bluuebunny/crossref_metadata_2025 huggingface dataset:
Tolerability and efficacy of perampanel in children with refractory epilepsy
Authors: Heyman Eli , Lahat Eli , Levin Noa , Epstein Orna , Lazinger Mirit , Berkovitch Matitiahu , Gandelman‐Marton Revital
Published: December 2016

Aim

There are few reports on the tolerability and efficacy of perampanel, a new antiepileptic drug with a novel mechanism of action, in children and adolescents. We aimed to describe our experience with perampanel add‐on and mono‐therapy in children with refractory epilepsy.

Method

Computerized medical records of children treated with perampanel in the paediatric neurology clinic from December 2012 to October 2015 were reviewed.

Results

Twenty‐four children treated with perampanel (15 females, 9 males) aged 1 year 6 months to 17 years (mean 10y, standard deviation [SD] 4y 5mo) were identified. Adverse events were more common in children aged 12 years or older (89%) compared to younger children (53%), and were mainly behavioural. Ten (42%) children had 50 per cent or higher seizure reduction, two (8%) children had 33 per cent seizure reduction, and seizures were less severe in one (4%) child. Perampanel was discontinued in 13 (54%) children mostly due to adverse events. The mean duration of follow‐up in the remaining 11 children was 8.1 months (SD 5.2) (range 1.3–17mo).

Interpretation

Perampanel is associated with a relatively high rate of behavioural adverse events mostly in adolescents with refractory epilepsy.
Long‐term use of dipeptidyl peptidase‐4 inhibitors and risk of fracture: A retrospective population‐based cohort study
Authors: Driessen Johanna H. M. , van den Bergh Joop P. W. , van Onzenoort Hein A. W. , Henry Ronald M. A. , Leufkens Hubert G. M. , de Vries Frank
Published: December 2016

Aims

To investigate the association between long‐term dipeptidyl peptidase‐4 (DPP‐4) inhibitor use and risk of fracture among people with type 2 diabetes mellitus (T2DM).

Methods

A retrospective population‐based cohort study, using data from the Clinical Practice Research Datalink database (2007‐2015), was conducted. All those (N = 328 254) with at least one prescription for a non‐insulin antidiabetic drug (NIAD), aged ≥18 years at the time of data collection, were included. Cox proportional hazards models were used to estimate the hazard ratios of any fracture, osteoporotic fracture and hip fracture in DPP‐4 inhibitor users compared with those using other NIADs. Analyses were stratified by continuous duration of DPP‐4 inhibitor use. Time‐dependent adjustments were made for age, sex, lifestyle, comorbidity and concomitant drug use.

Results

Current use of DPP‐4 inhibitors was not associated with risk of any fracture (adjusted hazard ratio [HR] 0.99 [95% confidence interval {CI} 0.93‐1.06]) as compared with current other NIAD use. Current use of DPP‐4 inhibitors was also not associated with risk of osteoporotic or hip fracture. After stratification by continuous duration of DPP‐4 inhibitor use the highest category was not associated with any (>4.0‐8.5 years of use, adjusted HR 0.99 [95% CI 0.70‐1.41]), osteoporotic (>3.0‐8.5 years of use, adjusted HR 0.75 [95% CI 0.52‐1.09]) or hip (>2.0‐8.5 years of use; adjusted HR 1.24 [95% CI 0.85‐1.79]) fracture.

Conclusion

Continuous long‐term DPP‐4 inhibitor use (defined as >4.0‐8.5 years of DPP‐4 inhibitor use for any fracture, >3.0‐8.5 years for osteoporotic fracture and >2.0‐8.5 years for hip fracture was not associated with risk of any, osteoporotic or hip fracture. These findings may be of value for clinical decisions regarding treatment of patients with T2DM, especially those at high risk of fracture.
Effect of race and ethnicity on vildagliptin efficacy: A pooled analysis of phase II and III studies
Authors: Kozlovski Plamen , Fonseca Marilia , Mohan Viswanathan , Lukashevich Valentina , Odawara Masato , Paldánius Päivi M. , Kothny Wolfgang
Published: December 2016

Aims

To determine the impact of race and ethnicity on the efficacy, body weight and hypoglycaemia incidence with vildagliptin treatment in patients with type 2 diabetes mellitus using patient‐level data from the vildagliptin clinical trial programme.

Methods

Data from 22 randomized, placebo‐controlled global and local (Japan, China) registration studies of vildagliptin (50 mg once‐daily or twice‐daily) of ≥12‐week duration were analysed by race (Caucasian [n = 2764] and Asian [n = 2232]) and by ethnicity (Japanese, Chinese, and Indian). The placebo‐subtracted differences in the change in glycated haemoglobin (HbA1c) and body weight from baseline to week 12 or week 24 were evaluated by race or ethnicity using repeated measure analysis of unstructured covariance. Hypoglycaemia incidences were summarized using descriptive statistics.

