bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome sequencing of evolved aspergilli populations reveals robust genomes, transversions in A. flavus, and sexual aberrancy in non-homologous end-joining mutants
Authors: Álvarez-Escribano Isidro , Sasse Christoph , Bok Jin Woo , Na Hyunsoo , Amirebrahimi Mojgan , Lipzen Anna , Schackwitz Wendy , Martin Joel , Barry Kerrie , Gutiérrez Gabriel , Cea-Sánchez Sara , Marcos Ana T. , Grigoriev Igor V. , Keller Nancy P. , Braus Gerhard H. , Cánovas David
Published: November 2019

Background

Aspergillusspp. comprises a very diverse group of lower eukaryotes with a high relevance for industrial applications and clinical implications. These multinucleate species are often cultured for many generations in the laboratory, which can unknowingly propagate hidden genetic mutations. To assess the likelihood of such events, we studied the genome stability of aspergilli by using a combination of mutation accumulation (MA) lines and whole genome sequencing.

Results

We sequenced the whole genomes of 30 asexual and 10 sexual MA lines of threeAspergillusspecies (A. flavus,A. fumigatusandA. nidulans) and estimated that each MA line accumulated mutations for over 4000 mitoses during asexual cycles. We estimated mutation rates of 4.2 × 10−11(A. flavus), 1.1 × 10−11(A. fumigatus) and 4.1 × 10−11(A. nidulans) per site per mitosis, suggesting that the genomes are very robust. Unexpectedly, we found a very high rate of GC → TA transversions only inA. flavus. In parallel, 30 asexual lines of the non-homologous end-joining (NHEJ) mutants of the three species were also allowed to accumulate mutations for the same number of mitoses. Sequencing of these NHEJ MA lines gave an estimated mutation rate of 5.1 × 10−11(A. flavus), 2.2 × 10−11(A. fumigatus) and 4.5 × 10−11(A. nidulans) per base per mitosis, which is slightly higher than in the wild-type strains and some ~ 5–6 times lower than in the yeasts. Additionally, inA. nidulans, we found a NHEJ-dependent interference of the sexual cycle that is independent of the accumulation of mutations.

Conclusions

We present for the first time direct counts of the mutation rate of filamentous fungal species and find thatAspergillusgenomes are very robust. Deletion of the NHEJ machinery results in a slight increase in the mutation rate, but at a rate we suggest is still safe to use for biotechnology purposes. Unexpectedly, we found GC→TA transversions predominated only in the speciesA. flavus, which could be generated by the hepatocarcinogen secondary metabolite aflatoxin. Lastly, a strong effect of the NHEJ mutation in self-crossing was observed and an increase in the mutations of the asexual lines was quantified.
Hormonal induction of spermiation in a Eurasian bufonid (Epidalea calamita)
Authors: Arregui Lucía , Diaz-Diaz Sergio , Alonso-López Elia , Kouba Andrew J.
Published: November 2019

Background

Amphibian diversity is declining at an alarming rate due to habitat loss, invasive species, climate change and diseases. Captive assurance colonies have been established for some species at risk; however, many species do not breed well in captivity and the development of assisted reproductive technologies (ART) is critical to help sustain genetic diversity. To date, the majority of the work has been accomplished in species from the American continent and Australia, and there is a need to address similar breeding challenges in Eurasian and African species of amphibians.

Methods

The aim of this study was to develop a hormone protocol for stimulation of spermiation inEpidalea calamitaas a model for Eurasian bufonids. Hence, the effect on sperm production and quality of three doses of chorionic gonadotropin hormone (5, 10 and 15 IU hCG/g) over time (1 to 24 h) was evaluated. In addition, cold storage (at 5 °C) of sperm for 24 and 48 h and three frequencies for hormonal treatment (weekly, biweekly and monthly) were examined.

Results

Hormone concentrations of 10 or 15 IU of hCG induced spermiation in 100% of males and produced sperm of comparable quality, while 5 IU hCG stimulated spermiation in only 40% of males. Total motility peaked between 1 to 4 h post-treatment with 10 IU hCG, whereas treatment with 15 IU hCG peaked between 2 to 6 h. After 24 h of cold storage total motility dropped by 20% and forward motility dropped by 10% for both the 10 and 15 IU treatments. Weekly hormone administration resulted in higher variation between trials in all motility parameters and a lower overall Total Motility and Forward Movement. Furthermore, the effect of exogenous hormone treatment overlapped between the last two trials in the weekly frequency. Sperm concentration was higher in the first trial for all frequencies but showed no differences among other trials.

Conclusions

Overall, these results show that hormone concentration, time after treatment, frequency of hormone treatment and cold storage should be borne in mind when developing a hormone stimulation protocol for Eurasian amphibian species.
A qualitative study of community elders’ perceptions about the underutilization of formal maternal care and maternal death in rural Nigeria
Authors: Fantaye Arone Wondwossen , Okonofua Friday , Ntoimo Lorretta , Yaya Sanni
Published: November 2019

Background

Underutilization of formal maternal care services and accredited health attendants is a major contributor to the high maternal mortality rates in rural communities in Nigeria. Perceptions of a poor quality of care and inaccessible services in health facilities strongly influence the low use of formal maternal care services. There is therefore a need to understand local perceptions about maternal health services utilization and maternal death. This study thereby aims to explore perceptions and beliefs about the underutilization of formal care and causes of maternal death, as well as to identify potential solutions to improve use and reduce maternal mortality in rural Nigeria.

