bluuebunny/crossref_metadata_2025 huggingface dataset:
Recommendation for performance verification of patient-based real-time quality control
Authors: Loh Tze Ping , Bietenbeck Andreas , Cervinski Mark A. , van Rossum Huub H. , Katayev Alex , Badrick Tony
Published: February 2020

Patient-based real-time quality control (PBRTQC) is a laboratory tool for monitoring the performance of the testing process. It includes well-established procedures like Bull’s algorithm, average of nomals, moving median, moving average (MA) and exponentially (weighted) MAs. Following the setup and optimization processes, a key step prior to the routine implementation of PBRTQC is the verification and documentation of the performance of the PBRTQC as part of the laboratory quality system. This verification process should provide a realistic representation of the performance of the PBRTQC in the environment it is being implemented in, to allow proper risk assessment by laboratory practitioners. This document focuses on the recommendation on performance verification of PBRTQC prior to implementation.
The IUPAC100 Global Women’s Breakfast Empowering Women in Chemistry
Authors: Garson Mary , McConnell Laura
Published: February 2020

On February 12, 2019, women chemists from over 50 different countries shared breakfast. They were taking part in the international networking event Empowering Women in Chemistry, an activity to celebrate the centenary of IUPAC. Women have made enormous contributions to the advancement of chemistry over the last 100 years, including as winners of Nobel prizes and many other major international awards, but they rarely take time to celebrate these achievements.
Ein neues Narrativ für Europa
Authors: Strachwitz Rupert Graf
Published: February 2020

Gedanken und Aufrufe zu einer neuen europäischen Ordnung gibt es schon bald 150 Jahre. Es scheint aber, daß wir keinen Schritt weitergekommen sind. Heute brauchen wir diese neue Ordnung dringender denn je. Uns nur auf technische Innovation zu verlassen, erscheint gefährlich. Gebraucht wird ein Ordnungsmodell für das 21. Jahrhundert. Es wird sich wahrscheinlich eher auf Regionen als auf Nationen und ganz sicher auf eine europäische Zivilgesellschaft stützen müssen. Auch diese muss sich allerdings erst entwickeln, obwohl es seit fast 100 Jahren zivilgesellschaftliche europäische Bewegungen gibt. Hierzu bedarf es eines neuen europäischen Narrativs.
Civil society and the European Union. From enthusiasm to disenchantment
Authors: Grote Jürgen R.
Published: February 2020

This paper adopts the wide definition of civil society, namely the one suggested by the EU. It includes all sorts of private collectives from producer groups, trade unions, care and common cause organizations, NGOs, to social and protest movements. Distinguishing between a structural (governance) and an actor-centred perspective (collective action) and, orthogonally, two levels of territorial complexity (the sub-, and the supranational), the history of the relationship between the EU and civil society is presented for the period of the past 35 years. It turns out that despite enormous efforts invested in the relationship from the part of both sides, and of many heroic declamations aimed at pathbreaking reform, the outcome tends to be relatively meagre and disenchanting both in institutional and organizational terms.
The endoplasmic reticulum-mitochondria encounter structure: coordinating lipid metabolism across membranes
Authors: Kornmann Benoît
Published: February 2020

Endosymbiosis, the beginning of a collaboration between an archaeon and a bacterium and a founding step in the evolution of eukaryotes, owes its success to the establishment of communication routes between the host and the symbiont to allow the exchange of metabolites. As far as lipids are concerned, it is the host that has learnt the symbiont’s language, as eukaryote lipids appear to have been borrowed from the bacterial symbiont. Mitochondria exchange lipids with the rest of the cell at membrane contact sites. In fungi, the endoplasmic reticulum-mitochondria encounter structure (ERMES) is one of the best understood membrane tethering complexes. Its discovery has yielded crucial insight into the mechanisms of intracellular lipid trafficking. Despite a wealth of data, our understanding of ERMES formation and its exact role(s) remains incomplete. Here, I endeavour to summarise our knowledge on the ERMES complex and to identify lingering gaps.
Accordion Governance
Authors: Berman Ayelet
Published: February 2020

Since the 1990s, western, developed countries have moved away from rule-making and standard-setting in multilateral intergovernmental organizations and have increasingly collaborated on those matters in clubs of developed countries, such as trans-governmental regulatory networks. Although clubs often generate rules or standards that affect developing countries, the latter have not had a voice in rule-making, resulting in a ‘participation gap’, for which clubs are being criticized. Against this background, I analyse a recent development that has largely gone unnoticed: Clubs have been integrating previously excluded developing countries. From small and exclusive clubs, they are growing into larger and more inclusive clubs. I call this trajectory of the past seventy years – the establishment of intergovernmental organizations, their increasing displacement in favour of clubs, and the recent reversion towards larger clubs – accordion governance. Like an accordion that expands or contracts as needed, so too have governance models and rule-making adjusted to changing conditions and preferences by becoming more or less inclusive. Focusing on club expansion, I address three questions: (1) How has participation – and the rules governing it – evolved over time? (2) Why are governments voluntarily sharing rule-making authority with new participants? (3) Can these reforms close the participation gap in international rule-making?
Performance of Msplit estimates in the context of vertical displacement analysis
Authors: Wyszkowska Patrycja , Duchnowski Robert
Published: February 2020

This paper concerns two types of Msplit estimation: squared Msplit estimation (SMS), which assumes normality of observation errors and absolute Msplit estimation (AMS), which applies

