bluuebunny/crossref_metadata_2025 huggingface dataset:
Self‐Efficacy: Changing the Tide of Evidence‐Based Practice
Authors: Boswell Carol , Ashcraft Alyce , Long JoAnn , Cannon Sharon , DiVito‐Thomas Pam , Delaney Terry
Published: April 2020

Aims

The specific aim for this study was to describe differences in evidence‐based practice (EBP) and self‐efficacy in frontline RNs. This project utilized a national study with a convenience selection of acute care agencies to examine the relationship between organizational and unit culture, EBP, and self‐efficacy in frontline nurses.

Methods

This national study used descriptive correlational methodology to describe differences in EBP and self‐efficacy among RNs. The sample included 245 frontline RNs employed in acute care settings. To measure the study variables, the Nursing Evidence‐Based Practice Survey (Titler, Hill, Matthews, & Reed, 1999)  and the Evidence‐Based Nursing Practice Self‐Efficacy Scale were used (Tucker, Olson, & Frusti, 2009). Each instrument was delivered via the Qualtrics online platform.

Results

The correlation of bivariate interval level variables was analyzed using Pearson’s r. The correlation between EBP and self‐efficacy was strongly correlated: r(170) = .537, p = .01. Sections within the Nursing Evidence‐Based Practice Survey were calculated and found to be significant (unit culture r = .241, p = .01; organizational culture r = .570, p = .01; knowledge, skills, attitude r = .538, p = .01).

Linking Evidence to Action

Several implications exist for education, staff development, and nursing management. Nursing school programs incorporate EBP into the curriculum so that nurses have a foundation for EBP. However, staff development professionals in clinical settings must continue to build on the nurses’ knowledge and skill, thus increasing self‐confidence for EBP. Nursing management can provide the resources for staffing models and policies to reinforce the value of EBP and positive patient outcomes. This combination provides frontline staff with EBP participation and increased self‐efficacy in its usage.
The Effect of Martensitic Transformation on the Evolution of Residual Stresses and Identification of the Critical Linear Mass Density in Direct Laser Metal Deposition–Based Repair
Authors: Vundru Chaitanya , Singh Ramesh , Yan Wenyi , Karagadde Shyamprasad
Published: April 2020

Direct laser metal deposition (DLMD) is a promising additive manufacturing technique which has a huge potential in remanufacturing and restoration of high-value dies/molds and aerospace components. The residual stresses developed in the material deposited via DLMD affect the structural integrity of the restored components. The service life of the restored component will be compromised if tensile residual stresses are present in the deposited layer. The residual stresses originate due to differential thermal expansion/contraction and martensitic transformation-driven volumetric dilation and transformation-induced plasticity. The influence of martensitic transformation and processing conditions on the residual stresses of DLMD-processed components needs to be understood and modeled for sustainable repair. Hence, a finite element model has been developed to capture the coupled effect of thermomechanics and martensitic transformation on the evolution of residual stresses in DLMD. In this study, the individual and coupled effects of strains due to volume dilation and transformation-induced plasticity on residual stress evolution have been analyzed for the deposition of crucible particle metallurgy (CPM) 9 V on H-13 tool steel. The finite element model has been experimentally validated using X-ray and neutron diffractions. The inclusion of both transformation strains in the residual stress decreases the prediction errors of peak tensile residual stress from ∼48% to ∼15%. The fully coupled thermomechanical and metallurgical model has been used to obtain a critical linear mass density (m˙/v) corresponding to the onset of a fully compressive longitudinal residual stress state in the deposited layer to ensure sustainable repair.
Extrapolating Green's functions using the waveguide invariant theory
Authors: Song H. C. , Byun Gihoon
Published: April 2020

The broadband interference structure of sound propagation in a waveguide can be described by the waveguide invariant, β, that manifests itself as striations in the frequency-range plane. At any given range (r), there is a striation pattern in frequency (ω), which is the Fourier transform of the multipath impulse response (or Green's function). Moving to a different range (r+Δr), the same pattern is retained but is either stretched or shrunken in ω in proportion to Δr, according to Δω/ω=β(Δr/r). The waveguide invariant property allows a time-domain Green's function observed at one location, g(r,t), to be extrapolated to adjacent ranges with a simple analytic relation: g(r+Δr,t)≃g(r,α(t−Δr/c)), where α=1+β(Δr/r) and c is the nominal sound speed of 1500 m/s. The relationship is verified in terms of range variation of the eigenray arrival times via simulations and by using real data from a ship of opportunity radiating broadband noise (200–900 Hz) in a shallow-water environment, where the steep-angle arrivals contributing to the acoustic field have β≈0.92.
Challenges Experienced by Women High-Performance Coaches: Sustainability in the Profession
Authors: Kenttä Göran , Bentzen Marte , Dieffenbach Kristen , Olusoga Peter
Published: April 2020

High-performance (HP) coaching is a demanding profession. The proportion of woman HP coaches is reported to be in the range of 8.4–20%. Mental health concerns in elite sports have recently gained attention, but mainly focusing on athletes. Beyond coach burnout, limited attention has been given to coaches’ mental health. A recent coach burnout review included only one paper that focused exclusively on women. It has been argued that women HP coaches face greater challenges in a male-dominated coaching culture. The purpose of this study was to explore challenges experienced by women HP coaches and their perceived associations with sustainability and mental health. Thirty-seven female HP coaches participated by answering a semistructured, open-ended questionnaire. All responses were analyzed using inductive thematic analysis, which resulted in two general dimensions: challenges of working as women HP coaches and sustainability and well-being as women HP coaches. Overall, results indicate that challenges reported might be common not only for all HP coaches, but also highlight gender-specific elements. Consequently, coach retention and sustainability would benefit from more attention on well-being and mental health among HP coaches.
A highly conserved cryptic epitope in the receptor binding domains of SARS-CoV-2 and SARS-CoV
Authors: Yuan Meng , Wu Nicholas C. , Zhu Xueyong , Lee Chang-Chun D. , So Ray T. Y. , Lv Huibin , Mok Chris K. P. , Wilson Ian A.
Published: April 2020

