bluuebunny/crossref_metadata_2025 huggingface dataset:
Hearing screening outcome in neonatal intensive care unit graduates from a tertiary care centre in Singapore
Authors: Jayagobi Pooja Agarwal , Yeoh Annie , Hee Karen Y.M. , Sok Bee Lim Lim , Choo Khoo Poh , Kun Kiaang Henry Tan , Lazaroo Derek , Daniel Lourdes Mary
Published: September 2019

Background

We aimed to analyse the outcome of universal newborn hearing screening (UNHS) and high‐risk hearing screening in neonatal intensive care unit (NICU) graduates in a tertiary care unit.

Methods

The hearing screen programme comprises a 2‐stage automated auditory brainstem response protocol followed by a high‐risk hearing screen at 3–6 months. This study is a retrospective study of NICU graduates born between April 2002 and December 2009. Data on hearing screening, audiological assessment, and management were extracted from a computerized data management system (HITRACK).

Results

Of 100,225 newborn infants, 2.9% were admitted to the NICU during the study period. The overall incidence of hearing loss (HL) of any type/severity was 35/1,000 infants. Of infants with HL, 92.4% had their first automated auditory brainstem response at/before 1 month of corrected age. The incidence of congenital permanent HL identified by the UNHS was 15.4/1,000. The corrected median age of diagnosis was 4.5 months (1–23.5 months). Of 2,552 NICU graduates who passed the UNHS, 75.5% were retested at 3–6 months of life. Twelve infants with permanent late‐onset HL were identified, raising the overall incidence of permanent HL to 19.9/1,000; 1.1/1,000 had auditory neuropathy. Of the 92 infants with HL, 89 (96.7%) had multiple risk factors.

Conclusions

There is a high incidence of HL in NICU graduates; 22.6% were late in onset. An early rescreen in those who pass the UNHS is a beneficial step for this high risk population.
Mechanisms of Dupilumab
Authors: Harb Hani , Chatila Talal A.
Published: September 2019

The Th2 cytokines interleukin 4 (IL‐4) and IL‐13 and the heterodimeric IL‐4 receptor (IL‐4R) complexes that they interact with play a key role in the pathogenesis of allergic disorders. Dupilumab is a humanized IgG4 monoclonal antibody that targets the IL‐4 receptor alpha chain (IL‐4Rα), common to both IL‐4R complexes: type 1 (IL‐4Rα/γc; IL‐4 specific) and type 2 (IL‐4Rα/IL‐13Rα1; IL‐4 and IL‐13 specific). In this review, we detail the current state of knowledge of the different signalling pathways coupled to the IL‐4R complexes and examine the possible mechanisms of Dupilumab action and survey its clinical efficacy in different allergic disorders. The development of Dupilumab and the widening spectrum of its clinical applications is relevant to the current emphasis on precision medicine approaches to the blockade of pathways involved in allergic diseases.
What is the appropriate management of nonfunctioning pancreatic neuroendocrine tumours disclosed on screening in adult patients with multiple endocrine neoplasia type 1?
Authors: Challis Benjamin G. , Casey Ruth T. , Grossman Ashley , Newell‐Price John , Newey Paul , Thakker Rajesh V.
Published: September 2019

Multiple endocrine neoplasia type 1 (MEN1) is an inherited tumour syndrome characterised by a predisposition to the development of endocrine tumours of the parathyroid glands, pituitary and pancreas: 30%‐80% of patients with MEN1 develop pancreatic neuroendocrine tumours (pNETs), with metastatic tumours and/or their sequelae contributing to increased morbidity and early mortality. The optimal management of nonfunctioning (NF) pNETs in MEN1 remains controversial. Whilst pancreatic resection is widely recommended for tumours >2 cm, for smaller tumours (≤2 cm) a well‐established consensus guiding the indications for surgical intervention does not exist. Although total pancreatectomy may be curative for some patients, both short‐ and long‐term complications make this an unsatisfactory option for many patients. For small (<2 cm) MEN1 NF‐pNETs, some clinicians advocate surveillance based largely on retrospective data that suggest 50%‐80% of these lesions are stable over time and infrequently exhibit accelerated growth rates. It is increasingly recognised, however, that NF‐pNETs exhibit unpredictable malignant behaviour that is not determined by tumour size alone, thereby prompting other clinicians to advocate surgery for all MEN1 NF‐pNETs, irrespective of size. Such uncertainty poses clinical management challenges with regards to the timing and extent of surgery, which is further hindered by the inability to stratify patients based on predicted tumour behaviour. It is therefore critical that future MEN1 research initiatives include: (a) the discovery of biomarkers that better predict tumour behaviour; (b) the evaluation of medical therapies that may delay, or even prevent, the need for pancreatic surgery; and, ultimately, (c) improvement in the quality of life for individuals with MEN1. Here, based on the published literature, we address the Clinical Question, ‘What is the management of NF‐pNETs disclosed on screening in adult patients with MEN1?’.
Trabecular micro‐bypass stent implantation with cataract extraction in pigmentary glaucoma
Authors: Ferguson Tanner J. , Ibach Mitch , Schweitzer Justin , Karpuk Kayla L. , Stephens John D. , Berdahl John P.
Published: September 2019

Importance

Use of the trabecular micro‐bypass stent with cataract surgery is well established to be safe and effective in primary open‐angle glaucoma. This is the first study to exclusively evaluate use of the device in pigmentary glaucoma.

Background

This study aimed to investigate the safety and efficacy of a trabecular micro‐bypass stent in combination with cataract surgery in pigmentary glaucoma.

Design

Retrospective, consecutive case series.