L

1

{\text{L}_{1}}

norm criterion. The main objective of the paper is to assess the accuracy of such estimators in vertical displacement analysis by applying Monte Carlo simulations. Another issue is to compare the accuracy of both estimators with the accuracy of the least squares estimation (LS). The paper shows that the accuracy of both Msplit estimates is like the accuracy of LS estimates. However, if some nonrandom errors occur, then accuracy of AMS estimates might be better than the accuracy of the rest of the estimates considered here. It stems from the fact that AMS estimates are robust against disturbances which have a small magnitude. It is also worth noting that the accuracy of both Msplit estimates might depend on the magnitude of the displacement.
Hermēneis in the Documentary Record from Hellenistic and Roman Egypt: interpreters, translators and mediators in a bilingual society
Authors: Mairs Rachel
Published: February 2020

Egypt of the Hellenistic and Roman periods remains the most thoroughly documented multilingual society in the ancient world, because of the wealth of texts preserved on papyrus in Egyptian, Greek, Latin and other languages. This makes the scarcity of interpreters in the papyrological record all the more curious. This study reviews all instances in the papyri of individuals referred to as hermēneus in Greek, or references to the process of translation/interpreting. It discusses the terminological ambiguity of hermēneus, which can also mean a commercial mediator; the position of language mediators in legal cases in Egyptian, Greek and Latin; the role of gender in language mediation; and concludes with a survey of interpreting in Egyptian monastic communities in Late Antiquity.
Knowledge and attitude: two fundamental factors that determine patient compliance in antibiotic therapy
Authors: Pristianty Liza , Kurniati Vivi Laily , Hidayati Ika Ratna
Published: February 2020

Background

With the development of infectious diseases, the use of antibiotics is increasing. Amoxicillin is a penicillin class of antibiotics that are widely used today. Compliance with amoxicillin can reduce the risk of microbial resistance. Two fundamental factors that determine patient compliance in antibiotic therapy are the patient's knowledge and attitude towards the antibiotic. In this study, we want to know the effect of knowledge and attitudes of patients on their compliance in using amoxicillin antibiotics.

Methods

This study was an observational study with a cross section approach, a purposive sampling method by giving questionnaires to 100 respondents who received amoxicillin in Arjuno Primary Health Care, Klojen District in April 2019. Research variables include knowledge, attitudes, and patient compliance in using amoxicillin antibiotics. Data analysis was performed to determine the effect of knowledge and attitudes of patients on compliance with amoxicillin antibiotic therapy.

Results

The results showed that knowledge significantly influences the complience (sig = 0.00), while attitude does not significantly influence compliance in using amoxicillin antibiotics(sig = 0,136). Knowledge and attitude were known to have a significant effect on compliance with amoxicillin antibiotic therapy (sig = 0.00), the magnitude of the influence of the two variables (R2 = 16.7%).

Conclusions

It can be concluded that the patient's knowledge and attitude influences his compliance to antibiotic therapy.
Oral health status of children with phenylketonuria
Authors: Ballikaya Elif , Yildiz Yilmaz , Sivri Hatice Serap , Tokatli Aysegul , Dursun Ali , Olmez Seval , Coskun Turgay , Uzamis Tekcicek Meryem
Published: February 2020

Background

Diet plays an integral role in the maintenance of oral health, but dietary modifications due to medical problems such as phenylketonuria (PKU) can have adverse effects on oral health. This descriptive study was performed to evaluate the oral health status of children with PKU.

Methods

One hundred and ninety-seven patients with PKU aged between 1 and 22 years were evaluated. Clinical evaluations were performed by one experienced dentist regarding dental caries, gingival health and dental erosion. Categorical variables were assessed with descriptive statistics. Differences in feeding frequencies and sociodemographic characteristics were compared regarding dental caries using chi-square (χ2) tests.

Results

One hundred and thirty-two patients (67%) had dental caries. The mean plaque index (PI) and gingival index (GI) values were 1.37 ± 0.58 and 1.40 ± 0.64, respectively, which shows moderate plaque accumulation and moderate gingival inflammation. Of the patients, 85.3% did not brush their teeth regularly and 90.4% had never visited a dentist before. No statistically significant differences were found in dental caries according to feeding frequencies (p = 0.448).

Conclusions

Despite the high prevalence of caries in patients with PKU, most had never seen a dentist. Physicians must encourage patients with PKU and their parents to have regular dental visits to maintain an optimal general and oral health.
Bestandsaufnahme der Ersatzfreiheitsstrafe in Mecklenburg-Vorpommern
Authors: Bögelein Nicole , Glaubitz Christoffer , Neumann Merten , Kamieth Josefine
Published: February 2020

Die jährliche Anzahl vollstreckter Ersatzfreiheitsstrafen (EFS) wird in keiner offiziellen Statistik erfasst, und damit liegt ein wichtiges kriminalpolitisches Thema im Dunkelfeld. Empirische Studien zeichnen – zumeist auf Basis kleiner Stichproben – von den Gefangenen ein Bild, das sozial schwache Personen mit unterschiedlichen Belastungen in gesundheitlicher, sozialer und finanzieller Hinsicht zeigt. Der vorliegende Text wertet Angaben zu allen Gefangenen in Mecklenburg-Vorpommern aus den Jahren 2014–2017 aus. Die Daten erlauben es, für ein Bundesland alle EFS-Verbüßenden zu beschreiben, sie mit Strafgefangenen zu vergleichen und im Rahmen einer Clusteranalyse Gruppen »typischer« EFS-Verbüßender aufzuzeigen.
Crystal structure of dimethylbis(diisopropyldithiocarbamato-κ2
S,S′)tin(IV), C16H34N2S4Sn
Authors: Haezam Farah Natasha , Awang Normah , Kamaludin Nurul Farahana , Tiekink Edward R.T.
Published: February 2020

