bluuebunny/crossref_metadata_2025 huggingface dataset:
Potentially inappropriate prescribing in dementia, multi-morbidity and incidence of adverse health outcomes
Authors: Delgado João , Jones Lindsay , Bradley Marie C , Allan Louise M , Ballard Clive , Clare Linda , Fortinsky Richard H , Hughes Carmel M , Melzer David
Published: July 2020

Importance

treatment of dementia in individuals with comorbidities is complex, leading to potentially inappropriate prescribing (PIP). The impact of PIP in this population is unknown.

Objective

to estimate the rate of PIP and its effect on adverse health outcomes (AHO).

Design

retrospective cohort.

Setting

primary care electronic health records linked to hospital discharge data from England.

Subjects

11,175 individuals with dementia aged over 65 years in 2016 and 43,463 age- and sex-matched controls.

Methods

Screening Tool of Older Persons’ Prescriptions V2 defined PIP. Logistic regression tested associations with comorbidities at baseline, and survival analyses risk of incident AHO, adjusted for age, gender, deprivation and 14 comorbidities.

Results

the dementia group had increased risk of PIP (73% prevalence; odds ratio [OR]: 1.92; confidence interval [CI]: 83–103%; P < 0.01) after adjusting for comorbidities. Most frequent PIP criteria were related to anti-cholinergic drugs and therapeutic duplication. Risk of PIP was higher in patients also diagnosed with coronary-heart disease (odds OR: 2.17; CI: 1.91–2.46; P < 0.01), severe mental illness (OR: 2.09; CI: 1.62–2.70; P < 0.01); and depression (OR: 1.81; CI: 1.62–2.01; P < 0.01). During follow-up (1 year), PIP was associated with increased all-cause mortality (hazard ratio: 1.14; CI: 1.02–1.26; P < 0.02), skin ulcer and pressure sores (hazard ratio: 1.66; CI: 1.12–2.46; P < 0.01), falls (hazard ratio: 1.37; CI: 1.15–1.63; P < 0.01), anaemia (hazard ratio: 1.61; CI: 1.10–2.38; P < 0.02) and osteoporosis (hazard ratio: 1.62; CI: 1.02–2.57; P < 0.04).

Conclusion

patients with dementia frequently receive PIPs, and those who do are more likely to experience AHO. These results highlight the need to optimise medication in dementia patients, especially those with comorbidities.
Suptavumab for the Prevention of Medically Attended Respiratory Syncytial Virus Infection in Preterm Infants
Authors: Simões Eric A F , Forleo-Neto Eduardo , Geba Gregory P , Kamal Mohamed , Yang Feng , Cicirello Helen , Houghton Matthew R , Rideman Ronald , Zhao Qiong , Benvin Sarah L , Hawes Alicia , Fuller Erin D , Wloga Elzbieta , Pizarro Jose M Novoa , Munoz Flor M , Rush Scott A , McLellan Jason S , Lipsich Leah , Stahl Neil , Yancopoulos George D , Weinreich David M , Kyratsous Christos A , Sivapalasingam Sumathi
Published: July 2020

Background

Respiratory syncytial virus (RSV) is a major cause of childhood medically attended respiratory infection (MARI).

Methods

We conducted a randomized, double-blind, placebo-controlled phase 3 trial in 1154 preterm infants of 1 or 2 doses of suptavumab, a human monoclonal antibody that can bind and block a conserved epitope on RSV A and B subtypes, for the prevention of RSV MARI. The primary endpoint was proportion of subjects with RSV-confirmed hospitalizations or outpatient lower respiratory tract infection (LRTI).

Results

There were no significant differences between primary endpoint rates (8.1%, placebo; 7.7%, 1-dose; 9.3%, 2-dose). Suptavumab prevented RSV A infections (relative risks, .38; 95% confidence interval [CI], .14–1.05 in the 1-dose group and .39 [95% CI, .14–1.07] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .0499), while increasing the rate of RSV B infections (relative risk 1.36 [95% CI, .73–2.56] in the 1-dose group and 1.69 [95% CI, .92–3.08] in the 2-dose group; nominal significance of combined suptavumab group vs placebo; P = .12). Sequenced RSV isolates demonstrated no suptavumab epitope changes in RSV A isolates, while all RSV B isolates had 2–amino acid substitution in the suptavumab epitope that led to loss of neutralization activity. Treatment emergent adverse events were balanced across treatment groups.

Conclusions

Suptavumab did not reduce overall RSV hospitalizations or outpatient LRTI because of a newly circulating mutant strain of RSV B. Genetic variation in circulating RSV strains will continue to challenge prevention efforts.

Clinical Trials Registration

NCT02325791.
Normal Ranges of Thiopurine Methyltransferase Activity Do Not Affect Thioguanine Nucleotide Concentrations With Azathioprine Therapy in Inflammatory Bowel Disease
Authors: Jonason David E , Sievers Tyson , Trocke Lindsay , Abraham James M , Vaughn Byron P
Published: July 2020

Background

Thiopurine methyltransferase (TPMT) activity influences azathioprine conversion into active metabolite 6-thioguanine nucleotide (6-TGN). Low TPMT activity correlates with high 6-TGN and risk for myelosuppression. Conversely, normal-to-high TPMT activity may be associated with low 6-TGN and drug resistance, the so-called hypermetabolizers. Our aim was to identify the effect of normal-to-high TPMT activity on 6-TGN concentrations in an inflammatory bowel disease population.

Methods

A retrospective chart review of patients aged ≥18 with inflammatory bowel disease, on azathioprine, with documented TPMT activity and 6-TGN concentration was performed. Correlations were evaluated via the Spearman rho correlation coefficient. Linear regression was used to determine the effect of TPMT activity on 6-TGN accounting for confounders. Relationships between TPMT activity, drug dose, and 6-TGN levels were defined via average causal mediation effects.

