bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of survival in non‐small cell lung cancer patients with pleural effusion undergoing thoracoscopy
Authors: Xie Li‐Xu , Wang Xing‐Guang , You Wen‐Jie , Ma Xiao‐Bin , Wang Yong‐Gang , Liu Ting‐Ting , Jiang Shu‐Juan
Published: May 2019

Background

Malignant pleural effusion (MPE) predicts advanced disease and poor prognosis, and is usually diagnosed by medical thoracoscopy. It remains unclear whether the various representations visualized on thoracoscopy are reliable prognostic factors. The aim of this study was to evaluate prognostic factors for survival in patients who underwent thoracoscopy for MPE.

Methods

The medical records of consecutive patients with MPE who underwent medical thoracoscopy from 2007 to 2015 at a tertiary hospital were reviewed and theKaplan‐Meier method and Cox regression analysis used to determine prognostic factors.

Results

A total of 125 patients with non‐small cell lung cancer (NSCLC) were confirmed on tissue biopsy as having pleural metastasis. In NSCLC, factors adversely affecting overall survival (OS) in univariate analysis included extent of pleural carcinomatosis (EPC) score (P = 0.031), grade of adhesions (P = 0.037), costoparietal pleural lesions (P = 0.035) and bloody MPE (P = 0.023); Cox multivariate analysis revealed that EPC score (P = 0.007) and grade of adhesions (P = 0.019) were independent predictors of OS.

Conclusions

Under traditional chemotherapy, higher EPC score and higher grades of adhesions predicted poor prognosis in advanced NSCLC patients with pleural metastasis. Taking into account these factors may allow doctors to make more accurate predictions and provide individual therapy when treating patients with MPE.
Interaction of Alt a 1 with SLC22A17 in the airway mucosa
Authors: Garrido‐Arandia María , Tome‐Amat Jaime , Pazos‐Castro Diego , Esteban Vanesa , Escribese Maria M. , Hernández‐Ramírez Guadalupe , Yuste‐Montalvo Alma , Barber Domingo , Pacios Luis F. , Díaz‐Perales Araceli
Published: May 2019

Background

Despite all the efforts made up to now, the reasons that facilitate a protein becoming an allergen have not been elucidated yet. Alt a 1 protein is the major fungal allergen responsible for chronic asthma, but little is known about its immunological activity. Our main purpose was to investigate the ligand‐dependent interactions of Alt a 1 in the human airway epithelium.

Methods

Alt a 1 with and without its ligand (holo‐ and apo‐ forms) was incubated with the pulmonary epithelial monolayer model, Calu‐3 cells. Allergen transport and cytokine production were measured. Pull‐down and immunofluorescence assays were employed to identify the receptor of Alt a 1 using the epithelial cell model and mouse tissues. Receptor‐allergen‐ligand interactions were analyzed by computational modeling.

Results

The holo‐form could activate human monocytes, PBMCs, and polarized airway epithelial (Calu‐3) cell lines. The allergen was also transported through the monolayer, without any alteration of the epithelial integrity (TEER). Alt a 1 also induced the production of proinflammatory IL8 and specific epithelial cytokines (IL33 and IL25) by Calu‐3 cells. The interaction between epithelial cells and holo‐Alt a 1 was found to be mediated by the SLC22A17 receptor, and its recognition of Alt a 1 was explained in structural terms.

Conclusions

Our findings identified the Alt a 1 ligand as a central player in the interaction of the allergen with airway mucosa, shedding light into its potential role in the immunological response, while unveiling its potential as a new target for therapy intervention.
Collaborative filmmaking and affective traces of belonging
Authors: Vasudevan Lalitha , Riina‐Ferrie Joseph
Published: May 2019

In order to explore how experiences with youth media production resonate with people throughout their lives, we conducted video interviews with alumni from the Educational Video Center's youth documentary programs across the organization's history of more than 30 years. We talked with alumni and watched their films together to see what memories and feelings they would share through revisiting their filmmaking. We devised a multimodal analysis method that places the films alongside the interview footage in order to observe how affect was embodied by the alumni, as well as their use of affect to reflect on their filmmaking experiences. Affective moments gave us clues about how to understand and situate the memories as lingering traces of alumni's past experiences, that centered on descriptions of belonging.
Supporting collaborative learning using a diagram‐based visible thinking tool based on cognitive load theory
Authors: Cai Huiying , Gu Xiaoqing
Published: May 2019

A natural concern in the field of computer‐supported collaborative learning is how participants in collaborative learning project attain individual deep understanding through pedagogical or technological support. This study explores such individual outcomes as influenced by designing a collaborative learning project supported with a diagram‐based thinking tool based on cognitive load theory (CLT). A comparative experiment was designed to evaluate the effectiveness of the diagram‐based thinking tool. A total of 49 first‐year graduate students were recruited and assigned to two conditions. In the experiment condition, the group students completed the collaborative learning project through a diagram‐based thinking tool, while the group students in the control condition completed the same project through an alternative text‐based thinking tool. Pre‐and posttesting of the domain knowledge was employed to evaluate each individual's learning outcome. Group discourse was employed to evaluate how group students actively engage during collaboration. Results show that the support of diagram‐based thinking tool integrated in collaborative learning can facilitate individual understanding intensively. Moreover, diagram‐based thinking tool can engage group students into cognitively demanding learning activities actively. Findings demonstrate that the semantic diagram tool provides promising technological support when designing collaborative learning project based on CLT. This study serves as a foundation to the design of technological support for future classroom‐based collaborative learning project.

