bluuebunny/crossref_metadata_2025 huggingface dataset:
The origin of species through system differentiation
Authors: Räwel Jörg
Published: November 2019

Purpose

Maturana and Mpodozis (2000) developed a theory of evolution that is based on the concept of autopoiesis and differs paradigmatically from the conventional theory derived from Darwin (1859). The present study aims to show that the authors have not exhausted the explanatory potential that the concept of autopoiesis can offer for the theory of evolution. Based on the critique of Maturana and Mpodozis, a system theoretic-oriented concept for the origin of species will be developed.

Design/methodology/approach

To render the explanatory potential of the concept of autopoiesis more fruitful for the theory of evolution, the proposition is made that the application of this concept is not limited to the molecular, or organismal level, as propounded by Maturana and Mpodozis, but should be also related to populations and species. By exempting the design of Maturana and Mpodozis from the rudiments of methodological individualism, a new field of application for the concept of autopoiesis is explored.

Findings

The proposed system theoretic concept of evolution theory makes it possible to shed new, constructive light on fundamental problems in the conventional biology of evolution. For example, with regard to the significance of the emergence of sexuality, or how phases of accelerated change in the course of evolution (e.g. the Cambrian explosion) are possible, or regarding the problem of the units of selection.

Originality/value

Although there have been attempts in the social sciences to interpret populations as autopoietic systems (for example by Niklas Luhmann), the proposed approach to evolutionary biology is new. Also original is a system theoretic conception of the evolutionary theory, in a strict renunciation of methodological individualism. This renunciation permits systems theories of evolution in social science and biology to be compared across disciplines.
Aggressive communication in aquatic environments
Authors: Frommen Joachim G.
Published: November 2019

Aggressive interactions are ubiquitous among animals. They are either directed towards heterospecifics, like predators or competitors, or conspecifics. During intraspecific encounters, aggression often serves to establish hierarchies within the social group. Thus, in order to understand the mechanisms mediating social organization, it is important to comprehend the escalation and avoidance of aggressive behaviour.

Overt aggressive interactions are costly not only in terms of increased risk of injury or death, but also due to opportunity costs and energy expenditure. In order to reduce these costs, animals are expected to communicate their strength and aggressive motivation prior to fights. For this purpose, they use different means of communication in various sensory modalities, that is visual, acoustic, chemical, mechanosensory and electric cues. These different modalities can convey different or similar information, underlining the importance of understanding the multimodal communication of aggression.

Thus far, most studies on signalling during aggressive encounters have focussed on visual or acoustic cues, most likely as these are the two modalities predominantly used by humans. However, depending on the species’ ecology, visual or acoustic cues might play a minor role for many species. Especially in aquatic systems, visual communication is often hampered due to high levels of turbidity or limited light conditions. Here, alternative modalities such as chemical, mechanical or electrical cues are expected to play a prominent role.

In this review, I provide an overview of different modalities used during aggressive communication in aquatic organisms. I highlight the importance of studying the role of multimodal communication during aggressive encounters in general and discuss the importance of understanding aquatic communication in the light of conservation and animal welfare issues.
Plant–bacteria–soil response to frequency of simulated nitrogen deposition has implications for global ecosystem change
Authors: Cao Jirong , Pang Shuang , Wang Qibing , Williams Mark A. , Jia Xiu , Dun Shasha , Yang Junjie , Zhang Yunhai , Wang Jing , Lü Xiaotao , Hu Yecui , Li Linghao , Li Yuncong , Han Xingguo
Published: November 2019

Atmospheric nitrogen (N) deposition, generally, has been simulated through a single or relatively few N applications per year for its ecological effect study. Despite the importance of timing in ecosystem processes, ecological experiments with more realistic N addition frequencies are rare.

We employed a novel design with typical twice (2X) versus atypical monthly (12X) N applications per year to explore effects of N addition frequency on above‐ and below‐ground biodiversity and function.

Each year, several response variables from either below‐ground or above‐ground growth, N status and cycling, or plant and bacterial diversity differed as a result of N addition frequency. BNPP showed a large frequency effect in the relatively moist year but not in the dry year. Nitrogen addition decreased root growth in the monthly relative to the biannual applications, which could be highly consequential for predicting changes in global carbon and nitrogen cycling. Simulated N deposition tended to perturb biodiversity, but it is noteworthy that 12X applications that spread N deposition more evenly through a year have much less negative impacts on plant and bacterial diversities than 2X amendments per year. Soil N mineralization rate in year 6 was much lower when N additions were monthly compared with a biannual amendment, especially when simulated N deposition was high.

We have established that amendment frequency matters for understanding ecosystem response to N deposition. Experiments that more closely mimic the anthropogenic process of N deposition are needed to best assess ecosystem and potential global biogeochemical changes.

