bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating success of vaginal birth after caesarean section in a regional Australian population: Validation of a prediction model
Authors: Mooney Samantha S , Hiscock Richard , Clarke Inkeri D'Arcy , Craig Simon
Published: April 2018

Background

Following a primary caesarean section (CS), women must decide between attempted vaginal birth after caesarean (VBAC) and elective repeat caesarean section (ERCS) in subsequent pregnancies. Both options carry potential morbidity and mortality for mother and child, with the most feared being uterine rupture and its consequences. In attempts to reduce morbidity, several predictive nomograms have been developed to assist in delivery mode decisions.

Aim

To assess the validity of the predictive nomogram developed by Grobman et al. in our regional Australian population.

Materials and Methods

In our retrospective analysis, patients at term, with one previous CS who had a trial of labour were assigned a ‘Grobman score’ based on antenatal details. Outcomes were noted and patient groups analysed according to percentage deciles of estimated VBAC success, compared with actual VBAC success rates.

Results

A total of 395 women underwent trial of labour after a single prior CS, with a VBAC success rate of 83%. The Grobman model displayed adequate calibration and the re‐calibrated model good calibration with the slope coefficient of 0.87 (95% CI 0.54–1.19) and intercept 0.19 (95% CI −0.34–0.72). Discrimination was moderate with receiver operating characteristic area of 0.71 (95% CI 0.67–0.76).

Conclusion

This analysis supports further validation studies in larger Australian settings, and suggests that use of the original Grobman predictive nomogram may be appropriate in Australia.
Rural–urban variation in injury‐related hospitalisation, health outcomes and treatment cost in New South Wales
Authors: Mitchell Rebecca J. , Lower Tony
Published: April 2018

Objective

To compare differences in injury characteristics, health outcomes and treatment costs between urban and rural residents who were hospitalised following an injury.

Design

A retrospective examination of injury‐linked hospitalisation and mortality data in New South Wales from 1 January 2010 to 30 June 2014.

Participants

Urban (496 325) and rural (213 139) residents who were hospitalised following an injury.

Main outcome measures

Demographic and injury characteristics, injury severity, hospital length of stay, 28‐day hospital readmission, 90‐day mortality and treatment cost.

Results

Rural residents had an increased likelihood of being hospitalised for injuries from motorcycles, vehicles, animate causes, venomous animals or plants and assault compared to urban residents. Rural residents were less likely to be readmitted to hospital within 28 days and had a lower length of stay and age‐adjusted length of stay than urban residents. Injury‐related hospitalisations for urban and rural residents cost $4.4 billion and $1.7 billion, respectively. Annually, acute injury treatment ($1.1 billion), rehabilitation ($130 million) and subacute non‐acute patient care ($57 million) cost $1.3 billion ($990 million for urban and $384 million for rural residents) in New South Wales. Fall‐related injuries and transport incidents were the costliest injury mechanisms for both urban and rural residents.

Conclusions

Injuries contribute substantially to hospitalised morbidity and its cost. The development and implementation of injury prevention strategies targeting the most common injuries for urban and rural residents will go some way towards reducing hospitalised injury and its cost.
Review article: novel oral‐targeted therapies in inflammatory bowel disease
Authors: White J. R. , Phillips F. , Monaghan T. , Fateen W. , Samuel S. , Ghosh S. , Moran G. W.
Published: April 2018

Background

There is a great unmet clinical need for efficacious, tolerable, economical and orally administrated drugs for the treatment of inflammatory bowel disease (IBD). New therapeutic avenues have become possible including the development of medications that target specific genetic pathways found to be relevant in other immune mediated diseases.

Aims

To provide an overview of recent clinical trials for new generation oral targeted medications that may have a future role in IBD management.

Methods

Pubmed and Medline searches were performed up to 1 March 2018 using keywords: “IBD”, “UC”, “CD”, “inflammatory bowel disease” “ulcerative colitis”, “Crohn's disease” in combination with “phase”, “study”, “trial” and “oral”. A manual search of the clinical trial register, article reference lists, abstracts from meetings of Digestive Disease Week, United European Gastroenterology Week and ECCO congress were also conducted.

Results

In randomised controlled trials primary efficacy endpoints were met for tofacitinib (JAK 1/3 inhibitor‐phase III), upadacitinib (JAK 1 inhibitor‐phase II) and AJM300 (α4‐integrin antagonist‐phase II) in ulcerative colitis. Ozanimod (S1P receptor agonist‐phase II) also demonstrated clinical remission. For Crohn's disease, filgotinib (JAK1 inhibitor‐phase II) met primary endpoints and laquinimod (quinolone‐3‐carboxide small molecule‐phase II) was also efficacious. Trials using mongersen (SMAD7 inhibitor) and vidofludimus (dihydroorotate dehydrogenase inhibitor) have been halted.

Conclusions

This is potentially the start of an exciting new era in which multiple therapeutic options are at the disposal of physicians to treat IBD on an individualised basis. Head‐to‐head studies with existing treatments and longer term safety data are needed for this to be possible.
Optical trocar access for initial trocar placement in laparoscopic gastrointestinal surgery: A propensity score‐matching analysis
Authors: Tanaka Chie , Fujiwara Michitaka , Kanda Mitsuro , Murotani Kenta , Iwata Naoki , Hayashi Masamichi , Kobayashi Daisuke , Yamada Suguru , Kodera Yasuhiro
Published: April 2018

Introduction

Optical trocar access is a technique to place the initial trocar in laparoscopic surgery. With optical trocar access, each tissue layer can be visualized before insertion, which can help prevent organ injury, and air leaks at the trocar site can be minimized even in obese patients. The aim of this study was to compare the time needed for trocar insertion using optical trocar access and an open method in patients who underwent laparoscopic gastrointestinal surgery.