Practitioner Notes

What is already known about this topic

According to cognitive load theory, the construction of shared knowledge and also the benefit of communication and coordination during social interaction should be optimized when design the collaborative learning.

To help learners benefit from social interaction during collaborative learning project, technological support should be carefully designed.

External representations have been recognized as one kind of suitable technological affordance for learners’ cognitive and social development.

What this paper adds

The diagram‐based visible thinking tool with conceptual and socio‐cognitive support integrated in collaborative learning can facilitate individual understanding intensively.

The diagram‐based thinking tool with conceptual and socio‐cognitive support can actively engage group students into cognitively demanding learning activities.

Implications for practice and/or policy

The idea of semantic diagram tool with conceptual and socio‐cognitive support is suitable technological support for effective collaborative learning from the perspective of cognitive load theory.

The idea of semantic diagram tool with conceptual and socio‐cognitive support provide teachers with more understandable guidance to design and conduct the collaborative learning project in the classroom.
Understanding What Has Been Happening to the Public‐Sector Pay Premium in Great Britain: A Distributional Approach Based on the Labour Force Survey
Authors: Murphy Philip , Blackaby David , O'Leary Nigel , Staneva Anita
Published: May 2019

This article investigates what has been happening to the public‐sector wage differential in Great Britain over the period 1994–2017. The evidence indicates that apart from men in the lower part of the pay distribution, the public‐sector pay premium has declined for all public‐sector workers. This decline has coincided with a decline in the overall pay gap, which is associated with changes in the composition of public‐ and private‐sector workforces. As the relative pay disadvantage experienced by public‐sector workers at the top of the pay distribution has worsened over time this must raise serious concerns about the ability of the public sector to recruit and retain the staff it needs to deliver public services.
Sex differences in the hypothalamic–pituitary–adrenal axis: An obstacle to antidepressant drug development?
Authors: Kokras Nikolaos , Hodes Georgia E. , Bangasser Debra A. , Dalla Christina
Published: May 2019

Hypothalamic–pituitary–adrenal (HPA) axis dysfunction has long been implicated in the pathophysiology of depression, and HPA axis‐based compounds have served as potential new therapeutic targets, but with no success. This review details sex differences from animal and human studies in the function of HPA axis elements (glucocorticoids, corticotropin releasing factor, and vasopressin) and related compounds tested as candidate antidepressants. We propose that sex differences contribute to the failure of novel HPA axis‐based drugs in clinical trials. Compounds studied preclinically in males were tested in clinical trials that recruited more, if not exclusively, women, and did not control, but rather adjusted, for potential sex differences. Indeed, clinical trials of antidepressants are usually not stratified by sex or other important factors, although preclinical and epidemiological data support such stratification. In conclusion, we suggest that clinical testing of HPA axis‐related compounds creates an opportunity for targeted, personalized antidepressant treatments based on sex.

LINKED ARTICLES

This article is part of a themed section on The Importance of Sex Differences in Pharmacology Research. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.21/issuetoc
Procognitive impact of ciproxifan (a histaminergic H3 receptor antagonist) on contextual memory retrieval after acute stress
Authors: Chauveau Frédéric , De Job Elodie , Poly‐Thomasson Betty , Cavroy Raphaël , Thomasson Julien , Fromage Dominique , Beracochea Daniel
Published: May 2019

Aim

Although cognitive deficits commonly co‐occur with stress‐related emotional disorders, effect of procognitive drugs such as histaminergic H3 receptor antagonists are scarcely studied on memory retrieval in stress condition.

Methods

Experiment 1. Memory of two successive spatial discriminations (D1 then D2) 24 hours after learning was studied in a four‐hole board in mice. H3 receptor antagonist ciproxifan (ip 3 mg/kg) and acute stress (three electric footshocks; 0.9 mA; 15 ms) were administered 30 and 15 minutes respectively before memory retrieval test. Fos immunostaining was performed to evaluate the neural activity of several brain areas. Experiment 2. Effects of ciproxifan and acute stress were evaluated on anxiety‐like behavior in the elevated plus maze and glucocorticoid activity using plasma corticosterone assay.

Results

Experiment 1. Ciproxifan increased memory retrieval of D2 in nonstress condition and of D1 in stress one. Ciproxifan mitigated the stress‐induced increase of Fos expression in the prelimbic and infralimbic cortex, the central and basolateral amygdala and the CA1 of dorsal hippocampus. Experiment 2. Ciproxifan dampened the stress‐induced anxiety‐like behavior and plasma corticosterone increase.

Conclusion

Ciproxifan improved contextual memory retrieval both in stress and nonstress conditions without exacerbating behavioral and endocrine responses to stress. Overall, these data suggest potential usefulness of H3 receptor antagonists as cognitive enhancer both in nonstress and stress conditions.
Female sexual problems after treatment for colorectal cancer – a population‐based study
Authors: Thyø A. , Elfeki H. , Laurberg S. , Emmertsen K. J.
Published: May 2019

Aim

There has been limited focus on female sexuality after treatment for colorectal cancer. The aim of this study was to investigate long‐term female sexual dysfunction in disease‐free colorectal cancer survivors in the Danish population.