A free Plain Language Summary can be found within the Supporting Information of this article.
Effective utilization of seismic reflection technique with moderate cost in uranium exploration
Authors: Hajnal Zoltán , Takács Ernő , Annesley Irvine R. , Pandit Bhaskar
Published: November 2019

In participation with numerous industrial partners, the Seismic Laboratory of the University of Saskatchewan has conducted a variety of active seismic reflection experiments; both on the west and east sides of the Athabasca Basin. Results of the investigations at Shea Creek, McArthur River and Keefe Lake illustrate that the seismic investigations deliver effective, highly relevant primary structural images of the subsurface, with resolution that no other geophysical technique can match. Correlation of similar seismic signatures, on several distant but inter‐related seismic sections, allowed spatial extension of promising exploration target zones previously unrecognized. Within the three‐dimensional seismic volume, comparable reflectivity patterns defined the complex areal distribution of mineralization‐related fault systems. Beyond these novel contributions, extended analysis of seismic signal attributes (amplitude and frequency), optical televiewer, and full‐wave sonic data offer detailed lithological characterization, including alteration zones, clay content, as well as porosity and fracture density information. Although these structural and geologically relevant anomalies are primary indicators of mineralization, presenting novel exploration advantages, the seismic method is still not a standard component of the Athabasca Basin exploration approach, due to the negative perception that ‘it is very expensive’. Comparing the costs of all geophysical techniques to the cost of a single logged drill hole illustrates that the results of a properly designed seismic data acquisition program not only leads to more effective planning of a drilling program, but also would lead to a much quicker recognition of the major mineralized zone(s), and a reduction in the number of required exploration boreholes. This integrated approach to exploration would then translate into a significant reduction of the total exploration expenditures. Unquestionably, the drilling of boreholes provides the most explicit, reliable information to a certain depth, but only within a very small area. Directly connecting the borehole information to seismic results extends the local reliable data; permitting reduction of the number of boreholes to create accurate two‐dimensional or three‐dimensional subsurface images and reduction of the expenditures of the total exploration program.
Attending to difference: enacting individuals in food provision for residents with dementia
Authors: Driessen Annelieke , Ibáñez Martín Rebeca
Published: November 2019

In the face of warnings about total institutions and growing concern about the quality of care, healthcare professionals in Western Europe and North America have increasingly been exhorted to tailor their services to individuals in their care. In this article, we invite our readers to become more interested in the kinds of differences care is being tailored to, and with what effects. Focusing on food provision for residents with dementia, we present three repertoires through which care workers attend to, and enact different sets of differences between individuals: providing choice allows residents to express fleeting preferences; knowing residents places emphasis on care providers’ familiarity with a person; and catering to identities brings to the fore the tastes which make up part of who someone is. The analysis brings attending to difference to the fore as a practical process and suggests that tailoring care requires sensitivity to the different kinds of individuals enacted when attending to difference.
Comparison of the Victorian Emergency Minimum Dataset to medical records for emergency presentations for acute cardiovascular conditions and unspecified chest pain
Authors: Bray Janet , Lim Michael , Cartledge Susie , Stub Dion , Mitra Biswadev , Newnham Harvey , Cameron Peter
Published: November 2019

Objective

The Victorian Emergency Minimum Dataset (VEMD) collects administrative and clinical data for all presentations to Victorian public ED. The present study aimed to examine the level of agreement between the VEMD data and the medical record for a sample of patients coded as having acute cardiovascular conditions (acute coronary syndrome, stroke and transient ischaemic attack [TIA]) and unspecified chest pain in the VEMD.

Methods

Six months of data provided to the VEMD from a large metropolitan hospital was obtained, and a random sample of 10% of cases (n = 310) were selected for review. Data for eight VEMD items were compared for concordance to data recorded in the ED medical record.

Results

Complete concordance between the VEMD and medical records for all eight items was observed only for 101 (33%) presentations. Overall, the least concordant variables were those with a high number of coding options: usual type of accommodation (76%), referral pattern (84%) and primary diagnosis (85%). The concordance of the VEMD primary diagnosis varied when examined as individual codes (range 75%–100%) and when combined (acute coronary syndrome = 94%, stroke or TIA = 85% and chest pain unspecified = 75%). The level of agreement for some items improved when VEMD codings were combined.

Conclusion

When compared to the medical record, our data suggest there is likely variation in the accuracy of some VEMD items, and suggests a larger prospective validation of the VEMD is warranted. For researchers using existing VEMD data, combining of some codes may be necessary.
Executive functions and memory in bipolar disorders I and II: new insights from meta‐analytic results
Authors: Cotrena C. , Damiani Branco L. , Ponsoni A. , Samamé C. , Milman Shansis F. , Paz Fonseca R.
Published: November 2019

Objective

To perform a systematic review and meta‐analysis of executive functions (EF) and episodic memory in bipolar disorder (BD).

Methods

A literature search was conducted on three electronic databases. Results were combined using random‐effects meta‐analysis.

