bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary evidence of different and clinically meaningful opioid withdrawal phenotypes
Authors: Dunn Kelly E. , Weerts Elise M. , Huhn Andrew S. , Schroeder Jennifer R. , Tompkins David Andrew , Bigelow George E. , Strain Eric C.
Published: October 2018

Opioid use disorder (OUD) is a public health crisis. Differences in opioid withdrawal severity that predict treatment outcome could facilitate the process of matching patients to treatments. This is a secondary analysis of a randomized controlled trial (RCT) that enrolled treatment seeking heroin‐users (N = 89, males = 78) into a residential study. Participants maintained on morphine (30 mg, subcutaneous, four‐times daily) underwent a naloxone (0.4 mg, IM = intramuscular) challenge session to precipitate withdrawal. Area‐under‐the‐curve (AUC) values from self‐reported withdrawal ratings during the challenge session were analyzed using K‐means clustering, revealing two phenotype groups. Withdrawal and retention from the subsequent 14‐day double‐blind, double‐dummy RCT comparing three study medications (clonidine, tramadol‐ER, and buprenorphine) were evaluated as a function of phenotype. Cluster analyses suggested HIGH (N = 37; mean [SD] subjective opiate withdrawal scale [SOWS]–AUC 123.7 [65.8]) and LOW (N = 52; SOWS‐AUC 68.0 [47.7]) withdrawal phenotype groups. HIGH participants were significantly more female and had lower body mass indices than LOW participants; no drug‐use variables were significant. Regarding RCT outcomes, HIGH phenotype participants were less likely to be retained in the study (P = 0.02) and had higher mean self‐reported withdrawal (P = 0.05) than LOW phenotype participants. A significant interaction in RCT retention was observed between phenotype (P = 0.02) and study medication (P < 0.01). Self‐reported withdrawal was significant for phenotype (P = 0.02); study medication trended towards significance (P = 0.07). Results suggest patients have meaningfully different experiences of opioid withdrawal that may predict differential response to opioid pharmacotherapies during supervised withdrawal. Additional prospective research to replicate and more thoroughly evaluate withdrawal phenotype correlates and sex differences is warranted.
An econometric analysis of demand for food quantity and quality in urban China
Authors: Hovhannisyan Vardges , Mendis Sachintha , Bastian Chris
Published: October 2018

This article offers an analytical framework for studying consumer demand for food quality based on a theory‐consistent demand model, namely, the Exact Affine Stone Index specification. Importantly, it accounts for unobserved consumer and regional heterogeneity, and allows for arbitrary Engel curves. The empirical value of our framework is illustrated in an econometric analysis of demand for food quality in China. Evaluating possible structural changes in consumer food expenditures in China is of paramount importance, given the ever‐increasing global role of China and the implications of the structural food preference changes for the global food system. The major findings emerging from this study indicate that income is an important determinant of demand for food quality and quantity with the relatively more affluent provinces having a higher affinity for food quality.
Willingness to contract versus opportunity to contract: a case study in Kenya's French bean export market
Authors: Rosch Stephanie D. , Ortega David L.
Published: October 2018

We characterize systematic differences in willingness and opportunity to contract for farmers in and out of the French bean supply market in Kenya. We find that the factors associated with being a low cost producer do not always align with the factors correlated with opportunity to contract. We also find that farmers in and out of the market differ on average in the premiums they place on buyer reliability, which suggests that imperfect contract enforcement could impact participation in French bean contracting.
Efficacy of interventions led by staff with geriatrics expertise in reducing hospitalisation in nursing home residents: A systematic review
Authors: Santosaputri Elita , Laver Kate , To Timothy
Published: October 2018

Objective

To determine the efficacy of interventions, delivered by geriatrics‐trained staff for nursing home residents, in reducing hospitalisation.

Methods

Multiple databases and clinical trial registers were searched. Studies that provided comparative data and involved residents aged ≥65 years evaluating patient‐level interventions delivered by geriatrics‐trained staff were included. The systematic review protocol was made available on PROSPERO (registration number CRD42017079928; www.crd.york.ac.uk/PROSPERO).

Results

Sixteen studies were included; six were randomised controlled trials. Studies were categorised according to intervention approaches into the following: (i) hospital prevention program; (ii) emergency department‐based hospital avoidance program; and (iii) post‐hospital supported discharge program. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) quality of evidence was low to moderate. Most studies demonstrated a favourable trend; however, only a few reported statistically significant reductions in hospitalisations. Results from the randomised studies were non‐significant.

Conclusions

Despite the heterogeneity of studies, there is limited evidence that interventions delivered by geriatrics‐trained staff reduce hospitalisations in nursing home residents. Further work examining decision‐making around hospital transfer may help inform future intervention design.
“The Courageous Conference”: British and American Newspaper Coverage of the 1915 Women’s Peace Congress at The Hague
Authors: Munro Thomas
Published: October 2018

From the outbreak of the First World War, newspapers in belligerent nations, such as Great Britain, and in neutral countries, such as the United States, discussed what the war might mean for the international order. The British and American public’s engagement with ideas of international organisation was particularly evident in April 1915 when the Women’s Peace Congress was held at The Hague. The overall purpose of the Congress may have been to protest the futility of war but what it produced was an alternative vision of international relations, one with both sexes and all the nations of the world equally represented. Relying on the negative stereotype of wartime newspapers, historians have argued that the contemporary press derided the Congress and the women involved. However, an examination of the British and American press demonstrates the extensive and positive coverage that a number of prominent newspapers gave the Congress. Newspaper reporting of the women’s meeting at The Hague reveals the widespread contemporary acceptance of the Congress as another contribution to the vibrant debate about issues of peace and internationalism that had occurred since the war began.
“We’re full”: Capacity, Finitude, and British Landscapes, 1945‐1979
Authors: Pikó Lauren
Published: October 2018