Targeting the SARS-CoV-2 spike

The surface of severe acute respiratory syndrome–coronavirus 2 (SARS-CoV-2) is decorated with trimeric spikes that bind to host cell receptors. These spikes also elicit an antibody response, so understanding antibody recognition may aid in vaccine design. Yuan
et al.
determined the structure of CR3022, a neutralizing antibody obtained from a convalescent SARS-CoV–infected patient, in complex with the receptor-binding domain of the SARS-CoV-2 spike. The antibody binds to an epitope conserved between SARS-CoV-2 and SARS-CoV that is distinct from the receptor-binding site. CR3022 likely binds more tightly to SARS-CoV because its epitope contains a glycan not present in SARS-CoV-2. Structural modeling showed that the epitope is only revealed when at least two of the three spike proteins are in a conformation competent to bind the receptor.

Science
, this issue p.
630
Aminoglycoside 6′-
N
-Acetyltransferase Variants of the Ib Type with Altered Substrate Profile in Clinical Isolates of
Enterobacter cloacae
and
Citrobacter freundii
Authors: Casin Isabelle , Bordon Florence , Bertin Philippe , Coutrot Anne , Podglajen Isabelle , Brasseur Robert , Collatz Ekkehard
Published: April 2020

Three clinical isolates,
Enterobacter cloacae
EC1562 and EC1563 and
Citrobacter freundii
CFr564, displayed an aminoglycoside resistance profile evocative of low-level 6′-
N
acetyltransferase type II [AAC(6′)-II] production, which conferred reduced susceptibility to gentamicin but not to amikacin or isepamicin. Aminoglycoside acetyltransferase assays suggested the synthesis in the three strains of an AAC(6′) which acetylated amikacin practically as well as it acetylated gentamicin in vitro. Both compounds, however, as well as isepamicin, retained good bactericidal activity against the three strains. The
aac
genes were borne by conjugative plasmids (pLMM562 and pLMM564 of ca. 100 kb and pLMM563 of ca. 20 kb). By PCR mapping and nucleotide sequence analysis, an
aac(6′)-Ib
gene was found in each strain upstream of an
ant
(3")-I gene in a
sulI
-type integron. The size of the AAC(6′)-Ib variant encoded by pLMM562 and pLMM564, AAC(6′)-Ib
7
, was deduced to be 184 (or 177) amino acids long, whereas in pLMM563 a 21-bp duplication allowing the recruitment of a start codon resulted in the translation of a variant, AAC(6′)-Ib
8
, of 196 amino acids, in agreement with size estimates obtained by Western blot analysis. Both variants had at position 119 a serine instead of the leucine typical for the AAC(6′)-Ib variants conferring resistance to amikacin. By using methods that predict the secondary structure, these two amino acids appear to condition an α-helical structure within a putative aminoglycoside binding domain of AAC(6′)-Ib variants.
Detection of
grlA
and
gyrA
Mutations in 344
Staphylococcus aureus
Strains
Authors: Wang Tong , Tanaka Mayumi , Sato Kenichi
Published: April 2020

Mutations in the
grlA
and
gyrA
genes of 344 clinical strains of
Staphylococcus aureus
isolated in 1994 in Japan were identified by combinations of single-strand conformation polymorphism analysis, restriction fragment length analysis, and direct sequencing to identify possible relationships to fluoroquinolone resistance. Five types of single-point mutations and four types of double mutations were observed in the
grlA
genes of 204 strains (59.3%). Four types of single-point mutations and four types of double mutations were found in the
gyrA
genes of 188 strains (54.7%). Among them, the
grlA
mutation of TCC→TTC or TAC (Ser-80→Phe or Tyr) and the
gyrA
mutation of TCA→TTA (Ser-84→Leu) were principal, being detected in 137 (39.8%) and 121 (35.9%) isolates, respectively. The
grlA
point mutations of CAT→CAC (His-77 [silent]), TCA→CCA (Ser-81→Pro), and ATA→ATT (Ile-100 [silent]) were novel, as was the GAC→GGC (Asp-73→Gly) change in
gyrA
. A total of 15 types of mutation combinations within both genes were related to ciprofloxacin resistance (MIC ≥ 3.13 μg/ml) and were present in 193 mutants (56.1%). Strains containing mutations in both genes were highly resistant to ciprofloxacin (MIC at which 50% of the isolates are inhibited [MIC
50
] = 50 μg/ml). Those with the Ser-80→Phe or Tyr alteration in
grlA
but wild-type
gyrA
showed a lower level of ciprofloxacin resistance (MIC
50
≤ 12.5 μg/ml). Levofloxacin was active against 68 of 193 isolates (35.2%) with mutations at codon 80 of
grlA
in the presence or absence of a concomitant mutation at codon 73, 84, or 88 in
gyrA
(MIC ≤ 6.25 μg/ml). The new fluoroquinolone DU-6859a showed good activity with 186 of 193 isolates (96.4%) for which the MIC was ≤6.25 μg/ml.
Pharmacokinetics and Absolute Bioavailability of Oral Foscarnet in Human Immunodeficiency Virus-Seropositive Patients
Authors: Noormohamed Faruq H. , Youle Michael S. , Higgs Christopher J. , Martin-Munley Sarah , Gazzard Brian G. , Lant Ariel F.
Published: April 2020