C16H34N2S4Sn, monoclinic, P21/n (no. 14), a = 10.6234(1) Å, b = 16.0898(1) Å, c = 13.2405(1) Å, β = 92.853(1)°, V = 2260.37(3) Å3, Z = 4, R
gt(F) = 0.0197, wR
ref(F
2) = 0.0513, T = 100(2) K.
Halogen bonding in crystal structure of bis(1,4,7,10-tetraoxacyclododecane-κ4O,O′,O′′,O′′′)cesium triiodide, C16H32CsI3O8
Authors: Bloukh Samir Haj , Edis Zehra
Published: February 2020

C16H32CsI3O8, triclinic, P1̄ (no. 2), a = 10.7930(5) Å, b = 11.5610(5) Å, c = 12.4880(5) Å, α = 73.050(10)°, β = 88.870(10)°, γ = 66.060(10)°, V = 1353.62(16) Å3, Z = 2, R
gt(F) = 0.0578, wR
ref(F
2) = 0.1875, T = 293(2) K.
Das Klimaschutzprogramm der Bundesregierung: Eine Wende der deutschen Klimapolitik?
Authors: Edenhofer Ottmar , Kalkuhl Matthias , Ockenfels Axel
Published: February 2020

Das Klimaschutzgesetz hat einen Paradigmenwechsel eingeleitet: den Einstieg in eine CO2-Bepreisung als künftiges Leitinstrument der Klimapolitik. Auf den ersten Blick ist der CO2-Preis unter einer Fülle von Fördermaßnahmen und ordnungsrechtlichen Regelungen verschüttet, deren Wirksamkeit und Kosten höchst unsicher sind. Der CO2-Preis ist aber so angelegt, dass er langfristig das dominante Instrument einer europäisch harmonisierten Klimapolitik werden kann. Der angedeutete Paradigmenwechsel der deutschen Klimapolitik öffnet damit die Tür, die europäische und internationale Kooperation zu stärken. Dazu ist es aber notwendig, neben der europäischen auch die globale Klimapolitik neu auszurichten. Auch dort sollten sich die Verhandlungen statt auf nationale Mengenziele auf CO2-Preise konzentrieren. Die erforderliche Kooperation wird möglich, wenn die Regierungen Transferzahlungen strategisch und reziprok nutzen. So könnte die Effektivität der Klimapolitik erhöht werden und es ließen sich die entstehenden Verteilungskonflikte entschärfen.
Age, gender and season dependent 25(OH)D levels in children and adults living in Istanbul
Authors: Yildiz Zeynep , Hürmeydan Özlem , Madenci Özlem Çakır , Orçun Asuman , Yücel Nihal
Published: February 2020

Background

We evaluated population characteristics of serum 25-hydroxyvitamin D (25(OH)D) levels and determined the influence of age, gender and season in an extensive dataset.

Materials and methods

Laboratory results of 103,509 adults and 19,186 children were retrospectively evaluated. Study group was classified regarding ages as; <40, 40–50, 50–60 and >60 years for adults and 0–1, 1–12 months,1–3, 4–6, 7–9, 10–12, 13–15 and 16–18 years for children. Seasonal values were also determined. Levels were measured by Architect i1000 SR (Abbott Diagnostics, USA).

Results

The median (2.5–97.5 percentiles) of 25(OH)D levels were 38.75 (9.5–158.25) nmol/L for adults and 43.25 (11.25–125.5) nmol/L for children. There were significant gender differences for both adults and children. Values differed significantly among age subgroups (p’s < 0.01). A total of 63% of adults and 59.5% of children had 25(OH)D levels below 50 nmol/L (p < 0.001). 25(OH)D levels were significantly lower in the winter compared with summer (p’s < 0.001). Even levels in summer were moderate deficient for all group.

Conclusion

The rate of 25(OH)D deficiency was remarkable during the whole year. This will provide large-scale data about 25(OH)D status in Turkish people and may contribute to the prevention and treatment of this condition for better healthcare outcomes.
Revisiting obligatory relatives in German
Authors: Blümel Andreas , Liu Mingya
Published: February 2020

In the literature on relative clauses (e. g. Alexiadou et al.2000: 4), it is occasionally observed that the German complex definite determiner d-jenige (roughly ‘the one’) must share company with a restrictive relative clause, in contrast to bare determiners der/die/das (Roehrs2006: 213–215; Gunkel2006; Gunkel2007). Previous works such as Sternefeld (2008: 378–379) and Blümel (2011) treat the relative clause as a complement of D to account for its mandatory occurrence. While such syntactic analyses have intuitive appeal, they pose problems for a compositional semantic analysis.

The goal of this paper is twofold. First, we report on two rating studies providing empirical evidence for the obligatoriness of relative clauses in German DPs introduced by the complex determiner d-jenige. Secondly, following Simonenko (2014, 2015), we provide an analysis of the phenomenon at the syntax-semantics interface that captures familiar (Blümel2011) as well as novel related observations. Particularly, the analysis accounts for the facts that postnominal modifiers can figure in d-jenige-DPs and that the element can have anaphoric demonstrative pronominal uses.
Band Gap Adjustment in Perovskite-type Eu1−xCaxTiO3via Ammonolysis
Authors: Widenmeyer Marc , Kohler Tobias , Samolis Margarita , Denko Alexandra T. De , Xiao Xingxing , Xie Wenjie , Osterloh Frank E. , Weidenkaff Anke
Published: February 2020