Methods

Data were collected through 9 community conversations, which were conducted with 158 community elders in 9 rural communities in Edo State, Nigeria. Data from transcripts were analyzed through inductive thematic analysis using NVivo 12 software.

Results

Perceived reasons for the underutilization of formal maternal care included poor qualities of care, physical inaccessibility, financial inaccessibility, and lack of community knowledge. Perceived reasons for maternal death were related to medical causes, maternal healthcare services deficiencies, uptake of native maternal care, and poor community awareness and negligence. Elders identified increased access to adequate maternal care, health promotion and education, community support, and supernatural assistance from a deity as solutions for increasing use of formal maternal care and reducing maternal mortality rates.

Conclusion

Study results revealed that multifaceted approaches that consider community contexts, challenges, and needs are required to develop acceptable, effective and long-lasting positive changes. Interventions aiming to increase use of formal care services and curb maternal mortality rates must target improvements to the technical and interpersonal qualities of care, ease of access, community awareness and knowledge, and allow community members to actively engage in implementation phases.
Higher rate of long-term serologic response of four double doses vs. standard doses of hepatitis B vaccination in HIV-infected adults: 4-year follow-up of a randomised controlled trial
Authors: Chaiwarith Romanee , Praparattanapan Jutarat , Kotarathititum Wilai , Wipasa Jiraprapa , Chaiklang Kanokporn , Supparatpinyo Khuanchai
Published: November 2019

Background

We previously reported that four doses or four double doses of hepatitis B vaccination regimens could not significantly increase a response rate compared with standard doses. However, the antibody levels were higher in the four doses and four double doses groups. This study followed those patients for at least 3 years and aimed to evaluate the immunogenicity of the three vaccination regimens.

Methods

HIV-infected adults who had CD4+ cell counts > 200 cells/mm3, undetectable plasma HIV-1 RNA, and negative for all hepatitis B virus markers were randomly assigned to receive one of three recombinant vaccines (Hepavax-Gene® Berna, Korea) regimens: 20 μg IM at months 0, 1, and 6 (standard doses group, n = 44), 20 μg IM at months 0, 1, 2, 6 (four doses group, n = 44), or 40 μg IM at months 0, 1, 2, and 6 (four double doses group, n = 44) between February 2011 and May 4, 2012. Of 132 participants, 126 were evaluated from August 2015 to January 2016; 42 in the standard doses, 43 in the four doses, and 41 in the four double doses groups.

Results

At a median duration of 49.7 months (range 46.7–53.7) after completion of the primary vaccination schedule, the percentages of responders with anti-HBs ≥ 10 mIU/mL were 57.1% (95% CI 41.5–72.8%) in the standard doses group; 76.7% (95% CI 63.6–89.9%) in the four doses group (P = 0.067 vs. the standard doses group); and 80.5% (95% CI 67.8–93.2%) in the four double doses group (P = 0.033 vs. the standard doses group). Factors associated with a responder were the vaccination schedule (either four doses or four double doses groups) and a younger age.

Conclusions

Despite the highly effectiveness of the standard hepatitis B vaccination regimen at 6 months after completion, the long-term immunogenicity was lower than the four double doses regimen among HIV-infected adults with CD4+ cell counts > 200 cells/mm3 and undetectable plasma HIV-1 RNA. The standard vaccination regimen may not be the best strategy to provide long-term immune response against hepatitis B virus among HIV-infected individuals.

Trial registration NCT1289106, NCT02713620
Expression of P63 and its correlation with prognosis in diffuse large B-cell lymphoma: a single center experience
Authors: Hu Wan-Ming , Jin Jie-Tian , Wu Chen-Yan , Lu Jia-Bin , Zhang Li-Hong , Zeng Jing , Lin Su-Xia
Published: November 2019

Background

Large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin’s lymphoma among adults. In some cases, DLBCL may seem similar to carcinoma cells, presenting a round, oval, or polygonal shape and clear nuclei. We found that the expression of P63 accounted for a considerable proportion of DLBCL cases. Under the circumstances, P63 expression may lead to a misdiagnosis, especially with a small biopsy. We aim to investigate the expression status and prognostic significance of P63 in a cohort of Chinese DLBCL patients.

Methods

P63, ΔNP63(P40), P53 and Ki67 were detected by immunohistochemistry (IHC). A ROC curve was adopted to find the best cut-off value for positive P63/P53 expression and high Ki67 expression. We defined P53 as positive when ≥50% of the tumor cells showed staining. The relationship between P63 and P53/Ki67 expression was examined. Time-to-event endpoints were estimated according to the Kaplan-Meier method. Moreover, multivariate analyses were conducted to evaluate the prognostic factors in DLBCL.

Results

Out of all the 159 DLBCL cases, 76 (47.8%) expressed P63 in the nuclei, while 41 (25.8%) were determined to have high expression by using a ROC cut-off value “≥6”. Examination of the different P63 isoforms revealed that the ΔNP63(P40) was unclearly and weakly expressed in only 3 cases, showing a fuzzy yellow cytoplasm. P63 expression was not correlated with subtype (GCB or non-GCB) or P53 but was correlated with a high proliferative index (Ki67). Kaplan-Meier analyses revealed that P63 expression was correlated with overall survival, and P63 positive cases showed poor survival outcomes (P<0.05) in our cohort.