Results

One hundred patients were included. No correlation was observed between TPMT activity, azathioprine dosing, and metabolite concentrations. Overall, 39% of the cohort had a therapeutic 6-TGN level of >230 pmol/8 × 108 red blood cells (RBCs). No patient under 1 mg/kg achieved a therapeutic 6-TGN level, whereas 42% of patients taking 2.5 mg/kg did. The median 6-TGN concentration was higher for those in remission (254 pmol/8 × 108 RBCs, interquartile range: 174, 309) versus those not in remission (177 pmol/8 × 108 RBCs, interquartile range: 94.3, 287.8), though not significantly (P = 0.08). Smoking was the only clinical factor associated with 6-TGN level. On multivariate linear regression, only age, azathioprine dose, and obese body mass index were predictive of metabolite concentration.

Conclusions

Variations within the normal range of TPMT activity do not affect 6-TGN concentration.
Gut Microbiota-driven Drug Metabolism in Inflammatory Bowel Disease
Authors: Crouwel Femke , Buiter Hans J C , de Boer Nanne K
Published: July 2020

Background and Aims

The gut microbiota plays an important role in the metabolization and modulation of several types of drugs. With this study we aimed to review the literature relating to microbial drug metabolism of medication prescribed in inflammatory bowel disease [IBD] practice.

Methods

A systematic literature search was performed in Embase and PubMed from inception to October 2019. The search was conducted with predefined MeSH/Emtree and text terms. All studies regarding drug metabolism by microbiota of medication prescribed in IBD practice were eligible. A total of 1018 records were encountered and 89 articles were selected for full text reading.

Results

Intestinal bacterial metabolism or modulation is of influence in four specific drugs used in IBD (mesalazines, methotrexate, glucocorticoids and thioguanine). The gut microbiota cleaves the azo-bond of sulfasalazine, balsalazide and olsalazine and releases the active moiety 5-aminosalicylic acid. It has an impact on the metabolization and potentially on the response of methotrexate therapy. In particular, thioguanine can be converted by intestinal bacteria into the pharmacologically active 6-thioguanine nucleotides without the requirement of host metabolism. Glucocorticoid compounds can be prone to bacterial degradation.

Conclusion

The human intestinal microbiota can have a major impact on drug metabolism and efficacy of medication prescribed in IBD practice. A better understanding of these interactions between microbiota and drugs is needed and should be an integral part of the drug development pathway of new IBD medication.
Diagnosis and treatment of atrioventricular nodal reentrant tachycardia: a case report illustrating clinical management and ablation strategy
Authors: Ector Joris , Haemers Peter , Garweg Christophe , Willems Rik
Published: July 2020

Background

Atrioventricular nodal reentrant tachycardia (AVNRT) is a common supraventricular arrhythmia that is frequently encountered in an otherwise healthy patient population. Recent guidelines of the European Society of Cardiology underline the role of catheter ablation in the long-term management of these patients.

Case summary

This case describes the clinical presentation and treatment options in a patient with typical slow/fast AVNRT, the most common subform of AVNRT, where antegrade conduction occurs over the slow pathway and retrograde conduction over the fast pathway. The ablation strategy in these patients is illustrated based on intracardiac recordings in combination with per-procedural three-dimensional imaging.

Discussion

Atrioventricular nodal reentrant tachycardia is a common arrhythmia with good prognosis but significant impact on quality of life of affected patients. Catheter ablation should be considered early as it can be performed safely and with a very high success rate.
Avoiding implant complications in cardiac implantable electronic devices: what works?
Authors: Frausing Maria Hee Jung Park , Kronborg Mads Brix , Johansen Jens Brock , Nielsen Jens Cosedis
Published: July 2020

Nearly one in ten patients experience complications in relation to cardiac implantable electronic device (CIED) implantations. CIED complications have serious implications for the patients and for the healthcare system. In light of the rising rates of new implants and consistent rate of complications, primary prevention remains a major concern. To guide future efforts, we sought to review the evidence base underlying common preventive actions made during a primary CIED implantation.
Through the Anti-Monopoly Lens: What Constitutes ‘Unfairly High Patent Pricing’ in China?
Authors: Hao Yuan
Published: July 2020

This article proposes that a patentee’s unilateral pricing of proprietary technology should be presumed legal per se under Sec. 55 IPR immunity framework provided by the Anti-Monopoly Law, unless a plaintiff overcomes all three of the following hurdles with actual evidence: (i) the patentee enjoys a dominant market position; (ii) such pricing constitutes de facto refusal to deal with or significant ‘margin squeeze’ for subsequent or follow-on innovators; and (iii) the constructive refusal or ‘margin squeeze’ would likely foreclose dynamic competition. This seemingly high evidentiary burden is justified by three cumulative resources: (i) the very patent mechanism in facilitating innovation, including a solid promise of supra-competitive profit through the right to lawfully exclude competition by imitation, and thus the instigation of a virtuous circle of dynamic competition through pivoting on the critical link of competition by substitution; (ii) the prevalent cautious attitude in sister jurisdictions when dealing with the concept; and (iii) the inevitable limitations of antitrust law, manifested in the administrative and error costs due to lack of proper information and economic analysis methodologies on dynamic efficiency. Through a detailed illustration with six specific scenarios, we see in a quasi-quantitative way that the actual likelihood of unilateral foreclosure on dynamic competition, even in the case of a monopolist patentee, is extremely low despite the existence of a theoretical possibility. Facing this meager likelihood and information deficiency, it would be unwise for a Chinese court to incur enormous costs of searching for a possibility in every case, with the mere guidance of a vague rule-of-reason framework.
Suction Feeding by Small Organisms: Performance Limits in Larval Vertebrates and Carnivorous Plants
Authors: Deban Stephen M , Holzman Roi , Müller Ulrike K
Published: July 2020

