of comparing to other modified electrodes. They respond linearly to chloramphenicol (CAP) in the range from 2.5 to 50 μM. Furthermore, they display am excellent long-term stability, reproducibility, and good selectivity, as well as their capacity of detecting CAP in the real milk sample.
The complexity of Alzheimer’s disease: an evolving puzzle
Authors: Ferrari Camilla , Sorbi Sandro
Published: January 2021

The history of Alzheimer’s disease (AD) started in 1907, but we needed to wait until the end of the century to identify the components of pathological hallmarks and genetic subtypes and to formulate the first pathogenic hypothesis. Thanks to biomarkers and new technologies, the concept of AD then rapidly changed from a static view of an amnestic dementia of the presenium to a biological entity that could be clinically manifested as normal cognition or dementia of different types. What is clearly emerging from studies is that AD is heterogeneous in each aspect, such as amyloid composition, tau distribution, relation between amyloid and tau, clinical symptoms, and genetic background, and thus it is probably impossible to explain AD with a single pathological process. The scientific approach to AD suffers from chronological mismatches between clinical, pathological, and technological data, causing difficulty in conceiving diagnostic gold standards and in creating models for drug discovery and screening. A recent mathematical computer-based approach offers the opportunity to study AD in real life and to provide a new point of view and the final missing pieces of the AD puzzle.
Optical Computed‐Tomographic Microscope for Three‐Dimensional Quantitative Histology
Authors: Chamgoulov Ravil , Lane Pierre , MacAulay Calum
Published: January 2021

A novel optical computed‐tomographic microscope has been developed allowing quantitative three‐dimensional (3D) imaging and analysis of fixed pathological material. Rather than a conventional two‐dimensional (2D) image, the instrument produces a 3D representation of fixed absorption‐stained material, from which quantitative histopathological features can be measured more accurately. The accurate quantification of these features is critically important in disease diagnosis and the clinical classification of cancer. The system consists of two high NA objective lenses, a light source, a digital spatial light modulator (DMD, by Texas Instrument), an x–y stage, and a CCD detector. The DMD, positioned at the back pupil‐plane of the illumination objective, is employed to illuminate the specimen with parallel rays at any desired angle. The system uses a modification of the convolution backprojection algorithm for reconstruction. In contrast to fluorescent images acquired by a confocal microscope, this instrument produces 3D images of absorption stained material. Microscopic 3D volume reconstructions of absorption‐stained cells have been demonstrated. Reconstructed 3D images of individual cells and tissue can be cut virtually with the distance between the axial slices less than 0.5 μm.
Methylation‐Specific PCR Unraveled
Authors: Derks Sarah , Lentjes Marjolein H. F. M. , Hellebrekers Debby M. E. I. , de Bruïne Adriaan P. , Herman James G. , van Engeland Manon
Published: January 2021

Methylation‐specific PCR (MSP) is a simple, quick and cost‐effective method to analyze the DNA methylation status of virtually any group of CpG sites within a CpG island. The technique comprises two parts: (1) sodium bisulfite conversion of unmethylated cytosine′s to uracil under conditions whereby methylated cytosines remains unchanged and (2) detection of the bisulfite induced sequence differences by PCR using specific primer sets for both unmethylated and methylated DNA. This review discusses the critical parameters of MSP and presents an overview of the available MSP variants and the (clinical) applications.
DNA Ploidy and Chromosome (FISH) Pattern Analysis of Peripheral Nerve Sheath Tumors
Authors: Hruska Anett , Bollmann Reinhard , Kovács Rita Beáta , Bollmann Magdolna , Bodó Miklós , Sápi Zoltán
Published: January 2021

Background and methods: 44 peripheral nerve sheath tumors (PNST) (27 schwannomas, 9 neurofibromas and 8 malignant peripheral nerve sheath tumors (MPNST)) were analyzed to determine DNA ploidy pattern and to clarify the conflicting data in the literature concerning this topic (whether benign PNSTs are aneuploid or not). For further insight we analyzed 6 schwannomas, one atypical neurofibroma and five MPNSTs by fluorescence in situ hybridization (FISH) technique using centromeric chromosome probes (7, 17 and 18) and automatic image analysis station, Metafer 4. Results: Benign schwannomas (including the problematic variants as ancient, cellular, neuroblastoma like and multiplex schwannomas) could be characterized by euploid‐polyploidisation and by their 4c peak height value which was usually more than 10% of total cell number measured. These characters were not found among neurofibromas and MPNST‐s. FISH analysis revealed and confirmed that the ‘normal’ euploid–polyploid cells are mainly eusomic–polysomic containing two, four, eight or sixteen signals for each chromosomes examined, but in a small proportion aneusomy was found among tumor cells of benign schwannomas (average: 2.58; range 1.33–3.44). In contrast, the atypical neurofibroma displayed marked aneusomy (18.44%) but it contained normal eusomic and polysomic cells too. Two diploid MPNSTs proved to be clearly aneusomic with trisomy of chromosome 17 and monosomy of chromosome 18. Conclusions: All these data suggest that ploidy pattern determination combined with FISH analysis may be a very useful supplementary tool for making a right diagnosis (to differentiate benign versus malignant schwannomas in problematic variants) and to understand better the malignant transformation in PNSTs.
DNA Copy Number Changes at 8q11–24 in Metastasized Colorectal Cancer
Authors: Buffart T. E. , Coffa J. , Hermsen M. A. J. A. , Carvalho B. , van der Sijp J. R. M. , Ylstra B. , Pals G. , Schouten J. P. , Meijer G. A.
Published: January 2021

