bluuebunny/crossref_metadata_2025 huggingface dataset:
A Simple Framework to Identify Optimal Cost-Effective Risk Thresholds for a Single Screen: Comparison to Decision Curve Analysis
Authors: A. Katki Hormuzd , Bebu Ionut
Published: March 2021

Decision curve analysis (DCA) is a popular approach for assessing biomarkers and risk models, but does not require costs and thus cannot identify optimal risk thresholds for actions. Full decision analyses can identify optimal thresholds, but typically used methods are complex and often difficult to understand. We develop a simple framework to calculate the incremental net benefit for a single-time screen as a function of costs (for tests and treatments) and effectiveness (life-years gained). We provide simple expressions for the optimal cost-effective risk threshold and, equally importantly, for the monetary value of life-years gained associated with the risk threshold. We consider the controversy over the risk threshold to screen women for mutations in BRCA1/2. Importantly, most, and sometimes even all, of the thresholds identified by DCA are infeasible based on their associated dollars per life-year gained. Our simple framework facilitates sensitivity analyses to cost and effectiveness parameters. The proposed approach estimates optimal risk thresholds in a simple and transparent manner, provides intuition about which quantities are critical, and may serve as a bridge between DCA and a full decision analysis.
Pension Eligibility Rules and the Local Causal Effect of Retirement on Cognitive Functioning
Authors: Fé Eduardo
Published: March 2021

We propose an identification framework to evaluate the exclusion restriction in a fuzzy regression discontinuity setting, by adopting results from the literature on partial identification with invalid instrumental variables. With this framework, we provide new estimates of the effect of retirement on cognitive functioning and the first empirical analysis of the validity of an age-based instrumental variable for retirement. Point estimates suggest an insignificant negative effect of retirement on cognitive functioning. Partial identification regions qualify this finding by suggesting that if retirement is, in fact, detrimental for cognitive functioning, then large drops are unlikely. Second, data alone cannot identify the sign of the treatment effect. In fact, our results support improvements in cognitive functioning following retirement. The bounds analysis suggest that, when studying the impact of retirement, the validity of eligibility as an instrumental variable depends on the time period considered for the analysis and that violations of the exclusion restriction are likely already in very small intervals of 8 months around the cut-off in regression discontinuity designs.
Immune reconstitution and severity of COVID‐19 among hematopoietic cell transplant recipients
Authors: Malek Alexandre E. , Adachi Javier A. , Mulanovich Victor E. , Sassine Joseph , Raad Issam I. , McConn Kelly , Seiler Garret T. , Dhal Udit , Khawaja Fareed , Chemaly Roy F.
Published: March 2021

Severe acute respiratory syndrome coronavirus 2 can lead to life‐threatening coronavirus disease 2019 (COVID‐19) infections in patients with hematologic malignancies, particularly among hematopoietic cell transplant (HCT) recipients. We describe two patients with COVID‐19 during the pre‐engraftment period after HCT and review previous reports of COVID‐19 in HCT recipients. Because of significant mortality from COVID‐19, primarily after allogeneic HCT, early, preemptive, and optimal directed therapy may improve outcomes and reduce the mortality rate but still needs to be established in clinical trials.
Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro
Authors: Thomas Kimberly A. , Shea Susan M. , Spinella Philip C.
Published: March 2021

Background

Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf‐stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction.

Study Design and Methods

Hemostatic adjunct study products were psoralen‐treated PR‐cryoprecipitated fibrinogen complex (PR‐Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR‐Cryo FC and Cryo were stored for 10 days at 20–24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation.

Results

PR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR‐Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20–24°C did not diminish the hemostatic function of PR‐Cryo FC.

Discussion

PR‐Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR‐Cryo FC has the potential to improve outcomes.
International Development Cooperation Today
Authors: Develtere Patrick , Huyse Huib , Van Ongevalle Jan
Published: March 2021

Over the past 60 years high-income countries have invested over 4000 billion euros in development aid. With varying degrees of success, these investments in low-income countries contributed to tackling structural problems such as access to water, health care, and education. Today, however, international development cooperation is no longer restricted to helping by giving. Instead, it is rather about opportunities, mutual interests, risk taking, and an inclusive societal approach. With the arrival of major new actors such as China, India, and Brazil, and the manifestation of private companies and foundations like the Bill and Melinda Gates Foundation, development aid is being eclipsed by new forms of international cooperation, increasingly accompanied by investments, trade, and give-and-take exchanges. The agenda for sustainable development, adopted by all United Nations Member States in 2015 and to be realised by 2030, is a case in point of new influential frameworks that usher in a global rather than a traditional North-South perspective. This book reviews 60 years of international development aid and its relevant actors, outlining today’s challenges and opportunities. Richly illustrated with case studies and examples, International Development Cooperation Today maps successes and failures and synthesizes visions and discussions from all over the world. By pointing out the radical shift from the traditional North-South perspective to a global paradigm, this book is essential reading for all practitioners, academics, and donors involved in development aid.
New Method Based on Model-Free Adaptive Control Theory and Kalman Filter for Multi-Product Unsteady Flow State Estimation
Authors: He Lei , Gong Jing , Wen Kai , Wu Changchun , Min Yuan
Published: March 2021