The pharmacokinetics, absolute bioavailability, accumulation, and tolerability over 8 days of an oral formulation of foscarnet (90 mg/kg of body weight once daily [QD] [
n
= 6], 90 mg/kg twice daily [BID] [
n
= 6], and 180 mg/kg QD [
n
= 3]) were investigated in 15 asymptomatic, human immunodeficiency virus-seropositive male patients free of active cytomegalovirus infection and with normal upper gastrointestinal function. Peak plasma drug concentrations were (mean ± standard deviation) 46.4 ± 10.8 μM (90 mg/kg QD), 45.7 ± 6.9 μM (90 mg/kg BID), and 64.9 ± 31.7 μM (180 mg/kg QD) on day 1 and rose to 86.2 ± 35.8, 78.7 ± 35.2, and 86.4 ± 25.0 μM, respectively, on day 8. The mean peak concentration in plasma following the intravenous administration of foscarnet (90 mg/kg) was 887.3 ± 102.7 μM (
n
= 13). The terminal half-life in plasma remained unchanged, averaging 5.5 ± 2.2 h on day 1 (
n
= 15) and 6.6 ± 1.9 h on day 8 (
n
= 13), whereas it was 5.7 ± 0.7 h following intravenous dosing. Oral bioavailabilities were 9.1% ± 2.2% (90 mg/kg QD), 9.5% ± 1.7% (90 mg/kg BID), and 7.6% ± 3.7% (180 mg/kg QD); the accumulation ratios on the 8th day of dosing were 2.1 ± 1.1, 1.8 ± 0.4, and 1.7 ± 0.7, respectively. The overall 24-h urinary excretion of oral foscarnet averaged 7.8% ± 2.6% (day 1) and 13.4% ± 6.0% (day 8), whereas it was 95.0% ± 4.9% after intravenous dosing. The glomerular filtration rate and creatinine clearance remained constant, and the mean 24-h renal clearances of foscarnet for the entire study group were 96 ± 18 ml/min (day 1), 88 ± 13 ml/min (day 8), and 103 ± 16 ml/min after intravenous dosing. Adverse effects were largely confined to gastrointestinal disturbances, with all subjects experiencing diarrhea that was dose dependent in its severity. The results suggest that the formulation studied would require significant improvement with respect to tolerability and bioavailability to gain clinical acceptance.
Synthesis and Evaluation of Dinitroanilines for Treatment of Cryptosporidiosis
Authors: Benbow John W. , Bernberg Erin L. , Korda Anna , Mead Jan R.
Published: April 2020

The efficacy of a series of dinitroaniline herbicide derivatives for the treatment of
Cryptosporidium parvum
infections has been studied. The lead compounds oryzalin (compound 1) and trifluralin (compound 2) have low water solubility (<3 ppm) which was alleged to be a major contributor to their poor pharmacokinetic availability. Derivatives of compounds 1 and 2 were synthesized. In these derivatives the functionality at the C-1 amine position or the C-4 position was substituted with groups with various hydrophilicities to determine if a direct relation existed between water solubility and overall activity. The chlorinated precursors of these derivatives were also examined and were found to be less active in the
C. parvum
assays, a result in direct contrast to earlier work with
Leishmania
. Enhanced water solubility alone did not overcome the drug availability problem; however, several candidates with similar activities but with toxicities lower than those of the lead compounds were produced.
Green Fluorescent Protein Reporter Microplate Assay for High-Throughput Screening of Compounds against
Mycobacterium tuberculosis
Authors: Collins L. A. , Torrero M. N. , Franzblau S. G.
Published: April 2020

An optimal assay for high-throughput screening for new antituberculosis agents would combine the microplate format and low cost of firefly luciferase reporter assays and redox dyes with the ease of kinetic monitoring inherent in the BACTEC system. The green fluorescent protein (GFP) of the jellyfish
Aequorea victoria
is a useful reporter molecule which requires neither substrates nor cofactors due to the intrinsically fluorescent nature of the protein. The gene encoding a red-shifted, higher-intensity GFP variant was introduced by electroporation into
Mycobacterium tuberculosis
H
37
Ra and
M. tuberculosis
H
37
Rv on expression vector pFPV2. A microplate-based fluorescence assay (GFP microplate assay [GFPMA]) was developed and evaluated by determining the MICs of existing antimycobacterial agents. The MICs of isoniazid, rifampin, ethambutol, streptomycin, amikacin, ofloxacin, ethionamide, thiacetazone, and capreomycin, but not cycloserine, determined by GFPMA were within 1 log
2
dilution of those determined with the BACTEC 460 system and were available in 7 days. Equivalent MICs of antituberculosis agents in the BACTEC 460 system for both the reporter and parent strains suggested that introduction of pFPV2 did not influence drug susceptibility, in general. GFPMA provides a unique tool with which the dynamic response of
M. tuberculosis
to the existing and potential antituberculosis agents can easily, rapidly, and inexpensively be monitored.
A Novel Peptide-Grafted Liposomal Delivery System Targeted to Macrophages
Authors: Banerjee Goutam , Medda Swapna , Basu Mukul K.
Published: April 2020

