bluuebunny/crossref_metadata_2025 huggingface dataset:
Cryoablation vs. radiofrequency ablation of the atrioventricular node in patients with His-bundle pacing
Authors: Zweerink Alwin , Bakelants Elise , Stettler Carine , Burri Haran
Published: October 2020

Aims

Radiofrequency ablation (RFA) of the atrioventricular node (AVN) with His-bundle pacing (HBP) can cause rise in capture thresholds. Cryoablation (CRYO) may offer reversibility in case of threshold rise but has never been tested for AVN ablation in this setting. Our aim was to compare procedural characteristics and outcome of CRYO compared with RFA for AVN ablation in patients with HBP.

Methods and results

Forty-four patients with HBP underwent AVN ablation for an ‘ablate and pace’ indication. Cryoablation was performed in the first 22 patients and RFA in the following 22 patients. Procedural characteristics, success rates, and change in His capture thresholds were compared between groups. Distance from the ablation site to the His lead was measured using biplane fluoroscopy. Acute success was 100% with both strategies. Median procedural duration was significantly longer for CRYO {50 [interquartile range (IQR) 38–63] min} compared with RFA [36 (IQR, 30–41) min; P = 0.027]. An acute threshold rise of ≥1 V was observed in four CRYO (one complete loss of capture) and three RFA patients (P = 0.38), with all of the applications being within 6 mm of the His lead tip. During follow-up, nine patients had AVN re-conduction (six CRYO vs. three RFA; P = 0.58), but only four patients required a redo procedure (all CRYO; P = 0.09).

Conclusion

Cryoablation does not offer any advantage over RFA for AVN ablation in patients with HBP and tended to require more redo procedures. If possible, a distance of ≥6 mm should be maintained from the His lead tip to avoid a rise in capture thresholds.
Are Older Populations at a Disadvantage? County-Level Analysis of Confirmed COVID-19 Cases in Urban and Rural America
Authors: Choi Seung-won Emily , Yang Tse-Chuan
Published: October 2020

Objectives

This study examines how areas with different older population compositions are affected by Coronavirus Disease 2019 (COVID-19) and whether urban and rural counties face different challenges.

Methods

Applying negative binomial regression to a data set of U.S. counties (N = 3,042), we estimated the relationship between older population ratios and the number of confirmed COVID-19 cases, and how this relationship changes over time in urban and rural counties, respectively.

Results

Although low-ratio counties show the highest number of confirmed cases of COVID-19 at the beginning of the pandemic, confirmed cases in high-ratio counties (>25% of the total population is aged 65 and older) increase exponentially with time in urban areas. High-ratio rural counties hit their peak later and recover more slowly compared to low- and medium-ratio rural counties.

Discussion

Both urban and rural counties with larger older populations are more vulnerable and their disadvantages in COVID-19 infections are more rapidly exacerbated over time in urban areas. This underscores the importance of early action in those counties for effective intervention and prevention.
‘We had to manage what we had on hand, in whatever way we could’: adaptive responses in policy for decentralized drug-resistant tuberculosis care in South Africa
Authors: Kielmann Karina , Dickson-Hall Lindy , Jassat Waasila , Le Roux Sacha , Moshabela Mosa , Cox Helen , Grant Alison D , Loveday Marian , Hill Jeremy , Nicol Mark P , Mlisana Koleka , Black John
Published: October 2020

In 2011, the South African National TB Programme launched a policy of decentralized management of drug-resistant tuberculosis (DR-TB) in order to expand the capacity of facilities to treat patients with DR-TB, minimize delays to access care and improve patient outcomes. This policy directive was implemented to varying degrees within a rapidly evolving diagnostic and treatment landscape for DR-TB, placing new demands on already-stressed health systems. The variable readiness of district-level systems to implement the policy prompted questions not only about differences in health systems resources but also front-line actors’ capacity to implement change in resource-constrained facilities. Using a grounded theory approach, we analysed data from in-depth interviews and small group discussions conducted between 2016 and 2018 with managers (n = 9), co-ordinators (n = 15), doctors (n = 7) and nurses (n = 18) providing DR-TB care. Data were collected over two phases in district-level decentralized sites of three South African provinces. While health systems readiness assessments conventionally map the availability of ‘hardware’, i.e. resources and skills to deliver an intervention, a notable absence of systems ‘hardware’ meant that systems ‘software’, i.e. health care workers (HCWs) agency, behaviours and interactions provided the basis of locally relevant strategies for decentralized DR-TB care. ‘Software readiness’ was manifest in four areas of DR-TB care: re-organization of service delivery, redressal of resource shortages, creation of treatment adherence support systems and extension of care parameters for vulnerable patients. These strategies demonstrate adaptive capacity and everyday resilience among HCW to withstand the demands of policy change and innovation in stressed systems. Our work suggests that a useful extension of health systems ‘readiness’ assessments would include definition and evaluation of HCW ‘software’ and adaptive capacities in the face of systems hardware gaps.
Neurostructural Correlates of Cannabis Use in Adolescent Bipolar Disorder
Authors: Sultan Alysha A , Kennedy Kody G , Fiksenbaum Lisa , MacIntosh Bradley J , Goldstein Benjamin I
Published: October 2020

Background

Little is known regarding the association of cannabis use with brain structure in adolescents with bipolar disorder (BD). This subject is timely, given expanded availability of cannabis contemporaneously with increased social acceptance and diminished societal constraints to access. Therefore, we set out to examine this topic in a sample of adolescents with BD and healthy control (HC) adolescents.