Method

All female Danish patients treated for colorectal cancer between 2001 and 2014 were included if they reported to have been sexually active at the time of diagnosis. They were requested to answer the validated Sexual Vaginal Changes Questionnaire.

Results

A total of 2402 patients were included for analysis (43%). Overall, rectal cancer patients reported more sexual inactivity and problems compared to colon cancer patients, but there were no differences in any sexual function domains when excluding irradiated patients and patients with a permanent stoma. A permanent stoma was associated with sexual inactivity [OR 2.56 (95% CI 1.42–4.70)] and overall sexual dysfunction [OR 2.95 (95% CI 1.05–6.38)] in colon cancer patients, as well as inactivity [OR 1.43 (95% CI 1.01–2.04)] and overall dysfunction [OR 2.0 (95% CI 1.18–3.41)] in rectal cancer patients. Furthermore, a permanent stoma was associated with dyspareunia [OR 2.17 (95% CI 1.39–3.38)] and reduced vaginal dimension [OR 3.16 (95% CI 1.99–5.01)]. In rectal cancer patients, radiotherapy exposure increased the odds for overall sexual dysfunction [OR 1.80 (95% CI 1.02–3.16)] and was associated with dyspareunia [OR 1.72 (95% CI 0.95–3.12)].

Conclusion

Sexual problems after treatment of colorectal cancer are common. Major risk factors are a permanent stoma and radiotherapy. Relevant patients should be offered professional counselling and treatment.
Golgi phosphoprotein 3 sensitizes the tumour suppression effect of gefitinib on gliomas
Authors: Wang Xu , Wang Zhaohao , Zhang Yu , Wang Yan , Zhang Hao , Xie Shao , Xie Peng , Yu Rutong , Zhou Xiuping
Published: May 2019

Objectives

We previously reported that Golgi phosphoprotein 3 (GOLPH3) promotes glioma progression by inhibiting EGFR endocytosis and degradation, leading to EGFR accumulation and PI3K‐AKT pathway over‐activation. In the current study, we examine whether GOLPH3 affects the response of glioma cells to gefitinib, an EGFR selective inhibitor.

Materials and Methods

The expression of GOLPH3 and EGFR in glioma cells was detected by immunofluorescence and immunoblotting. The cell viability or growth in vitro was determined by CCK‐8, EdU incorporation and clonogenic assays. The primary glioma cells were cultured by trypsin and mechanical digestion. The transwell invasion assay was used to examine the primary glioma cell motility. Intracranial glioma model in nude mice were established to explore the sensitivity of gefitinib to GOLPH3 high cancer cells in vivo.

Results

Both the immortalized and primary glioma cells with GOLPH3 over‐expression hold higher EGFR protein levels on the cell membrane and exhibited higher sensitivity to gefitinib. In addition, primary glioma cells with higher GOLPH3 level exhibited stronger proliferation behaviour. Importantly, GOLPH3 enhanced the anti‐tumour effect of gefitinib in vivo. Consistently, after gefitinib treatment, tumours derived from GOLPH3 over‐expression cells exhibited lower Ki67‐positive and higher cleaved caspase‐3–positive cells than control tumours.

Conclusions

Our results demonstrate that GOLPH3 increases the sensitivity of glioma cells to gefitinib. Our study provides foundation for further exploring whether GOLPH3 high gliomas will be more sensitive to anti‐EGFR therapy in clinic and give ideas for developing new possible treatments for individual glioma patients.
Congenital cutaneous pyogenic granuloma: Report of two cases and review of the literature
Authors: Schneider Mateus Henrique , Garcia Camila Foletto Vargas , Aleixo Pedro Bandeira , Kiszewski Ana Elisa
Published: May 2019

Congenital cutaneous pyogenic granuloma is a rare benign vascular tumor with clinical and histopathological features similar to infantile hemangioma. It usually presents as a red, pedunculated and highly friable papule. On histopathological analysis, one can see a capillary vessel proliferation with lobular pattern and endothelial proliferation. The differential diagnosis is based on negativity of glucose transporter 1 (GLUT1) immunochemistry studies. We report two infants with congenital pyogenic granuloma, one with a unique cutaneous lesion and the other with multiple lesions affecting both skin and mucosal surfaces. These two cases highlight the importance of the differential diagnosis based on the GLUT1 immunochemistry analysis considering the distinct treatments required to these infant vascular tumors.
A case of extramedullary hematopoiesis presenting as hemorrhagic panniculitis and evolving in acute myeloid leukemia
Authors: Gallo Graziana , Bigliardi Sara , Cesinaro Anna Maria
Published: May 2019