Participants

Twenty‐four eyes of 12 patients with pigmentary glaucoma implanted with one trabecular micro‐bypass stent with concomitant cataract surgery.

Methods

Baseline data was collected and compared to the following postoperative time points: 1 day, 1 week, 1 month out to 36 months (M36) after the procedure.

Main Outcome Measures

These included intraocular pressure (IOP), number of glaucoma medications and need for additional surgery.

Results

At M36 there was a 25% reduction in IOP to 14.68 ± 3.0 (P < .01) from 19.50 ± 6.7 mmHg at baseline. The mean number of glaucoma medications was 0.75 ± 1.0 prior to the surgery and 0.59 ± 0.6 (P > .05) at 36 M. At the 36 M time‐point, 95% of eyes had IOP ≤ 18 mmHg and 68% of eyes were ≤ 15 mmHg. No eyes underwent a secondary glaucoma procedure.

Conclusions and Relevance

The insertion of a single trabecular micro‐bypass stent in combination with cataract surgery effectively provides a sustained reduction in IOP up to 3 years after surgery in patients with pigmentary glaucoma. The safety profile is favourable with low rate of IOP spikes and no patients requiring additional surgery.
In vitro diagnostic accuracy of low‐dose CBCT for evaluation of peri‐implant bone lesions
Authors: Schwindling Franz Sebastian , Hilgenfeld Tim , Weber Dorothea , Kosinski Matthias Adalbert , Rammelsberg Peter , Tasaka Akinori
Published: September 2019

Objectives

To investigate the in vitro diagnostic accuracy of low‐dose cone‐beam computed tomography (LD‐CBCT) for the detection, classification, and measurement of peri‐implant bone lesions.

Material and methods

Titanium dental implants with all‐ceramic single crowns (n = 24) were inserted into bovine bone. At twelve implants, four types of peri‐implant bone lesions were created. Radiographic imaging was performed using three techniques: LD‐CBCT, high‐definition CBCT (HD‐CBCT), and intraoral radiography (IR). The datasets were presented twice to four observers in a random order. Diagnostic accuracy was measured by calculating sensitivity and specificity, and analyzed using the McNemar's test at a significance level of 0.05. Absolute agreement between the defect sizes was assessed by means of intraclass correlation coefficients (ICC).

Results

For all three techniques, diagnostic accuracy and reliability for the detection of defects were almost perfect. The following order was found for classification of the different defect types (sensitivity/specificity): HD‐CBCT (0.96/0.99) > LD‐CBCT (0.93/0.98) > IR (0.71/0.95). No significant difference was found between the two CBCT techniques. Their performance was superior to that of IR. With regard to absolute agreement of defect size, LD‐CBCT agreement with HD‐CBCT (ICC, 95% confidence interval) was slight for defect depth (0.342, 0.181–0.625) and substantial for defect width (0.911, 0.775–0.963).

Conclusion

Intraoral radiography is useful for detecting peri‐implant bone lesions. LD‐CBCT provides additional information regarding the geometry of defects. The even higher diagnostic accuracy of the HD‐CBCT protocol tested needs to be carefully weighed against its radiation dose, which is 14 times higher than that of LD‐CBCT.
Exploring the bi‐directional relationship between autophagy and Alzheimer’s disease
Authors: Kuang Huang , Tan Cheng‐Yong , Tian Hui‐Zhen , Liu Li‐Hua , Yang Mei‐Wen , Hong Fen‐Fang , Yang Shu‐Long
Published: September 2019

Alzheimer's disease (AD) is characterized by β‐amyloid (Aβ) deposition and Tau phosphorylation, in which its pathogenesis has not been cleared so far. The metabolism of Aβ and Tau is critically affected by the autophagy. Abnormal autophagy is thought to be involved in the pathogenesis of AD, regulating autophagy may become a new strategy for AD treatment. In the early stage of AD, the presence of Aβ and Tau can induce autophagy to promote their clearance by means of mTOR‐dependent and independent manners. As AD progress, the autophagy goes aberrant. As a result, Aβ and Tau generate continually, which aggravates both autophagy dysfunction and AD. Besides, several related genes and proteins of AD can also adapt autophagy to make an effect on the AD development. There seems to be a bi‐directional relationship between AD pathology and autophagy. At present, this article reviews this relationship from these aspects: (a) the signaling pathways of regulating autophagy; (b) the relationships between the autophagy and the processing of Aβ; (c) Aβ and Tau cause autophagy dysfunction; (d) normal autophagy promotes the clearance of Aβ and Tau; (e) the relationships between the autophagy and both genes and proteins related to AD: TFEB, miRNAs, Beclin‐1, Presenilin, and Nrf2; and (f) the small molecules regulating autophagy on AD therapy. All of the above may help to further elucidate the pathogenesis of AD and provide a theoretical basis for clinical treatment of AD.
GIT1 regulates angiogenic factor secretion in bone marrow mesenchymal stem cells via NF‐κB/Notch signalling to promote angiogenesis
Authors: Li Linwei , Tang Pengyu , Zhou Zheng , Wang Qian , Xu Tao , Zhao Shujie , Huang Yifan , Kong Fanqi , Liu Wei , Cheng Lin , Zhou Zhimin , Zhao Xuan , Gu Changjiang , Luo Yongjun , Tao Gaojian , Qian Dingfei , Chen Jian , Fan Jin , Yin Guoyong
Published: September 2019

Objectives

Osteogenesis is coupled with angiogenesis during bone remodelling. G‐protein‐coupled receptor (GPCR) kinase 2‐interacting protein‐1 (GIT1) is an important protein that participates in fracture healing by regulating angiogenesis. This study investigated whether GIT1 could affect bone mesenchymal stem cells (BMSCs) to secrete angiogenic factors to enhance fracture healing by promoting angiogenesis and its possible mechanism.