Methods

Participants included 144 adolescents (47 BD with cannabis use [BDCB+; including 13 with cannabis use disorder], 34 BD without cannabis use [BDCB−], 63 HC without cannabis use) ages 13–20 years. FreeSurfer-processed 3T MRI with T1-weighted contrast yielded measures of cortical thickness, surface area (SA), and volume. Region of interest (amygdala, hippocampus, ventrolateral prefrontal cortex, ventromedial prefrontal cortex, and anterior cingulate cortex) analyses and exploratory vertex-wise analysis were undertaken. A general linear model tested for between-group differences, accounting for age, sex, and intracranial volume.

Results

Vertex-wise analysis revealed significant group effects in frontal and parietal regions. In post-hoc analyses, BDCB+ exhibited larger volume and SA in parietal regions, and smaller thickness in frontal regions, relative to HC and BDCB−. BDCB− had smaller volume, SA, and thickness in parietal and frontal regions relative to HC. There were no significant region of interest findings after correcting for multiple comparisons.

Conclusion

This study found that cannabis use is associated with differences in regional brain structure among adolescents with BD. Future prospective studies are necessary to determine the direction of the observed association and to assess for dose effects.
Projection Effects and the Role of Political Ambiguity
Authors: Martin Danielle , Banducci Susan , Stevens Daniel , Coan Travis
Published: October 2020

Scholars studying political perceptions find evidence of the presence of projection effects. Yet several questions still need to be explored as to the time frame of the effect and the factors affecting projection. In particular, although the effect of ambiguity on projection has often been assumed and has been tested in a formal model (Jensen, 2009), no empirical evidence supports the idea that ambiguity fosters projection. We analyze an online survey conducted before and after the 2017 UK General Election. In addition to testing for the presence of projection effects on four different policy issues, we show that ambiguity fosters projection. This result suggests that ambiguity is not always necessarily a good strategy for political parties.
Molecular Epidemiology of Mansonella Species in Gabon
Authors: Sandri Thaisa Lucas , Kreidenweiss Andrea , Cavallo Simon , Weber David , Juhas Sascha , Rodi Miriam , Woldearegai Tamirat Gebru , Gmeiner Markus , Veletzky Luzia , Ramharter Michael , Tazemda-Kuitsouc Gildas B , Matsiegui Pierre Blaise , Mordmüller Benjamin , Held Jana
Published: October 2020

Mansonella perstans, a filarial nematode, infects large populations in Africa and Latin America. Recently, a potential new species, Mansonella sp “DEUX,” was reported. Carriage of endosymbiotic Wolbachia opens treatment options for Mansonella infections. Within a cross-sectional study, we assessed the prevalence of filarial infections in 834 Gabonese individuals and the presence of the endosymbiont Wolbachia. Almost half of the participants (400/834 [48%]) were infected with filarial nematodes, with Mansonella sp “DEUX” being the most frequent (295/400 [74%]), followed by Loa loa (273/400 [68%]) and Mansonella perstans (82/400 [21%]). Being adult/elderly, male, and living in rural areas was associated with a higher risk of infection. Wolbachia carriage was confirmed in M. perstans and Mansonella sp “DEUX.” In silico analysis revealed that Mansonella sp “DEUX” is not detected with currently published M. perstans–specific assays. Mansonella infections are highly prevalent in Gabon and might have been underreported, likely also beyond Gabon.
Malta’s only acute public hospital service during COVID-19: a diary of events from the first wave to transition phase
Authors: Cuschieri Sarah , Falzon Celia , Janulova Lina , Aguis Steve , Busuttil Walter , Psaila Noel , Farrugia Karl , Debono Joseph , Grech Victor
Published: October 2020

Introduction

COVID-19 has challenged healthcare systems worldwide. Some countries collapsed under surge conditions, while others (such as Malta) showed resilience. Public health measures in Malta quickly reined in COVID-19 spread. This review summarizes pandemic preparedness measures in Malta and the impact on routine services.

Methods

A literature search was conducted using Google, Google Scholar and PubMed and by reviewing Maltese online newspapers. A comprehensive summary of internal operations conducted at Mater Dei Hospital (MDH) was made available.

Results

A hospital ‘Incident Command Group’ was set up to plan an optimal COVID-19 response strategy. A ‘rapid response team’ was also created to cater for the logistics and management of supplies. A ‘COVID-19 Emergency Operation Centre’ simulated different COVID-19 scenarios. All elective services were suspended and all staff were mandatorily trained in wearing personal protective equipment. Staff were also retrained in the care of COVID-19 patients. In preparation for potential admission surges, MDH underwent rapid expansion of normal and intensive care beds. Swabbing was ramped up to one of the highest national rates worldwide. The cost for hospital COVID-19 preparedness exceeded €100 million for Malta’s half a million population.

Conclusion

Malta and its sole acute hospital coped well with the first wave with 680 cases and 9 deaths. The increased ability to deal with COVID-19 (a principally respiratory pathogen) will serve well for the anticipated combined annual influenza and the COVID-19 second wave this coming winter.
Restoring carbapenem efficacy: a novel carbapenem companion targeting metallo-β-lactamases in carbapenem-resistant Enterobacterales
Authors: Ooi Nicola , Lee Victoria E , Chalam-Judge Nathan , Newman Rebecca , Wilkinson Andrew J , Cooper Ian R , Orr David , Lee Sally , Savage Victoria J
Published: October 2020

Background

The dissemination of MBLs compromises effective use of many β-lactams in the treatment of patients with life-threatening bacterial infections. Predicted global increases in the prevalence of MBL-producing carbapenem-resistant Enterobacterales (CRE) are being realized, yielding infections that are untreatable with existing therapies including newly approved β-lactam/β-lactamase inhibitor combinations. Developing MBL inhibitors (MBLIs) now is essential to address the growing threat that MBL-producing CRE pose to patients.