Conclusions

ΔNP63(P40) is a useful marker in the differential diagnosis of poorly differentiated squamous cell carcinoma versus DLBCL in small needle biopsy. P63 may be involved in DLBCL tumor progression, and it is an unfavorable prognostic marker in DLBCL. A subgroup of P63 and P53 coexpression DLBCL patients with an extremely poor prognosis should be noted.
Adjuvant versus early salvage radiotherapy: outcome of patients with prostate cancer treated with postoperative radiotherapy after radical prostatectomy
Authors: Vogel Marco M. E. , Kessel Kerstin A. , Schiller Kilian , Devecka Michal , Gschwend Jürgen E. , Weichert Wilko , Wilkens Jan J. , Combs Stephanie E.
Published: November 2019

Background

Adjuvant (ART) and salvage radiotherapy (SRT) are two common concepts to enhance biochemical relapse free survival (BCRFS) in patients with prostate cancer (PC). We analyzed differences in outcome between ART and SRT in patients with steep decline of PSA-levels after surgery to compare outcome.

Methods

We evaluated 253 patients treated with postoperative RT with a median age of 66 years (range 42–85 years) treated between 2004 and 2014. Patients with additive radiotherapy due to PSA persistence and patients in the SRT group, who did not achieve a postoperative PSA level <0.1 ng/mL were excluded. Hence, data of 179 patients was evaluated. We used propensity score matching to build homogenous groups. A Cox regression model was used to determine differences between treatment options. Median follow-up was 32.5 months (range 1.4–128.0 months).

Results

Early SRT at PSA levels <0.3 ng/mL was associated with significant longer BCRFS than late SRT (HR: 0.32, 95%-CI: 0.14–0.75,p = 0.009). Multiple Cox regression showed pre-RT PSA level, tumor stage, and Gleason score as predictive factors for biochemical relapse. In the overall group, patients treated with either ART or early SRT showed no significant difference in BCRFS (HR: 0.17, 95%-CI: 0.02–1.44,p = 0.1). In patients with locally advanced PC (pT3/4) BCRFS was similar in both groups as well (HR: 0.21, 95%-CI:0.02–1.79,p = 0.15).

Conclusion

For patients with PSA-triggered follow-up, close observation is essential and early initiation of local treatment at low PSA levels (<0.3 ng/mL) is beneficial. Our data suggest, that SRT administered at early PSA rise might be equieffective to postoperative ART in patients with locally advanced PC. However, the individual treatment decision must be based on any adverse risk factors and the patients’ postoperative clinical condition.

Study registration

The present work is approved by the Ethics Commission of the Technical University of Munich (TUM) and is registered with the project number 320/14.
Cervical cancer in Ethiopia – predictors of advanced stage and prolonged time to diagnosis
Authors: Begoihn Matthias , Mathewos Assefa , Aynalem Abreha , Wondemagegnehu Tigeneh , Moelle Ulrike , Gizaw Muluken , Wienke Andreas , Thomssen Christoph , Worku Dawit , Addissie Adamu , Jemal Ahmedin , Kantelhardt Eva Johanna
Published: November 2019

Introduction

In Ethiopia, most cervical cancer patients present at advanced cancer stages, long time after they experience first symptoms. We investigated possible predictors of long time spans between symptom onset and pathologic diagnosis (patient intervals). We also aimed to seek out predictors for advanced cancer stage diagnosis.

Methods

We conducted a retrospective cohort study among 1575 cervical cancer patients who were registered at Tikur Anbessa Specialized Hospital (TASH), Addis Ababa, Ethiopia between September 2008 and September 2012. Cox proportional hazards regression was used to find predictors of long patient intervals. Cumulative odds ordinal logistic regression was used to identify predictors of cancer stage at diagnosis.

Results

Median patient interval was 30 weeks, with the interval substantially longer in patients residing in rural than urban areas. Longer patient intervals were associated with more advanced cancer stages at pathologic diagnosis. HIV-positive women had an almost 1.5 times increased risk of diagnosis at a more advanced stage.

Conclusion

Cervical cancer patients are diagnosed after long time periods leading to advanced stages at diagnosis. Measures to raise awareness about cervical cancer, to increase screening and to shorten the time interval from recognition of symptoms to diagnosis are urgently needed.
Unique N-glycosylation of a recombinant exo-inulinase from Kluyveromyces cicerisporus and its effect on enzymatic activity and thermostability
Authors: Ma Junyan , Li Qian , Tan Haidong , Jiang Hao , Li Kuikui , Zhang Lihua , Shi Quan , Yin Heng
Published: November 2019

Background

Inulinase can hydrolyze polyfructan into high-fructose syrups and fructoligosaccharides, which are widely used in food, the medical industry and the biorefinery of Jerusalem artichoke. In the present study, a recombinant exo-inulinase (rKcINU1), derived from Kluyveromyces cicerisporus CBS4857, was proven as an N-linked glycoprotein, and the removal of N-linked glycan chains led to reduced activity.

Results

Five N-glycosylation sites with variable high mannose-type oligosaccharides (Man3–9GlcNAc2) were confirmed in the rKcINU1. The structural modeling showed that all five glycosylation sites (Asn-362, Asn-370, Asn-399, Asn-467 and Asn-526) were located at the C-terminus β-sandwich domain, which has been proven to be more conducive to the occurrence of glycosylation modification than the N-terminus domain. Single-site N-glycosylation mutants with Asn substituted by Gln were obtained, and the Mut with all five N-glycosylation sites removed was constructed, which resulted in the loss of all enzyme activity. Interestingly, the N362Q led to an 18% increase in the specific activity against inulin, while a significant decrease in thermostability (2.91 °C decrease in Tm) occurred, and other single mutations resulted in the decrease in the specific activity to various extents, among which N467Q demonstrated the lowest enzyme activity.

