bluuebunny/crossref_metadata_2025 huggingface dataset:
Librational KAM tori in the secular dynamics of the υ Andromedæ planetary system
Authors: Caracciolo Chiara , Locatelli Ugo , Sansottera Marco , Volpi Mara
Published: December 2021

The υ Andromedæ system is the first extrasolar system where the mutual inclination between exoplanets has been determined using astrometric methods. We study a model of the υ Andromedæ planetary system considering the three-body problem formed by the central star and the two largest planets, υ And c and υ And d. We adopt a secular, three-dimensional model and initial conditions within the range of the observed values. The numerical integrations highlight that the system is orbiting around a one-dimensional elliptic torus (i.e. a periodic orbit that is linearly stable). This invariant object is used as a seed for an algorithm based on a sequence of canonical transformations. The algorithm determines the normal form related to a KAM torus, whose shape is in excellent agreement with the orbits of the secular model. We rigorously prove that the algorithm constructing the final KAM invariant torus is convergent, by adopting a suitable technique based on a computer-assisted proof. Thus, we are able to prove the stability of the secular dynamics for a set of values of the orbital elements that are in agreement with the observed ones. As a by-product, we can also extract a numerical indicator of robustness for the constructed invariant KAM tori. This allows us to identify ranges of the inclinations that are the most likely candidates according to the KAM stability prescription. In this context, we conclude that the most robust orbital configurations are those with large values of υ And c’s mass, that is about 16 time bigger than Jupiter’s one.
The correlation calibration of PAPER-64 data
Authors: Gogo Tamirat G , Ma Yin-Zhe , Kittiwisit Piyanat , Sievers Jonathan L , Parsons Aaron R , Pober Jonathan C , Jacobs Daniel C , Cheng Carina , Kolopanis Matthew , Liu Adrian , Kohn Saul A , Aguirre James E , Ali Zaki S , Bernardi Gianni , Bradley Richard F , DeBoer David R , Dexter Matthew R , Dillon Joshua S , Klima Pat , MacMahon David H E , Moore David F , Nunhokee Chuneeta D , Walbrugh William P , Walker Andre
Published: December 2021

Observation of redshifted 21-cm signal from the Epoch of Reionization (EoR) is challenging due to contamination from the bright foreground sources that exceed the signal by several orders of magnitude. Removal of this very high foreground relies on accurate calibration to keep the intrinsic property of the foreground with frequency. Commonly employed calibration techniques for these experiments are the sky model-based and the redundant baseline-based calibration approaches, which can suffer from sky-modelling error and array redundancy imperfection respectively. In this work, we introduce the hybrid correlation calibration (CorrCal) scheme, which aims to bridge the gap between redundant and sky-based calibration by relaxing redundancy of the array and including sky information into the calibration formalisms. We apply the CorrCal to the data of Precision Array for Probing the Epoch of Reionization (PAPER) experiment, which was pre-calibrated using redundant baseline calibration. We show about $6\%$ suppression at the bin right on the horizon limit of the foreground wedge-like structure, relative to the pre-calibrated power spectra. This small improvement of the foreground power spectra around the wedge limit could be suggestive of reduced spectral structure in the data after CorrCal calibration, which lays the foundation for future improvement of the calibration algorithm and implementation method.
Joint Inference of Migration and Reassortment Patterns for Viruses with Segmented Genomes
Authors: Stolz Ugnė , Stadler Tanja , Müller Nicola F , Vaughan Timothy G
Published: December 2021

The structured coalescent allows inferring migration patterns between viral subpopulations from genetic sequence data. However, these analyses typically assume that no genetic recombination process impacted the sequence evolution of pathogens. For segmented viruses, such as influenza, that can undergo reassortment this assumption is broken. Reassortment reshuffles the segments of different parent lineages upon a coinfection event, which means that the shared history of viruses has to be represented by a network instead of a tree. Therefore, full genome analyses of such viruses are complex or even impossible. Although this problem has been addressed for unstructured populations, it is still impossible to account for population structure, such as induced by different host populations, whereas also accounting for reassortment. We address this by extending the structured coalescent to account for reassortment and present a framework for investigating possible ties between reassortment and migration (host jump) events. This method can accurately estimate subpopulation dependent effective populations sizes, reassortment, and migration rates from simulated data. Additionally, we apply the new model to avian influenza A/H5N1 sequences, sampled from two avian host types, Anseriformes and Galliformes. We contrast our results with a structured coalescent without reassortment inference, which assumes independently evolving segments. This reveals that taking into account segment reassortment and using sequencing data from several viral segments for joint phylodynamic inference leads to different estimates for effective population sizes, migration, and clock rates. This new model is implemented as the Structured Coalescent with Reassortment package for BEAST 2.5 and is available at https://github.com/jugne/SCORE.
Rituximab administration during the second trimester of pregnancy for systemic lupus erythematosus: Case report and review of the literature on rheumatic disease
Authors: Colquhoun Matthew , Thanopoulou Vasiliki , Quick Vanessa , Mouyis Maria
Published: December 2021

