bluuebunny/crossref_metadata_2025 huggingface dataset:
Update on “What” and “Where” in Spatial Language: A New Division of Labor for Spatial Terms
Authors: Landau Barbara
Published: September 2016

In this article, I revisit Landau and Jackendoff's () paper, “What and where in spatial language and spatial cognition,” proposing a friendly amendment and reformulation. The original paper emphasized the distinct geometries that are engaged when objects are represented as members of object kinds (named by count nouns), versus when they are represented as figure and ground in spatial expressions (i.e., play the role of arguments of spatial prepositions). We provided empirical and theoretical arguments for the link between these distinct representations in spatial language and their accompanying nonlinguistic neural representations, emphasizing the “what” and “where” systems of the visual system. In the present paper, I propose a second division of labor between two classes of spatial prepositions in English that appear to be quite distinct. One class includes prepositions such as in and on, whose core meanings engage force‐dynamic, functional relationships between objects, with geometry only a marginal player. The second class includes prepositions such as above/below and right/left, whose core meanings engage geometry, with force‐dynamic relationships a passing or irrelevant variable. The insight that objects’ force‐dynamic relationships matter to spatial terms’ uses is not new; but thinking of these terms as a distinct set within spatial language has theoretical and empirical consequences that are new. I propose three such consequences, rooted in the fact that geometric knowledge is highly constrained and early‐emerging in life, while force‐dynamic knowledge of objects and their interactions is relatively unconstrained and needs to be learned piecemeal over a lengthy timeline. First, the two classes will engage different learning problems, with different developmental trajectories for both first and second language learners; second, the classes will naturally lead to different degrees of cross‐linguistic variation; and third, they may be rooted in different neural representations.
Predicted Pleistocene–Holocene range shifts of the tiger (Panthera tigris)
Authors: Cooper David M. , Dugmore Andrew J. , Gittings Bruce M. , Scharf Anne K. , Wilting Andreas , Kitchener Andrew C.
Published: September 2016

Aim

In this article, we modelled the potential range shifts of tiger (Panthera tigris) populations over the Late Pleistocene and Holocene, to provide new insights into the evolutionary history and interconnectivity between populations of this endangered species.

Location

Asia.

Methods

We used an ecological niche approach and applied a maximum entropy (Maxent) framework to model potential distributions of tigers. Bioclimatic conditions for the present day and mid‐Holocene, and for the Last Glacial Maximum (LGM), were used to represent interglacial and glacial conditions of the Late Pleistocene, respectively.

Results

Our results show that the maximum potential tiger range during modern climates (without human impacts) would be continuous from the Indian subcontinent to north‐east Siberia. During the LGM, distributions are predicted to have contracted to southern China, India and Southeast Asia and remained largely contiguous. A potential distribution gap between Peninsular Malaya and Sumatra could have effectively separated tigers on the Sunda Islands from those in continental Asia during interglacials.

Main conclusions

The continuous modelled distribution of tigers in mainland Asia supports the idea of mainly unimpeded gene flow between all populations throughout the Late Pleistocene and Holocene. Thus, our data support a pragmatic approach to tiger conservation management, especially of mainland populations, as it is likely that only recent anthropogenic changes caused separation of these populations. In contrast, Sunda tigers are likely to have separated and differentiated following the Last Glacial Maximum and thus warrant separate management.
Residual contamination and bioburden after reprocessing of single‐use endoscopic ultrasound needles: An ex vivo study
Authors: Bhatia Vikram , Gupta Anu , Sharma Shweta , Shandil Rajeev , Wadhawan Manav , Agrawal Nitesh , Kumar Ajay
Published: September 2016

Background and Aim

Endoscopic ultrasound (EUS) aspiration needles are single‐use devices. However, in many centers, because of cost‐constraints, these devices are reused multiple times. We studied microbiological contamination and bioburden on reprocessed needles to evaluate whether these devices can be successfully sterilized.

Methods

We studied 10 EUS needles each of 19 G, 22 G, and 25 G in size, and five 22‐G ProCore needles. After initial use, each needle was reprocessed by a standardized protocol. We used standard microbiological cultures, as well as ATP bioluminescence technique to quantify bioburden as relative light units (RLU). We defined significant soil contamination by RLU values >200. We also used extractant fluid to disrupt cell membranes in an attempt to enhance ATP detection.

Results

We found culture positivity in 3/34 (8.8%), and detectable bioburden on the exposed surface of 33/35 (94.3%), and inside lumen of 29 (82.9%) reprocessed FNA needles. Significant bioburden was found in three (8.6%) and two (5.7%) needles on the surface and lumen, respectively. We found that use of extractant fluid enhanced detection of bioburden. Larger (19 G) needles had higher surface contamination (P = 0.016), but there was no relation of luminal contamination with needle diameter (P = 0.138). Sheath design and presence of side bevel did not influence extent of contamination. There was significant correlation between the surface and intraluminal bioburden (P < 0.001).