Results

A total of 126 studies (6424 patients with BDI, 702 with BDII, and 8276 controls) were included. BDI was associated with moderate to large impairments across all cognitive functions and BDII with small‐to‐medium impairments. Small significant differences were identified between BDI and BDII on all cognitive functions except inhibition. The Trail Making Test (TMT) (g = 0.74, 95% CI: 0.67–0.80), Hayling Test (g = 0.58, 95% CI: 0.34–0.81), Digit Span Total (g = 0.79, 95% CI: 0.57–1.01), and Category Fluency (g = 0.59, 95% CI: 0.45–0.72) tasks were most sensitive to cognitive impairment in BDI. The TMT (g = 0.65, 95% CI: 0.50–0.80) and Category Fluency (g = 0.56, 95% CI: 0.37–0.75) were also sensitive to cognitive alterations in patients with BDII.

Conclusion

BD type I was associated with more severe and widespread impairments than BDII, which showed smaller impairments on all functions except inhibition, where impairments were larger. Education and (hypo)manic symptoms should be further investigated in future studies due to their possible influence on the neuropsychological profile of BD. The instruments identified in this review should be considered for inclusion in cognitive assessment batteries in BD.
Cyclooxygenase 2 (COX2) expression and prostaglandin synthesis in neonatal rat testicular germ cells: Effects of acetaminophen and ibuprofen
Authors: Manku Gurpreet , Papadopoulos Philippos , Boisvert Annie , Culty Martine
Published: November 2019

Background

In infants, fever is often treated with acetaminophen or ibuprofen, two antipyretic and analgesic drugs inhibiting cyclooxygenases (COXs), enzymes catalyzing prostaglandin production. Infancy represents a critical developmental period when neonatal germ cells/gonocytes differentiate to spermatogonial stem cells required for spermatogenesis.

Objectives

(a) Determine the expression of Cox2 and associated genes in postnatal day (PND)3 rat gonocytes compared to spermatogonia. (b) Examine whether acetaminophen or ibuprofen disrupts neonatal gonocyte functions. (c) Determine whether neonatal gonocytes produce prostaglandins and whether this process is altered by acetaminophen and ibuprofen.

Materials and methods

The expression of Cox2 and related genes was determined by gene arrays and qPCR. Cox2 protein levels were determined by immunocyto/histochemistry and immunoblots. The effects of acetaminophen and ibuprofen on PND3 gonocyte viability, apoptosis, proliferation, and differentiation were examined alone and with a proliferation cocktail or differentiation factor. Prostaglandins were examined by immunocyto/histochemistry and LC‐MS.

Results

Cox2 and related genes are highly expressed in gonocytes and spermatogonia. Acetaminophen and ibuprofen did not affect gonocyte survival or apoptosis, but they increased gonocyte proliferation. Ibuprofen significantly reduced RA‐induced Stra8 expression, indicating an inhibitory effect on differentiation. Ibuprofen combined with RA decreased Cox2 mRNA and protein expression. PGE2 and PGF2α were produced by neonatal gonocytes and decreased by acetaminophen and ibuprofen.

Discussion

The concomitant decrease of Stra8 expression, Cox2 expression, and PGE2 and PGF2a production in gonocytes co‐treated with RA suggests that Cox2 plays a role in PND3 gonocyte differentiation. The effects of acetaminophen and ibuprofen on proliferation suggest a negative relationship between Cox2 and proliferation. Treating neonates with acetaminophen or ibuprofen could disrupt gonocyte development, leading to adverse reproductive effects.

Conclusion

Understanding COX2 role in neonatal gonocytes and the potential risk of acetaminophen and ibuprofen treatment of infants may help prevent male reproductive pathologies.
Complete histologic normalisation is associated with reduced risk of relapse among patients with ulcerative colitis in complete endoscopic remission
Authors: Cushing Kelly C. , Tan William , Alpers David H. , Deshpande Vikram , Ananthakrishnan Ashwin N.
Published: November 2019

Background

Clinical and endoscopic remission are treatment targets in ulcerative colitis (UC). The value of histologic healing in altering clinical outcomes among patients with complete endoscopic healing is not well established.

Aim

To quantify the association between histologic activity and clinical relapse among patients with UC who were in complete endoscopic remission.

Methods

This study included patients with UC from a prospective registry who were in complete endoscopic remission. Histologic activity was quantified by a senior gastrointestinal pathologist. Histologic activity was defined as lack of normalisation (Geboes score > 0) as well as histologically active disease (Geboes score ≥2.1 and ≥3.1). The primary outcome was clinical relapse within 2 years. Multivariable regression adjusting for potential confounders examined the independent predictive value of histologic changes.

Results

The study included 83 patients (51% women) (median age 44 years; median disease duration 11 years). Forty‐one (49%) had complete histologic normalisation. Within two years, 26 (31%) experienced clinical relapse. Patients with complete histologic normalisation were less likely to experience relapse (5/41, 12%) compared to those without normalisation (21/42, 50%, P < 0.001) (multivariable OR 7.22, 95% confidence interval (CI) 2.48‐24.70) by the Geboes score. The individual components of the Geboes score predictive of relapse were architectural changes (P = 0.03) and increased chronic inflammatory infiltrate (P < 0.001).

