bluuebunny/crossref_metadata_2025 huggingface dataset:
3D Ultrastructural Study of Synapses in the Human Entorhinal Cortex
Authors: Domínguez-Álvaro M , Montero-Crespo M , Blazquez-Llorca L , DeFelipe J , Alonso-Nanclares L
Published: August 2020

The entorhinal cortex (EC) is a brain region that has been shown to be essential for memory functions and spatial navigation. However, detailed three-dimensional (3D) synaptic morphology analysis and identification of postsynaptic targets at the ultrastructural level have not been performed before in the human EC. In the present study, we used Focused Ion Beam/Scanning Electron Microscopy to perform a 3D analysis of the synapses in the neuropil of medial EC in layers II and III from human brain autopsies. Specifically, we studied synaptic structural parameters of 3561 synapses, which were fully reconstructed in 3D. We analyzed the synaptic density, 3D spatial distribution, and type (excitatory and inhibitory), as well as the shape and size of each synaptic junction. Moreover, the postsynaptic targets of synapses could be clearly determined. The present work constitutes a detailed description of the synaptic organization of the human EC, which is a necessary step to better understand the functional organization of this region in both health and disease.
The effects of liraglutide and dapagliflozin on cardiac function and structure in a multi-hit mouse model of heart failure with preserved ejection fraction
Authors: Withaar Coenraad , Meems Laura M G , Markousis-Mavrogenis George , Boogerd Cornelis J , Silljé Herman H W , Schouten Elisabeth M , Dokter Martin M , Voors Adriaan A , Westenbrink B Daan , Lam Carolyn S P , de Boer Rudolf A
Published: August 2020

Aims

Heart failure with preserved ejection fraction (HFpEF) is a multifactorial disease that constitutes several distinct phenotypes, including a common cardiometabolic phenotype with obesity and type 2 diabetes mellitus. Treatment options for HFpEF are limited, and development of novel therapeutics is hindered by the paucity of suitable preclinical HFpEF models that recapitulate the complexity of human HFpEF. Metabolic drugs, like glucagon-like peptide receptor agonist (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i), have emerged as promising drugs to restore metabolic perturbations and may have value in the treatment of the cardiometabolic HFpEF phenotype. We aimed to develop a multifactorial HFpEF mouse model that closely resembles the cardiometabolic HFpEF phenotype, and evaluated the GLP-1 RA liraglutide (Lira) and the SGLT2i dapagliflozin (Dapa).

Methods and results

Aged (18–22 months old) female C57BL/6J mice were fed a standardized chow (CTRL) or high-fat diet (HFD) for 12 weeks. After 8 weeks HFD, angiotensin II (ANGII), was administered for 4 weeks via osmotic mini pumps. HFD + ANGII resulted in a cardiometabolic HFpEF phenotype, including obesity, impaired glucose handling, and metabolic dysregulation with inflammation. The multiple hit resulted in typical clinical HFpEF features, including cardiac hypertrophy and fibrosis with preserved fractional shortening but with impaired myocardial deformation, atrial enlargement, lung congestion, and elevated blood pressures. Treatment with Lira attenuated the cardiometabolic dysregulation and improved cardiac function, with reduced cardiac hypertrophy, less myocardial fibrosis, and attenuation of atrial weight, natriuretic peptide levels, and lung congestion. Dapa treatment improved glucose handling, but had mild effects on the HFpEF phenotype.

Conclusions

We developed a mouse model that recapitulates the human HFpEF disease, providing a novel opportunity to study disease pathogenesis and the development of enhanced therapeutic approaches. We furthermore show that attenuation of cardiometabolic dysregulation may represent a novel therapeutic target for the treatment of HFpEF.
Case report: high-grade atrioventricular block in suspected COVID-19 myocarditis
Authors: Ashok Vishnu , Loke Wei Ian
Published: August 2020

Background

In the ongoing pandemic of COVID-19, respiratory failure has been reported as the main cause of death in those who develop critical illness. A few cases of concurrent myocarditis have been reported, but the extent of cardiac complications with the SARS-CoV-2 strain of coronavirus is still largely unknown.

Case summary

A 53-year-old man, suspected to have COVID-19 due to a new-onset cough, shortness of breath, and hypoxia, was referred to Cardiology with sudden symptomatic bradycardia. Initial rhythm analysis revealed Type 2 atrioventricular block (Mobitz II). On arrival at the coronary care unit, he was found to be in complete heart block (Type 3). Routine blood tests showed normal electrolytes and renal function, and no elevation in troponin-I levels. Echocardiography showed mild impairment in left ventricular systolic function, with no regional wall motion abnormalities or valvular lesions. He then developed high-degree AV block lasting 6.2 s, prompting the need for an urgent permanent pacemaker implantation.