Conclusions

There is significant bioburden in reprocessed EUS needles; standard microbiological cultures have low sensitivity for detection of needle contamination. We have provided objective evidence for the futility of reprocessing attempts, and practice of EUS needle reuse should be discontinued.
Early impairment of somatosensory evoked potentials in very young children with achondroplasia with foramen magnum stenosis
Authors: Fornarino Stefania , Rossi Daniela Paola , Severino Mariasavina , Pistorio Angela , Allegri Anna Elsa Maria , Martelli Simona , Doria Lamba Laura , Lanteri Paola
Published: September 2016

Aim

To evaluate the contribution of somatosensory evoked potentials after median nerve (MN‐SEPs) and posterior tibial nerve (PTN‐SEPs) stimulation in functional assessment of cervical and lumbar spinal stenosis in children with achondroplasia.

Method

We reviewed MN‐SEPs, PTN‐SEPs, and spinal magnetic resonance imaging (MRI) examinations performed in 58 patients with achondroplasia (25 males, 33 females; age range 21d–16y 10mo; mean age 4y 3mo [SD 4y 1mo]). Patients were subdivided into four age categories: <2 years, between 2 to 4 years, between 4 to 8 years, and ≥8 years. The peak latency of P37 for PTN‐SEPs, the peak latencies of N11, N13, P14, and N20, and the N13–N20 interpeak latency (IPL) for MN‐SEPs were collected; the diagnostic accuracy measures of these parameters (analysis of receiver operating characteristic [ROC] curves) with respect to the presence of foramen magnum or lumbar spinal stenosis were analysed in each age category.

Results

The ROC curve analysis showed that the most sensitive parameter in detecting the presence of foramen magnum stenosis was P37 latency in the first two age categories (<2y and ≥2–4y; sensitivity 0.63, specificity 1.00, and sensitivity 1.00, specificity 0.75 respectively). In the third age category (≥4–8y), the most sensitive parameter in detecting the presence of foramen magnum stenosis was IPLs N13–N20 (sensitivity 0.73, specificity 0.87), whereas in the last age category (≥8y), the most important parameter was N20 latency (sensitivity 0.75, specificity 0.77).

Interpretation

In children with achondroplasia, the cortical component of PTN‐SEPs is more sensitive than the cortical component and central conduction time of MN‐SEPs in detection of cervical spinal cord compression at early ages.
Integration of research and clinical practice: the future is now
Authors: Stevenson Richard D
Published: September 2016

This commentary is on the original article by Lowes et al. on pages 183–191 of this issue.
Debt dilution in 1920s America: lighting the fuse of a mortgage crisis
Authors: Postel‐Vinay Natacha
Published: September 2016

The idea that real estate could have contributed to banking crises during the Great Depression has been downplayed due to the conservatism of mortgage contracts at the time. For instance, loan‐to‐value ratios often did not exceed 50 per cent. Using newly discovered archival documents and data from 1934, this article uncovers a darker side of 1920s US mortgage lending: the so‐called ‘second mortgage system’. As borrowers often could not make a 50 per cent down payment, a majority of them took second mortgages at usurious rates. As theory predicts, debt dilution, even in the presence of seniority rules, can be highly detrimental to both junior and senior lenders. The probability of default on first mortgages was likely to increase, and commercial banks were more likely to foreclose. Through foreclosure they would still be able to retrieve 50 per cent of the property value, but often after a protracted foreclosure process. This would have put further strain on banks during liquidity crises. This article is thus a timely reminder that second mortgages, or ‘piggyback loans’ as they are called today, can be hazardous to lenders and borrowers alike. It provides further empirical evidence that debt dilution can be detrimental to credit.
Do Birds Alter Levels of Parental Investment Based on Nest‐Site Habitat Features?
Authors: Merrill Loren , Baehl Elizabeth M. , Ripple Kaitlyn E. , Benson Thomas J.
Published: September 2016

Many habitats have undergone rapid changes over the past century as a result of anthropogenic activities. Organisms can respond to changes in their environment in many ways, including how much they invest in a given reproductive bout. Optimality theory and life history theory together have provided a framework for understanding how individuals make decisions about the risks and rewards of investing high levels of resources into their offspring within the context of current vs. future reproduction. Shrubland birds in the United States often breed in habitat that has been impacted by humans to varying degrees and provide an ideal system for examining whether organisms alter their levels of parental investment based on the habitat around the nest site. In this study, we assessed levels of nest‐defense behavior during a simulated nest predation event in four shrubland birds: American robins (Turdus migratorius), gray catbirds (Dumetella carolinensis), brown thrashers (Toxostoma rufum), and northern cardinals (Cardinalis cardinalis). We found that thrashers and catbirds exhibited significantly higher levels of nest defense compared to robins and cardinals and that birds with larger broods acted more aggressively in defending them. We also found that thrashers acted less aggressively as the proportion of shrubland around the nest increased and as the proportion of developed land around the nest decreased and that cardinals acted less aggressively as the proportion of developed land around the nest increased. These patterns suggest that nest‐defense behavior can covary with features of the landscape surrounding the nest, but that the factors shaping that behavior can differ by species.
Can We Fix This? Parent–Child Repair Processes and Preschoolers' Regulatory Skills
Authors: Kemp Christine J. , Lunkenheimer Erika , Albrecht Erin C. , Chen Deborah
Published: September 2016