In this paper, a new methodology is proposed to realize real-time unsteady flow estimation for a multi-product pipeline system. Integrating transient flow model, adaptive control theory, and adaptive filter, this method is developed to solve the contradiction between the efficiency and accuracy in traditional model-based methods. In terms of improving computational efficiency, the linear flow model based on frequency response and difference transforming is established to replace the traditional nonlinear flow model for transient flow state estimation. To reduce the deviation between actual observations and linear model estimates, we first introduce a model-free adaptive control method as linear compensation of the reduced order unsteady flow state model. To overcome the interference of observation noise, the Kalman filter method is applied to the modified state space model to obtain the one-step-ahead transient flow estimation. The proposed method is applied to the transient flow state estimation of a multi-product pipeline system and compared with the model-based method and two data-driven methods. The proposed method can reduce the deviation of transient flow estimation between the reduced order linear model and the traditional nonlinear model to less than 0.5% under unforeseen conditions and shows strong robustness to noise interference and parameter drift.
Apparent size effects on dopant activation in nanometer-wide Si fins
Authors: Folkersma Steven , Bogdanowicz Janusz , Favia Paola , Wouters Lennaert , Petersen Dirch Hjorth , Hansen Ole , Henrichsen Henrik Hartmann , Nielsen Peter Former , Shiv Lior , Vandervorst Wilfried
Published: March 2021

Due to the dramatic downscaling of device features in recent technology nodes, characterizing the electrical properties of these structures is becoming ever more challenging as it often requires metrology able to probe local variations in dopant and carrier concentration with high accuracy. As no existing technique is able to meet all requirements, a correlative metrology approach is generally considered a solution. In this article, we study size-dependent effects on the dopant activation in nanometer-wide Si fins using a novel correlative approach. We start by showing that the micro four-point probe technique can be used to precisely measure the resistance of B doped and (laser) annealed Si fins. Next, we use transmission electron microscopy and scanning spreading resistance microscopy to show that the observed width dependence of the apparent sheet resistance of these fins can be explained by either a partially or a fully inactive region forming along the top of the fin sidewalls according to the annealing conditions.
TMEM16F mediates bystander TCR-CD3 membrane dissociation at the immunological synapse and potentiates T cell activation
Authors: Connolly Audrey , Panes Rébecca , Tual Margaux , Lafortune Raphaël , Bellemare-Pelletier Angélique , Gagnon Etienne
Published: March 2021

The scramblase TMEM16F flips the distribution of phosphatidylserine in the T cell plasma membrane to activate bystander TCRs.
Sensing mitochondrial damage
Authors: Foley John F.
Published: March 2021

Detection of cytosolic mitochondrial RNA resulting from mitochondrial DNA breaks triggers a type I interferon response.
Holomycin, an Antibiotic Secondary Metabolite, Is Required for Biofilm Formation by the Native Producer Photobacterium galatheae S2753
Authors: Zhang Sheng-Da , Isbrandt Thomas , Lindqvist Laura Louise , Larsen Thomas Ostenfeld , Gram Lone
Published: March 2021

Despite the societal impact of antibiotics, their ecological functions remain elusive and have mostly been studied by exposing nonproducing bacteria to subinhibitory concentrations. Here, we studied the effects of the antibiotic holomycin on its native producer,
Photobacterium galatheae
S2753, a
Vibrionaceae
bacterium.
A Systematic Approach to Promote Environmental Engineering Students’ Learning in Environmental Molecular Microbiology
Authors: Wang Shanquan , Lu Hui , Zhao Chunmei , Juneau Philippe
Published: March 2021

Environmental Molecular Microbiology (EMM) is a core course cluster for students majoring in environmental engineering. To help students learn the EMM courses, we developed a three-stage teaching approach to deliver EMM courses in a systematic manner: prerequisite course and survey studies; course cluster teaching; and feedback and improvement.
Genome Analysis of SARS-CoV-2 Case Study: An Undergraduate Online Learning Activity to Introduce Bioinformatics, BLAST, and the Power of Genome Databases
†
Authors: Steel J. Jordan
Published: March 2021