Conclusion

The increased enzyme activity in N362Q, combined with thermostability testing, 3D modeling, kinetics data and secondary structure analysis, implied that the N-linked glycan chains at the Asn-362 position functioned negatively, mainly as a type of steric hindrance toward its adjacent N-glycans to bring rigidity. Meanwhile, the N-glycosylation at the other four sites positively regulated enzyme activity caused by altered substrate affinity by means of fine-tuning the β-sandwich domain configuration. This may have facilitated the capture and transfer of substrates to the enzyme active cavity, in a manner quite similar to that of carbohydrate binding modules (CBMs), i.e. the chains endowed the β-sandwich domain with the functions of CBM. This study discovered a unique C-terminal sequence which is more favorable to glycosylation, thereby casting a novel view for glycoengineering of enzymes from fungi via redesigning the amino acid sequence at the C-terminal domain, so as to optimize the enzymatic properties.
Phosphorylation sites of microtubule-associated protein 1B (MAP 1B) are involved in axon growth and regeneration
Authors: Ishikawa Yuya , Okada Masayasu , Honda Atsuko , Ito Yasuyuki , Tamada Atsushi , Endo Naoto , Igarashi Michihiro
Published: November 2019

The growth cone is a specialized structure that forms at the tip of extending axons in developing and regenerating neurons. This structure is essential for accurate synaptogenesis at developmental stages, and is also involved in plasticity-dependent synaptogenesis and axon regeneration in the mature brain. Thus, understanding the molecular mechanisms utilized by growth cones is indispensable to understanding neuronal network formation and rearrangement. Phosphorylation is the most important and commonly utilized protein modification in signal transduction. We previously identified microtubule-associated protein 1B (MAP 1B) as the most frequently phosphorylated protein among ~ 1200 phosphorylated proteins. MAP 1B has more than 10 phosphorylation sites that were present more than 50 times among these 1200 proteins. Here, we produced phospho-specific antibodies against phosphorylated serines at positions 25 and 1201 of MAP 1B that specifically recognize growing axons both in cultured neurons and in vivo in various regions of the embryonic brain. Following sciatic nerve injury, immunoreactivity with each antibody increased compared to the sham operated group. Experiments with transected and sutured nerves revealed that regenerating axons were specifically recognized by these antibodies. These results suggest that these MAP 1B phosphorylation sites are specifically involved in axon growth and that phospho-specific antibodies against MAP 1B are useful markers of growing/regenerating axons.
Early lactate measurement is associated with better outcomes in septic patients with an elevated serum lactate level
Authors: Chen Hui , Zhao Chenyan , Wei Yao , Jin Jun
Published: November 2019

Background

The optimal timing of lactate measurement for septic patients in the intensive care unit (ICU) remains controversial, and whether initiating and repeating the lactate measurement earlier could make a difference for septic patients with an elevated lactate level remains unexplored.

Methods

This was a retrospective observational study that included septic patients with an initial lactate level > 2.0 mmol/L after ICU admission, and all data were extracted from the Medical Information Mart for Intensive Care III (MIMIC-III) database. The main exposure of interest was the early lactate measurement, which was defined as an initial lactate level measurement within 1 h after ICU admission. The primary outcome was 28-day mortality.

Results

A total of 2642 eligible subjects were enrolled, including 738 patients who had initial lactate measurements completed within 1 h (EL group) and 1904 patients who had initial lactate measurements completed more than 1 h after ICU admission (LL group). A significant beneficial effect of early lactate measurement in terms of 28-day mortality was observed: the adjusted odds ratio (OR) was 0.69 (95% CI 0.55–0.87; p = 0.001), and the mediation effect of the time to initial vasopressor administration was significant (average causal mediation effect (ACME) − 0.018; 95% CI − 0.005 approximately to − 0.036; p < 0.001). A strong relationship between delayed initial lactate measurement and risk-adjusted 28-day mortality was noted (OR 1.04; 95% CI 1.02–1.05; p < 0.001). Each hour of delay in remeasuring the lactate level was associated with an increase in 28-day mortality in the EL group (OR 1.09; 95% CI 1.04–1.15; p < 0.001). Further analysis demonstrated that repeating the measurement 3 h after the initial lactate measurement led to a significant difference.

Conclusions

Early lactate measurement is associated with a lower risk-adjusted 28-day mortality rate in septic patients with lactate levels > 2.0 mmol/L. A shorter time to the initial vasopressor administration may contribute to this relationship. Repeating the lactate measurement within 3 h after the initial measurement is appropriate for patients whose lactate levels were measured within 1 h of admission.
Non-real eigenvalues of nonlocal indefinite Sturm–Liouville problems
Authors: Sun Fu , Li Kun , Qi Jiangang , Liao Baochao
Published: November 2019

The present paper deals with non-real eigenvalues of regular nonlocal indefinite Sturm–Liouville problems. The existence of non-real eigenvalues of indefinite Sturm–Liouville differential equation with nonlocal potential $K(x,t)$K(x,t) associated with self-adjoint boundary conditions is studied. Furthermore, a priori upper bounds of non-real eigenvalues for a class of indefinite differential equation involving nonlocal point interference potential function is obtained.
Patient participation in research funding: an overview of when, why and how amongst Dutch health funds
Authors: den Oudendammer Willemijn M. , Noordhoek Jacquelien , Abma-Schouten Rebecca Y. , van Houtum Lieke , Broerse Jacqueline E. W. , Dedding Christine W. M.
Published: November 2019

Background

Patient participation in decision-making on health-related research has gained ground. Nineteen Dutch health-related research-funding organisations (HFs) have taken up the challenge to include patients in their funding process. A ‘Patient participation (PP) advisory team’ was set-up, with HF-representatives and patient advocates, who together initiated this study. We provide an overview of when, why, and how PP activities take place in HFs’ funding processes, share main challenges and identify possible solutions.