Suction feeding has evolved independently in two highly disparate animal and plant systems, aquatic vertebrates and carnivorous bladderworts. We review the suction performance of animal and plant suction feeders to explore biomechanical performance limits for aquatic feeders based on morphology and kinematics, in the context of current knowledge of suction feeding. While vertebrates have the greatest diversity and size range of suction feeders, bladderworts are the smallest and fastest known suction feeders. Body size has profound effects on aquatic organismal function, including suction feeding, particularly in the intermediate flow regime that tiny organisms can experience. A minority of tiny organisms suction feed, consistent with model predictions that generating effective suction flow is less energetically efficient and also requires more flow-rate specific power at small size. Although the speed of suction flows generally increases with body and gape size, some specialized tiny plant and animal predators generate suction flows greater than those of suction feeders 100 times larger. Bladderworts generate rapid flow via high-energy and high-power elastic recoil and suction feed for nutrients (relying on photosynthesis for energy). Small animals may be limited by available muscle energy and power, although mouth protrusion can offset the performance cost of not generating high suction pressure. We hypothesize that both the high energetic costs and high power requirements of generating rapid suction flow shape the biomechanics of small suction feeders, and that plants and animals have arrived at different solutions due in part to their different energy budgets.
Accurately computing the log-sum-exp and softmax functions
Authors: Blanchard Pierre , Higham Desmond J , Higham Nicholas J
Published: July 2020

Evaluating the log-sum-exp function or the softmax function is a key step in many modern data science algorithms, notably in inference and classification. Because of the exponentials that these functions contain, the evaluation is prone to overflow and underflow, especially in low-precision arithmetic. Software implementations commonly use alternative formulas that avoid overflow and reduce the chance of harmful underflow, employing a shift or another rewriting. Although mathematically equivalent, these variants behave differently in floating-point arithmetic and shifting can introduce subtractive cancellation. We give rounding error analyses of different evaluation algorithms and interpret the error bounds using condition numbers for the functions. We conclude, based on the analysis and numerical experiments, that the shifted formulas are of similar accuracy to the unshifted ones, so can safely be used, but that a division-free variant of softmax can suffer from loss of accuracy.
Bundle interventions including nontechnical skills for surgeons can reduce operative time and improve patient safety
Authors: Koike Daisuke , Nomura Yukihiro , Nagai Motoki , Matsunaga Takashi , Yasuda Ayuko
Published: July 2020

Objective

This study aimed to determine if introducing nontechnical skills to surgical trainees during surgical education can reduce the operation time and contribute to patient safety.

Design

Quality improvement initiatives using the KAIZEN as a problem-solving method.

Setting

Department of surgery in a referral and educational hospital.

Participants

Surgical team and quality management team.

Intervention

The KAIZEN was used as a problem-solving method between 2015 and 2018 to reduce the operation time. First, baseline measurement was performed to understand the current situations in our department. To achieve continuous improvement, periodical feedback of the current status was obtained from all staff. Bundles, including nontechnical skills, were established. Briefing and debriefing were performed by the surgical team.

Main Outcome Measures

Excessively long operation rates with a standard procedure.

Results

We included 1573 operations in this initiative. Excessively long operation rates were reduced in all types of surgeries, from 27.1% to 15.2% for herniorrhaphy (P = 0.005), 58.3–40.0% for gastrectomy (P = 0.03), 50.0–4.1% for total gastrectomy (P = 0.12), 65.6–45.0% for colectomy (P = 0.004), 67.8–43.2% for high anterior resection (P = 0.02) and 69.6–47.9% for low anterior resection (P = 0.03). The adherence to briefing and debriefing were improved, and majority of the surgeons favored the bundle elements.

Conclusions

The KAIZEN initiative was effective in clinical healthcare settings. In the event of scaling-up this initiative, the educational program for physicians should include project management strategies and leadership skills.
Lipid A profiling and metabolomics analysis of paired polymyxin-susceptible and -resistant MDR Klebsiella pneumoniae clinical isolates from the same patients before and after colistin treatment
Authors: Aye Su Mon , Galani Irene , Han Mei-Ling , Karaiskos Ilias , Creek Darren J , Zhu Yan , Lin Yu-Wei , Velkov Tony , Giamarellou Helen , Li Jian
Published: July 2020

Background

The increased incidence of polymyxin-resistant MDR Klebsiella pneumoniae has become a major global health concern.

Objectives

To characterize the lipid A profiles and metabolome differences between paired polymyxin-susceptible and -resistant MDR K. pneumoniae clinical isolates.

Methods

Three pairs of K. pneumoniae clinical isolates from the same patients were examined [ATH 7 (polymyxin B MIC 0.25 mg/L) versus ATH 8 (64 mg/L); ATH 15 (0.5 mg/L) versus ATH 16 (32 mg/L); and ATH 17 (0.5 mg/L) versus ATH 18 (64 mg/L)]. Lipid A and metabolomes were analysed using LC-MS and bioinformatic analysis was conducted.