The COVID19 pandemic has significantly impacted scientific research and higher education. With the chaos, confusion, and concern caused by the SARSCoV2/COVID19 pandemic, there are lots of questions and general curiosity about coronaviruses and infectious disease. This global health crisis provides an optimal platform for teaching and discussing scientific research. COVID19-specific learning activities can help guide students and the public to accurately find scientific answers to their questions and help educate and teach true scientific principles to those eagerly wanting answers about COVID19. A SARSCoV2/COVID19 case study has been developed that allows students to align the genomes of 4 different coronaviruses to identify potential origins of the virus. Additional questions direct students to think critically about how an RNA viral genome may have different implications than a DNA viral genome, or why mutations in the surface glycoprotein may have big impacts on viral transmission and immunity. This case study was developed and implemented in Spring 2020 and was well received by students. It provides an introduction to genomics and bioinformatics through a highly relevant and applicable topic that everyone is interested in: COVID19.
Supplemental Material 1: Geomorphic expression and slip rate of the Fairweather fault, southeast Alaska, and evidence for predecessors of the 1958 rupture
Authors: Witter R.C. , al. et
Published: March 2021

GIS material includes four shapefiles depicting geomorphic lines, fault lines, unit contacts, and geologic units mapped on lidar-based digital elevation models and in the field as explained in the paper.
Detailed analysis of ‘work as imagined’ in the use of intravenous insulin infusions in a hospital: a hierarchical task analysis
Authors: Iflaifel Mais Hasan , Lim Rosemary , Crowley Clare , Ryan Kath , Greco Francesca
Published: March 2021

Objective

Variable rate intravenous insulin infusions (VRIII) is a high-risk medication that has a potential to cause significant patient harm if used in error. Complex preparation of VRIII in clinical areas and the need for frequent monitoring and adjustment increase the complexity of using VRIII. An emerging approach, called Resilient Healthcare, proposes understanding complexity of work by exploring how work is assumed to be done and compare it with everyday work. This study aimed to explore how VRIII is perceived to be used by healthcare practitioners, focusing on one aspect of Resilient Healthcare: understanding how work is assumed to be done, using a method called hierarchical task analysis (HTA).

Design

A qualitative study using document analysis and focus groups.

Setting

A vascular surgery unit in an acute National Health Service teaching hospital in the UK.

Participants

Stakeholders/users in different professional roles involved in the process of using VRIII.

Results

The HTA showed the complexity of using VRIII and highlighted more than 115 steps required to treat elevated blood glucose. The process of producing hospital-specific guidelines was iterative. Careful consideration was taken to coordinate the development and implementation of guidelines. Documents provided detailed clinical instructions related to the use of VRIII but practitioners selectively used them, often in deference to senior colleagues. Intentional adaptations, for example, proactively asking for a VRIII prescription occurred and were acknowledged as part of providing individualised patient care.

Conclusion

Using VRIII to treat elevated blood glucose is a complex but necessary process mediated by a range of factors such as organisational influences. Adaptive strategies to mitigate errors were common and future research can build on insights from this study to develop a broader understanding of how VRIII is used and to understand how adaptations are made in relation to the use of VRIII.
Are there non-linear relationships between alcohol consumption and long-term health? Protocol for a systematic review of observational studies employing approaches to improve causal inference
Authors: Visontay Rachel , Sunderland Matthew , Slade Tim , Wilson Jack , Mewton Louise
Published: March 2021

Introduction

There is a substantial literature finding that moderate alcohol consumption is protective against certain health conditions. However, more recent research has highlighted the possibility that these findings are methodological artefacts, caused by confounding and other biases. While modern analytical and study design approaches can mitigate confounding and thus enhance causal inference in observational studies, they are not routinely applied in research assessing the relationship between alcohol use and long-term health outcomes. The purpose of this systematic review is to identify observational studies that employ these analytical/design-based approaches in assessing whether relationships between alcohol consumption and health outcomes are non-linear. This review seeks to evaluate, on a per-outcome basis, what these studies find the strength and form of the relationship between alcohol consumption and health to be.

Methods and analysis

Electronic databases (MEDLINE, PsycINFO, Embase and SCOPUS) were searched in May 2020. Study selection will comply with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Articles will be screened against eligibility criteria intended to capture studies using observational data to assess the relationship between varying levels of alcohol exposure and any long-term health outcome (actual or surrogate), and that have employed at least one of the prespecified approaches to enhancing causal inference. Risk of bias of included articles will be assessed using study design-specific tools. A narrative synthesis of the results is planned.

Ethics and dissemination

Formal ethics approval is not required given there will be no primary data collection. The results of the study will be disseminated through published manuscripts, conferences and seminar presentations.

PROSPERO registration number

CRD42020185861.
Change in prevalence rates of physical and sexual intimate partner violence against women: data from two cross-sectional studies in New Zealand, 2003 and 2019
Authors: Fanslow Janet , Hashemi Ladan , Malihi Zarintaj , Gulliver Pauline , McIntosh Tracey
Published: March 2021

Objectives

To explore changes in reported prevalence of physical and sexual intimate partner violence (IPV) between 2003 and 2019. The impact of sociodemographic differences between the two samples and between group differences were also examined. Changes in attitudes supportive of violence and in help-seeking behaviour following disclosure were also explored.

Design

Two cross-sectional studies.

Setting and participants

Cross-sectional studies on family violence conducted in New Zealand in 2003 and 2019. Ever-partnered female respondents aged 18–64 years old were included (2003 n=2674, 2019 n=944).