Perovskite-type oxynitridesAB(O,N)3are potential candidates for photoelectrode materials in solar water splitting. A drawback of these materials is their low sintering tendency resulting in low electrical conductivities. Typically, they are prepared by ammonia treatment of insulating, wide band gap oxides. In this study, we propose an approach starting from small band gap oxides Eu1−xCaxTiO3−δand then widen the band gaps in a controlled way by ammonolysis and partial Ca2+substitution. Both together induced a distortion of the octahedral network and dilution of the Eu4fand N2plevels in the valence band. The effect is the stronger the more Ca2+is present. Within the series of samples, Eu0.4Ca0.6Ti(O,N)3had the most suitable optical band gap (EG≈ 2.2 eV) for water oxidation. However, its higher Eu content compared to Eu0.1Ca0.9Ti(O,N)3slowed down the charge carrier dynamics due to enhanced trapping and recombination as expressed by large accumulation (τon) and decay (τoff) times of the photovoltage of up to 109 s and 486 s, respectively. In contrast, the highly Ca2+-substituted samples (x≥ 0.7) were more prone to formation of TiN and oxygen vacancies also leading to Ti3+donor levels below the conduction band. Therefore, a precise control of the ammonolysis temperature is essential, since even small amounts of TiN can suppress the photovoltage generation by fast recombination processes. Water oxidation tests on Eu0.4Ca0.6Ti(O,N)3revealed a formation of 7.5 μmol O2from 50 mg powder together with significant photocorrosion of the bare material. Combining crystal structure, chemical composition, and optical and electronical band gap data, a first simplified model of the electronical band structure of Eu1−xCaxTi(O,N)3could be proposed.
Seasonal variations and the risk of venous thromboembolism: A narrative review article
Authors: Hajizadeh Reza , Sakha Hanieh , Ghodratizadeh Sahar , Soleimany Ali
Published: February 2020

Different investigations on seasonal variations of the pulmonary thromboembolism and deep vein thrombosis (DVT) incidence have not yielded a definite conclusion. Some papers showed significant increase in incidence of thromboembolism in winter; on the other hand, others neglected that correlation. Some articles have tried to show infrastructure of these variations. Better understanding of the cornerstone of these variations can result in prevention of disease and saving lives of susceptible people. In this narrative review article, we reviewed previous articles according to the region of study and tried to find the factors affecting diverse results among different studies.
Effect of low-dose aspirin on platelet aggregation inhibition in patients with rheumatoid arthritis
Authors: Hajialilo Mehrzad , Ghorbanihaghjo Amir , Ghassemi Forough , Khabbazi Alireza , Malek Mahdavi Aida
Published: February 2020

Introduction
: The risk for coronary artery disease (CAD) and mortality has increased in patients with rheumatoid arthritis (RA). Aspirin has anti-thrombotic effects and causes reduction in CAD occurrence in high-risk individuals. The objective of present project was evaluating the influence of low-dose aspirin on inhibition of platelet aggregation in patients with RA. Methods: Forty-eight subjects with RA diagnosed based on the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) 2010 criteria and age- and sex-matched healthy participants were studied. All subjects received 81 mg/day aspirin for 10 days. Level of the serum thromboxane B2 (sTxB2), a permanent metabolite of thromboxane A2 (TxA2), was measured before and after therapy using enzyme-linked immunosorbent assay (ELISA) kit. The impotency to decrease sTxB2 production to less than 10 ng/ml indicates suboptimal suppression of platelet aggregation via aspirin. Results: Low-dose aspirin decreased sTxB2 significantly compared with baseline in patients with RA [median interquartile range (IQR): 25.72 (11.78, 90.10) to 7.74 (5.80, 8.82), P < 0.001] and in healthy controls [median (IQR): 40.50 (33.25, 50.90) to 7.30 (4.75, 8.85), P < 0.001]. No remarkable changes were seen in sTxB2 between patients and controls after adjustment (P > 0.050). Pharmacologic influence of aspirin was suboptimal in 6.25% of cases in the presence of higher erythrocyte sedimentation rate (ESR) and in 2.7% of controls. Low-dose aspirin decreased sTxB2 significantly only in patients with Framingham Risk Score (FRS) < 10%. Conclusion: Low-dose aspirin decreased sTxB2 level and suppressed platelet aggregation and therefore, was effective in primary prevention of cardiovascular (CV) events in patients with RA; however, additional studies are required to reach accurate conclusions.
Attitude of Nurses in Intensive Care Units towards Do Not Resuscitate order
Authors: Naghshbandi Shima , Salmasi Shiva , Parsian Zahra , Rahmani Farzad
Published: February 2020

Introduction
: Do Not Resuscitate (DNR) order has been studied ethically, legally, and religiously in different countries after presentation by the American Medical Association (AMA) in 1974. This study was conducted to investigate the attitude of nurses in intensive care units (ICUs) of hospitals of Tabriz University of Medical Sciences, Tabriz, Iran, towards DNR order. Methods: 255 nurses working in ICUs were included in a descriptive-analytical study at Tabriz University of Medical Sciences in 2018. The utilized checklist contained two sections: demographic information and 11 questions with a 5-point Likert scale about the attitude towards the DNR order. The scores relating to each question were collected and analyzed. Results: The average of the total score of the questionnaire was 29.97 8.39. The attitudes of participants were negative in all questions except for the 8th and 11th questions. The total score of the questionnaire was 29.49 8.09 in the group with work experience of 15 years and less and 32.49 9.50 (P = 0.036) in the group with a more than 15 years of work experience; which indicates more positive attitude towards the DNR order in individuals with more work experience. Conclusion: The results showed that in general, the participant nurses did not have positive attitudes concerning the DNR order; however, people with more than 15 years of work experience had more positive attitude towards this order and the investigation of this factor and the causes of its impact on the change of people’s attitude should be carried out in further studies.
An Erosion Test to Evaluate Moisture Damage of Cement-Treated Base under Dynamic Water Pressure
Authors: Che Tiankai , Pan Baofeng , Sha Dong , Lu Jiale
Published: February 2020