Methods

We reviewed our prospectively collected database and identified 384 patients who underwent laparoscopic gastrointestinal surgery involving initial trocar insertion near the umbilicus by either the optical trocar access or the open method. Before the two methods were compared, propensity score matching was used to adjust for essential variables between the optical trocar access and open groups.

Results

Patients categorized in the optical trocar access and open groups were matched one‐to‐one by propensity score matching, and 137 pairs of patients were generated. The time needed for trocar insertion was significantly shorter in the optical trocar access group than in the open group (36.6 vs 209.8 s, P < 0.01). The multivariable analysis identified an inexperienced surgeon as the only independent risk factor for prolonged time for initial trocar insertion using the optical trocar access.

Conclusions

This study indicated that optical trocar access may be recommended for inserting the initial trocar in laparoscopic gastrointestinal surgery.
Regulation of vascular permeability in anaphylaxis
Authors: Nakamura Tatsuro , Murata Takahisa
Published: April 2018

Anaphylaxis is a life‐threatening type I allergic reaction. Antigen–antibody complexes induce mast cells, basophils and neutrophils to release large amounts of histamine and/or PAF. These mediators induce hypotension and vascular hyper‐permeability and subsequent anaphylaxis dependent on the endothelial production of NO. Here, we have summarized previous studies reporting the mechanisms underlying the functional changes within the vasculature, specifically focusing on vascular permeability triggered by histamine or PAF. In addition to these pro‐inflammatory factors, PGD2 is abundantly released in anaphylaxis, mainly from mast cells. We recently demonstrated that mast cell‐derived PGD2 attenuates anaphylactic responses by inhibiting vascular hyper‐permeability in mouse models. Our findings suggest that pro‐ and anti‐inflammatory factors concurrently regulate vascular permeability in anaphylaxis. In this mini‐review, we discuss the multifactorial mechanisms underlying vascular hyper‐permeability in anaphylaxis.
Fine‐root exploitation strategies differ in tropical old growth and logged‐over forests in Ghana
Authors: Addo‐Danso Shalom D. , Prescott Cindy E. , Adu‐Bredu Stephen , Duah‐Gyamfi Akwasi , Moore Sam , Guy Robert D. , Forrester David I. , Owusu‐Afriyie Kennedy , Marshall Peter L. , Malhi Yadvinder
Published: April 2018

Understanding the changes in root exploitation strategies during post‐logging recovery is important for predicting forest productivity and carbon dynamics in tropical forests. We sampled fine (diameter < 2 mm) roots using the soil core method to quantify fine‐root biomass and architectural and morphological traits to determine root exploitation strategies in an old growth forest and in a 54‐yr‐old logged‐over forest influenced by similar parent material and climate. Seven root traits were considered: four associated with resource exploitation potential or an ‘extensive’ strategy (fine‐root biomass, length, surface area, and volume), and three traits which reflect exploitation efficiency or an ‘intensive’ strategy (specific root area, specific root length, and root tissue density). We found that total fine‐root biomass, length, surface area, volume, and fine‐root tissue density were higher in the logged‐over forest, whereas the old growth forest had higher total specific root length and specific root surface area than the logged‐over forest. The results suggest different root exploitation strategies between the forests. Plants in the old growth forest invest root biomass more efficiently to maximize soil volume explored, whereas plants in the logged‐over forest increase the spatial distribution of roots resulting in the expansion of the rhizosphere.
Insight into tetrodotoxin blockade and resistance mechanisms of Nav1.2 sodium channel by theoretical approaches
Authors: Xu Lei , Li Dayu , Ding Junjie , Pan Li , Ding Xiaoqin
Published: April 2018

Nav1.2, a member of voltage‐gated sodium channels (Navs) that are responsible for the generation and propagation of action potentials along the cell membrane, and play a vital role in the process of information transmission within the nervous system and muscle contraction, is preferentially expressed in the central nervous system. As a potent and selective blocker of Navs, tetrodotoxin (TTX) has been extensively studied in biological and chemical sciences, whereas the detailed mechanism by which it blocks nine Nav1 channel subtypes remain elusive. Despite the high structural similarity, the TTX metabolite 4,9‐anhydro‐TTX is 161 times less effective toward the mammalian Nav1.2, which puzzled us to ask a question why such a subtle structural variation results in the largely binding affinity difference. In the current work, an integrated computational strategy, including homology modeling, induced fit docking, explicit‐solvent MD simulations, and free energy calculations, was employed to investigate the binding mechanism and conformational determinants of TTX analogs. Based on the computational results, the H‐bond interactions between C4‐OH and C9‐OH of TTX and the outer ring carboxylates of the selectivity‐filter residues, and the cation–π interaction between the primary amine of guanidinium of TTX and Phe385 determine the difference of their binding affinities. Moreover, the computationally simulations were carried out for the D384N and E945K mutants of hNav1.2‐TTX, and the rank of the predicted binding free energies is in accordance with the experimental data. These observations provide a valuable model to design potent and selective neurotoxins of Nav1.2 and shed light on the blocking mechanism of TTX to sodium channels.
Dynamic risk stratification system in post‐lobectomy low‐risk and intermediate‐risk papillary thyroid carcinoma patients
Authors: Cho Jae Won , Lee Yu‐mi , Lee Yi Ho , Hong Suck Joon , Yoon Jong Ho
Published: April 2018

