bluuebunny/crossref_metadata_2025 huggingface dataset:
600 ESCALATION DECISIONS DURING THE COVID-19 PANDEMIC AMONGST OLDER ADULTS
Authors: Bishop L , Tiwari D
Published: June 2021

Introduction

NICE guidance recommends that during the COVID-19 pandemic all adults are assessed for frailty, suitability for resuscitation and escalation to critical care on admission to hospital. Risks, benefits and likely outcomes should be discussed with patients/relatives.

Aim

To investigate impact of intervention on treatment escalation plan (TEP) use during the first wave (W1) and second wave (W2) of pandemic.

Intervention

W1: An ethically approved TEP and a Critical Care Decision Aid (CCDA) was added to the admission booklet.

W2: The TEP update included a ‘confirm discussed with patient/relatives’ section.

Method

W1: We conducted retrospective review of 62 case-notes of patients admitted through COVID-19 pathway and grouped into >80 and ≤ 80 years old. Resuscitation, TEP, CCDA and communication with patient/relatives were collected.

W2: 60 further case-notes of patients with COVID-19 admitted in January 2021 were analysed.

Results

W1: 100% patients had resuscitation decisions and 95% had TEPs in both groups. Significantly higher proportions of Frailty scores were calculated in >80s (58% vs 35% p = 0.04). On average resuscitation and TEPs were made within 13.8 hours of admission (range 1–72 hours). 53.2% of resuscitation decisions and 30% TEPs were discussed with patients of whom higher proportions were discussed in younger age group, majority were discussed at the time of deterioration.

W2: 98.3% patients had resuscitation decisions made and 96.7% had TEPs across both groups. On average resuscitation decisions were made within 14.9 hours of admission. In the >80s, 86.7% of resuscitation decisions were discussed and 63.3% of the TEPs were discussed with patient/relatives. In the <80s, 82.8% of resuscitation decisions were discussed and 71.4% of TEPs were discussed with the patient/relatives.

Conclusion

We significantly improved Treatment Escalation planning during W1 and W2 of pandemic by introducing the TEP in W1 and adding prompt to improve communication with patients/relatives in W2 (p = 0.02).
500 30-DAY SURVIVAL AND RECOVERY AFTER HIP FRACTURE BY MOBILISATION TIMING AND DEMENTIA: A UK DATABASE STUDY
Authors: Sheehan K J , Goubar A , Martin F C , Potter C , Jones G D , Sackley C , Ayis S
Published: June 2021

Introduction

To compare 30-day survival and recovery of prefracture ambulation between patients mobilised early (on the day of or day after surgery) and patients mobilised late (2 days of more after surgery) in England and Wales. To determine whether the presence of dementia influences the association between mobilisation timing and 30-day survival and recovery.

Methods

Secondary analysis of the UK National Hip Fracture Database linked to hospitalisation records for 126,897 patients 60 years or older who underwent surgery for nonpathological first hip fracture in England or Wales between 2014 and 2016. We used logistic regression to regress survival and ambulation recovery at 30-days with respect to mobilisation timing, overall and by dementia, with adjustment for confounding using a propensity score for mobilisation treatment with respect to confounders.

Results

Overall, 99,667 (79%) patients mobilised early. Among those who mobilised early compared to those who mobilised late, the weighted odds ratio of survival was 1.92 (95% CI 1.80–2.05), of recovering outdoor ambulation was 1.25 (95% CI 1.03–1.51), and of recovering indoor ambulation was 1.53 (95% CI 1.32–1.78) by 30 days. Early compared with late mobilisation led to a 3.8% increase in the weighted probability of survival, 22.8% increase in weighted probability of recovering outdoor ambulation and 10.0% increase in the weighted probability of recovering indoor ambulation, by 30-days. Patients with dementia were less likely to mobilise early but increases in survival and ambulation recovery were observed both for those with and without dementia.

Conclusion

Early mobilisation led to increase probability of survival and recovery for patients (with and without dementia) after hip fracture. Early mobilisation should be incorporated as a measured indicator of quality internationally. Reasons for failure to mobilise early should also be captured to inform quality improvement initiatives.
416 ANALGESIA AND PERI-OPERATIVE PRACTICE IN FRACTURED NECK OF FEMURS AT YORK TEACHING HOSPITALS NHS FOUNDATION TRUST
Authors: Easby S , Dilley J
Published: June 2021

Introduction

Fractured neck of femurs are a significant public health issue. Prompt assessment and response to pain as per NICE guidelines aids speedy recovery and helps to prevent complications such as delirium in and already high risk, elderly population. Previous audits have found poor documentation of the assessment of pain and the rate of nerve blocks in A + E and theatres. This completed cycle audit will assess the interventions made in response to these audits including adding pain scores to e-observations and training staff to perform nerve blocks. The aim of this audit was to assess current anaesthetic and analgesic practice.

Method

This was a retrospective review of 32 case notes and electronic prescribing over November—December 2019. Data collected included documentation of pain assessment, which analgesia was prescribed as per NICE guideline CG124 [1] and rate of nerve block in A + E and theatres.

Results

The audit found that 100% of patients received analgesia as per NICE guidelines. Documenting the assessment of pain scores has improved from 44% to 63% in A + E, 64% to 81% on the ward pre-operatively and 0 to 100% post op. On admission, 41% of patients received a nerve block and 94% intra-operatively, up from 22% and 55% respectively, the majority of patients received a fascia iliaca block (FIB).