Different kinds of testing methods were used in recent studies to evaluate the moisture damage of a cement-treated base. However, these methods were based on the condition of static water, without considering the effect of dynamic water pressure and stress conditions in the pavement, which could not truly reflect the moisture damage process of the pavement base. This study presents details of a new method of evaluating the moisture damage of a cement-treated macadam under dynamic water pressure. Specimens with different curing times (7 d, 14 d, and 28 d) were scoured by means of a self-designed dynamic water scouring system, and the compressive strength was tested after scouring. The results show that most of the damage caused by scouring occurs in the early stage (less than 10 min), which accounts for more than 80 % of the total damage. Although the scouring damage continues in the later period (10∼40 min), the damage process is relatively slow. The results of the compressive test show that both the strength loss and strength loss rate of specimens at 28 d are much smaller than that of 14 d and 7 d. Results reveal that the curing time of the specimens has an essential influence on the scouring resistance.
An Unexpected Dependence of Cortical Depth in Shaping Neural Responsiveness and Selectivity in Mouse Visual Cortex
Authors: O’Herron Philip , Levy Manuel , Woodward John J. , Kara Prakash
Published: February 2020

Two-photon imaging studies in mouse primary visual cortex (V1) consistently report that around half of the neurons respond to oriented grating stimuli. However, in cats and primates, nearly all neurons respond to such stimuli. Here we show that mouse V1 responsiveness and selectivity strongly depends on neuronal depth. Moving from superficial layer 2 down to layer 4, the percentage of visually responsive neurons nearly doubled, ultimately reaching levels similar to what is seen in other species. Over this span, the amplitude of neuronal responses also doubled. Moreover, stimulus selectivity was also modulated, not only with depth but also with response amplitude. Specifically, we found that orientation and direction selectivity were greater in stronger responding neurons, but orientation selectivity decreased with depth whereas direction selectivity increased. Importantly, these depth-dependent trends were found not just between layer 2/3 and layer 4 but at different depths within layer 2/3 itself. Thus, neuronal depth is an important factor to consider when pooling neurons for population analyses. Furthermore, the inability to drive the majority of cells in superficial layer 2/3 of mouse V1 with grating stimuli indicates that there may be fundamental differences in the micro-circuitry and role of V1 between rodents and other mammals.
The Contribution of AMPA and NMDA Receptors to Persistent Firing in the Dorsolateral Prefrontal Cortex in Working Memory
Authors: van Vugt Bram , van Kerkoerle Timo , Vartak Devavrat , Roelfsema Pieter R.
Published: February 2020

Many tasks demand that information is kept online for a few seconds before it is used to guide behavior. The information is kept in working memory as the persistent firing of neurons encoding the memorized information. The neural mechanisms responsible for persistent activity are not yet well understood. Theories attribute an important role to ionotropic glutamate receptors, and it has been suggested that NMDARs are particularly important for persistent firing because they exhibit long time constants. Ionotropic AMPARs have shorter time constants and have been suggested to play a smaller role in working memory. Here we compared the contribution of AMPARs and NMDARs to persistent firing in the dlPFC of male macaque monkeys performing a delayed saccade to a memorized spatial location. We used iontophoresis to eject small amounts of glutamate receptor antagonists, aiming to perturb, but not abolish, neuronal activity. We found that both AMPARs and NMDARs contributed to persistent activity. Blockers of the NMDARs decreased persistent firing associated with the memory of the neuron's preferred spatial location but had comparatively little effect on the representation of the antipreferred location. They therefore decreased the information conveyed by persistent firing about the memorized location. In contrast, AMPAR blockers decreased activity elicited by the memory of both the preferred and antipreferred location, with a smaller effect on the information conveyed by persistent activity. Our results provide new insights into the contribution of AMPARs and NMDARs to persistent activity during working memory tasks.

SIGNIFICANCE STATEMENTWorking memory enables us to hold on to information that is no longer available to the senses. It relies on the persistent activity of neurons that code for the memorized information, but the detailed mechanisms are not yet well understood. Here we investigated the role of NMDARs and AMPARs in working memory using iontophoresis of antagonists in the PFC of monkeys remembering the location of a visual stimulus for an eye movement response. AMPARs and NMDARs both contributed to persistent activity. NMDAR blockers mostly decreased persistent firing associated with the memory of the neuron's preferred spatial location, whereas AMPAR blockers caused a more general suppression. These results provide new insight into the contribution of AMPARs and NMDARs to working memory.
Role of Projections between Piriform Cortex and Orbitofrontal Cortex in Relapse to Fentanyl Seeking after Palatable Food Choice-Induced Voluntary Abstinence
Authors: Reiner David J. , Lofaro Olivia M. , Applebey Sarah V. , Korah Hannah , Venniro Marco , Cifani Carlo , Bossert Jennifer M. , Shaham Yavin
Published: February 2020