Results

The HbA1c reduction from baseline with vildagliptin was similar across the racial/ethnic subgroups (−0.83% ± 0.02% to −1.01% ± 0.05%). Placebo‐corrected HbA1c reduction was similar between Caucasian (−0.68% ± 0.03%) and Asian (−0.80% ± 0.03%) patients (
P
value for interaction = .56); analysis by race and ethnicity showed better efficacy (
P
< .02) in Japanese patients. Japanese patients were drug‐naïve and treated with a single oral anti‐diabetes drug only; they showed no response to placebo. Weight neutrality of vildagliptin was demonstrated in all groups (0.47 ± 0.11 kg to −0.29 ± 0.08 kg). Hypoglycaemic events (≥1) were infrequent in all ethnic subgroups.

Conclusions

The glycaemic efficacy of vildagliptin was similar in Caucasian and Asian patients. The slightly better efficacy observed in Japanese patients was driven by the absence of placebo effect and might be explained by their earlier stage of diabetes compared to other subgroups.
Density dependence and temporal plasticity of competitive interactions during utilisation of resources by a community of lepidopteran stemborer species
Authors: Ntiri Eric Siaw , Calatayud Paul‐Andre , Van den Berg Johnnie , Le Ru Bruno Pierre
Published: December 2016

Interactions within and between species sharing the same resources are characterised by competition or facilitation, and can be influenced by factors such as larval numbers and phenotypic plasticity of the interactions. The effect of larval density on the survival and relative growth rate of the stemborers Busseola fusca (Fuller) and Sesamia calamistis Hampson (both Lepidoptera: Noctuidae), and Chilo partellus (Swinhoe) (Lepidoptera: Crambidae) were studied, as well as the temporal plasticity of their competitive interactions. These stemborers attack maize crops (Zea mays L.) (Poaceae) in sub‐Saharan Africa. Experiments were conducted in the laboratory under controlled conditions at the optimum development temperature (25 °C) for the three species. Surrogate stems filled with artificial diet were intra‐ and interspecifically infested with larvae of each species. The effect of larval density on competition was studied at low (six larvae) and high (12 larvae) levels of infestation, whereas the temporal plasticity of competition was evaluated at 7, 14, 21, or 28 days after infestation. The two experiments involved single‐ and multi‐species infestation treatments. Larval numbers and wet mass in each artificial stem were recorded in each experiment. Survival and relative growth rate of the three species were significantly higher at low‐infestation levels when facing either intra‐ or interspecific competition. The intensity of competition was also temporally plastic among the species and increased as the duration of competition increased. These results are discussed in terms of general infestations of cereal crops by borers.
Influence of no‐tillage practices and later planting date on the pea leaf weevil, Sitona lineatus, in pea, Pisum sativum
Authors: Hanavan Ryan P. , Bosque‐Pérez Nilsa A.
Published: December 2016

The pea leaf weevil, Sitona lineatus (L.) (Coleoptera: Curculionidae), is a periodic pest of pea, Pisum sativum L. (Fabaceae), in the Palouse region of northern Idaho and eastern Washington, USA. Previous work on‐station and in commercial pea fields showed initial adult weevil colonization was greater in conventional‐tillage than in no‐tillage fields. Increased surface residue of no‐tillage systems results in cooler soils with greater available moisture typically resulting in later planting dates for conventional‐tillage fields. Cereal residue, a characteristic of the region's no‐tillage systems, and planting date were investigated as potential inhibitors of adult pea leaf weevil colonization and feeding on peas via field experiments in 2005 and 2006. Plots without cereal residue and early‐planted plots had greater weevil abundance. Early‐planted peas had greater weevil feeding injury compared to late‐planted peas. The presence of cereal residue did not significantly impact injury levels. A laboratory choice‐test with peas grown in conventional‐tillage and no‐tillage fields indicated greater adult weevil feeding damage on conventional‐tillage‐grown peas. A separate laboratory choice‐test using peas planted 10 days apart demonstrated greater adult weevil feeding injury on early‐planted peas. However, adjusting for available leaf edge resulted in no differences between treatments in either choice test, indicating crop availability and plant apparency during peak weevil colonization rather than plant factors resulting from growing conditions likely explain greater injury on peas planted early and under conventional‐tillage in the field.
Mapping of QTLs conferring resistance in rice to brown planthopper, Nilaparvata lugens
Authors: Shabanimofrad M. , Rafii M.Y. , Ashkani S. , Hanafi M.M. , Adam N.A. , Harun A.R. , Latif M.A. , Miah G. , Sahebi M. , Azizi P.
Published: December 2016