The repair of difficult parent–child interactions is a marker of healthy functioning in infancy, but less is known about repair processes during early childhood. We used dynamic systems methods to investigate dyadic repair in mothers and their 3‐year‐old children (N = 96) and its prediction of children's emotion regulation and behavior problems at a 4‐month follow‐up. Mothers and children completed free play and challenging puzzle tasks. Repair was operationalized as the conditional probability of moving into a dyadic adaptive behavior region after individual or dyadic maladaptive behavior (e.g., child noncompliance, parental criticism). Overall, dyads repaired approximately half their maladaptive behaviors. A greater likelihood of repair during the puzzle task predicted better child emotion regulation and fewer behavior problems in preschool. Results suggest dyadic repair is an important process in early childhood and provide further evidence for the connection between parent–child coregulation and children's developing regulatory capacities. Implications for family‐based interventions are discussed.
The NtrY–NtrX two‐component system is involved in controlling nitrate assimilation in Herbaspirillum seropedicae strain SmR1
Authors: Bonato Paloma , Alves Lysangela R. , Osaki Juliana H. , Rigo Liu U. , Pedrosa Fabio O. , Souza Emanuel M. , Zhang Nan , Schumacher Jörg , Buck Martin , Wassem Roseli , Chubatsu Leda S.
Published: September 2016

Herbaspirillum seropedicae is a diazotrophic β‐Proteobacterium found endophytically associated with gramineae (Poaceae or graminaceous plants) such as rice, sorghum and sugar cane. In this work we show that nitrate‐dependent growth in this organism is regulated by the master nitrogen regulatory two‐component system NtrB–NtrC, and by NtrY–NtrX, which functions to specifically regulate nitrate metabolism. NtrY is a histidine kinase sensor protein predicted to be associated with the membrane and NtrX is the response regulator partner. The ntrYntrX genes are widely distributed in Proteobacteria. In α‐Proteobacteria they are frequently located downstream from ntrBC, whereas in β‐Proteobacteria these genes are located downstream from genes encoding an RNA methyltransferase and a proline‐rich protein with unknown function. The NtrX protein of α‐Proteobacteria has an AAA+ domain, absent in those from β‐Proteobacteria. An ntrY mutant of H. seropedicae showed the wild‐type nitrogen fixation phenotype, but the nitrate‐dependent growth was abolished. Gene fusion assays indicated that NtrY is involved in the expression of genes coding for the assimilatory nitrate reductase as well as the nitrate‐responsive two‐component system NarX–NarL (narK and narX promoters, respectively). The purified NtrX protein was capable of binding the narK and narX promoters, and the binding site at the narX promoter for the NtrX protein was determined by DNA footprinting. In silico analyses revealed similar sequences in other promoter regions of H. seropedicae that are related to nitrate assimilation, supporting the role of the NtrY–NtrX system in regulating nitrate metabolism in H. seropedicae.
Cell cycle proliferation decisions: the impact of single cell analyses
Authors: Matson Jacob P. , Cook Jeanette G.
Published: September 2016

Cell proliferation is a fundamental requirement for organismal development and homeostasis. The mammalian cell division cycle is tightly controlled to ensure complete and precise genome duplication and segregation of replicated chromosomes to daughter cells. The onset of DNA replication marks an irreversible commitment to cell division, and the accumulated efforts of many decades of molecular and cellular studies have probed this cellular decision, commonly called the restriction point. Despite a long‐standing conceptual framework of the restriction point for progression through G1 phase into S phase or exit from G1 phase to quiescence (G0), recent technical advances in quantitative single cell analysis of mammalian cells have provided new insights. Significant intercellular heterogeneity revealed by single cell studies and the discovery of discrete subpopulations in proliferating cultures suggests the need for an even more nuanced understanding of cell proliferation decisions. In this review, we describe some of the recent developments in the cell cycle field made possible by quantitative single cell experimental approaches.
Dexamethasone improves redox state in ataxia telangiectasia cells by promoting an NRF2‐mediated antioxidant response
Authors: Biagiotti Sara , Menotta Michele , Orazi Sara , Spapperi Chiara , Brundu Serena , Fraternale Alessandra , Bianchi Marzia , Rossi Luigia , Chessa Luciana , Magnani Mauro
Published: September 2016

Ataxia telangiectasia (A‐T) is a rare incurable neurodegenerative disease caused by biallelic mutations in the gene for ataxia‐telangiectasia mutated (ATM). The lack of a functional ATM kinase leads to a pleiotropic phenotype, and oxidative stress is considered to have a crucial role in the complex physiopathology. Recently, steroids have been shown to reduce the neurological symptoms of the disease, although the molecular mechanism of this effect is largely unknown. In the present study, we have demonstrated that dexamethasone treatment of A‐T lymphoblastoid cells increases the content of two of the most abundant antioxidants [glutathione (GSH) and NADPH] by up to 30%. Dexamethasone promoted the nuclear accumulation of the transcription factor nuclear factor (erythroid‐derived 2)‐like 2 to drive expression of antioxidant pathways involved in GSH synthesis and NADPH production. The latter effect was via glucose 6‐phosphate dehydrogenase activation, as confirmed by increased enzyme activity and enhancement of the pentose phosphate pathway rate. This evidence indicates that glucocorticoids are able to potentiate antioxidant defenses to counteract oxidative stress in ataxia telangiectasia, and also reveals an unexpected role for dexamethasone in redox homeostasis and cellular antioxidant activity.
Environmental and spatial characterisation of an unknown fauna using DNA sequencing – an example with Himalayan Hydropsychidae (Insecta: Trichoptera)
Authors: Hoppeler Felicitas , Tachamo Shah Ram Devi , Shah Deep Narayan , Jähnig Sonja C. , Tonkin Jonathan D. , Sharma Subodh , Pauls Steffen U.
Published: September 2016