Methods

A novel MBLI series was assessed by susceptibility testing and time–kill assays. Target activity and selectivity was evaluated using bacterial NDM, VIM and IMP enzyme assays and human matrix metallopeptidase enzyme assays, respectively, and cytotoxicity was assessed in HepG2 cells. In vivo efficacy of meropenem/MBLI combinations was evaluated in a mouse thigh infection model using an NDM-1-producing Escherichia coli strain.

Results

Combination of MBLIs with carbapenems reduced MICs for NDM/IMP/VIM-producing Enterobacterales by up to 128-fold compared with the carbapenems alone. Supplementation of meropenem with the promising compound 272 reduced the MIC90 from 128 to 0.25 mg/L in a panel of MBL-producing CRE clinical isolates (n = 115). Compound 272 restored the bactericidal activity of meropenem and was non-cytotoxic, potentiating the antimicrobial action of meropenem through specific inhibition of NDM, IMP and VIM. In vivo efficacy was achieved in a mouse thigh infection model with meropenem/272 dosed subcutaneously.

Conclusions

We have developed a series of rationally designed MBLIs that restore activity of carbapenems against NDM/IMP/VIM-producing Enterobacterales. This series warrants further development towards a novel combination therapy that combats antibiotic-resistant organisms, which pose a critical threat to human health.
Correlation of SARS-CoV-2 Neutralizing Antibodies to an Automated Chemiluminescent Serological Immunoassay
Authors: Grenache David G , Ye Chunyan , Bradfute Steven B
Published: October 2020

Introduction

Neutralizing antibodies (NAbs) are capable of binding to a virus to render it incapable of infection. The ability of commercially available SARS-CoV-2 serological tests to detect NAbs has not been widely reported. We sought to correlate the antibodies detected by an automated chemiluminescent immunoassay with NAbs.

Methods

Residual serum samples from 35 patients that had a positive antibody test using the LIAISON® SARS-CoV-2 S1/S2 IgG chemiluminescent immunoassay and 2 antibody-negative control sera were tested for NAbs using a plaque reduction neutralization test (PRNT).

Results

NAbs were detected in 66% (23/35) of the antibody-positive samples. The immunoassay signal value ranged from 21.7 to 131.3 AU/mL (median, 90.5) with significant correlation between it and the PRNT (r = 0.61, P = 0.002). In the samples without NAbs, the immunoassay signal ranged from 16.3 to 66.2 AU/mL (median, 27.2). An immunoassay signal cutoff of >41 AU/mL was 91% sensitive and 92% specific for the detection of NAbs.

Discussion

It is important that correlates of immunity to SARS-CoV-2 be identified and NAbs are considered to be central indicators of such. PRNT is the gold-standard test for identifying NAbs but it cannot be used for large-scale testing of populations. It is necessary to establish relationships between it and widely used commercial serological assays for SARS-CoV-2.
Towards a Right to Sustainable Security of Person in Times of Terrorism? Assessing Possibilities and Limitations Through a Critical Evaluation of Citizenship Stripping and Non-Repatriation Policies
Authors: Paulussen Christophe
Published: October 2020

On the basis of the case studies of deprivation of nationality and the non-repatriation and possible prosecution of foreign fighters and their families, this article will argue that some counter-terrorism measures, adopted under the justification of protecting national security, will not make these countries, and thus also the individuals under its jurisdiction, safer. Hence, it is wondered whether the notion of national security is both spatially and temporally still in sync with the hyperconnected world in which we live and in which terrorists operate—and whether it is not better to move to the adoption of the broader concept of sustainable security. This article will then turn to the question of whether ordinary citizens (or NGOs litigating on their behalf) could use their existing right to security of person to block those inefficient measures and if not, whether they should be able to operationalise the concept of sustainable security in the human rights context. The article will assert that while the general concept of sustainable security can certainly help at the policy level in encouraging governments to move away from mere national security thinking and thus assist in adopting counter-terrorism measures that provide true, durable security, the situation is different at the level of human rights. The existing right to security of person arguably does not go that far to be able to block the inefficient counter-terrorism measures as discussed in this article and an extension of this right, to a right to sustainable security of person, should not be pursued.
Dark Energy Survey Year 1 results: the lensing imprint of cosmic voids on the cosmic microwave background
Authors: Vielzeuf P , Kovács A , Demirbozan U , Fosalba P , Baxter E , Hamaus N , Huterer D , Miquel R , Nadathur S , Pollina G , Sánchez C , Whiteway L , Abbott T M C , Allam S , Annis J , Avila S , Brooks D , Burke D L , Carnero Rosell A , Carrasco Kind M , Carretero J , Cawthon R , Costanzi M , da Costa L N , De Vicente J , Desai S , Diehl H T , Doel P , Eifler T F , Everett S , Flaugher B , Frieman J , García-Bellido J , Gaztanaga E , Gerdes D W , Gruen D , Gruendl R A , Gschwend J , Gutierrez G , Hartley W G , Hollowood D L , Honscheid K , James D J , Kuehn K , Kuropatkin N , Lahav O , Lima M , Maia M A G , March M , Marshall J L , Melchior P , Menanteau F , Palmese A , Paz-Chinchón F , Plazas A A , Sanchez E , Scarpine V , Serrano S , Sevilla-Noarbe I , Smith M , Suchyta E , Tarle G , Thomas D , Weller J , Zuntz J ,   The DES Collaboration
Published: October 2020