Extramedullary hematopoiesis (EMH) in adults is a rare event, usually associated with myeloid disorders, and can be the first sign of chronic myelomonocytic leukemia. We report a case of EMH presenting as a hemorrhagic panniculitis in a patient who did not apparently present any myeloid disorders. The patient received previous chemotherapy for mantle cell lymphoma localized to the large bowel and had been in complete remission for 3 years. The diagnosis of EMH was achieved after a deep incisional biopsy of a nodule from the thigh, and with pathological examination that included immunohistochemical studies. After a follow‐up of 14 months, the patient developed an acute myeloid leukemia, classified as therapy‐related myeloid neoplasm, according to the 2016 World Health Organization (WHO) classification of hematological malignancies. As shown by the rare cases described in literature, the presence of cutaneous EMH should always be a trigger for investigating the patient's hematological system; also, in our experience, a long follow‐up is mandatory.
Plasmacytic cutaneous pathology: A review
Authors: Walsh Noreen M. , Kutzner Heinz , Requena Luis , Cerroni Lorenzo
Published: May 2019

We review the spectrum of cutaneous disorders associated with inflammatory and neoplastic plasmacytic pathology. Because plasma cells are derived from B‐lymphocytes our overview includes discussion of certain lymphoplasmacytic proliferations. It is structured along histopathological lines, addressing conditions characterized by (a) cutaneous plasma cell infiltrates, (b) deposits of plasma cell products or their derivatives in the skin and (c) miscellaneous, poorly understood cutaneous complications of plasmacytic disorders. Lesions arising primarily in the skin and those due to cutaneous involvement by multisystem disorders are addressed. The range includes a spectrum of tumefactive and circulatory manifestations. We highlight key clinical and pathological features of the different conditions and outline recent advances in our understanding of these entities. By emphasizing the dermatopathological characteristics of this spectrum of disorders we hope to hone the diagnostic accuracy of practitioners in the field.
The Golden Proportion in the scallop geometry of normal mitral valves. When nature plays with jigsaw puzzles
Authors: Deorsola Luca , Bellone Alessandra
Published: May 2019

Introduction

The Golden Proportion is a particular geometric ratio between two segments. It results in an irrational number, commonly rounded to 1.618, or 0.618, and showing unique geometrical/mathematical properties. Its presence has been documented in a huge amount of natural settings, as well as the human body and the heart. In light of a previous research of ours, about its presence in the Coaptation Triangle, we investigated the dimensions of both mitral leaflets in healthy mitral valves and then compared our results to literature data, in order to search whether this proportional pattern could be extended to other valve aspects.

Methods and Results

Forty‐one adults, with healthy mitral valves, underwent 2D echocardiography. Adequate long‐axis three‐chamber view images were chosen, at mid‐diastole, where the central scallop of both the anterior and posterior leaflets (A2 and P2, respectively) could be well identified and measured. We then investigated these measurements, calculating their ratio and comparing our findings to literature data on normal mitral anatomy. The ratio between the two scallop heights appeared very close to the Golden Ratio. Literature data supported our results and, apparently, showed the mitral leaflets to be like a jigsaw puzzle of components highly interconnected each other with an extremely simple geometry, based on the Golden Proportion.

Conclusion

The Golden Proportion looks to determine the geometry of normal mitral scallops. Studying such a pattern of anatomical proportions could improve surgical techniques for conservative surgery, as well as innovate the design of mitral repair rings and valve prostheses.
REVELATION MECHANISMS AND ALLOCATIVE EFFICIENCY
Authors: Plassmann Florenz , Tideman Nicolaus
Published: May 2019

We show that revelation mechanisms affect owners' valuations of the assets they own and that different mechanisms provide owners with the incentive to reveal—truthfully—different valuations. Self‐assessment of property with compulsory sale at the self‐assessed price is the only known mechanism that promotes allocative efficiency by providing efficient incentives for transferring property to those who value it most. We introduce two modifications of the standard self‐assessment mechanism that maintain full incentives to invest and raise as much public revenue as can be raised efficiently. (JEL D61, D82, H21, K11)
DeTerm: Software for automatic detection of neuronal dendritic branch terminals via an artificial neural network
Authors: Kanaoka Yasutetsu , Skibbe Henrik , Hayashi Yusaku , Uemura Tadashi , Hattori Yukako
Published: May 2019

Dendrites of neurons receive and process synaptic or sensory inputs. The Drosophila class IV dendritic arborization (da) neuron is an established model system to explore molecular mechanisms of dendrite morphogenesis. The total number of dendritic branch terminals is one of the frequently employed parameters to characterize dendritic arborization complexity of class IV neurons. This parameter gives a useful phenotypic readout of arborization during neurogenesis, and it is typically determined by laborious manual analyses of numerous images. Ideally, an automated analysis would greatly reduce the workload; however, it is challenging to automatically discriminate dendritic branch terminals from signals of surrounding tissues in whole‐mount live larvae. Here, we describe our newly developed software, called DeTerm, which automatically recognizes and quantifies dendrite branch terminals via an artificial neural network. Once we input an image file of a neuronal dendritic arbor and its region of interest information, DeTerm is capable of labeling terminals of larval class IV neurons with high precision, and it also provides positional data of individual terminals. We further show that DeTerm is applicable to other types of neurons, including mouse cerebellar Purkinje cells. DeTerm is freely available on the web and was successfully tested on Mac, Windows and Linux.
Global consumer study to identify water wastage in the usage of automatic dishwashers
Authors: Belke Lara , Maitra Writi , Nijhuis Bert , Presti Clara , Stamminger Rainer
Published: May 2019