The language of urban fullness and finitude has long had an active life in British politics and popular culture. After 1945, however, ideas of the finite, overspilling British city, teeming with inert masses of working‐class people, drove the development of paternalistic state urban reconstruction and new town programmes. More infamously, post‐war immigration anxieties often used a sinister metaphorical language of flooding and drowning to describe the arrival of people from Commonwealth countries as catastrophic. Despite this shared conceptualisation of British landscapes as finite, embattled, inert spaces, the interrelationships between these ideas of “human floods” have largely been treated separately by historians. This article proposes that these histories can be traced in terms of their shared cultural logic of landscape finitude and capacity, as part of a post‐imperial reimagining of heritage and national identity. Through reading representations of post‐war immigration and urban overcrowding together, a wider preservationist political logic can be seen entrenching and defending ideas of urban and national finitude against a range of post‐imperial ideological and demographic change. Through tracing symbolic representations of borders and population fullness, this paper gestures towards a more integrated history of post‐imperial landscape politics and their role in shaping policies and practices of exclusion in post‐war Britain.
“We went and did an Anzac job”: Memory, Myth, and the Anzac Digger in Vietnam
Authors: Martin Hobbs Mia
Published: October 2018

Australian martial identity is defined by the Anzac legend, and Australian veterans of all wars have struggled to remember their service through the prism of Anzac. For Australia’s Vietnam veterans, this struggle is particularly complex: powerful memories of conflict and division contest the values of Anzac. This oral history shows how Vietnam veterans’ personal memories of war are modified into tropes to create a collective identity of victimhood. Several historians have explored individual tropes that appear in veterans’ memories. This article, based on qualitative interviews with Vietnam veterans, builds on their work and identifies six memory tropes: the volunteer Nasho, the noble and skilful digger, no welcome home, baby killer, banned from the RSL, and belated recognition. Together, these tropes constitute a “cultural script” that retells the story of Anzac in Vietnam. This cultural script is a way for veterans to express their feelings of exclusion from Anzac status in Australia, and a way for them to reclaim this status. However, deconstructing the script shows how unattainable the ideal of Anzac is, requiring an ongoing creation of victimhood to legitimise martyrdom and further perpetuating the hierarchies of Anzac identity.
Supraglottic airway devices in difficult airway management: a retrospective cohort study of 658,104 general anaesthetics registered in the Danish Anaesthesia Database
Authors: Thomsen J. L. D. , Nørskov A. K. , Rosenstock C. V.
Published: October 2018

Indications for using supraglottic airway devices have widened over time and they now hold a prominent role in guidelines for difficult airway management. We aimed to describe the use of supraglottic airway devices in difficult airway management. We included adult patients undergoing general anaesthesia registered in the Danish Anaesthesia Database from 2008 to 2012 whose airway management had been recorded as difficult, defined as: ≥ 3 tracheal intubation attempts; failed tracheal intubation; or difficult facemask ventilation. In the Danish Anaesthesia Database, a separate difficult airway management module requires the technique used in each successive airway management attempt to be recorded. The primary aim of the study was to describe the use of supraglottic airway devices in cases of difficult airway management. Secondary aims were to examine success rates of supraglottic airway devices in difficult airway management cases, and specifically in the cases of ‘cannot intubate, cannot facemask ventilate’. Difficult airway management occurred in 4898 (0.74% (95%CI 0.72–0.76%)) of 658,104 records of general anaesthesia. Supraglottic airway devices were used or use was attempted in 607 cases of difficult airway management (12.4% (95%CI 11.5–13.3%)), and were successful in 395 (65.1% (95%CI 61.2–68.8%)) cases. In ‘cannot intubate, cannot facemask ventilate’ situations, supraglottic airway devices were used in 86 (18.9% (95%CI 15.6–22.8%)) of 455 records and were successful in 54 (62.8% (95%CI 52.2–72.3%)) cases. We found that supraglottic airway devices are not widely used in the management of the difficult airway despite their prominent role in difficult airway management guidelines.
Treatment of patients with primary retroperitoneal sarcoma: predictors of outcome from an Australian specialist sarcoma centre
Authors: Snow Hayden A. , Hitchen Tatiana X. , Head Jessica , Herschtal Alan , Bae Susie , Chander Sarat , Chu Julie , Hendry Shona , Ngan Samuel Y. , Desai Jayesh , Choong Peter F. M. , Henderson Michael , Gyorki David E.
Published: October 2018

Background

Several unanswered questions surround the management of retroperitoneal sarcoma (RPS). Guidelines recommend treatment by a multidisciplinary team at a specialized referral centre. The objective of this study was to describe the management of RPS at an Australian specialist sarcoma centre, comparing outcomes to international standards and analysing for predictors of local failure.

Methods

A retrospective review of a prospectively maintained database was performed on patients with RPS treated between 2008 and 2016. A 5‐year outcome analyses focussed on patients undergoing curative‐intent surgery for primary, non‐metastatic RPS.