Results

The predominant species of lipid A in all three paired isolates were hexa-acylated and 4-amino-4-deoxy-l-arabinose-modified lipid A species were detected in the three polymyxin-resistant isolates. Significant metabolic differences were evident between the paired isolates. Compared with their corresponding polymyxin-susceptible isolates, the levels of metabolites in amino sugar metabolism (UDP-N-acetyl-α-d-glucosamine and UDP-N-α-acetyl-d-mannosaminuronate) and central carbon metabolism (e.g. pentose phosphate pathway and tricarboxylic acid cycle) were significantly reduced in all polymyxin-resistant isolates [fold change (FC) > 1.5, P < 0.05]. Similarly, nucleotides, amino acids and key metabolites in glycerophospholipid metabolism, namely sn-glycerol-3-phosphate and sn-glycero-3-phosphoethanolamine, were significantly reduced across all polymyxin-resistant isolates (FC > 1.5, P < 0.05) compared with polymyxin-susceptible isolates. However, higher glycerophospholipid levels were evident in polymyxin-resistant ATH 8 and ATH 16 (FC > 1.5, P < 0.05) compared with their corresponding susceptible isolates.

Conclusions

To our knowledge, this study is the first to reveal significant metabolic perturbations associated with polymyxin resistance in K. pneumoniae.
Residual Analysis of Aflatoxins in Spice by HPLC Coupled with Solid-Phase Dispersive Extraction and Solid-Phase Fluorescence Derivatization Method
Authors: Saito Koichi , Ishii Junki , Naniwa Misaki , Ishii Rie , Kato Mihoko , Kondo Takahide , Sakurai Hikaru , Taniguchi Masaru , Hashiguchi Shigeki , Hayashi Takako , Ito Rie
Published: July 2020

Background

Aflatoxins (AFs) are carcinogenic mycotoxins. A simple, quick, and accurate method for the micro-analysis of AFs in foodstuffs, especially spices, is needed.

Objective

A sophisticated pretreatment method that combines solid-phase dispersive extraction (SPDE) and solid-phase fluorescence derivatization using immunoaffinity (IA) gel as the solid phase was developed to analyze AFs in spices simply, quickly, and sensitively by liquid chromatography with fluorescence detection.

Method

White and black pepper samples were extracted with a mixed solution of methanol/water (4:1) and then diluted with 7% aqueous solution of Triton-X. The solution was subjected to cleanup by SPDE using IA gel. Trifluoroacetic acid was added to the IA gel for on-site solid-phase fluorescence derivatization.

Results

Chromatograms containing well-separated peaks and few interference peaks from contaminants were obtained. The method detection limit of AFs in white and black pepper was 0.15–0.29 ng/g. Repeatability and intermediate precision were <10% and <15%, respectively, and accuracy was 61.7–87.8%. In addition, inter-laboratory precision was <29% and mean recovery was 61.5–76.7%. A favorable z-score of |Z| ≦ 1 was obtained in seven laboratories, although one laboratory gave 2 < |Z| < 3.

Conclusions

The validity, reliability, practicality, and robustness of the developed method were verified.

Highlights

By using SPDE and solid-phase fluorescence derivatization in combination for AF analysis, fluorescence derivatization during cleanup was realized, leading to simplification of the pretreatment operation.
Effects of bismuth subsalicylate and encapsulated calcium ammonium nitrate on ruminal fermentation of beef cattle
Authors: Henry Darren D , Ciriaco Francine M , Araujo Rafael C , Fontes Pedro L P , Oosthuizen Nicola , Mejia-Turcios Sebastian E , Garcia-Ascolani Mariana E , Rostoll-Cangiano Lautaro , Schulmeister Tessa M , Dubeux Jose C B , Lamb G Cliff , DiLorenzo Nicolas
Published: July 2020

A replicated 5 × 5 Latin square design with a 2 × 2 + 1 factorial arrangement of treatments was used to determine the effects of bismuth subsalicylate (BSS) and encapsulated calcium ammonium nitrate (eCAN) on ruminal fermentation of beef cattle consuming bahiagrass hay (Paspalum notatum) and sugarcane molasses. Ten ruminally cannulated steers (n = 8; 461 ± 148 kg of body weight [BW]; average BW ± SD) and heifers (n = 2; 337 ± 74 kg of BW) were randomly assigned to one of five treatments as follows: 1) 2.7 g/kg of BW of molasses (NCTRL), 2) NCTRL + 182 mg/kg of BW of urea (U), 3) U + 58.4 mg/kg of BW of BSS (UB), 4) NCTRL + 538 mg/kg of BW of eCAN (NIT), and 5) NIT + 58.4 mg/kg of BW of BSS (NITB). With the exception of NCTRL, all treatments were isonitrogenous. Beginning on day 14 of each period, ruminal fluid was collected and rectal temperature was recorded 4× per day for 3 d to determine ruminal changes every 2 h from 0 to 22 h post-feeding. Ruminal gas cap samples were collected at 0, 3, 6, 9, and 12 h on day 0 of each period followed by 0 h on days 1, 2, 3, and 14. Microbial N flow was determined using Cr-Ethylenediaminetetraacetic acid, YbCl3, and indigestible neutral detergent fiber for liquid, small particle, and large particle phases, respectively. Data were analyzed using the MIXED procedure of SAS. Orthogonal contrasts were used to evaluate the effects of nonprotein nitrogen (NPN) inclusion, NPN source, BSS, and NPN source × BSS. There was no treatment effect (P > 0.05) on concentrations of H2S on day 0, 1, 2, or 14; however, on day 3, concentrations of H2S were reduced (P = 0.018) when NPN was provided. No effect of treatment (P = 0.864) occurred for ruminal pH. There was an effect of NPN source on total concentrations of VFA (P = 0.011), where a 6% reduction occurred when eCAN was provided. There were effects of NPN (P = 0.001) and NPN source (P = 0.009) on the concentration of NH3-N, where cattle consuming NPN had a greater concentration than those not consuming NPN, and eCAN reduced the concentration compared with urea. Total concentrations of VFA and NH3-N were not affected (P > 0.05) by BSS. There was an effect of BSS (P = 0.009) on rectal temperature, where cattle not consuming BSS had greater temperatures than those receiving BSS. No differences for NPN, NPN source, nor BSS (P > 0.05) were observed for microbial N flow. In conclusion, eCAN does not appear to deliver equivalent ruminal fermentation parameters compared with urea, and BSS has limited effects on fermentation.
Involvement of PP2A methylation in the adipogenic differentiation of bone marrow-derived mesenchymal stem cell
Authors: Ikeda Shunta , Tsuji Shunya , Ohama Takashi , Sato Koichi
Published: July 2020