We recently developed a rat model of relapse to drug seeking after food choice-induced voluntary abstinence. Here, we used this model to study the role of the orbitofrontal cortex (OFC) and its afferent projections in relapse to fentanyl seeking. We trained male and female rats to self-administer palatable food pellets for 6 d (6 h/d) and intravenous fentanyl (2.5 μg/kg/infusion) for 12 d (6 h/d). We assessed relapse to fentanyl seeking after 13–14 voluntary abstinence days, achieved through a discrete choice procedure between fentanyl infusions and palatable food (20 trials/d). In both sexes, relapse after food choice-induced abstinence was associated with increased expression of the activity marker Fos in the OFC. Pharmacological inactivation of the OFC with muscimol plus baclofen (50 + 50 ng/side) decreased relapse to fentanyl seeking. We then determined projection-specific activation of OFC afferents during the relapse test by using Fos plus the retrograde tracer cholera toxin B (injected into the OFC). Relapse to fentanyl seeking was associated with increased Fos expression in the piriform cortex (Pir) neurons projecting to the OFC, but not in projections from the basolateral amygdala and thalamus. Pharmacological inactivation of the Pir with muscimol plus baclofen decreased relapse to fentanyl seeking after voluntary abstinence. Next, we used an anatomical disconnection procedure to determine whether projections between the Pir and OFC are critical for relapse to fentanyl seeking. Unilateral muscimol plus baclofen injections into the Pir in one hemisphere plus unilateral muscimol plus baclofen injections into the OFC in the contralateral, but not ipsilateral, hemisphere decreased relapse. Our results identify Pir–OFC projections as a new motivation-related pathway critical to relapse to opioid seeking after voluntary abstinence.

SIGNIFICANCE STATEMENTThere are few preclinical studies of fentanyl relapse, and these studies have used experimenter-imposed extinction or forced abstinence procedures. In humans, however, abstinence is often voluntary, with drug available in the drug environment but forgone in favor of nondrug alternative reinforcers. We recently developed a rat model of drug relapse after palatable food choice-induced voluntary abstinence. Here, we used classical pharmacology, immunohistochemistry, and retrograde tracing to demonstrate a critical role of the piriform and orbitofrontal cortices in relapse to opioid seeking after voluntary abstinence.
Noninvasive follicular thyroid neoplasm with papillary-like nuclear features: a problematic entity
Authors: Zajkowska Klaudia , Kopczyński Janusz , Góźdź Stanisław , Kowalska Aldona
Published: February 2020

Noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a borderline thyroid tumour formerly known as noninvasive encapsulated follicular variant of papillary thyroid carcinoma. The prevalence of NIFTP is estimated at 4.4–9.1% of all papillary thyroid carcinomas worldwide; however, the rate of occurrence of NIFTP is eight times lower in Asian countries than in Western Europe and America. At the molecular level, NIFTP is characterised by the lack of BRAF V600E and BRAF V600E-like mutations or other high-risk mutations (TERT, TP53) and a high rate of RAS mutations, which is similar to other follicular-pattern thyroid tumours. The diagnosis of NIFTP can only be made after histological examination of the entire tumour removed during surgery and is based on strictly defined inclusion and exclusion criteria. Although the diagnosis is postoperative, the combination of certain findings of preoperative tests including ultrasonography, cytology, and molecular testing may raise suspicion of NIFTP. These tumours can be effectively treated by lobectomy, although total thyroidectomy remains an option for some patients. Radioactive iodine and thyroid stimulating hormone suppression therapy are not required. NIFTP has an extremely good prognosis, even when treated conservatively with lobectomy alone. Nevertheless, it cannot be considered as a benign lesion. The risk of adverse outcomes, including lymph node and distant metastases, is low but not negligible.
Endothelin-1 predicts incident diabetic peripheral neuropathy in Type 2 Diabetes: a cohort study
Authors: Pek Sharon Li Ting , Lim Su Chi , Ang Keven , Kwan Pek Yee , Tang Wern Ee , Sum Chee Fang , Tavintharan Subramaniam
Published: February 2020

Introduction

Diabetic peripheral neuropathy (DPN) is a common microvascular complication in patients with type 2 diabetes (T2D). Apart from hyperglycemia, few modifiable risk factors have been identified. Endothelin-1 is a potent vasoconstrictor peptide, implicated in the causal pathway of microangiopathy. We investigated whether baseline plasma endothelin-1 and other metabolic and vascular risk factors predicted the incidence of DPN.

Design

This is a 3-year observational, cohort study.

Methods

In patients with T2D (n = 2057), anthropometric data, fasting blood, and urine were collected for biochemistry and urine albumin/creatinine measurements. Forearm cutaneous endothelial reactivity was assessed by iontophoresis and laser Doppler flowmetry/imaging. Measurements were repeated on follow-up. Incident DPN was considered present if an abnormal finding in monofilament (<8 of 10 points) or neurothesiometer testing was ≥25 volts on either foot at 3-year follow-up, but normal at baseline. Plasma endothelin-1 was assessed by ELISA.

Results

At baseline, mean age of patients was 57.4 ± 10.8 years old and prevalence of DPN was 10.8%. Of the 1767 patients without DPN, 1250 patients returned for follow-up assessment ((2.9 ± 0.7) years), with a 10.7% incidence of DPN. Patients with incident DPN had significantly higher baseline endothelin-1 (1.43 (1.19–1.73) vs 1.30 (1.06–1.63)) pg/mL, P < 0.0001. Multivariable Cox proportional hazards ratio showed a 1-s.d. increase in log endothelin-1 (adjusted HR: 4.345 (1.451–13.009), P = 0.009), systolic blood pressure (per 10-unit) (adjusted HR: 1.107 (1.001–1.223), P = 0.047) and diabetes duration (adjusted HR: 1.025 (1.004–1.047), P = 0.017) predicted incident DPN, after adjustment for glycemic control, eGFR, albuminuria, peripheral arterial disease and retinopathy status.