Conclusions

Complete histologic healing using the Geboes score was associated with reduced rates of clinical relapse among patients with UC in endoscopic remission.
Histochemical and immunohistochemical adaptations on the gastroesophageal tube of the blue‐fronted parrot (Amazona aestiva Linnaeus, 1758)
Authors: da Silva Macêdo Jaqueline , Machado-santos Clarice , Ferreira Ildemar
Published: November 2019

Amazona aestiva Linnaeus, 1758 is known as the blue‐fronted parrot. These animals are considered seed dispersion, contributing to ecological balance. Despite its ecological importance, A. aestiva is listed as an imminent danger of becoming extinct, as it is one of the most illegally traded native species in Brazil, besides losing its habitat due to deforestation and forest fires. The cranial oesophagus mucosa is lined with a non‐keratinized stratified squamous epithelium, and the basal layer presents melanocyte accumulation. No mucous glands were observed in the lamina propria/submucosa. The ingluvium two different muscular layer patterns were observed, one internal and circular and one very thick, external and longitudinal. The proventriculum submucosa consists of polygonal proventricular glands and contents into a broad central duct lined with simple columnar epithelium Periodic acid‐reactive Schiff positive (PAS+) and Alcian blue positive (AB+). The 5‐HT cells are dispersed in the proventricular glands located at base and apex. The ventricle mucous layer contains numerous branched folds lined by a simple columnar epithelium. The epithelium was negative reaction for PAS and positive for AB only on the fold surfaces. The 5‐HT cells were scarce and observed only at the base of the ventricular gland, as well as in the adjacent connective tissue.
Development of body knowledge as measured by arm differentiation in infants: From global to local?
Authors: Jacquey Lisa , Popescu Sergiu Tcaci , Vergne Judith , Fagard Jacqueline , Esseily Rana , O’Regan Kevin
Published: November 2019

The ability to sense and use the body parts in an organized and differentiated manner is a precursor of body knowledge in infancy. To acquire this ability, the infant's brain might explore the perceptual consequences of its bodily actions. Undifferentiated body movements would gradually be replaced by more precise actions. Only a very few studies have tested this ‘global‐to‐local’ hypothesis, and none of them have so far been replicated. In this study, we assessed arm differentiation in 4‐, 6‐, and 8‐month‐old infants using a new contingency detection task in which infants have to detect a contingency between one of their arms’ activity and an audiovisual stimulus on a screen. We found that 4‐ to 8‐month‐old infants seem to be able to use their arms in a differentiated manner. However, surprisingly, we were not able to show a developmental trend in arm differentiation between 4 and 8 months of age.

Statement of contribution

What is already known on this subject?

Foetuses and infants possess coarse control of their body and may be sensitive to sensory feedback caused by their own movements.

Body knowledge might develop during the first year of life in what can be called a ‘global‐to‐local’ manner. Nevertheless, the precise age at which infants come to possess well‐differentiated local body knowledge requires further investigation.

What the present study adds?

4‐ to 8‐month‐old infants seem able to use their arms in a differentiated manner when exposed to an audiovisual stimulation contingent on movements of one of their arms.

However, we found no developmental trend in arm differentiation between 4 and 8 months of age.

We hypothesize that infants' sensitivity to sensorimotor contingencies and their ability to narrow down contingencies to a specific limb might evolve with age as a function of the infant's current sensorimotor interests.
Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice
Authors: Cantacorps Lídia , Montagud‐Romero Sandra , Luján Miguel Ángel , Valverde Olga
Published: November 2019

Background and Purpose

Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring.

Experimental Approach

Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement.

Key Results

The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement.

Conclusion and Implications

Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.
FK506 regulates Ca2+ release evoked by inositol 1,4,5‐trisphosphate independently of FK‐binding protein in endothelial cells
Authors: Buckley Charlotte , Wilson Calum , McCarron John G.
Published: November 2019

Background and Purpose

FK506 and rapamycin are modulators of FK‐binding proteins (FKBP) that are used to suppress immune function after organ and hematopoietic stem cell transplantations. The drugs share the unwanted side‐effect of evoking hypertension that is associated with reduced endothelial function and nitric oxide production. The underlying mechanisms are not understood. FKBP may regulate IP3 receptors (IP3R) and ryanodine receptors (RyR) to alter Ca2+ signalling in endothelial cells.

Experimental Approach

We investigated the effects of FK506 and rapamycin on Ca2+ release via IP3R and RyR in hundreds of endothelial cells, using the indicator Cal‐520, in intact mesenteric arteries from male Sprague‐Dawley rats. IP3Rs were activated by acetylcholine or localised photo‐uncaging of IP3, and RyR by caffeine.