Discussion

Just over a third of patients with myocarditis reportedly develop a rise in cardiac troponin. Clinically suspected myocarditis can occur in the absence of a troponin rise and rarely can cause high-grade bradyarrhythmias. Myocarditis and non-specific cardiac arrhythmias have been reported in a few cases of COVID-19, but this is the first reported case of a high-grade atrioventricular conduction block with SARS-CoV-2 infection.
Coronary artery ectasia presenting with ST-elevation myocardial infarction in a young indigenous man: a case report
Authors: Lee John , Ramkumar Satish , Khav Nancy , Dundon Benjamin K
Published: August 2020

Background

Coronary artery ectasia (CAE) is often an incidental finding on angiography, however, patients can present with acute coronary syndrome due to a large thrombus burden requiring treatment with percutaneous coronary intervention or with emergency surgery.

Case summary

A 26-year-old Indigenous Australian male was admitted with anterior ST-elevation myocardial infarction associated with an out of hospital ventricular fibrillation arrest. Coronary angiography demonstrated thrombotic occlusion of the proximal left anterior descending (LAD) artery with heavy thrombus burden and prominent vascular ectasia of all three coronary arteries. He was managed with surgical thrombectomy and coronary artery bypass graft of his LAD.

Discussion

This is the first case of triple CAE in an Indigenous Australian. The case highlights the lack of consensus approach in the management of CAE due to paucity of prospective studies.
Network Structure and Performance
Authors: Lindenlaub Ilse , Prummer Anja
Published: August 2020

We develop a theory that links individuals’ network structure to their productivity and earnings. While a higher degree leads to better access to information, more clustering leads to higher peer pressure. Both information and peer pressure affect effort in a model of team production, with each being beneficial in a different environment. We find that information is particularly valuable under high uncertainty, whereas peer pressure is more valuable in the opposite case. We apply our theory to gender disparities in performance. We document the novel fact that men establish more connections (a higher degree) whereas women possess denser networks (a higher clustering coefficient). We therefore expect men to outperform women in jobs that are characterised by high uncertainty in project outcomes and earnings. We provide suggestive evidence that supports our predictions.
Impact of inter-amoebic phagocytosis on the L. pneumophila growth
Authors: Dey Rafik , Mameri Mouh Rayane , Trajkovic-Bodennec Selena , Bodennec Jacques , Pernin Pierre
Published: August 2020

Free-living amoebae are known to act as replication niches for the pathogenic bacterium Legionella pneumophila in freshwater environments. However, we previously reported that some strains of the Willaertia magna species are more resistant to L. pneumophila infection and differ in their ability to support its growth. From this observation, we hypothesize that L. pneumophila growth in environment could be partly dependent on the composition of amoebic populations and on the possible interactions between different amoebic species. We tested this hypothesis by studying the growth of L. pneumophila and of a permissive free-living amoeba, Vermamoeba vermiformis (formerly named Hartmannella vermiformis), in co-culture with or without other free-living amoebae (Acanthamoeba castellanii and W. magna). We demonstrate the occurrence of inter-amoebic phagocytosis with A. castellanii and W. magna being able to ingest V. vermiformis infected or not infected with L. pneumophila. We also found that L. pneumophila growth is strongly impacted by the permissiveness of each interactive amoeba demonstrating that L. pneumophila proliferation and spread are controlled, at least in part, by inter-amoebic interactions.
Older Persons’ and Their Caregivers’ Perspectives and Experiences of Research Participation With Impaired Decision-Making Capacity: A Scoping Review
Authors: Hosie Annmarie , Kochovska Slavica , Ries Nola , Gilmore Imelda , Parker Deborah , Sinclair Craig , Sheehan Caitlin , Collier Aileen , Caplan Gideon A , Visser Mandy , Xu Xiaoyue , Lobb Elizabeth , Sheahan Linda , Brown Linda , Lee Wei , Sanderson Christine R , Amgarth-Duff Ingrid , Green Anna , Edwards Layla , Agar Meera R
Published: August 2020

Background and Objectives

Human research ethics statements support the equitable inclusion of diverse groups. Yet older people are underrepresented in clinical research, especially those with impaired decision-making capacity. The aim of this study was to identify the perspectives and experiences of older persons and their caregivers of research participation with impaired decision-making capacity.

Research Design and Methods

Scoping review of the literature and online sources in January–February 2019 (updated June 2020) according to Joanna Briggs Institute methodology and PRISMA Extension for Scoping Reviews. English-language peer-reviewed research articles and Australian online narratives were included. Data were tabulated and narratively synthesized.

Results

From 4,171 database records and 93 online resources, 22 articles (2000–2019, 82% United States, 16 first authors) and one YouTube webinar (2018) were initially included; updated searches yielded an additional article (2020) and YouTube webinar (2020). Studies were heterogeneous in terminology, methods, and foci, with hypothetical scenarios, quantitative analyses, and examination of proxy consent predominating. Participants (N = 7,331) were older persons (71%), caregivers of older persons with dementia/cognitive impairment (23%), and older persons with dementia/cognitive impairment (6%). Synthesis identified 2 themes: willingness to participate and decision-making approaches.