Conclusions

The large increase in post op pain assessment is likely credited to mandatory input as part of e-observations and overall practice has improved significantly. A refresher training session will be provided for nursing staff to re-iterate the importance of assessing and responding to pain. The Hip Fracture Specialist Nurse is now competent to perform FIBs which may further increase the number performed on admission.

Reference

1. NICE. Hip fracture: management. Clinical guideline [CG124]. https://www.nice.org.uk/guidance/cg124 (accessed 15/11/2020).
Aquila_stLFR: diploid genome assembly based structural variant calling package for stLFR linked-reads
Authors: Liu Yichen Henry , Grubbs Griffin L , Zhang Lu , Fang Xiaodong , Dill David L , Sidow Arend , Zhou Xin
Published: June 2021

Motivation

Identifying structural variants (SVs) is critical in health and disease, however, detecting them remains a challenge. Several linked-read sequencing technologies, including 10X Genomics, TELL-Seq and single tube long fragment read (stLFR), have been recently developed as cost-effective approaches to reconstruct multi-megabase haplotypes (phase blocks) from sequence data of a single sample. These technologies provide an optimal sequencing platform to characterize SVs, though few computational algorithms can utilize them. Thus, we developed Aquila_stLFR, an approach that resolves SVs through haplotype-based assembly of stLFR linked-reads.

Results

Aquila_stLFR first partitions long fragment reads into two haplotype-specific blocks with the assistance of the high-quality reference genome, by taking advantage of the potential phasing ability of the linked-read itself. Each haplotype is then assembled independently, to achieve a complete diploid assembly to finally reconstruct the genome-wide SVs. We benchmarked Aquila_stLFR on a well-studied sample, NA24385, and showed Aquila_stLFR can detect medium to large size deletions (50 bp–10 kb) with high sensitivity and medium-size insertions (50 bp–1 kb) with high specificity.

Availability and implementation

Source code and documentation are available on https://github.com/maiziex/Aquila_stLFR.

Supplementary information

Supplementary data are available at Bioinformatics Advances online.
A meta-analysis on continuous versus interrupted skin closure following appendicectomy
Authors: Sharma A , Rajalingam V , Nageswaran H , Best L
Published: June 2021

Background

The aim of this review was to analyse RCTs comparing wound-related outcomes between continuous subcuticular and interrupted transdermal wound closures for open appendicectomies in all age groups.

Methods

A systematic literature search was conducted in April 2020 (MEDLINE, Embase, CENTRAL, Web of Science, PROSPERO, Google Scholar, WHO International Clinical Trials Registry Platform). RCTs without restrictions on study language, year, status of publication, and patient age were included. The risk of bias was assessed using the risk-of-bias tool for RCTs. Pooled risk ratios (RRs) and mean differences (MDs) for binary and continuous variables were calculated using random-effects models. A summary-of-findings table was generated to assess the level of evidence.

Results

Eleven trials were included (1781 patients analysed, 891 in continuous and 890 in interrupted groups). The overall rate of wound infection was 7.1 per cent. There was no significant difference in the risk of wound infection (11 trials, 1781 patients; RR 1.13, 95 per cent c.i. 0.77 to 1.66; P = 0.530) or wound exploration (7 trials, 1129 patients; RR 0.74, 0.41 to 1.34, P = 0.320) between the two groups. Continuous wound closure had a significantly reduced risk of wound dehiscence (6 trials, 865 patients; RR 0.16, 0.05 to 0.50; P = 0.002) and smaller wound scar (3 trials, 417 patients; MD –2.11 (95 per cent c.i. –2.57 to –1.66) mm; P < 0.001). The absolute risk reduction and number needed to treat for wound dehiscence were 6.1 per cent and 16 respectively. There was no significant statistical heterogeneity for all outcomes (I2 0–15 per cent, χ2 P > 0.100). Most RCTs had a high risk of bias.

Conclusion

Continuous subcuticular open appendicectomy wound closure is not associated with an increased risk of wound infection and exploration. This method of closure has a reduced risk of wound dehiscence and better cosmetic outcomes.
Prophylactic anticoagulation in sinus rhythm for stroke prevention in cardiovascular disease: contemporary meta-analysis of large randomized trials
Authors: Lander Krystle , Thakeria Priyanka , Nayyar Sachin
Published: June 2021

Aims

Anticoagulation with non-vitamin K oral anticoagulants (NOACs) to prevent stroke is a mainstay of atrial fibrillation (AF) management. However, multiple cardiovascular diseases (CVDs) are associated with elevated ischaemic stroke risk even in sinus rhythm. In this meta-analysis, we assess efficacy and safety of prophylactic NOAC agents for stroke prevention in patients without AF.

Methods and results

A search was conducted for randomized controlled trials (RCTs) that evaluated an NOAC and control drug (placebo or antiplatelet) in non-AF patients with mixed CVD. The primary efficacy and safety outcomes were ischaemic stroke and major bleeding, respectively. Results were stratified based on primary- and mini-NOAC doses. Thirteen RCTs were identified with a total of 89 383 patients with CVD in sinus rhythm (53 778 on NOAC, 35 605 on control drug; mean age 65.5 ± 2.7 years). Over a mean follow-up of 18.3 months, 1429 (1.6%) ischaemic strokes occurred. Use of NOAC was associated with 26% reduction in stroke [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.62–0.87; 1.1 vs. 1.8 events per 100 person-years], with numbers needed to treat of 153 patients to prevent one stroke. Major bleeding was increased with NOAC (OR 1.74, 95% CI 1.44–2.09; 2.1 vs. 1.0 events per 100 person-years). The weighted net clinical benefit (wNCB, composite of ischaemic stroke and bleeding) did not suggest a favourable effect with any NOAC dose (wNCB for primary-dose: −0.35; mini-dose: −0.06).