Brown planthopper (BPH), Nilaparvata lugens Stål (Hemiptera: Delphacide), is a destructive insect pest of rice, Oryza sativa L. (Poaceae), in rice‐producing areas worldwide. Host plant resistance is a major aspect of managing this pest. In this study, a mapping population consisting of 150 F3 lines, derived from a cross of MR276 and Rathu Heenati, was used to detect and analyse quantitative trait loci (QTLs) for the resistance to BPH. Composite Interval Mapping (CIM) was used for QTL detection. In total 10 QTLs controlling BPH resistance were mapped on chromosomes 1, 3, 6, 7, 9, 10, and 12. Four QTLs – qBph‐1‐1, qBph‐3‐1, qBph‐6‐1, and qBph‐7‐1 – were mapped on chromosomes 1, 3, 6, and 7 in the standard seedbox screening test, explaining 41% of the phenotypic variance. Two QTLs, qBph‐6‐1 and qBph‐9‐1, were detected on chromosomes 6 and 9 in the honeydew test, accounting for 32% of the total phenotypic variance. Moreover, four QTLs – qBph‐3‐1, qBph‐6‐1, qBph‐10‐1, and qBph‐12‐1 – were identified on chromosomes 3, 6, 10, and 12 expressing antixenosis to BPH and explaining 41% of the phenotypic variance. QTL qBph‐3‐1 was located in the chromosomal region between markers RM231 and RM3872 on chromosome 3, and QTL qBph‐6‐1 was located in the region between RM588 and RM204 on chromosome 6, indicating that these regions have a major effect in controlling the resistance to BPH in the population studied. The molecular markers linked to QTLs that are identified will be useful in the development of varieties resistant to BPH. Our study contributes to the development of genetic material for breeding programmes and marker‐assisted selection (MAS) in rice to improve BPH resistance.
Associative learning of color and firmness of oviposition substrates in Drosophila suzukii
Authors: Takahara Baku , Takahashi Kazuo H.
Published: December 2016

Drosophila suzukii Matsumura (Diptera: Drosophilidae), also known as the spotted‐wing drosophila, is a global pest fly. The degree of infestation of D. suzukii varies greatly among host plants, possibly depending on the physical properties of the fruits. Because some of the physical properties of fruits can only be judged by touching them, D. suzukii may choose to oviposit based on the physical properties of fruits and remote sensory information such as visual cues. Here, we conducted associative learning experiments with artificial substrates consisting of water, cornmeal, fructose, and agarose with different colors and firmness. We assessed associative learning by conditioning flies with combinations of two colors (purple or green) and degrees of firmness (firm or soft), and comparing their choice between the conditioned color and the other color afterward. We demonstrated that D. suzukii had an associative learning ability but it was limited to the association between green and soft. Drosophila suzukii conditioned with green and soft substrate preferred green as the first choice in the test phase. The proximate cause of this asymmetrical associative learning ability is completely unknown, but the pattern of learning coincides with D. suzukii's preference for immature fruits on the tree in nature, possibly to avoid competition with other fruit flies. The associative learning ability of D. suzukii was found to be limited to a certain combination of color and firmness. It suggests that the asymmetrical association of the natural fruit color and physical properties played a role in the evolution of color‐specific associative learning ability of D. suzukii.
Community‐wide impacts of early season herbivory on flower visitors on tall goldenrod
Authors: IKEMOTO MITO , IDA TAKASHI Y. , UTSUMI SHUNSUKE , OHGUSHI TAKAYUKI
Published: December 2016

1. The flower visitor community consists not only of pollinators but also of non‐pollinators, such as florivores, thieves and predators that attack flower visitors. Although there is increasing evidence that early‐season foliar herbivory influences pollinator visitation through changes in floral traits, few studies have explored indirect effects of foliar herbivory on community structure of the flower visitors. We examined how early‐season foliar herbivory influences the flower visitor community established in late season.

2. We conducted an inoculation experiment using a lacebug (Corythucha marmorata), which is a predominantly herbivorous insect attacking leaves of tall goldenrod (Solidago altissima) in Japan.

3. Flower abundance significantly decreased when damaged by the lacebug. The numbers of pollinators, florivores and thieves were positively correlated with flower abundance, whereas predators were not. In response to flower abundance, florivores decreased on damaged plants. On the other hand, thieves increased on damaged plants, and pollinators and predators did not differ between damaged and undamaged plants.

4. When effects of flower abundance were excluded, foliar herbivory still influenced florivores negatively and thieves positively. This implies that factors besides flower abundance may have affected the numbers of florivores and thieves.

5. Community composition of flower visitors on damaged plants significantly differed from undamaged plants, although overall abundance, taxonomic richness and taxonomic evenness were unaffected by foliar herbivory in the early season. It is important to recognise that only evaluating species diversity and overall abundance may fail to detect the significant consequence of early‐season herbivory on the flower visitor community.
Limnology and trophic status of glacial lakes in the tropical Andes (Cajas National Park, Ecuador)
Authors: Van Colen Willem R. , Mosquera Pablo , Vanderstukken Maarten , Goiris Koen , Carrasco Maria‐Cecilia , Decaestecker Ellen , Alonso Miguel , León‐Tamariz Fabián , Muylaert Koenraad
Published: December 2016

The tropical Andes has a high density of glacial lakes that are situated in the high‐altitude páramo (3500–4500 m). Ecological information about such lakes is scant despite the fact that these lakes are an important source of water for drinking, irrigation and electricity generation and feed several major tributaries of the Amazon. In this study, we provide data on a survey of 31 lakes in Cajas National Park (Ecuador). Two of the lakes were monitored monthly during one year. In situ nutrient addition experiments were carried out in three of the lakes.