Materials and methods

The angiogenesis of mice post‐fracture was detected by micro‐CT and immunofluorescence. Subsequently, vascular endothelial growth factor (VEGF) level in mouse and human BMSCs (hBMSCs) under TNF‐α stimulation was detected. The hBMSCs were transfected with GIT1 shRNAs to further explore the relationship between GIT1 and VEGF and angiogenesis in vitro. Furthermore, based on previous research on GIT1, possible signal pathways were investigated.

Results

GIT1 knockout mice exhibited impaired angiogenesis and delayed fracture healing. And GIT1 deficiency remarkably reduced the expression of VEGF mRNA in BMSCs, which affected the proliferation and migration of human umbilical vein endothelial cells. GIT1 knockdown inhibited the activation of Notch and NF‐κB signals by decreasing nuclear transportation of NICD and P65/P50, respectively. Overexpression of the canonical NF‐κB subunits P65 and P50 markedly increased NICD‐dependent activation of recombination signal‐binding protein‐jκ reporter. Finally, GIT1 enhanced the affinity of NF‐κB essential modulator (NEMO) for K63‐linked ubiquitin chains via interaction with NEMO coiled‐coil 2 domains.

Conclusion

These data revealed a positive role for GIT1 by modulating the Notch/NF‐κB signals which promoting paracrine of BMSCs to enhance angiogenesis and fracture healing.
Ant–hemipteran association decreases parasitism of Phenacoccus solenopsis by endoparasitoid Aenasius bambawalei
Authors: Xu Chong , Li Qiuling , Qu Xiaobin , Chen Jian , Zhou Aiming
Published: September 2019

1. Mutualism between ants and honeydew‐excreting hemipterans is ubiquitous in the ecosystem. It is widely accepted that ant tending facilitates the colony growth of hemipterans by protecting them from predators and parasitoids. However, few studies have explored how ant tending helps defend against natural enemies.

2. Ghost ant Tapinoma melanocephalum and the invasive mealybug Phenacoccus solenopsis have a close mutual relationship. Previous studies have shown that ghost ant tending can definitely reduce parasitism and visit frequency of Aenasius bambawalei, the dominant endoparasitoid of P. solenopsis. However, the ghost ant workers seldom attack the parasitoids. It is still unclear how the ghost ant adversely affects parasitoids. This study explored the mechanism underlying the impacts of ants on natural enemies of the mealybugs.

3. Honeydew produced by P. solenopsis was an attractant to A. bambawalei. Parasitoids exhibited less searching activity, shorter longevity and lower parasitism when supplied with less honeydew. Aenasius bambawalei showed significant avoidance of pygidial gland secretions and visual cues of ghost ants. Parasitism in plants treated with 6‐methyl‐5‐hepten‐2‐one, actinidine, and gland extracts was significantly lower than that in plants treated only with solvents (paraffin oil or double‐distilled water).

4. It is concluded that honeydew consumption by ghost ants could negatively influence the performance of parasitoids. The pygidial gland secretions and visual cues of ghost ants also significantly inhibit the parasitism. These results may contribute to a better understanding of the regulation mechanism in ant–hemipteran–enemy interactions.
Determinants of pathways to care among young adults with early psychosis entering a coordinated specialty care program
Authors: Marino Leslie , Scodes Jennifer , Ngo Hong , Nossel Ilana , Bello Iruma , Wall Melanie , Dixon Lisa
Published: September 2019

Aim

To describe the characteristics of the pathway to coordinated specialty care for young adults with early psychosis in the United States, to examine how various factors correlate with the duration of untreated psychosis (DUP), and to explore factors associated with time from onset of symptoms to first mental health service contact (help‐seeking DUP).

Methods

The sample included 779 individuals ages 16 to 30 with recent‐onset non‐affective psychosis enrolled in OnTrackNY. Domains assessed included demographics, clinical characteristics, mental health service utilization and characteristics of the pathway to care. Primary outcomes included the time from onset of psychotic symptoms to admission to OnTrackNY (DUP) and time from onset of psychotic symptoms to first mental health service contact (help‐seeking DUP).

Results

The mean DUP was 231.2 days (SD = 87.7, median = 169) and mean help‐seeking DUP was 73.7 days (SD = 110.8, median = 27). Being in school, better social functioning, and greater number of ER visits or hospitalizations were associated with shorter DUP. Violent ideation or behaviour and having an outpatient mental health visit as the first service contact or hallucinations as the reason for first service contact were significantly associated with longer DUP. Only the type of first service contact (outpatient mental health treatment or other non‐mental health service provider) and having hallucinations as the clinical reason for the first service contact were associated with help‐seeking DUP.

Conclusions

Referral delays were longer than help‐seeking delays. Strategies to reduce treatment referral delays through systems‐level interventions may be most likely to reduce the overall DUP in this population.
Successful closed reduction and conservative management with traumatic elbow luxation and medial collateral ligament rupture in an equid
Authors: Collar E. M. , Watson L. J. , Whitmer C. , Hansen S.
Published: September 2019