Objective

The dynamic risk stratification (DRS) and its current definition of each response‐to‐therapy category in post‐lobectomy papillary thyroid carcinoma (PTC) patients have not been well studied. This study aimed to validate the DRS system and to investigate useful thyroglobulin (Tg) or anti‐Tg antibody (Ab)‐related parameters in defining each response‐to‐therapy category.

Design

Retrospective observational study.

Patients

This historical cohort study included 619 patients with PTC treated by thyroid lobectomy.

Measurements

All enrolled participants were stratified according to the American Thyroid Association (ATA) initial risk stratification system and DRS system, respectively. The association between these stratifications and structural recurrence was evaluated.

Results

The median follow‐up period was 103 months. Structural recurrence occurred in 1.6% of the patients with excellent response, 3.8% of those with indeterminate response, 2.9% of those with biochemical incomplete response, and all patients with structural incomplete response. Five (1.5%) of the low‐risk patients and 14 (5.0%) of the intermediate‐risk patients had structural recurrence. The disease‐free survival curves showed significant differences according to the DRS (P < .001) and ATA initial risk stratification (P = .012), respectively. The proportion of variance explained the DRS system and ATA risk stratification system for structural recurrence was 32.4% and 29.4%, respectively. A thyroid‐stimulating hormone (TSH) level >2.75 μU/mL at 1 year after the initial operation (P < .001) was the only valuable risk factor for structural recurrence identified in this study.

Conclusion

The long‐term postoperative management of PTC patients treated with thyroid lobectomy could be guided based on the DRS.
Growth hormone—Insulin‐like growth factor 1 axis hyperactivity on bone fibrous dysplasia in McCune‐Albright Syndrome
Authors: Tessaris Daniele , Boyce Alison M , Zacharin Margaret , Matarazzo Patrizia , Lala Roberto , De Sanctis Luisa , Collins Michael T
Published: April 2018

Context

In fibrous dysplasia (BFD), normal bone and bone marrow are replaced by fibro‐osseous tissue, leading to fracture, deformity and pain. BFD may be isolated, or in association with cutaneous hyperpigmentation and/or hyperfunctioning endocrinopathies, termed McCune‐Albright syndrome (MAS). GH hypersecretion has been described in 10%‐20% of MAS‐BFD patients. Aim of the study was to determine the impact of GH‐insulin like growth factor 1 (IGF1) axis hyperactivity on MAS‐BFD morbidities and the efficacy of GH excess therapy.

Design and patients

A multicentric cross‐sectional analysis was conducted on three different MAS cohorts. From 195 MAS patients, 37 subjects (19%) with GH excess were identified and compared with 34 MAS controls without GH hypersecretion.

Results

Mean head circumference SDS was significantly higher in GH excess: 4.025 SDS vs 0.683 SDS (P < .0001). The risk of optic neuropathy (Odds ratio 4.231; P = .039), hearing deficit (Odds ratio 2.961; P = .0481), facial asymmetry (Odds ratio 6.563; P = .0192), malignancies (Odds ratio 15.24; P = .0173) were higher in GH excess group. Overall, pharmacotherapy (octreotide alone 10‐30 mg/mo or with pegvisomant 10‐20 mg/d) was effective in IGF1 normalization (IGF1 Z‐score between −2 and +2 SDS) in 21/29 patients (72.4%) with good compliance to the regimen. Late diagnosis and GH excess treatment after 16 years old of age was associated with an increased risk of optic neuropathy (Odds ratio 4.500; P = .0491) and growth of pituitary adenomas (Odds ratio 7.846; P = .050).

Conclusions

GH‐IGF1 hyperactivity increases risk of morbidities in MAS. Medical therapy is effective in normalizing IGF1 in most patients, and early treatment during paediatric age is associated with a decreased risk of optic neuropathy and GH‐secreting adenomas growth.
Developmental disorders with intellectual disability driven by chromatin dysregulation: Clinical overlaps and molecular mechanisms
Authors: Larizza L. , Finelli P.
Published: April 2018

Advances in genomic analyses based on next‐generation sequencing and integrated omics approaches, have accelerated in an unprecedented way the discovery of causative genes of developmental delay (DD) and intellectual disability (ID) disorders. Chromatin dysregulation has been recognized as common pathomechanism of mendelian DD/ID syndromes due to mutation in genes encoding chromatin regulators referred as transcriptomopathies or epigenetic disorders. Common to these syndromes are the wide phenotypic breadth and the recognition of groups of distinct syndromes with shared signs besides cognitive impairment, likely mirroring common molecular mechanisms. Disruption of chromatin‐associated transcription machinery accounts for the phenotypic overlap of Cornelia de Lange with KBG and with syndromes of the epigenetic machinery. The genes responsible for Smith‐Magenis‐related disorders act in interconnected networks and the molecular signature of histone acetylation disorders joins Rubinstein‐Taybi‐related syndromes. Deciphering pathway interconnection of clinically similar ID syndromes may enhance search of common targets useful for developing new therapeutics.
Biogeographical patterns of endemic diversity and its conservation in Australia's artesian desert springs
Authors: Rossini R. A. , Fensham R. J. , Stewart‐Koster B. , Gotch T. , Kennard M. J.
Published: April 2018

Aim

Springs in the Australian arid zone are distinct from other waterways because they house a large number of endemic species. We aimed to assess spatial patterns in endemic diversity at a basin‐wide scale and whether environmental features can help to explain them. In doing so, we take the opportunity to summarize the current state of conservation in the system.