Main outcome measures

Prevalence rates of lifetime and past 12-month physical and sexual IPV, attitudes towards gender roles and acceptability of a man hitting his wife, help sought and received following disclosure were compared between the study years.

Results

Lifetime prevalence of physical IPV was unchanged between 2003 and 2019 (AOR=0.89; 95% CI 0.73 to 1.08). There was a significant decrease in the proportion of women who reported experiencing 12-month physical IPV (AOR=0.53; 95% CI 0.29 to 0.97). Small reductions in rates for lifetime sexual IPV were also observed (AOR=0.74; 95% CI 0.59 to 0.95). In 2019, fewer women agreed with one or more statements supportive of traditional gender roles (48.1% (95% CI 45.7% to 50.5%) in 2003; 38.4% (95% CI 33.8% to 43.2%) in 2019). A significant decrease was noted in the proportion of women who sought help from informal sources (from 71.3% (95% CI 68.1% to 74.2%) in 2003 to 64.6% (95% CI 58.7% to 70.1%) in 2019). No significant changes in seeking help from formal sources, or perceived helpfulness from any source were noted.

Conclusion

While the reductions in 12-month physical and lifetime sexual IPV are positive, prevention efforts need to be established, maintained and strengthened to address the substantial lifetime prevalence of IPV. Efforts to strengthen responses from formal and informal sources continue to be needed.
Prospective observational cohort study of factors influencing trial participation in people with motor neuron disease (FIT-participation-MND): a protocol
Authors: Beswick Emily , Glasmacher Stella A , Dakin Rachel , Newton Judith , Carson Alan , Abrahams Sharon , Chandran Siddharthan , Pal Suvankar
Published: March 2021

Introduction

Motor neuron disease (MND) is a rapidly progressive and fatal neurodegenerative disorder with limited treatment options. The Motor Neuron Disease Systematic Multi-Arm Randomised Adaptive Trial (MND-SMART) is a multisite UK trial seeking to address the paucity in effective disease-modifying drugs for people with MND (pwMND). Historically, neurological trials have been plagued by suboptimal recruitment and high rates of attrition. Failure to recruit and/or retain participants can cause insufficiently representative samples, terminated trials or invalid conclusions. This study investigates patient-specific factors affecting recruitment and retention of pwMND to MND-SMART. Improved understanding of these factors may improve trial protocol design, optimise recruitment and retention.

Methods and analysis

PwMND on the Scottish MND Register, Clinical Audit Research and Evaluation of MND (CARE-MND), will be invited to participate in a prospective observational cohort study that investigates factors affecting trial participation and attrition. We hypothesise that patient-specific factors will significantly affect trial recruitment and retention. Participants will complete the Hospital Anxiety and Depression Scale, 9-Item Patient Health Questionnaire and State-Trait Anxiety Inventory-Form Y to evaluate neuropsychiatric symptoms, the ALS-Specific Quality of Life Questionnaire-Brief Form and Centre for Disease Control and Prevention-Health-Related Quality of Life for quality of life and a novel study-specific questionnaire on Attitudes towards Clinical Trial Participation (ACT-Q). Clinical data on phenotype, cognition (Edinburgh Cognitive and Behavioural ALS Screen) and physical functioning (Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised) will also be collated. Caregivers will complete the Brief Dimensional Apathy Scale. After 12 months, a data request to MND-SMART will evaluate recruitment and retention. Descriptive statistics will summarise and compare assessments and participants reaching impairment thresholds. Variable groupings: attitudes, quality of life, cognition, behaviour, physical functioning, neuropsychiatric and phenotype. Univariate and multivariable logistic regression will explore association with participation/withdrawal in MND-SMART; presented as ORs and 95% CIs.

Ethics and dissemination

Ethical approval was provided by the West of Scotland Research Ethics Committee 3 (20/WS/0067) on 12 May 2020. The results of this study will be published in a peer-reviewed journal, presented at academic conferences and disseminated to participants and the public.
Prevalence of frailty and pain in hospitalised adult patients in an acute hospital: a protocol for a point prevalence observational study
Authors: Saunders Rosemary , Crookes Kate , Atee Mustafa , Bulsara Caroline , Bulsara Max K , Etherton-Beer Christopher , Ewens Beverley , Gallagher Olivia , Graham Renee M , Gullick Karen , Haydon Sue , Nguyen Kim-Huong , O"Connell Bev , Seaman Karla , Hughes Jeff
Published: March 2021

Introduction

Frailty and pain are associated with adverse patient clinical outcomes and healthcare system costs. Frailty and pain can interact, such that symptoms of frailty can make pain assessment difficult and pain can exacerbate the progression of frailty. The prevalence of frailty and pain and their concurrence in hospital settings are not well understood, and patients with cognitive impairment are often excluded from pain prevalence studies due to difficulties assessing their pain. The aim of this study is to determine the prevalence of frailty and pain in adult inpatients, including those with cognitive impairment, in an acute care private metropolitan hospital in Western Australia.