Conclusion

Current evidence does not support use of NOACs for stroke prevention in non-AF CVD population as risk of major bleeding still exceeds ischaemic stroke benefit.
The Organization of the Sinoatrial Node Microvasculature Varies Regionally to Match Local Myocyte Excitability
Authors: Grainger Nathan , Guarina Laura , Cudmore Robert H , Santana L Fernando
Published: June 2021

The cardiac cycle starts when an action potential is produced by pacemaking cells in the sinoatrial node. This cycle is repeated approximately 100 000 times in humans and 1 million times in mice per day, imposing a monumental metabolic demand on the heart, requiring efficient blood supply via the coronary vasculature to maintain cardiac function. Although the ventricular coronary circulation has been extensively studied, the relationship between vascularization and cellular pacemaking modalities in the sinoatrial node is poorly understood. Here, we tested the hypothesis that the organization of the sinoatrial node microvasculature varies regionally, reflecting local myocyte firing properties. We show that vessel densities are higher in the superior versus inferior sinoatrial node. Accordingly, sinoatrial node myocytes are closer to vessels in the superior versus inferior regions. Superior and inferior sinoatrial node myocytes produce stochastic subthreshold voltage fluctuations and action potentials. However, the intrinsic action potential firing rate of sinoatrial node myocytes is higher in the superior versus inferior node. Our data support a model in which the microvascular densities vary regionally within the sinoatrial node to match the electrical and Ca2+ dynamics of nearby myocytes, effectively determining the dominant pacemaking site within the node. In this model, the high vascular density in the superior sinoatrial node places myocytes with metabolically demanding, high-frequency action potentials near vessels. The lower vascularization and electrical activity of inferior sinoatrial node myocytes could limit these cells to function to support sinoatrial node periodicity with sporadic voltage fluctuations via a stochastic resonance mechanism.
Technological paradigms and the power of convergence
Authors: Pedota Mattia , Grilli Luca , Piscitello Lucia
Published: June 2021

With the advent of Industry 4.0, technological interdependence is becoming increasingly important in the delineation of technological development dynamics. In the present paper, we propose an extension of the theory of technological paradigms conceptualizing the role of technological interdependence in the emergence of paradigms and the coevolution of the corresponding trajectories. We corroborate our conceptual extension by means of an in-depth historical account of the genesis and evolution of the additive manufacturing paradigm. Accordingly, we elucidate how different technological paradigms may give rise to an aggregate paradigm through a process of convergence and how the aggregate paradigm may contribute to steering the direction of technological change alongside traditional science-push, demand-pull, institutional, and socioeconomic factors. Our work has two main implications: first, it shows that a technological paradigm may emerge from a process of incremental convergence and not only from radical innovations and scientific breakthroughs. Second, it shows that the dynamics of epistemological interdependence (i.e., interdependence between paradigms) matter significantly in the determination of technological development paths.
Market Court of Finland rules on reasonable compensation in a trade mark infringement case concerning cheaper foreign alcohol and a national retailing monopoly
Authors: Malvikko Max , Matikainen Teemu
Published: June 2021

Alko Oy v Aldar Latvia SIA, MAO:48/21, 9 February 2021

The Market Court of Finland recently determined trade mark damages in the light of complex circumstances.
Current plant diversity but not its soil legacy influences exotic plant invasion
Authors: Xue Wei , Yao Si-Mei , Huang Lin , Roiloa Sergio R , Ji Bao-Ming , Yu Fei-Hai
Published: June 2021

Current plant diversity can influence exotic plant invasion, but it is unclear whether there is a legacy effect of plant diversity on exotic plant invasion. As plant diversity can affect soil microbial communities and physio-chemical properties, which may cascade to impact subsequent exotic plant growth, we hypothesize that the soil legacy effect of plant diversity can influence exotic plant invasion. We conducted a plant–soil feedback experiment. In the conditioning phase, we trained soils by monocultures of 12 plant species from three functional groups (4 grasses, 3 legumes and 5 forbs) and mixtures of 8 randomly selected species with all three functional groups from this 12-species pool. In the test phase, we grew the invasive plant Bidens pilosa with a co-occurring native grass (Arthraxon hispidus), with a co-occurring native forb (Pterocypsela indica) or with both in each type of the conditioned soils. The performance of B. pilosa relative to its native competitors varied depending on the functional type of both conditioning plant species in the conditioning phase and competing plant species in the test phase. Diversity of the conditioning plants did not influence the growth difference between B. pilosa and its native competitors. However, increasing diversity of the competing plant species reduced the performance of B. pilosa relative to its native competitors. Our results suggest that current plant diversity can reduce exotic plant invasion through increasing growth inequality between invasive and native plants, but the soil legacy effect of plant diversity may have little impact on exotic plant invasion.
Hesperidin mitigates inflammation and modulates ectoenzymes activity and some cellular processes in complete Freund’s adjuvant-induced arthritic rats
Authors: Adefegha Stephen Adeniyi , Saccol Renata da Silva Pereira , Jantsch Matheus Henrique , da Silveira Karine Lanes , Leal Daniela Bitencourt Rosa
Published: June 2021

Objectives

This study was aimed at assessing the anti-arthritic effects of hesperidin on the inflammatory markers in serum/plasma, ectoenzymes activity in platelet, reactive oxygen species (ROS), apoptosis and cell cycle in bone marrow cells of a rat model of arthritis.