Location

Great Artesian Basin (GAB), arid and semiarid regions of eastern Australia

Methods

We combine data regarding the location of springs with published GIS layers regarding environmental characteristics and a literature review of all species and subspecies documented in the published literature to be endemic to GAB springs.

Results

We found evidence of 96 species and subspecies of fishes, molluscs, crustaceans and plants endemic to these springs. The majority of endemic species are invertebrates with geographical distributions limited to a single spring complex (<61 km2). Endemic taxa are concentrated in 75 of the 326 spring complexes. Spring complexes with a large number of springs, high connectivity via drainage basins and low rainfall were more likely to contain endemic taxa, but environmental models were poor predictors of diversity. Only 24% spring complexes with high conservation value are within conservation reserves, and the majority of endemic species are unassessed under the IUCN and Australian conservation legislation, particularly the invertebrates.

Main conclusions

Diversity in this system is underestimated given the current rate of species discovery and prevailing data deficiency for many taxa. Historical processes and species‐specific environmental requirements may be more important for explaining why diversity is concentrated in particular complexes. Almost a decade after this system was listed as endangered, most complexes of high conservation value remain outside of conservation reserves, and the endangered species status of many taxa, and particularly the invertebrates, remain unassessed.
Manual dexterity and cognitive outcome after neonatal stroke
Authors: Alderson Lucy
Published: April 2018

This commentary is on the original article by Thébault et al. on pages 1045–1051 of this issue.
Occurrence and pathogenicity of Phytophthora × cambivora on Prunus laurocerasus in Serbia
Authors: Milenković I. , Keča N. , Karadžić D. , Radulović Z. , Tomšovský M. , Jung T.
Published: April 2018

Cherry laurel (Prunus laurocerasus) is a native plant species in Serbian forests, but is also widely used for ornamental plantings. Following two extremely wet summers in 2014 and 2015, in spring and summer of 2016 and 2017, numerous cherry laurel plants with symptoms indicative for Phytophthora diseases, like wilting and chlorosis of leaves, dieback and bleeding bark necroses, were recorded in a park in Belgrade and in two ornamental nurseries in central Serbia. From necrotic bark samples and rhizosphere soil, self‐sterile Phytophthora isolates with woolly colonies were obtained. Due to the production of ellipsoid and elongated, non‐papillate sporangia in water and of ornamented oogonia with two‐celled antheridia in mating tests with tester strains of both Phytophthora × cambivora and P. cryptogea, these isolates were identified as P. ×cambivora which was confirmed by ITS sequence analysis. Pathogenicity of P. ×cambivora from cherry laurel (PCCL) was tested by inoculating one‐year‐old seedlings of cherry laurel under the bark. P. ×cambivora from European beech (PCB), and isolates of P. cactorum (CAC), P. cryptogea (CRY), P. plurivora (PLU) and P. ×serendipita (SER) were included as comparison. Three and a half months after inoculation, nine of the twelve plants in PCB, three in PCCL and CAC and two in PLU declined with longitudinal necroses and chlorosis, wilting and premature shedding of leaves. These results demonstrate the ability of P. ×cambivora to infect and cause decline of cherry laurel plants. The particularly high aggressiveness of the P. ×cambivora isolate from beech shows that this pathogen poses a serious risk to cherry laurel in the rare natural communities of cherry laurel and beech in Serbia.
Aggressive mimicry of the cleaner wrasse by Aspidontus taeniatus functions mainly for small blennies
Authors: Fujisawa Misaki , Sakai Yoichi , Kuwamura Tetsuo
Published: April 2018

The mimic blenny Aspidontus taeniatus Quoy & Gaimard is well known for its resemblance to the juvenile and adult cleaner wrasse Labroides dimidiatus (Valenciennes) in colour and shape. As various reef fishes including piscivores actively approach the cleaner wrasse to solicit cleaning by posing, two types of benefits have been suggested for this resemblance, that is, protective mimicry and aggressive mimicry. In aggressive mimicry, the mimic blenny is supposed to have considerable opportunities to bite the fin of deceived fishes when they pose, but some studies have confirmed that fin biting does not seem to be the main feeding tactic in the blenny in nature. Here, we examined the feeding tactics including fin biting by the mimic blenny in relation to its body size in a field observational survey in the coral reefs of Sesoko Island, Okinawa, Japan. The blenny was observed feeding mainly on four food items: the tentacles of Christmas tree worms, the mantle edges of boring clams, the demersal eggs in damselfishes’ nests and the fins of fishes. The feeding frequency by fin biting significantly decreased with body size, while that by egg predation significantly increased with body size of the blenny. When predating on eggs, the blenny was vigorously attacked by egg‐guarding fish, but often succeeded in raiding their nests by forming a feeding group. When feeding by fin biting, the blenny attacked prey fish without performing any cleaning. The ratio of fin biting was considerably higher in small‐sized blennies, suggesting reliance on this feeding tactic because of a difficulty in conducting a risky egg predation. Thus, our results suggest that the mimic blenny utilizes aggressive mimicry only when it is small as an alternative feeding tactic.
Ontario Racehorse Death Registry, 2003–2015: Descriptive analysis and rates of mortality
Authors: Physick‐Sheard P. W. , Avison A. , Chappell E. , MacIver M.
Published: April 2018

Background

The Province of Ontario maintains a registry of racehorse deaths occurring within 60 days of a race or trial entry that provides insight into mortality rates and costs of competition.