In dishcleaning automatic dishwashers do clearly win over manual cleaning when it comes to efficiency: Resources can be saved without compromising on hygiene. But mistakes in the usage behaviour can equalize saving advantages. Consumers in nine countries, covering different regions of the world, were asked about their dishcleaning behaviour to identify if this household work is done in a resource saving way. By analysing mistakes in the current behaviour, the potential of water savings shall be estimated.
The characteristics of the electrocardiogram and the intracardiac electrogram in left bundle branch pacing
Authors: Chen Xueying , Wu Shengjie , Su Lan , Su Yangang , Huang Weijian
Published: May 2019

Introduction

Left bundle branch pacing (LBBP) has recently been reported to maintain left ventricular electrical synchrony with a low and stable threshold. However, the electrocardiogram (ECG) definitions of LBBP have not been well established. We report four cases to show the characteristics of the ECG and the intracardiac electrogram (EGM) in LBBP.

Methods and Results

Four patients, two with an atrioventricular block (AVB) and two with left bundle branch block (LBBB), were included in the study. LBBP was performed and the ECGs and EGMs were collected and compared at different pacing outputs. Selective LBBP (S‐LBBP) was defined as only capturing the LBB with a typical RBBB morphology and a discrete component between the pacing stimulus and ventricular activation in the EGMs. While nonselective LBBP (NS‐LBBP) captured both the LBB and the local myocardium, resulting in a narrow right bundle branch block (RBBB) morphology without the discrete component. The left bundle branch (LBB) potential was recorded in two cases during narrow QRS complex or LBBB correction by selective His bundle pacing and SLBBP (n = 3) was achieved. A constant and shortest stimulus to left ventricular activation time (LVAT) in LBBP was obtained at different pacing outputs.

Conclusion

The ECG and EGM characteristics of LBBP can be summarized as: 1) RBBB pattern; 2) usually with the LBB potential; 3) SLBBP with specific ECG changes and a discrete component in EGM; and 4) with a constant and shortest stimulus to LVAT at different pacing outputs. Further studies are necessary to confirm these observations.
Measurement of arterial stiffness and vascular aging in community pharmacies—The ASINPHAR@2action project
Authors: Pereira Telmo , Paulino Ema , Maximiano Sofia , Rosa Mariana , Pinto Ana Luísa , Mendes Maria João , Brito Joana , Soares Patrícia , Risse Johannes , Gose Sonja
Published: May 2019

The ASINPHAR@2action project aims at raising awareness to arterial stiffness (AS) and early vascular aging (EVA) through a community pharmacy–based intervention. This preliminary analysis is focused on the analysis of the proportion of participants with increased AS and the identification of its main determinants. We performed an observational cross‐sectional study of participants enrolled in 11 community pharmacies in Portugal, between April and November 2017. Blood pressure (BP) and arterial function parameters were measured with a validated device. Clinical and demographic information was gathered, as well as the estimation of global cardiovascular risk, health‐related quality of life, and dietary profile. Cholesterol and glycaemia were taken from a recent laboratory bulletin. The cohort includes 658 participants with a mean age of 57.3 ± 16.3 years, 66% women. Brachial BP was 126.6 ± 16.4 mm Hg and 79.9 ± 11.5 mm Hg, and central BP was 115.8 ± 15.4 mm Hg and 81.2 ± 11.6 mm Hg, respectively, for systolic and diastolic BP. Mean pulse wave velocity (PWV) was 8.5 ± 2.3 m/s, and the augmentation index was 23.6 ± 15.6%. The proportion of participants with increased AS was 19.8%. The overall best‐fitting model for AS included age, gender, aortic PP, visceral fat, HDL cholesterol, AIx@75, total vascular resistance, hypertension, and diabetes, corresponding to an AUC of 0.910 (CI: 0.883, 0.937; P < 0.001) in the ROC curve analysis. The preliminary results of this pioneering large‐scale study measuring arterial function in community pharmacies provide the grounds for the operationalization of subclinical target organ damage screening in pharmacies, as a strategy to improve cardiovascular risk monitoring and to promote adherence to treatment.
Clinical and enzymatic phenotypes in congenital hyperinsulinemic hypoglycemia due to glucokinase‐activating mutations: A report of two cases and a brief overview of the literature
Authors: Ping Fan , Wang Zhixin , Xiao Xinhua
Published: May 2019

Aims/Introduction

The principal aim of this study was to investigate the clinical, genetic and functional characteristics of two cases of congenital hyperinsulinism (CHI) caused by glucokinase (GCK) mutations in young patients.

Materials and Methods

Novel mutations were detected by CHI next‐generation sequencing, and the kinetic parameters and thermal stability of recombinant wild‐type and mutant glucokinase were determined in vitro. In addition, 18 naturally occurring GCK‐CHI mutations reported previously were also summarized.

Results

A de novo mutation (M197V) was found in a 17‐year‐old male with an epilepsy history, whereas an autosomal dominant mutation (K90R) was found in a 20‐year‐old female with inherited asymptomatic hypoglycemia. Kinetic analysis showed increased enzyme activity for both mutants (RAI 4.7 for M197V and 1.6 for K90R) and enhanced thermal stability for the M197V mutant. However, of all the GCK‐CHI mutants, the increase in enzyme activity (RAI between 1.6 and 130) did not correlate strongly with the severity of hypoglycemia. The de novo group (7/19) showed distinctive phenotypes from the autosomal dominant group (12/19), such as a higher proportion of diazoxide unresponsiveness (28.6% vs 0%), a higher incidence of macrosomia (85.7% vs 40%) and a rarer incidence of adulthood onset (0% vs 25%).