Methods and analysis

A prospective, observational, single-day point prevalence, cross-sectional study of frailty and pain intensity of all inpatients (excluding day surgery and critical care units) will be undertaken. Frailty will be assessed using the modified Reported Edmonton Frail Scale. Current pain intensity will be assessed using the PainChek smart-device application enabling pain assessment in people unable to report pain due to cognitive impairment. Participants will also provide a numerical rating of the intensity of current pain and the worst pain experienced in the previous 24 hours. Demographic and clinical information will be collected from patient files. The overall response rate of the survey will be reported, as well as the percentage prevalence of frailty and of pain in the sample (separately for PainChek scores and numerical ratings). Additional statistical modelling will be conducted comparing frailty scores with pain scores, adjusting for covariates including age, gender, ward type and reason for admission.

Ethics and dissemination

Ethical approval has been granted by Ramsay Health Care Human Research Ethics Committee WA/SA (reference: 2038) and Edith Cowan University Human Research Ethics Committee (reference: 2020–02008-SAUNDERS). Findings will be widely disseminated through conference presentations, peer-reviewed publications and social media.

Trial registration number

ACTRN12620000904976.
Variation in referral rates to emergency departments and inpatient services from a GP out of hours service and the potential impact of alternative staffing models
Authors: Lasserson Daniel , Smith Honora , Garland Sophie , Hunt Helen , Hayward Gail
Published: March 2021

Introduction

Out of hours (OOHs) primary care is a critical component of the acute care system overnight and at weekends. Referrals from OOH services to hospital will add to the burden on hospital assessment in the ED and on-call specialties.

Methods

We studied the variation in referral rates (to the ED and direct specialty admission) of individual clinicians working in the Oxfordshire, UK OOH service covering a population of 600 000 people. We calculated the referral probability for each clinician over a 13-month period of practice (1 December 2014 to 31 December 2015), stratifying by clinician factors and location and timing of assessment. We used Simul8 software to determine the range of hospital referrals potentially due to variation in clinician referral propensity.

Results

Among the 119 835 contacts with the service, 5261 (4.4%) were sent directly to the ED and 3474 (3.7%) were admitted directly to specialties. More referrals were made to ED by primary care physicians if they did not work in the local practices (5.5% vs 3.5%, p=0.011). For clinicians with >1000 consultations, percentage of patients referred varied from 1% to 21% of consultations. Simulations where propensity to refer was made less extreme showed a difference in maximum referrals of 50 patients each week.

Conclusions

There is substantial variation in clinician referral rates from OOHs primary care to the acute hospital setting. The number of patients referred could be influenced by this variation in clinician behaviour. Referral propensity should be studied including casemix adjustment to determine if interventions targeting such behaviour are effective.
Indigenous Peoples, concentrated disadvantage, and income inequality in New Mexico: a ZIP code-level investigation of spatially varying associations between socioeconomic disadvantages and confirmed COVID-19 cases
Authors: Huyser Kimberly R , Yang Tse-Chuan , Yellow Horse Aggie J
Published: March 2021

Background

The coronavirus disease pandemic has disproportionately affected poor and racial/ethnic minority individuals and communities, especially Indigenous Peoples. The object of this study is to understand the spatially varying associations between socioeconomic disadvantages and the number of confirmed COVID-19 cases in New Mexico at the ZIP code level.

Methods

We constructed ZIP code-level data (n=372) using the 2014–2018 American Community Survey and COVID-19 data from the New Mexico Department of Health (as of 24 May 2020). The log-linear Poisson and geographically weighted Poisson regression are applied to model the number of confirmed COVID-19 cases (total population as the offset) in a ZIP code.

Results

The number of confirmed COVID-19 cases in a ZIP code is positively associated with socioeconomic disadvantages—specifically, the high levels of concentrated disadvantage and income inequality. It is also positively associated with the percentage of American Indian and Alaskan Native populations, net of other potential confounders at the ZIP code level. Importantly, these associations are spatially varying in that some ZIP codes suffer more from concentrated disadvantage than others.

Conclusions

Additional attention for COVID-19 mitigation effort should focus on areas with higher levels of concentrated disadvantage, income inequality, and higher percentage of American Indian and Alaska Native populations as these areas have higher incidence of COVID-19. The findings also highlight the importance of plumbing in all households for access to clean and safe water, and the dissemination of educational materials aimed at COVID-19 prevention in non-English language including Indigenous languages.
MYC oncogene is associated with suppression of tumor immunity and targeting Myc induces tumor cell immunogenicity for therapeutic whole cell vaccination
Authors: Wu Xiaofang , Nelson Marie , Basu Mousumi , Srinivasan Priya , Lazarski Christopher , Zhang Peng , Zheng Pan , Sandler Anthony David
Published: March 2021

Background

MYC oncogene is deregulated in 70% of all human cancers and is associated with multiple oncogenic functions including immunosuppression in the tumor microenvironment. The role of MYC in the immune microenvironment of neuroblastoma and melanoma is investigated and the effect of targeting Myc on immunogenicity of cancer cells is evaluated.