Results

Eighty‐eight patients underwent surgery for primary RPS. Five‐year overall survival was 66%, 5‐year freedom from local recurrence was 65% and 5‐year freedom from distant metastasis was 71%. Overall survival was associated with tumour grade (hazard ratio (HR) 6.1, P < 0.001) and histologic organ invasion (HR 5.7, P < 0.001). Variables associated with improved freedom from local recurrence were macroscopically complete resection (HR 0.14, P < 0.001) and neoadjuvant radiotherapy (HR 0.33, P = 0.014). Treatment at a specialist sarcoma centre was associated with a higher rate of preoperative biopsy and neoadjuvant radiotherapy (both with P < 0.001). There was a trend towards improved local control for patients undergoing surgery at a specialist centre (P = 0.055).

Conclusion

This is the largest Australian series of RPS and outcomes are comparable to major international sarcoma centres. Patients treated at a specialist centre had higher rates of preoperative diagnosis and tailored therapy which was associated with improved outcomes. Patients with suspected RPS should be referred to a specialist centre for optimal preoperative evaluation and multidisciplinary management.
Long‐term neurotoxicity and Raynaud's phenomenon in patients treated with cisplatin‐based chemotherapy for malignant ovarian germ cell tumor
Authors: Solheim Olesya , Skalleberg Jacob , Warncke Torhild , Ørstavik Kristin , Tropé Claes , Fosså Sophie D.
Published: October 2018

Introduction

The aim was to evaluate “overall neuropathy”, defined as peripheral paresthesia and Raynaud's phenomenon, in long‐term survivors of malignant ovarian germ cell tumors (MOGCTs) treated with cisplatin‐based chemotherapy (CBCT).

Material and methods

Ninety‐three MOGCT survivors recorded in Norway in 1980‐2009 (median follow up: 15 years) were included in this analysis. Forty‐nine received CBCT (CBCT group) and 44 received other or no chemotherapy (non‐CBCT group). Applying the scale for chemotherapy‐induced neurotoxicity, the prevalence of overall neuropathy (ie score >1 on a 0‐3 scale) was compared between the two groups. Forty women from the CBCT group also underwent neurophysiological and neurological examinations; results from the neurological examination were graded according to the National Cancer Institute‐Common Terminology Criteria for Adverse Effects version 4 (NCI‐CTCAE scale v4). These women were then categorized into subgroups of low (≤3 cycles of CBCT, n = 23) and high CBCT (≥4 cycles of CBCT, n = 17).

Results

Twenty‐eight (57%) women from the CBCT group reported overall neuropathy, compared with 20 (45%) in the non‐CBCT group (P = .06). Of the 40 MOGCT survivors in the CBCT group who underwent neurophysiological and neurological examinations, 14 (35%) showed NCI‐CTCAE grade ≥1 signs or symptoms of peripheral neuropathy. Pathological findings of NCI‐CTCAE grade 2 or 3 signs or symptoms were found in four survivors (10%) from the high CBCT subgroup, all of whom also showed objective signs of neuropathy.

Conclusions

Though about half of our MOGCT survivors reported overall neuropathy after CBCT, more severe pathological neurological/neurophysiological findings that impacted daily living were recorded in only 10% of them. Our observations of a similar prevalence of self‐reported overall neuropathy in the CBCT and non‐CBCT group, combined with limited objective neurological findings, warrant further study to increase the understanding of the specific pathophysiological pathways of long‐term CBCT‐induced neuropathy.
Bone Marrow Stem Cells‐Seeded Polyethylene Terephthalate Scaffold in Repair and Regeneration of Rabbit Achilles Tendon
Authors: Cai Jiangyu , Yang Yimeng , Ai Chengchong , Jin Wenhe , Sheng Dandan , Chen Jun , Chen Shiyi
Published: October 2018

The objective of this study was to evaluate the effect of bone marrow stem cells (BMSCs)‐seeded polyethylene terephthalate (PET) scaffold for Achilles tendon repair in a rabbit model. The allogeneic BMSCs were seeded onto the PET scaffold and cultured in vitro for 14 days. Sixteen mature New Zealand rabbits underwent surgery to establish a 2‐cm Achilles tendon defect model. The BMSCs‐seeded PET scaffold was implanted into the defect of one limb (BMSCs‐PET group), while the PET scaffold without BMSCs was implanted into the defect of contralateral limb as the control (PET group). All rabbits were sacrificed at 6 and 12 weeks after surgery. At 12 weeks after surgery, macroscopic and histological results showed formation of tendon‐like tissues, and the structure was more mature in the BMSCs‐PET group. Immunohistochemical analysis and real‐time polymerase chain reaction (RT‐PCR) demonstrated that the collagen I and collagen III were significantly higher in the BMSCs‐PET group compared with those in the PET group. Mechanically, both the failure load and the average stiffness were significantly higher in the BMSCs‐PET group than those in the PET group. In conclusion, BMSCs‐seeded PET scaffold could effectively facilitate the healing process after being implanted in a rabbit Achilles tendon defect model.
Change in subfoveal choroidal thickness secondary to orthokeratology and its cessation: a predictor for the change in axial length
Authors: Li Zhouyue , Hu Yin , Cui Dongmei , Long Wen , He Mingguang , Yang Xiao
Published: October 2018

Purpose

To investigate changes in subfoveal choroidal thickness (SFChT) during orthokeratology (Ortho‐K) lens wear and after its cessation and the association of short‐term change in SFChT with the long‐term eye elongation in Ortho‐K subjects.