Methods

Fifty-six adult female Wistar rats (245–274 g) were grouped into eight of seven rats each: control rats given normal saline or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, 0.2 mg/kg of dexamethasone, arthritic rats given normal saline, or 40 mg/kg of hesperidin or 80 mg/kg of hesperidin, and 0.2 mg/kg of dexamethasone. Myeloperoxidase and nitrate plus nitrite levels were evaluated in the plasma and serum, respectively. The ecto-nucleoside triphosphate diphosphohydrolases, ecto-5′-nucleotidase and ecto-adenosine deaminase activities were assessed in platelets. Subsequently, the cells of the bone marrow were obtained, and the assays for ROS, apoptosis and cell cycle were evaluated using flow cytometry.

Key findings

The results showed that hesperidin mitigated inflammation, modulated adenosine nucleotides and nucleoside hydrolysing enzymes and levels, minimized ROS intracellularly, attenuated apoptotic process and activated cell cycle arrest in arthritic rat.

Conclusion

This study suggests that hesperidin could be a natural and promising anti-inflammatory compound for the management of arthritis.
Beyond the Partnership Debate: Localizing Knowledge Production in Refugee and Forced Migration Studies
Authors: Shivakoti Richa , Milner James
Published: June 2021

There is a growing recognition in refugee and forced migration studies that research partnerships, especially those that cross geographies of the global North and global South, are both a blessing and a potential curse. They are a blessing as they encourage new approaches to the co-creation of knowledge, build solidarity networks, and leverage support for scholars based in the global South. But they can also be a curse as they typically function within and can inadvertently reproduce deeply embedded structures of inequality. Drawing on the results of a review of forced displacement research centres based in the global South and interviews with the directors of these centres, this article encourages a shift from focusing on research partnerships to an approach that supports the localization of knowledge production in refugee and forced migration studies. This approach seeks to change the structures of knowledge production, including direct funding to researchers and research centres based in the global South, an emphasis on the transfer of power to researchers in the South, a recognition of the diverse forms and sources of knowledge produced within the field, and an appreciation for the diverse understandings of success and impact across contexts.
Prevalence of vulvovaginal candidiasis in Brazil: A systematic review
Authors: Carvalho Gabriela Corrêa , de Oliveira Rafaela Aparecida Prata , Araujo Victor Hugo Sousa , Sábio Rafael Miguel , de Carvalho Lídia Raquel , Bauab Taís Maria , Corrêa Ione , Chorilli Marlus
Published: June 2021

Vulvovaginal candidiasis (CVV) is a condition in which signs and symptoms are related to inflammation caused by Candida spp infection. It is the second leading cause of vaginitis in the world, representing a public health problem. The present systematic review comes with the proposal of analyze and identify the available evidence on CVV prevalence in Brazil, pointing out its variability by regions. For this, a systematic literature review was carried out with meta-analysis of cross-sectional and cohort studies, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guide recommendations, and was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2020 CRD42020181695). The databases used for survey were LILACS, Scielo, Scopus, PUBMED, Web of Science and CINAHL. Fifteen studies were selected to estimate CVV prevalence in the Brazilian territory. South and Southeast regions have higher prevalences than the North and Northeast regions, no data were found for the Midwest region. The estimated prevalence for Brazil is 18%, however, it is suggested that this number is higher due to underreporting and the presence of asymptomatic cases. Therefore, new epidemiological studies are recommended throughout Brazil, to elucidate the profile of this disease in the country, in addition to assisting in the elaboration of an appropriate prevention plan by state.

Lay summary

Data found in the literature regarding the epidemiological profile of vulvovaginal candidiasis in Brazil are obsolete and incomplete, so the present systematic review has the proposal to analyze and identify the evidence on vulvovaginal candidiasis prevalence in Brazil. The estimated prevalence is 18%; however, this number can be higher.
Asteroseismology of RRab variable star EZ Cnc from K2 photometry and LAMOST spectroscopy
Authors: Wang Jiangtao , Fu Jian-Ning , Zong Weikai , Wang Jiaxin , Zhang Bo
Published: June 2021

EZ Cnc, or EPIC 212182292, is a non-Blažko RRab variable star located in the field of K2 Campaign 16. Its atmospheric parameters (Teff, log g, [M/H]) and radial velocities are measured from the 55 high-quality LAMOST medium-resolution spectra. The fundamental frequency of pulsation is derived as f = 1.8323(17) d−1 from the K2 light curves. The amplitude ratios R21 = 0.5115(15), 0.490(8), R31 = 0.3249(20), 0.279(7) and Fourier phase differences φ21 = 2.7550(20), 2.764(16), φ31 = 5.7194(25), 5.719(31) are determined from the Fourier decomposition of K2 light curve and LAMOST radial velocity curve, respectively. Through the constraints of the parameters, four optimal models are obtained in a time-dependent turbulent convection model survey for EPIC 212182292. The parameters of EPIC 212182292 are derived as M = 0.48 ± 0.03 M⊙, L = 42 ± 2 L⊙, Teff = 6846 ± 50 K, log g = 2.79 ± 0.01 dex, and Z = 0.006 ± 0.002, respectively. The precisely determined parameters for RRab variable stars like EPIC 212180092 might help to better understand the period–luminosity relationship of RR Lyrae stars.
An empirical calibration of the helium abundance in H ii regions based in literature and CALIFA survey data
Authors: Valerdi M , Barrera-Ballesteros J K , Sánchez S F , Espinosa-Ponce C , Carigi L , Mejía-Narváez A
Published: June 2021