Key Results

While FKBPs were present, FKBP modulation with rapamycin did not alter IP3‐evoked Ca2+ release. Conversely, FK506, which modulates FKBP and blocks calcineurin, increased IP3‐evoked Ca2+ release. Inhibition of calcineurin (okadiac acid or cypermethrin) also increased IP3‐evoked Ca2+ release and blocked FK506 effects. When calcineurin was inhibited, FK506 reduced IP3‐evoked Ca2+ release. These findings suggest that IP3‐evoked Ca2+ release is not modulated by FKBP, but by FK506‐mediated calcineurin inhibition. The RyR modulators caffeine and ryanodine failed to alter Ca2+ signalling suggesting that RyR is not functional in native endothelium.

Conclusion and Implications

The hypertensive effects of the immunosuppressant drugs FK506 and rapamycin, while mediated by endothelial cells, do not appear to be exerted at the documented cellular targets of Ca2+ release and altered FKBP binding to IP3 and RyR.
Osteosarcoma‐initiating cells show high aerobic glycolysis and attenuation of oxidative phosphorylation mediated by LIN28B
Authors: Mizushima Emi , Tsukahara Tomohide , Emori Makoto , Murata Kenji , Akamatsu Asuka , Shibayama Yuji , Hamada Shuto , Watanabe Yuto , Kaya Mitsunori , Hirohashi Yoshihiko , Kanaseki Takayuki , Nakatsugawa Munehide , Kubo Terufumi , Yamashita Toshihiko , Sato Noriyuki , Torigoe Toshihiko
Published: November 2019

Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non‐responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma‐initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC‐related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA‐sequencing, we identified LIN28B as a SIC‐related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low‐dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so‐called cancer/testis antigen, might be a good approach.
Basal serum luteinising hormone cut‐off, and its utility and cost‐effectiveness for aiding the diagnosis of the onset of puberty in girls with early stages of breast development
Authors: Wankanit Somboon , Mahachoklertwattana Pat , Pattanaprateep Oraluck , Poomthavorn Preamrudee
Published: November 2019

Objective

To determine basal and gonadotrophin‐releasing hormone analogue (GnRHa)‐stimulated peak luteinising hormone (LH) cut‐offs to diagnose onset of early or normal puberty in girls with each Tanner stage of breast (II and III).

Design, Patients and Measurements

A retrospective study of 601 girls with breast onset before 8 years of age who underwent GnRHa test was conducted. Patients were categorized as CPP and premature thelarche. Each group was divided into two subgroups; Tanner II and III. Cost‐effectiveness analysis was performed.

Results

In comparison with basal LH cut‐off of 0.3 IU/L, basal LH cut‐off of 0.2 IU/L had comparable specificity (Tanner II: 98.0% vs 94.8%, Tanner III: 98.8% vs 93.8%), but greater sensitivity (Tanner II: 28.3% vs 41.7%, Tanner III: 45.2% vs 59.3%). Specificity of basal LH cut‐off of 0.2 IU/L was not inferior to that of the traditionally used peak LH of 5 IU/L. Using basal LH cut‐off of 0.2 IU/L followed by GnRHa test in girls with negative basal LH was more cost‐saving when compared with using the cut‐off of 0.3 IU/L. Moreover, using basal LH cut‐off of 0.2 IU/L followed by GnRHa test provided a cost reduction when compared with performing GnRHa test in all patients.

Conclusions

Basal serum LH cut‐off of 0.2 IU/L could be a simple and cost‐saving tool for initial diagnosis of onset of early or normal puberty in girls with Tanner II and III before proceeding to GnRH testing.
Investigating the social environment of the A‐not‐B search task
Authors: Dunn Kirsty , Bremner James Gavin
Published: November 2019

Controversy exists concerning the origins of object permanence, with different measures suggesting different conclusions. Looking measures have been interpreted as evidence for early understanding (Baillargeon, 1987, Developmental Psychology, 23:655), while Piaget (The construction of reality in the child, 1954) interpreted perseverative reaching behaviour on his AB search task to be indicative of limited understanding. However, looking measures are often reported to be an unreliable index of infant expectation (Haith, 1998, Infant Behaviour and Development, 21:167) and reaching behaviour has been explained by many alternative processes (e.g. Smith et al., 1999, Psychological Review, 106:235; Topál et al., 2008, Science, 321:1831). We aimed to investigate whether social looking (Dunn & Bremner, 2017, Developmental Science, 20:e12452; Walden et al., 2007, Developmental Science, 10:654) can be used as a valid measure of infant expectation of object location during the Piagetian AB search task. Furthermore, we aimed to test the social accounts of perseverative reaching by investigating how the direction of experimenter gaze would affect infant search and social behaviour. Infant search and social behaviour was compared on B trials across three different conditions, namely experimenter gaze to midline, location A and location B. Search performance significantly improved when the experimenter looked to location B. Infant social looking indicated that infants expect the object to be found in the location in which they search and are actively seeking information about object location from the experimenter. We conclude that social looking is a valid index of infant expectation that has provided support for the importance of the social environment on the AB search task. This casts doubt on the potential for this task to provide information related to the development of object permanence in infancy.
Elevated fasting vs post‐load glucose levels and pregnancy outcomes in gestational diabetes: a population‐based study
Authors: Ryan E. A. , Savu A. , Yeung R. O. , Moore L. E. , Bowker S. L. , Kaul P.
Published: November 2019

Aims

To examine the relative association between fasting plasma glucose vs post‐load (1‐h and 2‐h) glucose levels based on the oral glucose tolerance test in pregnancy and large‐for‐gestational‐age and hypertensive disorders of pregnancy outcomes.