The interaction of chemotactic peptide (e.g., fMet-Leu-Phe)-grafted liposomes with macrophages is noted to be rapid and specific. At a grafted peptide concentration of 100 nmol, internalization of the peptide-grafted liposomes by the macrophages is found to reach equilibrium in 30 min. The peptide alone and the peptide-grafted empty liposomes are found to show moderate antileishmanial activity in vitro. Primaquine, which is known to generate O2−in phagocytic cells, showed leishmanicidal properties when it was tested in vitro against parasite-infected macrophages over a certain range of concentrations. It showed much better efficacy against experimental leishmaniasis when it was used in the fMet-Leu-Phe-grafted liposomal form in comparison with its efficacy when it was either in the free form or encapsulated in ungrafted liposomes. The conventional toxicity parameters (e.g., blood pathology and tissue histology-specific enzyme levels related to normal liver function) are found to be very close to normal when fMet-Leu-Phe-grafted liposomal primaquine is used. The biodegradabilities of both the drug and the delivery systems are also found to be very satisfactory. Thus, this delivery system may have possible applications for the treatment of leishmaniasis as well as other macrophage-associated disorders.
Mathematical Modeling of the Interrelationship of CD4 Lymphocyte Count and Viral Load Changes Induced by the Protease Inhibitor Indinavir
Authors: Drusano George L. , Stein Daniel S.
Published: April 2020

While CD4 cell counts are widely used to predict disease progression in human immunodeficiency virus (HIV)-infected patients, they are poorly explanatory of the progression to AIDS or death after the introduction of chemotherapy. Changes in HIV load (as measured by RNA PCR) have been shown to be a much better predictor of the risk of disease progression. Since the interrelationship of these markers is of great clinical interest, we modeled the time-averaged return of CD4 cell count and change in viral load subsequent to therapy with the HIV protease inhibitor indinavir. We found that CD4 cell return was significantly related to both the baseline CD4 count (
r
2
= 0.86,
P
< 0.001) and the decline in HIV RNA PCR-determined viral load (also referred to in this work as the HIV RNA PCR decline) (
r
2
= 0.60,
P
< 0.01). Simultaneously modeling both influences in a linked nonlinear model (
r
2
= 0.93,
P
< 0.001) demonstrated that (i) the starting number of CD4 cells accounted for the majority of the change in CD4 cell return and (ii) the return of CD4 cells attributable to viral load decrease was 50% of maximal with only a decrease of approximately 0.2 log of HIV RNA as modeled from the first 12 weeks of therapy. Much greater viral inhibition beyond that necessary for maximal CD4 cell return is possible. Given that HIV RNA PCR decline is more strongly linked to ultimate clinical course in HIV disease, our findings indicate that CD4 return is potentially misleading as an indicator of antiviral effect, since it is determined more by the starting CD4 value than by viral load decline and since near-maximal changes occur with minimal antiviral effect.
Doxycycline Hyclate Treatment of Experimental Canine Ehrlichiosis Followed by Challenge Inoculation with TwoEhrlichia canisStrains
Authors: Breitschwerdt Edward B. , Hegarty Barbara C. , Hancock Susan I.
Published: April 2020

Dogs were experimentally inoculated withEhrlichia canisFlorida to assess the efficacy of doxycycline hyclate for the treatment of acute ehrlichiosis. Treatment with doxycycline eliminated infection in eight of eight dogs. Untreated infected control dogs appeared to eliminate the infection or, alternatively, suppress the degree of ehrlichiemia to a level not detectable by tissue culture isolation or PCR or by transfusion of blood into recipient dogs. Prior infection did not infer protection against homologous (strain Florida) or heterologous (strain NCSU Jake) strains ofE. canis. We conclude that doxycycline hyclate is an effective treatment for acuteE. canisinfection; however, these results may not be applicable to chronic infections in nature. Spontaneous resolution of infection, induced by the dog’s innate immune response, provides evidence that anE. canisvaccine, once developed, might potentially confer protective immunity against the organism.
Comparison of Pharmacodynamics of Azithromycin and Erythromycin In Vitro and In Vivo
Authors: den Hollander Jan G. , Knudsen Jenny D. , Mouton Johan W. , Fuursted Kurt , Frimodt-Møller Niels , Verbrugh Henri A. , Espersen Frank
Published: April 2020

In this study, we determined the efficacy of various dosing regimens for erythromycin and azithromycin against four pneumococci with different susceptibilities to penicillin in an in vitro pharmacokinetic model and in a mouse peritonitis model. The MIC was 0.03 μg/ml, and the 50% effective doses (determined after one dose) of both drugs were comparable for the four pneumococcal strains and were in the range of 1.83 to 6.22 mg/kg. Dosing experiments with mice, using regimens for azithromycin of one to eight doses/6 h, showed the one-dose regimen to give the best result; of the pharmacodynamic parameters tested (the maximum drug concentration in serum [
C
max
], the times that the drug concentration in serum remained above the MIC and above the concentration required for maximum killing, and the area under the concentration time curve),
C
max
was the best predictor of outcome. The bacterial counts in mouse blood or peritoneal fluid during the first 24 h after challenge were not correlated to survival of the mice. The serum concentration profiles obtained with mice for the different dosing regimens were simulated in the in vitro pharmacokinetic model. Here as well, the one-dose regimen of azithromycin showed the best result. However, the killing curves in vivo in mouse blood and peritoneal fluid and in the vitro pharmacokinetic model were not similar. The in vitro killing curves showed a decrease of 2 log
10
within 2 and 3 h for azithromycin and erythromycin, respectively, whereas the in vivo killing curves showed a bacteriostatic effect for both drugs. It is concluded that the results in terms of predictive pharmacodynamic parameters are comparable for the in vitro and in vivo models and that high initial concentrations of azithromycin favor a good outcome.
Intrinsic Resistance to Inhibitors of Fatty Acid Biosynthesis in
Pseudomonas aeruginosa
Is Due to Efflux: Application of a Novel Technique for Generation of Unmarked Chromosomal Mutations for the Study of Efflux Systems
Authors: Schweizer Herbert P.
Published: April 2020