A 9‐year‐old donkey jenny (212 kg) presented with an acute, nonweight‐bearing left forelimb lameness of 24‐ to 36‐h duration. The limb was held in flexion and abduction, with the toe above the ground, and was unable to be manually straightened. There was significant palpable swelling along the medial aspect of the elbow joint. Radiographic evaluation revealed a medial luxation of the elbow joint with rupture of the medial collateral ligament. Closed reduction was accomplished under injectable anaesthesia without complication. The patient was weight‐bearing and comfortable on the limb immediately upon recovery from anaesthesia. The jenny was tied and kept standing for 60 days. Full limb bandages, splints (extending proximal to the scapula), hobbles,NSAIDs and cold laser therapy were utilised, decreased and discontinued. At 74 days, a rehab programme was initiated. At 8 months post‐injury, the patient was not lame and was back to her previous level of exercise. Although elbow luxation has been described as having a guarded prognosis, there has now been success in 4/5 (80%) reported cases when treatment has been attempted. Closed reduction without surgical intervention in adult animals with elbow luxation can be successful, likely dependent on the level of associated injury.
Increased expression of GAB1 promotes inflammation and fibrosis in systemic sclerosis
Authors: Shi Xiangguang , Liu Qingmei , Zhao Han , Lu Jiaying , Huang Yan , Ma Yanyun , Xia Jingjing , Liu Mengguo , Tu Wenzhen , Jin Li , Wang Jiucun , Zhao Yinhuan , Wu Wenyu
Published: September 2019

Systemic sclerosis (SSc) is an autoimmune disease mainly characterized by persistent inflammation and fibrosis. The receptor tyrosine kinase (RTK) signal pathway plays an important role in the process of SSc, and Grb2‐associated binding protein (GAB) is crucial in activating RTK signalling. A previous study found elevated levels of GAB1 in bleomycin (BLM)‐induced fibrotic lungs, but the effects of GAB1 in SSc remain unclear. Our aim was to investigate whether GAB1 was dysregulated and its potential role in SSc. Compared with healthy donors, we found GAB1 expression was 1.6‐fold higher in peripheral blood mononuclear cells (PBMC), 2.5‐fold higher in CD4 + T cells, and 2‐fold higher in skin from of SSc patients (P < .01). At the same time, the levels of type one collagen (COLI) were also significantly increased (1.8‐fold higher) in SSc skin. Additionally, BLM‐induced SSc mice showed mRNA levels of Gab1 2‐fold higher than saline‐treated controls, and Gab1 expression correlated positively with collagen content. A further in vitro study showed silencing of GAB1 suppressed inflammatory gene expression in TNF‐α induced fibroblasts. Additionally, GAB1 deficiency prominently inhibited cell proliferation and reduced COLI protein levels in TGF‐β induced fibroblasts. Taken together, these data suggest that GAB1 has a relatively high expression rate in SSc, and knockdown of GAB1 may attenuate SSc by stimulating inflammatory and fibrotic processes.
Interleukin‐4 and interleukin‐13 evoke scratching behaviour in mice
Authors: Campion Michelle , Smith Leila , Gatault Solène , Métais Charles , Buddenkotte Jörg , Steinhoff Martin
Published: September 2019

Persistent and relapsing itch commonly manifests in inflammatory skin disorders such as atopic dermatitis (AD). AD pathogenesis is driven by interleukin‐4 (IL‐4) and interleukin‐13 (IL‐13). Dupilumab, a monoclonal antibody blocking the action of IL‐4 and IL‐13 effectively reduces the symptoms of AD and itch. Little is known whether IL‐4 and IL‐13 directly contribute to itch transduction. A recently published study (Oetjen et al, Cell, 2017, 171, 217) found IL‐4 and IL‐13 to directly activate itch‐sensory neurons in vitro. Surprisingly, they found no significant increase in scratching after intradermally injecting high doses (2.5 ug/ml) of IL‐4 and IL‐13 into mice. Similar experiments in our lab, however, suggested that both IL‐4 and IL‐13 contribute to acute itch in vivo. We intradermally injected lower doses (1 ug/ml) of IL‐4 and IL‐13 into mice and found a significant increase of scratching bouts compared to vehicle. Interestingly, the combined treatment of IL‐4 and IL‐13 produced additive increase of scratching and acute pruritus at an earlier time point compared to each cytokine administered alone. In summary, our study shows a rapid and significant increase of scratching after intradermal injection of IL‐4, IL‐13 or combined IL‐4/ IL‐13 compared to vehicle in mice 5‐10 minutes after injection. Our data suggest that IL‐4 and IL‐13 alone and combined directly act as potent acute pruritogens on sensory nerves. This finding expands our understanding of cytokines as pruritogens, how targeted anticytokine medications act in AD, and about neuroimmune communication in the skin.
Refining the therapeutic range of posaconazole and isavuconazole for efficient therapeutic drug monitoring using a bioassay approach
Authors: Willeman Théo , Tonini Julia , Garnaud Cécile , Bailly Sébastien , Gandia Peggy , Stanke‐Labesque Françoise , Maubon Danièle , Gautier‐Veyret Elodie
Published: September 2019

Therapeutic drug monitoring (TDM) of antifungal triazole was recommended, except for isavuconazole (ISA) whose target trough concentrations (Cmin) need to be specified. Concerning posaconazole (POS), tablet formulation results in higher exposure but no upper Cmin threshold has been yet proposed. We aimed to investigate the pharmacokinetic–pharmacodynamic relationship of POS and ISA, using a bioassay approach as surrogate marker of antifungal activity, in order to refine the therapeutic Cmin of both antifungals. A bioassay using a cellulose disk diffusion method was performed to determine the growth inhibition zone (GIZ) of POS and ISA on Aspergillus fumigatus and Candida parapsilosis (ISA only). GIZs of plasma from patients undergoing TDM for POS (n = 136) or ISA (n = 40) were determined. GIZs of plasma patients and antifungal Cmin were highly correlated for ISA (A. fumigatus: ρ = 0.942, P < 0.0001; C. parapsilosis: ρ = 0.949, P < 0.0001) and POS (ρ = 0.922, P < 0.0001), and these relationships were represented with a Michaelis–Menten model. Based on this modeling, the recommended thresholds of 0.7, 1, and 1.25 mg/L for the POS Cmin corresponded to 50.1, 55.2, and 59.1% of the maximal GIZ, respectively. We propose an upper threshold of 4.8 mg/L for the POS Cmin and a lower threshold of 2.0 mg/L for the Cmin of ISA, as they respectively corresponded to concentrations leading to 90% and 50% of the maximal GIZ on A. fumigatus. The determination of antifungal activity using this bioassay allowed refining target Cmin of POS and ISA, especially the upper threshold of POS (4.8 mg/L) and the lower threshold of ISA (2.0 mg/L).
What Factors Are Important in Aversion to Education Debt?
Authors: Lim HanNa , Lee Jae Min , Kim Kyoung Tae
Published: September 2019

