bluuebunny/crossref_metadata_2025 huggingface dataset:
Preventing unwanted situations and gaining trust: a qualitative study of older people and families’ experiences with advance care planning in the daily practice of primary care
Authors: Glaudemans Jolien J , Willems Dick L , Wind Jan , Onwuteaka Philipsen Bregje D
Published: November 2019

Background

Using advance care planning (ACP) to anticipate future decisions can increase compliance with people’s end-of-life wishes, decrease inappropriate life-sustaining treatment and reduce stress, anxiety and depression. Despite this, only a minority of older people engage in ACP, partly because care professionals lack knowledge of approaches towards ACP with older people and their families.

Objective

To explore older people’s and their families’ experiences with ACP in primary care.

Methods

We conducted qualitative, semi-structured, face-to-face interviews with 22 older people (aged >70 years, v/m: 11/11), with experience in ACP, and eight of their family members (aged 40–79 years, f/m: 7/1). Transcripts were inductively analysed using a grounded theory approach.

Results

We distinguished three main themes. (i) Openness and trust: Respondents were more open to ACP if they wanted to prevent specific future situations and less open if they lacked trust or had negative thoughts regarding general practitioners’ (GPs’) time for and interest in ACP. Engaging in ACP appeared to increase trust. (ii) Timing and topics: ACP was not initiated too early. Quality of ACP seemed to improve if respondents’ views on their current life and future, a few specific future care scenarios and expectations and responsibilities regarding ACP were discussed. (iii) Roles of family: Quality of ACP appeared to improve if family was involved in ACP.

Conclusions

Quality and accessibility of ACP may improve if GPs and nurses involve family, explain GPs’ interest in ACP and discuss future situations older people may want to prevent, and views on their current life and future.
Generalized stiffness reduction method to remove the artificial edge-effects for seismic wave modelling in elastic anisotropic media
Authors: Zhou Bing , Won Moosoo , Greenhalgh Stewart , Liu Xu
Published: November 2019

In seismic wave modelling, the boundary reflections caused by the computational grid edges should be reduced to produce accurate simulation results. The perfectly matched layer (PML) method is one of the popular techniques to suppress such artificial reflections, because it can be easily applied to the first-order wave equation in many numerical methods. However, one issue of the PML method is that the stability condition might be violated in complex elastic anisotropic media. In these cases, the PML method will not attenuate the boundary reflections but rather introduce strong artefacts in the simulation results. To tackle this problem, we propose a generalized stiffness reduction method (GSRM) as a substitute for the PML method. We first derive the stability conditions of the PML method and analyse the suitable conditions for their application to time- and frequency-domain seismic wave modelling. Then, we develop a simple and effective numerical implementation of the GSRM to attenuate the boundary reflections and apply it to seismic wave modelling in elastic anisotropic media. We give some numerical experiments to demonstrate the feasibility and advantages of the GSRM compared to the PML method. Numerical examples show the GSRM is conceptually simpler, more computationally efficient and more straightforward in terms of numerical implementation than the PML method for seismic modelling using either first- or second-order time- and frequency-domain wave equations.
Addressing food insecurity in Australia through education for sustainability
Authors: Nuttman Sonia , Patrick Rebecca , Townsend Mardie
Published: November 2019

Within Australia food insecurity affects an estimated 4 million people annually. Health promotion degrees traditionally prepare pre-service graduates to address food insecurity from a social determinants perspective, little consideration of integrating ecological determinants, however, has been noted. This is a significant problem considering unprecedented environmental challenges facing future food production. Education for sustainability (EfS) is purported to develop graduates who can respond to significant sustainability issues in the 21st century. This study examined the potential for health promotion degrees to utilize EfS to address food insecurity through an ecological lens. The study also illustrates why it might be valuable for academics to use such an approach. Semi-structured interviews with 15 Australian health and sustainability academics and document analysis of 26 associated teaching units was undertaken. Thematic analysis informed the data analysis process to provide meaning and insight into emerging themes. Academics were unaware of EfS or its potential for developing ecologically literate graduates. A lack of university commitment towards sustainability and knowledge and skills to implement EfS were identified as potential barriers. Academics, however, were ascribing to the central tenets used in EfS such as interdisciplinary thinking and reflective practice, demonstrating its potential use in health promotion. EfS, as a framework for incorporating an ecological perspective into health promotion degrees has not been fully realized. This study suggests capacity building of academics with regard to the use of EfS as an approach within health promotion degrees to address significant sustainability issues in the 21st century, such as food insecurity.
Frontotemporal dementia non-sense mutation of progranulin rescued by aminoglycosides
Authors: Kuang Lisha , Hashimoto Kei , Huang Eric J , Gentry Matthew S , Zhu Haining
Published: November 2019