Many strains of
Pseudomonas aeruginosa
are resistant to the antibiotics cerulenin and thiolactomycin, potent inhibitors of bacterial fatty acid biosynthesis. A novel yeast Flp recombinase-based technique was used to isolate an unmarked
mexAB-oprM
deletion encoding an efflux system mediating resistance to multiple antibiotics in
P. aeruginosa
. The experiments showed that the MexAB-OprM system is responsible for the intrinsic resistance of this bacterium to cerulenin and thiolactomycin. Whereas thiolactomycin was not a substrate of the MexCD-OprJ pump expressed in a Δ(
mexAB-oprM
)
nfxB
mutant, cerulenin was efficiently effluxed by the MexCD-OprJ system. It was also found that the MexAB-OprM system is capable of efflux of irgasan, a broad-spectrum antimicrobial compound used in media selective for
Pseudomonas.
In Vitro Activities of Y-688, a New 7-Substituted Fluoroquinolone, against Anaerobic Bacteria
Authors: MacGowan A. P. , Bowker K. E. , Wootton M. , Holt H. A. , Reeves D. S.
Published: April 2020

The in vitro activities of Y-688, a new 7-substituted fluoroquinolone derivative, against 317 nonduplicate anaerobic isolates were determined. Eighty-five percent of the
Bacteroides fragilis
group (
n
= 89) were inhibited by ≤2 mg of Y-688 per liter, while 78, 100, 89, and 98% of gram-negative bacilli (
n
= 135), gram-positive cocci (
n
= 59), and non-spore-forming (
n
= 58) and spore-forming (
n
= 51) gram-positive bacilli, respectively, were inhibited by ≤1 mg of Y-688 per liter.
Nucleotide and Amino Acid Sequences of the Metallo-β-Lactamase, ImiS, from
Aeromonas veronii
bv. sobria
Authors: Walsh T. R. , Neville W. A. , Haran M. H. , Tolson D. , Payne D. J. , Bateson J. H. , Macgowan A. P. , Bennett P. M.
Published: April 2020

The
Aeromonas veronii
bv. sobria metallo-β-lactamase gene,
imiS
, was cloned. The
imiS
open reading frame extends for 762 bp and encodes a protein of 254 amino acids with a secreted modified protein of 227 amino acids and a predicted pI of 8.1. To confirm the predicted sequence, purified ImiS was digested and the resulting peptides were identified, yielding an identical sequence for ImiS, with 98% identity to CphA. Both possessed the putative active-site sequence Asn-Tyr-His-Thr-Asp at positions 88 to 92, which is unique to the
Aeromonas
metallo-β-lactamases.
In Vitro Comparative Efficacy of Voriconazole and Itraconazole against Fluconazole-Susceptible and -Resistant
Cryptococcus neoformans
Isolates
Authors: Nguyen M. Hong , Yu Christine Y.
Published: April 2020

In vitro susceptibility testing for 50 clinical isolates of fluconazole-susceptible or -resistant
Cryptococcus neoformans
was performed with itraconazole and voriconazole. Voriconazole was more potent than itraconazole for fluconazole-susceptible isolates and as potent as itraconazole for fluconazole-susceptible dose-dependent isolates and for fluconazole-resistant isolates. For fluconazole-resistant isolates, the voriconazole and itraconazole MICs ranged from 1 to 2 μg/ml.
Histone Deacetylase Inhibitors Promote Latent Adenovirus Reactivation from Tonsillectomy Specimens
Authors: Wang Lingling , Zhang Mengyu , Li Jingjing , Yang Guang , Huang Qun , Li Jingwen , Wang Hongwei , He Susu , Li Erguang
Published: April 2020

Respiratory tract infection by adenoviruses is among the most common diseases in children, attributing to approximately 20% of hospitalizations of children with acute respiratory infection (ARI). Adenovirus transmits by direct contact, but recurrent infection is common. Ever since its isolation, adenovirus has been known to have the ability to establish persistent or latent infection. We found 87.7% tonsillectomy specimens contained detectable amounts of adenoviral DNA. Isolated lymphocytes did not produce infectious adenoviruses without stimulation. By screening an epigenetic informer compound library, we identified several histone deacetylase inhibitors that promoted adenovirus reactivation that was evidenced by increased viral DNA replication and production of infectious viruses. The human tonsils are covered with bacterial pathogens that may utilize pathogen-associated pattern molecules or metabolites to cause epigenetic activation and proinflammatory gene transcription, which may lead to viral reactivation from latency. The study shows that recurrent adenovirus infection could arise from reactivation of residing virus from previous infections.
Potential Role of Nonneutralizing IgA Antibodies in Cross-Protective Immunity against Influenza A Viruses of Multiple Hemagglutinin Subtypes
Authors: Okuya Kosuke , Yoshida Reiko , Manzoor Rashid , Saito Shinji , Suzuki Tadaki , Sasaki Michihito , Saito Takeshi , Kida Yurie , Mori-Kajihara Akina , Kondoh Tatsunari , Sato Masahiro , Kajihara Masahiro , Miyamoto Hiroko , Ichii Osamu , Higashi Hideaki , Takada Ayato
Published: April 2020

Mucosal immunity represented by pSIgA plays important roles in protection from IAV infection. Furthermore, IAV HA-specific pSIgA antibodies are thought to contribute to cross-protective immunity against multiple IAV subtypes. However, the mechanisms by which pSIgA exerts such versatile antiviral activity are not fully understood. In this study, we generated broadly cross-reactive recombinant IgG and pSIgA having the same antigen-recognition site and compared their antiviral activities
in vitro
. These recombinant antibodies did not show “classical” neutralizing activity, whereas pSIgA, but not IgG, significantly inhibited the production of progeny virus particles from infected cells. Plaque formation was also significantly reduced by pSIgA, but not IgG. These effects were seen in infection with IAVs of several different HA subtypes. Based on our findings, we propose an antibody-mediated host defense mechanism by which mucosal immunity may contribute to broad cross-protection from IAVs of multiple HA subtypes, including viruses with pandemic potential.
Extent and consequences of lymphadenectomy in oesophageal cancer surgery: case vignette survey
Authors: de Gouw Didi JJM , Scholte Mirre , Gisbertz Suzanne S , Wijnhoven Bas P L , Rovers Maroeska M , Klarenbeek Bastiaan R , Rosman Camiel
Published: April 2020

Objectives

Lymph node dissection (LND) is part of the standard operating procedure in patients with resectable oesophageal cancer after neoadjuvant chemoradiotherapy regardless of lymph node (LN) status. The aims of this case vignette survey were to acquire expert opinions on the current practice of LND and to determine potential consequences of non-invasive LN staging on the extent of LND and postoperative morbidity.