Objectives

To characterise and quantify mortality and identify breed differences.

Study design

Retrospective annualised cohort study.

Methods

The Ontario Death Registry for 2003–2015, containing 1713 cases, was audited and information on the relationship between death and official work added. Race and trial data from industry performance databases were used to determine mortality rates according to breed, year, age, sex and circumstances of death.

Results

Breed differences in mortality rate and individual risk were found. Thoroughbreds (Tb) had the greatest exercise‐associated mortality (EAM) rate and risk by all measures (2.27 deaths/1000 race starts, 0.95–1.0% annual individual risk), followed by Quarter horses (Qh, 1.49, 0.60–0.69%). Rate and risk were lowest for Standardbreds (Sb, 0.28, 0.23–0.24%). Nonexercise annual individual risk was highest for the Sb (0.45%, vs. Tb 0.33%, and Qh 0.32%). Pattern and type ofEAMmirrored the characteristics of competitive activity in each industry, with high Tb and Qh mortality being associated with exercise and involving musculoskeletal injuries, dying suddenly and accidents. Low SbEAMreflected the more extensive nature of training preparation and racing for this breed.

Main limitations

Available data provided no information on morbidity, mortality beyond the 60‐day horizon or for horses not racing. Numbers for the Qh were low.

Conclusions

Race‐intensity exercise is clearly hazardous for horses, with hazards varying widely between breeds and showing parallels with industry cultural and management norms. Breed differences provide insights concerning strategies that could reduce mortality, while improving welfare and reducing costs of participation. For all breeds, musculoskeletal injury was the major contributing cause of mortality.
Functional anatomy of the hair follicle: The Secondary Hair Germ
Authors: Panteleyev Andrey A.
Published: April 2018

The secondary hair germ (SHG)—a transitory structure in the lower portion of the mouse telogen hair follicle (HF)—is directly involved in anagen induction and eventual HF regrowth. Some crucial aspects of SHG functioning and ontogenetic relations with other HF parts, however, remain undefined. According to recent evidence (in contrast to previous bulge‐centric views), the SHG is the primary target of anagen‐inducing signalling and a source of both the outer root sheath (ORS) and ascending HF layers during the initial (morphogenetic) anagen subphase. The SHG is comprised of two functionally distinct cell populations. Its lower portion (originating from lower HF cells that survived catagen) forms all ascending HF layers, while the upper SHG (formed by bulge‐derived cells) builds up the ORS. The predetermination of SHG cells to a specific morphogenetic fate contradicts their attribution to the “stem cell” category and supports SHG designation as a “germinative” or a “founder” cell population. The mechanisms of this predetermination driving transition of the SHG from “refractory” to the “competent” state during the telogen remain unknown. Functionally, the SHG serves as a barrier, protecting the quiescent bulge stem cell niche from the extensive follicular papilla/SHG signalling milieu. The formation of the SHG is a prerequisite for efficient “precommitment” of these cells and provides for easier sensing and a faster response to anagen‐inducing signals. In general, the formation of the SHG is an evolutionary adaptation, which allowed the ancestors of modern Muridae to acquire a specific, highly synchronized pattern of hair cycling.
Entropy and the conceit of biodiversity management
Authors: Tait Morgan , Larson Brendon M. H.
Published: April 2018

Many conservation biologists and ecologists consider invasive species to be one of the greatest threats to biodiversity because their spread across biogeographical boundaries may endanger unique and localized expressions of biodiversity (whether species or communities). Consequently, they imagine a future, the ‘Homogocene’, in which a small set of species dominates ecosystems around the world, and they promote policies and practices to lessen the spread of these species. Here, we consider some thermodynamic dimensions of the efforts to maintain current biogeographical boundaries. We wish to explore an important conceptual analogy between thermodynamically‐closed systems and isolated biogeographical regions in ecology. The conceptual tools developed in the context of thermodynamic systems can be shown to have relevance in a wide variety of systems contexts. The ‘Maxwell's demon’ thought experiment suggests that entropy is best thought of as information‐relative rather than a ‘law of nature’. Adopting this Maxwellian thermodynamic approach to managing complexity can shed new light on the challenges of biodiversity management. To prevent the dispersion of invasive species, people must invest energy on a scale to counteract global trade and concomitant dispersal of species. We show that removing barriers to species interaction through globalization is akin to allowing a previously isolated thermal system to interact with its environment; in both cases, the system will tend towards mixing or ‘equilibrium’, and fighting this tendency is costly. Unless social and economic integration declines, the energetic input required to lessen the spread of invasive species will continue to grow.
What's in a name? The impact of reputation and rankings on the teaching income of English universities
Authors: Wolf Alison , Jenkins Andrew
Published: April 2018