Frontotemporal dementia (FTD) is an early onset dementia characterized by progressive atrophy of the frontal and/or temporal lobes. FTD is highly heritable with mutations in progranulin accounting for 5–26% of cases in different populations. Progranulin is involved in endocytosis, secretion and lysosomal processes, but its functions under physiological and pathological conditions remains to be defined. Many FTD-causing non-sense progranulin mutations contain a premature termination codon (PTC), thus progranulin haploinsufficiency has been proposed as a major disease mechanism. Currently, there is no effective FTD treatment or therapy. Aminoglycosides are a class of antibiotics that possess a less-known function to induce eukaryotic ribosomal readthrough of PTCs to produce a full-length protein. The aminoglycoside-induced readthrough strategy has been utilized to treat multiple human diseases caused by PTCs. In this study, we tested the only clinically approved readthrough small molecule PTC124 and 11 aminoglycosides in a cell culture system on four PTCs responsible for FTD or a related neurodegenerative disease amyotrophic lateral sclerosis. We found that the aminoglycosides G418 and gentamicin rescued the expression of the progranulin R493X mutation. G418 was more effective than gentamicin (~50% rescue versus <10%), and the effect was dose- and time-dependent. The progranulin readthrough protein displayed similar subcellular localization as the wild-type progranulin protein. These data provide an exciting proof-of-concept that aminoglycosides or other readthrough-promoting compounds are a therapeutic avenue for familial FTD caused by progranulin PTC mutations.
Bounded Volume Denominators and Bounded Negativity
Authors: Bauer Thomas , Harbourne Brian , Küronya Alex , Nickel Matthias
Published: November 2019

In this paper, we study the question of whether on smooth projective surfaces the denominators in the volumes of big line bundles are bounded. In particular, we investigate how this condition is related to bounded negativity (i.e., the boundedness of self-intersections of irreducible curves). Our 1st result shows that boundedness of volume denominators is equivalent to primitive bounded negativity, which in turn is implied by bounded negativity. We connect this result to the study of semi-effective orders of divisors: our 2nd result shows that negative classes exist, which become effective only after taking an arbitrarily large multiple.
Levels of Human Immunodeficiency Virus DNA Are Determined Before ART Initiation and Linked to CD8 T-Cell Activation and Memory Expansion
Authors: Martin Genevieve E , Pace Matthew , Shearer Freya M , Zilber Eva , Hurst Jacob , Meyerowitz Jodi , Thornhill John P , Lwanga Julianne , Brown Helen , Robinson Nicola , Hopkins Emily , Olejniczak Natalia , Nwokolo Nneka , Fox Julie , Fidler Sarah , Willberg Christian B , Frater John
Published: November 2019

Initiation of antiretroviral therapy (ART) in early compared with chronic human immunodeficiency virus (HIV) infection is associated with a smaller HIV reservoir. This longitudinal analysis of 60 individuals who began ART during primary HIV infection (PHI) investigates which pre- and posttherapy factors best predict HIV DNA levels (a correlate of reservoir size) after treatment initiation during PHI. The best predictor of HIV DNA at 1 year was pre-ART HIV DNA, which was in turn significantly associated with CD8 memory T-cell differentiation (effector memory, naive, and T-bet−Eomes− subsets), CD8 T-cell activation (CD38 expression) and T-cell immunoglobulin and mucin-domain containing-3 (Tim-3) expression on memory T cells. No associations were found for any immunological variables after 1 year of ART. Levels of HIV DNA are determined around the time of ART initiation in individuals treated during PHI. CD8 T-cell activation and memory expansion are linked to HIV DNA levels, suggesting the importance of the initial host-viral interplay in eventual reservoir size.
The Colonization of Carbapenem-Resistant Klebsiella pneumoniae: Epidemiology, Resistance Mechanisms, and Risk Factors in Patients Admitted to Intensive Care Units in China
Authors: Qin Xiaohua , Wu Shi , Hao Min , Zhu Jing , Ding Baixing , Yang Yang , Xu Xiaogang , Wang Minggui , Yang Fan , Hu Fupin
Published: November 2019

Background

Carbapenem-resistant Klebsiella pneumoniae (CRKP) has become a threat to public health, most notably as a superbug causing nosocomial infections. Patients in the intensive care unit (ICU) are at increased risk of hospital-acquired K pneumoniae infection, especially CRKP. This study was conducted to investigate the frequency of gastrointestinal and nasopharyngeal K pneumoniae colonization and its contribution to infections in ICU patients.

Methods

A 3-month prospective cohort study was performed in which 243 ICU patients were screened for intestinal and nasopharyngeal carriage of K pneumoniae at admission and once per week thereafter. The colonization and clinical infection isolates were analyzed by antimicrobial susceptibility testing to identify CRKP and were characterized by multilocus sequence typing (MLST) and whole-genome sequencing combined with epidemiological data to investigate the resistance mechanisms and assess the possible transmitted infection.

Results

Twenty-eight percent (68 of 243) of patients tested positive for carriage of K pneumoniae immediately upon admission to ICU, 54% (37 of 68) of which were nonduplicate CRKP isolates. Patients with carbapenem-susceptible K pneumoniae (CSKP) colonization at admission were more likely to acquire CRKP colonization during the ICU stay compared with patients without K pneumoniae colonization at admission. The incidence of subsequent CRKP infection in the baseline CSKP (32.3%, 10 of 31) and CRKP (45.9%, 17 of 37) carrier group was significantly higher than that of the baseline non-KP carrier group (8.6%, 15 of 175). The risk factors associated with acquired CRKP colonization during the ICU stay among negative CRKP colonization at admission included previous exposure to carbapenem, tigecycline or β-lactam/β-lactamases inhibitor, and invasive processes or surgical operations. Sixty-four percent (27 of 42) of patients with K pneumoniae infection were colonized by clonally related K pneumoniae strains according to enterobacterial repetitive intergenic consensus sequence-polymerase chain reaction analysis. ST11 (72%, 53 of 74) was the most predominant MLST type of clonally related CRKP isolate colonizing these patients, followed by ST15 (26%, 19 of 74).