Helium is the second most common chemical species in the Universe. The study of helium abundance has the potential to unravel the chemical evolution of and within galaxies. In this study, we provide an empirical calibration for the singly ionized helium abundance: 12 + log10(He+/H+), based on the emission line flux ratio Heλ5876/H α from Galactic and extragalactic H ii regions compiled from the literature. Based on this calibrator, we explore for the first time the helium abundance in a large sample of H ii regions located in galaxies representative of the nearby Universe from the CALIFA survey. Furthermore, this calibrator allows us to explore the variations of the helium abundance with respect to the oxygen abundance. The observed trends are in agreement with a change in the chemical enrichment with mass/oxygen abundance similar to the one observed due to the inside-out model in a MW-galaxy (highlighting the connection between resolved and global trends in galaxies). Our calibrator provides an empirical proxy to estimate the helium abundance at kpc scales as well as to constrain chemical evolutionary models.
Does concentration drive the scatter in the stellar-to-halo mass relation of galaxy clusters?
Authors: Zu Ying , Shan Huanyuan , Zhang Jun , Singh Sukhdeep , Shao Zhiwei , Chen Xiaokai , Yao Ji , Golden-Marx Jesse B , Cui Weiguang , Jullo Eric , Kneib Jean-Paul , Zhang Pengjie , Yang Xiaohu
Published: June 2021

Concentration is one of the key dark matter halo properties that could drive the scatter in the stellar-to-halo mass relation of massive clusters. We derive robust photometric stellar masses for a sample of brightest central galaxies (BCGs) in SDSS redmapper clusters at 0.17 < z < 0.3, and split the clusters into two equal-halo mass subsamples by their BCG stellar mass $M_*^{\mathrm{BCG}}$. The weak lensing profiles ΔΣ of the two cluster subsamples exhibit different slopes on scales below $1\, h^{-1}\, {\mathrm{Mpc}}$. To interpret such discrepancy, we perform a comprehensive Bayesian modelling of the two ΔΣ profiles by including different levels of miscentring effects between the two subsamples as informed by X-ray observations. We find that the two subsamples have the same average halo mass of $1.74\times 10^{14}\, h^{-1}\, \mathrm{M}_{\odot }$, but the concentration of the low-$M_*^{\mathrm{BCG}}$ clusters is $5.87_{-0.60}^{+0.77}$, ∼1.5σ smaller than that of their high-$M_*^{\mathrm{BCG}}$ counterparts ($6.95_{-0.66}^{+0.78}$). Furthermore, both cluster weak lensing and cluster-galaxy cross-correlations indicate that the large-scale bias of the low-$M_*^{\mathrm{BCG}}$, low-concentration clusters are ${\sim}10{{\ \rm per\ cent}}$ higher than that of the high-$M_*^{\mathrm{BCG}}$, high-concentration systems, hence possible evidence of the cluster assembly bias effect. Our results reveal a remarkable physical connection between the stellar mass within $20{-}30\, h^{-1}\, {\mathrm{kpc}}$, the dark matter mass within ${\sim}200\, h^{-1}\, {\mathrm{kpc}}$, and the cosmic overdensity on scales above $10\, h^{-1}\, {\mathrm{Mpc}}$, enabling a key observational test of theories of co-evolution between massive clusters and their central galaxies.
Feasibility and Morbidity of Magnetic Resonance Imaging-Guided Stereotactic Laser Ablation of Deep Cerebral Cavernous Malformations: A Report of 4 Cases
Authors: Malcolm James G , Douglas J Miller , Greven Alex , Rich Christopher , Dawoud Reem A , Hu Ranliang , Reisner Andrew , Barrow Daniel L , Gross Robert E , Willie Jon T
Published: June 2021

BACKGROUND

Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (MRgLITT) has been used successfully to treat epileptogenic cortical cerebral cavernous malformations (CCM). It is unclear whether MRgLITT would be as feasible or safe for deep CCMs

OBJECTIVE

To describe our experience with MRgLITT for symptomatic deep CCMs

METHODS

Patients’ records were reviewed retrospectively. MRgLITT was carried out using a commercially available system in an interventional MRI suite with efforts to protect adjacent brain structures. Immediate postoperative imaging was used to judge ablation adequacy. Delayed postoperative MRI was used to measure lesion volume changes during follow-up.

RESULTS

Four patients with CCM in the thalamus, putamen, midbrain, or subthalamus presented with persistent and disabling neurological symptoms. A total of 2 patients presented with disabling headaches and sensory disturbances and 2 with recurrent symptomatic hemorrhages, of which 1 had familial CCM. Patients were considered by vascular neurosurgeons to be poor candidates for open surgery or had refused it. Multiple trajectories were used in most cases. Adverse events included device malfunction with leakage of saline causing transient mass effect in one patient, and asymptomatic tract hemorrhage in another. One patient suffered an expected mild but persistent exacerbation of baseline deficits. All patients showed improvement from a previously aggressive clinical course with lesion volume decreased by 20% to 73% in follow-up.

CONCLUSION

MRgLITT is feasible in the treatment of symptomatic deep CCM but may carry a high risk of complications without the benefit of definitive resection. We recommend cautious patient selection, low laser power settings, and conservative temperature monitoring in surrounding brain parenchyma.
Cefiderocol Activity Against ClinicalPseudomonas aeruginosaIsolates Exhibiting Ceftolozane-Tazobactam Resistance
Authors: Simner Patricia J , Beisken Stephan , Bergman Yehudit , Posch Andreas E , Cosgrove Sara E , Tamma Pranita D
Published: June 2021

Background

Mutations in the AmpC-AmpR region are associated with treatment-emergent ceftolozane-tazobactam (TOL-TAZ) and ceftazidime-avibactam (CAZ-AVI) resistance. We sought to determine if these mutations impact susceptibility to the novel cephalosporin-siderophore compound cefiderocol.