Methods

All live singleton births between October 2008 and December 2014 in Alberta, Canada were included. Gestational diabetes mellitus was diagnosed using Diabetes Canada criteria. Logistic regression models were used to examine the association between fasting plasma glucose vs post‐load values and large‐for‐gestational‐age infants and hypertensive disorders of pregnancy after adjusting for maternal characteristics and pharmaceutical intervention in gestational diabetes pregnancies.

Results

Among 257 547 pregnancies, 208 344 (80.9%) had negative 50‐g glucose challenge tests, 36 261 (14.1%) had negative 75‐g oral glucose tolerance tests, and 12 942 (5.0%) had gestational diabetes based on either elevated fasting plasma glucose (n=4130, 1.6%) or elevated 1‐h and/or 2‐h oral glucose tolerance test values (n=8812, 3.4%). Large‐for‐gestational‐age and hypertensive disorders of pregnancy rates were 8.1% and 5.1% in negative glucose challenge test pregnancies, 11.0% and 7.0% in negative oral glucose tolerance test pregnancies, 22.4% and 11.9% in gestational diabetes pregnancies with elevated fasting plasma glucose, and 9.1% and 8% in gestational diabetes pregnancies with elevated post‐load levels, respectively. Among gestational diabetes pregnancies, those with elevated fasting plasma glucose were at higher risk of large‐for‐gestational age (adjusted odds ratio 2.66, 95% CI 2.39–2.96) and hypertensive disorders of pregnancy (adjusted odds ratio 1.51, 95% CI 1.33–1.72) outcomes relative to pregnancies with post‐load glucose elevations only. Fasting plasma glucose remained significantly associated with adverse outcomes in gestational diabetes pregnancies with and without pharmacological intervention.

Conclusions

Elevated fasting plasma glucose in women with gestational diabetes is a stronger predictor of large‐for‐gestational‐age and hypertensive disorders of pregnancy outcomes than elevated post‐load glucose.
β‐Cell and renal transplantation options for diabetes
Authors: Flatt A. J. S. , Bennett D. , Counter C. , Brown A. L. , White S. A. , Shaw J. A. M.
Published: November 2019

Despite major advances in structured education, insulin delivery and glucose monitoring, diabetes self‐management remains an unremitting challenge. Insulin therapy is inextricably linked to risk of dangerous hypoglycaemia and sustained hyperglycaemia remains a leading cause of renal failure. This review sets out to demystify transplantation for diabetes multidisciplinary teams, facilitating consideration and incorporation within holistic overall person‐centred management. Deceased and living donor kidney, whole pancreas and isolated islet transplant procedures, indications and potential benefits are described, in addition to outcomes within the integratedUKtransplant programme.
Insulin degludec/liraglutide (IDegLira) maintains glycaemic control and improves clinical outcomes, regardless of pre‐trial insulin dose, in people with type 2 diabetes that is uncontrolled on basal insulin
Authors: Meneghini L. , Doshi A. , Gouet D. , Vilsbøll T. , Begtrup K. , Őrsy P. , Ranthe M. F. , Lingvay I.
Published: November 2019

Aims

To assess whether people with type 2 diabetes transferring from higher basal insulin doses (> 20 units) to a starting dose of 16 units of insulin degludec/liraglutide (IDegLira) benefit from IDegLira with/without transient loss of glycaemic control.

Methods

Post hoc analysis of DUAL V and VII assessed fasting self‐measured blood glucose (SMBG) over weeks 1–8, changes in HbA1c, body weight and mean insulin dose over 26 weeks, and percentage of participants achieving HbA1c < 53 mmol/mol (7.0%) by end of trial in participants with type 2 diabetes uncontrolled with basal insulin. IDegLira was compared with continued up‐titration of insulin glargine (IGlar U100) in DUAL V, or switching to basal–bolus therapy in DUAL VII (IGlar U100 and insulin aspart), across pre‐trial insulin dose groups (20–29, 30–39 and 40–50 units/day).

Results

In all subgroups, participants treated with IDegLira experienced significant improvements in HbA1c by end of trial, which were greater than with IGlar U100 up‐titration (estimated treatment difference –5.86, –6.59 and –6.91 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively) and similar to basal–bolus therapy (estimated treatment difference –0.16, –1.0 and –0.01 mmol/mol for pre‐trial insulin doses of 20–29, 30–39 and 40–50 units/day, respectively). Compared with IGlar U100 and basal–bolus therapy, IDegLira participants experienced weight loss vs. weight gain, lower rates of hypoglycaemia and a lower mean end of trial total daily insulin dose. In both trials, mean fasting SMBG decreased from weeks 1 to 8 across all subgroups, despite a temporary increase in mean fasting SMBG in the 40–50 units pre‐trial insulin dose group during week 1 [mean increase (sd) +1.1 (2.0) mmol/l for DUAL V and +1.1 (2.1) mmol/l for DUAL VII], which reverted to baseline by week 4.