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are multipotent stem cells with ability to self-replicate and differentiate into mesodermal derivatives, such as adipocytes and osteoblasts. BM-MSCs are a critical component of the tumour microenvironment. They support tumour progression by recruiting additional BM-MSCs and by differentiating into myofibroblasts (also called cancer-associated fibroblasts). Protein phosphatase 2A (PP2A) is an essential serine/threonine protein phosphatase that regulates a broad range of cellular signalling. PP2A forms a heterotrimer to dephosphorylate specific substrates. The reversible methylesterification (methylation) of Leu309 in the catalytic subunit of PP2A (PP2Ac) regulates biogenesis of the PP2A holoenzyme. It is unknown whether the methylation of PP2Ac plays a role in BM-MSC differentiation. Our experiments determined that protein levels of PP2A subunits and PP2A methyltransferase (LCMT-1) are significantly altered during differentiation. PP2Ac methylation levels in BM-MSCs decrease over time in response to an adipogenic differentiation stimulus. However, blockage of PP2A demethylation using the PP2A dimethyl-esterase inhibitors enhanced adipocyte differentiation. This suggests that PP2Ac demethylation is involved in adipocyte differentiation resistance. The results of our study provide a greater understanding of the regulation of BM-MSCs differentiation by PP2A holoenzyme.
Gothic Secret Histories and Representing Australian Colonial Deaths at Sea: The Case of Captain Charles Wright Harris and the Wreck of the SS Admella (1859)
Authors: Anae Nicole
Published: July 2020

Extant ephemera documenting the wreck of the SS Admella off the South Australian coast on 6 August 1859 offers a compelling story of real-life maritime calamity characterized by death and extraordinary heroism. The much less written about account, however, is the story lying in between ‘official accounts’ of the wreck, and those that emerged in the contemporary reports of the day, including a body of verse termed ‘Admella poetry’. Verse forms and telegraphic reports of the wreck appear to be at odds with other witness statements, and official records have corrupted details from either telegraphic reports or published survivor statements, or both. This re-reading of one of the key heroic fatalities in the story of the wreck of the SS Admella – 37-year-old Captain Charles Wright Harris, a passenger aboard the Admella – theorizes on his death at sea as mapping plural histories. I argue that the account of the event preserved as political and bureaucratic memory – and its counterpoint – the account of the event preserved in the popular press and Admella poems, characterizes an alternative Victorian cultural memory, a gothic secret history concerning the wreck of the SS Admella and colonial deaths at sea.
Candida tropicalis RON1is required for hyphal formation, biofilm development, and virulence but is dispensable for N-acetylglucosamine catabolism
Authors: Song Yu-De , Hsu Chih-Chieh , Lew Shi Qian , Lin Ching-Hsuan
Published: July 2020

NDT80-like family genes are highly conserved across a large group of fungi, but the functions of each Ndt80 protein are diverse and have evolved differently among yeasts and pathogens. The unique NDT80 gene in budding yeast is required for sexual reproduction, whereas three NDT80-like genes, namely, NDT80, REP1, and RON1, found in Candida albicans exhibit distinct functions. Notably, it was suggested that REP1, rather than RON1, is required for N-acetylglucosamine (GlcNAc) catabolism. Although Candida tropicalis, a widely dispersed fungal pathogen in tropical and subtropical areas, is closely related to Candida albicans, its phenotypic, pathogenic and environmental adaptation characteristics are remarkably divergent. In this study, we focused on the Ron1 transcription factor in C. tropicalis. Protein alignment showed that C. tropicalis Ron1 (CtRon1) shares 39.7% identity with C. albicans Ron1 (CaRon1). Compared to the wild-type strain, the C. tropicalis ron1Δ strains exhibited normal growth in different carbon sources and had similar expression levels of several GlcNAc catabolic genes during GlcNAc treatment. In contrast, C. tropicalis REP1 is responsible for GlcNAc catabolism and is involved in GlcNAc catabolic gene expressions, similar to C. albicans Rep1. However, REP1 deletion strains in C. tropicalis promote hyphal development in GlcNAc with low glucose content. Interestingly, CtRON1, but not CaRON1, deletion mutants exhibited significantly impaired hyphal growth and biofilm formation. As expected, CtRON1 was required for full virulence. Together, the results of this study showed divergent functions of CtRon1 compared to CaRon1; CtRon1 plays a key role in yeast-hyphal dimorphism, biofilm formation and virulence.

Lay Abstract

In this study, we identified the role of RON1, an NDT80-like gene, in Candida tropicalis. Unlike the gene in Candida albicans, our studies showed that RON1 is a key regulator of hyphal formation, biofilm development and virulence but is dispensable for N-acetylglucosamine catabolism in C. tropicalis.
Propagation of weak shocks in cool-core galaxy clusters in two-temperature magnetohydrodynamics with anisotropic thermal conduction
Authors: Komarov S , Reynolds C , Churazov E
Published: July 2020