Methods

Immune cell infiltrates and immunogenic pathway signatures in the context of MYCN amplification were analyzed in human neuroblastoma tumors and in metastatic melanoma. Dose response and cell susceptibility to MYC inhibitors (I-BET726 and JQ1) were determined in mouse cell lines. The influence of downregulating Myc in tumor cells was characterized by immunogenic pathway signatures and functional assays. Myc-suppressed tumor cells were used as whole cell vaccines in preclinical neuroblastoma and melanoma models.

Results

Analysis of immune phenotype in human neuroblastoma and melanoma tumors revealed that MYCN or c-MYC amplified tumors respectively are associated with suppressed immune cell infiltrates and functional pathways. Targeting Myc in cancer cells with I-BET726 and JQ1 results in cell cycle arrest and induces cell immunogenicity. Combining vaccination of Myc-inhibited tumor cells with checkpoint inhibition induced robust antitumor immunity and resulted in therapeutic cancer vaccine therapy in mouse neuroblastoma tumors. Despite vigorous antitumor immunity in the mouse melanoma model, upregulation of immunosuppressive pathways enabled tumor escape.

Conclusions

This study demonstrates that the Myc oncogene is an appropriate target for inducing tumor cell immunogenicity and suggests that Myc-suppressed whole tumor cells combined with checkpoint therapy could be used for formulating a personalized therapeutic tumor vaccine.
Impact of ultrasound contrast agent during transoesophageal echocardiography on the sizing of the left atrial appendage
Authors: Ebelt Henning , Goetze Sarah , Weida Anja , Offhaus Alexandra
Published: March 2021

Introduction

Interventional closure of the left atrial appendage closure (LAAC) has been established as an alternative treatment in patients with atrial fibrillation (AF) and an increased risk of stroke. So far it is unknown whether the use of ultrasound contrast agent (UCA) would influence the correct sizing of the LAA and thereby have an impact on device selection during interventional LAAC.

Methods

Between January 2017 and April 2018, 223 transoesophageal echocardiography (TOE) examinations were prospectively performed in adult patients with non-valvular AF (Impact of the use of ultrasound contrast agent on the detection of thrombi in the left atrial appendage during transesophageal echocardiography (CONDOR) study). LAA was examined both with and without the use of UCA. The following measurements were taken at 0o, 45o, 90oand 135o: diameter of LAA ostium, maximal depth of the LAA, maximal available depth of the LAA orthogonal to the ostial plane and area of the LAA.

Results

The use of UCA had no relevant influence on the size determination of the LAA. Additionally, Bland-Altman blots demonstrate a high degree of correlation between the measurements with and without UCA with no evidence for a systematic effect arising from the use of UCA. When comparing the measurements of two independent investigators, the use of UCA rather leads to a higher variability than to an improved precision.

Discussion

Despite the fact that the use of UCA during TOE leads to an improved rule out of thrombi, our study shows that there is no advantageous effect of UCA on the size determination of the LAA and should therefore not be used for this purpose.
Interventional procedure plans generated by telemedicine visits in spine patients are rarely changed after in-person evaluation
Authors: Crawford Alexander M , Lightsey Harry M , Xiong Grace X , Striano Brendan M , Greene Nattaly , Schoenfeld Andrew J , Simpson Andrew K
Published: March 2021

Background and objectives

The role of telemedicine in the evaluation and treatment of patients with spinal disorders is rapidly expanding, brought on largely by the COVID-19 pandemic. Within this context, the ability of pain specialists to accurately diagnose and plan appropriate interventional spine procedures based entirely on telemedicine visits, without an in-person evaluation, remains to be established. In this study, our primary objective was to assess the relevance of telemedicine to interventional spine procedure planning by determining whether procedure plans established solely from virtual visits changed following in-person evaluation.

Methods

We reviewed virtual and in-person clinical encounters from our academic health system’s 10 interventional spine specialists. We included patients who were seen exclusively via telemedicine encounters and indicated for an interventional procedure with documented procedural plans. Virtual plans were then compared with the actual procedures performed following in-person evaluation. Demographic data as well as the type and extent of physical examination performed by the interventional spine specialist were also recorded.

Results

Of the 87 new patients included, the mean age was 60 years (SE 1.4 years) and the preprocedural plan established by telemedicine, primarily videoconferencing, did not change for 76 individuals (87%; 95% CI 0.79 to 0.94) following in-person evaluation. Based on the size of our sample, interventional procedures indicated solely during telemedicine encounters may be accurate in 79%–94% of cases in the broader population.

