bluuebunny/crossref_metadata_2025 huggingface dataset:
Understanding the dopability of p-type Mg2(Si,Sn) by relating hybrid-density functional calculation results to experimental data
Authors: Kamila Hasbuna , Ryu Byungki , Ayachi Sahar , Sankhla Aryan , Mueller Eckhard , de Boor Johannes
Published: April 2022

It is crucial to reach a sufficiently high carrier concentration in order to optimize the thermoelectric (TE) material in the development of Mg2X(X= Si, Ge, and Sn)-based TE generators. While n-type Mg2(Si,Sn) has excellent TE properties, p-type shows suboptimal TE performance because of insufficient carrier concentration, in particular for Mg2Si and Si-rich Mg2(Si,Sn). A systematic investigation of Li-doped Mg2Si1-xSnxhas been performed as Li, in contrast to other typical dopants, has a high solubility in the material system and has been shown to yield the highest reported carrier concentrations. We observe that the carrier concentration increases with Li content, but the dopant efficiency decreases. With respect to the Si:Sn ratio, we find a clear increase in maximum achievable carrier concentration and dopant efficiency with increasing Sn content. The trends can be understood by employing defect formation energies obtained within the hybrid-density functional theory (DFT) for the binaries. Further, we use a linear interpolation of the hybrid-DFT results from the binaries to the ternary Mg2(Si,Sn) compositions and a simple single parabolic band model to predict the maximal achievable carrier concentration for the solid solutions, providing a simple guideline for experimental work. Finally, we show that the approach is transferable to other material classes. This work highlights that, besides dopant solubility, the interplay between intrinsic and extrinsic defects determines the achievable carrier concentration.
Equivalent pin-forces or equivalent moments for the modelling of piezoelectric patches: a parametric study
Authors: Ajnada Taha , Corcolle Romain , Bernard Yves , Daniel Laurent
Published: April 2022

Many piezoelectric (PZ) actuation or sensing systems consist of PZ patches bonded on elastic beams or blades. In order to optimise the design of such systems, Finite Element Analysis (FEA) can be used. However, this option is relatively time consuming and not necessarily appropriate to the first steps of the design process. The replacement of FEA by simple analytical tools is desirable in the early design stages in order to explore the optimal configurations for the device (beam dimensions, patch position and properties). Two main modelling approaches can be found in the literature, based on the Solid Mechanics beam theory. The first approach consists in replacing the PZ patch by two opposite forces positioned at the surface of the beam, each at one extremity of the PZ patch. The second approach consists in replacing the PZ patch by two opposite moments positioned at the neutral axis of the beam, each at one extremity of the PZ patch. The object of this paper is to detail these options, and to evaluate their range of validity. For this purpose, a parametric study is conducted on a cantilever beam structure to compare the different approaches for standard dimensions and material properties. The results of corresponding FEA simulations are taken as reference. It is shown that the validity of analytical models is restricted to a narrow range of material properties and dimensions. This range is chosen when the error between the normalised displacements obtained analytically and those obtained by numerical calculation does not exceed 6%. Within this range, the two-moment model is revealed a more precise choice than two pin-forces. As a consequence, its validity range is larger compared to other analytical approaches. This is due to the introduction of the flexural stiffness of the PZ patch and of a realistic strain profile across the section of the structure. These results can be used to obtain analytical expressions of stress and strains in PZ actuation and sensing devices.
Polygamy: A Very Short Introduction
Authors: Pearsall Sarah M. S.
Published: April 2022

Polygamy: A Very Short Introduction offers a broad global and temporal history of polygamy and its importance in a range of settings. Polygamy, or plural marriage, has been an accepted form of union in the majority of human societies. People living on every continent have practiced this form of marriage; some still do. Plural marriages, like more recent same-sex marriages, offer intriguing access to the workings of the institution of marriage, as well as the controversies linking public and private, sex and politics, that have surrounded it. Confrontations over this type of marriage have also been historically important, especially in a range of colonial, imperial, and missionary encounters. Polygamy has come to symbolize a problematic, even “barbaric,” form of marriage. Yet, even amid Christians, it has had notable defenders, including a number of radical Protestants such as Martin Luther, John Milton, and, of course, Joseph Smith. This book illuminates the public importance of the intimate, considering issues of cultural contact and confrontation, the shape of empires, slavery and hierarchy, royal and aristocratic power, religion and conflict, war and expansion, race and nation.
Introduction
Authors: Pearsall Sarah M. S.
Published: April 2022

‘Introduction’ offers an introduction to the topic of polygamy by considering the usual stereotypes of polygamy, centering on the Church of Jesus Christ of Latter-day Saints (Mormons) and the harem of the Ottoman Turks, arguing that polygamy has a much richer and fuller history than these images suggest. Key terms such as polygamy, polygyny, polyandry, and marriage need a definition in order to fully appreciate this topic, as do key themes, including gender, the relations between women and men, and the relations between women and between men. Another theme is sex and reproduction. Labor and slavery, especially the role of women in domestic work, as well as rank and status, are also themes that inform this topic. Finally, an important element to consider is the clash of religion and culture and a consideration of race and ideas of progress.
Origins and overview
Authors: Pearsall Sarah M. S.
Published: April 2022