Ecological studies of freshwater biota in understudied regions are often obstructed by poor taxonomic knowledge. We posit that molecular tools can help alleviate this issue and present an example where we combined molecular tools, environmental data and ecological statistics to investigate the distribution and community ecology of an unknown fauna of hydropsychid caddisflies along altitudinal gradients in four Himalayan river systems of Central and Eastern Nepal.

A total of 484 larval specimens from 34 tributaries were examined. Phylogenetic analysis of the mitochondrial cytochrome c oxidase I (COI) and the nuclear ribosomal RNA 28S were used to delineate molecular operational taxonomic units (MOTUs) applying three analytical methods: general mixed Yule‐coalescent (GMYC) model, Automatic Barcode Gap Discovery (ABGD) and Bayesian Phylogenetics and Phylogeography (BPP). Spatial distributional patterns and potential differences in ecological niches among MOTUs were statistically tested using regression and correlation approaches. Further, we examined the data for signs of non‐random structure in MOTU communities.

MOTU diversity within the family of Hydropsychidae was generally high but varied across evaluated gene fragments and slightly among delineation methods. Yet, the subsequent evaluation of environmental and spatial drivers and resulting distributional patterns were highly consistent among the different MOTU estimates.

Within each river system, we found community composition varied greatly along the altitudinal gradients, with many MOTUs associated with specific altitudinal ranges. Prevalent MOTU turnover at the river system scale indicated high β‐diversity in the hydropsychid community leading to high degrees of regional endemism. In the Langtang river system, we found fewer MOTU co‐occurrences than expected by chance.

These results highlight the utility of DNA‐based approaches using variable genetic markers (mitochondrial or ribosomal nuclear) for primary biodiversity assessment of poorly studied groups or regions. Our study further shows that DNA‐based biodiversity measures are suitable for downstream applications, such as exploring fundamental questions in stream ecology.
Pushing precipitation to the extremes in distributed experiments: recommendations for simulating wet and dry years
Authors: Knapp Alan K. , Avolio Meghan L. , Beier Claus , Carroll Charles J. W. , Collins Scott L. , Dukes Jeffrey S. , Fraser Lauchlan H. , Griffin‐Nolan Robert J. , Hoover David L. , Jentsch Anke , Loik Michael E. , Phillips Richard P. , Post Alison K. , Sala Osvaldo E. , Slette Ingrid J. , Yahdjian Laura , Smith Melinda D.
Published: September 2016

Intensification of the global hydrological cycle, ranging from larger individual precipitation events to more extreme multiyear droughts, has the potential to cause widespread alterations in ecosystem structure and function. With evidence that the incidence of extreme precipitation years (defined statistically from historical precipitation records) is increasing, there is a clear need to identify ecosystems that are most vulnerable to these changes and understand why some ecosystems are more sensitive to extremes than others. To date, opportunistic studies of naturally occurring extreme precipitation years, combined with results from a relatively small number of experiments, have provided limited mechanistic understanding of differences in ecosystem sensitivity, suggesting that new approaches are needed. Coordinated distributed experiments (CDEs) arrayed across multiple ecosystem types and focused on water can enhance our understanding of differential ecosystem sensitivity to precipitation extremes, but there are many design challenges to overcome (e.g., cost, comparability, standardization). Here, we evaluate contemporary experimental approaches for manipulating precipitation under field conditions to inform the design of ‘Drought‐Net’, a relatively low‐cost CDE that simulates extreme precipitation years. A common method for imposing both dry and wet years is to alter each ambient precipitation event. We endorse this approach for imposing extreme precipitation years because it simultaneously alters other precipitation characteristics (i.e., event size) consistent with natural precipitation patterns. However, we do not advocate applying identical treatment levels at all sites – a common approach to standardization in CDEs. This is because precipitation variability varies >fivefold globally resulting in a wide range of ecosystem‐specific thresholds for defining extreme precipitation years. For CDEs focused on precipitation extremes, treatments should be based on each site's past climatic characteristics. This approach, though not often used by ecologists, allows ecological responses to be directly compared across disparate ecosystems and climates, facilitating process‐level understanding of ecosystem sensitivity to precipitation extremes.
Injection‐induced seismicity in Carbon and Emery Counties, central Utah
Authors: Brown M. R. M. , Liu M.
Published: September 2016