Conclusions

Our findings suggest that telemedicine evaluations are a generally accurate means of preprocedural assessment and development of interventional spine procedure plans. These findings clearly demonstrate the capabilities of telemedicine for evaluating spine patients and planning interventional spine procedures.
Predicting long-term outcomes in acute intracerebral haemorrhage using delayed prognostication scores
Authors: Lun Ronda , Yogendrakumar Vignan , Ramsay Tim , Shamy Michel , Fahed Robert , Selim Magdy H , Dowlatshahi Dar
Published: March 2021

Objective

The concept of the ‘self-fulfilling prophecy’ is well established in intracerebral haemorrhage (ICH). The ability to improve prognostication and prediction of long-term outcomes during the first days of hospitalisation is important in guiding conversations around goals of care. We previously demonstrated that incorporating delayed imaging into various prognostication scores for ICH improves the predictive accuracy of 90-day mortality. However, delayed prognostication scores have not been used to predict long-term functional outcomes beyond 90 days.

Design, setting and participants

We analysed data from the ICH Deferoxamine trial to see if delaying the use of prognostication scores to 96 hours after ICH onset will improve performance to predict outcomes at 180 days. 276 patients were included.

Interventions and measurements

We calculated the original ICH score (oICH), modified-ICH score (MICH), max-ICH score and the FUNC score on presentation (baseline), and on day 4 (delayed). Outcomes assessed were mortality and poor functional outcome in survivors (defined as modified Rankin Scale of 4–5) at 180 days. We generated receiver operating characteristic curves, and measured the area under the curve values (AUC) for mortality and functional outcome. We compared baseline and delayed AUCs with non-parametric methods.

Results

At 180 days, 21 of 276 (7.6%) died. Out of the survivors, 54 of 255 had poor functional outcome (21.2%). The oICH, MICH and max-ICH performed significantly better at predicting 180-day mortality when calculated 4 days later compared with their baseline equivalents ((0.74 vs 0.83, p=0.005), (0.73 vs 0.80, p=0.036), (0.74 vs 0.83, p=0.008), respectively). The delayed calculation of these scores did not significantly improve our accuracy for predicting poor functional outcomes.

Conclusion

Delaying the calculation of prognostication scores in acute ICH until day 4 improved prediction of 6-month mortality but not functional outcomes.

Trial registration number

ClinicalTrials.gov Registry (NCT02175225).
Impact of surface charge on the motion of light-activated Janus micromotors
Authors: Huang Tao , Ibarlucea Bergoi , Caspari Anja , Synytska Alla , Cuniberti Gianaurelio , de Graaf Joost , Baraban Larysa
Published: March 2021

Control over micromotors’ motion is of high relevance for lab-on-a-chip and biomedical engineering, wherein such particles encounter complex microenvironments. Here, we introduce an efficient way to influence Janus micromotors’ direction of motion and speed by modifying their surface properties and those of their immediate surroundings. We fabricated light-responsive Janus micromotors with positive and negative surface charge, both driven by ionic self-diffusiophoresis. These were used to observe direction-of-motion reversal in proximity to glass substrates for which we varied the surface charge. Quantitative analysis allowed us to extract the dependence of the particle velocity on the surface charge density of the substrate. This constitutes the first quantitative demonstration of the substrate’s surface charge on the motility of the light-activated diffusiophoretic motors in water. We provide qualitative understanding of these observations in terms of osmotic flow along the substrate generated through the ions released by the propulsion mechanism. Our results constitute a crucial step in moving toward practical application of self-phoretic artificial micromotors.

Graphic abstract
Pear-shaped nuclei
Authors: Pancholi S. C.
Published: March 2021

This brief review presents current experimental evidence on the existence of deformed axially symmetric but reflection asymmetric or pear shapes in nuclei. A summary of the main findings on the properties of nuclear energy levels and electric transition probabilities is given. These experimental investigations have been possible due to the development of high efficiency gamma-detector arrays and production and availability of exotic radioactive ion beams which facilitated in-beam Coulomb excitation. The nuclear structure of odd-mass pear-shaped nuclei has assumed importance as they can be vital in solving some of the fundamental problems in physics. This paper is sequel to the publication of the book by the author on Pear-shaped Nuclei (World Scientific, 2020).
Thermal quantum correlations in the two-qubit Heisenberg XYZ spin chain with Dzyaloshinskii–Moriya interaction
Authors: Khedif Youssef , Daoud Mohammed
Published: March 2021

We investigate the quantum correlations of a two-qubit XYZ Heisenberg spin-1/2 chain model with Dzyaloshinskii–Moriya interaction. The two-qubit system is considered in thermal equilibrium. The variations of logarithmic negativity, uncertainty-induced quantum nonlocality (UIN) and trace distance discord, versus the parameters characterizing the system, are analyzed. The results show that the UIN measure captures quantum correlations that cannot be revealed by entanglement and trace discord. We also show that the Dzyaloshinskii–Moriya interaction enhances the non-classical correlations between the spins and can weaken the undesirable destructive effects of thermal fluctuations. In addition, an entangled–unentangled phase transition can be detected from the behavior of logarithmic negativity.
Generations Y and X Perception Towards Bitcoin in Malaysia
Authors: Gafar Amjad , Abenoh Nazrul‘Aini Binti , Ahmed Elsadig Musa
Published: March 2021