Conclusions

The colonization of K pneumoniae may increase the incidence of corresponding K pneumoniae infection in critically ill patients in the ICU. High prevalence of ST11 CRKP (due to blaKPC-2) carriage and infection in ICU was observed.
Incidence and Clearance of Anal Human Papillomavirus (HPV)-16 and HPV-18 Infection, and Their Determinants, Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in France
Authors: Alberts Catharina J , Heard Isabelle , Canestri Ana , Marchand Lucie , Fléjou Jean-François , Piroth Lionel , Ferry Tristan , Didelot Jean-Michel , Siproudhis Laurent , Henno Sébastien , Poizot-Martin Isabelle , Darragh Teresa M , Clifford Gary M , Combes Jean-Damien , Etienney Isabelle ,   for the ANRS EP57 APACHES Study group, Arvieux C , Canestri A , Clifford G M , Combes J D , Costes-Martineau V , Del Grande J , Didelot J M , Etienney I , Falguières M , Ferry T , Fischer H , Flejou J F , Heard I , Henno S , Hoyau N , Landon M , Laude H , Le Breton F , Lesage A C , Lion A , Maincent G , Marchand L , Njatonirina H , Patey O , Petrov Sanchez V , Pialoux V , Piroth L , Poizot-Martin I , Zaegel-Faucher O , Ressiot E , Radenne S , Reynes J , Siproudhis L , Tamalet C , Tattevin P
Published: November 2019

Background

Prospective data on the natural history of anal human papillomavirus (HPV) infection are scarce in human immunodeficiency virus (HIV)-infected men who have sex with men (MSM).

Methods

We analyzed incidence and clearance of HPV-16 and HPV-18 in a French cohort of HIV-infected MSM, aged ≥35 years, followed-up annually (n = 438, 2014–2018).

Results

Human papillomavirus-16 and HPV-18 incidence were similar (~10% incident infections at 24 months). Human papillomavirus-16 incidence was higher among high-grade versus no lesion at baseline (adjusted incidence rate ratio = 3.0; 95% confidence interval, 1.07–8.18). Human papillomavirus-16 cleared significantly slower than HPV-18 (32% versus 54% by 24 months).

Conclusions

In conclusion, anal HPV-16 is more persistent than HPV-18, and its incidence correlates with a prior detection of high-grade lesions.
Escherichia coli O80 hybrid pathotype strains producing Shiga toxin and ESBL: molecular characterization and potential therapeutic options
Authors: Cointe Aurélie , Birgy André , Bridier-Nahmias Antoine , Mariani-Kurkdjian Patricia , Walewski Violaine , Lévy Corinne , Cohen Robert , Fach Patrick , Delannoy Sabine , Bidet Philippe , Bonacorsi Stéphane
Published: November 2019

Objectives

Enterohaemorrhagic Escherichia coli (EHEC) infections may be complicated by haemolytic uraemic syndrome (HUS). The emerging worldwide EHEC serogroup O80 has acquired a mosaic plasmid combining extraintestinal virulence and antibiotic resistance. This hybrid pathotype is associated with invasive infections that require antibiotic therapy, classically not recommended in EHEC infections, increasing the risk of HUS. We characterized two ESBL-producing O80 EHEC strains, which is an unusual resistance mechanism among EHECs, and determined the safest therapy to be used for invasive infections.

Methods

WGS of two strains isolated from the stools of an asymptomatic carrier and a patient with HUS was performed using Illumina and Nanopore technologies. Generated reads were combined to assemble genomes. We determined the safest therapy by comparing Shiga toxin (Stx) production by the two strains in the presence of several antibiotics.

Results

The strains were genetically close to the O80 EHEC clone, belonging to ST301 and harbouring stx2d, eae-ξ, ehxA and genes characteristic of the extraintestinal virulence plasmid pS88. Long-read sequencing identified the acquisition of an additional plasmid harbouring CTX-M-type genes (blaCTX-M-14 and blaCTX-M-1). Azithromycin decreased Stx production at subinhibitory concentrations, ciprofloxacin increased it and imipenem had no major effect. The combination of azithromycin and imipenem overall reduced Stx production.

Conclusions

Acquisition of an additional plasmid harbouring ESBL genes is a step towards increasing the risk of O80 EHEC dissemination and represents a serious public health concern. The combination of azithromycin and imipenem reduced Stx production and suggests that this combination could be tested in clinical trials.
Dynamics of the leaf endoplasmic reticulum modulate β-glucosidase-mediated stress-activated ABA production from its glucosyl ester
Authors: Han Yiping , Watanabe Shunsuke , Shimada Hiroshi , Sakamoto Atsushi
Published: November 2019