‘Origins and overthrows’ considers the origins of polygamy and its representation in the book of Genesis in the Hebrew Bible, telling the story of Abraham, Sarah, and Hagar, who were involved in a plural union. The issues of fruitfulness and population growth have animated many practices of polygamy. It is worth considering a range of geographical settings and the ubiquity of polygamy around the world. Polygamy was a vital political aspect of the Incan Empire in what is now Peru, as well as the Siamese kingdom in what is now Thailand and the kingdom of Buganda in eastern Africa. Concubinage systems in places such as China also receive attention, as does the practice of polygamy among indigenous Americans, Māori, and Aboriginal people as well as medieval Europeans, including the Irish.
Contemporary debates
Authors: Pearsall Sarah M. S.
Published: April 2022

‘Contemporary debates’ opens with a government raid on the residents of the Arizona town of Short Creek in 1953. They were practicing polygamy as members of the Fundamentalist Church of Jesus Christ of Latter-day Saints, an organization that had separated from the Mormon Church over their continued devotion to polygamy. In many such situations, the revival of so-called traditional polygamy has been connected with religious fundamentalism and limits on women’s public participation, as is also the case among some Muslims in Saudi Arabia. Yet there have also been “campaigns for monogamy” among Muslims in places like Malaysia. At the same time, there has been pressure on monogamy from US left-wing critics, who question married monogamy as the correct or only path for domestic organization. There is a liberal, even libertarian, celebration of “poly,” especially polyamory, in Western liberal democracies.
Impact of Ergonomic Posture on the Chemical Exposure of Workers in the Petroleum and Chemical Industry
Authors: Whitehead Carson , Maier M Andrew , Rao Marepalli B , Eturki Mohamed , Snawder John E , Davis Kermit G
Published: April 2022

Objectives

Despite a rise in automation, workers in the petroleum refining and petrochemical manufacturing industry are potentially exposed to various chemicals through inhalation while performing routine job duties. Many factors contribute to the degree of exposure experienced in this setting. The study objective was to characterize the impact of workplace conditions, anthropometric variability, and task orientation on exposure for a simulated routine operations task.

Methods

A chemical exposure laboratory simulation study was designed to evaluate the dependent variable of chemical exposure level in the breathing zone for methane and sulfur hexafluoride. The independent variables were (i) posture of the worker, (ii) worker anthropometry, (iii) process configuration, and (iv) gas density.

Results

Pipe height was a significant predictor of gas concentration measured in the breathing zone when located in a position that encouraged the gas to enter the breathing zone of the worker. Worker anthropometry had a major impact; tall worker’s (male) chemical concentrations exceeded those of the short worker (female) for methane simulations but the opposite resulted for sulfur hexafluoride. Also, worker posture had a significant impact on gas exposure where nonneutral postures were found to have higher levels of chemical concentration.

Conclusions

The study findings indicate that the breathing zone location is altered by posture and worker height, which changes the exposures relative to the emission source depending on the gas density of the chemicals that are present. As a result, qualitative risk assessment cannot be performed accurately without accounting for these factors. Practically, controls may need to account for worker size differences and posture adaptations.
Oligoribonucleotide interference-PCR: principles and applications
Authors: Shimizu Takeshi , Fujita Toshitsugu , Fujii Hodaka
Published: April 2022

Polymerase chain reaction (PCR) amplification of multiple templates using common primers is used widely for molecular biological research and clinical diagnosis. However, amplifying a specific DNA sequence harboring a mutation that is present in a small number of mutant cells within a large population of normal cells (e.g., as in cancer) in a tissue is difficult using the original PCR protocol. Thus, some measures are necessary to suppress amplification of background signals. To achieve this, we developed the oligoribonucleotide (ORN) interference-PCR (ORNi-PCR) technology in which an ORN (short RNA) hybridizes with a complementary DNA sequence to inhibit PCR amplification across the specific target sequence. ORNs can be prepared inexpensively, and ORNi-PCR can be carried out easily by adding ORNs to the PCR reaction mixture. Suppressing amplification of target sequences by ORNi-PCR is useful for detecting target sequence mutations. We showed that ORNi-PCR can discriminate single-nucleotide mutations in cancer cells and indel mutations introduced by genome editing. We also showed that ORNi-PCR can identify the CpG methylation status of a target sequence within bisulfite-treated DNA, and can enrich DNA sequences of interest from a DNA mixture by suppressing amplification of unwanted sequences. Thus, ORNi-PCR has many potential applications in various fields, including medical diagnosis and molecular biology. In this review, we outline the principles of the ORNi-PCR method and its use to detect nucleotide mutations in a variety of specimens.
Favipiravir for Treatment of Outpatients With Asymptomatic or Uncomplicated Coronavirus Disease 2019: A Double-Blind, Randomized, Placebo-Controlled, Phase 2 Trial
Authors: Holubar Marisa , Subramanian Aruna , Purington Natasha , Hedlin Haley , Bunning Bryan , Walter Katharine S , Bonilla Hector , Boumis Athanasia , Chen Michael , Clinton Kimberly , Dewhurst Liisa , Epstein Carol , Jagannathan Prasanna , Kaszynski Richard H , Panu Lori , Parsonnet Julie , Ponder Elizabeth L , Quintero Orlando , Sefton Elizabeth , Singh Upinder , Soberanis Luke , Truong Henry , Andrews Jason R , Desai Manisha , Khosla Chaitan , Maldonado Yvonne
Published: April 2022

Background

Favipiravir, an oral, RNA-dependent RNA polymerase inhibitor, has in vitro activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite limited data, favipiravir is administered to patients with coronavirus disease 2019 (COVID-19) in several countries.