This study examined the factors related to attitude toward education debt. Based on the conceptual framework of the multidimensional nature of attitude toward debt, empirical models were constructed with variables focused on debt utility and debt fear. Using the 2016 Survey of Consumer Finances dataset, this study found that debt utility variables, such as having a higher educational level and holding a student loan balance, were negatively associated with an aversion to education debt. However, debt fear variables, such as unfavorable attitudes about debt in general and not having applied for credit, were positively associated with aversion to education debt. Subgroup analyses across different income and educational levels showed that the negative relationship between education level and aversion to education debt was more evident in the high‐income group and that most of the debt utility and debt fear variables were statistically significant only in the lower education level. These results suggest that aspects of debt utility and fear of debt contribute to attitudes about education debt, but there is inconsistency across socioeconomic status.
Influence of the annealing and defects on the VHCF behavior of an SLM AlSi10Mg alloy
Authors: Tridello Andrea , Fiocchi Jacopo , Biffi Carlo A. , Chiandussi Giorgio , Rossetto Massimo , Tuissi Ausonio , Paolino Davide S.
Published: September 2019

In the paper, the influence of the annealing temperature on the Very High Cycle Fatigue (VHCF) of AlSi10Mg specimens produced through selective laser melting (SLM) is experimentally assessed. VHCF tests at 20 kHz are carried out on Gaussian specimens subjected to a heat treatment suggested by the system supplier (heating for 2 hours to 320°C and air cooling) and to a heat treatment proposed by the authors (heating for 2 hours to 244°C and air cooling). The defects originating failure and the conditional P‐S‐N curves are compared. Experimental results show that an annealing temperature of 320 ° C induces the spheroidization of the Si network, which enhances the ductility but has a negative effect on the VHCF response. On the contrary, by reducing the heating temperature to 244 ° C, the original as‐built microstructure is not altered and the minimization of the residual stresses permits to enhance the VHCF response.
The effect of canopy openness of European beech (Fagus sylvatica) forests on ground‐dwelling spider communities
Authors: Černecká Ľudmila , Mihál Ivan , Gajdoš Peter , Jarčuška Benjamín
Published: September 2019

The composition of spider communities in forests is affected by habitat characteristics, such as canopy openness, vegetation cover or tree species diversity; therefore, we assume that the effect of canopy will differ among tree species.

As research in European beech forests has not been conducted, we studied the effect of understory environmental characteristics associated with a gradient of overstory canopy openness in beech forest on ground‐dwelling spider richness, abundance and guild composition in the Western Carpathians, Slovakia. Canopy openness, the cover of understory vegetation and litter, litter thickness and variability and soil reaction were recorded. In total, 17 332 individuals of 174 spider species were trapped during 518 days. We used Generalised Linear Models to explain the effect of environmental characteristics on the assemblages of ground‐dwelling spiders; the unique and shared contributions of the predictors were calculated using variation partitioning.

The association of canopy openness with spider species richness was hump‐shaped and displayed positive linear relationship with abundance. Abundance was also affected by soil pH.

The composition of spider communities was significantly affected by canopy openness and understory characteristics; a major part of this variation was shared between all variables. The guild composition of the assemblages interacted with canopy openness, as sheet‐web weavers were dominant under the most closed canopy, that below 20% of canopy openness, while ground hunters dominated in the rest of the canopy gradient.

The gradient of beech forest canopy openness affected spider species richness, abundance and guild composition and supported distinct assemblages.
Direct and indirect measurement of large electrocaloric effect in barium strontium titanate ceramics
Authors: Dai Guangzhou , Wang Shibin , Huang Guanhua , Chen Guirong , Lu Biao , Li Dandan , Tao Tao , Yao Yingbang , Liang Bo , Lu Sheng‐Guo
Published: September 2019

Barium strontium titanate (Ba1‐xSrxTiO3‐BST) ceramics, where x = 0.05, 0.15, 0.25, and 0.35, was prepared via a solid‐state reaction method. The lattice structures and morphologies of the ceramic samples were analyzed using X‐ray diffraction and scanning electron microscopy technologies. The dielectric and ferroelectric properties of the BST ceramics were characterized using a precision impedance analyzer and a ferroelectric polarization‐electric field (P‐E) hysteresis loop tester, respectively. The electrocaloric effect was indirectly calculated using the Maxwell relations and P‐E loops as a function of temperature and electrical field, and also directly measured using a computer‐controlled thermocouple and high‐voltage power supply. An adiabatic temperature change of 1.82 K was procured, indicating a promising potential in the applications as cooling devices.
Free, free, set them free? Are programmes effective that allow job centres considerable freedom to choose the exact design?
Authors: Harrer Tamara , Moczall Andreas , Wolff Joachim
Published: September 2019