Rituximab (RTX) is an anti-CD20 monoclonal antibody that is used in the treatment of many rheumatic diseases, for both licensed and unlicensed indications. Due to concerns regarding foetal B cell depletion and possible infection, there is conflicting advice about whether the drug should be administered during pregnancy, with some organisations advising administration if the potential benefit to the mother outweighs the risk to the foetus and some advising stopping RTX 6 months prior to conception. Caution in particular is advised about administering RTX in later trimesters when maternal immunoglobulin G (IgG) is transported across the placenta. There have been few literatures thus far examining the safety of administering RTX from the second trimester onwards in rheumatic diseases. We present a case where RTX was used during the second trimester for the treatment of refractory systemic lupus erythematosus, without adverse effect on the neonate.
Measuring metacognitive performance: type 1 performance dependence and test-retest reliability
Authors: Guggenmos Matthias
Published: December 2021

Research on metacognition—thinking about thinking—has grown rapidly and fostered our understanding of human cognition in healthy individuals and clinical populations. Of central importance is the concept of metacognitive performance, which characterizes the capacity of an individual to estimate and report the accuracy of primary (type 1) cognitive processes or actions ensuing from these processes. Arguably one of the biggest challenges for measures of metacognitive performance is their dependency on objective type 1 performance, although more recent methods aim to address this issue. The present work scrutinizes the most popular metacognitive performance measures in terms of two critical characteristics: independence of type 1 performance and test-retest reliability. Analyses of data from the Confidence Database (total N = 6912) indicate that no current metacognitive performance measure is independent of type 1 performance. The shape of this dependency is largely reproduced by extending current models of metacognition with a source of metacognitive noise. Moreover, the reliability of metacognitive performance measures is highly sensitive to the combination of type 1 performance and trial number. Importantly, trial numbers frequently employed in metacognition research are too low to achieve an acceptable level of test-retest reliability. Among common task characteristics, simultaneous choice and confidence reports most strongly improved reliability. Finally, general recommendations about design choices and analytical remedies for studies investigating metacognitive performance are provided.
Precision medicine biomarkers in brain metastases: applications, discordances, and obstacles
Authors: Steindl Ariane , Brastianos Priscilla K , Preusser Matthias , Berghoff Anna S
Published: December 2021

Brain metastases (BM) present a common cause of mortality and morbidity in several metastatic cancer entities. New therapeutic developments during the last decades, including targeted and immune-related therapies, have shown considerable extra- and intracranial response rates in specific subgroups of BM patients. However, differences in the molecular alteration in the BM tumor tissue compared to extracranial tumors leads to heterogeneous therapeutic responses. Therefore, an accurate molecular analyzation of BM tissue, if possible, has become an essential part in therapeutic decision making in BM patients. The concordance of predictive molecular biomarkers between multiple sites including extracranial and intracranial tumor tissue have been analyzed for some but not all biomarkers routinely applied in modern precision medicine approaches. In the present review, we summarize the current evidence of predictive biomarkers for personalized therapy approaches in the treatment of parenchymal BM.
Management of brain metastases in lung cancer: evolving roles for radiation and systemic treatment in the era of targeted and immune therapies
Authors: Myall Nathaniel J , Yu Helena , Soltys Scott G , Wakelee Heather A , Pollom Erqi
Published: December 2021

Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity. As a result, the management of brain metastases in lung cancer has evolved, with both local and systemic therapies now playing an important role. Factors such as tumor histology (non-small versus small cell), oncogenic driver mutations, and symptom burden from intracranial disease impact treatment decisions. Here, we review the current management of brain metastases in lung cancer, highlighting the roles of stereotactic radiosurgery and novel systemic therapies as well as the ongoing questions that remain under investigation.
Laser interstitial thermal therapy for brain metastases
Authors: Srinivasan Ethan S , Grabowski Matthew M , Nahed Brian V , Barnett Gene H , Fecci Peter E
Published: December 2021

Laser interstitial thermal therapy (LITT) is a minimally invasive treatment for intracranial lesions entailing thermal ablation via a stereotactically placed laser probe. In metastatic disease, it has shown the most promise in the treatment of radiographically progressive lesions after initial stereotactic radiosurgery, whether due to recurrent metastatic disease or radiation necrosis. LITT has been demonstrated to provide clinical benefit in both cases, as discussed in the review below. With its minimal surgical footprint and short recovery period, LITT is further advantaged for patients who are otherwise high-risk surgical candidates or with lesions in difficult to access locations. Exploration of the current data on its use in metastatic disease will allow for a better understanding of the indications, benefits, and future directions of LITT for these patients.
Motor neuron disease risk and magnetic field exposures
Authors: Sorahan Tom , Nichols Linda
Published: December 2021

Background

Many studies have investigated magnetic field exposure and the risks of motor neuron disease (MND). Meta-analyses have found positive associations but a causal relationship has not been established.

Aims

To investigate the risks of MND and occupational exposure to magnetic fields in a large UK cohort.

Methods

Mortality of 37 986 employees of the former Central Electricity Generating Board of England and Wales was investigated for the period 1987–2018. Employees were first employed in the period 1942–82 and were still in employment on the 1 November, 1987. Detailed calculations enabled estimates to be made of magnetic field exposures. Observed deaths were compared with expected numbers based on mortality rates for the general population of England and Wales and Poisson regression was used to calculate rate ratios (relative risks) for categories of lifetime, lagged (distant) and lugged (recent) magnetic field exposure.