Conclusions

The clinical phenotypes of GCK‐CHIs were highly heterogeneous. We have identified two novel GCK‐CHI mutations in young patients and investigated their pathogenicity by enzyme kinetic analysis, which expanded the spectrum of this rare disease.
Bactrocera dorsalis (Hendel) (Diptera: Tephritidae) is not invasive through Asia: It's been there all along
Authors: Clarke Anthony R. , Li Zhi‐hong , Qin Yu‐jia , Zhao Zi‐Hua , Liu Li‐jun , Schutze Mark K.
Published: May 2019

Oriental fruit fly, Bactrocera dorsalis (Hendel), is a highly polyphagous fruit fly which, in the last 15 years, has invaded (with or without establishment) Africa, Europe and North America. As a direct result of these invasions, there is increasing research interest in the invasion history and spread patterns of this fly. A statement being repeatedly used in the B. dorsalis invasion literature is that the species was first identified from Taiwan in 1912 and that it subsequently spread through South‐East and South Asia during the 20th century. This assumption is incorrect and stems from: (a) an incomplete knowledge of B. dorsalis taxonomic history; and (b) a confounding of first taxonomic record with first invasion record. Rather than being first detected in Taiwan in 1912, the first record of oriental fruit fly was from “East India” (India orientali) under the synonymous name of Musca ferruginea by Fabricius in 1794, and in the 1910s, it was known not only from Taiwan, but widely across tropical Asia with records from India, Burma, Bengal, Sri Lanka (as Ceylon), Singapore and Indonesia (multiple islands). The taxonomic literature is very clear that oriental fruit fly has not invaded the rest of Asia from Taiwan since 1912, and this error should not continue to be repeated in the literature.
Ten years of severe respiratory syncytial virus infections in a tertiary paediatric intensive care unit
Authors: Pham Hiep , Thompson Jenny , Wurzel Danielle , Duke Trevor
Published: May 2019

Aim

To describe the epidemiology and treatment of respiratory syncytial virus (RSV) infection in a tertiary paediatric intensive care unit (PICU), including the clinical presentations, comorbidities, respiratory support required, costs and outcomes.

Methods

This study was an analysis of a database for all children with RSV infections admitted to the PICU in Melbourne between 2005 and 2015.

Results

A total of 604 episodes of community‐acquired RSV infections were analysed, and the median age of children was 4 months (interquartile range 2–14 months); 94% of cases had lower respiratory tract infection, principally bronchiolitis, and 8.9% presented with extrapulmonary features. Respiratory support included humidified high‐flow nasal cannula oxygen therapy (76% of patients since its introduction in 2011), non‐invasive ventilation (41%) and intubation and mechanical ventilation (32%). Almost half (n = 270; 45%) had one or more pre‐existing comorbid condition. Risk factors for intubation and mechanical ventilation were presence of comorbidities (odds ratio 1.97; confidence interval 1.39–2.79, P < 0.001) and transfer from an external hospital (odds ratio 1.82; confidence interval 1.58–2.57, P < 0.001). Of the children without pre‐existing comorbidities, 25% required intubation and mechanical ventilation. Following the introduction of humidified high‐flow nasal cannula oxygen therapy, the number of annual PICU admissions for RSV infection doubled; however, the number of children requiring intubation remained unchanged. The median length of intensive care unit stay was 3.7 days and further hospital stay was 3.6 days, and the average cost per case was approximately AU$20000.

Conclusions

RSV infection carries a high burden in PICU, in bed‐days and cost. Chronic comorbidities and transfer from a peripheral hospital were associated with a higher rate of need for mechanical ventilation.
More Than Frequency? Exploring Predictors of Word Difficulty for Second Language Learners
Authors: Hashimoto Brett J. , Egbert Jesse
Published: May 2019

Frequency is often the only variable considered when researchers or teachers develop vocabulary materials for second language (L2) learners. However, researchers have also found that many other variables affect vocabulary acquisition. In this study, we explored the relationship between L2 vocabulary acquisition and a variety of lexical characteristics using vocabulary recognition test data from L2 English learners. Conducting best subsets multiple regression analysis to explore all possible combinations of variables, we produced a best‐fitting model of vocabulary difficulty consisting of six variables (R2 = .37). The fact that many variables significantly contributed to the regression model and that a large amount of variance remained yet unexplained by the frequency variable considered in this study indicates that much more than frequency alone affects the likelihood that learners will learn certain L2 words.
Associations of retinal microvascular caliber with intermediate phenotypes of large arterial function and structure: A systematic review and meta‐analysis
Authors: Liu Mengjiao , Wake Melissa , Wong Tien Yin , He Mingguang , Xiao Yinzong , Burgner David P. , Lycett Kate
Published: May 2019

Objective

Intermediate phenotypes of microcirculation (retinal microvascular caliber) are associated with cardiovascular (CV) risk factors and independently predict CV events. However, the effect of microcirculation variation on the vascular system is unclear. We conducted a systematic review and meta‐analysis of observational studies to quantify associations of retinal microvascular caliber (arteriolar, venular caliber, arteriole‐to‐venule ratio) and preclinical CV measures (large arterial function and structure).