The phytohormone abscisic acid (ABA) is produced via a multistep de novo biosynthesis pathway or via single-step hydrolysis of inactive ABA-glucose ester (ABA-GE). The hydrolysis reaction is catalyzed by β-glucosidase (BG, or BGLU) isoforms localized to various organelles, where they become activated upon stress, but the mechanisms underlying this organelle-specific activation remain unclear. We investigated the relationship between the subcellular distribution and stress-induced activation of BGLU18 (BG1), an endoplasmic reticulum enzyme critical for abiotic stress responses, in Arabidopsis thaliana leaves. High BGLU18 levels were present in leaf petioles, primarily in endoplasmic reticulum bodies. These Brassicaceae-specific endoplasmic reticulum-derived organelles responded dynamically to abiotic stress, particularly drought-induced dehydration, by changing in number and size. Under stress, BGLU18 distribution shifted toward microsomes, which was accompanied by increasing BGLU18-mediated ABA-GE hydrolytic activity and ABA levels in leaf petioles. Under non-stress conditions, impaired endoplasmic reticulum body formation caused a microsomal shift of BGLU18 and increased its enzyme activity; however, ABA levels increased only under stress, probably because ABA-GE is supplied to the endoplasmic reticulum only under these conditions. Loss of BGLU18 delayed dehydration-induced ABA accumulation, suggesting that ABA-GE hydrolysis precedes the biosynthesis. We propose that dynamics of the endoplasmic reticulum modulate ABA homeostasis and abiotic stress responses by activating BGLU18-mediated ABA-GE hydrolysis.
Comparison of risk factors and outcomes of Candida auris candidemia with non-Candida auris candidemia: A retrospective study from Pakistan
Authors: Sayeed Muneeba Ahsan , Farooqi Joveria , Jabeen Kauser , Mahmood Syed Faisal
Published: November 2019

Candida auris has emerged as a nosocomial multi-drug resistant pathogen. This study aimed to compare the risk factors and outcomes of C. auris candidemia patients with non-C. auris candidemia, at a single center in Pakistan. A retrospective study compared 38 C. auris with 101 non-C. auris (36 C. albicans, 38 C. tropicalis, and 27 C. parapsilosis) candidemia patients between September 2014 and March 2017 at the Aga Khan University Hospital, Pakistan. Demographics, clinical history, management and outcomes were studied. Prior history of surgery (adjusted odds ratio [aOR] 4.9, 95% confidence interval [CI]: 1.4–17.5), antifungals exposure (aOR 38.3, 95% CI: 4.1–356) and prior MDR bacteria isolation (aOR 5.09, 95% CI: 1.6–15.9) were associated with C. auris candidemia. On survival analysis both groups of patients had similar outcome in terms of mortality (62.6% vs. 52.54%, hazard ratio [HR] 1.45, 95% CI: 0.84–2.4, P-value = .17) and microbiological failure rates (42.3% vs. 32.2%, HR 0.65, 95% CI: 0.35–1.2, P-value = .17) however, C. auris patients had a higher mean hospital stay (36.32 days vs. 14.8 days, P-value = <.001) and higher >15-day in-hospital stay from positive culture (HR 2.68, 95% CI: 1.1–6.3, P-value = .025). Antifungal susceptibility was different, with C. auris more often resistant to voriconazole (29.6% vs. 0%) and amphotericin (3.7 vs. 0%); though no echinocandin resistance was detected in either group. As opposed to other Candida species, C. auris candidemia occurred after nosocomial exposure, and its source was most commonly an indwelling line. Although these patients had a higher in-hospital stay, but there was no excess mortality when compared to other Candida species.
FIESTA – disentangling stellar variability from exoplanets in the Fourier domain
Authors: Zhao J , Tinney C G
Published: November 2019

We propose a new analysis methodology – FourIEr phase SpecTrum Analysis (FIESTA, or $\mathit {\Phi }$ESTA) – for the study of spectral line profile variability in Fourier space. The philosophy of $\mathit {\Phi }$ESTA is highlighted in its interpretation of a line deformation as various shifts of the composing Fourier modes. With this ability, $\mathit {\Phi }$ESTA excels in distinguishing the effects of a bulk shift in a line profile, from changes in a line profile shape. In other words, it can distinguish a radial velocity shift due to orbiting companions like planets, from an apparent radial velocity shift due to stellar variability (often referred to as ‘jitter’). Most importantly, it can quantify the radial velocity impact of stellar jitter on each epoch. Our simulations show that (compared to a model that does not account for stellar activity), $\mathit {\Phi }$ESTA can almost triple the fraction of planets recovered with orbital parameters measured to within 10 per cent of their input parameters, when extracting a 2 m s−1 amplitude planetary signal in the midst of ∼2 m s−1 amplitude starspot jitter for high signal-to-noise ratio (>200 pixel−1) data. $\mathit {\Phi }$ESTA can also be used to identify stellar activity related periods in a periodogram analysis and classify relative amplitudes of stellar jitter and planetary signals, with examples for the analysis of HARPS data of the active star HD 224789 and the active planet-host star HD 103720. In the end, we demonstrate that $\mathit {\Phi }$ESTA’s framework is working as well as other activity indicators in correlating with stellar jitter.
Ultra-low-frequency waves in the ion foreshock of Mercury: a global hybrid modelling study
Authors: Jarvinen R , Alho M , Kallio E , Pulkkinen T I
Published: November 2019