Seasonal monitoring in two lakes revealed a thermal stratification of the water column between October and June, with a small temperature difference between epi‐ and hypolimnion (2–3 °C). Oxygen depletion of the hypolimnion towards the end of the stratification period indicated that no complete mixing of the water column occurred during stratification. There was no evidence of depletion of nutrients in the epilimnion or accumulation in the hypolimnion during stratification. There were also no clear seasonal changes in chlorophyll‐a (Chl‐a) concentration nor in phytoplankton community composition in the two lakes.

Inputs of dissolved organic carbon (DOC) from the vegetated catchment resulted in high DOC concentrations (median 2.9 mg L−1) compared to temperate mountain lakes. Water transparency was relatively low, with a median extinction coefficient for photosynthetic active radiation of 0.50 m−1 and for UV‐B radiation of 10.13 m−1. Although the thermocline was deep and water transparency was low, estimates of the critical depth for photosynthesis were deeper than the mean water depth in all lakes, suggesting that phytoplankton was not light limited.

The phytoplankton community was dominated by chlorophytes (e.g. Oocystis), diatoms (small Cyclotella spp.) or small colonial cyanobacteria (Aphanocapsa, Merismopedia). The zooplankton community was either dominated by large cladocerans and cyclopoid copepods, or by the calanoid copepod Boeckella occidentalis.

Total concentrations of phosphorus (P) and nitrogen (N) were comparable to those in temperate mountain lakes (4–35 μg P L−1 and 162–758 μg N L−1) while Chl‐a concentrations were in the lower range (<1 μg L−1). A large part of the total nutrient pool consists of dissolved organic N and P that appeared to have a low bioavailability to phytoplankton. The median seston N:P ratio of 44, a positive correlation between Chl‐a and total P concentration, as well as nutrient addition assays carried out in three lakes all pointed to P limitation of phytoplankton.
Patterns of metal distribution in hypersaline microbialites during early diagenesis: Implications for the fossil record
Authors: Sforna M. C. , Daye M. , Philippot P. , Somogyi A. , van Zuilen M. A. , Medjoubi K. , Gérard E. , Jamme F. , Dupraz C. , Braissant O. , Glunk C. , Visscher P. T.
Published: December 2016

The use of metals as biosignatures in the fossil stromatolite record requires understanding of the processes controlling the initial metal(loid) incorporation and diagenetic preservation in living microbialites. Here, we report the distribution of metals and the organic fraction within the lithifying microbialite of the hypersaline Big Pond Lake (Bahamas). Using synchrotron‐based X‐ray microfluorescence, confocal, and biphoton microscopies at different scales (cm–μm) in combination with traditional geochemical analyses, we show that the initial cation sorption at the surface of an active microbialite is governed by passive binding to the organic matrix, resulting in a homogeneous metal distribution. During early diagenesis, the metabolic activity in deeper microbialite layers slows down and the distribution of the metals becomes progressively heterogeneous, resulting from remobilization and concentration as metal(loid)‐enriched sulfides, which are aligned with the lamination of the microbialite. In addition, we were able to identify globules containing significant Mn, Cu, Zn, and As enrichments potentially produced through microbial activity. The similarity of the metal(loid) distributions observed in the Big Pond microbialite to those observed in the Archean stromatolites of Tumbiana provides the foundation for a conceptual model of the evolution of the metal distribution through initial growth, early diagenesis, and fossilization of a microbialite, with a potential application to the fossil record.
Vulnerability of eastern US tree species to climate change
Authors: Rogers Brendan M. , Jantz Patrick , Goetz Scott J.
Published: December 2016

Climate change is expected to alter the distribution of tree species because of critical environmental tolerances related to growth, mortality, reproduction, disturbances, and biotic interactions. How this is realized in 21st century remains uncertain, in large part due to limitations on plant migration and the impacts of landscape fragmentation. Understanding these changes is of particular concern for forest management, which requires information at an appropriately fine spatial resolution. Here we provide a framework and application for tree species vulnerability to climate change in the eastern United States that accounts for influential drivers of future distributions. We used species distribution models to project changes in habitat suitability at 800 m for 40 tree species that vary in physiology, range, and environmental niche. We then developed layers of adaptive capacity based on migration potential, forest fragmentation, and propagule pressure. These were combined into metrics of vulnerability, including an overall index and spatially explicit categories designed to inform management. Despite overall favorable changes in suitability, the majority of species and the landscape were considered vulnerable to climate change. Vulnerability was significantly exacerbated by projections of pests and pathogens for some species. Northern and high‐elevation species tended to be the most vulnerable. There were, however, some notable areas of particular resilience, including most of West Virginia. Our approach combines some of the most important considerations for species vulnerability in a straightforward framework, and can be used as a tool for managers to prioritize species, areas, and actions.
Going with the flow: the role of ocean circulation in global marine ecosystems under a changing climate
Authors: van Gennip Simon J. , Popova Ekaterina E. , Yool Andrew , Pecl Gretta T. , Hobday Alistair J. , Sorte Cascade J. B.
Published: December 2016