Methods

We identified studies in MEDLINE, EMBASE, and PubMed (1946 to March 2018) studying (a) general population samples and (b) patients with cardiometabolic disease. Study‐specific correlation estimates were combined into meta‐analysis where possible.

Results

Of 1294 studies identified, 26 met inclusion criteria (general population 16, patients 10), of which five studies were included in meta‐analysis. Most studied middle‐aged adults cross‐sectionally, with one childhood study. Large arterial function and structure were predominantly assessed by pulse wave velocity and carotid intima‐media thickness, respectively. Only arteriolar caliber was consistently associated with arterial function and structure, with stronger associations observed in cardiometabolic patients. Narrower (worse) arteriolar caliber was associated with faster (poorer) pulse wave velocity (correlation coefficient (r) −0.17, 95% CI −0.25 to −0.10) and greater (poorer) intima‐media thickness (r −0.05, 95%CI −0.09 to −0.02) across all adult participants.

Conclusions

Retinal arteriolar, but not venular caliber, was modestly associated with large arterial function and weakly associated with large arterial structure, with stronger evidence in patients with cardiometabolic disease. This suggests that preclinical changes in large arteries and the microcirculation have some shared but mainly unique pathways to associate with cardiovascular disease.
Predicting rail defect frequency: An integrated approach using fatigue modeling and data analytics
Authors: Ghofrani Faeze , Pathak Abhishek , Mohammadi Reza , Aref Amjad , He Qing
Published: May 2019

In maintenance planning of rail track, it is imperative to assess the potential and frequency of rail defects. Although this problem has been mainly studied in the literature by either data‐driven or mechanic‐based models, in the present study a new method is proposed to account for the strengths of both approaches in a single model. The envisaged model incorporates fatigue crack growth model, through Finite Element Modeling (FEM), into Approximate Bayesian Computation (ABC) framework. The method is applied to the prediction of rail defect frequency for transverse defects obtained from a US Class I Railroad. The results of the proposed model show that inducing the mechanics of rail defects into a data‐driven model outperforms the traditional pure data‐driven models by over 20%. The outcome of this study, along with necessary future developments to broaden the scope of applicability of the method, will benefit railroad existing practice in capital and maintenance planning.
A graph‐based method for social sensing of infrastructure disruptions in disasters
Authors: Fan Chao , Mostafavi Ali
Published: May 2019

Damages in critical infrastructure occur abruptly, and disruptions evolve with time dynamically. Understanding the situation of critical infrastructure disruptions is essential to effective disaster response and recovery of communities. Although the potential of social media data for situation awareness during disasters has been investigated in recent studies, the application of social sensing in detecting disruptions and analyzing evolutions of the situation about critical infrastructure is limited. To address this limitation, this study developed a graph‐based method for detecting credible situation information related to infrastructure disruptions in disasters. The proposed method was composed of data filtering, burst time‐frame detection, content similarity calculation, graph analysis, and situation evolution analysis. The application of the proposed method was demonstrated in a case study of Hurricane Harvey in 2017 in Houston. The findings highlighted the capability of the proposed method in detecting credible situational information and capturing the temporal and spatial patterns of critical infrastructure events that occurred in Harvey, including disruptive events and their adverse impacts on communities. The proposed methodology can improve the ability of community members, volunteer responders, and decision makers to detect and respond to infrastructure disruptions in disasters.
The upper level: examining the risk of excess micronutrient intake in pregnancy from antenatal supplements
Authors: Gernand Alison D.
Published: May 2019

Micronutrient deficiencies are prevalent and co‐occurring among pregnant women in low‐ and middle‐income countries (LMIC). To prevent and treat deficiencies, antenatal vitamin and mineral supplements are the most common interventions during gestation. With most micronutrients, there can be health risks when intake regularly exceeds a high amount, and an upper threshold value set by the United States and Canada, the World Health Organization, and other groups is commonly called an upper intake level (UL). This review summarizes what is known about risks in pregnancy when ULs are exceeded and assesses the potential risk of exceeding the UL if a pregnant woman is taking a multiple micronutrient supplement. Overall, there is limited information on pregnancy‐specific risks from excess intake. When assuming high dietary intake plus the amount in a standard multiple micronutrient supplement (with 30 mg of iron), only niacin and iron would be expected to slightly exceed the UL. Known risks for this level intake for each nutrient are transient and mild.
Genetic diversity ofPseudomonas syringaepv.actinidiae, pathogen of kiwifruit bacterial canker
Authors: Sawada H. , Fujikawa T.
Published: May 2019