We investigate how different magnetohydrodynamic models of propagation of a weak (Mach number ∼1.2) shock in the core of a galaxy cluster affect its observational appearance, using the Perseus cluster as our fiducial model. In particular, we study how thermal conduction, both isotropic and anisotropic, and ion–electron temperature equilibration modify a weak shock. Strong thermal conduction is expected to produce an electron temperature precursor. Less prominent pressure and density precursors are formed as well. A longer equilibration time largely reduces the density precursor but does not change the electron temperature precursor much. When thermal conduction becomes anisotropic, the intracluster magnetic field imprints its characteristic spatial scale on the distortions of the shock induced by heat fluxes.
Swift/XRT, Chandra, and XMM–Newton observations of IGR J17091–3624 as it returns into quiescence
Authors: Pereyra M , Altamirano D , Court J M C , Degenaar N , Wijnands R , Parikh A S , Cúneo V A
Published: July 2020

IGR J17091–3624 is a low-mass X-ray binary (LMXB), which received wide attention from the community thanks to its similarities with the bright black hole system GRS 1915+105. Both systems exhibit a wide range of highly structured X-ray variability during outburst, with time-scales from few seconds to tens of minutes, which make them unique in the study of mass accretion in LMXBs. In this work, we present a general overview into the long-term evolution of IGR J17091–3624, using Swift/XRT observations from the onset of the 2011–2013 outburst in 2011 February till the end of the last bright outburst in 2016 November. We found four re-flares during the decay of the 2011 outburst, but no similar re-flares appear to be present in the latter one. We studied, in detail, the period with the lowest flux observed in the last 10 yr, just at the tail end of the 2011–2013 outburst, using Chandra and XMM-Newton observations. We observed changes in flux as high as a factor of 10 during this period of relative quiescence, without strong evidence of softening in the spectra. This result suggests that the source has not been observed at its true quiescence so far. By comparing the spectral properties at low luminosities of IGR J17091–3624 and those observed for a well-studied population of LMXBs, we concluded that IGR J17091–3624 is most likely to host a black hole as a compact companion rather than a neutron star.
Impact of PAH photodissociation on the formation of small hydrocarbons in the Orion Bar and the horsehead PDRs
Authors: Murga M S , Kirsanova M S , Vasyunin A I , Pavlyuchenkov Ya N
Published: July 2020

We study whether polycyclic aromatic hydrocarbons (PAHs) can be a weighty source of small hydrocarbons in photodissociation regions (PDRs). We modelled the evolution of 20 specific PAH molecules in terms of dehydrogenation and destruction of the carbon skeleton under the physical conditions of two well-studied PDRs, the Orion Bar, and the Horsehead nebula that represent prototypical examples of PDRs irradiated by ‘high’ and ‘low’ ultraviolet radiation field. PAHs are described as microcanonical systems. The acetylene molecule is considered as the main carbonaceous fragment of the PAH dissociation, as it follows from laboratory experiments and theory. We estimated the rates of acetylene production in gas phase chemical reactions and compared them with the rates of the acetylene production through the PAH dissociation. It is found that the latter rates can be higher than the former rates in the Orion Bar at AV < 1 and also at AV > 3.5. In the Horsehead nebula, the chemical reactions provide more acetylene than the PAH dissociation. The produced acetylene participate in the reactions of the formation of small hydrocarbons (C2H, C3H, C3H+, C3H2, C4H). Acetylene production via the PAH destruction may increase the abundances of small hydrocarbons produced in gas phase chemical reactions in the Orion Bar only at AV > 3.5. In the Horsehead nebula, the contribution of PAHs to the abundances of the small hydrocarbons is negligible. We conclude that the PAHs are not a major source of small hydrocarbons in both PDRs except some locations in the Orion Bar.
The stringent upper limit on jet power in the persistent soft-state source 4U 1957+11
Authors: Maccarone Thomas J , Osler Arlo , Miller-Jones James C A , Atri P , Russell David M , Meier David L , McHardy Ian M , Longa-Peña Penelope A
Published: July 2020

We present extremely deep upper limits on the radio emission from 4U 1957+11, an X-ray binary that is generally believed to be a persistently accreting black hole that is almost always in the soft state. We discuss a more comprehensive search for Type I bursts than in past work, revealing a stringent upper limit on the burst rate, bolstering the case for a black hole accretor. The lack of detection of this source at the 1.07 μJy/beam noise level indicates jet suppression that is stronger than expected even in the most extreme thin disc models for radio jet production – the radio power here is 1500–3700 times lower than the extrapolation of the hard state radio/X-ray correlation, with the uncertainties depending primarily on the poorly constrained source distance. We also discuss the location and velocity of the source and show that it must have either formed in the halo or with a strong asymmetric natal kick.
The origin of the black hole offset in M31
Authors: Boldrini Pierre
Published: July 2020

Using state-of-the-art high-resolution fully GPU N-body simulations, we demonstrate for the first time that the infall of a dark matter-rich satellite naturally explains a present black hole offset by subparsecs in M31. Observational data of the tidal features provide stringent constraints on the initial conditions of our simulations. The heating of the central region of M31 by the satellite via dynamical friction entails a significant black hole offset after the first pericentric passage. After having reached its maximum offset, the massive black hole sinks towards the M31 centre due to dynamical friction and it is determined to be offset by subparsecs as derived by observations.
Predicting Postoperative Outcomes in Brain Tumor Patients With a 5-Factor Modified Frailty Index
Authors: Huq Sakibul , Khalafallah Adham M , Jimenez Adrian E , Gami Abhishek , Lam Shravika , Ruiz-Cardozo Miguel A , Oliveira Leonardo A P , Mukherjee Debraj
Published: July 2020

BACKGROUND

Frailty indices may represent useful decision support tools to optimize modifiable drivers of quality and cost in neurosurgical care. However, classic indices are cumbersome to calculate and frequently require unavailable data. Recently, a more lean 5-factor modified frailty index (mFI-5) was introduced, but it has not yet been rigorously applied to brain tumor patients.

OBJECTIVE

To investigate the predictive value of the mFI-5 on length of stay (LOS), complications, and charges in surgical brain tumor patients.