Methods

Thirty-two paired isolates from 16 patients with index P. aeruginosa isolates susceptible to TOL-TAZ and subsequent P. aeruginosa isolates available after TOL-TAZ exposure from January 2019 to December 2020 were included. TOL-TAZ, CAZ-AVI, imipenem-relebactam (IMI-REL), and cefiderocol minimum inhibitory concentrations (MICs) were determined using broth microdilution. Whole-genome sequencing of paired isolates was used to identify mechanisms of resistance to cefiderocol that emerged, focusing on putative mechanisms of resistance to cefiderocol or earlier siderophore-antibiotic conjugates based on the previously published literature.

Results

Analyzing the 16 pairs of P. aeruginosa isolates, ≥4-fold increases in cefiderocol MICs occurred in 4 of 16 isolates. Cefiderocol nonsusceptibility criteria were met for only 1 of the 4 isolates, using Clinical and Laboratory Standards Institute criteria. Specific mechanisms identified included the following: AmpC E247K (2 isolates), MexR A66V and L57D (1 isolate each), and AmpD G116D (1 isolate) substitutions. For both isolates with AmpC E247K mutations, ≥4-fold MIC increases occurred for both TOL-TAZ and CAZ-AVI, while a ≥4-fold reduction in IMI-REL MICs was observed.

Conclusions

Our findings suggest that alterations in the target binding sites of P. aeruginosa–derived AmpC β-lactamases have the potential to reduce the activity of 3 of 4 novel β-lactams (ie, ceftolozane-tazobactam, ceftazidime-avibactam, and cefiderocol) and potentially increase susceptibility to imipenem-relebactam. These findings are in need of validation in a larger cohort.
Novel Applications of Spinal Navigation in Deformity and Oncology Surgery—Beyond Screw Placement
Authors: Massaad Elie , Shankar Ganesh M , Shin John H
Published: June 2021

Computer-assisted navigation has made a major impact on spine surgery, providing surgeons with technological tools to safely place instrumentation anywhere in the spinal column. With advances in intraoperative image acquisition, registration, and processing, many surgeons are now using navigation in their practices. The incorporation of navigation into the workflow of surgeons continues to expand with the evolution of minimally invasive techniques and robotic surgery. While numerous investigators have demonstrated the benefit of navigation for improving the accuracy of instrumentation, few have reported applying this technology to other aspects of spine surgery. Surgeries to correct spinal deformities and resect spinal tumors are technically demanding, incorporating a wide range of techniques not only for instrumentation placement but also for osteotomy planning and executing the goals of surgery. Although these subspecialties vary in their objectives, they share similar challenges with potentially high complications, invasiveness, and consequences of failed execution. Herein, we highlight the utility of using spinal navigation for applications beyond screw placement: specifically, for planning and executing osteotomies and guiding the extent of tumor resection. A narrative review of the work that has been done is supplemented with illustrative cases demonstrating these applications.
Present and Future Spinal Robotic and Enabling Technologies
Authors: Khalsa Siri Sahib S , Mummaneni Praveen V , Chou Dean , Park Paul
Published: June 2021

Enabling technologies include surgical planning software, computer-assisted navigation, intraoperative three-dimensional (3D) imaging, and robotic systems. Presently, these technologies are in various stages of refinement. Spinal robots in particular are currently limited to the positioning of an alignment guide for pedicle screw placement. Current generation spinal robots, therefore, play a more limited role in spinal surgery. In contrast to spinal robots, intraoperative imaging technology has been developed further, to a stage that allows accurate 3D spinal image acquisition that can be readily utilized for spinal navigation. The integration of these various technologies has the potential to maximize the safety, consistency, reliability, and efficacy of surgical procedures. To that end, the trend for manufacturers is to incorporate various enabling technologies into the spinal robotic systems. In the near-term, it is expected that integration of more advanced planning software and navigation will result in wider applicability and value. In the long-term, there are a variety of enabling technologies such as augmented reality that may be a component of spinal robots. This article reviews the features of currently available spinal robots and discusses the likely future advancements of robotic platforms in the near- and long-term.
Operationalizing Intersectionality in Social Work Research: Approaches and Limitations
Authors: Matsuzaka Sara , Hudson Kimberly D , Ross Abigail M
Published: June 2021

Despite intersectionality’s relevance to social work, scholars have raised concerns that its misguided applications place it “in danger of being co-opted, depoliticized, and diluted.” This scoping review examined the use of intersectionality in empirical social work research, specific to the extent, contexts, and degree of responsibility with which it has been applied. Using the search term convention [“social work” OR “social services”] AND [“intersectional” OR “intersectionality”], 22 databases were searched for peer-reviewed research published between 2009 and 2019, yielding 153 articles. The 33 studies meeting inclusion criteria were examined according to two frameworks: (1) typologies for intersectional conceptual approach and (2) intersectionality responsible use guidelines (RUG). Most studies used an intracategorical approach (n = 24), while fewer used an intercategorical (n = 7) or a mixed intra- and intercategorical approach (n = 2). On average, studies met approximately half of the RUG. Studies most frequently (n = 29) aligned with the guideline “Recommend ways to promote positive social transformation and justice through research, teaching, and practice.” Studies least frequently (n = 3) conformed to the guideline “Credits Black feminist activist roots of intersectionality.” Responsible stewardship is recommended to address power in knowledge production, researcher positionalities, and social justice action.
Phase Resolution of Heterozygous Sites in Diploid Genomes is Important to Phylogenomic Analysis under the Multispecies Coalescent Model
Authors: Huang Jun , Bennett Jeremy , Flouri Tomáš , Leaché Adam D , Yang Ziheng
Published: June 2021