Discussion and Implications

Research participation by older persons with dementia may be optimized through reducing risks and burdens and increasing benefits for participants, greater consumer input into study development, and shared and supported decision-making. Older persons’ and caregivers’ perspectives and experiences of research participation with impaired decision-making capacity require investigation in a greater range of countries and conditions other than dementia, and dissemination through more varied media.
Modelling high-frequency seismograms at ocean bottom seismometers: effects of heterogeneous structures on source parameter estimation for small offshore earthquakes and shallow low-frequency tremors
Authors: Takemura Shunsuke , Yabe Suguru , Emoto Kentaro
Published: August 2020

The source characteristics of offshore seismic events, especially regular (or fast) and slow earthquakes, can provide key information on their source physics and frictional conditions at the plate boundary. Due to strong 3-D heterogeneities in offshore regions, such as those relating to sea water, accretionary prism and small-scale velocity heterogeneity, conventional methods using a 1-D earth model may mis-estimate source parameters such as the duration and radiation energy. Estimations could become severe inaccuracies for small offshore seismic events because high-frequency (>1 Hz) seismograms, which are strongly affected by 3-D heterogeneities, are only available for analysis because of their signal-to-noise ratio. To investigate the effects of offshore heterogeneities on source parameter estimation for small seismic events, we analysed both observed and simulated high-frequency seismograms southeast off the Kii Peninsula, Japan, in the Nankai subduction zone. Numerical simulations of seismic wave propagation using a 3-D velocity structure model clarified the effects of each heterogeneity. Comparisons between observations and model simulations demonstrated that the thick low-velocity accretionary prism has significant effects on high-frequency seismic wave propagation. Especially for shallow low-frequency tremors occurring at depths just below the accretionary prism toe, seismogram durations are significantly broader than an assumed source duration, even for stations with epicentral distances of approximately 10 km. Spindle-shape seismogram envelopes were observed even at such close stations. Our results suggest that incorporating 3-D heterogeneities is necessary for practical estimation of source parameters for small offshore events.
Perspectives and practices of healthcare providers and caregivers on healthcare-associated infections in the neonatal intensive care units of two hospitals in Ghana
Authors: Sunkwa-Mills Gifty , Rawal Lal , Enweronu-Laryea Christabel , Aberese-Ako Matilda , Senah Kodjo , Tersbøl Britt Pinkowski
Published: August 2020

Healthcare-associated infections (HAIs) remain a serious threat to patient safety worldwide, particularly in low- and middle-income countries. Reducing the burden of HAIs through the observation and enforcement of infection prevention and control (IPC) practices remains a priority. Despite growing emphasis on HAI prevention in low- and middle-income countries, limited evidence is available to improve IPC practices to reduce HAIs. This study examined the perspectives of healthcare providers (HPs) and mothers in the neonatal intensive care unit on HAIs and determined the major barriers and facilitators to promoting standard IPC practices. This study draws on data from an ethnographic study using 38 in-depth interviews, four focus group discussions and participant observation conducted among HPs and mothers in neonatal intensive care units of a secondary- and tertiary-level hospital in Ghana. The qualitative data were analysed using a grounded theory approach, and NVivo 12 to facilitate coding. HPs and mothers demonstrated a modest level of understanding about HAIs. Personal, interpersonal, community, organizational and policy-level factors interacted in complex ways to influence IPC practices. HPs sometimes considered HAI concerns to be secondary in the face of a heavy clinical workload, a lack of structured systems and the quest to protect professional authority. The positive attitudes of some HPs, and peer interactions promoted standard IPC practices. Mothers expressed interest in participation in IPC activities. It however requires systematic efforts by HPs to partner with mothers in IPC. Training and capacity building of HPs, provision of adequate resources and improving communication between HPs and mothers were recommended to improve standard IPC practices. We conclude that there is a need for institutionalizing IPC policies and strengthening strategies that acknowledge and value mothers’ roles as caregivers and partners in IPC. To ensure this, HPs should be better equipped to prioritize communication and collaboration with mothers to reduce the burden of HAIs.
A social network analysis approach to group and individual perceptions of child physical activity
Authors: Prochnow Tyler , Patterson Megan S , Umstattd Meyer M Renee
Published: August 2020

Child physical activity (PA) is influenced by social environment. Self-perception and perception of others’ behaviors may impact health behaviors such as PA. This study examines associations between child networks, perception of their own PA and the network’s perception of their PA. Children (n = 89, M age = 10.00, SD = 1.34) at a summer care program reported demographics (54% female; 46% Black), PA, and physical skill competency. Children indicated up to five people they interacted with the most while at the program and how active they perceived each person to be. Multilevel modeling was used to determine significant associations between skill competency, network measures, and child’s perception of their own PA, the network’s perception of their PA, and the absolute difference between the two. Children perceived themselves to be more physically active if they perceived their friends were more physically active. Children who were central in the network and more physically competent were perceived as more active by their peers. Absolute differences between self-reported and network perceived PA were significantly larger for females. This work builds on understanding of how network position may impact child PA perceptions at summer care programs. Implications of these perceptions for PA promotion programs are discussed.
Biomarkers of Crohn’s Disease to Support the Development of New Therapeutic Interventions
Authors: Porter Amy C , Aubrecht Jiri , Birch Chandler , Braun Jonathan , Cuff Carolyn , Dasgupta Suryasarathi , Gale Jeremy D , Hinton Robert , Hoffmann Steven C , Honig Gerard , Linggi Bryan , Schito Marco , Casteele Niels Vande , Sauer John-Michael
Published: August 2020

Background

Currently, 2 coprimary end points are used by health authorities to determine the effectiveness of therapeutic interventions in patients with Crohn’s disease (CD): symptomatic remission (patient-reported outcome assessment) and endoscopic remission (ileocolonoscopy). However, there is lack of accepted biomarkers to facilitate regulatory decision-making in the development of novel therapeutics for the treatment of CD.