METHODS

We retrospectively reviewed data for brain tumor patients who underwent primary surgery from 2017 to 2018. Bivariate (ANOVA) and multivariate (logistic and linear regression) analyses assessed the predictive power of the mFI-5 on postoperative outcomes.

RESULTS

Our cohort included 1692 patients with a mean age of 55.5 yr and mFI-5 of 0.80. Mean intensive care unit (ICU) and total LOS were 1.69 and 5.24 d, respectively. Mean pulmonary embolism (PE)/deep vein thrombosis (DVT), physiological/metabolic derangement, respiratory failure, and sepsis rates were 7.2%, 1.1%, 1.6%, and 1.7%, respectively. Mean total charges were $42 331. On multivariate analysis, each additional point on the mFI-5 was associated with a 0.32- and 1.38-d increase in ICU and total LOS, respectively; increased odds of PE/DVT (odds ratio (OR): 1.50), physiological/metabolic derangement (OR: 3.66), respiratory failure (OR: 1.55), and sepsis (OR: 2.12); and an increase in total charges of $5846.

CONCLUSION

The mFI-5 is a pragmatic and actionable tool which predicts LOS, complications, and charges in brain tumor patients. It may guide future efforts to risk-stratify patients with subsequent impact on postoperative outcomes.
Influence of restoration age on egg bank richness and composition: an ex situ experiment
Authors: Olmo Carla , Antón-Pardo MarÍa , Ortells Raquel , Armengol Xavier
Published: July 2020

Zooplankton community assembly after flooding in temporary ponds depends mostly on abundance and diversity of the dormant propagule bank. However, our understanding of the hatching patterns of zooplankton is imperfect. We performed an ex situ experiment to study the species composition and temporal sequence of zooplankton emergence from sediments in three ponds that were restored at different times: 1998, 2003 and 2007. The patterns of species hatching observed in our microcosms were compared with the emergent zooplankton community of their equivalent, synchronically inundated ponds. An escalation in species richness and a delay in hatching time were detected with increasing restoration age. In addition, some discrepancies between the egg bank and active populations were observed, especially in the oldest pond. This study illustrates the use of hatching experiments in comparing ponds with different characteristics. Nevertheless, egg bank hatching and water column sampling should complement each other in order to afford a full reflection of past diversity and contribute to a better understanding of the efficiency of restoration practices.
The impact of COVID-19 on Bangladeshi readymade garment (RMG) workers
Authors: Kabir Humayun , Maple Myfanwy , Usher Kim
Published: July 2020

This paper describes the potential impact of the coronavirus disease 2019 (COVID-19) pandemic on the readymade garment (RMG) workers of Bangladesh. It articulates the RMG workers’ existing vulnerability during the COVID-19 pandemic based on currently available evidence and personal conversations/communications with RMG workers. COVID-19 has already impacted RMG workers’ health (both physical and mental health status) and wellbeing, and resulted in loss of employment. We argue that the COVID-19 pandemic will have long-lasting effects on the garment workers, especially related to their health issues, financial hardship and inability to pay for essentials such as food, and future employment opportunities. The stakeholders (such as the international retailers/brands, Bangladesh Garment Manufacturers and Exporters Association, Government of Bangladesh) responsible for the global supply chain RMG factories should reconsider the health and overall wellbeing needs of the RMG workers during the ongoing COVID-19 pandemic.
A BESSEL DELTA METHOD AND EXPONENTIAL SUMS FOR GL(2)
Authors: Aggarwal Keshav , Holowinsky Roman , Lin Yongxiao , Qi Zhi
Published: July 2020

In this paper, we introduce a simple Bessel $\delta $-method to the theory of exponential sums for $\textrm{GL}_2$. Some results of Jutila on exponential sums are generalized in a less technical manner to holomorphic newforms of arbitrary level and nebentypus. In particular, this gives a short proof for the Weyl-type subconvex bound in the $t$-aspect for the associated $L$-functions.
Quantitative Trait Loci Mapping for Spot Blotch Resistance in Two Biparental Mapping Populations of Bread Wheat
Authors: He Xinyao , Dreisigacker Susanne , Sansaloni Carolina , Duveiller Etienne , Singh Ravi P. , Singh Pawan K.
Published: July 2020

Spot blotch (SB), caused by Bipolaris sorokiniana, is a major fungal disease of wheat in South Asia and South America. Two biparental mapping populations with 232 F2:7 progenies each were generated, with CIMMYT breeding lines CASCABEL and KATH as resistant parents and CIANO T79 as the common susceptible parent. The two populations were evaluated for field SB resistance in CIMMYT’s Agua Fria station for three consecutive cropping seasons, with artificial inoculation. Genotyping was done with the DArTseq platform and approximately 1,500 high quality and nonredundant markers were used for quantitative trait loci (QTL) mapping. In both populations, a major QTL was found on chromosome 5A in the Vrn-A1 region, explaining phenotypic variations of 13.5 to 25.9%, which turned up to be less- or nonsignificant when days to heading and plant height were used as covariates in the analysis, implying a disease escape mechanism. Another major QTL was located on chromosome 5B in CASCABEL, accounting for 8.9 to 21.4% of phenotypic variation. Minor QTL were found on 4A and 4B in CASCABEL; 1B, 4B, and 4D in KATH; and 1B, 2B, and 4B in CIANO T79. Through an analysis of QTL projection onto the IWGSC Chinese Spring reference genome, the 5B QTL in CASCABEL was mapped in the Sb2 region, delimited by the single nucleotide polymorphism marker wsnp_Ku_c50354_55979952 and the simple sequence repeat marker gwm213, with a physical distance of about 14 Mb to the Tsn1 locus.
Proximal Femoral Shortening and Varus Collapse After Fixation of “Stable” Pertrochanteric Femur Fractures
Authors: Ciufo David J. , Ketz John P.
Published: July 2020

Objectives:

To evaluate and compare femoral neck shortening and varus collapse in stable pertrochanteric femur fractures treated with sliding hip screws (SHSs) or cephalomedullary nails (CMNs).