Genome sequencing projects routinely generate haploid consensus sequences from diploid genomes, which are effectively chimeric sequences with the phase at heterozygous sites resolved at random. The impact of phasing errors on phylogenomic analyses under the multispecies coalescent (MSC) model is largely unknown. Here, we conduct a computer simulation to evaluate the performance of four phase-resolution strategies (the true phase resolution, the diploid analytical integration algorithm which averages over all phase resolutions, computational phase resolution using the program PHASE, and random resolution) on estimation of the species tree and evolutionary parameters in analysis of multilocus genomic data under the MSC model. We found that species tree estimation is robust to phasing errors when species divergences were much older than average coalescent times but may be affected by phasing errors when the species tree is shallow. Estimation of parameters under the MSC model with and without introgression is affected by phasing errors. In particular, random phase resolution causes serious overestimation of population sizes for modern species and biased estimation of cross-species introgression probability. In general, the impact of phasing errors is greater when the mutation rate is higher, the data include more samples per species, and the species tree is shallower with recent divergences. Use of phased sequences inferred by the PHASE program produced small biases in parameter estimates. We analyze two real data sets, one of East Asian brown frogs and another of Rocky Mountains chipmunks, to demonstrate that heterozygote phase-resolution strategies have similar impacts on practical data analyses. We suggest that genome sequencing projects should produce unphased diploid genotype sequences if fully phased data are too challenging to generate, and avoid haploid consensus sequences, which have heterozygous sites phased at random. In case the analytical integration algorithm is computationally unfeasible, computational phasing prior to population genomic analyses is an acceptable alternative. [BPP; introgression; multispecies coalescent; phase; species tree.]
A relational theory of fiduciary accountability
Authors: Flannigan Robert
Published: June 2021

Believing that the law of fiduciary accountability lacks coherent definition, various active writers have sought to provide that definition. Their analyses, however, are misinformed or misconceived. The consequence is that the fiduciary literature continues to be a source of obfuscation, rather than illumination. Here I examine the attempt of one writer to frame the law in what he describes as a ‘relational’ theory. I discuss the diverse misconceptions that impair his work.
Beware the ‘gifted’ Trojan horse: analysing the equitable maxim—‘Equity will not perfect an imperfect gift’
Authors: Keat Edwin Teong Ying
Published: June 2021

This article analyses and argues for the continued relevance of the maxim—Equity will not perfect an imperfect gift for three reasons. First, it is principally sound. Centuries of historical development should not be discarded due to its arbitrary application. Second, the deviations from the maxim were justified. The cases which were decided wrongly have subsequently been accounted for. Third, common law jurisdictions including Singapore, Malaysia and the United Kingdom still apply Milroy v Lord, as proven by empirical analysis. Last, this article proposes a new three-step test to prevent further arbitrary application: (i) As a starting point, Equity will not perfect an imperfect gift. (ii) However, it may do so where the settlor has objectively done all he could to transfer legal title. (iii) If step (ii) conflicts with step (i), Equity looks to the substance, not the form, considering the facts of each case.
Necessary lives: reformulating the rule against perpetuities
Authors: Pratt Simon D
Published: June 2021

The discussions in two preceding articles are now consolidated to help reformulate the Rule Against Perpetuities and to explain its search for a so-called measuring life in being. Here, it is argued that unsolved problems regarding the Effective Lives and Causal Connection hypotheses are overcome by applying Aristotelian and Avicennian ideas of necessary and proximate causation to Bractonian notions that valid conditions must be annexed to the limitation.
Genomic Reconstruction of the Introduction and Diversification of Golden Potato Cyst Nematode Populations in Indonesia
Authors: Handayani Nurul Dwi , Lestari Prabowo , van As Wouter , Holterman Martijn , van den Elsen Sven , Dikin Antarjo , Bert Wim , Helder Johannes , Van Steenbrugge Joris J. M.
Published: June 2021

Potato cyst nematodes (PCNs), the umbrella term for Globodera rostochiensis and G. pallida, coevolved with their Solanaceous hosts in the Andean Mountain region. From there, PCN proliferated worldwide to virtually all potato production areas. PCN is a major factor limiting the potato production in Indonesia. In our survey, only G. rostochiensis was found. Fourteen field populations were collected on Java and Sumatra, and unique variants were called by mapping resequencing data on a G. rostochiensis reference genome. A phylogenetic tree based on 1.4 million unique variants showed a genotypic separation between the outgroup, a Scottish Ro1 population, and all Indonesian populations. This separation was comparable in size with the genotypic distinction between the Javanese and the Sumatran PCN populations. Next, variants within PCN effector gene families SPRYSEC, 1106, 4D06, and venom allergen-like protein (VAL) that all interfere with the host innate immune system were compared. Distinct selective pressures acted on these effector families; while SPRYSECs (4,341 single-nucleotide polymorphisms [SNPs]/insertions or deletions of bases [indels]) behaved like neutral genes, the phylogenetic trees of 1106, 4D06, and VAL proteins (235, 790, and 150 SNPs/indels, respectively) showed deviating topologies. Our data suggest that PCN was introduced on Java not too long after the introduction of potato in the middle of the eighteenth century. Soon thereafter, the pathogen established on Sumatra and started to diversify independently. This scenario was corroborated by diversification patterns of the effector families 1106, 4D06, and VAL. Our data demonstrate how genome resequencing data from a nonindigenous pathogen can be used to reconstruct the introduction and diversification process.
Ouch! Neuronal pathways responsible for conduction of somatosensory and visceral pain
Authors: McBride Jennifer M
Published: June 2021