Ocean warming, acidification, deoxygenation and reduced productivity are widely considered to be the major stressors to ocean ecosystems induced by emissions of CO2. However, an overlooked stressor is the change in ocean circulation in response to climate change. Strong changes in the intensity and position of the western boundary currents have already been observed, and the consequences of such changes for ecosystems are beginning to emerge. In this study, we address climatically induced changes in ocean circulation on a global scale but relevant to propagule dispersal for species inhabiting global shelf ecosystems, using a high‐resolution global ocean model run under the IPCC RCP 8.5 scenario. The ¼ degree model resolution allows improved regional realism of the ocean circulation beyond that of available CMIP5‐class models. We use a Lagrangian approach forced by modelled ocean circulation to simulate the circulation pathways that disperse planktonic life stages. Based on trajectory backtracking, we identify present‐day coastal retention, dominant flow and dispersal range for coastal regions at the global scale. Projecting into the future, we identify areas of the strongest projected circulation change and present regional examples with the most significant modifications in their dominant pathways. Climatically induced changes in ocean circulation should be considered as an additional stressor of marine ecosystems in a similar way to ocean warming or acidification.
Predicting future biomass yield in Miscanthus using the carbohydrate metabolic profile as a biomarker
Authors: Maddison Anne L. , Camargo‐Rodriguez Anyela , Scott Ian M. , Jones Charlotte M. , Elias Dafydd M. O. , Hawkins Sarah , Massey Alice , Clifton‐Brown John , McNamara Niall P. , Donnison Iain S. , Purdy Sarah J.
Published: December 2016

In perennial energy crop breeding programmes, it can take several years before a mature yield is reached when potential new varieties can be scored. Modern plant breeding technologies have focussed on molecular markers, but for many crop species, this technology is unavailable. Therefore, prematurity predictors of harvestable yield would accelerate the release of new varieties. Metabolic biomarkers are routinely used in medicine, but they have been largely overlooked as predictive tools in plant science. We aimed to identify biomarkers of productivity in the bioenergy crop, Miscanthus, that could be used prognostically to predict future yields. This study identified a metabolic profile reflecting productivity in Miscanthus by correlating the summer carbohydrate composition of multiple genotypes with final yield 6 months later. Consistent and strong, significant correlations were observed between carbohydrate metrics and biomass traits at two separate field sites over 2 years. Machine‐learning feature selection was used to optimize carbohydrate metrics for support vector regression models, which were able to predict interyear biomass traits with a correlation (R) of >0.67 between predicted and actual values. To identify a causal basis for the relationships between the glycome profile and biomass, a 13C‐labelling experiment compared carbohydrate partitioning between high‐ and low‐yielding genotypes. A lower yielding and slower growing genotype partitioned a greater percentage of the 13C pulse into starch compared to a faster growing genotype where a greater percentage was located in the structural biomass. These results supported a link between plant performance and carbon flow through two rival pathways (starch vs. sucrose), with higher yielding plants exhibiting greater partitioning into structural biomass, via sucrose metabolism, rather than starch. Our results demonstrate that the plant metabolome can be used prognostically to anticipate future yields and this is a method that could be used to accelerate selection in perennial energy crop breeding programmes.
Could Miscanthus replace maize as the preferred substrate for anaerobic digestion in the United Kingdom? Future breeding strategies
Authors: Purdy Sarah J. , Maddison Anne L. , Nunn Christopher P. , Winters Ana , Timms‐Taravella Emma , Jones Charlotte M. , Clifton‐Brown John C. , Donnison Iain S. , Gallagher Joe A.
Published: December 2016

Fodder maize is the most commonly used crop for biogas production owing to its high yields, high concentrations of starch and good digestibility. However, environmental concerns and possible future conflict with land for food production may limit its long‐term use. The bioenergy grass, Miscanthus, is a high‐yielding perennial that can grow on marginal land and, with ‘greener’ environmental credentials, may offer an alternative. To compete with maize, the concentration of non‐structural carbohydrates (NSC) and digestibility may need to be improved. Non‐structural carbohydrates were quantified in 38 diverse genotypes of Miscanthus in green‐cut biomass in July and October. The aim was to determine whether NSC abundance could be a target for breeding programmes or whether genotypes already exist that could rival maize for use in anaerobic digestion systems. The saccharification potential and measures of N P and K were also studied. The highest concentrations of NSC were in July, reaching a maximum of 20% DW. However, the maximum yield was in October with 300–400 g NSC plant−1 owing to higher biomass. The digestibility of the cell wall was higher in July than in October, but the increase in biomass meant yields of digestible sugars were still higher in October. Nutrient concentrations were at least twofold higher in July compared to November, and the abundance of potassium showed the greatest degree of variation between genotypes. The projected maximum yield of NSC was 1.3 t ha−1 with significant variation to target for breeding. Starch accumulated in the highest concentrations and continued to increase into autumn in some genotypes. Therefore, starch, rather than sugars, would be a better target for breeding improvement. If harvest date was brought forward to autumn, nutrient losses in non‐flowering genotypes would be comparable to an early spring harvest.
Granulomatosis With Polyangiitis‐Associated Hypertrophic Pachymeningitis Mimicking Spontaneous Intracranial Hypotension: A Case Report
Authors: Jung Young Hee , Lee Mi Ji , Lee Chungbin , Cha Jihoon , Chung Chin‐Sang
Published: December 2016