Conclusions

Regardless of pre‐trial insulin dose, IDegLira resulted in improved clinical outcomes, even in participants transferring from 40–50 units of basal insulin, despite a transient (< 4 weeks), clinically non‐relevant, elevation in pre‐breakfast SMBG. (Clinical Trial Registry Number NCT01952145 and NCT02420262).
Multilateral trade liberalisation helps promote export product diversification: Trade tensions damage the prospects of the poorest economies
Authors: Gnangnon Sena Kimm
Published: November 2019

Using a large panel dataset over a 20‐year period, this article explores the effect of multilateral trade liberalisation on export product diversification. Empirical results show that multilateral trade liberalisation is positively associated with export product diversification. However, less‐developed economies experience a greater positive effect than relatively advanced economies. This analysis suggests that if trade tensions reduce cooperation on trade matters among World Trade Organization members, it may hinder export product diversification in developing countries, and the poorest countries might be the most adversely affected.
Two‐dimensional speckle‐tracking strain detects subclinical cardiotoxicity in older patients treated for acute myeloid leukemia
Authors: Cascino Gregory J. , Voss Woo Bin , Canaani Jonathan , Furiasse Nicholas , Rademaker Alfred , Ky Bonnie , Luger Selina , Altman Jessica K. , Foran James M. , Litzow Mark R. , Tallman Martin S. , Rigolin Vera , Akhter Nausheen
Published: November 2019

Background

Patients with acute myeloid leukemia (AML) are surviving longer. There are no data on changes in myocardial mechanics from standard of care low‐dose anthracycline‐based induction chemotherapy in older patients with AML. The aim of this study was to demonstrate the potential utility of strain imaging in detecting early changes in left ventricular function in this patient population after induction chemotherapy.

Methods

Thirty two patients enrolled in the ECOG‐ACRIN E2906 study (cytarabine and daunorubicin vs clofarabine [Genzyme/Sanofi]) from 2011 to 2014 were evaluated retrospectively. Two‐dimensional transthoracic echocardiography (TTE) imaging with Doppler and two‐dimensional speckle‐tracking echocardiography (2DSTE) using EchoInsight software (Epsilon imaging) were performed before and after induction chemotherapy.

Results

Eighteen patients received cytarabine and daunorubicin (7 + 3) and 14 received clofarabine. The clofarabine group was older than the 7 + 3 cohort (67.8 ± 4.0 vs 63.7 ± 3.8, P = .007). There were no other significant differences in cardiac risk factors between groups. The 7 + 3 group had a decrease in average peak systolic global longitudinal (−19.1 ± 2.8 to −17.2 ± 3.0, P = .01) and circumferential strain (−29.4 ± 6.3 to −23.9 ± 4.3, P = .011). These changes were not demonstrated in the clofarabine group and were not associated with a decline in left ventricular ejection fraction (LVEF).

Conclusions

In older AML patients, standard cytarabine and daunorubicin chemotherapy causes early changes in global longitudinal and circumferential strain not seen with clofarabine therapy. These findings demonstrate subclinical left ventricular dysfunction after exposure to low cumulative doses of anthracycline‐based induction chemotherapy and may help us better identify those patients at risk for adverse long‐term cardiovascular outcomes.
Eden Baysal Dental Trauma Index: Face and content validation
Authors: Eden Ece , Baysal Mehmet , Andersson Lars
Published: November 2019

Background/Aim

Recording of traumatic dental injuries in the emergency situation with a simple and easily recordable index that will also enable computer registration is advantageous. The aim of this paper is to present a new index to facilitate recording traumatic dental injuries and assess its face and content validity.

Materials and methods

The index included information on the type of injury related to the affected structures (enamel, dentin, cement, pulp, periodontal ligament, and alveolar bone) in accordance with Andreasen's classification. In addition, injuries to the alveolar bone and the maturity of the root were included. Fifteen dental trauma experts from 11 different countries rated the codes and content of the “Eden Baysal Dental Trauma Index” using the RAND modified e‐Delphi consensus method. A statement was considered valid after reaching 75% consensus among panel members. Two rounds were necessary for reaching consensus on seven statements and the definition. The last version of the index was then presented online to a feedback group that included 10 experts from five countries to determine the external validity by representative cases.

Results

The wording of the definition showed 92.8% agreement in the first round. Statements 1 and 2 gave information about the structure of the index and both reached 90% agreement in the first round. Definition and statements from 1 to 7 reached agreement as 93.3%, 93.3%, 100%, 93.3%, 80%, 93.3%, 80%, and 93.3%, respectively, in the second round. Most of the experts in the feedback group reported that the index was useful and user‐friendly.