Methods

With support from the Helmsley Charitable Trust, Critical Path Institute formed the Crohn’s Disease Biomarkers preconsortium (CDBpC) with members from the pharmaceutical industry, academia, and nonprofit organizations to evaluate the CD biomarker landscape. Biomarkers were evaluated based on biological relevance, availability of biomarker assays, and clinical validation data.

Results

The CDBpC identified the most critical need as pharmacodynamic/response biomarkers to monitor disease activity in response to therapeutic intervention. Fecal calprotectin (FC) and serum C-reactive protein (CRP) were identified as biomarkers ready for the regulatory qualification process. A number of exploratory biomarkers and potential panels of these biomarkers was also identified for additional development. Given the different factors involved in CD and disease progression, a combination of biomarkers, including inflammatory, tissue injury, genetic, and microbiome-associated biomarkers, will likely have the most utility.

Conclusions

The primary focus of the Inflammatory Bowel Disease Regulatory Science Consortium will be development of exploratory biomarkers and the qualification of FC and CRP for IBD. The Inflammatory Bowel Disease Regulatory Science Consortium, focused on tools to support IBD drug development, will operate in the precompetitive space to share data, biological samples for biomarker testing, and assay information for novel biomarkers.
De-escalation of antimicrobial therapy in ICU settings with high prevalence of multidrug-resistant bacteria: a multicentre prospective observational cohort study in patients with sepsis or septic shock
Authors: Routsi Christina , Gkoufa Aikaterini , Arvaniti Kostoula , Kokkoris Stelios , Tourtoglou Alexandros , Theodorou Vassiliki , Vemvetsou Anna , Kassianidis Georgios , Amerikanou Athena , Paramythiotou Elisabeth , Potamianou Efstathia , Ntorlis Kyriakos , Kanavou Angeliki , Nakos Georgios , Hassou Eleftheria , Antoniadou Helen , Karaiskos Ilias , Prekates Athanasios , Armaganidis Apostolos , Pnevmatikos Ioannis , Kyprianou Miltiades , Zakynthinos Spyros , Poulakou Garyfallia , Giamarellou Helen
Published: August 2020

Background

De-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance.

Objectives

To assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance.

Methods

Multicentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation.

Results

A total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11–0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14–0.70, P = 0.005).

Conclusions

In ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.
Development of a predictive model for retention in HIV care using natural language processing of clinical notes
Authors: Oliwa Tomasz , Furner Brian , Schmitt Jessica , Schneider John , Ridgway Jessica P
Published: August 2020

Objective

Adherence to a treatment plan from HIV-positive patients is necessary to decrease their mortality and improve their quality of life, however some patients display poor appointment adherence and become lost to follow-up (LTFU). We applied natural language processing (NLP) to analyze indications towards or against LTFU in HIV-positive patients’ notes.

Materials and Methods

Unstructured lemmatized notes were labeled with an LTFU or Retained status using a 183-day threshold. An NLP and supervised machine learning system with a linear model and elastic net regularization was trained to predict this status. Prevalence of characteristics domains in the learned model weights were evaluated.

Results

We analyzed 838 LTFU vs 2964 Retained notes and obtained a weighted F1 mean of 0.912 via nested cross-validation; another experiment with notes from the same patients in both classes showed substantially lower metrics. “Comorbidities” were associated with LTFU through, for instance, “HCV” (hepatitis C virus) and likewise “Good adherence” with Retained, represented with “Well on ART” (antiretroviral therapy).

Discussion

Mentions of mental health disorders and substance use were associated with disparate retention outcomes, however history vs active use was not investigated. There remains further need to model transitions between LTFU and being retained in care over time.

Conclusion

We provided an important step for the future development of a model that could eventually help to identify patients who are at risk for falling out of care and to analyze which characteristics could be factors for this. Further research is needed to enhance this method with structured electronic medical record fields.
Computed Tomography Measurements of Sarcopenia Predict Length of Stay in Older Burn Patients
Authors: Romanowski Kathleen S , Fuanga Praman , Siddiqui Sheryar , Lenchik Leon , Palmieri Tina L , Boutin Robert D
Published: August 2020