Active labour market programmes are expected to be quite effective if job centres have a substantial degree of freedom to deliver tailor‐made individual services. For Germany, we studied the effectiveness of Schemes for Activation and Integration (SAI), which were introduced in 2009 to grant such freedoms to implement short training and private placement services. We estimated SAI participation effects on welfare recipients’ earnings and employment rate using propensity score matching and rich administrative data. We distinguished between participation in in‐firm training or training in other settings, and considered effect heterogeneity by gender, region and non‐employment duration. Participation substantially improved the participants’ earnings and employment rate, in‐firm training more so than training in other settings. Our employment effect estimates were not considerably larger than those previously found for comparable pre‐reform programmes. A lack of experience with SAI and a still inadequate client focus in the period studied might explain this.
Global employment and decent jobs, 2010–2030: The forces of demography and automation
Authors: Bloom David E. , McKenna Mathew J. , Prettner Klaus
Published: September 2019

Globally, an estimated 734 million jobs will be required between 2010 and 2030 to accommodate recent and ongoing demographic shifts, account for plausible changes in labour force participation rates, and achieve target unemployment rates of at or below 4 per cent for adults and at or below 8 per cent for youth. The facts that most new jobs will be required in countries where “decent” jobs are less prevalent and workers in many occupations are increasingly subject to risks of automation further compound the challenge of job creation, which is already quite sizable in historical perspective. Failure to create the jobs that are needed through 2030 would put currently operative social security systems under pressure and undermine efforts to guarantee the national social protection floors enshrined in the Sustainable Development Goals (SDGs).
Relationship between time‐to‐isolation and freeze duration: Computational modeling of dosing for Arctic Front Advance and Arctic Front Advance Pro cryoballoons
Authors: Getman Michael K. , Wissner Erik , Ranjan Ravi , Lalonde Jean‐Pierre
Published: September 2019

Background

Preclinical and clinical studies have utilized periprocedural parameters to optimize cryoballoon ablation dosing, including acute time‐to‐isolation (TTI) of the pulmonary vein, balloon rate of freezing, balloon nadir temperature, and balloon‐thawing time. This study sought to predict the Arctic Front Advance (AFA) vs Arctic Front Advance Pro (AFA Pro) ablation durations required for transmural pulmonary vein isolation at varied tissue depths.

Methods

A cardiac‐specific, three‐dimensional computational model that incorporates structural characteristics, temperature‐dependent cellular responses, and thermal‐conductive properties was designed to predict the propagation of cold isotherms through tissue. The model assumed complete cryoballoon‐to‐pulmonary vein (PV) circumferential contact. Using known temperature thresholds of cardiac cellular electrical dormancy (at 23°C) and cellular nonviability (at −20°C), transmural time‐to‐isolation electrical dormancy (TTIED) and cellular nonviability (TTINV) were simulated.

Results

For cardiac thickness of 0.5, 1.25, 2.0, 3.0, 4.0, and 5.0 mm, the 23°C isotherm passed transmurally in 33, 38, 46, 62, 80, and 95 seconds during cryoablation utilizing AFA and 33, 38, 46, 63, 80, and 95 seconds with AFA Pro. Using the same cardiac thicknesses, the −20°C isotherm passed transmurally in 40, 55, 78, 161, 354, and 696 seconds during cryoablation with AFA and 40, 54, 78, 160, 352, and 722 seconds with AFA Pro.

Conclusion

This model predicted a minimum duration of cryoballoon ablation (TTINV) to obtain a transmural lesion when acute TTI of the PV was observed (TTIED). Consequently, the model is a useful tool for characterizing CBA dosing, which may guide future cryoablation dosing strategies.
Association between epicardial adipose tissue and embolic stroke after catheter ablation of atrial fibrillation
Authors: Ahn Jinhee , Shin Seung Yong , Shim Jaemin , Kim Young‐Hoon , Han Sang‐Jin , Choi Eue‐Keun , Oh Seil , Shin Ji Yeon , Choe Jeong Cheon , Park Jin Sup , Lee Hye Won , Oh Jun‐Hyok , Choi Jung Hyun , Lee Han‐Cheol , Cha Kwang Soo , Hong Taek Jong , Lip Gregory Y. H. , Lim Hong Euy
Published: September 2019

Introduction

Risk factors of embolic stroke (ES) after atrial fibrillation (AF) ablation have not been fully elucidated especially among the Asian subjects, particularly regarding epicardial adipose tissue (EAT) in cardiac imaging. We aimed to assess the incidence of ES during a long‐term follow‐up period after AF ablation and to identify the risk factors associated with postablation ES, specifically focusing on EAT.

Methods and Results

We enrolled patients who experienced postablation ES and control subjects from a consortium of AF ablation registries from three institutes in Korea. EAT was assessed using multislice computed tomography before AF ablation. A total of 3464 patients who underwent AF ablation were recruited and followed‐up. During a follow‐up of 47.2 ± 36.4 months, ES occurred in 47 patients (1.36%) with a CHA2DS2‐VASc score of 1.48 ± 1.39 and the overall annual incidence of ES was 0.34%. Compared with the control group (n = 190), the ES group showed significantly higher prior thromboembolism (TE) and AF recurrence rates, larger left atrium size, lower creatinine clearance rate (CCr), and greater total and peri‐atrial EAT volume. Multivariate regression analysis demonstrated larger peri‐atrial EAT volume (hazards ratio, 1.065; 95% confidence interval, 1.005‐1.128), in addition to a prior history of TE and lower CCr, was independently associated with postablation ES. When a cut‐off value of peri‐atrial EAT volume of ≥20.15 mL was applied, patients with smaller peri‐atrial EAT volume showed significantly higher ES‐free survival.