Design

A prospective clinical trial.

Methods

Fifty myopic children aged between 9 and 14 years were enrolled. Twenty‐nine subjects continuously wore Ortho‐K lens for 12 months and discontinued for 1 month. Twenty‐one subjects wearing single vision distance spectacles for 12 months were included as the control group. SFChT was assessed using optical coherence tomography. Ocular parameters, including axial length (AL), central corneal thickness (CCT), anterior chamber depth (ACD), lens thickness (LT) and apical corneal power (ACP), were also measured.

Results

After 12 months of follow‐up, AL elongation was larger and SFChT change was smaller in the control group compared to the Ortho‐K group (both p < 0.001). In the Ortho‐K group, SFChT increased by 16 μm from baseline at the 1‐month visit (p < 0.001), and the magnitude of choroidal thickening remained unchanged at the 6‐ and 12‐month visit (p = 0.289). One month after discontinuation of Ortho‐K lens, SFChT and ocular parameters of the anterior segment, including ACP, CCT and ACD recovered to baseline level (All p > 0.05), and AL increased by 0.23 ± 0.18 mm compared to baseline (p = 0.018). SFChT change at 1‐month was negatively associated with AL change at 13‐month (standard β, −0.581, p = 0.001) after adjusting for other influencing factors, including baseline age and the ocular parameters.

Conclusion

Subfoveal ChT (SFChT) significantly increased after short‐term Ortho‐K lens treatment and the increase maintained throughout the period of treatment. One month after Ortho‐K lens cessation, SFChT, ACP, CCT and ACD returned to baseline. Short‐term response in SFChT is associated with long‐term change in AL in children undergoing Ortho‐K lens and may be a predictor for the effectiveness of the treatment.
Influence of glaucoma surgery on visual function: a clinical cohort study and meta‐analysis
Authors: Junoy Montolio Francisco G. , Müskens Rogier P.H.M. , Jansonius Nomdo M.
Published: October 2018

Purpose

To determine the cost (loss of visual function associated with the procedure) and benefit (long‐term preservation of the visual field) of glaucoma surgery.

Methods

We included 100 patients who underwent glaucoma surgery (Baerveldt glaucoma implant [BGI], n = 61; trabeculectomy [TE], n = 39). Preoperatively, the median (interquartile range [IQR]) standard automated perimetry mean deviation (MD) was −12 (−16 to −6) dB. We analysed the change in visual acuity (BCVA) and MD due to the procedure and, in a subset with at least 5 years of perimetric follow‐up both pre‐ and postoperatively (n = 20), the change in rate of progression (ROP; time rate of change in MD). For the surgery‐induced change in ROP, we also performed a meta‐analysis including the current and previously published studies. From the surgery‐induced decrease in MD and change in ROP, we calculated the average postoperative duration needed for the benefit to surpass the cost.

Results

Mean (standard deviation) MD decline was 1.3 (2.7) and 1.0 (2.3) dB for BGI (p < 0.001) and TE (p = 0.009), respectively; no significant surgery‐induced changes in BCVA were found (p = 0.08 and p = 0.12, respectively). In our study, surgery was associated with a non‐significant deceleration of ROP (from −0.37 [0.52] to −0.15 [0.48] dB/year; p = 0.23). The meta‐analysis, based on eight studies, showed an overall surgery‐induced change in ROP of 0.44 (95% confidence interval 0.25 to 0.64; p < 0.0001) dB/year.

Conclusion

Glaucoma surgery significantly reduces the progression velocity in glaucoma. On average, the benefit of glaucoma surgery surpasses the cost after approximately 1.5 years.
Evidence‐based clinical guidelines on analgesia and sedation in newborn infants undergoing assisted ventilation and endotracheal intubation
Authors: Ancora Gina , Lago Paola , Garetti Elisabetta , Merazzi Daniele , Savant Levet Patrizia , Bellieni Carlo Valerio , Pieragostini Luisa , Pirelli Anna
Published: October 2018

Aim

This review informed pain control guidelines for clinicians performing mechanical ventilation, nasal continuous positive airway pressure and endotracheal intubation on term and preterm newborn infants.

Methods

We reviewed literature published between 1986 and June 2017 on analgesia and sedation during assisted ventilation and before endotracheal intubation in newborn infants admitted to neonatal intensive care units. The subsequent guidelines were developed using the Grading of Recommendations Assessment, Development and Evaluation approach.

Results

Our review produced five strong standard of care recommendations. One, reduce neonatal stress and use nonpharmacological analgesia during invasive ventilation. Two, favour intermittent boluses of opioids, administered after pain scores and before invasive procedures, during short expected periods of mechanical ventilation, mainly in preterm infants affected by respiratory distress syndrome. Three, do not use morphine infusion in preterm infants under 27 gestational weeks. Four, always use algometric scores to titrate analgesic drugs doses. Five, use premedication before endotracheal intubation for a more rapid, less painful, less traumatic and safer manoeuvre. We also developed 30 conditional recommendations on therapeutic options.