Utah is one of the top producers of oil and natural gas in the United States. Over the past 18 years, more than 4.2 billion gallons of wastewater from the petroleum industry has been injected into the Navajo Sandstone, Kayenta Formation, and Wingate Sandstone in Carbon and Emery Counties, central Utah, where seismicity has increased during the same period. Previous studies have attributed this seismicity to coal mining. Here, we present evidence for wastewater injection being a major cause of the increased seismicity. We show that, in the coal mining area, seismicity rate increased significantly 1–5 years following the wastewater injection, and the earthquakes, mostly with magnitudes <3.0, are concentrated in areas seismically active prior to the injection. Using simple analytical and numerical models, we show that the injection in central Utah can sufficiently raise pore pressure to trigger seismicity within 10–20 km of the injection wells, and the time needed for the diffusion of pore pressure may explain the observed lag of seismicity increase behind the commencement of injection. The b‐value of these earthquakes increased following the wastewater injection, which is consistent with these events being injection‐induced. We conclude that the marked increase in seismicity rate in central Utah is induced by both mining activity and wastewater injection, which raised pore pressure along preexisting faults.
The biases and trends in fault zone hydrogeology conceptual models: global compilation and categorical data analysis
Authors: Scibek J. , Gleeson T. , McKenzie J. M.
Published: September 2016

To investigate the biases and trends in observations of the permeability structures of fault zones in various geoscience disciplines, we review and compile a database of published studies and reports containing more than 900 references. The global data are categorized, mapped, and described statistically. We use the chi‐square test for the dependency of categorical variables to show that the simplified fault permeability structure (barrier, conduit, barrier–conduit) depends on the observation method, geoscience discipline, and lithology. In the crystalline rocks, the in situ test methods (boreholes or tunnels) favor the detection of permeable fault conduits, in contrast to the outcrop‐based measurements that favor a combined barrier–conduit conceptual models. These differences also occur, to a lesser extent, in sedimentary rocks. We provide an estimate of the occurrence of fault conduits and barriers in the brittle crust. Faults behave as conduits at 70% of sites, regardless of their barrier behavior that may also occur. Faults behave as barriers at at least 50% of the sites, in addition to often being conduits. Our review of published data from long tunnels suggests that in crystalline rocks, 40–80% (median about 60%) of faults are highly permeable conduits, and 30–70% in sedimentary rocks. The trends with depth are not clear, but there are less fault conduits counted in tunnels at the shallowest depths. The barrier hydraulic behavior of faults is more uncertain and difficult to observe than the conduit.
Palliative care needs and symptoms of nursing home residents with and without dementia: A cross‐sectional study
Authors: Hermans Kirsten , Cohen Joachim , Spruytte Nele , Van Audenhove Chantal , Declercq Anja
Published: September 2016

Aim

The aims of the present study were: (i) to describe palliative care needs and symptoms of older adults anticipated to be in the last year of their life in Flemish nursing homes (Belgium); and (ii) to evaluate whether these needs differ between residents with and without dementia.

Methods

A cross‐sectional study was carried out in 2014. Nurses and nursing assistants in 15 Flemish nursing homes (Belgium) completed the Palliative care Outcome Scale for 109 residents with palliative care needs.

Results

Pain, as well as other physical symptoms, was present in more than half of the nursing home residents according to caregivers. The most prominent needs occurred on psychosocial and spiritual domains, such as patient anxiety, support, finding life worth living and self‐worth. Caregivers reported that residents with dementia experienced fewer physical symptoms apart from pain than did residents without dementia (coeffficient –0.73, 95% CI –1.18–0.84; P = 0.001. Furthermore, residents with dementia received higher scores on the items “support” (coefficient 0.75; 95% CI 0.15–1.34, P = 0.015), “life worthwhile” (coeffficient 0.58; 95% CI 0.090–1.07, P = 0.020) and “self‐worth” (coefficient 0.58, 95% CI 0.13–1.03, P = 0.012).

Conclusions

According to caregivers, residents with dementia experienced fewer other physical symptoms (e.g. nausea) than residents without dementia. This, however, might be a result of an underdetection of other symptoms in nursing home residents with dementia. Furthermore, most challenges in nursing homes lie within the spiritual and psychosocial domains of palliative care, particularly in people with dementia. These aspects should be integrated in the professional education of caregivers. Assessment tools might be of help to improve the identification of needs and symptoms. Geriatr Gerontol Int 2017; 17: 1501–1507.
TRPM8 and Migraine
Authors: Dussor Greg , Cao Yu‐Qing
Published: September 2016