Traditionally, money served as a medium of financial transaction but now the system advances to the introduction of a new electronic payment through Blockchain technology known as cryptocurrency. The phenomenon of this cryptocurrency in Malaysia is very new and it is still in debate among Malaysians especially Bitcoin’s cryptocurrency. This research is to investigate the perception of generation Y and Generation X to Bitcoin. The research is conducted based on both primary data gathered from questionnaire and secondary data collected from valid sources. The results of the research indicate that the value of Bitcoin and the extending network of operations are considered as significant factors towards the perception towards Bitcoin, while security of Bitcoin has an opposite status. In conclusion, Bitcoin does have high potentials in the near future, and it will change the current monetary system, as it is classically known.
Compacted CPU/GPU Data Compression via Modified Virtual Address Translation
Authors: Seiler Larry , Lin Daqi , Yuksel Cem
Published: March 2021

We propose a method to reduce the footprint of compressed data by using modified virtual address translation to permit random access to the data. This extends our prior work on using page translation to perform automatic decompression and deswizzling upon accesses to fixed rate lossy or lossless compressed data.

Our compaction method allows a virtual address space the size of the uncompressed data to be used to efficiently access variable-size blocks of compressed data. Compression and decompression take place between the first and second level caches, which allows fast access to uncompressed data in the first level cache and provides data compaction at all other levels of the memory hierarchy. This improves performance and reduces power relative to compressed but uncompacted data.

An important property of our method is that compression, decompression, and reallocation are automatically managed by the new hardware without operating system intervention and without storing compression data in the page tables. As a result, although some changes are required in the page manager, it does not need to know the specific compression algorithm and can use a single memory allocation unit size.

We tested our method with two sample CPU algorithms. When performing depth buffer occlusion tests, our method reduces the memory footprint by 3.1x. When rendering into textures, our method reduces the footprint by 1.69x before rendering and 1.63x after. In both cases, the power and cycle time are better than for uncompacted compressed data, and significantly better than for accessing uncompressed data.
High-Performance Image Filters via Sparse Approximations
Authors: Schuster Kersten , Trettner Philip , Kobbelt Leif
Published: March 2021

We present a numerical optimization method to find highly efficient (sparse) approximations for convolutional image filters. Using a modified parallel tempering approach, we solve a constrained optimization that maximizes approximation quality while strictly staying within a user-prescribed performance budget. The results are multi-pass filters where each pass computes a weighted sum of bilinearly interpolated sparse image samples, exploiting hardware acceleration on the GPU. We systematically decompose the target filter into a series of sparse convolutions, trying to find good trade-offs between approximation quality and performance. Since our sparse filters are linear and translation-invariant, they do not exhibit the aliasing and temporal coherence issues that often appear in filters working on image pyramids. We show several applications, ranging from simple Gaussian or box blurs to the emulation of sophisticated Bokeh effects with user-provided masks. Our filters achieve high performance as well as high quality, often providing significant speed-up at acceptable quality even for separable filters. The optimized filters can be baked into shaders and used as a drop-in replacement for filtering tasks in image processing or rendering pipelines.
Aversion to Versions
Authors: Neville-Neil George V.
Published: March 2021

One should never hardcode a version or a path inside the code itself. Code needs to be flexible so that it can be installed anywhere and run anywhere so long as the necessary dependencies can be resolved, either at build time for statically compiled code or at runtime for interpreted code or code with dynamically linked libraries. There are current, good ways to get this right, so it's a shame that so many people continue to get it wrong.
Open source column: Deep learning in the browser
Authors: Kletz Sabrina , Bertini Marco , Lux Mathias
Published: March 2021

Having already discussed MatConvNet and Keras, let us continue with an open source framework for deep learning, which takes a new and interesting approach. TensorFlow.js is not only providing deep learning for JavaScript developers, but it's also making applications of deep learning available in the WebGL enabled web browsers, or more specifically, Chrome, Chromium-based browsers, Safari and Firefox. Recently node.js support has been added, so TensorFlow.js can be used to directly control TensorFlow without the browser.

TensorFlow.js is easy to install. As soon as a browser is installed one is ready to go. Browser based, cross platform applications, e.g. running with Electron, can also make use of TensorFlow.js without an additional install. The performance, however, depends on the browser the client is running, and memory and GPU on the client device. More specifically, one cannot expect to analyze 4K videos on a mobile phone in real time.

While it's easy to install, and it's easy to develop based on TensorFlow.js, there are drawbacks: (i) developers have less control over where the machine learning actually takes place (e.g. on CPU or GPU), that it is running in the same sandbox as all web pages in the browser do, and (ii) that in the current release it still has rough edges and is not considered stable enough to use in production.