Nociceptive input is relayed from polymodal nociceptors (Latin nocere, “to hurt”) to various axonal pathways for the perception and modulation of pain by the central nervous system. The pathways carrying this afferent information depend on the class and origin of the nociceptors and the axons associated with them. Classically, the spinothalamic tract is identified as the main pathway carrying nociceptive information from the periphery. Other recognized nociceptive pathways include the spinal trigeminal tract from the face and smaller, less defined pathways from the thoracic, abdominal and pelvic viscera. This talk will focus on the organization of these three pathways throughout the central nervous system.
Decreased aconitase and cytochrome c oxidase activity in skeletal muscle of ATM‐deficient mice
Authors: McDonald Todd M. , Patel Akshar Y. , Fisher Jonathan S.
Published: June 2021

Cells that lack ataxia telangiectasia mutated (ATM) reportedly have high levels of reactive oxygen species (ROS) and impaired mitochondrial function. We hypothesized that activities of mitochondrial enzymes that are susceptible to modification by ROS, such as aconitase and cytochrome c oxidase (COX), would be decreased by ATM deficiency. In tibialis anterior muscles, aconitase activity was ~50% lower for ATM‐deficient (ATM −/−) mice than for wild‐type (ATM +/+) animals (P<0.05, n=7/group). However, aconitase activity from ATM −/− muscle was completely rescued by preincubation of muscle homogenates under reducing conditions. COX activity was ~40% lower in tibialis anterior from ATM −/− animals than for wild‐type mice (P<0.005, n=9/group). Inhibition of COX activity by ATP was greater for ATM +/+ muscles than for ATM −/− muscles (38±7% vs. 15±5%, P<0.05, n=7/group), suggesting that COX tends to be in its inefficient, ROS‐producing state in ATM −/− muscle. Incubation of wild‐type soleus muscles for 1 h with the ATM inhibitor KU55933 tended to cause a 22% reduction (P=0.17, n=4/group) in COX activity compared to muscles incubated with vehicle alone. Overall, the findings suggest that activities of ROS‐susceptible mitochondrial enzymes are decreased by ATM deficiency.

This work was supported by NIH R15DK080437 and ARRA funding. Todd McDonald was an APS Frontiers in Physiology Fellow.
Vitamin E effects on oxidative damage and cell morphology in AGE‐treated SH‐SY5Y cells
Authors: Pazdro Robert , Burgess John R
Published: June 2021

Chronic hyperglycemia generates reactive oxygen species in part through the formation and downstream signaling effects of advanced glycation end products (AGEs). In cultured cells, AGEs promote apoptosis and oxidative damage and these effects are diminished by several antioxidants, including vitamin E. This work further investigated the role of vitamin E in cellular protection against AGE‐induced oxidative damage and cell morphology changes in SH‐SY5Y cells. Glycated BSA (1 mg/ml) decreased cell viability and increased lipid and protein oxidation markers in comparison to cells treated with unglycated BSA. Cotreatment with either α‐tocopherol (200 uM) or n‐acetyl‐cysteine (NAC) (2 mM) improved cell viability, but differentially affected lipid and protein oxidation markers. Although α‐tocopherol decreased lipid and protein oxidation, it had no effect on the AGE‐mediated changes in cell morphology or intracellular GSH concentration. In contrast, NAC increased cellular GSH concentrations, decreased protein oxidation, and prevented AGE‐mediated changes in cell morphology but did not affect elevated lipid oxidation. Thus, although vitamin E protects SH‐SY5Y cells against AGE‐induced macromolecular damage and improves viability, it failed to protect against cell morphology changes caused by AGEs.
Palmitoylation of platelet‐activating factor receptor is required for its lipid raft targeting and signaling
Authors: Lu Jing , Caplan Michael S , Jilling Tamas
Published: June 2021

Platelet‐activating factor receptor (PAFR) signaling has been implicated in a broad range of pathologies. Site‐directed mutagenesis, recombinant protein analysis, sucrose density fractionation and radiolabeling studies indicate that the PAFR is targeted to lipid rafts and can be palmitoylated on cysteine 317. Polyunsaturated fatty acids (PUFA) block PAF‐induced apoptosis, ion transport and proinflammatory gene expression. Palmitate incorporation into the PAFR is inhibited in the presence of excess arachidonic acid (AA), docosahexaenoic acid (DHA), and a palmitoylation inhibitor 2‐bromopalmitate (2‐BP). PAFR solubilized from membranes of untreated HT29‐CL19A colonocytes sediments to the 30% sucrose density fraction similar to occludin, a bone fide lipid raft marker in these cells. Both the PAFR and occludin are displaced from this fraction and they are detected in the lighter 15% to 30% interface (both PAFR and occludin) and in the 15% sucrose fraction (occludin) when solubilized from mebranes derived from HT29‐CL19A cells treated with 2‐BP AA or DHA. These data are consistent with the notion that, in addition to their well known effects on prostaglandin biosytnthesis, PUFA can act via a novel mechanism by which they alter posttranslational modification and they displace PAFR from lipid rafts. Supported by NIH DK062960.