Sarcopenia and frailty are associated with aging. In older burn patients, frailty has been associated with mortality and discharge disposition, but sarcopenia has not been examined. This study aims to investigate the relationship between frailty and computed tomography (CT)-derived sarcopenia with length of stay and mortality in older burn patients. Burn patients ≥60 years old admitted between 2008 and 2017 who had chest or abdomen CT scans within 1 week of admission were evaluated. Frailty was assessed using the Canadian Study of Health and Aging Clinical Frailty Scale (CFS). Sarcopenia was assessed on CT exams by measuring skeletal muscle index (SMI) of paraspinal muscles at T12 and all skeletal muscles at L3. The relationship between frailty scores and SMI with length of stay (LOS) and mortality was determined using logistic regression. Eighty-three patients (59 men; mean age 70.2 ± 8.5 years) had chest (n = 50) or abdomen (n = 60) CT scans. Mean TBSA = 14.3 ± 14.0%, LOS = 25.8 ± 21.3 days, CFS = 4.36 ± 0.99. Sixteen patients (19.3%) died while in the hospital. CT-derived measurement of SMI at T12 was significantly associated with LOS (P < .05), but not with mortality (P = .561). CT-derived metrics at L3 were not significantly associated with outcomes. CFS was not associated with LOS (P = .836) or mortality (P = .554). In older burn patients, low SMI of the paraspinal muscles at T12 was associated with longer LOS.
Transient Improvement in Erythropoiesis Is Achieved Via the Chaperone AHSP With Early Administration of Propranolol in Burn Patients
Authors: Walczak Julia , Bunn Corinne , Saini Pravesh , Liu Yuk Ming , Baldea Anthony J , Muthumalaiappan Kuzhali
Published: August 2020

Burn patients experience erythropoietin resistant anemia in which early commitment and late maturation of erythroblasts are defective. The authors previously showed that propranolol (Prop) treatment restores erythroid committed progenitors, but terminal maturation remains impaired. Hemoglobinization and maturation occur during terminal erythropoiesis and these processes are aided by an erythroblast intrinsic functional protein called alpha-hemoglobin stabilizing protein (AHSP). The authors evaluated the role of AHSP in PBMC- (peripheral blood mono nuclear cell) derived erythroblasts and the implications of Prop in burn patients. Blood samples were collected at three time points from 17 patients receiving standard burn care (SBC) or Prop. Five healthy volunteers provided control plasma (CP). PBMCs were placed in biphasic cultures with 5% autologous plasma (BP) or CP. Erythroblasts were harvested during mid and late maturation stages; the percentage of AHSP+ erythroblasts, AHSP expression, and relative distribution of reticulocytes and polychromatophilic erythroblasts (PolyE) were determined by cytometry. During the second time point (7–10 days postburn), Prop cohort required 35% less transfusions. At mid maturation, PBMCs from Prop-treated patients cultured in BP had 33% more AHSP+ erythroblasts and 40% more AHSP expression compared with SBC. Furthermore, at late maturation, Prop had 50% more reticulocytes and 30% less PolyEs in CP vs BP compared with SBC (11% and 6%, respectively). AHSP is positively associated with late-stage maturation of PBMC-derived erythroblasts in the presence of CP. Albeit transiently, this is more pronounced in Prop than SBC. Early administration of propranolol in burn patients supports erythropoiesis via the chaperone AHSP.
Myoelectric prosthesis: a potential emerging therapeutic in restoring function post-arm amputation complicated by necrotizing fasciitis
Authors: Adams D’Shaun D , Schwartz-Fernandes Francisco A
Published: August 2020

A literature search confirmed no previous cases of an arm amputation secondary to necrotizing fasciitis (NF) being successfully treated with a myoelectric prosthesis. This report explores a case of a 55-year-old right-handed male with flexor tenosynovitis infection of the hand after a small laceration. Following infectious disease consult of the infection, a diagnosis of NF was made. Broad-spectrum antibiotics were initiated but the infection worsened after 12 hours. Two debridements with wound vacuum were undertaken in the next 48 hours. After further patient deterioration, a distal left forearm amputation was undertaken. The patient fully recovered and then underwent occupational therapy training with a myoelectric prosthesis to restore hand function. The patient was seen for follow-up 3, 6, 12 and 24 months after amputation. At 2-year follow-up, the patient was continuing rehabilitation with an occupational therapist to acclimate to the prosthesis with some gain of function in gross movement.
Three-stage approach to resection of left pancoast tumour with spinal and major vessel involvement
Authors: Wallace Alison M , Oreopoulos George D , Rampersaud Yoga R , Waddell Thomas K
Published: August 2020

Here we describe the successful outcome of a complex and challenging resection of a left-sided pancoast tumour involving the left subclavian artery and vertebral bodies. The resection was performed following neoadjuvant chemoradiotherapy in a multi-staged fashion involving multiple teams including thoracic surgery, plastic surgery, neurosurgery and vascular surgery. Each operation was less than 6 h, without complication, and the patient was discharged within 1 week of each procedure. This case report highlights the importance of multidisciplinary team collaboration and planning in order to achieve a successful oncologic outcome and a good quality of life following treatment of these challenging tumours. The patient had a good functional outcome and no evidence of recurrence 1.5 years later.
Reconceptualising the Interest in Knowing One’s Origins: A Case for Mandatory Disclosure
Authors: Wade Katherine
Published: August 2020