We study the solar wind interaction with Mercury using a global three-dimensional hybrid model. In the analysed simulation run, we find a well-developed, dynamic Hermean ion foreshock ahead of the quasi-parallel bow shock under upstream solar wind and interplanetary magnetic field (IMF) conditions corresponding to the orbital perihelion of the planet. A portion of the incident solar wind ion flux is scattered back upstream near the quasi-parallel bow shock including both major solar wind ion species, protons and alphas. The scattered particles form the Hermean suprathermal foreshock ion population. A significant part of the suprathermal population is backstreaming with a velocity component towards the Sun in the near-foreshock at the planetocentric distance of few planetary radii in the plane of the IMF. The ion foreshock is associated with large-scale, oblique fast magnetosonic waves in the ultra-low-frequency (ULF) range convecting downstream with the solar wind. The ULF wave period is about 5 s in the analysed upstream condition case at Mercury, which corresponds to the 30-s foreshock waves at Earth when scaled by the IMF magnitude.
Searching for gamma-ray emission from galaxy clusters at low redshift
Authors: Colavincenzo Manuel , Tan Xiuhui , Ammazzalorso Simone , Camera Stefano , Regis Marco , Xia Jun-Qing , Fornengo Nicolao
Published: November 2019

We report the identification of a positive cross-correlation signal between the unresolved gamma-ray emission, measured by the Fermi Large Area Telescope, and four different galaxy cluster catalogues. The selected catalogues peak at low-redshift and span different frequency bands, including infrared, optical, and X-rays. The signal-to-noise ratio of the detected cross-correlation amounts to 3.5 in the most significant case. We investigate and comment about its possible origin, in terms of compact gamma-ray emission from AGNs inside clusters or diffuse emission from the intracluster medium. The analysis has been performed by introducing an accurate estimation of the cross-correlation power-spectrum covariance matrix, built with mock realizations of the gamma and galaxy cluster maps. Different methods to produce the mock realizations starting from the data maps have been investigated and compared, identifying suitable techniques which can be generalized to other cross-correlation studies.
Bifurcation in the history of Uranus and Neptune: the role of giant impacts
Authors: Reinhardt Christian , Chau Alice , Stadel Joachim , Helled Ravit
Published: November 2019

Despite many similarities, there are significant observed differences between Uranus and Neptune: While Uranus is tilted and has a regular set of satellites, suggesting their accretion from a disc, Neptune’s moons are irregular and are captured objects. In addition, Neptune seems to have an internal heat source, while Uranus is in equilibrium with solar insulation. Finally, structure models based on gravity data suggest that Uranus is more centrally condensed than Neptune. We perform a large suite of high-resolution SPH simulations to investigate whether these differences can be explained by giant impacts. For Uranus, we find that an oblique impact can tilt its spin axis and eject enough material to create a disc where the regular satellites are formed. Some of the discs are massive and extended enough, and consist of enough rocky material to explain the formation of Uranus’ regular satellites. For Neptune, we investigate whether a head-on collision could mix the interior, and lead to an adiabatic temperature profile, which may explain its larger flux and higher moment of inertia value. We find that massive and dense projectiles can penetrate towards the centre and deposit mass and energy in the deep interior, leading to a less centrally concentrated interior for Neptune. We conclude that the dichotomy between the ice giants can be explained by violent impacts after their formation.
Point mutations in topoisomerase I alter the mutation spectrum in E. coli and impact the emergence of drug resistance genotypes
Authors: Bachar Amit , Itzhaki Elad , Gleizer Shmuel , Shamshoom Melina , Milo Ron , Antonovsky Niv
Published: November 2019

Identifying the molecular mechanisms that give rise to genetic variation is essential for the understanding of evolutionary processes. Previously, we have used adaptive laboratory evolution to enable biomass synthesis from CO2 in Escherichia coli. Genetic analysis of adapted clones from two independently evolving populations revealed distinct enrichment for insertion and deletion mutational events. Here, we follow these observations to show that mutations in the gene encoding for DNA topoisomerase I (topA) give rise to mutator phenotypes with characteristic mutational spectra. Using genetic assays and mutation accumulation lines, we find that point mutations in topA increase the rate of sequence deletion and duplication events. Interestingly, we observe that a single residue substitution (R168C) results in a high rate of head-to-tail (tandem) short sequence duplications, which are independent of existing sequence repeats. Finally, we show that the unique mutation spectrum of topA mutants enhances the emergence of antibiotic resistance in comparison to mismatch-repair (mutS) mutators, and leads to new resistance genotypes. Our findings highlight a potential link between the catalytic activity of topoisomerases and the fundamental question regarding the emergence of de novo tandem repeats, which are known modulators of bacterial evolution.
Inhibition of histone deacetylase 1 (HDAC1) and HDAC2 enhances CRISPR/Cas9 genome editing
Authors: Liu Bin , Chen Siwei , Rose Anouk La , Chen Deng , Cao Fangyuan , Zwinderman Martijn , Kiemel Dominik , Aïssi Manon , Dekker Frank J , Haisma Hidde J
Published: November 2019