Methods

We conducted a phase 2, double-blind, randomized controlled outpatient trial of favipiravir in asymptomatic or mildly symptomatic adults with a positive SARS-CoV-2 reverse-transcription polymerase chain reaction assay (RT-PCR) within 72 hours of enrollment. Participants were randomized to receive placebo or favipiravir (1800 mg twice daily [BID] day 1, 800 mg BID days 2–10). The primary outcome was SARS-CoV-2 shedding cessation in a modified intention-to-treat (mITT) cohort of participants with positive enrollment RT-PCRs. Using SARS-CoV-2 amplicon-based sequencing, we assessed favipiravir’s impact on mutagenesis.

Results

We randomized 149 participants with 116 included in the mITT cohort. The participants’ mean age was 43 years (standard deviation, 12.5 years) and 57 (49%) were women. We found no difference in time to shedding cessation overall (hazard ratio [HR], 0.76 favoring placebo [95% confidence interval {CI}, .48–1.20]) or in subgroups (age, sex, high-risk comorbidities, seropositivity, or symptom duration at enrollment). We detected no difference in time to symptom resolution (initial: HR, 0.84 [95% CI, .54–1.29]; sustained: HR, 0.87 [95% CI, .52–1.45]) and no difference in transition mutation accumulation in the viral genome during treatment.

Conclusions

Our data do not support favipiravir at commonly used doses in outpatients with uncomplicated COVID-19. Further research is needed to ascertain if higher favipiravir doses are effective and safe for patients with COVID-19.

Clinical Trials Registration

NCT04346628.
Relationship between ischaemia, coronary artery calcium scores, and major adverse cardiovascular events
Authors: Miller Robert J H , Han Donghee , Singh Ananya , Pieszko Konrad , Slomka Piotr J , Gransar Heidi , Park Rebekah , Otaki Yuka , Friedman John D , Hayes Sean , Thomson Louise , Rozanski Alan , Berman Daniel S
Published: April 2022

Aims

Positron emission tomography (PET) myocardial perfusion imaging (MPI) is often combined with coronary artery calcium (CAC) scanning, allowing for a combined anatomic and functional assessment. We evaluated the independent prognostic value of quantitative assessment of myocardial perfusion and CAC scores in patients undergoing PET.

Methods and results

Consecutive patients who underwent Rb-82 PET with CAC scoring between 2010 and 2018, with follow-up for major adverse cardiovascular events (MACE), were identified. Perfusion was quantified automatically with total perfusion deficit (TPD). Our primary outcome was MACE including all-cause mortality, myocardial infarction (MI), admission for unstable angina, and late revascularization. Associations with MACE were assessed using multivariable Cox models adjusted for age, sex, medical history, and MPI findings including myocardial flow reserve.

In total, 2507 patients were included with median age 70. During median follow-up of 3.9 years (interquartile range 2.1–6.1), 594 patients experienced at least one MACE. Increasing CAC and ischaemic TPD were associated with increased MACE, with the highest risk associated with CAC > 1000 [adjusted hazard ratio (HR) 1.67, 95% CI 1.24–2.26] and ischaemic TPD > 10% (adjusted HR 1.80, 95% CI 1.40–2.32). Ischaemic TPD and CAC improved overall patient classification, but ischaemic TPD improved classification of patients who experienced MACE while CAC mostly improved classification of low-risk patients.

Conclusions

Ischaemic TPD and CAC were independently associated with MACE. Combining extent of atherosclerosis and functional measures improves the prediction of MACE risk, with CAC 0 identifying low-risk patients and regional ischaemia identifying high-risk patients in those with CAC > 0.
The AAV-PCSK9 murine model of atherosclerosis and metabolic dysfunction
Authors: Keeter William Coles , Carter Nigeste M , Nadler Jerry L , Galkina Elena V
Published: April 2022

Aims

Mouse models with genetic modifications are required to investigate atherogenesis and associated metabolic syndrome. Adeno-associated virus-8 (AAV8)-mediated overexpression of PCSK9 (AAV8-PCSK9) induces hyperlipidaemia and promotes atherosclerosis in C57BL/6 mice. We aimed to assess whether AAV8-PCSK9-injected C57BL/6 mice fed high-fat diet with added cholesterol (HFD-C) would serve as a model of combined metabolic syndrome and atherosclerosis.