The aim of this article is to make a case for mandatory disclosure in assisted reproduction. This refers to a system whereby those who are born through gamete donation and/or surrogacy would be notified about the manner of their birth and the availability of information about their genetic and/or gestational origins. The article argues that, to date, the law has interpreted an individual’s interest in knowing their origins as being predominately about identity. However, the central importance of the principle of autonomy in the conceptualisation of this interest has been overlooked. A reconceptualisation of the interest in knowing one’s origins as being concerned predominantly with autonomy provides a justification for mandatory disclosure. It is argued that the interest of individuals born through assisted reproduction in having autonomous choice regarding the significance of information about their origins should be prioritised over the autonomous choices of parents not to disclose to their offspring the manner of their birth.
An improved parametric method for evaluating radiative accelerations in stellar interiors
Authors: Alecian G , LeBlanc F
Published: August 2020

The single-valued parameter (SVP) method is a parametric method that offers the possibility of computing radiative accelerations in stellar interiors much faster than other methods. It has been implemented in a few stellar evolution numerical codes for about a decade. In this paper, we describe improvements we have recently brought in the process of preparing, from atomic/opacity data bases, the SVP tables that are needed to use the method, and their extension to a larger stellar mass domain (from 1 to 10 solar mass) on the main sequence. We discuss the validity domain of the method. We also present the website from where new tables and codes can be freely accessed and implemented in stellar evolution codes.
The baryonic Tully–Fisher relation in the simba simulation
Authors: Glowacki M , Elson E , Davé R
Published: August 2020

We investigate the Baryonic Tully–Fisher relation (BTFR) in the $(100\, h^{-1}{\rm Mpc})^3$simba hydrodynamical galaxy formation simulation together with a higher resolution $(25\, h^{-1}{\rm Mpc})^3$simba run, for over 10 000 disc-dominated, H i-rich galaxies. We generate simulated galaxy rotation curves from the mass distribution, which we show yields similar results to using the gas rotational velocities. From this, we measure the galaxy rotation velocity Vcirc using four metrics: $V_{\rm max}, V_{\rm flat}, V_{2R_e},$ and Vpolyex. We compare the predicted BTFR to the SPARC observational sample and find broad agreement. In detail, however, simba is biased towards higher Vcirc by up to 0.1 dex. We find evidence for the flattening of the BTFR in Vcirc > 300  km s−1 galaxies, in agreement with recent observational findings. simba’s rotation curves are more peaked for lower mass galaxies, in contrast with observations, suggesting overly bulge-dominated dwarf galaxies in our sample. We investigate for residuals around the BTFR versus H i mass, stellar mass, gas fraction, and specific star formation rate, which provide testable predictions for upcoming BTFR surveys. simba’s BTFR shows sub-optimal resolution mass convergence, with the higher resolution run lowering V in better agreement with data.
A thousand days after the merger: Continued X-ray emission from GW170817
Authors: Troja E , van Eerten H , Zhang B , Ryan G , Piro L , Ricci R , O’Connor B , Wieringa M H , Cenko S B , Sakamoto T
Published: August 2020

Recent observations with the Chandra X-ray telescope continue to detect X-ray emission from the transient GW170817. In a total exposure of 96.6 ks, performed between 2020 March 9 and 16 (935–942 d after the merger), a total of 8 photons are measured at the source position, corresponding to a significance of ≈5σ. Radio monitoring with the Australian Telescope Compact Array (ATCA) shows instead that the source has faded below our detection threshold (<33 $\mu$Jy, 3σ). By assuming a constant spectral index of β  = 0.585, we derive an unabsorbed X-ray flux of ≈1.4 × 10−15 erg cm−2 s−1, higher than earlier predictions, yet still consistent with a simple structured jet model. We discuss possible scenarios that could account for prolonged emission in X-rays. The current data set appears consistent both with energy injection by a long-lived central engine and with the onset of a kilonova afterglow, arising from the interaction of the sub-relativistic merger ejecta with the surrounding medium. Long-term monitoring of this source will be essential to test these different models.
Novel strategy for manufacturing autologous dendritic cell/allogeneic tumor lysate vaccines for glioblastoma
Authors: Parney Ian F , Gustafson Michael P , Solseth Mary , Bulur Peggy , Peterson Timothy E , Smadbeck James B , Johnson Sarah H , Murphy Stephen J , Vasmatzis George , Dietz Allan B
Published: August 2020

Background

Glioblastoma, the most common primary malignant brain tumor, is nearly universally fatal by 5 years. Dendritic cell vaccines are promising but often limited clinically by antigen choice, dendritic cell potency, and/or manufacturing yield. We optimized vaccine manufacture, generating potent mature autologous dendritic cells pulsed with allogeneic glioblastoma lysates.

Methods

Platelet lysate-based supplement was used to establish human glioblastoma cell lines. Phenotype and genotype were assessed. An improved culture technique to generate mature dendritic cells from glioblastoma patients’ monocytes was developed. The ability of T cells stimulated with autologous dendritic cells pulsed with allogeneic glioblastoma cell lysate to kill HLA-A2-matched glioblastoma cells was assessed.