Results

Mortality from MND in the total cohort was similar to national rates (observed 69, expected 71.3, SMR 97, 95% CI 76–122). There were no statistically significant trends of risks increasing with lifetime, recent or distant magnetic field exposure, although positive associations were observed for some categories of recent exposure.

Conclusions

The study did not find that the cohort had elevated risks of MND as a consequence of occupational lifetime exposure to magnetic fields, although a possible role for recent exposures could usefully be investigated in other datasets.
Darunavir/Cobicistat/Emtricitabine/Tenofovir Alafenamide Versus Dolutegravir/Abacavir/Lamivudine in Antiretroviral-Naive Adults (SYMTRI): A Multicenter Randomized Open-Label Study (PReEC/RIS-57)
Authors: Podzamczer D , Micán R , Tiraboschi J , Portilla J , Domingo P , Llibre J M , Ribera E , Vivancos M J , Morano L , Masiá M , Gómez C , Fanjul F , Payeras A , Inciarte A , Estrada V , Rivero A , Castro Á , Bernal E , Vinuesa D , Knobel H , Troya J , Macías J , Montero M , Sanz J , Navarro-Alcaraz A , Caicedo A , Fernández G , Martínez E , Moreno S
Published: December 2021

Background

Darunavir/cobicistat/emtricitabine/tenofovir alafenamide (D/C/F/TAF) is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naive patients are lacking.

Methods

Adult (>18 years old) human immunodeficiency virus-infected antiretroviral-naive patients (HLA-B∗5701 negative and hepatitis B virus negative), with viral load (VL) ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or dolutegravir/abacavir/lamivudine (DTG/3TC/ABC) after stratifying by VL and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the intention-to-treat (ITT)-exposed population (US Food and Drug Administration snapshot analysis, 10% noninferiority margin).

Results

Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. Forty percent had a baseline VL >100 000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median body mass index was 24 kg/m2. At 48 weeks, 79% (D/C/F/TAF) versus 82% (DTG/3TC/ABC) had VL <50 c/mL (difference, −2.4%; 95% confidence interval [CI], −11.3 to 6.6). Eight percent versus four percent experienced virologic failure but no resistance-associated mutations emerged. Four percent versus six percent had drug discontinuation due to adverse events. In the per-protocol analysis, 94% versus 96% of patients had VL <50 c/mL (difference, −2%; 95% CI, −8.1 to 3.5). There were no differences in CD4 cell count or weight changes.

Conclusions

We could not demonstrate the noninferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial antiretroviral therapy, although both regimens were similarly well tolerated.
Can lightning strike twice? Wild-type transthyretin cardiac amyloidosis associated with rare liver disease
Authors: Bhattacharya Priyanka T , Fox Alyson N , Marboe Charles C , Lagana Stephen M , Remotti Helen E , D’Armiento Jeanine M , Goldklang Monica P , Eisenberger Andrew B , Griffin Jan M , Maurer Mathew S
Published: December 2021

Wild-type ATTR cardiac amyloidosis (ATTRwt-CA) is not as rare as previously thought to be. Patients with infiltrative cardiac amyloidosis often present with right-sided heart failure (HF) symptomatology. Clinically significant liver disease and cirrhosis has not been reported in ATTRwt-CA. We present two cases of ATTRwt-CA with right-sided HF and abnormal liver function tests initially thought to be secondary to congestive hepatopathy but found to have rare and unrelated liver disease. These cases highlight the importance of developing a broad differential diagnosis and leveraging a multidisciplinary team approach in evaluating patients for unusual causes of cirrhosis/other chronic liver diseases when ATTR cardiac amyloidosis patients present with congestive hepatopathy.
Assessing nephrology competence in general paediatrics—A survey of general paediatricians, paediatric nephrologists, residents, and program directors
Authors: Kirpalani Amrit , Prasad Charushree , Jawa Natasha A , Atkinson Adelle R , Feldman Mark , Jeffers Justin M , Noone Damien G
Published: December 2021

Objective

The objective of this study was to identify nephrology topics of lowest perceived competency and importance for general paediatricians.

Methods

Surveys were distributed to general paediatricians, paediatric residents, paediatric residency program directors, and paediatric nephrologists. Perceived importance and competence were rated on a 5-point Likert scale. Means and 95% confidence intervals were calculated.

Results

Mean perceived competency from general paediatricians across all nephrology domains was 3.0, 95%CI (2.9 to 3.1) and mean importance was 3.2, 95%CI (3.1 to 3.3). Domains scoring below the means for competence and importance, respectively were kidney stones (2.5, 95%CI [2.2 to 2.7]) and 2.6, 95%CI [2.3 to 2.8]), acute kidney injury (2.5, 95%CI [2.2 to 2.8] and 2.4, 95%CI [2.1 to 2.8]), chronic kidney disease (1.9, 95%CI [1.7 to 2.2] and 2.1, 95%CI [1.8 to 2.4]), tubular disorders (1.8, 95%CI [1.6 to 2.0] and 2.0, 95%CI [1.8 to 2.3]), and kidney transplant (1.6, 95%CI [1.4 to 1.8] and 1.7, 95%CI [1.4 to 1.9]). Residents, program directors, and paediatric nephrologists agreed that stones, chronic kidney disease, tubular disorders, and transplant were of lower importance. However, acute kidney injury was the domain with the largest discrepancy in perceived importance between residents (4.4, 95%CI [4.2 to 4.6]), nephrologists (4.2, 95%CI [3.8 to 4.6]), and program directors (4.2, 95%CI [3.7 to 4.7]) compared to general paediatricians ([2.4, 95%CI [2.1 to 2.8]; P<0.05).