Methods and results

C57BL/6 mice received i.v. injection of AAV-PCSK9 and sex- and age-matched Ldlr−/− and C57BL/6 control mice were placed on HFD-C or chow diet for 20 weeks (B6-PCSK9-HFD-C, Ldlr−/− HFD-C, B6-HFD-C, and B6-Chow, respectively). High-fat diet with added cholesterol feeding led to insulin resistance and impaired glucose clearance in B6-PCSK9-HFD-C mice compared with B6-Chow controls. This decrease in metabolic health in B6-PCSK9-HFD-C mice as well as the development of atherosclerosis was similar to Ldlr−/− HFD-C mice. Importantly, HFD-C feeding induced pancreatic islet hyperplasia in B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls. In line with alterations in the metabolic phenotype, there was an increase in the number of pro-inflammatory Ly6Chigh/med monocytes within the adipose tissues of B6-PCSK9-HFD-C and B6-HFD-C compared with B6-Chow controls.

Conclusion

High-fat diet with added cholesterol-fed AAV-PCSK9-injected C57BL/6 mice can serve as a useful model of integrated metabolic syndrome and atherosclerosis that does not require genetic manipulations.
Factors associated with excess female mortality in obstructive hypertrophic cardiomyopathy
Authors: Javidgonbadi Davood , Schaufelberger Maria , Östman-Smith Ingegerd
Published: April 2022

Background

Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown.

Aims

To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM).

Methods and results

Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P < 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = <0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048).

Conclusion

Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.
Invasive candidiasis in Africa, what is the current picture?
Authors: Okoye Chinonyelum A , Nweze Emeka , Ibe Chibuike
Published: April 2022

Invasive candidiasis is a serious, progressive, and potentially deadly infection that can affect the brain, heart, bones, eyes, and other parts of the body. It is associated with risk factors such as the use of indwelling medical devices, prolonged hospital stay, and broad-spectrum antibiotics use. It is especially seen in immunocompromised individuals such as patients with prolonged hospital stay, gastrointestinal surgery, haematological malignancies, and respiratory diseases. We have conducted a systematic search of literature using a select group of databases and appropriate search words and found that in Africa, there are 18 293 documented/reported cases of invasive candidiasis in the last few decades (1976–2021) and 16 636(91%) were cases of candidaemia. South Africa had the highest number of reported cases—15 002(82%), which may be due to underreporting of cases in other countries. HIV positive persons with invasive candidiasis in Africa accounted for 1 052(5.8%). Candida albicans was the most frequently isolated species 6 328(32.6%), followed by Candida parapsilosis 5 910(30.4%), and Candida auris 1 505(7.8%). Due to the affordability and availability of blood culture, it was used for diagnosis in most of the studies examined, while a few studies combined other techniques and just three studies from two countries used serological tests. Echinocandins are recommended as first-line therapy but are only available in 12 countries and are highly priced. The use of fluconazole, because of its availability and relatively inexpensive nature, has led to increased resistance of Candida species to the drug.
A Polynesian-specific copy number variant encompassing the MICA gene associates with gout
Authors: Wang Ke , Cadzow Murray , Bixley Matt , Leask Megan P , Merriman Marilyn E , Yang Qiangzhen , Li Zhiqiang , Takei Riku , Phipps-Green Amanda , Major Tanya J , Topless Ruth , Dalbeth Nicola , King Frances , Murphy Rinki , Stamp Lisa K , de Zoysa Janak , Wang Zhuo , Shi Yongyong , Merriman Tony R
Published: April 2022

Gout is of particularly high prevalence in the Māori and Pacific (Polynesian) populations of Aotearoa New Zealand (NZ). Here, we investigated the contribution of common population-specific copy number variation (CNV) to gout in the Aotearoa NZ Polynesian population. Microarray-generated genome-wide genotype data from Aotearoa NZ Polynesian individuals with (n = 1196) and without (n = 1249) gout were analyzed. Comparator population groups were 552 individuals of European ancestry and 1962 of Han Chinese ancestry. Levels of circulating major histocompatibility complex (MHC) class I polypeptide-related sequence A (MICA) were measured by enzyme-linked immunosorbent assay. Fifty-four CNV regions (CNVRs) appearing in at least 10 individuals were detected, of which seven common (>2%) CNVRs were specific to or amplified in Polynesian people. A burden test of these seven revealed associations of insertion/deletion with gout (odds ratio (OR) 95% confidence interval [CI] = 1.80 [1.01; 3.22], P = 0.046). Individually testing of the seven CNVRs for association with gout revealed nominal association of CNVR1 with gout in Western Polynesian (Chr6: 31.36–31.45 Mb, OR = 1.72 [1.03; 2.92], P = 0.04), CNVR6 in the meta-analyzed Polynesian sample sets (Chr1: 196.75–196.92 Mb, OR = 1.86 [1.16; 3.00], P = 0.01) and CNVR9 in Western Polynesian (Chr1: 189.35–189.54 Mb, OR = 2.75 [1.15; 7.13], P = 0.03). Analysis of European gout genetic association data demonstrated a signal of association at the CNVR1 locus that was an expression quantitative trait locus for MICA. The most common CNVR (CNVR1) includes deletion of the MICA gene, encoding an immunomodulatory protein. Expression of MICA was reduced in the serum of individuals with the deletion. In summary, we provide evidence for the association of CNVR1 containing MICA with gout in Polynesian people, implicating class I MHC-mediated antigen presentation in gout.
Real-world Short-term Effectiveness of Ustekinumab in Crohn’s Disease: Results from a Multicenter, Prospective Study in China
Authors: Cao Qian , Chen Chunxiao , Gao Xiang , Chen Yan , Hu Naizhong , Liang Jie , Wu Kaichun
Published: April 2022