Results

Glioblastoma cell lines established with platelet lysate supplement grew faster and expressed more stem-like markers than lines grown in neural stem cell media or in the presence of serum. They expressed a variety of glioma-associated antigens and had genomic abnormalities characteristic of glioblastoma stable up to 15 doublings. Unlike standard culture techniques, our optimized technique produced high levels of mature dendritic cells from glioblastoma patients’ monocytes. Autologous T cells stimulated with mature dendritic cells pulsed with allogeneic glioblastoma cell line lysate briskly killed HLA-A2-matched glioblastoma cells.

Conclusions

Our glioblastoma culture method provides a renewable source for a broad spectrum glioblastoma neoantigens while our dendritic cell culture technique results in more mature dendritic cells in glioblastoma patients than standard techniques. This broadly applicable strategy could be easily integrated into patient care.
Alternatives to Opioid Education and a Prescription Drug Monitoring Program Cumulatively Decreased Outpatient Opioid Prescriptions
Authors: Sigal Adam , Shah Ankit , Onderdonk Alex , Deaner Traci , Schlappy David , Barbera Charles
Published: August 2020

Introduction

Deaths have increased, and prescription medications are involved in a significant percentage of deaths. Emergency department (ED) changes to managing acute pain and prescription drug monitoring programs (PDMPs) can impact the potential for abuse.

Methods

We analyzed the impact of a series of quality improvement initiatives on the opioid prescribing habits of emergency department physicians and advanced practice providers. We compared historical prescribing patterns with those after three interventions: 1) the implementation of a PDMP, 2) clinician education on alternatives to opioids (ALTOs), and 3) electronic health record (EHR) process changes.

Results

There was a 61.8% decrease in the percentage of opioid-eligible ED discharges that received a prescription for an opioid from 19.4% during the baseline period to 7.4% during the final intervention period. Among these discharges, the cumulative effect of the interventions resulted in a 17.3% decrease in the amount of morphine milligram equivalents (MME) prescribed per discharge from a mean of 104.9 MME/discharge during the baseline period to 86.8 MME/discharge. In addition, the average amount of MME prescribed per discharge became aligned with recommended guidelines over the intervention periods.

Conclusions

Initiating a PDMP and instituting an aggressive ALTO program along with EHR-modified process flows have cumulative benefits in decreasing MME prescribed in an acute ED setting.
Optical shape analysis based on discrete Fourier transform and second-order moment analysis of the brightness distribution for the detection of sub-micron range tracks in nuclear emulsion
Authors: Umemoto Atsuhiro , Naka Tatsuhiro , Nakano Toshiyuki , Kobayashi Ryuta , Shiraishi Takuya , Asada Takashi
Published: August 2020

To recognize sub-micron-range low-energy tracks recorded in a super-fine-grained nuclear emulsion (Nano Imaging Tracker), an elliptical fitting method was devised to analyze anisotropic images taken by an optical microscope. We report on this newly developed method using a discrete Fourier transform and second-order moment analysis of the brightness distribution. We succeeded in lowering the ellipticity threshold, thereby improving the selection efficiency and angular resolution. Notably, the success of detecting carbon 30 keV tracks is the first such achievement in the world, where the incident direction of carbon 30 keV ions was determined with an accuracy of 41$^\circ$ and an efficiency of $1.7 \pm 0.1\%$.
Tackling the elective case backlog generated by Covid-19: the scale of the problem and solutions
Authors: Macdonald Nathanael , Clements Caterina , Sobti Anshul , Rossiter Daniel , Unnithan Ashwin , Bosanquet Nicholas
Published: August 2020

Background

In April 2020, Covid-19 brought NHS elective procedures to a halt. The aim of this paper is to produce accurate forecasts on the building backlog, highlight the state of waiting lists currently and propose solutions required to prevent a public health crisis.

Method

Using data published by NHS digital and NHS England on previous years, we have analysed and used this to produce estimates of cancellations and missed cases. We also analyse government data on waiting lists and show compliance or lack of with these.

Results

We show that compliance with waiting list times pre pandemic was falling year on year (83.2% in 2020 down from 87% in 2019). Every month that passes we estimate that 400 000 cases are not being performed. This may include urgent cancer care work in some trusts.

Conclusions

Waiting lists have been governed by strict rules since 2004. Given falling compliance with 18-week intention to treat we believe the scale of the backlog combined with NHS capacity diminished due to Covid-19 precautions is a public health crisis waiting to occur. We identify difficulties in resuming elective work and suggest strategies that could be employed to avoid a public health crisis.
Dedications, Epistles to the Reader, and Prefatory Custom in Printed English Playbooks, 1559–1642
Authors: Singh Devani
Published: August 2020