Conclusion

Our review produced 35 recommendations on standard care and therapeutic options relating to the analgesia and sedation of newborn infants during ventilation and before endotracheal intubation.
Molecular stressors underlying exercise training‐induced improvements in K+ regulation during exercise and Na+,K+‐ATPase adaptation in human skeletal muscle
Authors: Christiansen Danny
Published: October 2018

Despite substantial progress made towards a better understanding of the importance of skeletal muscle K+ regulation for human physical function and its association with several disease states (eg type‐II diabetes and hypertension), the molecular basis underpinning adaptations in K+ regulation to various stimuli, including exercise training, remains inadequately explored in humans. In this review, the molecular mechanisms essential for enhancing skeletal muscle K+ regulation and its key determinants, including Na+,K+‐ATPase function and expression, by exercise training are examined. Special attention is paid to the following molecular stressors and signaling proteins: oxygenation, redox balance, hypoxia, reactive oxygen species, antioxidant function, Na+,K+, and Ca2+ concentrations, anaerobic ATP turnover, AMPK, lactate, and mRNA expression. On this basis, an update on the effects of different types of exercise training on K+ regulation in humans is provided, focusing on recent discoveries about the muscle fibre‐type‐dependent regulation of Na+,K+‐ATPase‐isoform expression. Furthermore, with special emphasis on blood‐flow‐restricted exercise as an exemplary model to modulate the key molecular mechanisms identified, it is discussed how training interventions may be designed to maximize improvements in K+ regulation in humans. The novel insights gained from this review may help us to better understand how exercise training and other strategies, such as pharmacological interventions, may be best designed to enhance K+ regulation and thus the physical function in humans.
Facebook use and sleep quality: Light interacts with socially induced alertness
Authors: Bowler Jenny , Bourke Patrick
Published: October 2018

It has been demonstrated that the use of social networking sites late at night can lead to sleep‐related problems that extend into the next day. A common explanation is that the light emitted from screens is disrupting the users’ circadian rhythms. An alternative explanation is that the social cognition inherent in the use of social networking sites is responsible. Here, the two factors were looked at together. Participants used Facebook on iPad tablets before sleep. This was done on different nights with two lighting conditions and with two levels of content. In the ‘light’ condition, blue wavelength light was manipulated so that it was either full wavelength or blue light filtered. In the ‘alertness’ condition, the personal significance of the content was changed from personally relevant to irrelevant. A modified version of the Pittsburgh Sleep Quality Index was used to measure sleep‐related problems. No evidence was found that simply filtering blue light or simply removing relevant content improved sleep quality. However, the two factors interacted. The results suggest that the light emitted from screens can affect sleep quality under some conditions but this is behaviourally irrelevant in the context of normal Facebook usage.
Evaluation of axitinib to downstage cT2a renal tumours and allow partial nephrectomy: a phase II study
Authors: Lebacle Cedric , Bensalah Karim , Bernhard Jean‐Christophe , Albiges Laurence , Laguerre Brigitte , Gross‐Goupil Marine , Baumert Herve , Lang Herve , Tricard Thibault , Duclos Brigitte , Arnoux Armelle , Piedvache Celine , Patard Jean‐Jacques , Escudier Bernard
Published: October 2018

Objective

To evaluate the ability of neoadjuvant axitinib to reduce the size of T2 renal cell carcinoma (RCC) for shifting from a radical nephrectomy (RN) to a partial nephrectomy (PN) indication, offering preservation of renal function.

Patients and Methods

Patients with cT2aN0NxM0 clear‐cell RCC, considered not suitable for PN, were enrolled in a prospective, multicentre, phase II trial (AXIPAN). Axitinib 5 mg, and up to 7–10 mg, was administered twice daily, for 2–6 months before surgery, depending on the radiological response. The primary outcome was the number of patients receiving PN for a tumour <7 cm in size after neoadjuvant axitinib.

Results

Eighteen patients were enrolled. The median (range) tumour size and RENAL nephrometry score were 76.5  (70–98) mm and 11 (7–11), respectively. After axitinib neoadjuvant treatment, 16 tumours decreased in diameter, with a median size reduction of 17% (64.0 vs 76.5 mm; P < 0.001). The primary outcome was considered achieved in 12 patients who underwent PN for tumours <7 cm. Sixteen patients underwent PN. Axitinib was tolerated in the present study, as has been previously shown in the metastatic setting. Five patients had grade 3 adverse events. Five patients experienced Clavien III–V post‐surgery complications. At 2‐year follow‐up, six patients had metastatic progression, and two had a recurrence.

Conclusion

Neoadjuvant axitinib in cT2 ccRCC is feasible and, even with a modest decrease in size, allowed a tumour shrinkage <7 cm in 12 cases; however, PN procedures remained complex, requiring surgical expertise with possible morbidity.
Student Protest and the Nueva Mayoría Reforms in Chile
Authors: Palacios‐Valladares Indira , Ondetti Gabriel
Published: October 2018

Chile's Nueva Mayoría government (2014–2018) responded more forcefully to student demands for a more assertive public role in education than any of its post‐authoritarian predecessors. Existing scholarship suggests that this change reflected the success of the 2011 student protests in tapping into latent public discontent with neoliberalism and the politics of consensus. This article argues that it is also crucial to understand how the wave of protest interacted with the dynamics of party politics at the elite level. Public support translated into substantive policy and institutional changes because it contributed to a coalition and platform shift that favoured more extensive reform.
The community and ecosystem consequences of intraspecific diversity: a meta‐analysis
Authors: Raffard Allan , Santoul Frédéric , Cucherousset Julien , Blanchet Simon
Published: October 2018