Cosmic voids gravitationally lens the cosmic microwave background (CMB) radiation, resulting in a distinct imprint on degree scales. We use the simulated CMB lensing convergence map from the Marenostrum Institut de Ciencias de l’Espai (MICE) N-body simulation to calibrate our detection strategy for a given void definition and galaxy tracer density. We then identify cosmic voids in Dark Energy Survey (DES) Year 1 data and stack the Planck 2015 lensing convergence map on their locations, probing the consistency of simulated and observed void lensing signals. When fixing the shape of the stacked convergence profile to that calibrated from simulations, we find imprints at the 3σ significance level for various analysis choices. The best measurement strategies based on the MICE calibration process yield S/N ≈ 4 for DES Y1, and the best-fitting amplitude recovered from the data is consistent with expectations from MICE (A ≈ 1). Given these results as well as the agreement between them and N-body simulations, we conclude that the previously reported excess integrated Sachs–Wolfe (ISW) signal associated with cosmic voids in DES Y1 has no counterpart in the Planck CMB lensing map.
The environmental dependence of rapidly quenching and rejuvenating galaxies
Authors: Cleland Cressida , McGee Sean L
Published: October 2020

By combining H α flux measurements from the Sloan Digital Sky Survey (SDSS) with ultraviolet (UV) flux observations from the Galaxy Evolution Explorer (GALEX), we examine the environmental dependence (through central/satellite distinction) of the rapid quenching and rejuvenation of galaxies. H α emissions trace the most massive stars, thereby indicating star formation on time-scales of ∼10 Myr, while UV emission traces star formation on time-scales of ∼100 Myr. These varying time-scales are exploited to probe the most recent star formation histories of galaxies. In this work, we define a class of transient galaxies that have UV emission typical of star formation but negligible H α emission. We find that the occurrence of these transients has a strong stellar mass dependence in both the satellite and central populations. However, while at stellar masses greater than M* ∼ 1010 M⊙ they occur with equal frequency regardless of environmental class, at lower stellar masses they are more common in satellites only, with an excess of about 1 percentage point across all low stellar mass galaxies. These satellite transients also have a strong halo mass and group-centric radial dependence suggesting they are driven by an environmental process. Finally, we select a sample of galaxies with H α emission but not UV emission that could contain short time-scale rejuvenating galaxies. These rejuvenating candidates are few in number and do not have a strong difference in their occurrence rate in centrals or satellites. These unique probes point to an environmental quenching mechanism that occurs on short time-scales after the satellite has been in the group environment for a significant time – consistent with ‘delayed-then-rapid’ quenching.
WISDOM project – VI. Exploring the relation between supermassive black hole mass and galaxy rotation with molecular gas
Authors: Smith Mark D , Bureau Martin , Davis Timothy A , Cappellari Michele , Liu Lijie , Onishi Kyoko , Iguchi Satoru , North Eve V , Sarzi Marc
Published: October 2020

Empirical correlations between the masses of supermassive black holes (SMBHs) and properties of their host galaxies are well established. Among these is the correlation with the flat rotation velocity of each galaxy measured either at a large radius in its rotation curve or via a spatially integrated emission-line width. We propose here the use of the deprojected integrated CO emission-line width as an alternative tracer of this rotation velocity, which has already been shown useful for the Tully–Fisher (luminosity–rotation velocity) relation. We investigate the correlation between CO line widths and SMBH masses for two samples of galaxies with dynamical SMBH mass measurements, with spatially resolved and unresolved CO observations, respectively. The tightest correlation is found using the resolved sample of 25 galaxies as $\log (M_\mathrm{BH}/\mathrm{M_\odot })=(7.5\pm 0.1)+(8.5\pm 0.9)[\log (W_\mathrm{50}/\sin i \, \mathrm{km\, s}^{-1})-2.7]$, where MBH is the central SMBH mass, W50 is the full width at half-maximum of a double-horned emission-line profile, and i is the inclination of the CO disc. This relation has a total scatter of $0.6\,$ dex, comparable to those of other SMBH mass correlations, and dominated by the intrinsic scatter of $0.5\,$ dex. A tight correlation is also found between the deprojected CO line widths and the stellar velocity dispersions averaged within one effective radius. We apply our correlation to the COLD GASS sample to estimate the local SMBH mass function.
Predictions for the FAST telescope’s CRAFTS extragalactic H i survey
Authors: Zhang Kai , Wu Jingwen , Li Di , Tsai Chao-Wei , Staveley-Smith Lister , Wang Jing , Fu Jian , McIntyre Travis , Yuan Mao ,   (FAST collaboration), Marko Krčo , Michael G Jones , Ying Zu , Sean E
Published: October 2020