This study examines the impact of universities’ reputation on teaching income and demonstrates how strongly reputation may affect the fees that they can charge. Higher Education is increasingly competitive and international, and institutions are preoccupied with national and international prestige. Research output is demonstrably central to reputation and, specifically, to global rankings, but less has been written about the benefits of high prestige for teaching income and the ability to charge high fees. This article uses English data to show the impact when fees are partially deregulated. Public universities with high rankings in global league tables and on domestic measures can command teaching income per student which is very much higher (in this case typically more than a third) than lower‐prestige institutions. This financial return to prestige further increases universities’ incentives to seek high positions in league tables and establish a reputational brand.
Frequent loss of claudin‐4 expression in dedifferentiated and undifferentiated endometrial carcinomas
Authors: Tessier‐Cloutier Basile , Soslow Robert A , Stewart Colin J R , Köbel Martin , Lee Cheng‐Han
Published: April 2018

Aims

Dedifferentiated endometrial carcinomas (DDECs)/undifferentiated endometrial carcinomas (UECs) are aggressive endometrial cancers with frequent genomic inactivation of core components of switch/sucrose non‐fermentable (SWI/SNF) complex proteins. Claudin‐4, an epithelial intercellular tight junction protein, was recently found to be expressed in SWI/SNF‐deficient undifferentiated carcinomas but not in SWI/SNF‐deficient sarcomas. The aim of this study was to examine claudin‐4 expression in UECs/DDECs and other high‐grade uterine carcinomas.

Methods and results

We examined claudin‐4 expression by immunohistochemistry (clone 3E2C1) on tissue microarrays that contained 44 UECs/DDECs (24 SWI/SNF‐deficient), 50 carcinosarcomas, 164 grade 3 endometrioid carcinomas, 57 serous carcinomas, and 20 clear cell carcinomas. Tumours with <5% claudin‐4 expression were considered to be negative. Nearly all SWI/SNF‐deficient, and most SWI/SNF‐proficient, UECs/DDECs showed a complete absence of claudin‐4 expression in the undifferentiated component, whereas the differentiated component in DDECs showed consistent and diffuse claudin‐4 expression. Only one SWI/SNF‐deficient DDEC showed focal expression of claudin‐4 in the undifferentiated component, as compared with diffuse expression in the corresponding differentiated component. Claudin‐4 expression was consistently absent in the sarcomatous component of carcinosarcoma, and it was absent in 24% of grade 3 endometrioid carcinomas and serous carcinomas.

Conclusion

Claudin‐4 expression can be absent or very focal in a subset of high‐grade endometrial carcinomas, and is almost always absent in the undifferentiated components of SWI/SNF‐deficient UECs/DDECs, despite the apparent epithelial origin in the case of DDECs. Therefore, claudin‐4 expression cannot be used to infer mesenchymal or epithelial tumour origin in the endometrium. The consistent loss or down‐regulation of claudin‐4, a tight junction protein, in SWI/SNF‐deficient UECs/DDECs further supports the undifferentiated nature of these tumours.
Charting the unexplored extracellular matrix in cancer
Authors: Filipe Elysse C. , Chitty Jessica L. , Cox Thomas R.
Published: April 2018

The extracellular matrix (ECM) is present in all solid tissues and considered a master regulator of cell behaviour and phenotype. The importance of maintaining the correct biochemical and biophysical properties of the ECM, and the subsequent regulation of cell and tissue homeostasis, is illustrated by the simple fact that the ECM is highly dysregulated in many different types of disease, especially cancer. The loss of tissue ECM homeostasis and integrity is seen as one of the hallmarks of cancer and typically defines transitional events in progression and metastasis. The vast majority of cancer studies place an emphasis on exploring the behaviour and intrinsic signalling pathways of tumour cells. Their goal was to identify ways to target intracellular pathways regulating cancer. Cancer progression and metastasis are powerfully influenced by the ECM and thus present a vast, unexplored repository of anticancer targets that we are only just beginning to tap into. Deconstructing the complexity of the tumour ECM landscape and identifying the interactions between the many cell types, soluble factors and extracellular‐matrix proteins have proved challenging. Here, we discuss some of the emerging tools and platforms being used to catalogue and chart the ECM in cancer.
The TLR4‐IRE1α pathway activation contributes to palmitate‐elicited lipotoxicity in hepatocytes
Authors: Shen Chen , Ma Wang , Ding Lei , Li Songtao , Dou Xiaobing , Song Zhenyuan
Published: April 2018