Bacterial canker disease of kiwifruit currently occurs in at least 15 countries, causing serious damage. The causative agent of the disease isPseudomonas syringaepv.actinidiae(Psa), which is genetically diverse and is currently classified into five biovars, namely, biovars 1, 2, 3, 5 and 6. In Japan, four biovars except biovar 2 have been found so far. These biovars have been confirmed to have differences in the virulence and composition of pathogenicity‐related genes, such as toxin biosynthesis and typeIIIeffector genes. Biovars 1 and 6 possess thetoxisland, a genomic island of approximately 38 kb, which contains phaseolotoxin biosynthesis genes (argK‐toxcluster) and is confirmed to have been acquired from other bacteria through horizontal transfers. Also, on the megaplasmid possessed by biovar 6, there exist coronatine biosynthesis genes, and biovar 6 has the ability to produce two phytotoxins, phaseolotoxin and coronatine. In 2014, biovar 3, considered to be of foreign origin, was confirmed for the first time in Japan. Biovar 5, whose virulence is relatively weak, is distributed only in a limited area. In addition to thetoxisland and various plasmids, a large number of mobile genetic elements are confirmed to be present on the Psa genomes, which might have played a major role in helping Psa to acquire new features. In order to understand how Psa acquired the ability to infect kiwifruit systemically, it is important to make polyphasic comparisons with related pathovars, such asP. syringaepv.theaeand pv.actinidifoliorum.
Open social innovation dynamics and impact: exploratory study of a fab lab network
Authors: Rayna Thierry , Striukova Ludmila
Published: May 2019

The aim of this research is to explore the dynamics and impact of open social innovation, within the context of fab labs and makerspaces. Using an exploratory methodology based on 12 semi‐structured interviews of fab lab founders belonging to The Centres for Maker Innovation and Technology (CMIT) programme – a network of 170 fab labs located in Eastern Europe – this research explores the impact of an adopting an open approach in relation to the different stages of social innovation (prompts, proposals, prototypes, sustaining, scaling and diffusion, systemic change) as well as social impact. The main results of this study are that while the CMIT programme provided each fab lab with similar initial conditions (identical funding, objectives and rules), the open social innovation approached adopted enabled to give birth to a wide diversity of fab labs, each being very well adapted to the local environment, social needs and constraints and able to deliver social impact in just a matter of years; a result that would be hard to achieve with a centralised top‐down approach. The study identified three types of CMITs – Education, Industry and Residential – which could be similar or different depending on the stage of social open innovation. Furthermore, this paper discusses the main difficulties social entrepreneurs encounter as a part of the open social innovation process, as well as means to overcome them. In this respect, this study adds to the literature on fab labs by providing more comprehensive view of the challenges faced by fab labs (and makerspaces) founders, as well as suggestions of strategies enabling to ensure their long‐term sustainability.
Sonic biopsy: A new tool for the assessment of peripheral pulmonary lesions
Authors: Shah Pallav L.
Published: May 2019

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Clinical trial design for acute exacerbations in idiopathic pulmonary fibrosis: A thorny path
Authors: Renzoni Elisabetta A. , Wells Athol U.
Published: May 2019

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The Impact of the London Bombings on the Well‐Being of Adolescent Muslims*
Authors: Hole Arne Risa , Ratcliffe Anita
Published: May 2019

We exploit the timing of the London bombings of July 2005, coinciding with a large‐scale national survey of adolescents, to identify the impact of extremist Islamic terror attacks on the well‐being of adolescent Muslims. Our analysis reveals interesting gender differences. We find evidence of a decline in the happiness of Muslim teenage girls after the bombings, which is also accompanied by a rise in expectations of facing discrimination in the labour market. These findings are robust to several falsification tests. However, we fail to uncover compelling evidence of any impact of the bombings on Muslim teenage boys.
Effect of Sport Training and Education on Q Angle in Young Males and Females
Authors: Şener Orhan Ahmet , Durmaz Mehmet
Published: May 2019

The purpose of this study investigation of the effect of sport training and education on Q angle in young males and females. The Quadriceps Q angles of 240 female and 600 male subject were measured in both supine and standing positions by goniometer. It was used t-tests for statistical analyses. In this study, the average age was found to be 19.16 for women and 21.120 for men. The vast majority of participants are in the 17-22 age range. In this study, was found the mean Q angle of female and male subjects at supine position 15.710 and 13.020. On the other hand Q angle of female and male subjects at standing position were 17.050 and 14.040 respectively. The difference between mean Q angle of female and male subject was statistically significant (p<0.001). Between undergraduate study group and non-undergraduate group wasn't differences Standing Q angle and Supine Q angle statistically significant (p>0.05). Finally, the mean dominant knee Q angle of young females and males seemed to be in normal range. The high value of the knee Q angle of the dominant leg should be considered to be greater than 17 for males and 20 for females. The effect of physical activity on Q-angle should be investigated more extensively. It is thought that sport education has a decreasing effect on Q angle.
2018 Millikan Medal Award Lecture: Breaking out of the physics silo
Authors: Forinash Kyle
Published: May 2019

According to his autobiography, Robert Millikan became a physics teacher when his Greek professor at Oberlin College asked him to teach a preparatory class in physics at the college. I'm sure this was not an easy transition for Millikan but the world is better off for him having been obliged to venture into unfamiliar territory. Most of us would prefer to stay within our comfort zone, especially in the classroom. But sometimes we decide (or are forced, kicking and screaming) to try something new that can make us flourish as teachers. Millikan had good advice for anyone faced with a new challenge: "All right, said I, you will have to take the consequences, but I will try and see what I can do with it." In this presentation I will offer some suggestions, grounded in fortuitous events that have caused me to grow as a teacher, for ways to take risks, leave the physics silo and learn new things. Your teaching will be better for it.