The Five-hundred-meter Aperture Spherical radio Telescope (FAST) has started the Commensal Radio Astronomy FasT Survey (CRAFTS). In this paper, we use the technical parameters of FAST derived from commissioning observations to simulate the completeness function for extragalactic H i survey of CRAFTS, H i galaxies from two kinds of mock catalogues are selected. One is generated by Monte Carlo simulation based on the interpolated mass–velocity width function of the ALFALFA $100{{\ \rm per\ cent}}$ (a.k.a. α.100) catalogue. The other is constructed by semi-analytical N-body simulation based on the ΛCDM model. Our results suggest that a two-pass CRAFTS extragalactic H i survey will be able to detect nearly 4.8 × 105 galaxies, from which the ‘faint end’ slope of the H i mass function (HIMF) can be recovered to $\mathrm{10^{7}\, M_{\odot }}$ and the ‘knee mass’ of the HIMF can be measured to a redshift of 0.1. Considering the radio frequency interference status and sensitivity limitation, CRAFTS will be efficient in detecting H i galaxies at redshifts below 0.1, which implies a tremendous potential in exploring the galaxy interactions in different environments and the spatial distribution of H i galaxies in the local universe.
The ssDNA-binding protein MEIOB acts as a dosage-sensitive regulator of meiotic recombination
Authors: Guo Rui , Xu Yang , Leu N Adrian , Zhang Lei , Fuchs Serge Y , Ye Lan , Wang P Jeremy
Published: October 2020

Meiotic recombination enables reciprocal exchange of genetic information between parental chromosomes and is essential for fertility. MEIOB, a meiosis-specific ssDNA-binding protein, regulates early meiotic recombination. Here we report that the human infertility-associated missense mutation (N64I) in MEIOB causes protein degradation and reduced crossover formation in mouse testes. Although the MEIOB N64I substitution is associated with human infertility, the point mutant mice are fertile despite meiotic defects. Meiob mutagenesis identifies serine 67 as a critical residue for MEIOB. Biochemically, these two mutations (N64I and S67 deletion) cause self-aggregation of MEIOB and sharply reduced protein half-life. Molecular genetic analyses of both point mutants reveal an important role for MEIOB in crossover formation in late meiotic recombination. Furthermore, we find that the MEIOB protein levels directly correlate with the severity of meiotic defects. Our results demonstrate that MEIOB regulates meiotic recombination in a dosage-dependent manner.
Building a tRNA thermometer to estimate microbial adaptation to temperature
Authors: Cimen Emre , Jensen Sarah E , Buckler Edward S
Published: October 2020

Because ambient temperature affects biochemical reactions, organisms living in extreme temperature conditions adapt protein composition and structure to maintain biochemical functions. While it is not feasible to experimentally determine optimal growth temperature (OGT) for every known microbial species, organisms adapted to different temperatures have measurable differences in DNA, RNA and protein composition that allow OGT prediction from genome sequence alone. In this study, we built a ‘tRNA thermometer’ model using tRNA sequence to predict OGT. We used sequences from 100 archaea and 683 bacteria species as input to train two Convolutional Neural Network models. The first pairs individual tRNA sequences from different species to predict which comes from a more thermophilic organism, with accuracy ranging from 0.538 to 0.992. The second uses the complete set of tRNAs in a species to predict optimal growth temperature, achieving a maximum ${r^2}$ of 0.86; comparable with other prediction accuracies in the literature despite a significant reduction in the quantity of input data. This model improves on previous OGT prediction models by providing a model with minimum input data requirements, removing laborious feature extraction and data preprocessing steps and widening the scope of valid downstream analyses.
Hypoxia changes the shape of the biomass size spectrum of planktonic communities: a case study in the eastern Mediterranean (Elefsina Bay)
Authors: Batziakas Stratos , Frangoulis Constantin , Tsiola Anastasia , Nikolioudakis Nikolaos , Tsagaraki Tatiana M , Somarakis Stylianos
Published: October 2020

Hypoxia is a major stressor on biological communities in many oceanic and coastal ecosystems. Various size-dependent processes (e.g. growth and reproduction rates, predator–prey interactions) are adversely affected by hypoxia. We hypothesized that the impacts of hypoxia on planktonic communities would also be reflected in their Normalized Biomass Size Spectra (NBSS) as steeper slopes and lower intercepts. To explore this hypothesis, we studied the planktonic communities (from bacteria to mesozooplankton) of Elefsina, an enclosed bay that exhibits near bottom hypoxia during summer, and Aghios Kosmas, an adjacent coastal site outside the bay. Bottom layer hypoxia formed during the stratification period in Elefsina Bay significantly altered the distribution of planktonic organisms in the water column. Several unicellular and mesozooplanktonic groups avoided the hypoxic layer, in which the biomass of autotrophic picoeukaryotes was markedly higher. Community changes related to hypoxia were clearly reflected in the NBSS. The slope was significantly steeper in the hypoxic layer (−1.330 vs −1.193) and the intercept was lower (−2.222 vs −0.972, hypoxic vs oxic layer). This result can be interpreted as reduced trophic transfer efficiency to the higher trophic levels due to hypoxia.
Budget impact analysis of an early identification and referral model for diagnosing patients with suspected rheumatoid arthritis in Ireland
Authors: Kelleher Dan , Barry Luke , McGowan Bernie , Doherty Edel , Carey John J , Kane David
Published: October 2020

Objective

To estimate the budget impact from the perspective of the Irish health-care system attributable to a reconfiguration in the diagnostic care pathway for patients with suspected RA by adopting an early identification and referral model (EIM).

Methods

The budget impact model evaluated the total health-care use and costs attributable to an EIM to diagnose patients with suspected RA relative to the reference scenario of current practice. The modelling also assessed a primary outcome of effect, which examined how many patients can be diagnosed by a rheumatologist within 3 months of symptom onset. The budget impact analysis model was estimated over a 5-year time frame.