Understanding the relationships between biodiversity and ecosystem functioning has major implications. Biodiversity–ecosystem functioning relationships are generally investigated at the interspecific level, although intraspecific diversity (i.e. within‐species diversity) is increasingly perceived as an important ecological facet of biodiversity. Here, we provide a quantitative and integrative synthesis testing, across diverse plant and animal species, whether intraspecific diversity is a major driver of community dynamics and ecosystem functioning. We specifically tested (i) whether the number of genotypes/phenotypes (i.e. intraspecific richness) or the specific identity of genotypes/phenotypes (i.e. intraspecific variation) in populations modulate the structure of communities and the functioning of ecosystems, (ii) whether the ecological effects of intraspecific richness and variation are strong in magnitude, and (iii) whether these effects vary among taxonomic groups and ecological responses. We found a non‐linear relationship between intraspecific richness and community and ecosystem dynamics that follows a saturating curve shape, as observed for biodiversity–function relationships measured at the interspecific level. Importantly, intraspecific richness modulated ecological dynamics with a magnitude that was equal to that previously reported for interspecific richness. Our results further confirm, based on a database containing more than 50 species, that intraspecific variation also has substantial effects on ecological dynamics. We demonstrated that the effects of intraspecific variation are twice as high as expected by chance, and that they might have been underestimated previously. Finally, we found that the ecological effects of intraspecific variation are not homogeneous and are actually stronger when intraspecific variation is manipulated in primary producers than in consumer species, and when they are measured at the ecosystem rather than at the community level. Overall, we demonstrated that the two facets of intraspecific diversity (richness and variation) can both strongly affect community and ecosystem dynamics, which reveals the pivotal role of within‐species biodiversity for understanding ecological dynamics.
Are pulp consumers effective seed dispersers? Tests with a large‐seeded tropical relict tree
Authors: Peña‐Egaña Mara , Loayza Andrea P. , Squeo Francisco A.
Published: October 2018

Several plant species in the Neotropics bear large, fleshy fruits that suggest adaptation to endozoochorous seed dispersal by large vertebrates. Many of these plants occur in areas where large vertebrates are no longer present; consequently, their seeds are dispersed by pulp consumers; small vertebrates that only ingest the pulp reward because they are uncapable of swallowing the fruits whole. Few studies have examined the role of these pulp consumers on the regeneration of large‐fruited/seeded plants. Here, we assessed seed disperser effectiveness (SDE) and context‐dependence in SDE of pulp consumers of Pouteria splendens, a large‐seeded tree, considered a tropical relict in Mediterranean Chile. We found that P. splendens fruits are consumed by six species of non‐flying vertebrates; four of which act as dispersers with very low effectiveness. Low SDE resulted from the quantitative, rather than the qualitative component, specifically from low visitation rates. Most seeds remained under P. splendens trees, either from being dispersed there or because they were not dispersed at all. However, both emergence and establishment probabilities were higher under conspecific plants than in other habitats, suggesting no negative density‐dependent effects on P. splendens recruitment. Although the absence of more effective dispersers does not seem to affect local recruitment probabilities, it results in the absence of long‐distance dispersal, further isolating the remnant P. splendens populations. Finally, although pulp consumers have very low disperser effectiveness, the key functional role of these species is to remove the fleshy pulp from P. splendens’ seed as its presence significantly reduces germination probability.
Editorial Perspective: Key issues in children with intellectual disability for practitioners
Authors: Rathwell Iris , Simonoff Emily
Published: October 2018

One in seven children with an impairing mental health disorder has intellectual disability (ID). Despite the ubiquity of ID, many clinicians are less confident in the assessment and management of mental disorders in youth with ID. Key to determining how to modify these is a good understanding of the child's developmental/cognitive strengths and weaknesses. There is very limited evidence for mental health interventions specific to children with ID. In this context, NICE guidelines generally recommend the same interventions identified for typically developing children. However, psychological interventions should be adapted for developmental level and communication ability. Medication should be selected carefully taking account of co‐existing conditions, drug interactions and the greater sensitivity to adverse effects in this population. Assessment and intervention should always take account of the child's wider context, including education. There is little evidence regarding the best service models in relation to efficacy and efficiency, but the high prevalence of ID amongst youth with mental health problems suggests that all mental health professionals should have competence in working with youth with milder levels of ID.
Exploration of resistance mechanisms for epidermal growth factor receptor‐tyrosine kinase inhibitors based on plasma analysis by digital polymerase chain reaction and next‐generation sequencing
Authors: Iwama Eiji , Sakai Kazuko , Azuma Koichi , Harada Daijiro , Nosaki Kaname , Hotta Katsuyuki , Nishio Makoto , Kurata Takayasu , Fukuhara Tatsuro , Akamatsu Hiroaki , Goto Koichi , Shimose Takayuki , Kishimoto Junji , Nakanishi Yoichi , Nishio Kazuto , Okamoto Isamu
Published: October 2018