Methods

A qualitative research design was used. Data was gathered by questionnaires (n = 14) and semi-structured interviews (n = 18) with HF employees responsible for patient participation, followed by a workshop (n = 27) with involved employees of HFs and key players in PP from national patient organisations and research organisations. A descriptive analysis was used for the questionnaire. A semi-directed content analysis was used for the interviews and the workshop.

Results

Three stages can be identified in the funding process in which HFs carry out PP activities: (1) strategic decision-making about focus of research (e.g. shared research agendas); (2) call for and receipt of research proposals (e.g. mandatory inclusion of letter of recommendation from patient organisation); (3) decision-making about the funding of research proposals (e.g. patients reside in a patient panel to co-review research proposals). Main challenges identified to carry out PP activities include: how to accommodate diversity of the patient body (mainly encountered in stage 1 and 3); to what extent should patients receive training to successfully participate (mainly encountered in stage 1 and 3); and who is responsible for patient-researcher dialogues (mainly encountered in stage 1 and 2). All nineteen HFs agree that patients should be included in at least one stage of the funding process for health-related research. CONCLUSION: Further broadening and optimising patient involvement is still needed. The proposed solutions to the identified challenges could serve as inspiration for national and international research funding foundations that aim to structurally include patients in their funding process.
Beyond ethical approval: fostering ethical research practices within inter-sectoral research projects involving academic and NGO sector partners
Authors: McDermott Ronan , Gibbons Pat , Mpanje Desire , McGrath Sinéad , Markey Anne , Ferrandez Pablo Cortés , Haryati Dini , Azizah Nur
Published: November 2019

While research and innovation collaborations between NGOs and academic organisations can create considerable synergies with positive effects for the humanitarian sector, the inter-sectoral nature of such collaborations can generate challenges due to the varying mandates, objectives and ways of working of the organisations involved. By drawing on the experiences of a 4-year project involving a consortium of academic and NGO partners, this paper outlines three broad and inter-related ethical challenges that such projects can encounter and how they can be practically negotiated. Firstly, how are the knowledge-generation requirements of such projects addressed without engaging in the mere extraction of data from participants? Secondly, how are potential risks to participants arising from their participation balanced with the need to include their voices within the research project? Finally, how are the formal requirements laid down by institutional review committees, primarily within academic organisations, to be adhered to within field contexts in which there are well-established expectations and ways of working on the part of NGO partners and beneficiaries? While these dilemmas are merely illustrative of the potential ethical dilemmas that inter-sectoral collaboration might encounter, the paper highlights that ethical dilemmas ought to be addressed reflexively by all stakeholders in order to facilitate improved collaboration and, ultimately, better quality, more relevant and more ethically informed research.
Roads less traveled: understanding the “why” in simulation as an integrated continuing professional development activity
Authors: Tavares Walter
Published: November 2019

Background

The simulation community has experienced significant advances, strengthening the case for the use of simulation in medical education toward improving patient outcomes. However, an underlying assumption particularly regarding utilization of simulation by those who are in practice, is that simulation will be selected as a continuing professional development (CPD) strategy. Exploring reasons for choices of educational formats, particularly regarding simulation, is poorly integrated into CPD research.

Discussion

Despite significant advances the scientific simulation community has been slow to produce evidence regarding why practitioners may be reserved in engaging in simulation or not. Using examples from related education contexts the author attempts to bridge simulation science, CPD and less commonly used theoretical frameworks to address this issue. The author argues that theoretical perspectives that recognize the use of simulation for CPD as a socio-personal process and/or a personal or group issue (e.g., theories of intelligence, self-determination theory, theory of planned behavior, social identity theory) and that are conceptually distinct from educational mechanisms/ provision are necessary to advance simulation use in CPD contexts.

Conclusion

Given the close relationship practicing clinicians have to patient outcomes a new imperative may be to focus on the theoretical and practical links informing simulation use for CPD at the level of the individual and individual-among-professional groups. The simulation community may therefore need to engage in research that attempts to further uncover and address underlying issues of “why” clinicians integrate simulation as CPD activities or not.
Effects of environmental enrichment on forebrain neural plasticity and survival success of stocked Atlantic salmon
Authors: Mes Daan , van Os Renske , Gorissen Marnix , Ebbesson Lars O. E. , Finstad Bengt , Mayer Ian , Vindas Marco A.
Published: November 2019