Lay Summary

Ustekinumab effectively induced a clinical response and clinical remission, with remission rates superior to those in the UNITI-1 study. Ustekinumab is more effective in biologic-naive patients with Crohn’s disease than those who were not responsive to anti–tumor necrosis factor treatment.
Network Clinical Collaboration to Improve Quality of Care of Patients With Inflammatory Bowel Disease in China
Authors: Mao Ren , Chien Ng Siew , Chen Minhu
Published: April 2022

Lay Summary

The burden of IBD management in China is increasing due to the mounting number of patients. We presented in the 2021 China IBD Special Issue a series of original articles, which will be important for encouraging and inspiring more network collaboration to improve quality of care of patients with IBD in China.
Guidelines for Discontinuation of Antipsychotics in Patients Who Recover From First-Episode Schizophrenia Spectrum Disorders: Derived From the Aggregated Opinions of Asian Network of Early Psychosis Experts and Literature Review
Authors:   Asian Network of Early Psychosis Writing Group, Hui Christy L M , Chen Eric Y H , Swapna Verma , Tagata Hiromi , Mizuno Masafumi , Liu Chen‑Chung , Takeuchi Hiroyoshi , Kim Sung-Wan , Chung Young-Chul
Published: April 2022

Objective

Antipsychotic discontinuation has been a long-standing clinical and medicolegal issue. The Asian Network of Early Psychosis developed guidelines for antipsychotic discontinuation in patients who recover from first-episode non-affective psychosis. We reviewed the existing studies and guidelines on antipsychotic discontinuation to develop guidelines for antipsychotic discontinuation in such patients.

Methods

We reviewed the relevant studies, reviews, guidelines, and ongoing trials related to antipsychotic discontinuation in patients with first-episode psychosis or schizophrenia. The quality of randomized controlled trials was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Results

Most studies had low to very low quality, and 2 had moderate quality. All studies, except 1, advised against antipsychotic discontinuation because of higher relapse rates in the antipsychotic discontinuation group (19%–82% at 1-year follow-up) than the treatment maintenance group compared with the maintenance group. Based on expert opinion and Grading of Recommendations Assessment, Development, and Evaluation evidence of trials, guidelines have been recommended for future discontinuation studies on patients with first-episode schizophrenia spectrum disorders.

Conclusions

Currently, there are no recommendations for antipsychotic discontinuation in patients with first-episode schizophrenia spectrum disorders. However, there is a pressing need to conduct more rigorous research in remitted patients using more stringent criteria of full recovery, which can form the basis of guidelines on when and how antipsychotics should be tapered and discontinued. Studies that evaluate the patient characteristics and biomarkers that predict successful antipsychotic discontinuation are also needed.
Antibiotic susceptibility patterns of viridans group streptococci isolates in the United States from 2010 to 2020
Authors: Singh Nidhi , Poggensee Linda , Huang Yanqin , Evans Charlesnika T. , Suda Katie J. , Bulman Zackery P.
Published: April 2022

Background

Viridans group streptococci (VGS) are typically part of the commensal flora but can also cause severe invasive diseases such as infective endocarditis. There are limited data available showing antibiotic susceptibility over time for VGS.

Objectives

To evaluate antibiotic susceptibility trends in VGS over time.

Methods

In vitro susceptibility patterns for 33 antibiotics were examined for Streptococcus mitis, Streptococcus oralis, and non-speciated VGS isolates from patients in Veterans Affairs (VA) Medical Centers in the United States between 2010 and 2020. Susceptibility determinations were made by the individual clinical microbiology laboratories and data were retrospectively collected from the VA Corporate Data Warehouse. Susceptibility trends were analysed using Poisson regression.

Results

A total of 14 981 VGS isolates were included of which 19.5%, 0.7% and 79.8% were S. mitis, S. oralis and non-speciated VGS isolates, respectively. Cumulative susceptibility rates across all years were similar between species for ceftriaxone (range: 96.0% to 100%), clindamycin (81.3% to 84.5%), and vancomycin (99.7% to 100%). For penicillin, susceptibility rates were 71.0%, 80.9% and 86.3% for S. mitis, S. oralis and non-speciated isolates, respectively. From 2010 to 2020, susceptibility of non-speciated VGS isolates decreased for erythromycin (P = 0.0674), penicillin (P = 0.0835), and tetracycline (P = 0.0994); though the decrease was only significant for clindamycin (P = 0.0033). For S. mitis, a significant susceptibility rate decrease was observed for erythromycin (P = 0.0112).