Migraine is among the most common diseases on earth and one of the most disabling, the latter due in large part to poor treatment efficacy. Development of new therapeutics is dependent on the identification of mechanisms contributing to migraine and discovery of targets for new drugs. Numerous genome‐wide association studies (GWAS) have implicated the transient receptor‐potential M8 (TRPM8) channel in migraine. This channel is predominantly expressed on peripheral sensory neurons and is known as the sensor for cold temperature in cutaneous tissue but is also expressed on deep visceral afferents where cold is not likely a stimulus. Consequently, a number of alternative endogenous agonists have been proposed. Apart from its role in cold sensation, TRPM8 also contributes to cold allodynia after nerve injury or inflammation, and it is necessary for cooling/menthol‐based analgesia. How it might contribute to migraine is less clear. The purpose of this review is to discuss the anatomical and physiological mechanisms by which meningeal TRPM8 may play a role in migraine as well as the potential of TRPM8 as a therapeutic target. TRPM8 is expressed on sensory afferents innervating the meninges, and these neurons are subject to developmental changes that may influence their contribution to migraine. As in viscera, meningeal TRPM8 channels are unlikely to be activated by temperature fluctuations and their endogenous ligands remain unknown. Preclinical migraine studies show that activation of meningeal TRPM8 by exogenous agonists can both cause and alleviate headache behaviors, depending on whether other meningeal afferents concurrently receive noxious stimuli. This is reminiscent of the fact that cold can trigger migraine in humans but menthol can also alleviate headache. We propose that both TRPM8 agonists and antagonists may be potential therapeutics, depending on how migraine is triggered in individual patients. In this regard, TRPM8 may be a novel target for personalized medicine in migraine treatment.
Mutational landscape of combined hepatocellular carcinoma and cholangiocarcinoma, and its clinicopathological significance
Authors: Sasaki Motoko , Sato Yasunori , Nakanuma Yasuni
Published: September 2016

Aims

Combined hepatocellular carcinoma and cholangiocarcinoma (cHC‐CC), which generally has a poor prognosis, comprises hepatocellular carcinoma (HCC), cholangiocarcinoma (CC), and diverse components with intermediate features between HCC and CC. Histological subtypes with stem cell (SC) features (the SC subtype) have different clinicopathological significance in cHC‐CC. The mutational status may reflect the clinicopathological subgroup of cHC‐CC together with the histological subtype.

Methods and results

We examined the mutational statuses of KRAS, IDH1 or IDH2 (IDH1/2), ARID1A, the TERT promoter, and TP53, and their relationships with clinicopathological features in 53 patients with cHC‐CC. Background liver diseases were hepatitis B (n = 9), hepatitis C (n = 22), alcoholic liver disease (n = 5), non‐alcoholic fatty liver disease (NAFLD) (n = 8), and unknown (n = 9). Mutations in KRAS, IDH1/2, ARID1A, the TERT promoter and TP53 were detected in four (7.5%), six (11.8%) seven (13.2%), 16 (31.3%), and 24 patients (45.3%), respectively. KRAS mutations correlated with higher histological diversity scores and a higher M‐factor (P < 0.05). ARID1A mutations correlated with alcoholic liver disease, smaller tumour size, a lower grade of coexistent HCC, and α‐fetoprotein (AFP) positivity, and were associated with cholangiolocellular carcinoma subtype predominance (P < 0.05). TERT promoter mutations correlated with hepatitis B, an intermediate subtype‐predominant histology, higher clinical stage, and a higher N‐factor (P < 0.05), and were associated with gender (female‐predominant) and previous therapy. TP53 mutations correlated with AFP positivity (P < 0.05).

Conclusions

The results of the mutational analysis revealed that cHC‐CC has diverse types of mutations, and also that mutations in the TERT promoter and ARID1A may reflect aetiological impact, different histological subtypes, histogenesis, and tumour aggressiveness. These results suggest the potential efficacy of molecular‐based subclassification of cHC‐CC.
Superficial CD34‐positive fibroblastic tumour: a clinicopathological and immunohistochemical study of an additional series
Authors: Lao I Weng , Yu Lin , Wang Jian
Published: September 2016

Aims

To describe an additional series of superficial CD34‐positive fibroblastic tumour, a newly described neoplasm, in order to enhance the recognition of an emerging novel entity.

Methods and results

The clinicopathological features and immunophenotypes of 11 cases of superficial CD34‐positive fibroblastic tumour were studied. There were eight males and three females, with a median age of 36 years. Tumours occurred in the thigh (n = 4), buttock (n = 3), shoulder (n = 2), upper arm (n = 1), and waist (n = 1). Histologically, all tumours were characterized by relative circumscription, pleomorphic spindled to polygonal cells with variably enlarged bizarre‐appearing cells, intranuclear cytoplasmic pseudoinclusions, and extremely low mitotic activity. Immunohistochemically, neoplastic cells showed diffuse and strong expression of CD34 and focal staining of cytokeratin. Follow‐up thus far has revealed an indolent clinical behaviour.

Conclusions

Superficial CD34‐positive fibroblastic tumour represents a new member of the family of cutaneous CD34‐positive spindle‐cell tumours. Familiarity with its clinicopathological characteristics is helpful in avoiding confusion with a variety of cutaneous mesenchymal tumours with overlapping features.
Floral abundance and resource quality influence pollinator choice
Authors: Fowler Robert E. , Rotheray Ellen L. , Goulson Dave
Published: September 2016

Pollinator declines caused by forage habitat loss threaten insect pollination services. Pollinating insects depend on adequate floral resources, and their ability to track these resources. Variability of these resources and the effect on insect foraging choice is poorly understood.

We record patterns of visitation to six wildflower species and test the hypotheses that: pollinators preferentially visit the most rewarding flowers; nectar diurnal variations affect foraging preferences; pollinators respond most strongly to nectar rewards.