Design

An online survey including five short clinical cases (case vignettes) was sent to 272 oesophageal surgeons worldwide.

Participants

86 oesophageal surgeons (median experience in oesophageal surgery of 15 years) participated in the survey (response rate 32%).

Main outcome measures

Extent of standard LND, potential changes in LND based on accurate LN staging and consequences for postoperative morbidity were evaluated.

Results

Standard LND varied considerably between experts; for example, pulmonary ligament, splenic artery, aortopulmonary window and paratracheal LNs are routinely dissected in less than 60%. The omission of (parts of) LND is expected to decrease the number of chyle leakages, pneumonias, and laryngeal nerve pareses and to reduce operating time. In order to guide surgical treatment decisions, a diagnostic test for LN staging after neoadjuvant therapy requires a minimum sensitivity of 92% and a specificity of 90%.

Conclusions

This expert case vignette survey study shows that there is no consensus on the extent of standard LND. Oesophageal surgeons seem more willing to extend LND rather than omit LND, based on accurate LN staging. The majority of surgeons expect that less extensive LND can reduce postoperative morbidity.
Medical students as simulation educators: students’ experience of a 7-week
simulation-based education rotation
Authors: Brazil Victoria , Caughley Melissah , Middleton Lauren , Powell Georgia , Alsaba Nemat
Published: April 2020

Medical students will have future roles as clinician educators, and need to
develop knowledge and skills for that role. Specific skills in simulation-based
education (SBE) may be valuable in many educational settings. We aimed to
understand the impact of a 7-week placement in SBE on the development of medical
students’ knowledge, skills and perspectives as educators. We reviewed the
experience of three graduated students (also coauthors of this article) who
participated in the rotation in 2018. This case study includes analysis of the
students’ electronic portfolios, rotation reports and subsequent reflections of
the student coauthors. Five themes were identified:—‘Development as a
professional’, ‘Active participation in an educator team’, ‘Diverse experience in
simulation skills and techniques’, ‘Role models and mentoring’ and ‘Rethinking
feedback’. Students describe the development of practical knowledge and skills,
and more fundamental reflections on the nature of learning, feedback and their
personal professional development. We suggest that integration of a simulation
education elective within a medical school curriculum helps build capacity for
effective SBE delivery, and has positive impacts on students for their future
roles as doctors, educators and lifelong learners.
Inflammatory bowel disease psychological support pilot reduces inflammatory bowel disease symptoms and improves psychological wellbeing
Authors: Eccles Jessica Anne , Ascott Anna , McGeer Rona , Hills Emma , St.Clair Jones Anja , Page Lisa A , Smith Melissa A , Loewenberger Alana , Gregory Jemima
Published: April 2020

This prospective service evaluation aimed to determine if integrated psychological support for patients with inflammatory bowel disease (IBD) enhanced outcomes. 75 patients were assessed and treated by a specialist liaison psychiatric service between 2015 and 2017; 43 received psychiatric intervention alone, 32 were referred for psychological intervention by clinical health psychologist; 26 completed this. Pre–post data (n=15 available) included global impression, quality of life, and psychiatric and IBD symptom scores. Referrer/patient satisfaction and cost-effectiveness were retrospectively calculated. Psychological intervention led to reductions in IBD symptoms (ΔSIBD; p=0.003), alongside improvements in depression scores (ΔPHQ-9, p=0.006) and global impression (ΔCGI; p=0.046). Patient/referrer satisfaction was very high. Indicative data comparing service utilisation 1 year before and after engagement found reductions in outpatient appointments and in imaging. This small study suggests consideration of increased access to integrated psychological support services to improve outcomes and gather further evidence of efficacy.
Using nursing care plans to support effective working
Authors: Ballantyne Helen
Published: April 2020

Nursing care plans provide an organised framework to facilitate and record the assessment, planning and implementation of nursing care. They have the potential to improve patient care by supporting individually tailored treatment and may also be used as a tool to improve communication between members of the multidisciplinary team, and between the team and their clients. This article highlights the importance of care plans for patient care, and discusses their use by the entire multidisciplinary team with the aim of promoting more effective working practices.
Interaction between time, ASPECTS, and clinical mismatch
Authors: Desai Shashvat M , Tonetti Daniel A , Molyneaux Bradley J , Atchaneeyasakul Kunakorn , Rocha Marcelo , Jovin Tudor G , Jadhav Ashutosh P
Published: April 2020

Background

Imaging-based patient selection for neurothrombectomy is reliant on the identification of irreversibly damaged brain tissue (core) and salvageable tissue (penumbra). The DAWN trial used the clinical-core mismatch (CCM) paradigm (clinical deficit out of proportion to infarct volume). We aim to determine the prevalence of CCM in large vessel occlusion (LVO) strokes and study the impact of time and the Alberta Stroke Program Early CT Score (ASPECTS) on the likelihood of mismatch.

Methods

We performed a retrospective observational analysis of internal carotid artery/middle cerebral artery M1 occlusions with available advanced imaging (relative cerebral blood flow/MRI). We used automated software for infarct volume analysis and ASPECTS determination. The prevalence of CCM and the impact of time and ASPECTS were analyzed.