Background

Dural enhancement is a characteristic finding in both spontaneous intracranial hypotension and hypertrophic pachymeningitis. Positional headache is the most important feature that distinguishes the two diseases. We report a patient with granulomatosis with polyangiitis (formerly Wegener's granulomatosis) who initially manifested like spontaneous intracranial hypotension.

Case presentation

We report here the case of a 63‐year old man who presented with severe positional headache. The patient had typical symptoms, symmetric dural enhancement, and a recent history of nontraumatic subdural hygroma which led to the diagnosis of spontaneous intracranial hypotension, but was finally diagnosed as granulomatosis with polyangiitis‐associated secondary hypertrophic pachymeningitis. Cyclophosphamide therapy was effective for the maintenance of remission.

Conclusions

Hypertrophic pachymeningitis associated with granulomatosis with polyangiitis can present with positional headache and subdural hygroma, mimicking spontaneous intracranial hypotension. Granulomatosis with polyangiitis should be suspected when patients with spontaneous intracranial hypotension or hypertrophic pachymeningitis show atypical features.
The prevalence of ALK rearrangement in pulmonary adenocarcinomas in an unselected Caucasian population from a defined catchment area: impact of smoking
Authors: Skov Birgit G , Clementsen Paul , Larsen Klaus R , Sørensen Jens B , Mellemgaard Anders
Published: December 2016

Aims

To assess the prevalence of EML4–ALK rearrangement gene measured by immunohistochemistry in an unselected population‐based consecutive cohort of patients with adenocarcinoma of the lung (ACL), and the correlation with smoking history, thyroid transcription factor 1 (TTF1), gender and age.

Methods and results

All patients diagnosed in the population of the greater Copenhagen area were included, irrespective of gender, age, smoking habits, stage or type of available diagnostic material. Tumours were stained with immunohistochemistry (clone 5A4). Immunohistochemistry‐positive tumours were tested by fluorescence in‐situ hybridization (FISH). During a 16‐month period, 760 patients in the population were diagnosed with ACL. In 2.6% there was insufficient material for ALK testing (20 of 760). Eleven per cent of the remaining 740 ACL patients were never smokers, 43% were ex‐smokers smokers and 46% were current smokers. Fourteen patients [1.9%, 95% confidence interval (CI) = 1.1–3.2] were ALK‐positive by immunohistochemistry. Nine of 82 never‐smokers (11%, 95% CI = 5.9–19.6) and five of 652 ex‐ or current smokers (0.8%, 95% CI = 0.4–2.1) were ALK‐positive. Only two ALK‐positive patients were found among 586 heavy smokers (> 15 pack‐years) (0.3%, 95% CI = 0.09–1.2). Thirteen of the 14 immunohistochemistry‐positive patients were FISH‐positive. All ALK‐positive tumours were TTF1‐positive. The number needed to test (NNT) to identify one ALK positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.

Conclusions

Immunohistochemical analysis of ALK rearrangement was possible in 97.4% of patients. ALK rearrangement was found primarily in never smokers. NNT to identify one ALK‐positive patient was 9, 22 and 293 among never smokers, light and heavy smokers, respectively.
Pore orientation of the gadolinia‐doped ceria cathode interlayer for a tubular SOFC using dip‐coating
Authors: Liang Bo , Zhang Silong , Lu Shengguo , Sui Sheng , Shang Jinlei
Published: December 2016

An active region of cathode interlayer in a tubular solid oxide fuel cell (SOFC) is structurally analyzed using a dual‐beam focused ion beam/scanning electron microscope (FIB/SEM). The GDC (10 mol% gadolinia‐doped ceria) cathode interlayer (about 1 μm in thickness) is dip‐coated, and then sintered on YSZ (8 mol% yttria‐stabilized zirconia) electrolyte. At 1150°C sintering temperature, the pores oriented more along the axial direction than the radial direction. The anisotropy of pore shape is accounted for the withdrawal force during the dip‐coating of the GDC interlayer.
Barriers to spousal contribution to childbirth pain relief in Nigeria
Authors: Emelonye A.U. , Pitkäaho T. , Aregbesola A. , Vehviläinen‐Julkunen K.
Published: December 2016

Aim

The aim of this study was to investigate the barriers inhibiting the use of spousal presence for childbirth pain relief in health facilities and recommendations from three perspectives: the midwife, the woman, and the spouse.