Despite the rapid development of CRISPR/Cas9-mediated gene editing technology, the gene editing potential of CRISPR/Cas9 is hampered by low efficiency, especially for clinical applications. One of the major challenges is that chromatin compaction inevitably limits the Cas9 protein access to the target DNA. However, chromatin compaction is precisely regulated by histone acetylation and deacetylation. To overcome these challenges, we have comprehensively assessed the impacts of histone modifiers such as HDAC (1–9) inhibitors and HAT (p300/CBP, Tip60 and MOZ) inhibitors, on CRISPR/Cas9 mediated gene editing efficiency. Our findings demonstrate that attenuation of HDAC1, HDAC2 activity, but not other HDACs, enhances CRISPR/Cas9-mediated gene knockout frequencies by NHEJ as well as gene knock-in by HDR. Conversely, inhibition of HDAC3 decreases gene editing frequencies. Furthermore, our study showed that attenuation of HDAC1, HDAC2 activity leads to an open chromatin state, facilitates Cas9 access and binding to the targeted DNA and increases the gene editing frequencies. This approach can be applied to other nucleases, such as ZFN and TALEN.
Adenosine-Induced Cardiac Arrest for Transvenous Embolization of Midbrain Arteriovenous Malformation
Authors: Lim Jaims , Shallwani Hussain , Vakharia Kunal , Siddiqui Adnan H
Published: November 2019

BACKGROUND AND IMPORTANCE

Few studies describe the use of adenosine-induced cardiac systole for treatment of cerebrovascular pathologies. We describe a midbrain arteriovenous malformation (AVM) treated with transvenous embolization using adenosine-induced asystole to achieve transient systemic hypotension with the purpose of furthering discussion on the technique and operative considerations for adenosine use in endovascular AVM treatments.

CLINICAL PRESENTATION

A 29-yr-old man presented with sudden onset of severe bilateral headache, blurred vision, and numbness on the right side of his face and tongue. Noncontrast head computed tomography revealed fourth ventricle hemorrhage. Diagnostic cerebral angiography revealed a high-flow midbrain AVM with a posterior wall perforator from the basilar artery terminus and a draining vein into the straight sinus. Transarterial AVM embolization was successful. The patient was discharged with no residual neurological deficits but returned 1 wk later with slurred speech and left-sided dysmetria. Repeat angiography revealed partial AVM filling. Attempts at transarterial embolization were unsuccessful. Thus, transvenous AVM embolization with adenosine-induced cardiac asystole and systemic hypotension was performed. A total of 60 mg of adenosine was administered, followed by 2 additional doses of 60 and 40 mg; and complete cardiac asystole with a mean arterial pressure of 40 mmHg was maintained, resulting in successful embolization of the AVM. No residual filling was visualized on postembolization arterial angiography runs. The patient was neurologically stable and discharged on postoperative day 2.

CONCLUSION

With appropriate and safe dosing, adenosine-induced asystole and systemic hypotension may be a feasible, safe option to reduce flow and assist endovascular transvenous embolization of high-flow AVMs.
Early China and the Quest for Mastery
Authors: Stalnaker Aaron
Published: November 2019

This chapter introduces early Chinese history, texts, and thought sufficiently to make the rest of the work intelligible to nonspecialists, and positions this study in relation to current debates in Chinese philosophy and the study of early China. The main argument is that we should stop seeing “China” as an inverted mirror image of the West, and let go of the enduring myth of Chinese and specifically Confucian authoritarianism. The chapter criticizes extreme versions of Confucian role ethics put forward by Ames and Rosemont, in favor of a Confucian relational self that possesses a conditioned form of autonomy, as advocated by Wong.
Social Democratic Capitalism and the Good Society
Authors: Kenworthy Lane
Published: November 2019

Abstract: To this point in history, the most successful societies have been those that feature capitalism, a democratic political system, good elementary and secondary (K–12) schooling, a big welfare state, public services that are conducive to employment, and moderate regulation of product and labor markets. I call this set of policies and institutions “social democratic capitalism.” Social democratic capitalism improves living standards for the least well-off, enhances economic security, and very likely boosts equality of opportunity. It does so without sacrificing the many other things we want in a good society, from liberty to economic growth to health to happiness and much more.
Islamic Law and International Law
Authors: Powell Emilia Justyna
Published: November 2019

This chapter explores in considerable detail differences and similarities between the Islamic legal tradition and international law. It discusses in detail the historical interaction between these legal traditions, their co-evolution, and the academic conversations on this topic. The chapter also addresses the Islamic milieu’s contributions to international law, and sources of Islamic law including the Quran, sunna, judicial consensus, and analogical reasoning. It talks about the role of religion in international law. Mapping the specific characteristics of Islamic law and international law offers a glimpse of the contrasting and similar paradigms, spirit, and operation of law. This chapter identifies three points of convergence: law of scholars, customary law, and rule of law; as well as three points of departure: relation between law and religion, sources of law, and religious features in the courtroom (religious affiliation and gender of judges, holy oaths).
Divine Women, Femmes, and Whores
Authors: Hedenborg White Manon
Published: November 2019

The chapter presents the frameworks utilized within the study to analyze the construction of femininities. Beginning with an overview of how feminist theorists have approached the complex of femininity, I contend that femininity has remained undertheorized in academic research, frequently associated with lack, artifice, subordination, and restriction. Building on the work of scholars working within queer and poststructuralist feminist paradigms—including Luce Irigaray, Judith Butler, Mimi Schippers, and Rosi Braidotti—I assert that any social system contains multiple femininities, which relate to each other as well as to masculinity. Moreover, femininities are neither exclusively oriented toward heterosexuality nor do they exist in any given relationship to (female) biology. Throughout the discussion, I also engage with feminist theorization of feminine sexuality, allying myself with sex-radical theorists who have argued that an analysis of feminine sexuality must account for mechanisms of both oppression and resistance.
The Scarlet Goddess and the Wine of Her Fornications
Authors: Hedenborg White Manon
Published: November 2019