Result

One hundred and eighty-five LVO strokes were included. Mean age was 71±15 years and median National Institutes of Health Stroke Scale score was 17 (range 12–21). Mean ischemic core volume was 50±69 mL. Within 0–24 hours, CCM was present in 53% and ranged from 63% in 0–3 hours to 25% at 21–24 hours (p=0.03). Prevalence of mismatch reduced 1.6% for every 1 hour increase in time to imaging. CCM prevalence by ASPECTS groups was: ASPECTS 9–10: 77%, ASPECTS 6–8: 65%, ASPECTS 0–5: 13% (p<0.01), with a 6.4% decrement for every 1 point decrease in ASPECTS. The prevalence of mismatch did not diminish over time among ASPECTS groups and higher ASPECTS was an independent predictor of CCM (OR 1.4 (95% CI 1.1 to 1.7), p<0.001).

Conclusions

CCM is present in 57% and 50% of LVO strokes in the 0–6 and 6–24 hour window, respectively. The prevalence of mismatch declines with increasing time (1.6%/hour) and decreasing ASPECTS (6.4%/point). Among ASPECTS groups the prevalence of mismatch does not decline over time. These data support the use of an ASPECTS-based paradigm for late window patient selection.
COVID-19 outbreak and its monetary implications for dental practices, hospitals and healthcare workers
Authors: Farooq Imran , Ali Saqib
Published: April 2020

The novel COVID-19 came under limelight few months back (December 2019) and has recently been declared a pandemic by WHO. It has resulted in serious financial implications being faced by dental practices, hospitals and healthcare workers. Dental practice currently is restricted to provision of emergency dental care whereas, many hospitals have also cancelled elective procedures to save finances for COVID-19 treatment which is expensive and unpredictable. In addition, healthcare workers are also facing financial challenges in this difficult time. Competent authorities should step in to help dental practices, hospitals and healthcare workers in order to ensure the provision of all types of healthcare efficiently in these testing times and beyond.
Age and growth variability of the yellow clam (Mesodesma mactroides) in two populations from Argentina: implications under climate change
Authors: Risoli M.C. , Baldoni A. , Giménez J. , Lomovasky B.J.
Published: April 2020

Morphometric relationships and age and growth rates of the yellow clam (Mesodesma mactroides Reeve, 1854 = Amarilladesma mactroides (Reeve, 1854)) were compared in two populations from Argentina: Santa Teresita (36°32′00″S) and Mar del Plata (37°57′52″S). The Santa Teresita clams were heavier (shell, soft parts) than the Mar del Plata clams. Cross sections stained with Mutvei’s solution and acetate peels revealed an internal shell growth pattern of well-defined slow-growing translucent bands and alternating fast-growing opaque bands. Translucent bands (clusters) representing external rings were formed mostly during October in both sites, coinciding with gonadal maturation processes and spawning. Data confirm the annual formation of translucent bands in this species. Comparison of growth parameters showed a higher growth rate k and lower maximum age in Mar del Plata (8 years) than in Santa Teresita (9 years), which could be triggered by differences in salinity between localities due to the influence of the Rio de la Plata estuary, which is strongly linked to climate variability. Shell mass condition index and Oceanic Niño Index were negatively correlated, showing the influence of El Niño in shell properties of the species. Considering that events are becoming more intense and frequent, changes in growth rates and shell properties of Santa Teresita’s population could be expected to be more vulnerable under climate change.
The blackholic quantum
Authors: Rueda J. A. , Ruffini R.
Published: April 2020

We show that the high-energy emission of GRBs originates in the inner engine: a Kerr black hole (BH) surrounded by matter and a magnetic field $$B_0$$B0. It radiates a sequence of discrete events of particle acceleration, each of energy $${{\mathscr {E}}} = \hbar \,\varOmega _{\mathrm{eff}}$$E=ħΩeff, the blackholic quantum, where $$\varOmega _{\mathrm{eff}} =4(m_{\mathrm{Pl}}/m_n)^8(c\,a/G\,M)(B_0^2/\rho _\mathrm{Pl})\varOmega _+$$Ωeff=4(mPl/mn)8(ca/GM)(B02/ρPl)Ω+. Here M, $$a=J/M$$a=J/M, $$\varOmega _+=c^2\partial M/\partial J=(c^2/G)\,a/(2 M r_+)$$Ω+=c2∂M/∂J=(c2/G)a/(2Mr+) and $$r_+$$r+ are the BH mass, angular momentum per unit mass, angular velocity and horizon; $$m_n$$mn is the neutron mass, $$m_{\mathrm{Pl}}$$mPl, $$\lambda _{\mathrm{Pl}}=\hbar /(m_{\mathrm{Pl}}c)$$λPl=ħ/(mPlc) and $$\rho _{\mathrm{Pl}}=m_{\mathrm{Pl}}c^2/\lambda _{\mathrm{Pl}}^3$$ρPl=mPlc2/λPl3, are the Planck mass, length and energy density. Here and in the following use CGS-Gaussian units. The timescale of each process is $$\tau _{\mathrm{el}}\sim \varOmega _+^{-1}$$τel∼Ω+-1, along the rotation axis, while it is much shorter off-axis owing to energy losses such as synchrotron radiation. We show an analogy with the Zeeman and Stark effects, properly scaled from microphysics to macrophysics, that allows us to define the BH magneton, $$\mu _{\mathrm{BH}}=(m_{\mathrm{Pl}}/m_n)^4(c\,a/G\,M)e\,\hbar /(M c)$$μBH=(mPl/mn)4(ca/GM)eħ/(Mc). We give quantitative estimates for GRB 130427A adopting $$M=2.3~M_\odot $$M=2.3M⊙, $$c\, a/(G\,M)= 0.47$$ca/(GM)=0.47 and $$B_0= 3.5\times 10^{10}$$B0=3.5×1010 G. Each emitted quantum, $$\mathcal{E}\sim 10^{37}$$E∼1037 erg, extracts only $$10^{-16}$$10-16 times the BH rotational energy, guaranteeing that the process can be repeated for thousands of years. The inner engine can also work in AGN as we here exemplified for the supermassive BH at the center of M87.
An introduction to the C# language and .NET infrastructure
Authors: Brosgol Ben
Published: April 2020