Conclusions

Susceptibility rates for some clinically relevant antibiotics declined between 2010 and 2020. This worrisome trend highlights the need to improve antimicrobial stewardship efforts to limit unnecessary antibiotic use and preserve empirical treatment options.
ICU Cockpit: a platform for collecting multimodal waveform data, AI-based computational disease modeling and real-time decision support in the intensive care unit
Authors: Boss Jens Michael , Narula Gagan , Straessle Christian , Willms Jan , Azzati Jan , Brodbeck Dominique , Luethy Rahel , Suter Susanne , Buehler Christof , Muroi Carl , Mack David Jule , Seric Marko , Baumann Daniel , Keller Emanuela
Published: April 2022

ICU Cockpit: a secure, fast, and scalable platform for collecting multimodal waveform data, online and historical data visualization, and online validation of algorithms in the intensive care unit. We present a network of software services that continuously stream waveforms from ICU beds to databases and a web-based user interface. Machine learning algorithms process the data streams and send outputs to the user interface. The architecture and capabilities of the platform are described. Since 2016, the platform has processed over 89 billion data points (N = 979 patients) from 200 signals (0.5–500 Hz) and laboratory analyses (once a day). We present an infrastructure-based framework for deploying and validating algorithms for critical care. The ICU Cockpit is a Big Data platform for critical care medicine, especially for multimodal waveform data. Uniquely, it allows algorithms to seamlessly integrate into the live data stream to produce clinical decision support and predictions in clinical practice.
Reports of Adverse Events Associated with Use of Novel Psychoactive Substances, 2017–2020: A Review
Authors: Mohr Amanda L A , Logan Barry K , Fogarty Melissa F , Krotulski Alex J , Papsun Donna M , Kacinko Sherri L , Huestis Marilyn A , Ropero-Miller Jeri D
Published: April 2022

An important role of modern forensic and clinical toxicologists is to monitor the adverse events of novel psychoactive substances (NPS). Following a prior review from 2013 to 2016, this critical literature review analyzes and evaluates published case reports for NPS from January 2017 through December 2020. The primary objective of this study is to assist in the assessment and interpretation of these cases as well as provide references for confirmation methods. Chemistry, pharmacology, adverse events and user profiles (e.g., polypharmacy) for NPS are provided including case history, clinical symptoms, autopsy findings and analytical results. Literature reviews were performed in PubMed and Google Scholar for publications using search terms such as NPS specific names, general terms (e.g., ‘designer drugs’ and ‘novel psychoactive substances’), drug classes (e.g., ‘designer stimulants’) and outcome-based terms (e.g., ‘overdose’ and ‘death’). Government and website drug surveillance databases and abstracts published by professional forensic science organizations were also searched. Toxicological data and detailed case information were extracted, tabulated, analyzed and organized by drug category. Case reports included overdose fatalities (378 cases), clinical treatment and hospitalization (771 cases) and driving under the influence of drugs (170 cases) for a total of 1,319 cases providing details of adverse events associated with NPS. Confirmed adverse events with associated toxidromes of more than 60 NPS were reported including synthetic cannabinoid, NPS stimulant, NPS hallucinogen, NPS benzodiazepine and NPS opioid cases. Fifty of these NPS were reported for the first time in January 2017 through December 2020 as compared to the previous 4 years surveyed. This study provides insight and context of case findings described in the literature and in digital government surveillance databases and websites during a recent 4-year period. This review will increase the awareness of adverse events associated with NPS use to better characterize international emerging drug threats.
SARS-CoV-2 productively infects primary human immune system cells in vitro and in COVID-19 patients
Authors: Pontelli Marjorie C , Castro Ítalo A , Martins Ronaldo B , La Serra Leonardo , Veras Flávio P , Nascimento Daniele C , Silva Camila M , Cardoso Ricardo S , Rosales Roberta , Gomes Rogério , Lima Thais M , Souza Juliano P , Vitti Brenda C , Caetité Diego B , de Lima Mikhael H F , Stumpf Spencer D , Thompson Cassandra E , Bloyet Louis-Marie , Toller-Kawahisa Juliana E , Giannini Marcela C , Bonjorno Letícia P , Lopes Maria I F , Batah Sabrina S , Siyuan Li , Luppino-Assad Rodrigo , Almeida Sergio C L , Oliveira Fabiola R , Benatti Maíra N , Pontes Lorena L F , Santana Rodrigo C , Vilar Fernando C , Auxiliadora-Martins Maria , Shi Pei-Yong , Cunha Thiago M , Calado Rodrigo T , Alves-Filho José C , Zamboni Dario S , Fabro Alexandre T , Louzada-Junior Paulo , Oliveira Rene D R , Whelan Sean P J , Cunha Fernando Q , Arruda Eurico
Published: April 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is associated with a hyperinflammatory state and lymphocytopenia, a hallmark that appears as both signature and prognosis of disease severity outcome. Although cytokine storm and a sustained inflammatory state are commonly associated with immune cell depletion, it is still unclear whether direct SARS-CoV-2 infection of immune cells could also play a role in this scenario by harboring viral replication. We found that monocytes, as well as both B and T lymphocytes, were susceptible to SARS-CoV-2 infection in vitro, accumulating double-stranded RNA consistent with viral RNA replication and ultimately leading to expressive T cell apoptosis. In addition, flow cytometry and immunofluorescence analysis revealed that SARS-CoV-2 was frequently detected in monocytes and B lymphocytes from coronavirus disease 2019 (COVID-19) patients. The rates of SARS-CoV-2-infected monocytes in peripheral blood mononuclear cells from COVID-19 patients increased over time from symptom onset, with SARS-CoV-2-positive monocytes, B cells, and CD4+ T lymphocytes also detected in postmortem lung tissue. These results indicated that SARS-CoV-2 infection of blood-circulating leukocytes in COVID-19 patients might have important implications for disease pathogenesis and progression, immune dysfunction, and virus spread within the host.
‘In the End, There Was No End’: Colonial Modernism and Moral Perfectionism in Patrick White’s The Tree of Man
Authors: Bowyer Andrew D
Published: April 2022