Lipotoxicity induced by saturated fatty acids (SFAs) plays a pathological role in the development of non‐alcoholic fatty liver disease (NAFLD); however, the exact mechanism(s) remain to be clearly elucidated. Toll‐like receptor (TLR) 4 plays a fundamental role in activating the innate immune system. Intriguingly, hepatocytes express TLR4 and machinery for TLR4 signalling pathway. That liver‐specific TLR4 knockout mice are protective against diet‐induced NAFLD suggests that hepatocyte TLR4 signalling pathway plays an important role in NAFLD pathogenesis. Herein, using cultured hepatocytes, we sought to directly examine the role of TLR4 signalling pathway in palmitate‐elicited hepatotoxicity and to elucidate underlying mechanism(s). Our data reveal that palmitate exposure up‐regulates TLR4 expression at both mRNA and protein levels in hepatocytes, which are associated with NF‐κB activation. The inhibition of TLR4 signalling pathway through both pharmacological and genetic approaches abolished palmitate‐induced cell death, suggesting that TLR4 signalling pathway activation contributes to palmitate‐induced hepatotoxicity. Mechanistic investigations demonstrate that inositol‐requiring enzyme 1α (IRE1α), one of three major signal transduction pathways activated during endoplasmic reticulum (ER) stress, is the downstream target of palmitate‐elicited TLR4 activation and mechanistically implicated in TLR4 activation‐triggered cell death in response to palmitate exposure. Collectively, our data identify that the TLR4‐IRE1α pathway activation contributes to palmitate‐elicited lipotoxicity in hepatocytes. Our findings suggest that targeting TLR4‐IRE1α pathway can be a potential therapeutic choice for the treatment of NAFLD as well as other metabolic disorders, with lipotoxicity being the principal pathomechanism.
MYCN is a novel oncogenic target in adult B‐ALL that activates the Wnt/β‐catenin pathway by suppressing DKK3
Authors: Kong Desheng , Zhao Linlin , Sun Lili , Fan Shengjin , Li Huibo , Zhao Yanqiu , Guo Zhibo , Lin Leilei , Cui Lin , Wang Ke , Chen Wenjia , Zhang Yihui , Zhou Jin , Li Yinghua
Published: April 2018

Dickkopf‐3 (DKK3) is frequently down‐regulated by promoter hypermethylation and is closely associated with a poor prognosis in many cancers. Our previous studies have shown that miR‐708 down‐regulates DKK3 at the post‐transcriptional level in B‐ALL. However, whether transcriptional mechanisms lead to DKK3 silencing remains unclear. Here, we analysed the promoter regions of DKK3 by bioinformatics and found binding sites for MYCN. A dual‐luciferase reporter gene assay and ChIP experiments revealed that MYCN negatively regulates DKK3 at the transcriptional level in B‐ALL cell lines, and using bisulphite sequencing PCR, we affirmed that MYCN has no effect on the methylation of the DKK3 promoter. MYCN silencing in B‐ALL cells resulted in reduced cell proliferation, increased apoptosis and G1 phase arrest. Treatment with MYCN siRNA or 5‐aza‐2′‐deoxycytidine (5‐AdC), a demethylating agent, significantly increased the levels of DKK3 mRNA and protein and decreased the protein levels of p‐GSK3β and nuclear β‐catenin, which indicates inhibition of the Wnt/β‐catenin pathway in vitro. MYCN knockdown significantly decreased the tumorigenic capacity of Nalm6 cells, which restored DKK3 levels and inhibited the Wnt/β‐catenin pathway in vivo. Our study provides an increased understanding of adult B‐ALL pathogenesis, which may be beneficial to the development of effective prognostic markers or therapeutic targets.
Association of circulating inflammation proteins and gallstone disease
Authors: Liu Zhiwei , Kemp Troy J , Gao Yu‐Tang , Corbel Amanda , McGee Emma E , Wang Bingsheng , Shen Ming‐Chang , Rashid Asif , Hsing Ann W , Hildesheim Allan , Pfeiffer Ruth M , Pinto Ligia A , Koshiol Jill
Published: April 2018

Background and Aim

Inflammation plays a role in the development of both gallstones and gallbladder cancer; however, few studies have investigated the association of circulating inflammation proteins with risk of gallstones.

Methods

This study measured 13 cytokines (including 10 interleukins [ILs]) that have been associated with cancer in serum samples collected from 150 gallstone patients and 149 population‐based controls from Shanghai, China, in 1997–2001. This study estimated the associations of each cytokine, categorized into quartiles and coded as a trend, with risk of gallstones using logistic regression models adjusted for potential confounders.

Results

Higher levels of IL‐6, IL‐10, IL‐12 (p70), and IL‐13 were associated with increased risk of gallstones (i.e.Ptrend < 0.003, Bonferroni corrected), with odds ratios (ORs) that ranged from ORhighest quartile [Q4]versuslowest quartile [Q1] = 3.2 (95% confidence interval: 1.4, 7.5) for IL‐13 to ORQ4versusQ1 = 5.7 (95% confidence interval: 2.5, 13.5) for IL‐12 (p70). In a regression model including all four ILs, only IL‐12 retained statistical significance (P < 0.05).

Conclusion

This study found four circulating ILs that were associated with gallstones. Future studies are needed to validate the findings and evaluate the common pathway or mechanism in the development of gallbladder diseases associated with these cytokine signatures.
Short‐term memory impairment in vestibular patients can arise independently of psychiatric impairment, fatigue, and sleeplessness
Authors: Smith Laura , Wilkinson David , Bodani Mayur , Bicknell Rowena , Surenthiran S. S.
Published: April 2018