Fish reared for stocking programs are severely stimulus-deprived compared to their wild conspecifics raised under natural conditions. This leads to reduced behavioural plasticity and low post-release survival of stocked fish. Environmental enrichment can have positive effects on important life-skills, such as predator avoidance and foraging behaviour, but the neural mechanisms underpinning these behavioural changes are still largely unknown. In this study, juvenile Atlantic salmon (Salmo salar) were reared in an enriched hatchery environment for seven weeks, after which neurobiological characteristics and post-release survival were compared to fish reared under normal hatchery conditions. Using in situ hybridisation and qPCR, we quantified the expression of brain-derived neurotrophic factor (bdnf) and the neural activity marker cfos in telencephalic subregions associated with relational memory, emotional learning, and stress reactivity. Aside from lower expression of bdnf in the Dlv (a region associated with relational memory) of enriched salmon, we observed no other significant effects of enrichment in the studied regions. Exposure to an enriched environment increased post-release survival during a five-month residence in a natural river by 51%. Thus, we demonstrate that environmental enrichment can improve stocking success of Atlantic salmon parr and that EE is associated with changes in bdnf expression in the fish's hippocampus-equivalent structure.
Experimental evidence that physical activity affects the multivariate associations among muscle attachments (entheses)
Authors: Karakostis Fotios Alexandros , Wallace Ian , Konow Nicolai , Harvati Katerina
Published: November 2019

The morphology of entheses (muscle/tendon attachment sites) on bones is routinely used in paleontological and bioarcheological studies to infer the physical activity patterns of ancient vertebrate species including hominins. However, such inferences have often been disputed due to limitations of the quantitative methods commonly employed and a lack of experimental evidence demonstrating direct effects of physical activity on entheseal morphology. Recently, we introduced a new and improved method of quantifying and analyzing entheseal morphology that involves repeatable three-dimensional measurements combined with multivariate statistics focused on associations among multiple entheses. Here, to assess the validity of our method for investigating variation in entheseal morphology related to physical activity patterns, we analyzed femora of growing turkeys that were experimentally exercised for 10 weeks on either an inclined or declined treadmill or served as controls (n= 15 specimens, 5/group). Our multivariate approach identified certain patterns involving three different entheses (associated with muscles gluteus primus, medial gastrocnemius, vastus medialis and adductor magnus) that clearly differentiated controls from runners. Importantly, these differences were not observable when comparing groups within each of the three entheseal structures separately. Body mass was not correlated with the resulting multivariate patterns. These results provide the first experimental evidence that variation in physical activity patterns has a direct influence on entheseal morphology. Moreover, our findings highlight the promise of our newly-developed quantitative methods for analyzing the morphology of entheses to reconstruct the behavior of extinct vertebrate species based on their skeletal remains.
Australian state influenza notifications and school closures in 2019
Authors: Scott Anna Mae , Bakhit Mina , Clark Justin , Vermeulen Melanie , Jones Mark , Looke David , Del Mar Chris , Glasziou Paul
Published: November 2019

Background: The impact of school holidays on influenza rates has been sparsely documented in Australia. In 2019, the early winter influenza season coincided with mid-year school breaks, enabling us the unusual opportunity to examine how influenza incidence changed during school closure dates.

Methods: The weekly influenza data from five Australian state and one territory health departments for the period of week 19 (mid-May) to week 35 (early September) 2019 were compared to each state’s public school closure dates. We used segmented regression to model the weekly counts and a negative binomial distribution to account for overdispersion due to autocorrelation. The models’ goodness-of-fit was assessed by plots of observed versus expected counts, plots of residuals versus predicted values, and Pearson’s Chi-square test. The main exposure was the July two-week school vacation period, using a lag of one week. The effect is estimated as a percent change in incidence level, and in slope. We also dichotomized the change in weekly counts into decreases versus increases (or no change). The proportion of decreases were then compared for each of three periods (pre-vacation, vacation, post-vacation) using Fishers exact test.

Results: School holidays were associated with significant declines in influenza incidence. The models showed acceptable goodness-of-fit. The numbers and percentages of decreases in weekly influenza counts from the previous week for all states combined were: 19 (33%) pre-vacation; 11 (92%) decreases during the vacation; and 19 (59%) decreases post-vacation (P=0.0002). The first decline during school holidays is seen in the school aged (5-19 years) population, with the declines in the adult and infant populations being smaller and following a week later.

Conclusions: Given the significant and rapid reductions in incidence, these results have important public health implications. Closure or extension of holiday periods could be an emergency option for state governments.
Etiology, pathogenesis and prevention of seven metabolic pandemics - " diseases of civilization»
Authors: Титов Владимир , Titov Vladimir , Амелюшкина Вера , Amelyushkina Vera , Тарасов Александр , Tarasov Aleksandr
Published: November 2019

In the monograph, from the standpoint of the phylogenetic theory of General pathology proposed By V. N. Titov, the causes, conditions of formation and bases of prevention of seven metabolic pandemics, diseases of civilization are described. They are widespread in populations of all highly developed countries of the world; they are seven pathological processes: 1) atherosclerosis and atheromatosis; 2) essential, metabolic arterial hypertension; 3) metabolic syndrome; 4) insulin resistance syndrome; 5) obesity syndrome; 6) non-alcoholic fatty liver disease and 7) endogenous hyperuricemia.
Seven metabolic pandemics for a long time are only functional disorders, the development of pathology of which, if the doctor understands what is happening in the body and the great desire of patients, can be prevented. They arise as a result of patients ' abuse of the benefits of civilization. And if you understand the conditions of their formation, give up such pleasant "bad habits", really form an effective prevention of the physiological effects of environmental factors, you can significantly reduce the frequency of metabolic pandemics in the populations of developed countries. This is the practical significance of this monograph.
It is necessary for clinicians of different specialties, as well as patients of developed countries.
That Could Have Been Me: Director Deaths, CEO Mortality Salience, and Corporate Prosocial Behavior
Authors: Chen Guoli , Crossland Craig , Huang Sterling
Published: November 2019