Conclusion

After a total of two rounds with the panel members and one round with the feedback group, the “Eden Baysal Dental Trauma Index” was approved for face and content validity and external validity was obtained.
Sex, stress and steroids
Authors: Sze Ying , Brunton Paula J.
Published: November 2019

The hypothalamo–pituitary–adrenal (HPA) axis plays a key role in the neuroendocrine response to stress and in maintaining physiological homoeostasis. However, stress that is chronic in nature can lead to HPA axis dysfunction and increase the risk for developing affective disorders, particularly if the stress is experienced during vulnerable periods in life. Sex differences in how the HPA axis responds to stress are well established, with females typically displaying heightened responses. The underlying cause of these sex differences is important to understand, as many neuropsychiatric disorders disproportionately affect females. Much research has provided evidence for gonadal sex steroids in underpinning sex differences in HPA axis responsivity; however, we suggest that neuroactive metabolites of these steroids also play a key role in the brain in mediating sex differences in HPA axis responses to stress. The relationship between neuroactive steroids and stress is complex. Acute stress rapidly increases neuroactive steroid production, which can in turn modulate activity of the HPA axis. However, under chronic stress conditions, stress can impact the brain's capacity to generate steroids, and this in turn has corollary effects on HPA axis function that may increase the propensity for psychopathology, given both HPA axis dysfunction and deficits in neuroactive steroids are implicated in affective disorders. Hence, here we review the evidence from animal and human studies for sex differences in the interactions between neuroactive steroids and the stress axis at various stages of life, under physiological and pathophysiological stress conditions and consider the implications for health and disease.
Activation of the RAS/B‐RAF‐MEK‐ERK pathway in satellite glial cells contributes to substance p‐mediated orofacial pain
Authors: Zhang Yan‐yan , Song Ning , Liu Fei , Lin Jiu , Liu Meng‐ke , Huang Chao‐lan , Liao Da‐qing , Zhou Cheng , Wang Hang , Shen Jie‐fei
Published: November 2019

The cross talk between trigeminal ganglion (TG) neurons and satellite glial cells (SGCs) is crucial for the regulation of inflammatory orofacial pain. Substance P (SP) plays an important role by activating neurokinin (NK)‐I receptors in this cross talk. The activation of extracellular signal‐regulated kinase (ERK) 1/2, protein kinase A (PKA) and protein kinase C (PKC) in neurons and SGCs of peripheral ganglions by peripheral inflammation is associated with inflammatory hypersensitivity. This study tested the hypothesis that SP evoked SP‐NK‐I receptor positive feedback via the Renin–Angiotensin System/B‐Protein Kinase A‐Rapidly Accelerates Fibrosarcoma‐MEK‐Extracellular Signal‐Regulated Kinase (RAS/PKA‐RAF‐MEK‐ERK) pathway, which is involved in pain hypersensitivity. Inflammatory models were induced in vivo by injecting Complete Freund's adjuvant (CFA) into the whisker pad of rats. SP was administrated to SGCs in vitro for investigating, whether SP regulates the expression of NK‐I receptor in the SGC nucleus. The effects of RAS‐RAF‐MEK, PKA and PKC pathways in this process were measured by co‐incubating SGCs with respective Raf, PKA, PKC and MEK inhibitors in vitro and by pre‐injecting these inhibitors into the TG in vivo. SP significantly upregulated NK‐I receptor, p‐ERK1/2, Ras, B‐Raf, PKA and PKC in SGCs under inflammatory conditions. In addition, L703,606 (NK‐I receptor antagonist), U0126 (MEK inhibitor), Sorafenib (Raf inhibitor) and H892HCL (PKA inhibitor) but not chelerythrine chloride (PKC inhibitor) significantly decreased NK‐I mRNA and protein levels induced by SP. The allodynia‐related behavior evoked by CFA was inhibited by pre‐injection of L703,606, U0126, Sorafenib and H892HCL into the TG. Overall, SP upregulates NK‐I receptor in TG SGCs via PKA/RAS‐RAF‐MEK‐ERK pathway activation, contributing to a positive feedback of SP‐NK‐I receptor in inflammatory orofacial pain.
Cladribine in myasthenia gravis: a pilot open‐label study
Authors: Rejdak K. , Szklener S. , Korchut A. , Baranowski D.
Published: November 2019

Background and purpose

The aim of this study was to assess the effectiveness of cladribine treatments in a population of patients with refractory myasthenia gravis (MG).

Methods

In a prospective open‐label study of cladribine in refractory MG, 13 patients received cladribine at baseline with repetitive cycles driven by clinical response. A Myasthenia Gravis Composite (MGC) score was obtained and a standard dose of steroids was administered.

Results

A total of 11 patients achieved significant clinical improvement in MGC score during their therapy. The mean MGC score declined from 15.1 to 6.3 points within 4 months of observation. The dosage of prednisolone declined from 9.5 to 1.9 mg. None of the patients required intravenous immunoglobulin or plasma exchange treatments and no adverse events occurred in the study period.

Conclusion

Cladribine seems to be a safe and effective emergency therapy in a population of patients with refractory MG.