Results

The EIM generated a cost saving for the Irish health-care system of €237 547 over the time frame relative to current practice. The cost savings were realized owing to a reduction in the number of general practitioner (GP) visits of 18 790 and a reduction in diagnostic tests carried out by GPs. The results showed that 1027 (510%) more patients were diagnosed within 3 months of symptom onset in the EIM compared with current practice.

Conclusion

This paper has presented an alternative rheumatologist-led service design that can be used in diagnosing patients with suspected RA. The rheumatologist-led service provision detailed in this study has the potential simultaneously to reduce demand for primary care services and to improve the health outcomes of patients. The use of an EIM sees rheumatologist activity incorporate patient demand.
Proinflammatory and bone protective role of calcitonin gene-related peptide alpha in collagen antibody-induced arthritis
Authors: Maleitzke Tazio , Hildebrandt Alexander , Weber Jérôme , Dietrich Tamara , Appelt Jessika , Jahn Denise , Zocholl Dario , Baranowsky Anke , Duda Georg N , Tsitsilonis Serafeim , Keller Johannes
Published: October 2020

Objectives

Calcitonin gene-related peptide alpha (αCGRP) represents an immunomodulatory neuropeptide implicated in pain perception. αCGRP also functions as a critical regulator of bone formation and is overexpressed in patients with rheumatoid arthritis (RA). In the present study, we investigated the role of αCGRP in experimental RA regarding joint inflammation and bone remodelling.

Methods

Collagen II-antibody-induced arthritis (CAIA) was induced in wild type (WT) and αCGRP-deficient (αCGRP-/-) mice. Animals were monitored over 10 and 48 days with daily assessments of the semiquantitative arthritis score and grip strength test. Joint inflammation, cartilage degradation and bone erosions were assessed by histology, gene expression analysis and µCT.

Results

CAIA was accompanied by an overexpression of αCGRP in WT joints. αCGRP-/- mice displayed reduced arthritic inflammation and cartilage degradation. Congruently, the expression of TNF-α, IL-1β, CD80 and MMP13 was induced in WT, but not αCGRP-/- animals. WT mice displayed an increased bone turnover during the acute inflammatory phase, which was not the case in αCGRP-/- mice. Interestingly, WT mice displayed a full recovery from the inflammatory bone disease, whereas αCGRP-/- mice exhibited substantial bone loss over time.

Conclusion

This study demonstrates a proinflammatory and bone protective role of αCGRP in CAIA. Our data indicate that αCGRP not only enhances joint inflammation, but also controls bone remodelling as part of arthritis resolution. As novel αCGRP inhibitors are currently introduced clinically for the treatment of migraine, their potential impact on RA progression warrants further clinical investigation.
Causal association of adipokines with osteoarthritis: a Mendelian randomization study
Authors: Fan Jiayao , Zhu Jiahao , Sun Lingling , Li Yasong , Wang Tianle , Li Yingjun
Published: October 2020

Objective

This two-sample Mendelian randomization study aimed to delve into the effects of genetically predicted adipokine levels on OA.

Methods

Summary statistic data for OA originated from a meta-analysis of a genome-wide association study with an overall 50 508 subjects of European ancestry. Publicly available summary data from four genome-wide association studies were exploited to respectively identify instrumental variables of adiponectin, leptin, resistin, chemerin and retinol-blinding protein 4. Subsequently, Mendelian randomization analyses were conducted with inverse variance weighted (IVW), weighted median and Mendelian randomization-Egger regression. Furthermore, sensitivity analyses were then conducted to assess the robustness of our results.

Results

The positive causality between genetically predicted leptin level and risk of total OA was indicated by IVW [odds ratio (OR): 2.40, 95% CI: 1.13–5.09] and weighted median (OR: 2.94, 95% CI: 1.23–6.99). In subgroup analyses, evidence of potential harmful effects of higher level of adiponectin (OR: 1.28, 95% CI: 1.01–1.61 using IVW), leptin (OR: 3.44, 95% CI: 1.18–10.03 using IVW) and resistin (OR: 1.18, 95% CI: 1.03–1.36 using IVW) on risk of knee OA were acquired. However, the mentioned effects on risk of hip OA were not statistically significant. Slight evidence was identified supporting causality of chemerin and retinol-blinding protein 4 for OA. The findings of this study were verified by the results from sensitivity analysis.

Conclusions

An association between genetically predicted leptin level and risk of total OA was identified. Furthermore, association of genetically predicted levels of adiponectin, leptin and resistin with risk of knee OA were reported.
High prevalence of steroid-induced glucose intolerance with normal fasting glycaemia during low-dose glucocorticoid therapy: an oral glucose tolerance test screening study
Authors: Nowak Karolina M , Rdzanek-Pikus Monika , Romanowska-Próchnicka Katarzyna , Nowakowska-Płaza Anna , Papierska Lucyna
Published: October 2020

Objectives

To evaluate the prevalence and risk factors of new-onset glucose metabolism impairment using an oral glucose tolerance test (OGTT) in patients with normal fasting glycaemia on long-term glucocorticoid (GC) treatment.

Methods

An OGTT was performed in 150 patients without a previous history of pre-diabetes or diabetes who were diagnosed with inflammatory rheumatic diseases and treated with GCs >3 months. All participants underwent clinical and biochemical evaluation for risk factors of diabetes: age, sex, current and cumulative dose of steroids, treatment duration, waist circumference, BMI, Homeostatic Model Assessment for Insulin Resistance, fasting insulin concentration, family history of diabetes, CRP, 28-joint DAS with CRP, type of connective tissue disease and trunk fat percentage measured by DXA. Logistic regression analysis was conducted to evaluate the association between the presence of impaired glucose tolerance (IGT) in the OGTT and analysed risk factors.