Prerequisites: Familiarity with Object Oriented Programming principles in a language such as Ada, Java, or C++. No previous experience with C# or .NET is assumed. This tutorial will describe the main elements of the C# programming language and the Common Language Infrastructure (whose implementation by Microsoft is knows as .NET). It will focus on C#'s more novel language features, using examples and comparisons with other languages (in particular, Ada and Java) to describe the semantics. Specific C# language topics to be covered include the compilation model, namespaces, types, generics, exception handling, and threading. Common Language Infrastructure / .NET topics include summaries of the Base Class Library, Common Intermediate Language, Common Language System, Common Type System and Virtual Execution System. In short, this tutorial may be considered as the presenter's response to the following question: "C# is sometimes described as Microsoft's answer to Java. Is this an accurate assessment, and in any event how do C# and .NET relate to Ada?"
SPARK
Authors: Jennings Trevor J.
Published: April 2020

Level -Intermediate

SPARK is an annotated sub-language of Ada which is unambiguous and suitable for rigorous static analysis. It has been extensively used in industrial applications where safety and security are paramount, such as miltary aerospace, rail signaling, and high-grade cryptographic systems.

The design of SPARK aligns closely with rigorous engineering approaches such as PSP/TSP, Six- Sigma, and the principles of the Lean Engineering movement in taking a "zero tolerance" approach to defect reduction.

In this light, SPARK is far more than "just a programming language" - it offers a distinct engineering mindset and discipline for the development of high-assurance systems.

The tutorial, which is extracted from the four-day "Software Engineering with SPARK" course will cover: The rationale and design goals of SPARK, the core SPARK language, and SPARK analyses including information flow, exception freedom, and formal verification, and the impact of SPARK on software process. The tutorial will also cover the "Libre" release of the SPARK technology and the research topics that this opens, such as more advanced forms of analysis and proof, modelchecking, and language extensions.
Echo
Authors: Knight John
Published: April 2020

Echo is a novel yet practical approach to the formal verification of large software systems. The Echo approach splits verification into two major parts. In the first part, the SPARK tools are used to verify an implementation written in SPARK Ada against a low-level specification written using the SPARK source-code annotations. In the second part, a high-level specification is extracted automatically from the annotated implementation, and a proof constructed using the PVS theorem proving system that the extracted specification implies the original specification. Part of what makes Echo practical is a technique called verification refactoring. The program to be verified is mechanically refactored specifically to facilitate verification. In both parts of the proof process, semantics-preserving refactorings are applied to the implementation to reduce the complexity of the software and thereby to reduce the difficulty of verification proof. Much of the Echo approach is automated. The verification burden is reduced by distributing the burden over separate tools and techniques. In this presentation, the Echo verification technology will be described. The technology will be illustrated using the verification of two security applications and a novel medical device.
Complementing Ada with other programming languages
Authors: Tardieu Samuel , Polti Alexis
Published: April 2020

This paper presents our experience in using Ada and the Ravenscar profile in a robotics non-profit association and in a robotics competition. While Ada is our primary and dominant language, we have complemented it with a hardware description language (Verilog) and an interactive language (Forth). We describe the interface between those languages, and the design choices that have been made to minimize the risks taken by leaving the Ada world. We also explain why we chose in some conditions to relax restrictions imposed by the use of the Ravenscar profile.
Multilingual component programming in racket
Authors: Felleisen Matthias
Published: April 2020

In the world of Racket, software systems consist of inter-operating components in different programming languages. A component's implementation language may provide the full functionality of Racket, or it may support a small domain-specific notation. Naturally, Racketeers construct languages as Racket components and compose them to create new languages. This talk will present the ideas behind Racket: language-specific components, the composition of components, and, most importantly, the rich support for building languages.
Infrastructure for component-based DDS application development
Authors: Otte William R. , Gokhale Aniruddha , Schmidt Douglas C. , Willemsen Johnny
Published: April 2020

Enterprise distributed real-time and embedded (DRE) systems are increasingly being developed with the use of component-based software techniques. Unfortunately, commonly used component middleware platforms provide limited support for event-based publish/subscribe (pub/sub) mechanisms that meet both quality-of-service (QoS) and configurability requirements of DRE systems. On the other hand, although pub/sub technologies, such as OMG Data Distribution Service (DDS), support a wide range of QoS settings, the level of abstraction they provide make it hard to configure them due to the significant source-level configuration that must be hard-coded at compile time or tailored at run-time using proprietary, ad hoc configuration logic. Moreover, developers of applications using native pub/sub technologies must write large amounts of boilerplate "glue" code to support run-time configuration of QoS properties, which is tedious and error-prone. This paper describes a novel, generative approach that combines the strengths of QoS-enabled pub/sub middleware with component-based middleware technologies. In particular, this paper describes the design and implementation of DDS4CIAO which addresses a number of inherent and accidental complexities in the DDS4CCM standard. DDS4CIAO simplifies the development, deployment, and configuration of component-based DRE systems that leverage DDS's powerful QoS capabilities by provisioning DDS QoS policy settings and simplifying the development of DDS applications.