Background

Spousal presence is a non‐invasive, participatory and inexpensive technique used in pain management during childbirth. Although it contributes to a large extent in relieving childbirth pain, it is underutilized in Nigerian hospitals. Overcoming the challenges impeding spousal presence and participation during childbirth will improve maternal outcome, satisfaction and midwifery care practices.

Method

A cross‐sectional survey conducted in four hospitals in Nigeria involving midwives (n = 100), women (n = 142) and their spouses (n = 142) from June to December 2014 using pretested questionnaires.

Results

Five themes were identified: poor infrastructural facility, lack of adequate pain management policy, lack of midwife pain management practices, midwives' attitudes towards spousal presence during childbirth and feelings about spousal presence during childbirth pain relief.

Conclusion

Infrastructural defects in the health facilities resulting in the lack of privacy in maternity units for both spouses and partners negatively influence the presence of a spouse during childbirth and pain relief. Adopting effective strategies such as good infrastructural facilities, staff training and spouse‐friendly hospital policies will encourage spouses to fully participate in and contribute to childbirth pain relief.

Implications for nursing and health policy

This study identified poor staff attitudes towards pain relief and spousal presence during childbirth as barriers. Providing adequate policies on pain management, continuous staff education and orientation on spousal relationship will improve active spousal participation and maternal satisfaction during childbirth.
Nurses’ attitudes towards enforced measures to increase influenza vaccination: A qualitative study
Authors: Pless Anina , Shaw David , McLennan Stuart , Elger Bernice S.
Published: December 2016

Background

Despite studies demonstrating that the annual influenza vaccination of healthcare workers reduces morbidity and mortality among vulnerable patients, vaccination rates remain very low, particularly in nursing staff. Educational programmes have failed to improve rates, which has led to a diverse range of enforced approaches being advocated and implemented.

Objectives

To examine the attitudes of non‐vaccinated nursing staff towards various enforced measures aimed at increasing rates of influenza vaccination.

Methods

Semi‐structured qualitative interviews with a purposive sample of 18 non‐vaccinated nurses, working in units with high‐risk patients at two hospitals in Switzerland. Analysis of interviews was done using conventional content analysis.

Results

Nurses were critical of enforced measures. However, measures that include an element of choice were perceived as more acceptable. Declination forms and mandatory vaccinations as part of the employment requirements were found to be the most accepted measures.

Conclusion

The perception of choice is crucial to the acceptance of a measure. Respect for choice and autonomy has a positive effect on behavioural change.

Mandatory influenza vaccination as a condition of new (and perhaps ongoing) employment could be a feasible, effective and ethical measure to increase vaccination rates among nurses who oppose vaccination.
Spicule and flagellated chamber formation in a growth zone of Aphrocallistes vastus (Porifera, Hexactinellida)
Authors: Kahn Amanda S. , Leys Sally P.
Published: December 2016

Three species of glass sponges (Class Hexactinellida) form massive deep‐water reefs by growing on the skeletons of past generations, with new growth largely vertical and away from sediment that buries the lower portions. Growth is therefore essential for reef health, but how glass sponges produce new skeleton or tissue is not known. We used fluorescence, light, and electron microscopy to study skeletal and tissue growth in the reef‐forming glass sponge Aphrocallistes vastus. The sponge consists of a single large tube (the osculum), usually with several side branches, each of which can function as an effective excurrent vent. New tissue forms at the tips of each of these extensions, but how this occurs in a syncytial animal, and how the tubes expand laterally as the sponge gets larger, are both unknown. The fluorescent dye PDMPO labeled more spicule types in the tips of the sponge than elsewhere, indicating growth that was concentrated at the edge of the osculum. New tissue production was tracked using the thymidine analog EdU. EdU‐labeled nuclei were found predominantly at the edge or lip of the osculum. In that region new flagellated chambers were formed from clusters of choanoblasts that spread out around the enlarging chamber. In cellular sponges clusters of choanocytes form flagellated chambers through several rounds of mitotic divisions, and also by immigration of mesohyl cells, to expand the chamber to full size. By contrast, chambers in glass sponges expand as choanoblasts produce enucleate collar bodies to fill them out. Growing chambers with enucleate structures may be an adaptation to life in the deep sea if chambers with cells, and therefore more nuclei, are costly to build.
Epistemic Privilege and Victims’ Duties to Resist their Oppression
Authors: Vasanthakumar Ashwini
Published: December 2016