Design:

Retrospective review.

Setting:

Academic medical center.

Patients:

A total of 290 patients were included in the study. The average age was 82 years, and most were women. All sustained low-energy pertrochanteric femur fractures (OTA/AO A1.1, 1.2, 1.3, 2.2) treated operatively with SHSs or CMNs. Minimum radiographic follow-up was 3 months, with an average of 28 (range 3–162) months.

Intervention:

CMN or SHS fixation.

Main Outcome Measures:

Varus collapse of the femoral neck-shaft angle and proximal femoral shortening.

Results:

Both implants allowed some varus collapse. Univariate analysis demonstrated a significantly greater portion of patients with SHSs progressed to varus collapse >5 degrees (P = 0.02), mild horizontal shortening >5 mm (P < 0.01), and severe horizontal shortening >10 mm (P < 0.01). There was no statistical difference in vertical shortening (P = 0.3). There was no difference in implant failure (P = 0.5), with failure rates of 3% for cephalomedullary implants and 5% for SHS constructs.

Conclusions:

The SHS group experienced greater varus collapse and horizontal shortening. There was no difference in overall implant failure. These findings suggest that the CMN is a superior construct for maintenance of reduction in stable pertrochanteric fractures, which may lead to improved functional outcomes as patients recover.

Level of Evidence:

Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
Efficacy of a Novel Ophthalmic Antimicrobial Drug Combination Toward a Large Panel of Staphylococcus aureus Clinical Ocular Isolates From Around the World
Authors: Laskey Emily , Chen Yimin , Sohn Michael B. , Gruber Emma , Chojnacki Michaelle , Wozniak Rachel A. F.
Published: July 2020

Purpose:

Staphylococcus aureus is a leading cause of keratitis requiring urgent antimicrobial treatment. However, rising antibiotic resistance has rendered current ophthalmic antibiotics increasingly ineffective. First, a diverse, ocular S. aureus strain set was evaluated for resistance to 6 commonly used ophthalmic antibiotics. Next, a recently discovered antimicrobial drug combination containing polymyxin B/trimethoprim (PT) + rifampin that displayed impressive efficacy toward S. aureus in both in vitro and in vivo studies was evaluated as a potential novel keratitis therapeutic through testing this combination's efficacy against the clinical strain set.

Methods:

A total of 163 S. aureus isolates were collected either commercially or from the Flaum Eye Institute, University of Rochester. The minimum inhibitory concentrations of moxifloxacin, levofloxacin, vancomycin, erythromycin, tobramycin, rifampin, and PT were determined for the entire strain set to establish the incidence of resistance to current treatment options among a contemporary clinical isolate set and compared with the performance of PT + rifampin.

Results:

Among all 163 isolates tested, high rates of antibiotic resistance were found toward erythromycin (69% resistance), moxifloxacin (33%), levofloxacin (40%), and tobramycin (17%). Conversely, the entire strain set, including multidrug resistant isolates, was sensitive to PT + rifampin, demonstrating the potency of this combination.

Conclusions:

We established that antibiotic resistance is pervasive among clinical S. aureus isolates, underscoring the concern for the effectiveness of current ophthalmic antibiotics. The drug combination of PT + rifampin, however, eradicated 100% of isolates tested, demonstrating the ability to overcome existing circulating resistance factors, and as such, might represent a promising therapeutic for S. aureus keratitis.
Facing SARS-CoV-2 Pandemic at a COVID-19 Regional Children’s Hospital in Italy
Authors: Ciofi degli Atti Marta Luisa , Campana Andrea , Muda Andrea Onetti , Concato Carlo , Ravà Lucilla , Ricotta Lara , Reale Antonino , Barbieri Maria , D’Argenio Patrizia , Lancella Laura , Villani Alberto , Raponi Massimiliano
Published: July 2020

Background:

In Italy, the response to coronavirus disease 2019 (COVID-19) pandemic upgraded from social distancing on February 23, 2020, to national lockdown on March 11, 2020. We described how the pandemic affected a tertiary care children hospital with a dedicated COVID-19 regional center.

Methods:

We analyzed the characteristics of emergency department (ED) visits, urgent hospitalizations and severe acute respiratory syndrome (SARS)-COV-2 reverse transcription-polymerase chain reaction testing, and COVID-19 patients across 3 response phases: before the first Italian case, before national lockdown and during lockdown.

Results:

ED visits decreased from a daily mean of 239.1 before the first COVID-19 Italian case, to 79.6 during lockdown; urgent hospitalizations decreased from 30.6 to 21.2. As of April 20, 2020, 1970 persons were tested for SARS-CoV-2 reverse transcription-polymerase chain reaction and 2.6% were positive. Positive rates were 1.2% in the ED, 21.1% in the COVID center and 0.5% in other wards. The median age of COVID-19 patients (N = 33) was 6.7 years, 27% had coexisting conditions and 79% were related to family clusters.

Conclusions:

The pandemic strongly impacted on the use of hospital services, with a 67% reduction in ED visits and a 31% reduction in urgent hospitalizations. Separating the flows of suspected patients from all other patients, and centralization of suspected and confirmed cases in the COVID center enabled to control the risk of nosocomial SARS-CoV-2 transmission. Delay in hospital use for urgent care must be avoided, and clear communication on infection prevention and control must be provided to families. Further studies are needed to assess how the reduction in hospital use affected children healthcare needs during the pandemic.