Liquid biopsy offers a potential alternative to tissue biopsy for detection of genetic alterations in cancer, and it has been introduced into clinical practice to detect the tyrosine kinase inhibitor (TKI) resistance‐conferring T790M mutation of epidermal growth factor receptor (EGFR) in patients with non‐small‐cell lung cancer (NSCLC). We prospectively collected tumor and plasma samples from 25 NSCLC patients who harbored activating mutations of EGFR and experienced failure of treatment with afatinib. The samples were analyzed by digital PCR (dPCR) and next‐generation sequencing (NGS). T790M was detected in plasma with a respective sensitivity and specificity of 83.3% and 70.0% by dPCR and 50.0% and 70.0% by NGS relative to analysis of corresponding tumor samples. Quantitation of T790M based on the ratio of the number of T790M alleles to that of activating mutation alleles (T/A ratio) improved the specificity of plasma analysis to 100% for both dPCR and NGS without a reduction in sensitivity. Although several afatinib resistance mechanisms other than T790M—including copy number gain of NRAS or MET—were identified in tumor samples, the corresponding genetic alterations were not detected in plasma. TP53 mutations were frequently identified in plasma and tumor samples, with most such mutations also having been detected before afatinib treatment. The presence of de novo TP53 mutations was associated with reduced progression‐free survival. Quantitation of T790M in plasma is thus a clinically relevant approach to determine the T790M status of tumors. In addition, genetic alterations coexisting with EGFR mutations can affect the efficacy of EGFR‐TKI treatment.
Dual functions of ARP101 in targeting membrane type‐1 matrix metalloproteinase: Impact on U87 glioblastoma cell invasion and autophagy signaling
Authors: Desjarlais Michel , Annabi Borhane
Published: October 2018

Membrane type‐1 matrix metalloproteinase (MT1‐MMP) possesses both extracellular proteolytic and intracellular signal‐transducing functions in tumorigenesis. An imbalance in MT1‐MMP expression and/or function triggers a metastatic, invasive, and therapy resistance phenotype. MT1‐MMP is involved in extracellular matrix (ECM) proteolysis, activation of latent MMPs, as well as in autophagy signaling in human hepatoma and glioblastoma cells. A low autophagy index in tumorigenesis has been inferred by recent studies where autophagic capacity was decreased during tumor progression. Here, we establish ARP101 as a dual‐function small‐molecule inhibitor against MT1‐MMP ECM hydrolysis and autophagy signal‐transducing functions in a model of grade IV glioblastoma cells. ARP101 inhibited concanavalin‐A‐mediated proMMP‐2 activation into MMP‐2, as well as MT1‐MMP auto‐proteolytic processing. When overexpressing recombinant Wt MT1‐MMP, ARP101 inhibited proMMP‐2 activation and triggered the formation of MT1‐MMP oligomers that required trafficking to the plasma membrane. ARP101 further induced cell autophagy as reflected by increased formation of acidic vacuole organelles, LC3 puncta, and autophagy‐related protein ATG9 transcription. These were all significantly reversed upon siRNA‐mediated gene silencing of MT1‐MMP. ARP101 can thus concomitantly inhibit MT1‐MMP extracellular catalytic function and exploit its intracellular transducing signal function to trigger autophagy‐mediated cell death in U87 glioblastoma cancer cells.
Early Crying, Sleeping, and Feeding Problems and Trajectories of Attention Problems From Childhood to Adulthood
Authors: Bilgin Ayten , Baumann Nicole , Jaekel Julia , Breeman Linda D. , Bartmann Peter , Bäuml Josef G. , Avram Mihai , Sorg Christian , Wolke Dieter
Published: October 2018

This study investigated if crying, sleeping or feeding problems that co‐occur (multiple regulatory problems [RPs]) or are persistent predict attention problems and diagnoses of attention deficit hyperactivity disorder (ADHD) in childhood and adulthood. Participants were 342 individuals who were assessed at 5, 20, and 56 months for crying, sleeping, and feeding (RPs) and at 6, 8, and 28 years for ADHD diagnoses, attention problems, and attention span. Infants/toddlers with multiple/persistent RPs had an increased risk of receiving an ADHD diagnosis both in childhood and adulthood compared to those who never had RPs. Multiple/persistent RPs were further associated with a high‐decreasing attention problems trajectory from childhood to adulthood. Interventions to alleviate early RPs may prevent the development of attention problems.
Orthographic‐Phonological Mapping and the Emergence of Visual Expertise for Print: A Developmental Event‐Related Potential Study
Authors: Varga Vera , Tóth Dénes , Csépe Valéria
Published: October 2018

The N1 effect is an electrophysiological marker of visual specialization for print. The phonological mapping hypothesis (Maurer & McCandliss, 2007) posits that the left‐lateralized effect reflects grapheme‐phoneme integration. In this event‐related potential study, first (age = 7.06 years, N = 32) and third‐grade readers (age = 9.29 years, N = 28) were presented with pairs of pseudowords and Armenian character strings in a novel implicit same‐different paradigm. To test the phonological mapping hypothesis, stimuli were presented in visual‐only and audiovisual conditions. The results demonstrated that tuning for print already emerges in first grade. Moreover, the parallel presentation of auditory stimuli enhanced the N1 effect suggesting a role of orthographic‐phonological mapping in the development of specialization for print.
Discrimination and Ethnic‐Racial Socialization Among Youth Adopted From South Korea Into White American Families
Authors: Schires Samantha M. , Buchanan NiCole T. , Lee Richard M. , McGue Matt , Iacono William G. , Burt S. Alexandra
Published: October 2018