The modernism of Patrick White’s 1955 pastoral epic The Tree of Man is the focus of this study. The novel tracks the generational transition within one pioneering family around the time of the First World War in rural Australia, and its structure approximates the biblical pattern of edenic beginning, tragic fall, and eschatological recovery. Biblical motifs are evident in the novel’s treatment of natality and death, and in the way narrative landscapes are sign-posted with symbolic trees and riven by apocalyptic floods and fires that portend epiphany and judgement. My analysis of the novel draws on scholarship that characterises modernism in relation to settler colonialism, the temptations of scepticism, the negotiation of Christian inheritances, and the ambivalent ‘endings’ that occur in the wake of modernity’s ‘new beginnings’.
Improved distance measures for ‘fixed-content miscellanies’: an adaptation for the collections of sayings of the desert fathers and mothers
Authors: Göransson Elisabet , Maurits Luke , Dahlman Britt , Åkerman Sarkisian Karine , Rubenson Samuel , Dunn Michael
Published: April 2022

Collections of sayings of the desert fathers and mothers are extant in manuscripts in many languages and are organized differently. They are ‘fixed-content miscellanies’ (FCM): they include material that belongs to the same genre, but is variable both when it comes to appearance and order. Distance measurement methods are particularly suitable for large text traditions including variable content in the so-called mixed-content miscellanies, such as recipes, anthological compilations of shorter text passages, or catalogues, but can also be suitable for text genres like collections of sayings, that are equally variable in appearance and order of sayings, even though the genre is fixed; hence ‘fixed-content miscellanies’. In the article, collections of sayings in seven languages were compared using four distance measures methods. Each segment of the sayings was given a unique id to be comparable. The first method used, the Jaccard distance measure, disregards the linear order of items and instead considers each collection compared only as a ‘bag of stories’. In two other methods used (Birnbaum and Levenshtein methods), the order in which the narratives of each saying appear is compared. All three methods yielded interesting results, but the collections that were apparently closely related were clustered together so tightly that it was not possible to make more nuanced analyses. In order to remove false negatives, particulars concerning lacunes in the material were taken into account in the proposed modified Levenshtein method, the fixed-content miscellanies (FCM)-Levenshtein method. By applying the FCM-Levenshtein method, previously unknown relations between collections witnessed in different languages could be detected.
In a behavioural bioassay, effluents from cigarette butts, cured tobacco and tree leaves differentially affect resting site selection in the land snail Cornu aspersum
Authors: Bergey Elizabeth A , Shakir Mariam F
Published: April 2022

Cigarette butts (CBs) contain a plethora of chemicals, including many that are toxic. Although numerous studies have demonstrated the toxicity of CBs to aquatic organisms, there is less evidence that terrestrial organisms are severely impacted. Because CBs are commonly discarded on the ground, ground-dwelling organisms such as land snails may be especially affected. Many land snails are generalist detritivores/herbivores and ingest a variety of plant secondary compounds as they feed. This evolutionary exposure may render CBs (made principally of cured tobacco leaves) less toxic to these land snails than CBs are to less exposed aquatic animals. We investigated this possibility of reduced effects using a new behavioural assay to test the choice of ‘flavoured’ vertical resting sites in the land snail Cornu aspersum, which commonly rests on upright surfaces. In four experiments, regions of container walls were coated with different concentrations of CB and cured tobacco effluents, and effluents from three tree species and cured tobacco. Snails avoided high CB and tobacco effluent concentrations, which is consistent with toxicity. However, snails preferentially rested on dilute concentrations of both CBs and tobacco. Preference among tree leaf effluents was less evident, with a trend towards snails preferring the more readily eaten maple than the less readily eaten oak. Selection of the preferred tobacco concentration did not differ from that of tree leaves, indicating that C. aspersum was not repelled by dilute tobacco effluent. These results indicate that compounds leaching from discarded CBs may have little effect on snails and perhaps other soil organisms under environmentally realistic conditions.
An omics approach to study trace metals in sera of hemodialysis patients treated with erythropoiesis stimulating agents
Authors: Vignoli Alessia , Tenori Leonardo , Luchinat Claudio
Published: April 2022