Conclusion

Larger peri‐atrial EAT volume, in addition to prior TE and lower CCr, was independently associated with postablation ES regardless of AF recurrence and CHA2DS2‐VASc score. (ClinicalTrials.gov number, NCT03479073).
Right ventricular outflow tract low‐voltage areas identify the site of origin of idiopathic ventricular arrhythmias: A high‐density mapping study
Authors: Letsas Konstantinos P. , Efremidis Michael , Vlachos Konstantinos , Asvestas Dimitrios , Takigawa Masateru , Bazoukis George , Frontera Antonio , Giannopoulos George , Saplaouras Athanasios , Sakellaropoulou Antigoni , Mililis Panagiotis , Dragasis Stylianos , Megarisiotou Athanasia , Valkanas Kosmas , Tse Gary , Liu Tong , Deftereos Spyridon , Sideris Antonios , Baranchuk Adrian , Jais Pierre
Published: September 2019

Introduction

Electronatomical mapping allows direct and accurate visualization of myocardial abnormalities. This study investigated whether high‐density endocardial bipolar voltage mapping of the right ventricular outflow tract (RVOT) during sinus rhythm may guide catheter ablation of idiopathic ventricular arrhythmias (VAs).

Methods and Results

Forty‐four patients (18 males, mean age: 38.1 ± 13.8 years) with idiopathic RVOT VAs and negative cardiac magnetic resonance imaging underwent a stepwise mapping approach for the identification of the site of origin (SOO). High‐density electronatomical mapping (1096.6 ± 322.3 points) was performed during sinus rhythm and identified at least two low bipolar voltage areas less than 1 mV (mean amplitude of 0.20 ± 0.10 mV) in 39 of 44 patients. The mean low‐voltage surface area was 1.4 ± 0.8 cm2. Group 1 consisted of 28 patients exhibiting low‐voltage areas and high‐arrhythmia burden during the procedure. Pace match to the clinical VAs was produced in one of these low‐voltage areas. Activation mapping established the SOO at these sites in 27 of 28 cases. Group 2 comprised 11 patients exhibiting abnormal electroanatomical mapping, but very low‐arrhythmia burden during the procedure. Pace mapping produced a near‐perfect or perfect match to the clinical VAs in one of these areas in 9 of 11 patients which was marked as potential SOO and targeted for ablation. During the follow‐up period, 25 of 28 patients from group 1 (89%) and 7 of 9 patients from group 2 (78%) were free from VAs.

Conclusions

Small but detectable very low‐voltage areas during mapping in sinus rhythm characterize the arrhythmogenic substrate of idiopathic RVOT VAs and may guide successful catheter ablation.
MCU Up‐regulation contributes to myocardial ischemia‐reperfusion Injury through calpain/OPA‐1–mediated mitochondrial fusion/mitophagy Inhibition
Authors: Guan Lichun , Che Zhimei , Meng Xiangdong , Yu Yong , Li Minghui , Yu Ziqin , Shi Hui , Yang Dicheng , Yu Min
Published: September 2019

Mitochondrial dynamic disorder is involved in myocardial ischemia/reperfusion (I/R) injury. To explore the effect of mitochondrial calcium uniporter (MCU) on mitochondrial dynamic imbalance under I/R and its related signal pathways, a mouse myocardial I/R model and hypoxia/reoxygenation model of mouse cardiomyocytes were established. The expression of MCU during I/R increased and related to myocardial injury, enhancement of mitochondrial fission, inhibition of mitochondrial fusion and mitophagy. Suppressing MCU functions by Ru360 during I/R could reduce myocardial infarction area and cardiomyocyte apoptosis, alleviate mitochondrial fission and restore mitochondrial fusion and mitophagy. However, spermine administration, which could enhance MCU function, deteriorated the above‐mentioned myocardial cell injury and mitochondrial dynamic imbalanced. In addition, up‐regulation of MCU promoted the expression and activation of calpain‐1/2 and down‐regulated the expression of Optic atrophy type 1 (OPA1). Meantime, in transgenic mice (overexpression calpastatin, the endogenous inhibitor of calpain) I/R model and OPA1 knock‐down cultured cell. In I/R models of transgenic mice over‐expressing calpastatin, which is the endogenous inhibitor of calpain, and in H/R models with siOPA1 transfection, inhibition of calpains could enhance mitochondrial fusion and mitophagy, and inhibit excessive mitochondrion fission and apoptosis through OPA1. Therefore, we conclude that during I/R, MCU up‐regulation induces calpain activation, which down‐regulates OPA1, consequently leading to mitochondrial dynamic imbalance.
Tail Risk Networks of Insurers Around the Globe: An Empirical Examination of Systemic Risk for G‐SIIs vs Non‐G‐SIIs
Authors: Chen Hua , Sun Tao
Published: September 2019

Abstract

In this article, we investigate systemic risk of 157 insurers around the globe. We construct tail risk networks among these insurers using a single‐index model for quantile regressions with a variable selection technique. We develop a new network‐based systemic risk indices, taking into account expected tail losses of insurers, direct and indirect contagion effects, and the time‐varying strength of tail risk spillover. Our systemic risk indices successfully recognize global systemically important insurers (G‐SIIs). We find that on average G‐SIIs are more systemically relevant than non‐G‐SIIs, particularly during the recent U.S. financial crisis. We also find a small group of non‐G‐SIIs that are more important than G‐SIIs. Our results have significant implications for systemic risk regulation.
Time‐dependent improvement of liver inflammation, fibrosis and metabolic liver function after successful direct‐acting antiviral therapy of chronic hepatitis C
Authors: Laursen Tea Lund , Siggaard Cecilie Brøckner , Kazankov Konstantin , Sandahl Thomas Damgaard , Møller Holger Jon , Tarp Britta , Kristensen Lena Hagelskjær , Laursen Alex Lund , Leutscher Peter , Grønbæk Henning
Published: September 2019