The current study examined how discrimination relates to adjustment outcomes in a sample of internationally, transracially adopted Korean Americans from the Minnesota Sibling Interaction and Behavior Study (N = 456 adoptees; Mage at T1 = 14.9, Mage at T2 = 18.3, Mage at T3 = 22.3). The moderating roles of ethnic socialization and preparation for bias by parents (i.e., ethnic‐racial socialization) were also examined. Results indicated that discrimination predicted higher levels of depressive and externalizing symptoms in youth who reported less preparation for bias. In those experiencing more preparation for bias, associations were not significantly different from zero. Ethnic socialization did not moderate these associations. Such findings provide important information for adoptive parents regarding how to prepare their children to cope with discrimination.
The Impact of Caregiving Disruptions of Previously Institutionalized Children on Multiple Outcomes in Late Childhood
Authors: Almas Alisa N. , Papp Leanna J. , Woodbury Margaret R. , Nelson Charles A. , Zeanah Charles H. , Fox Nathan A.
Published: October 2018

This study examined disruptions in caregiving, as well as the association of these disruptions, with cognitive, behavioral, and social outcomes at age 12 in a sample of 136 Romanian children who were abandoned to institutions as infants and who experienced a range of subsequent types of care. Children were found to experience significantly more caregiving disruptions (CGD) earlier in life than later in childhood. More frequent CGD predicted increases in externalizing and internalizing behavior problems at age 12. Results are discussed in terms of the association between CGD and the long‐term development of children who have experienced institutional rearing.
Food‐induced fatal anaphylaxis: From epidemiological data to general prevention strategies
Authors: Pouessel Guillaume , Turner Paul J. , Worm Margitta , Cardona Victòria , Deschildre Antoine , Beaudouin Etienne , Renaudin Jean‐Marie , Demoly Pascal , Tanno Luciana K.
Published: October 2018

Background

Anaphylaxis hospitalizations are increasing in many countries, in particular for medication and food triggers in young children. Food‐related anaphylaxis remains an uncommon cause of death, but a significant proportion of these are preventable.

Aim

To review published epidemiological data relating to food‐induced anaphylaxis and potential risk factors of fatal and/or near‐fatal anaphylaxis cases, in order to provide strategies to reduce the risk of severe adverse outcomes in food anaphylaxis.

Methods

We identified 32 published studies available in MEDLINE (1966‐2017), EMBASE (1980‐2017), CINAHL (1982‐2017), using known terms and synonyms suggested by librarians and allergy specialists.

Results

Young adults with a history of asthma, previously known food allergy particularly to peanut/tree nuts are at higher risk of fatal anaphylaxis reactions. In some countries, cow's milk and seafood/fish are also becoming common triggers of fatal reactions. Delayed adrenaline injection is associated with fatal outcomes, but timely adrenaline alone may be insufficient. There is still a lack of evidence regarding the real impact of these risk factors and co‐factors (medications and/or alcohol consumption, physical activities, and mast cell disorders).

Conclusions

General strategies should include optimization of the classification and coding for anaphylaxis (new ICD 11 anaphylaxis codes), dissemination of international recommendations on the treatment of anaphylaxis, improvement of the prevention in food and catering areas, and dissemination of specific policies for allergic children in schools. Implementation of these strategies will involve national and international support for ongoing local efforts in relationship with networks of centres of excellence to provide personalized management (which might include immunotherapy) for the most at‐risk patients.
Staphylococcus aureus‐derived extracellular vesicles induce monocyte recruitment by activating human dermal microvascular endothelial cells in vitro
Authors: Kim Jihye , Bin Bum‐Ho , Choi Eun‐Jeong , Lee Hyun Gee , Lee Tae Ryong , Cho Eun‐Gyung
Published: October 2018

Background

Atopic dermatitis (AD) represents the most common inflammatory skin disorder in children showing massive infiltration of immune cells. The colonization of AD‐afflicted skin by Staphylococcus aureus and S. aureus‐derived extracellular vesicles (SEVs) has been associated with AD pathogenesis; however, the molecular mechanism underlying SEV‐mediated inflammatory responses remains unclear.

Objective

We investigated how SEVs can mediate inflammatory responses in AD pathogenesis by examining the effect of SEVs on human dermal microvascular endothelia cells (HDMECs).

Methods

HDMECs were treated with SEVs, and the expression of cell adhesion molecules or cytokines was assessed using RT‐qPCR, Western blot or cytokine array analyses. The receptor for SEVs and related signalling molecules in HDMECs were addressed and verified via gene knockdown or inhibitor experiments. The recruitment assay of human THP‐1 monocytic cells on HDMECs was performed after SEV treatment in the presence or absence of the verified receptor or signalling molecule.

Results

SEVs, but not other gram‐positive bacteria‐derived extracellular vesicles, directly activated HDMECs by increasing the expression of cell adhesion molecules (E‐selectin, VCAM1 and ICAM1) and that of IL‐6, the inflammatory cytokine; consequently, they enhanced the recruitment of THP‐1 monocytic cells to HDMECs. The SEV‐induced HDMEC activation was dependent on Toll‐like receptor 4 and the NF‐κB signalling pathway, which was rapidly activated within 1 hour post‐treatment and followed by an upregulation of cell adhesion molecules and IL‐6 at later time‐points. Moreover, SEV‐mediated HDMEC responses were more rapid and intense than those induced by the same protein concentrations of S. aureus extracts.

Conclusions & Clinical Relevance

SEVs as proinflammatory factors could mediate immune cell infiltration in AD by efficiently inducing endothelial cell activation and monocyte recruitment, which may provide insights into alleviating the S. aureus‐mediated onset or progression of AD and its phenotypes.