Nectar volume and sugar concentration were negatively correlated within plant species over time of day where greater concentration and lower volume was evident in the afternoon, but this did not correspond to pollinator visitation. Both floral abundance and nectar quality (total sugar per inflorescence) positively affect insect visitation. For some foragers, the positive effects of high‐quality rewards were only evident when floral abundance was high (>50 inflorescences per patch), perhaps reflecting the low probability of pollinators detecting scarce rewards. Pollen quality (total protein per inflorescence) was negatively related to visitation of Apis mellifera and Bombus pascuorum.

Fewer pollinators visiting flowers of higher pollen quality could reflect plant allocation trade‐offs or the presence of secondary metabolites in pollen, meaning pollen foraging is likely affected by factors other than protein concentration. Nectar rather than pollen appeared to be the main driver of floral choice by insects in this system.

Conservation schemes for bees in farmland or gardens might benefit from ensuring that rewarding plant species are present at high density and/or are aggregated in space.
A mixed methods study of the administration of flucloxacillin oral liquid; identifying strategies to overcome administration issues of medicines with poor palatability
Authors: Rouse Claudia , Mistry Punam , Rayner Oli , Nickless Jess , Wan Mandy , Southern Kevin W , Batchelor Hannah K
Published: September 2016

Background

The palatability of flucloxacillin oral liquid is poor. Parents/carers use strategies to aid the administration of poorly palatable medicines.

Aim

To assess views on the palatability of flucloxacillin oral liquid and identify factors associated with successful administration.

Methods

A mixed methods study which included a structured review of online forums and a survey of parent/carers of children with cystic fibrosis (CF) to obtain parent/carer views on the administration of flucloxacillin oral liquid.

Results

A total of 18 strategies to aid the administration of flucloxacillin suspension to children were identified on 10 different public online forums. A total of 255 responses to the open online survey were received with 47% of respondents reporting that administration of flucloxacillin was more problematic compared to other medicines and 38% reporting the need to improve the palatability.

The brand of flucloxacillin oral liquid significantly influenced the degree of difficulty associated with administration to children. A significant relationship was found between the concentration of flucloxacillin and the reported number of doses successfully administered. The use of food and drink to aid administration was more commonly stated in online forums (44%) compared to the survey data of parents/carers of children with CF (15.9%).

Conclusion

The administration of flucloxacillin oral liquid is perceived as a challenge by parent/carers because of palatability. For chronic use, a more concentrated oral liquid and certain brands are likely to improve acceptability.
Your position in society matters for how happy you are
Authors: Ejrnæs Anders , Greve Bent
Published: September 2016

This article shows that people's perception of their position in society is strongly correlated with their level of happiness, and thus that differences in happiness levels among countries in different welfare state clusters are influenced by people's perceptions of their relative position in society (subjective position). The study drew on data from the European Social Survey. Two important findings emerged from the analysis. First, an individual's subjective position in society is a more important predictor of happiness than objective measures such as income, education and labour market position. Second, the link between individuals’ perceived position in society and their level of happiness is moderated by the welfare state. In the Nordic countries, people's perceptions of their position in society have less influence on happiness whereas in Eastern European countries we found a strong connection between subjective position and happiness.
Eosinophilic myocarditis: characteristics, diagnostics and outcomes of a rare condition
Authors: Wang T. K. M. , Watson T. , Pemberton J. , Pemberton L. , Lowe B. , Ellis C. , Kingston N. , Ruygrok P.
Published: September 2016

Eosinophilic myocarditis is a rare and potentially fatal condition characterised by eosinophilic inflammatory infiltration of myocardium. We report seven consecutive cases of eosinophilic myocarditis at our centre and discuss the important characteristics, investigation and management of this disease.
Gene editing advance re‐ignites debate on the merits and risks of animal to human transplantation
Authors: Fung R. K. F. , Kerridge I. H.
Published: September 2016

In Australia, and internationally, the shortage of organ and tissue donors significantly limits the number of patients with critical organ or tissue failure who are able to receive a transplant each year. The rationale for xenotransplantation – the transplantation of living cells, tissues or organs from one species to another – is to meet this shortfall in human donor material. While early clinical trials showed promise, particularly in patients with type I diabetes whose insulin dependence could be temporarily reversed by the transplantation of porcine islet cells, these benefits have been balanced with scientific, clinical and ethical concerns revolving around the risks of immune rejection and the potential transmission of porcine endogenous retroviruses or other infectious agents from porcine grafts to human recipients. However, the advent of CRISPR/Cas9, a revolutionary gene editing technology, has reignited interest in the field with the possibility of genetically engineering porcine organs and tissues that are less immunogenic and have virtually no risk of transmission of porcine endogenous retroviruses. At the same time, CRISPR/Cas9 may also open up a myriad of possibilities for tissue engineering and stem cell research, which may complement xenotransplantation research by providing an additional source of donor cells, tissues and organs for transplantation into patients. The recent international symposium on gene editing, organised by the US National Academy of Sciences, highlights both the enormous therapeutic potential of CRISPR/Cas9 and the raft of ethical and regulatory challenges that may follow its utilisation in transplantation and in medicine more generally.
The role of mucosal‐associated invariant T cells in infectious diseases
Authors: Wong Emily B. , Ndung'u Thumbi , Kasprowicz Victoria O.
Published: September 2016