Beginning with an overview of feminine stereotypes in fin-de-siècle culture, the chapter introduces Aleister Crowley and his concepts of Babalon and the related figure of the Scarlet Woman. An unconventional figure and founder of the religion Thelema, Crowley led an openly bisexual life and advocated free sexuality. In 1909, Crowley experimented with Enochian magic in the Algerian desert with his lover and disciple Victor B. Neuburg, beholding a series of visions, including one featuring a great goddess. Based on a positive reinterpretation of the Whore of Babylon (Rev. 17), Crowley linked this goddess—called Babalon—to the initiatory ordeal of crossing the Abyss, when the seeker must annihilate their ego to become one with all. I argue that Crowley’s articulation of Babalon built on the fin-de-siècle trope of the femme fatale, which he reinterpreted as a soteriological ideal, thus challenging notions of feminine sexual modesty and bourgeois, masculine rationality.
Feminist Difference
Authors: Hedenborg White Manon
Published: November 2019

This chapter analyzes how contemporary esotericists conceptualize Babalon as a challenge to hegemonic perceptions of femininity. As highlighted in previous chapters, the 1990s onward has witnessed increasing gender-critical awareness in the esoteric milieu. Present-day esotericists connect Babalon to assertiveness, liberated sexuality, sexual aggression, and dominance, thus presenting her as a symbol that runs counter to normative ideas about femininity as nurturing, maternal, soft, and family-oriented. The chapter also explores how the Babalon discourse intersects with critiques of historical Western esotericism and Thelema as well as how esotericists today address perceived sexism in the writings of Crowley and other male occultists. A number of esoteric writers and practitioners posit Babalon as the epitome of the empowered woman magician. While some of these interpretations emphasize the link between femininity and biology, others stress femininity as something more flexible in ways that acknowledge genderqueer and transgendered experience.
Religious Dissent in Late Antiquity, 350-450
Authors: Kahlos Maijastina
Published: November 2019

Religious Dissent in Late Antiquity reconsiders the religious history of the late Roman Empire, focusing on the shifting position of dissenting religious groups. The groups under consideration are non-Christians (‘pagans’) and deviant Christians (‘heretics’). The period from the mid-fourth century until the mid-fifth century ce witnessed a significant transformation of late Roman society and a gradual shift from the world of polytheistic religions into the Christian Empire. This book demonstrates that the narrative is much more nuanced than the simple Christian triumph over the classical world. It looks at everyday life, economic aspects, day-to-day practices, and conflicts of interest in the relations of religious groups. The book addresses two aspects: rhetoric and realities, and consequently delves into the interplay between the manifest ideologies and daily life found in late antique sources. We perceive constant flux between moderation and coercion that marked the relations of religious groups, both majorities and minorities, as well as the imperial government and religious communities. Religious Dissent in Late Antiquity is a detailed analysis of selected themes and a close reading of selected texts, tracing key elements and developments in the treatment of dissident religious groups. The book focuses on specific themes, such as the limits of imperial legislation and ecclesiastical control, the end of sacrifices, and the label of magic. It also examines the ways in which dissident religious groups were construed as religious outsiders in late Roman society.
Introduction: Rhetoric and realities
Authors: Kahlos Maijastina
Published: November 2019

The introduction defines several concepts that are used throughout the book. The religious dissidents in late Roman society were pagans and heretics. These terms are only shorthand: ‘pagans’ for non-Christians, and ‘heretics’ for deviant Christians. They are relational, meaning that there would have been no pagans without the viewpoint of Christians. Similarly, the question of who was a heretic depended on the perceiver. The period under scrutiny saw the Christianization of imperial and ecclesiastical discourses of control. Imperial power is understood as the emperors in both the East and the West, the imperial courts, and the administration. Ecclesiastical power refers to church leaders—mainly bishops, whose authority was increasing during the fourth and fifth centuries. There was no uniform church, and Christian congregations were miscellaneous assemblages of adherents.
The realities of legislation
Authors: Kahlos Maijastina
Published: November 2019

This chapter explores the development of the legal status of religious dissidents. The imperial rhetoric of alienation and aggression is counterbalanced by a discussion of the limits of power, such as the realities of making laws. Late antique legislation was articulated in uncompromising and moralizing language. Religious groups were condemned with harsh, insulting terms. The morally charged language of the legislation implies severe imperial authority. However, the authoritative language of legislation was used not only to manifest imperial power, but also to reinforce it. Furthermore, there was no imperial programme of efficient and organized coercive legislation from Constantine until Theodosius II and beyond. Instead, there was a great deal of incoherence and ambivalence. Moreover, the existence of harsh legislation does not necessarily imply that laws were widely obeyed. The prohibitions were renewed again and again, and punishments became more severe. Enforcement of laws often depended on regional circumstances and the initiatives of local leaders such as bishops.
Sacred times and spaces
Authors: Kahlos Maijastina
Published: November 2019