Mortality salience—the awareness of the inevitability of death—is often traumatic. However, it can also be associated with a range of positive, self-transcendent cognitive responses, such as a greater desire to help others, contribute to society, and make a more meaningful contribution in one’s life and career. In this study, we provide evidence of a link between chief executive officer (CEO) mortality salience—triggered by the death of a director at the same firm—and a subsequent increase in firm-level prosocial behavior or corporate social responsibility (CSR). We further show that this core relationship is amplified in situations where the death of the director is likely to have been especially salient (i.e., the director was appointed within the CEO’s tenure, or the death was sudden/expected). In supplementary analyses, we find suggestive evidence of increased CEO prosociality in other professional domains as well as evidence that prosociality seems to be preferentially directed toward ingroups.

This paper was accepted by Olav Sorenson, organizations.
Making Only America Great? Non-U.S. Market Reactions to U.S. Tax Reform
Authors: Gaertner Fabio B. , Hoopes Jeffrey L. , Williams Braden M.
Published: November 2019

We study the foreign externalities of the recent U.S. tax reform, commonly known as the Tax Cuts and Jobs Act (TCJA). Specifically, we examine foreign firms’ stock returns around key tax reform events. We find significant heterogeneity in market responses by country, industry, and firm. Chinese firms experience large negative returns, especially in steel, business equipment, and chemical manufacturers, whereas the rest of the world experiences positive returns. Firms operating in more differentiated product markets experience positive returns, whereas firms in financial distress experience negative returns, consistent with the TCJA having competitive repercussions. We also find that firms experiencing decreases in effective tax rates following tax reform experience positive returns. Overall, our results suggest that the TCJA had varied, yet systematic effects on foreign firms’ shareholders’ wealth and the global competitive landscape.

This paper was accepted by Brian Bushee, accounting.
Kinetic and Thermodynamic Study of Adsorption of Copper (II) Ion on Moroccan Clay
Authors: Essebaai Hanane , Ismi Ilham , Lebkiri Ahmed , Marzak Said , Rifi El Housseine
Published: November 2019

Highly efficient low-cost adsorbent was applied for copper (II) ions uptake from aqueous solution. Characteristics of natural adsorbent were established using scanning X-ray diffraction (XRD), X-ray fluorescence, electron microscope (SEM) and Fourier Transform Infra-Red (FTIR). Various physicochemical parameters such as contact time, initial copper(II) ions concentration, adsorbent dosage, pH of copper (II) ions solution and temperature were investigated. The result showed that the adsorption of copper (II) ions by natural clay was favorable at pH=5,5. The adsorption was found to increase with increase in initial copper (II) ions concentration, and contact time. Equilibrium adsorption data were fitted using three isotherms and kinetic data tested with four kinetic models. Freundlich isotherm best described the adsorption of copper (II) ions onto utilised clay, the maximum monolayer adsorption capacity (qmax) was 8 mg/g. Pseudo-second-order model best described the kinetics of the adsorption process. Thermodynamic parameters such as Gibbs free energy, enthalpy and entropy were determined. It was found that copper (II) ions adsorption was spontaneous (ΔG°<0) and endothermic (ΔH°>0).
Adsorptive Removal Study of the Frequently Used Fluoroquinolone Antibiotics - Moxifloxacin and Norfloxacin from Wastewaters using Natural Zeolites
Authors: Rubashvili Imeda , Eprikashvili Luba , Kordzakhia Teimuraz , Zautashvili Marine , Pirtskhalava Nino , Dzagania Maia
Published: November 2019

Residual antibiotics pollution has become one of the most severe environmental problems today.Â  Antibiotics from hospitals and drug factories represent a potential risk for human and ecological health. Therefore, it has been a high exigency to develop some efficient and cost-effective treatment methods and technologies for antibiotics removal from industrial and household contaminated water. Adsorption is one of the most utilised techniques and has many competitive advantages such as the unique properties of flexibility, effectiveness, superior performance and the robustness for consecutive cycles. The present research concerns the adsorption of two frequently used fluoroquinolone antibiotics - moxifloxacin and norfloxacin on natural zeolite - clinoptilolite and its acid-modified form from aqueous solutions. For the first time, the adsorption of the antibiotics mentioned above on the selected natural zeolite was investigated under static and dynamic conditions. Adsorption experiment under dynamic conditions carried out using the specially constructed dynamic type of laboratory equipment. The effect of the inlet concentration, the flow rate and the pH value of the antibiotic solution, also, the contact time of system zeolite/antibiotic solution on the adsorption process were examined and evaluated using the Langmuir and Freundlich adsorption models. The results showed that the highest static adsorption capacities were observed at low initial concentration - 0.2 mg/mL of antibiotic solution for both adsorbents; the highest dynamic adsorption capacities - at low flow rate - 1.5 mg/mL and low inlet concentration - 0.2 mg/mL of antibiotic solution for both adsorbents. The static adsorption capacity was up to 2.71 mg/g for moxifloxacin hydrochloride; 4.14 mg/g for norfloxacin and the dynamic adsorption capacity was up to 1.20 mg/g for moxifloxacin hydrochloride; 2.10 mg/g for norfloxacin at a neutral pH value and constant temperature of 200°C. Each antibiotic was determined quantitatively in sample solutions using the developed and validated HPLC methods with a limit of quantitation - 0.05 Âµg/mL. Hence, this study demonstrates and proves that natural zeolite could be an effective adsorbent for the removal of the selected antibiotics from wastewaters.
Removal of methyl orange from aqueous solution using synthetic clay type MgAl-LDH: Characterization, Isotherm and thermodynamic studies
Authors: Zaghloul Ahmed , Abali Mâ€™hamed , Benhiti Ridouan , Ait ichou Abdejalil , Soudani Amina , Chiban Mohamed , Zerbet Mohamed , Sinan Fouad
Published: November 2019