Conclusion

Higher baseline endothelin-1, blood pressure and diabetes duration were significant and independent predictors for incident DPN. Validation of our findings in independent cohorts and molecular mechanistic studies will help better our understanding on the role of endothelin-1 in DPN.
Testosterone replacement therapy in men who conceived with intracytoplasmic sperm injection: nationwide register study
Authors: Elenkov Angel , Al-Jebari Yahia , Giwercman Yvonne Lundberg , Giwercman Aleksander
Published: February 2020

Objectives

Male hypogonadism is associated with higher risk of co-morbidity and premature mortality. It is, therefore, of utmost importance to identify young men who are at the highest risk of testosterone deficiency and who may benefit from preventive measures. In this context, infertile men constitute a high-risk group. The extent of testosterone replacement therapy (TRT) among infertile men, defined as men who have to undergo assisted reproduction for fatherhood, is currently unknown. Therefore, we evaluated the pattern of prescription of TRT in the years following child conception among men who have fathered children with the help of intracytoplasmic sperm injection (ICSI) or in vitro fertilization (IVF).

Design

By sourcing data from national population registries, hazard ratio (HR) for subsequent TRT was assessed for IVF and ICSI-treated men and compared to those who conceived spontaneously with age Cox regression analysis adjusted for age, educational level and previous intake of medicines for metabolic diseases.

Results

ICSI and IVF fathers had increased incidence of newly prescribed TRT compared to fathers conceiving spontaneously (ICSI: HR = 3.81, 95% CI = 3.09–4.69, P < 0.001; IVF: HR = 1.54, 95% CI = 1.15–2.05, P = 0.003). After adjustment for prescription of medication for one or more components of the MetS prior to TRT, the risk estimates attenuated but remained robust both for ICSI-treated (HR = 3.17 (95% CI: 2.56–3.9) and IVF-treated men (HR = 1.06 (95% CI: 1.05–1.07).

Conclusion

Men who have to utilise powerful techniques, such as ICSI for fathering children, may be at risk for testosterone deficiency. Routine endocrine evaluation of men seeking fertility treatment is hence warranted.
Endocrine testing in obesity
Authors: Wilding John P H
Published: February 2020

Endocrine disorders such as Cushing’s syndrome and hypothyroidism may cause weight gain and exacerbate metabolic dysfunction in obesity. Other forms of endocrine dysfunction, particularly gonadal dysfunction (predominantly testosterone deficiency in men and polycystic ovarian syndrome in women), and abnormalities of the hypothalamic-pituitary-adrenal axis, the growth hormone-IGF-1 system and vitamin D deficiency are common in obesity. As a result, endocrinologists may be referred people with obesity for endocrine testing and asked to consider treatment with various hormones. A recent systematic review and associated guidance from the European Society of Endocrinology provide a useful evidence summary and clear guidelines on endocrine testing and treatment in people with obesity. With the exception of screening for hypothyroidism, most endocrine testing is not recommended in the absence of clinical features of endocrine syndromes in obesity, and likewise hormone treatment is rarely needed. These guidelines should help reduce unnecessary endocrine testing in those referred for assessment of obesity and encourage clinicians to support patients with their attempts at weight loss, which if successful has a good chance of correcting any endocrine dysfunction.
Genetic Contributions to Maternal and Neonatal Vitamin D Levels
Authors: Traglia Michela , Windham Gayle C , Pearl Michelle , Poon Victor , Eyles Darryl , Jones Karen L , Lyall Kristen , Kharrazi Martin , Croen Lisa A , Weiss Lauren A
Published: February 2020

Vitamin D is essential for several physiological functions and biological processes. Increasing levels of maternal vitamin D are required throughout pregnancy as a unique source of vitamin D for the fetus, and consequently maternal vitamin D deficiency may result in several adverse outcomes in newborns. However, the genetic regulation of vitamin D in pregnancy and at birth is not yet well understood. We performed genome-wide association studies of maternal midgestational serum-derived and neonatal blood-spot-derived total 25-hydroxyvitamin D from a case-control study of autism spectrum disorder (ASD). We identified one fetal locus (rs4588) significantly associated with neonatal vitamin D levels in the GC gene, encoding the binding protein for the transport and function of vitamin D. We also found suggestive cross-associated loci for neonatal and maternal vitamin D near immune genes, such as CXCL6-IL8 and ACKR1. We found no interactions with ASD. However, when including a set of cases with intellectual disability but not ASD (N = 179), we observed a suggestive interaction between decreased levels of neonatal vitamin D and a specific maternal genotype near the PKN2 gene. Our results suggest that genetic variation influences total vitamin D levels during pregnancy and at birth via proteins in the vitamin D pathway, but also potentially via distinct mechanisms involving loci with known roles in immune function that might be involved in vitamin D pathophysiology in pregnancy.
УЧАСТЬ УКРАЇНИ В МАКРОРЕГІОНАЛЬНИХ СТРАТЕГІЯХ ЕС: КОНЦЕПТУАЛЬНЕ БАЧЕННЯ ТА ВИКЛИКИ ГЛОБАЛІЗАЦІЇ
Authors: МАСЛОВ Юрій
Published: February 2020