Results

A total of 102 patients (68%) had fully normal glucose tolerance. Diabetes, isolated impaired fasting glucose, isolated IGT and combined impaired fasting glucose + IGT was diagnosed in 3.3, 4.67, 19.33 and 4.67% of patients, respectively; 20% of participants had IGT or diabetes despite normal fasting glucose concentration. The median cumulative dose and current dose (5 mg) of GCs and treatment duration were similar compared with the normal glucose tolerance group. In a multivariate logistic regression model, only older age (particularly ≥50 years of age) and trunk fat percentage remained significant factors predicting IGT or diabetes in the OGTT.

Conclusion

New-onset GC-induced glucose intolerance, even in patients on long-term low-dose treatment, is prevalent despite normal fasting glucose concentration and patients should be screened with an OGTT despite the absence of classic risk factors of diabetes.
Investigating the affordances of a flipped mathematics classroom from an activity theoretical perspective
Authors: Fredriksen Helge
Published: October 2020

Flipped Classroom as a pedagogical framework has gained popularity at secondary and tertiary levels of mathematics education, but there is a lack of research based on a solid theoretical foundation. This article considers the flipped mathematics classroom from the perspective of affordances and cultural–historical activity theory. The empirical background is based on semi-structured interview data from eight first-year computer-engineering students following 1 year of flipped classroom teaching. The thematic analysis of the data indicates that the flipped format offers a range of affordances at various levels of the activity system. This article advances research on affordances for mathematical learning in a flipped classroom pedagogical frame, presenting operational affordances out-of-class, action affordances at the mathematical task level and finally activity affordances at the collective level.
Effects of Soybean Cultivar, Foliar Application of Azoxystrobin, and Year on Seed Vigor and Microflora Under Delayed Harvest Conditions
Authors: Cochran Kimberly , Steger Adele J. , Holland Robert , Rupe John C.
Published: October 2020

The effects of cultivar and foliar fungicide applications on soybean seed germination, vigor, microflora, and yield after delayed harvest were determined at the University of Arkansas Vegetable Research Station in Kibler, AR, from 2008 to 2010. Seven cultivars with varying levels of resistance to Diaporthe spp. or Cercospora spp. were treated or not treated with a foliar application of azoxystrobin at the R5 growth stage. Plots were harvested 3 weeks after the plants had reached harvest maturity. Yields were recorded, samples of seed were collected, and standard germination (SG) and accelerated aging (AA) were assessed. Seeds were also assayed for infection by fungi on modified potato dextrose agar and by bacteria on nutrient agar. Seed vigor was significantly reduced by infection with Diaporthe spp., Fusarium spp., and Bacillus subtilis, but not with Cercospora spp. Cultivar had a significant impact on yield, seed vigor, and seed infection levels. The cultivar Osage had consistently high seed vigor and low overall seed infection incidence throughout the study. MO/PSD-0259, AG 4403, and UA 4805 also had relatively high seed vigor and low seed infection rates. PI 80837 had a low incidence of seed infection by Diaporthe spp. and Fusarium spp. in 2008 and 2010, but high levels in 2009, when environmental conditions were especially favorable for these pathogens. AP 350 and Suweon97 had relatively high seed infection incidences, particularly of Diaporthe spp. and Fusarium spp., and relatively low seed vigor. Application of the foliar fungicide azoxystrobin at the R5 growth stage significantly increased AA across years and cultivars and increased seed infection by Diaporthe spp. in 2009 across cultivars. There were significant negative correlations between yield and seed infection by Diaporthe spp. and Bacillus subtilis during 1 year and with Fusarium spp. during all 3 years. Overall, resistance to seed infection can persist even when harvest is delayed. In addition to Diaporthe spp., other seedborne pathogens may reduce seed vigor and yield.
Low Superior Pubic Ramus Screw Failure Rate With Combined Anterior and Posterior Pelvic Ring Fixation
Authors: Shieh Alvin K. , Hayes Christopher B. , Shelton Trevor J. , Chip Routt Milton L. , Eastman Jonathan G.
Published: October 2020

Objectives:

To determine whether fracture pattern, implant size, fixation direction, or the amount of posterior pelvic ring fixation influences superior ramus medullary screw fixation failure.

Design:

Retrospective cohort review.

Setting:

Regional Level 1 trauma center.

Patients/Participants:

After exclusion criteria, 95 patients with 111 superior ramus fractures with 3 months minimum follow-up were included.

Intervention:

All patients underwent anterior and posterior pelvic ring fixation.

Main Outcome Measurements:

Comparison of immediate postoperative radiographs and/or computer tomography scan with the latest postoperative image to calculate interval fracture displacement and implant position. Postoperative fracture displacement or implant position change greater than 1 cm were considered fixation failures.

Results:

Five screws were defined as failures (4.5%), including 3 retrograde, 3 with bicortical fixation, 4 with a 4.5-mm screw, and 1 with a 7.0-mm screw. Fracture patterns included 2 oblique and 3 comminuted fractures. Based on the Nakatani classification, there were 3 zone II, 1 zone I, and 1 zone III. Failure modes included 3 with cut-out along the screw head and 1 cut-out and 1 cut-through at the screw tip.