Conclusion

Paediatricians did not believe acute kidney injury was important to their practice, despite expert opinion and evidence of long-term consequences. Educational interventions must address deficits in crucial domains of renal health in paediatrics.
Long-term follow-up after lymphodepleting autologous haematopoietic cell transplantation for treatment-resistant systemic lupus erythematosus
Authors: Goklemez Sencer , Hasni Sarfaraz , Hakim Frances T , Muraro Paolo A , Pirsl Filip , Rose Jeremy , Memon Sarfraz , Fowler Daniel F , Steinberg Seth M , Baker Eva H , Panch Sandya R , Gress Ronald , Illei Gabor G , Lipsky Peter E , Pavletic Steven Z
Published: December 2021

Objective

Autologous haematopoietic cell transplantation (AHSCT) improves immunologic dysfunction in patients with SLE. However, the curative potential of this therapy remains uncertain. This study reports outcomes in SLE patients receiving a lymphodepleting, reduced intensity regimen for AHSCT in SLE.

Methods

Eight patients with SLE refractory to treatment, including i.v. cyclophosphamide (CYC), were enrolled. Five had LN and three CNS involvement as primary indications for transplant. Haematopoietic cell mobilization with CYC, G-CSF and rituximab was followed by collection of CD34+ positively selected cells. The conditioning regimen consisted of concurrent administration of CYC, fludarabine and rituximab. All immunosuppressive medications were discontinued at the start of mobilization and CS were rapidly tapered after the transplant.

Results

Five of eight patients achieved a complete response, including a decline in the SLEDAI to zero, which was sustained in four patients for a median of 165 months (range 138–191). One patient achieved a partial response, which was followed by relapse at month 18. Two patients with nephritis and underlying comorbidities in most organs had early deaths from infection and multiorgan failure. AHSCT resulted in profound lymphodepletion, followed by expansion of Treg cells and repopulation of naive T and B cells. Patients with a complete response showed a sustained suppression of the SLE-associated IFN-induced gene signature, marked depletion of memory and plasmablast B cells and resultant sustained elimination of anti-dsDNA antibody.

Conclusion

Durable clinical and serologic remissions with suppression in the IFN gene signature can be achieved in refractory SLE following lymphodepleting AHSCT.

Trial registration

ClinicalTrials.gov, https://clinicaltrials.gov, NCT00076752.
Screening for preclinical parenchymal lung disease in rheumatoid arthritis
Authors: Esposito Anthony J , Sparks Jeffrey A , Gill Ritu R , Hatabu Hiroto , Schmidlin Eric J , Hota Partha V , Poli Sergio , Fletcher Elaine A , Xiong Wesley , Frits Michelle L , Iannaccone Christine K , Prado Maria , Zaccardelli Alessandra , Marshall Allison , Dellaripa Paul F , Weinblatt Michael E , Shadick Nancy A , Rosas Ivan O , Doyle Tracy J
Published: December 2021

Objectives

Pulmonary disease is a common extraarticular manifestation of RA associated with increased morbidity and mortality. No current strategies exist for screening this at-risk population for parenchymal lung disease, including emphysema and interstitial lung disease (ILD).

Methods

RA patients without a diagnosis of ILD or chronic obstructive pulmonary disease underwent prospective and comprehensive clinical, laboratory, functional and radiological evaluations. High resolution CT (HRCT) scans were scored for preclinical emphysema and preclinical ILD and evaluated for other abnormalities.

Results

Pulmonary imaging and/or functional abnormalities were identified in 78 (74%) of 106 subjects; 45% had preclinical parenchymal lung disease. These individuals were older with lower diffusion capacity but had similar smoking histories compared with no disease. Preclinical emphysema (36%), the most commonly detected abnormality, was associated with older age, higher anti-cyclic citrullinated peptide antibody titres and diffusion abnormalities. A significant proportion of preclinical emphysema occurred among never smokers (47%) with a predominantly panlobular pattern. Preclinical ILD (15%) was not associated with clinical, laboratory or functional measures.

Conclusion

We identified a high prevalence of undiagnosed preclinical parenchymal lung disease in RA driven primarily by isolated emphysema, suggesting that it may be a prevalent and previously unrecognized pulmonary manifestation of RA, even among never smokers. As clinical, laboratory and functional evaluations did not adequately identify preclinical parenchymal abnormalities, HRCT may be the most effective screening modality currently available for patients with RA.
Paternal inflammatory arthritis is associated with a higher risk of miscarriage: results of a large multicentre study (iFAME-Fertility)
Authors: Perez-Garcia Luis F , Röder Esther , Smeele Hieronymus T W , Goekoop Robbert , Hazes Johanna M W , Kok Marc R , Tchetverikov Ilja , van der Helm-van Mil Annette , van der Kaap Jos , Kok Petra , Krijthe Bouwe P , Dolhain Radboud J E M
Published: December 2021

Objectives

Paternal preconception health is recognized as an important contributor to pregnancy outcomes. Nonetheless, pregnancy outcomes of partners of men with inflammatory arthritis (IA) have never been studied. Our objective was to describe the pregnancy outcomes of partners of men diagnosed with IA.