Mucosal‐associated invariant T (MAIT) cells are donor‐unrestricted lymphocytes that are surprisingly abundant in humans, representing 1–10% of circulating T cells and further enriched in mucosal tissues. MAIT cells recognize and are activated by small molecule ligands produced by microbes and presented by MR1, a highly conserved MHC‐related antigen‐presenting protein that is ubiquitously expressed in human cells. Increasing evidence suggests that MAIT cells play a protective role in anti‐bacterial immunity at mucosal interfaces. Some fungi are known to produce MAIT‐activating ligands, but the role of MAIT cells in fungal infections has not yet been investigated. In viral infections, specifically HIV, which has received the most study, MAIT cell biology is clearly altered, but the mechanisms explaining these alterations and their clinical significance are not yet understood. Many questions remain unanswered about the potential of MAIT cells for protection or pathogenesis in infectious diseases. Because they interact with the universal, donor‐unrestricted ligand‐presenting MR1 molecule, MAIT cells may be attractive immunotherapy or vaccine targets. New tools, including the development of MR1‐ligand tetramers and next‐generation T‐cell receptor sequencing, have the potential to accelerate MAIT cell research and lead to new insights into the role of this unique set of lymphocytes in infectious diseases.
Positive psychotherapy for depression and self‐efficacy in undergraduate nursing students: A randomized, controlled trial
Authors: Guo Yu‐Fang , Zhang Xia , Plummer Virginia , Lam Louisa , Cross Wendy , Zhang Jing‐Ping
Published: September 2016

Nursing students across the globe experience depressive symptoms, and many interventions have been used to alleviate their depression. However, few interventions focus on students' personal strengths and advantages. The aim of the present study was to explore the effects of an 8‐week group positive psychotherapy (PPT) programme on depression and self‐efficacy in full‐time undergraduate nursing students. A randomized, controlled trial was conducted for 76 nursing students (34 in the experimental group, 42 in the control group). The Beck Depression Inventory‐II and the General Self‐Efficacy Scale were used to collect data prior to, immediately after PPT, 3 months', and 6 months' post‐PPT. Repeated‐measures analysis of variance indicated that the intervention significantly alleviated depression and improved self‐efficacy (each P < 0.05); the effect of time and time–group interaction was also significant (each P < 0.05). The findings suggest that PPT could significantly relieve depressive symptoms and improve self‐efficacy. We recommend that PPT is effective in alleviating depression and improving self‐efficacy in undergraduate nursing students. Academic mental health nurses should appreciate the value of PPT and consider incorporating it in psychological support methods in order to facilitate nursing students' mental health.
Feelings Thermometer: An Early Intervention Scale for Seclusion/Restraint Reduction Among Children and Adolescents in Residential Psychiatric Care
Authors: Andrassy Briana Marie
Published: September 2016

PROBLEM

Restraints and/or seclusions (R/S) are events that have the potential to cause patient injury, staff injury, re‐traumatization, and even death. There is a gap in available data regarding alternative strategies for reducing R/S.

METHOD

A 140‐bed children and adolescent residential treatment hospital implemented a “Feelings Thermometer Scale” on each unit. The “Feelings Thermometer” allowed the resident to point to a face on the scale to rate how they were feeling from “Cool” to “On Fire!” Once the resident identified with a feeling and rating, options were offered for alternative cool down locations corresponding to each level of escalation. Data were analyzed 6 weeks before and 6 weeks after implementation of the “Feelings Thermometer.”

FINDINGS

There were 129 R/S during the 6‐week period prior to the implementation of the “Feelings Thermometer.” There were a total of 91 R/S during the 6‐week period postimplementation of the “Feelings Thermometer.” Overall, a 29.1% decrease in R/S was experienced throughout the hospital.

CONCLUSION

The findings of this study suggest that further investigation may be warranted to promote alternative R/S reduction strategies.
Assessing reproductive isolation using a contact zone between parapatric lake‐stream stickleback ecotypes
Authors: Hanson D. , Moore J.‐S. , Taylor E. B. , Barrett R. D. H. , Hendry A. P.
Published: September 2016

Ecological speciation occurs when populations evolve reproductive isolation as a result of divergent natural selection. This isolation can be influenced by many potential reproductive barriers, including selection against hybrids, selection against migrants and assortative mating. How and when these barriers act and interact in nature is understood for relatively few empirical systems. We used a mark–recapture experiment in a contact zone between lake and stream three‐spined sticklebacks (Gasterosteus aculeatus, Linnaeus) to evaluate the occurrence of hybrids (allowing inferences about mating isolation), the interannual survival of hybrids (allowing inferences about selection against hybrids) and the shift in lake‐like vs. stream‐like characteristics (allowing inferences about selection against migrants). Genetic and morphological data suggest the occurrence of hybrids and no selection against hybrids in general, a result contradictory to a number of other studies of sticklebacks. However, we did find selection against more lake‐like individuals, suggesting a barrier to gene flow from the lake into the stream. Combined with previous work on this system, our results suggest that multiple (most weakly and often asymmetric) barriers must be combining to yield substantial restrictions on gene flow. This work provides evidence of a reproductive barrier in lake–stream sticklebacks and highlights the value of assessing multiple reproductive barriers in natural contexts.