The MgAl-LDH adsorbent (2:1) was developed by the urea method and used as an adsorbent for the removal of methyl orange from aqueous solution.Â The synthesized adsorbent was characterized by a different analytical technique: scanning electron microscope SEM, X-ray diffraction (XRD) and infrared spectroscopy (FT-IR). The effect of adsorption parameters such as solution pH, initial concentration of dye, and the temperature was studied using a static system. X-ray diffraction analysis of the samples confirms the crystal structure of the MgAl-LDH material. The MgAl-LDH adsorbent was efficient in removing MO from aqueous solution, and maximum removal of 98.5 % was observed in the pH range from 2 to 10. The maximum adsorption capacity of MgAl-LDH (2:1) was calculated from the Langmuir isotherm; the maximum quantity is 1250 mg. g-1. The determination of the thermodynamic parameters indicates that the reaction between methyl orange and MgAl-LDH (2:1) is spontaneous and exothermic (Î”HÂ°<0 and Î”GÂ°<0).It can be concluded that LDH adsorbent can be used effectively for the removal of anionic dyes fromÂ industrial wastewater.
Behavior of 3-hydrazino-6-aryl-1,2,4-triazin-5-one as a strong nucleophile towards active electrophilic compounds and their antibacterial evaluation
Authors: Al-Romaizan Abeer N.
Published: November 2019

The behavior of 3-hydrazino-6-aryl-1,2,4-triazin-5-one towards the active electrophilic compounds in polar and/ or non-polar solvents and various times and temperatures, has been studied. N-[2-(3-(3/5-(4-Nitrophenyl)-5/3-thioxo-1H-1,2,4-triazol-1-yl)-5-oxo-1,2,4-triazin-6-yl)phenyl]pivalamides were obtained from the reaction of N-(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)-pivalamide with 4-nitrobenzoyl isothiocyanate in THF and/ or EtOH-piperidine respectively. Also, N-(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)-pivalamide was shown a strong nucleophilic behavior by reaction with N-phenyl-thiourea to produceÂ N-[2-(5-oxo-3-(2-(phenylcarbamothioyl)-hydrazineyl)-1,2,4-triazin-6-yl)phenyl]pivalamide, which upon cyclization with diethyl carbonate produced N-(2-(5-oxo-3-(5-oxo-4-phenyl-3-thioxo-1,2,4-triazolidin-1-yl)- 1,2,4-triazin-6-yl)phenyl)pivalamide. Moreover, N-(2-(3-hydrazineyl-5-oxo-1,2,4-triazin-6-yl)phenyl)pivalamide studied its behavior by reaction with cyanoacetic acid, chloroacetonitrile, and/ or benzoyl carbonitrile to produce N-(2-(3-amino-4,8-dioxo-4H-[1,2,4]triazino[4,3-b][1,2,4]triazin-7-yl)phenyl)pivalamide,N-(2-(4-amino-8-oxo-2H-[1,2,4]triazino[4,3-b][1,2,4]triazin-7-yl)phenyl)pivalamide and N-(2-(4-imino-8-oxo-3-phenyl-4H-[1,2,4] triazino [4,3-b][1,2,4]triazin-7-yl)phenyl)pivalamide. Structure of the products was established upon their elemental analysis and FT-IR, 1H/ 13C NMR, and MS. The new compounds were evaluated as antibacterial agents some Gram-positive and negative bacteria. Some compounds were showed the highest inhibition activity towards Pseudomonas aeruginosa, Bacillus subtilis, Bacillus cereus, and Sarcina lutea bacteria and lowest inhibitory activity against Escherichia coli bacteria.
Calcite, the main corrosion inhibitor contained in the raw clay (Rhassoul) of brass in 3% NaCl medium.
Authors: Ben Seddik Nordin , Raissouni Ihssane , Draoui Khalid , Ait Aghzzaf Ahmed , Chraka Anas , Aznag Badr , Chaouket Faiza , Bouchta Dounia
Published: November 2019

Corrosion control of copper alloys such as brass is of great interest to researchers and scientists. Clays become materials of choice as corrosion inhibitors and as their reservoir in corrosive environments. The effect of Rhassoul on the corrosion of Cu-36Zn alloy in 3% NaCl solution has been studied. Electrochemical techniques showed that the optimum concentration was 1g/L showing the highest inhibition efficiency (82%). This concentration was evaluated at five different temperatures. In order to determine the influence of purification, this result was compared to that of the homoionic clay labeled Na+-ST and to the pure calcite. Chemical composition of the brass specimen and solutions were done by inductively coupled plasma atomic emission spectrometry (ICP-AES) and atomic absorption (AA) respectively. The effectiveness of this clay against the dissolution of Zinc reached 61%. XRD technique demonstrated the homoionization of this clay by shifting the basal spacing d001.