Methods

We performed a multicentre cross-sectional retrospective study conducted in the Netherlands. Men with IA who were over 40 years old that reported at least one positive pregnancy test were included. To analyse the impact of IA on pregnancy outcomes, pregnancies were classified into two groups: pregnancies conceived after the diagnosis of IA and before the diagnosis of IA.

Results

In total, 408 male participants diagnosed with IA reported 897 singleton pregnancies that resulted in 794 live births. Pregnancies conceived after the diagnosis of IA had higher rate of miscarriage (12.27 vs 7.53%, P = <0.05). This increased risk was still present after adjusting for confounders [OR 2.03 (95% CI 1.12, 3.69) P = 0.015].

Conclusions

This is the largest study to describe the pregnancy outcomes of partners of men diagnosed with IA and the first to demonstrate that paternal IA is associated with a higher risk of miscarriage. Notwithstanding, the overall rate of miscarriage reported in our study could be comparable to previously reported population estimates.
The association between obstructive sleep apnea and sleep spindles in middle-aged and older men: a community-based cohort study
Authors: Parker Jesse L , Melaku Yohannes Adama , D’Rozario Angela L , Wittert Gary A , Martin Sean A , Catcheside Peter G , Lechat Bastien , Teare Alison J , Adams Robert J , Appleton Sarah L , Vakulin Andrew
Published: December 2021

Study Objectives

Sleep spindles show morphological changes in obstructive sleep apnea (OSA). However, previous small studies have limited generalizability, leaving associations between OSA severity measures and spindle metrics uncertain. This study examined cross-sectional associations between OSA severity measures and spindle metrics among a large population-based sample of men.

Methods

Community-dwelling men with no previous OSA diagnosis underwent home-based polysomnography. All-night EEG (F4-M1) recordings were processed for artifacts and spindle events identified using previously validated algorithms. Spindle metrics of interest included frequency (Hz), amplitude (µV2), overall density (11–16 Hz), slow density (11–13 Hz), and fast density (13–16 Hz) (number/minute). Multivariable linear regression models controlling for demographic, biomedical, and behavioral confounders were used to examine cross-sectional associations between OSA severity measures and spindle metrics.

Results

In adjusted analyses, higher apnea-hypopnea index (AHI/h, as a continuous variable) and percentage total sleep time with oxygen saturation <90% (TST90) were associated with decreased slow spindle density (AHI, B = −0.003, p = 0.032; TST90, B = −0.004, p = 0.047) but increased frequency (AHI, B = 0.002, p = 0.009; TST90, B = 0.002, p = 0.043). Higher TST90 was also associated with greater spindle amplitude (N2 sleep, B = 0.04, p = 0.011; N3 sleep, B = 0.11, p < 0.001). Furthermore, higher arousal index was associated with greater spindle amplitude during N2 sleep (B = 0.31, p < 0.001) but decreased overall density (B = −1.27, p = 0.030) and fast density (B = −4.36, p = 0.028) during N3 sleep.

Conclusions

Among this large population-based sample of men, OSA severity measures were independently associated with spindle abnormalities. Further population studies are needed to determine associations between spindle metrics and functional outcomes.
The preparation phase in the multiphase optimization strategy (MOST): a systematic review and introduction of a reporting checklist
Authors: Landoll Ryan R , Vargas Sara E , Samardzic Kristen B , Clark Madison F , Guastaferro Kate
Published: December 2021

Multicomponent behavioral interventions developed using the multiphase optimization strategy (MOST) framework offer important advantages over alternative intervention development models by focusing on outcomes within constraints relevant for effective dissemination. MOST consists of three phases: preparation, optimization, and evaluation. The preparation phase is critical to establishing the foundation for the optimization and evaluation phases; thus, detailed reporting is critical to enhancing rigor and reproducibility. A systematic review of published research using the MOST framework was conducted. A structured framework was used to describe and summarize the use of MOST terminology (i.e., preparation phase and optimization objective) and the presentation of preparation work, the conceptual model, and the optimization. Fifty-eight articles were reviewed and the majority focused on either describing the methodology or presenting results of an optimization trial (n = 38, 66%). Although almost all articles identified intervention components (96%), there was considerable variability in the degree to which authors fully described other elements of MOST. In particular, there was less consistency in use of MOST terminology. Reporting on the MOST preparation phase is varied, and there is a need for increased focus on explicit articulation of key design elements and rationale of the preparation phase. The proposed checklist for reporting MOST studies would significantly advance the use of this emerging methodology and improve implementation and dissemination of MOST. Accurate reporting is essential to reproducibility and rigor of scientific trials as it ensures future research fully understands not only the methodology, but the rationale for intervention and optimization decisions.
Waiting for the Doctor: Managing Time and Emotion in the British National Health Service, 1948–80
Authors: Moore Martin D
Published: December 2021