Hemodialysis (HD) represents a life-sustaining treatment for patients with end-stage renal disease. However, it is associated with several complications, including anemia. Erythropoiesis-stimulating agents (ESAs) are often administered to HD patients with renal anemia, but a relevant proportion of them fail to respond to the therapy. Since trace metals are involved in several biological processes and their blood levels can be altered by HD, we study the possible association between serum trace metal concentrations and ratios with the administration and response to ESA. For this study, data and sample information of 110 HD patients were downloaded from the UC San Diego Metabolomics Workbench public repository (PR000565). The blood serum levels (and ratios) of antimony, cadmium, copper, manganese, molybdenum, nickel, selenium, tin, and zinc were studied applying an omics statistical approach. The Random Forest model was able to discriminate between HD-dependent patients treated and not treated with ESAs, with an accuracy of 71.7% (95% CI 71.5–71.9%). Logistic regression analysis identifies alterations of Mn, Mo, Cd, Sn, and several of their ratios as characteristic of patients treated with ESAs. Moreover, patients with scarce response to ESAs were shown to be characterized by reduced Mn to Ni and Mn to Sb ratios. In conclusion, our results show that trace metals, in particular manganese, play a role in the mechanisms underlying the human response to ESAs, and if further confirmed, the re-equilibration of their physiological levels could contribute to a better management of HD patients, hopefully reducing their morbidity and mortality.
Scenes from a Long Distance Music, 1970–1976Long Distance Music, 1970
Authors: Cimini Amy
Published: April 2022

This chapter explores long distance music and multi-sited listening in writings, text pieces, tape pieces, recording sessions, and City-Links projects that Amacher created between 1970 and 1976. In performances, installations, and research-based contexts, Amacher attuned distinct and often speculative embodiments to distanciated listening that combined remote transmission, environmental sound, and auditory dimension. This chapter discusses infrastructural and perceptual approaches to environmental remediation and civic value that Amacher encountered at MIT’s Center for Advanced Visual Studies, amid social, political and economic contestation about urban interzones and waterfronts. City-Links’ entanglements with industrial telecommunications also linked its technological supports to changed working conditions for telephone operators via automation in early computational environments. While the chapter concludes with No More Miles—An Acoustic Twin (1974), an exemplar of City-Links proto-diegetic dynamics, it imagines long distance music as an alternative tele-technological network that captured cycles of change and obsolescence in its historical moment.
Eartones and Third Ears
Authors: Cimini Amy
Published: April 2022

This chapter examines how Amacher studied auditory processing in order to compose differential interchanges between responsivities along the auditory pathway and inside a listener’s body. These interchanges she called “perceptual geography.” Through the autodidactic research program documented in her Additional Tones Workbook IV (1976/rev. 1987), this chapter identifies a dramatic epistemic charge in psychoacoustic and otological discourses on response tones in the cochlea (or “eartones”) and considers how Amacher extrapolated their scientific, historical and social meanings. Complementing analyses of her 1999 album Sound Characters (making the third ear), this chapter takes up the third ear, following philosopher Sarah Kofman, within a broader history of listening that registers and challenges distributions of life and sensation across a body. As an analytic of difference and power, the third ear emphasizes critical edges, in Amacher’s approach to eartones, that proved central to how she developed their dramatic and diegetic horizons in subsequent work.
An Uneasy Guest in the Schoolhouse
Authors: Winner Ellen
Published: April 2022

An Uneasy Guest recounts how art education has been conceptualized, justified, and taught in the United States while all the time being a marginalized and vulnerable presence in our schools. The teaching of art has often been justified in terms non-art outcomes. In the 19th century children dutifully copied, line by line, pictures given to them by their teachers; the goal was to develop drawing skills for industry. In the first part of the 20th century, with the rise of John Dewey-inspired progressive classrooms, children were encouraged to express themselves freely; now the goal was to nurture the artist in the child and promote emotional well-being. Later, with the accountability movement, art education was justified in terms of its putative ability to raise standardized test scores. Since the 19th century, there have been recurrent pendulum swings between progressive and traditional approaches to art education in the United States. These swings are documented in this book along with vivid comparisons to the traditional approach the author observed in China (much like the American 19th century approach) and also to the progressive approach the author observed in preschools in Northern Italy. In the face of this uncertain past, 21st century art education has exploded with a wealth of new ideas aligned with—but going far beyond—the progressivism of the early 20th century. This book documents what art education in America used to be, and portrays how it can become a strong and central presence in the schools of tomorrow.
A 1982 Journey to Reggio Emilia
Authors: Winner Ellen
Published: April 2022

This chapter describes the author’s observations of the progressive approach to art education in the famous Reggio Emilia preschools in northern Italy founded by Loris Malaguzzi. Children in these schools are able to create art that is far more complex than what is normally seen in U.S. progressive art classrooms. The chapter discusses the key principles underlying the Reggio method: An “atelierista” trained in art works together with the teacher to design the projects; both the atelierista and the teacher listen and ask probing questions of the children as they work; children work on the same artworks together, collaboratively, and discuss what they are doing among themselves and with the teacher and atelierista; the art projects require investigation, research, and observation and often take weeks or months to complete, with multiple drafts along the way; the school interior is aesthetically designed and filled with mirrors and lights to create multiple representations of reality; and the children’s works and comments and questions are meticulously documented. Under these circumstances, the art children produce challenges the prevailing understanding of the capabilities of preschoolers.