Sofosbuvir‐based direct‐acting antiviral (DAA) therapy generally cures chronic hepatitis C (CHC) infections, however, the effects on the underlying liver disease and the potential rate of recovery are unclear. We aimed to investigate the effects of DAA therapy on liver inflammation, fibrosis, metabolic function and cognitive function and the time course in CHC patients with advanced liver disease. Seventy‐one CHC patients with advanced liver disease were studied before, during and one year after successful sofosbuvir‐based DAA therapy. Liver inflammation was assessed by plasma sCD163 and sMR levels (ELISA), fibrosis by liver stiffness (transient elastography), function by galactose elimination capacity (GEC) and cognitive performance by continuous reaction time (CRT). During DAA therapy, we observed a rapid sCD163 decline from baseline to end of treatment (6.9 vs 3.8 mg/L, P < .0001), whereas the change in sMR was more subtle (0.37 vs 0.30 mg/L, P < .0001). Liver stiffness decreased by 20% at end of treatment (17.8 vs 14.3 kPa, P < .0001), together suggesting rapid resolution of liver inflammation. One year after treatment, liver stiffness decreased by an additional 15% (P < .0001), suggestive of fibrosis regression. The GEC improved at follow‐up (all: 1.74 vs 1.98 mmol/min), mainly at 12 weeks post‐treatment, both in patients with cirrhosis (n = 56) and those with advanced liver fibrosis (n = 15) (P < .001). The CRT improved at one‐year follow‐up (1.86 vs 2.09, P = .04). In conclusion, successful DAA therapy of CHC proves beneficial in advanced liver disease, with an initial rapid resolution of liver inflammation and a subsequent gradual but steady improvement in liver fibrosis, metabolic liver function and reaction time.
The Bacillus subtilis endospore crust: protein interaction network, architecture and glycosylation state of a potential glycoprotein layer
Authors: Bartels Julia , Blüher Anja , López Castellanos Sebastián , Richter Marcus , Günther Markus , Mascher Thorsten
Published: September 2019

The endospore of Bacillus subtilis is formed intracellularly upon nutrient starvation and is encased by proteinaceous shells. The outermost layer, the crust, is a postulated glycoprotein layer that is composed of six proteins: CotV, W, X, Y, Z and CgeA. Despite some insight into protein interactions and the identification of players in glycosylation, a clear picture of its architecture is still missing. Here, we report a comprehensive mutational analysis that confirms CotZ as the anchor of the crust, while the crust structure is provided by CotV, CotX and CotY. CotY seems to be the major structural component, while CotV and CotX are polar and co‐depend on each other and partially on CotW. CotW is independent of other crust proteins, instead depending on outer coat proteins, indicating a role at the interface of crust and coat. CgeA is co‐expressed with putative glycosyltransferases (CgeB and CgeD) and implicated in crust glycosylation. In accordance, we provide evidence that CgeB, CgeCDE, SpsA‐L, SpsM and SpsNOPQR (formerly YfnHGFED) contribute to the glycosylation state of the spore. The crust polysaccharide layer consists of functionally linked rhamnose‐ and galactose‐related variants and could contain rare sugars. It may therefore protect the crust against biological degradation and scavenging.
COLONIAL, POPULAR, AND SCIENTIFIC? TheExposition du Sahara(1934) and the Formation of the Musée de l'Homme
Authors: Bernasek Lisa
Published: September 2019

This article explores the collection and exhibition practices surrounding theExposition du Sahara(1934), an exhibit organized at a key moment in the transformation of the Musée d'Ethnographie du Trocadéro into France's modernized anthropological museum, the Musée de l'Homme. Through an analysis of archival material and exhibit publications, the article traces how the institutionalization of ethnographic collecting practices was shaped by interactions between museum personnel and collectors on the ground, and by the organizers’ desire to make theExposition du Sahara, and the Musée d'Ethnographie itself, simultaneously scientific, popular, and a successful colonial institution. The account also tells the story of some of the objects from North Africa now housed at the Musée du Quai Branly, where very different modes of interpretation have been applied.
Mating system variation in hybrid zones: facilitation, barriers and asymmetries to gene flow
Authors: Pickup Melinda , Brandvain Yaniv , Fraïsse Christelle , Yakimowski Sarah , Barton Nicholas H. , Dixit Tanmay , Lexer Christian , Cereghetti Eva , Field David L.
Published: September 2019

Plant mating systems play a key role in structuring genetic variation both within and between species. In hybrid zones, the outcomes and dynamics of hybridization are usually interpreted as the balance between gene flow and selection against hybrids. Yet, mating systems can introduce selective forces that alter these expectations; with diverse outcomes for the level and direction of gene flow depending on variation in outcrossing and whether the mating systems of the species pair are the same or divergent. We present a survey of hybridization in 133 species pairs from 41 plant families and examine how patterns of hybridization vary with mating system. We examine if hybrid zone mode, level of gene flow, asymmetries in gene flow and the frequency of reproductive isolating barriers vary in relation to mating system/s of the species pair. We combine these results with a simulation model and examples from the literature to address two general themes: (1) the two‐way interaction between introgression and the evolution of reproductive systems, and (2) how mating system can facilitate or restrict interspecific gene flow. We conclude that examining mating system with hybridization provides unique opportunities to understand divergence and the processes underlying reproductive isolation.