This article examines patients’ and doctors’ emotional and psychological entanglements with the development of appointment systems in British general practice between the 1948 and 1980. Waiting, especially in the form of the queue, has been subject to recent historical analyses. However, the focus has often been on negative emotional responses, on how waiting has been politicized, and on the disciplinary power of the waiting room. Frameworks of rationalization and discipline have also dominated historical and sociological assessments of temporal regulation, and especially the rise of standardized, ordered, clock and calendar time that appointments embodied. Though productive, focusing too closely on these processes in relation to time and waiting risks underplaying the complex affective life of regulatory technologies, for both their operators and their subjects. By focusing tightly on how myriad, often contradictory, responses to appointment systems operated within the setting of post-war general practice, this article looks to place such emotional and psychological relations in historical context. In so doing, it develops recent work on the emotional history of the National Health Service and, by extension, of the diverse affective and temporal modes of the British welfare state.
Nurses' Ability to Recognize and Prevent Opioid-Induced Respiratory Depression
Authors: McNaughton Molly A. , Lundberg Jamie , Schenian Meghan , Maynard Leslie , Aplin Amanda , Kautza-Farley Amanda , Finch-Guthrie Patricia
Published: December 2021

Opioids are the primary therapy for acute postoperative pain, despite being associated with opioid-induced respiratory depression (OIRD). The purpose of this study was to improve nurses' knowledge, confidence, and ability to recognize, prevent, and treat OIRD in postoperative inpatients and evaluate the feasibility of using the Pasero Opioid-Induced Sedation Scale (POSS). Registered nurses completed three tools: (1) an Opioid Knowledge Self-Assessment, which was administered pre- and post-education; (2) a Confidence Scale, which was administered pre- and post-education; and (3) a POSS Perceptions and Usability Scale that was administered post-education. Nurses were educated on the POSS and then immediately following the training practiced by undertaking a patient assessment using the instrument. They then completed the POSS Perceptions and Usability Scale to rate their perception of the feasibility of using the POSS. Between preeducation and posteducation, participant knowledge increased in the following areas: recognizing opioid-induced side effects, dose selection, risk factors for oversedation, and information to make clinical decisions. However, there was a drop in scores when asked about knowledge of who is at risk for opioid-related side effects. These findings support our conclusion that OIRD education improves nursing confidence and knowledge. There was significant agreement between the nurse and subject matter experts POSS scores, indicating that this tool is easy to use.
Preoperative and Postoperative Opioid Prescription Rates in the Total Hip Replacement Surgical Patient
Authors: Schmidt Shawna , Shrian-Chang Kuang , Silva Susan , Goode Victoria , Horn Maggie , Cary Michael P.
Published: December 2021

The United States is facing an opioid epidemic that has only worsened with the COVID-19 pandemic. There is little evidence regarding patterns of opioid use among patients with total hip replacement (THR). Although the Centers for Disease Control and Prevention has put forward guidelines for prescribing opioids, it does not include guidance specifically for THR patients suffering from presurgical and postsurgical pain. The purpose of this study was to (1) compare presurgical and postsurgical opioid rates, (2) compare presurgical and postsurgical morphine milligram equivalents (MME), and (3) determine whether having a presurgical opioid prescription predicts the receipt of postsurgical opioid prescriptions among patients undergoing THR surgery. Retrospective cohort analysis of 4,405 patients undergoing THR at a major academic medical center in the United States from April 30, 2015, to April 30, 2018, was done. Patient characteristics, opioid rates, and average MME/day/person were described. Logistic regression was used to determine whether presurgical opioid prescription and opioid risk level predicted postsurgical opioid prescribing. Median age was 64 years (range = 18–85 years); patients were primarily Caucasian/White (78.8%) and female (54.7%). Opioid prescription rates in this sample for the 12-month presurgical and postsurgical periods were 66.1% and 95.6%, respectively. Oxycodone was the most common opioid prescribed in both periods. Among those prescribed an opioid, moderate/high risk for overdose and/or death was 6.3% presurgery and 19.8% postsurgery. Patients with a comorbidity were two times more likely to receive an opioid prescription in the postsurgical period. The median average MME/day/person was 26.5 (range = 0.3–180.0) for patients with an opioid prescribed during the presurgery period and 40.4 (range = 1.5–270.0) during the postsurgery period. Opioid use, regardless of strength, in the presurgical period as well as having one or more comorbidities predicted opioid use in the postsurgical period.
Cost and cost-effectiveness of dolutegravir-based antiretroviral regimens: an economic evaluation of a clinical trial
Authors: Jamieson Lise , Serenata Celicia , Makhubele Lebogang , Sokhela Simiso , Mashabane Nkuli , Akpomiemie Godspower , Johnson Leigh F. , Venter Willem D.F. , Meyer-Rath Gesine
Published: December 2021

Background:

HIV programmes world-wide currently make decisions regarding new antiretroviral therapy (ART) regimens with less side-effects and higher resistance barriers, which may improve adherence and viral suppression. Economic evaluation helps inform these decisions.

Methods:

We conducted an economic evaluation of three ART regimens included in the ADVANCE trial from the provider's perspective: tenofovir alafenamide (TAF)/emtricitabine (FTC)+dolutegravir (DTG) and tenofovir disoproxil fumarate (TDF)/FTC+DTG, compared with TDF/FTC/efavirenz (EFV). We used top–down and bottom–up cost analysis with resource utilization based on trial data and adjusted to emulate routine care. We estimated the cost-effectiveness of each regimen as cost per person virally suppressed or retained and per life-year saved, at 48 and 96 weeks.