Background: C‐Myc, a well‐known oncogene located on 8q24.12–q24.23, is often amplified and over‐expressed in both primary and metastasizing colorectal cancer. In addition, PRL‐3 (also known as PTP4A3), a tyrosine phosphatase located on 8q24.3, is amplified in colorectal cancer metastasis. Beside PRL‐3 and c‐myc, other oncogenes located on the 8q23–24 region might be involved in this process. Therefore, the present study aims to correlate DNA copy number status of a series of genes at 8q23–24 in colorectal cancer at high resolution in correlation to metastatic disease. Materials and Methods: Thirty‐two cases of colorectal cancer, 10 stage B1, 10 B2 and 12 D (Astler–Coller) with their corresponding liver metastasis and one colorectal cell line (colo205, previously analyzed by array‐CGH), were included in this study. A chromosome 8 specific MLPA probe mixture was used to analyze the presence of DNA copy number changes. The probe mixture contained 29 probes covering 25 genes on chromosome 8, as well as 6 control probes on other chromosomes. Results and Discussion: MLPA results obtained of the colo205 colorectal cell line were comparable with previous array‐CGH results, thus validating the MLPA probe mixture. Astler–Coller B1 and B2 colorectal cancers differed significantly in DNA copy number of the genes, MOS (p = 0.04), MYC (p = 0.007), DDEF1 (p = 0.004), PTK2 (p = 0.02) and PTP4A3 (p = 0.04). When comparing these with Astler–Coller D primary tumors, significant differences were seen for several genes as well (MYC (p < 0.000), DDEF1 (p < 0.000), SLA (p < 0.000), PTK2 (p < 0.000), PTP4A3 (p = 0.002), and RECQL4 (p = 0.01)). When comparing primary Astler–Coller D tumors and their corresponding liver metastases, a similar pattern of gains and losses was observed. Most of the liver metastases showed higher DNA copy number ratios than the corresponding primary tumors, but this difference was only significant for TPD52 (p = 0.02) and EIF3S6 (p = 0.007). Conclusion: In addition to c‐myc, multiple genes on chromosome 8 differed significantly between primary colorectal cancers with and without liver metastases. This observation is consistent with the concept that clinical behaviour, like risk of liver metastasis, is determined by the genomic profile that is already present in the primary tumor.
Digital Image DNA Cytometry: A Useful Tool for the Evaluation of Malignancy in Biliary Strictures
Authors: Osterheld M. C. , Andrejevic Blant S. , Caron L. , Braunschweig R. , Dorta G. , Bouzourene H. , Mihaescu A.
Published: January 2021

Background: Cytologic evaluation of the biliary tract strictures is nowadays widely used for distinguishing between benign and malignant lesions but remains a challenge for some problematic cases. Digital Image cytometry (DNA‐cytometry) helps cytopathologists to resolve some unclear situations.

Methods: We have analysed 41 specimens of bile duct brushings obtained from patients during ERCP (11 benign cases, 7 suspicious for malignancy cases and 23 malignant cases) by DNA‐cytometry and correlated them with the histological biopsy counterpart.

Results: All eleven cytological and histological benign cases were DNA‐diploid and among 22 patients with malignant cytological and histological diagnosis 21 were DNA‐aneuploid. One case considered malignant by the cytopathologist revealed DNA‐aneuploid but malignancy could not be confirmed by histology. The analysis of the suspicious for malignancy cases revealed that all DNA‐aneuploid cases were malignant and all DNA‐diploid cases were benign referring to the follow‐up of the patients.

The comparison between cytology alone and cytology combined with DNA‐cytometry related to the histological diagnosis (gold standard) resulted in a sensitivity of 100% and a specificity of 79% for cytology alone; a specificity of 94% and a sensitivity 92% for DNA‐cytometry and a specificity of 93% and a sensitivity of 100% with combined analyses. The positive predictive value was 90% for cytology, 96% for DNA‐cytometry and for both analyses. The negative predictive value showed 100% for cytology, 89% for DNA‐cytometry and 100% for combined studies.

Conclusions: Despite the limited number of patients involved in the study, the Results obtained indicate an increased of specificity and of positive predictive value using DNA‐cytometry. These Results confirm the pertinence of these method for challenging cases, in conjunction with other available diagnostic tools.
Multi‐Resolution Wavelet‐Transformed Image Analysis of Histological Sections of Breast Carcinomas
Authors: Hwang Hae-Gil , Choi Hyun-Ju , Lee Byeong-Il , Yoon Hye-Kyoung , Nam Sang-Hee , Choi Heung-Kook
Published: January 2021

Multi‐resolution images of histological sections of breast cancer tissue were analyzed using texture features of Haar‐ and Daubechies transform wavelets. Tissue samples analyzed were from ductal regions of the breast and included benign ductal hyperplasia, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (CA). To assess the correlation between computerized image analysis and visual analysis by a pathologist, we created a two‐step classification system based on feature extraction and classification. In the feature extraction step, we extracted texture features from wavelet‐transformed images at 10× magnification. In the classification step, we applied two types of classifiers to the extracted features, namely a statistics‐based multivariate (discriminant) analysis and a neural network. Using features from second‐level Haar transform wavelet images in combination with discriminant analysis, we obtained classification accuracies of 96.67 and 87.78% for the training and testing set (90 images each), respectively. We conclude that the best classifier of carcinomas in histological sections of breast tissue are the texture features from the second‐level Haar transform wavelet images used in a discriminant function.