This essay argues for the value of approaching printed dedications and addresses to readers through a comparative lens. For printed drama in particular, the presence of readerly paratexts has been a means of charting the genre’s literary ascent. The essay presents a bibliometric survey of the two paratexts in plays printed between 1559 and 1642, and compares their rates of occurrence in plays from the professional theatres with those from nonprofessional contexts. Contrary to the critical commonplace that the establishment of early modern literary culture saw the decline of patronage and the rise of the figure of the reader, the rates of publication of dedications and addresses to readers suggest the opposite. The essay documents a striking absence of attention to readers in the preliminaries of playbooks and finds that the dedication was the more popular form of prefatory address for both professional and nonprofessional plays, although professional plays initially favoured addresses to readers. After suggesting ways of accounting for these trends and considering their implications, the essay concludes with a discussion of dramatic prefaces which self-reflexively invoke the ‘custom’ of having a printed preface. The essay argues that this rhetorical convention shows authors and stationers weighing the merits of prefatory matter and negotiating the attendant question of literary worth as they sought to position their plays favourably in the print marketplace.
Interferon-stimulated GTPases in autoimmune and inflammatory diseases: promising role for the guanylate-binding protein (GBP) family
Authors: Haque Mahamudul , Siegel Ruby J , Fox David A , Ahmed Salahuddin
Published: August 2020

Human IFNs are secreted cytokines shown to stimulate the expression of over one thousand genes. These IFN-inducible genes primarily encode four major protein families, known as IFN-stimulated GTPases (ISGs), namely myxovirus-resistance proteins, guanylate-binding proteins (GBPs), p47 immunity-related GTPases and very large inducible guanosine triphosphate hydrolases (GTPases). These families respond specifically to type I or II IFNs and are well reported in coordinating immunity against some well known as well as newly discovered viral, bacterial and parasitic infections. A growing body of evidence highlights the potential contributory and regulatory roles of ISGs in dysregulated inflammation and autoimmune diseases. Our focus was to draw attention to studies that demonstrate increased expression of ISGs in the serum and affected tissues of patients with RA, SS, lupus, IBD and psoriasis. In this review, we analysed emerging literature describing the potential roles of ISGs, particularly the GBP family, in the context of autoimmunity. We also highlighted the promise and implications for therapeutically targeting IFNs and GBPs in the treatment of rheumatic diseases.
COVID-19 and myositis – unique challenges for patients
Authors: Gupta Latika , Lilleker James B , Agarwal Vikas , Chinoy Hector , Aggarwal Rohit
Published: August 2020

Objective

The COVID-19 pandemic and the subsequent effects on healthcare systems is having a significant effect on the management of long-term autoimmune conditions. The aim of this study was to assess the problems faced by patients with idiopathic inflammatory myopathies (IIM).

Methods

An anonymized eSurvey was carried out with a focus on effects on disease control, continuity of medical care, drug procurance and prevalent fears in the patient population.

Results

Of the 608 participants (81.1% female, median (s.d.) age 57  (13.9) years), dermatomyositis was the most frequent subtype (247, 40.6%). Patients reported health-related problems attributable to the COVID-19 pandemic (n = 195, 32.1%); specifically 102 (52.3%) required increase in medicines, and 35 (18%) required hospitalization for disease-related complications. Over half (52.7%) of the surveyed patients were receiving glucocorticoids and/or had underlying cardiovascular risk factors (53.8%), placing them at higher risk for severe COVID-19. Almost one in four patients faced hurdles in procuring medicines. Physiotherapy, critical in the management of IIM, was disrupted in 214 (35.2%). One quarter (159, 26.1%) experienced difficulty in contacting their specialist, and 30 (4.9%) were unable to do so. Most (69.6%) were supportive of the increased use of remote consultations to maintain continuity of medical care during the pandemic.

Conclusion

This large descriptive study suggests that the COVID-19 pandemic has incurred a detrimental effect on continuity of medical care for many patients with IIM. There is concern that delays and omissions in clinical care may potentially translate to poorer outcomes in the future.
Overexpression of MdIAA24 improves apple drought resistance by positively regulating strigolactone biosynthesis and mycorrhization
Authors: Huang Dong , Wang Qian , Jing Guangquan , Ma Mengnan , Li Chao , Ma Fengwang
Published: August 2020

Most land plant species have the ability to establish a symbiosis with arbuscular mycorrhizal (AM) fungi. These fungi penetrate into root cortical cells and form branched structures (known as arbuscules) for nutrient exchange. We cloned the MdIAA24 from apple (Malus domestica) following its up-regulation during AM symbiosis. Results demonstrate the positive impact of the overexpression (OE) of MdIAA24 in apple on AM colonization. We observed the strigolactone (SL) synthesis genes, including MdD27, MdCCD7, MdCCD8a, MdCCD8b and MdMAXa, to be up-regulated in the OE lines. Thus, the OE lines exhibited both a higher SL content and colonization rate. Furthermore, we observed that the OE lines were able to maintain better growth parameters under AM inoculation conditions. Under drought stress with the AM inoculation, the OE lines were less damaged, which was demonstrated by a higher relative water content, a lower relative electrolytic leakage, a greater osmotic adjustment, a higher reactive oxygen species scavenging ability, an improved gas exchange capacity and an increased chlorophyll fluorescence performance. Our findings demonstrate that the OE of MdIAA24 in apple positively regulates the synthesis of SL and the formation of arbuscules as a drought stress coping mechanism.