Results:

Though the DTG-based trial arms were 2% more costly than TDF/FTC/EFV, both had slightly lower cost-per-outcome ($9783 and $9929/patient virally suppressed for TDF/FTC+DTG and TAF/FTC+DTG, respectively) than TDF/FTC/EFV ($10 365). The trial cost per additional virally suppressed patient, compared with TDF/FTC/EFV, was lower in the TDF/FTC+DTG arm ($2967) compared with TAF/FTC+DTG ($3430). In routine care, cost per virally suppressed patient was estimated as similar between TDF/FTC+DTG ($426) and TDF/FTC/EFV ($424) but more costly under TAF/FTC+DTG. Similar results were seen in the cost per additional person retained across scenarios. When modelled over 20 years, TDF/FTC+DTG was more cost-effective than TAF/FTC+DTG ($10 341 vs $41 958/life-year saved).

Conclusion:

TDF/FTC+DTG had similar costs per outcome as TDF/FTC/EFV in the routine care scenario but TDF/FTC+DTG was more cost-effective when modelled over 20 years.
Self-generated oxygen gradients control collective aggregation of photosynthetic microbes
Authors: Fragkopoulos Alexandros A. , Vachier Jérémy , Frey Johannes , Le Menn Flora-Maud , Mazza Marco G. , Wilczek Michael , Zwicker David , Bäumchen Oliver
Published: December 2021

For billions of years, photosynthetic microbes have evolved under the variable exposure to sunlight in diverse ecosystems and microhabitats all over our planet. Their abilities to dynamically respond to alterations of the luminous intensity, including phototaxis, surface association and diurnal cell cycles, are pivotal for their survival. If these strategies fail in the absence of light, the microbes can still sustain essential metabolic functionalities and motility by switching their energy production from photosynthesis to oxygen respiration. For suspensions of motile
C. reinhardtii
cells above a critical density, we demonstrate that this switch reversibly controls collective microbial aggregation. Aerobic respiration dominates over photosynthesis in conditions of low light, which causes the microbial motility to sensitively depend on the local availability of oxygen. For dense microbial populations in self-generated oxygen gradients, microfluidic experiments and continuum theory based on a reaction–diffusion mechanism show that oxygen-regulated motility enables the collective emergence of highly localized regions of high and low cell densities.
Substrate recognition determinants of human eIF2α phosphatases
Authors: Hodgson George , Andreeva Antonina , Bertolotti Anne
Published: December 2021

Phosphorylation of the translation initiation factor eIF2α is a rapid and vital cellular defence against many forms of stress. In mammals, the levels of eIF2α phosphorylation are set through the antagonistic action of four protein kinases and two heterodimeric protein phosphatases. The phosphatases are composed of the catalytic subunit PP1 and one of two related non-catalytic subunits, PPP1R15A or PPP1R15B (R15A or R15B). Here, we generated a series of R15 truncation mutants and tested their properties in mammalian cells. We show that substrate recruitment is encoded by an evolutionary conserved region in R15s, R15A
325–554
and R15B
340–639
. G-actin, which has been proposed to confer selectivity to R15 phosphatases, does not bind these regions, indicating that it is not required for substrate binding. Fragments containing the substrate-binding regions but lacking the PP1-binding motif trapped the phospho-substrate and caused accumulation of phosphorylated eIF2α in unstressed cells. Activity assays in cells showed that R15A
325–674
and R15B
340–713
, encompassing the substrate-binding region and the PP1-binding region, exhibit wild-type activity. This work identifies the substrate-binding region in R15s, that functions as a phospho-substrate trapping mutant, thereby defining a key region of R15s for follow up studies.
Pollutant removal from municipal sewage by a microaerobic up-flow oxidation ditch coupled with micro-electrolysis
Authors: Zhao Zhen-dong , Lin Qiang , Zhou Yang , Feng Yu-hong , Huang Qi-mei , Wang Xiang-hui
Published: December 2021

The development of efficient and low-cost wastewater treatment processes remains an important challenge. A microaerobic up-flow oxidation ditch (UOD) with micro-electrolysis by waterfall aeration was designed for treating real municipal wastewater. The effects of influential factors such as up-flow rate, waterfall height, reflux ratio, number of stages and iron dosing on pollutant removal were fully investigated, and the optimum conditions were obtained. The elimination efficiencies of chemical oxygen demand (COD), ammonia nitrogen (NH
4
+
-N), total nitrogen (TN) and total phosphorus (TP) reached up to 84.33 ± 2.48%, 99.91 ± 0.09%, 93.63 ± 0.60% and 89.27 ± 1.40%, respectively, while the effluent concentrations of COD, NH
4
+
-N, TN and TP were 20.67 ± 2.85, 0.02 ± 0.02, 1.39 ± 0.09 and 0.27 ± 0.02 mg l
−1
, respectively. Phosphorous removal was achieved by iron–carbon micro-electrolysis to form an insoluble ferric phosphate precipitate. The microbial community structure indicated that carbon and nitrogen were removed via multiple mechanisms, possibly including nitrification, partial nitrification, denitrification and anammox in the UOD.
Prestress behaviour and ductility requirements in structures: solutions from a unified algebraic approach
Authors: Cervera Bravo Jaime , Navas-Sánchez Laura
Published: December 2021