Vestibular dysfunction is associated with visual short‐term memory impairment; however, it remains unclear if this impairment arises as a direct result of the vestibular dysfunction or is a consequence of comorbid changes in mood, affect, fatigue, and/or sleep. To this end, we assessed the concurrence and interdependence of these comorbidities in 101 individuals recruited from a tertiary balance clinic with a neuro‐otological diagnosis. Over fifty per cent of the sample showed reduced visuospatial short‐term memory, 60% and 37% exceeded cut‐off on the Beck Anxiety and Depression Inventories, respectively, 70% exceeded cut‐off on the Fatigue Severity Scale, 44% reported daytime sleepiness on the Epworth Sleepiness Scale, and 78% scored above cut‐off on the Pittsburgh Sleep Quality Index. The high concurrence of these symptoms gives reason to infer the existence of a vestibular cognitive affective syndrome. Structural equation modelling indicated that the significant statistical association between general unassisted posture (a marker of chronic vestibular dysfunction and strong predictor of falls risk) and short‐term memory was not mediated by mood and wakefulness. Instead, the memory impairment related more directly to vestibular dysfunction. From a rehabilitation perspective, the implication is that if the vestibular disorder is treated successfully then the memory problem will likewise improve.
Measuring the financial and productivity burden of paediatric hospitalisation on the wider family network
Authors: Mumford Virginia , Baysari Melissa T , Kalinin Djala , Raban Magdalena Z , McCullagh Cheryl , Karnon Jonathon , Westbrook Johanna I
Published: April 2018

Aim

To estimate the non‐medical out‐of‐pocket costs for families with a child in hospital.

Methods

This study was a survey of 225 parents of paediatric inpatients on nine wards of an Australian public paediatric teaching hospital on two separate days. Our primary outcomes were the costs associated with: (i) time taken off work to care for the child in hospital; (ii) time off work or contributed by family and friends to care for other dependents; and (iii) travel, meals, accommodation and incidental expenses during the child's stay. Demographic data included postcode (to assess distance, socio‐economic status and remoteness), child's age, ward and whether this was their child's first admission.

Results

Mean patient age was 6.5 years (standard deviation 5.2). On an average per patient day basis, parents took 1.12 days off work and spent 0.61 (standard deviation 0.53) nights away from home, with 83.8% of nights away at the child's bedside. Parents spent Australian dollars (AUD)89 per day on travel and AUD36 on meals and accommodation. Total costs (including productivity costs) were AUD589 per patient day. Higher costs per patient day were correlated with living in a more remote area (0.48) and a greater travel distance to the hospital (0.41). A higher number of days off work was correlated (0.69) with number of school days missed.

Conclusion

These results demonstrate the considerable time and financial resources expended by families caring for a child in hospital and are important inputs in evaluating health‐care interventions that affect risk of hospitalisation and length of stay in paediatric care.
Effects of fat supplementation on plasma glucose, insulin and fatty acid analysis in ponies maintained on a forage‐based diet
Authors: Williams T. , Rude B. , Liao S. , Mochal‐King C. , Nicodemus M.
Published: April 2018

The objective of this study was to observe how fat incorporated into an equine forage‐based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14‐day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14‐day period before a five‐day trial period. Each pony received all four diets by the end of the study. Each trial was a five‐day period with a three‐day sample collection. Blood samples for each collection week were taken 0, 30, 60, 90, 120, 150, 180, 210, 240 and 270 min and at 5, 6, 7, 8, 9 and 10 hr post‐feeding. Excess fat did not impact plasma glucose (p > .1), nor did it affect blood plasma insulin concentration. While there was no time alteration found for plasma fatty acid concentration (p > .1), C14:0 increased when ponies were fed 0% fat and C18:2 decreased when ponies were fed 0% fat. Plasma fatty acids (% of totalFA) were higher in C18:0, C18:1, C18:2 and C20:1 in the added fat diets (p < .1). These findings suggest the amounts reported in this study of fat supplementation on a forage‐based diet did influence the fatty acid analysis within the pony, but did not negatively impact blood glucose and insulin concentrations.
Effects of a DHA‐rich unextracted microalgae as a dietary supplement on performance, carcass traits and meat fatty acid profile in growing‐finishing pigs
Authors: Moran C. A. , Morlacchini M. , Keegan J. D. , Delles R. , Fusconi G.
Published: April 2018

Two 125‐day experiments of the same design were conducted to evaluate the effects of a heterotrophically grown microalgae (AURA) containing docosahexaenoic acid (DHA) on pig performance, carcass traits and the fatty acid composition of lean and adipose tissue. In each experiment, 144 Hypor pigs were blocked by sex, allocated to three treatment groups, and fed 0, 0.25% or 0.50% AURA in isonutritive, isocaloric diets. Pigs were weighed on days 0, 28, 56, 84 and 112. Feed and water intakes were measured every 28 days. Pigs were slaughtered on day 125. Data from the two studies were analysed as a single data set. Performance and carcass traits did not differ between treatments. Both microalgae treatment levels enriched (p < .05) Longissimus lumborum (LL) and backfat in DHA and improved (p < .05) their ratios of n‐6 to n‐3 fatty acids.
Testing the CVAR in the Fractional CVAR Model
Authors: Johansen Søren , Nielsen Morten Ørregaard
Published: April 2018

We consider the fractional cointegrated vector autoregressive (CVAR) model of Johansen and Nielsen (2012a) and show that the likelihood ratio test statistic for the usual CVAR model is asymptotically chi‐squared‐distributed. Because the usual CVAR model lies on the boundary of the parameter space for the fractional CVAR in Johansen and Nielsen (2012a), the analysis requires the study of the fractional CVAR model on a slightly larger parameter space so that the CVAR model lies in the interior. This in turn implies some further analysis of the asymptotic properties of the fractional CVAR model.