During the fourth and fifth centuries, Christian festivals gradually developed and were merged into the life of cities and villages. At the same time, many traditional local celebrations important to the communal life of these localities continued. This chapter examines the late antique bishops’ condemnations from the viewpoint of discursive boundary-marking in which the borders of ‘pagan’, ‘Christian’, ‘cultic’, and ‘civic’ were constantly shifting. The same persons took part in both pagan and Christian festivities. Practices that in the eyes of bishops appeared incompatible with Christian conduct were not irreconcilable for the participants themselves. One of the most popular feasts was the celebration of the New Year, which remained popular in the Christian Empire. Christian emperors did not prohibit festivals of this kind, which they defined as a common pleasure for all. The imperial government defined the content of urban celebrations in a manner that diverged from the delineations of ecclesiastical leaders.
Body, Sex/Gender, and Integration of Women into Combat Roles
Authors: Harel-Shalev Ayelet , Daphna-Tekoah Shir
Published: November 2019

Chapter 5 addresses narratives of women in combat and in combat-support roles regarding their bodily experiences and struggles to integrate in traditionally masculine roles in the military, particularly in the light of objections to women’s integration into combat forces. Accounts of bodily experiences disturb conventional IR and hegemonic masculine war metanarratives, whose tendency is either to abstract or to glorify combat (or both). These otherwise silenced narratives reveal juxtapositions of feelings of competence and vulnerability. The chapter shows how women combatants situate themselves in a masculine environment and demonstrates the ways in which, having crossed the pre-established imaginary boundary between male and female, they form unique meanings for their war experiences. Through the women’s narratives, issues of body and sex/gender are addressed, alongside nuanced interpretations of what it means to be feminine or masculine in the military environment, to carry a weapon, and to be a combatant.
Umar
Authors: Chiovenda Andrea
Published: November 2019

Umar is a man from Jalalabad, now in his mid-thirties, who early in adolescence became a religious preacher for the Taliban movement. The defeat of the Taliban at the hands of the US-led coalition shook his beliefs and political convictions. After a period of personal confusion, he found a new path for himself, and now is a financial officer for an international organization that funds agricultural works in Afghanistan. The chapter elaborates further on phenomena of multiple subjectivities and healthy, adaptive dissociation between them, which it claims are key to understanding the developments in Umar’s life. By looking closely at Umar’s personal struggle, the chapter also investigates the depth with which enculturation and social arrangements shape the individual’s subjectivity. It argues, and shows, that culturally mandated life choices and behaviors may become authentically “one’s own,” and still conflict with more purely private and personally derived ones.
Meaning
Authors: Kozak Mariusz
Published: November 2019

This chapter develops two claims that are central to the book’s overall argument. The first is that certain temporal musical objects exist only as ephemera—always remaining outside of symbolic representation. These objects are constituted by lived time, or time as it shows up in human lives. The second claim is that the ephemeral meaning of music consists of its significance, which the author defines as a practical meaning that arises in the moment of one’s perception of, and action upon, one’s immediate environment. Significance is a process that is enacted in the dyadic relationships between environmental affordances—opportunities for and constraints of action—and a situated agent.
Housing
Authors: Hershkoff Helen , Loffredo Stephen
Published: November 2019

This chapter discusses the major federal programs providing rental and homeownership assistance to poor and low-income people. On the supply side, for decades the United States has not funded new Public Housing that it owns and manages; instead, tax credits are the major driver of new construction, with buildings owned and operated by private developers who commit to time-limited affordability requirements. On the demand side, the leading rental support program gives tenants “vouchers,” allowing them choice where they can live but no guarantee that a landlord will rent to them at the subsidized payment levels. Moreover, many households, and disproportionately people of color, have been or continue to be arbitrarily denied rental assistance because of a family member’s prior contact with the criminal justice system, even just an arrest—a policy that has caused great hardship and contributed to homelessness. For those tenants who receive it, federal housing assistance is a critical lifeline. This chapter focuses on how prospective tenants can apply for and maintain eligibility for Public Housing or subsidized units in Multifamily Programs, and how to obtain and keep a voucher. The chapter also discusses issues critical to housing justice—tenant participation in assisted housing; rights of tenants when a private owner leaves an assisted program; housing support for the homeless; the government’s duty to affirmatively further fair housing; and problems of environmental displacement.
Access to Justice: Enforcing Rights and Securing Protection
Authors: Hershkoff Helen , Loffredo Stephen
Published: November 2019

This chapter provides an overview of civil litigation as it affects poor and low-income people. The U.S. Constitution is intended to “establish Justice,” but many poor and low-income people experience the court system as a source of injustice—subjecting them to meritless default judgments, fees and fines, imprisonment and forfeiture of property when no crime has been committed, and enforcing harsh collateral consequences of contacts with the criminal justice system. Moreover, many low-income people are blocked from going to court at all, because employment and consumer contracts include boilerplate terms that mandate arbitration, consigning the claimant to a private system of dispute resolution that has been questioned as unfair and in conflict with statutory and constitutional rights. Part of the problem is that the legal system assumes that litigants have the resources they need to bring or defend a civil action. The U.S. Constitution does not guarantee a right to counsel in civil litigation, and fee waivers, even when they are available, do not cover all of the costs of litigation. A rising number of civil litigants face stiff obstacles when seeking justice under law, for they cannot afford legal representation and lack resources to litigate in a meaningful way. This chapter is designed to help low-income people navigate the civil court system so that it moves closer to the ideal of equal justice under law, rather than exacerbate poverty or further entrench racial inequality.