Conclusions:

Our incidence of superior pubic ramus intramedullary screw fixation failure was 4.5%. Even with anterior and posterior fixation along with precise technique, failures still occur without a common failure predictor. The percutaneous advantages and proven strength provided by an intramedullary implant make it desirable to help reestablish global pelvic ring stability. Biomechanical and clinical studies are needed to further understand intramedullary superior ramus screw fixation.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Olecranon Osteotomy Implant Removal Rates and Associated Complications
Authors: Meldrum Alexander , Kwong Cory , Archibold Katherine , Cinats David , Schneider Prism
Published: October 2020

Objective:

This study reports on olecranon osteotomy implant removal rates, fixation types, and associated complications.

Design:

Multicentre case series.

Setting:

Patients were identified through an electronic medical database at one Level 1 trauma center and three Level 2 trauma centers.

Patients:

Two hundred thirty-five patients were identified through the database, of which 92 patients met inclusion criteria.

Intervention:

Patients underwent olecranon osteotomy for fixation of distal humerus fractures and the implant used was at the surgeon's discretion.

Main Outcome Measurement:

Implant removal rate.

Results:

Thirty-four of 92 (37.0%) patients underwent removal of implant from their olecranon osteotomy. Implant removal rates were as follows: 28 of the 63 patients for tension band wiring (TBW) (44.4%), 6 of the 18 patients for plates (33.3%), 0 of the 1 patient for cable-pin, and 0 of the 10 patients for osteotomies fixed with a screw fixation. Screw fixation was removed less frequently than TBW (P = 0.01). Screws were less commonly removed than all other fixation types (P = 0.01). TBWs (28/63) were more commonly removed than all other implants (6/29) (P < 0.05). The nonunion rate for olecranon osteotomies was 3.3%. TBWs (18/18) are more likely to be removed for implant irritation than plates. TBWs had an odds ratio of 3.29 for requiring implant removal if they were left >1 mm off of the olecranon tip.

Conclusion:

In this study, 34 of the 92 (37%) patients undergoing an olecranon osteotomy for treatment of a distal humerus fracture required removal of olecranon implant. Screw fixation (0/10) was found to be removed less frequently than TBW fixation 28 of the 63 patients (44.4%).

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Does Size Matter for Cephalomedullary Nails in Geriatric Intertrochanteric Fractures?
Authors: Rinehart Dustin B. , O'Neill David E. , Liu Jennifer W. , Sanders Drew T.
Published: October 2020

Objectives:

To evaluate the need for reoperation of geriatric intertrochanteric hip fractures treated with 10-mm cephalomedullary nails versus those treated with nails larger than 10 mm.

Design:

Retrospective review at a single institution.

Setting:

Level I trauma center.

Patients/Participants:

All patients age 60 and over treated with cephalomedullary fixation for an intertrochanteric femur fracture at a single institution.

Intervention:

Cephalomedullary fixation with variable nail diameters.

Main Outcome Measurements:

Reoperation rates of geriatric intertrochanteric fractures treated with a size 10-mm diameter cephalomedullary nail compared with patients treated with nails larger than 10 mm.

Results:

There were no significant differences in reoperation rates when the 10-mm cohort was compared with an aggregate cohort of all nails larger than 10 mm (P = 0.99). This result was true for both all-cause reoperation and noninfectious reoperation. There was no difference between cohorts in regards to age, gender, or fracture pattern.

Conclusions:

A 10-mm cephalomedullary nail can be used in lieu of a larger diameter fixation in patients age 60 and older with intertrochanteric femur fractures while still maintaining a comparable rate of reoperation.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Comparison of Clinical Outcomes and Sagittal Alignment After Different Levels of Anterior Cervical Discectomy and Fusion in Patients With Cervical Spondylotic Myelopathy: From One-level to Three-level
Authors: Guo Shuming , Lu Shibao , Kong Chao , Li Xiangyu , Liu Chengxin
Published: October 2020

Study Design.

A nonrandomized and prospective study.

Objective.

The aim of this study was to compare clinical outcomes and sagittal alignment after one-level, two-level, and three-level anterior cervical discectomy and fusion (ACDF) in patients with cervical spondylotic myelopathy (CSM).

Summary of Background Data.

ACDF is a widely used surgical approach for CSM. It remains controversial regarding to whether corrected lordosis can be maintained over time after different levels ACDF.

Methods.

A total of 175 patients with cervical spondylotic myelopathy who underwent ACDF were enrolled in this retrospective study. The neurofunctional assessment was performed with the Japanese Orthopedic Association (JOA) score and the recovery rate of JOA score. Radiographic parameters included C2–C7 lordosis, fused segments lordosis, T1 slope, the cervical sagittal vertical axis (cSVA).

Results.

Patients with more fusion levels had more operative time and blood loss and higher rate of complications. All patients showed a larger cervical lordosis than that preoperatively and the restored lordosis increased with more segments involved. The restored lordosis had little change during the whole follow-up in one-level and two-level group. CL decreased from 25.65 ± 9.31° on the third postoperative day to 20.25 ± 10.03° at the final follow-up in three-level group (P = 0.001). Only T1 slope in three-level increased significantly from preoperative 26.55 ± 9.36° to 29.06 ± 7.54° on the third postoperative day (P = 0.011) and decreased to 26.89 ± 7.22° (P = 0.043) at final follow-up. The JOA score all increased significantly at the last follow-up in each group, but the recovery rate of the JOA score in each group was similar (P = 0.096).

Conclusion.

ACDF with different levels had similar postoperative clinical outcomes. Three-level ACDF has an apparent advantage in restoring lordosis, a poor ability to maintain lordosis, and a higher incidence of complications compared to one-level or two-level ACDF.

Level of Evidence: 3