This paper presents an algebraic approach that unifies both the elastic and limit theories of static structural analysis. This approach reveals several previously unpublished improvements, which are based on several dualities in the mathematical description. Firstly, we show a novel duality between the solutions to two different problems: the elastic solution to the internal forces of an externally loaded structure, and the nodal displacements induced by prestressing in one or several elements of the same structure. This duality is proven and discussed. The application of this solution to the limit state analysis is very productive, and includes the determination of the ductility requirements necessary to achieve full plastic behaviour, and the assessment of the prestress needed to limit or eliminate such requirements. The unified framework also allows to obtain the elasto-plastic deformed state at the beginning of the plastic structural collapse. We have also detailed the theoretical duality between two classes of structures—hyperstatic and hypostatic—which was derived from the linear algebra principles that define these solutions. Finally, we studied and exposed the dimensionality reduction of structural problems given by the singular value decomposition and the eigenvalues problem. An illustrative example that clearly illustrates all these points is provided.
New Zealand's extinct giant raptor (Hieraaetus moorei) killed like an eagle, ate like a condor
Authors: van Heteren A. H. , Wroe S. , Tsang L. R. , Mitchell D. R. , Ross P. , Ledogar J. A. , Attard M. R. G. , Sustaita D. , Clausen P. , Scofield R. P. , Sansalone G.
Published: December 2021

The extinct Haast's eagle or harpagornis (Hieraaetus moorei) is the largest known eagle. Historically, it was first considered a predator, then a scavenger, but most recent authors have favoured an active hunting ecology. However, the veracity of proposed similarities to carrion feeders has not been thoroughly tested. To infer feeding capability and behaviour in harpagornis, we used geometric morphometric and finite-element analyses to assess the shape and biomechanical strength of its neurocranium, beak and talons in comparison to five extant scavenging and predatory birds. The neurocranium of harpagornis is vulture-like in shape whereas its beak is eagle-like. The mechanical performance of harpagornis is closer to extant eagles under biting loads but is closest to the Andean condor (Vultur gryphus) under extrinsic loads simulating prey capture and killing. The talons, however, are eagle-like and even for a bird of its size, able to withstand extremely high loads. Results are consistent with the proposition that, unlike living eagles, harpagornis habitually killed prey larger than itself, then applied feeding methods typical of vultures to feed on the large carcasses. Decoupling of the relationship between neurocranium and beak shape may have been linked to rapid evolution.
Assessment of mycoviral diversity in Pakistani fungal isolates revealed infection by 11 novel viruses of a single strain of Fusarium mangiferae isolate SP1
Authors: Khan Haris Ahmed , Shamsi Wajeeha , Jamal Atif , Javaied Memoona , Sadiq Mashal , Fatma Tehsin , Ahmed Aqeel , Arshad Maleeha , Waseem Mubashra , Babar Samra , Dogar Midhat Mustafa , Virk Nasar , Janjua Hussnain Ahmed , Kondo Hideki , Suzuki Nobuhiro , Bhatti Muhammad Faraz
Published: December 2021

An extensive screening survey was conducted on Pakistani filamentous fungal isolates for the identification of viral infections. A total of 396 fungal samples were screened, of which 36 isolates were found double-stranded (ds) RNA positive with an overall frequency of 9% when analysed by a classical dsRNA isolation method. One of 36 dsRNA-positive strains, strain SP1 of a plant pathogenic fungus Fusarium mangiferae, was subjected to virome analysis. Next-generation sequencing and subsequent completion of the entire genome sequencing by a classical Sanger sequencing method showed the SP1 strain to be co-infected by 11 distinct viruses, at least seven of which should be described as new taxa at the species level according to the ICTV (International Committee on Taxonomy of Viruses) species demarcation criteria. The newly identified F. mangiferae viruses (FmVs) include two partitivirids, one betapartitivirus (FmPV1) and one gammapartitivirus (FmPV2); six mitovirids, three unuamitovirus (FmMV2, FmMV4, FmMV6), one duamitovirus (FmMV5), and two unclassified mitovirids (FmMV1, FmMV3); and three botourmiavirids, two magoulivirus (FmBOV1, FmBOV3) and one scleroulivirus (FmBOV2). The number of coinfecting viruses is among the largest ones of fungal coinfections. Their molecular features are thoroughly described here. This represents the first large virus survey in the Indian sub-continent.
AImmune: a new blood-based machine learning approach to improving immune profiling analysis on COVID-19 patients
Authors: Han Runpeng Harris , Zhang Xi Tom
Published: December 2021

A massive number of transcriptomic profiles of blood samples from COVID-19 patients has been produced since pandemic COVID-19 begins, however, these big data from primary studies have not been well integrated by machine learning approaches. Taking advantage of modern machine learning arthrograms, we integrated and collected single cell RNA-seq (scRNA-seq) data from three independent studies, identified genes potentially available for interpretation of severity, and developed a high-performance deep learning-based deconvolution model AImmune that can predict the proportion of seven different immune cells from the bulk RNA-seq results of human peripheral mononuclear cells. This novel approach which can be used for clinical blood testing of COVID-19 on the ground that previous research shows that mRNA alternations in blood-derived PBMCs may serve as a severity indicator. Assessed on real-world data sets, the AImmune model outperformed the most recognized immune profiling model CIBERSORTx. The presented study showed the results obtained by the true scRNA-seq route can be consistently reproduced through the new approach AImmune, indicating a potential replacing the costly scRNA-seq technique for the analysis of circulating blood cells for both clinical and research purposes.