Досліджено теоретичні аспекти міжстратегічної співпраці з реалізації макрорегіональних стратегій ЄС. Наголошено, що необхідність розробки макрорегіональних стратегій зумовлена наявністю комплексних проблем територіальних громад, для розв’язання яких традиційні методи галузевого і територіального управління виявляються недостатніми, а сфера поширення територіальних проблем не збігається з економічним і адміністративним районуванням. Відзначено, що участь України в процесі розробки і подальшій реалізації макрорегіональних стратегій ЄС відкриває шанс долучитися до втілення в життя важливої ініціативи Європейської комісії, а також практично підтвердити євроінтеграційні прагнення.Зосереджено увагу на Стратегії ЄС для Дунайського регіону. Визначено основні напрями розвитку Дунайського макрорегіону. Обґрунтовано, що активна участь України в даній Стратегії ЄС сприятиме підвищенню конкурентоспроможності її регіонів, прискоренню євроінтеграційних процесів та наближенню рівня життя населення прикордонних регіонів до середньоєвропейського рівня.Сформовано концептуальне бачення щодо імплементації макрорегіональної стратегії для Дунайського регіону на території України в контексті глобалізаційних викликів. Акцентовано увагу на необхідності тісної співпраці України та інших країн-учасниць над визначенням і узгодженням спільних пріоритетних проєктів (поновлення роботи спільної президентської комісії, активізація діалогу в рамках існуючих єврорегіонів тощо).Підкреслено доцільність адаптації національної системи планування до європейських принципів, необхідність узгодження системи цілей національної та регіональних стратегій з планом дій та проєктами реалізації макрорегіональних стратегій на територіях, охоплених сферою впливу останніх, важливість кореляції системи стратегічних заходів з політикою ЄС.Визначено ключові компоненти, на яких має ґрунтуватися стратегічне планування розвитку української частини Дунайського регіону. Визначено пріоритети активної участі України в реалізації макрорегіональної Стратегії ЄС для Дунайського регіону.
Історія розвитку сільськогосподарського машинобудування на Харківщині (1950–1991 рр.)
Authors: Кривоконь О. Г. , Писарська Н. В.
Published: February 2020

Досліджено історію галузі двигунобудування, починаючи з повоєнних років, на території м. Харкова. Проаналізовано діяльність підприємств, що виготовляли двигуни, зокрема, заводу «Серп і молот» і Харківського заводу тракторних двигунів. Слід зазначити, що це не єдині підприємства на території Харкова, які виготовляли двигуни, проте увагу у статті зосереджено лише на заводах, що виробляли продукцію для сільського господарства.

Здійснено розгляд обох підприємств у зазначений період, спираючись на архівні матеріали та дослідження науковців-істориків. З’ясовано причини, що призвели до занепаду підприємств, незважаючи на їхній початковий стрімкий розвиток.
Розвиток та виробнича діяльність луганських залізничих майстерень у складі "Донецьких залізниць" (1920–1930)
Authors: Рубан М. Ю.
Published: February 2020

У статті здійснено спробу дослідження історичних обставин довкола функціонування Луганських залізничних майстерень у складі Донецьких залізниць. У першій половині 1920-х рр. залізниці України перебували в катастрофічному стані. Існували численні проблеми із забезпеченням робітників, технічним станом інфраструктури та рухомого складу. Навесні 1920 р. почалося поступове відновлення транспортного господарства країни. З метою забезпечення оперативного управління відновленням інфраструктури та перевізного процесу донецькі гілки Катерининської залізниці, в тому числі лінія Дебальцеве – Луганськ – Міллерове, були приєднані до націоналізованої Північно-Донецької залізниці, яка в грудні 1920 р. отримала назву «Донецькі залізниці». Проаналізовано історію виробничої діяльності обслуговуючих підприємств Луганського залізничного вузла в перше десятиліття радянської влади в Україні.
У середині 1920-х рр. у Луганських залізничних майстернях були вжиті заходи щодо модернізації застарілої інфраструктури і технічного оснащення підприємства, а також створення на їх базі спеціалізованого вагоноремонтного заводу. На підставі аналізу історичних джерел, періодичних видань та наукової літератури проаналізовано основні виробничі показники та висвітлено організаційні заходи щодо підвищення виробничої діяльності ремонтного осередку. Протягом 1920-х рр. колектив луганських майстерень – згодом вагоноремонтного заводу – боровся за підвищення виробничих показників, постійно відчуваючи серйозний брак матеріально-технічного забезпечення. У квітні 1930 р. на хвилі зростання вуглевидобувної галузі в регіоні та потреб у будівництві нових шахт, Луганський вагоноремонтний завод був реорганізований у механічний завод вугільного машинобудування.
BIOLOGICAL REFERENCE POINTS OF PAINTED SPINY LOBSTER Panulirus versicolor (Latreille, 1804) IN KARIMUNJAWA WATERS, INDONESIA
Authors: Ernawati Tri , Priatna Asep , Satria Fayakun
Published: February 2020

A biological reference point is a term used to explain of stock status using a biological approach as a basic of fisheries management. Biological reference points of painted spiny lobster Panulirus versicolor are limited in Karimunjawa waters. This study aims to investigate the stock status of P. versicolor and management options to ensure the sustainability of the resources. The research was conducted in Karimunjawa islands of the Java Sea by collecting lobster from local fishers from March to November 2016. A total of 495 lobster were measured, weighed, and their maturity status assessed to allow the size at maturity and selectivity of the fishery to be estimated. The size at maturity L50 (62.2 mm CL) and L95 (82.0 mm CL) were larger than SL50 (48.2 mm CL) and SL95 (75.0 mm CL), respectively. Natural mortality (M) which was 0.579 year-1 is lower than fishing mortality (F). The current spawning potential ratio (SPR) of P. versicolor is 19% at the current F of 0.82, which is below SPR limit of 20% and target reference point of 40%. Hence, to increase SPR level to 40%, the fishing mortality should be reduced by about 40% to 60%. Closed season, legal size, and defining no take zone are options to consider by fishery manager with appropriate surveillance control. Single or combining those measures can reduce its fishing mortality and take back the stocks to the level of target reference point.