Victims of injustice are prominent protagonists in efforts to resist injustice. I argue that they have a duty to do so. Extant accounts of victims’ duties primarily cast these duties as self‐regarding duties (say, of Kantian self‐respect) or duties based on collective identities and commitments. I provide an account of victims’ duties to resist injustice that is grounded in the duty to assist. I argue that victims are epistemically privileged with respect to injustice and are therefore uniquely positioned to assist fellow victims. Primarily, they discharge this duty through testimony: victims alert other actors to the need for assistance and initiate and coordinate resistance efforts. I briefly provide an account of oppression that ranges from persecution to structural injustice. Through the examples of torture and ‘manterrupting’, I illustrate the duty and its limits. I outline shortcomings in victims’ epistemic privilege and explore means by which these can be overcome. I respond to objections from demandingness and fairness, arguing that victims have an essential, albeit circumscribed, role to play in defeating injustice.
Education, Sufficiency, and the Relational Egalitarian Ideal
Authors: Macfarlane Kirsty
Published: December 2016

In recent decades political philosophers have increasingly been engaged with the issue of educational equality. However, egalitarians typically focus on achieving equality in the distribution of education, and ignore the relevance of an alternative, relational conception of equality. An exception to this is Elizabeth Anderson, who applies relational egalitarian principles to education in her 2007 article ‘Fair Opportunity in Education: A Democratic Equality Perspective’. Although Anderson remains one of the few relational egalitarians to consider what this ideal requires in education, her arguments have received less attention than they deserve. In this article I examine Anderson's theory of fair educational opportunities for a democratic society of equals and develop an internal critique of her approach. I suggest that the sufficientarian standard Anderson proposes for education has the propensity to undermine the process of integration and the relations of equality she aspires to. Even if all children receive a sufficient education, inequality above the threshold could result in social divisions and status differentials that encourage informal segregation because people typically prefer to associate with other people who are similar to themselves. The article will finish by considering what implications this has for Anderson's relational egalitarian approach to education.
Annual Research Review: Breaking cycles of violence – a systematic review and common practice elements analysis of psychosocial interventions for children and youth affected by armed conflict
Authors: Brown Felicity L. , de Graaff Anne M. , Annan Jeannie , Betancourt Theresa S.
Published: December 2016

Background

Globally, one in 10 children live in regions affected by armed conflict. Children exposed to armed conflict are vulnerable to social and emotional difficulties, along with disrupted educational and occupational opportunities. Most armed conflicts occur in low‐ and middle‐income countries (LMICs), where mental health systems are limited and can be further weakened by the context of war. Research is needed to determine feasible and cost‐effective psychosocial interventions that can be delivered safely by available mental health workforces (including nonspecialists). A vital first step toward achieving this is to examine evidence‐based psychosocial interventions and identify the common therapeutic techniques being used across these treatments.

Methods

A systematic review of psychosocial interventions for conflict‐affected children and youth living in LMICs was performed. Studies were identified through database searches (PsycINFO, PubMed, Cochrane Central Register of Controlled Trials, PILOTS and Web of Science Core Collection), hand‐searching of reference lists, and contacting expert researchers. The PracticeWise coding system was used to distill the practice elements within clinical protocols.

Results

Twenty‐eight randomized controlled trials and controlled trials conducted in conflict‐affected settings, and 25 efficacious treatments were identified. Several practice elements were found across more than 50% of the intervention protocols of these treatments. These were access promotion, psychoeducation for children and parents, insight building, rapport building techniques, cognitive strategies, use of narratives, exposure techniques, and relapse prevention.

Conclusions

Identification of the common practice elements of effective interventions for conflict‐affected children and youth can inform essential future treatment development, implementation, and evaluation for this vulnerable population. To further advance the field, research should focus on identifying which of these elements are the active ingredients for clinical change, along with attention to costs of delivery, training, supervision and how to sustain quality implementation over time.
Effects of a Safe Transportation Educational Program for Older Drivers on Driving Exposure and Community Participation: A Randomized Controlled Trial
Authors: Coxon Kristy , Chevalier Anna , Brown Julie , Clarke Elizabeth , Billot Laurent , Boufous Soufiane , Ivers Rebecca , Keay Lisa
Published: December 2016

Objectives

To ascertain whether a safe‐transportation program can change driving exposure while maintaining community participation of older drivers.

Design

Randomized controlled trial.

Setting

Northwest Sydney.

Participants

Drivers aged 75 and older (mean 80 ± 4) (n = 380).

Intervention

Intervention group participated in an individualized, one‐on‐one safe‐transportation program adapted from the Knowledge Enhances Your Safety curriculum. A registered occupational therapist delivered the intervention in two sessions held approximately 1 month apart.

Measurements

An in‐vehicle monitoring device hardwired into participants’ vehicles measured driving exposure. Community participation was measured using the Keele Assessment of Participation. A staging algorithm based on the Precaution Adoption Process Model measured behavior change toward increased and sustained driving self‐regulation. Main outcomes were distance driven per week over 12 months and community participation. Secondary outcomes were behavior change, depressive symptoms, and alternate transportation use. Generalized estimating equations were used to model effect on driving exposure, adjusting for weekly measures, and ordinal regression was used to analyze differences in behavior change profiles between groups using an intention‐to‐treat approach.

Results

Participants were randomized after baseline assessment—190 each to the intervention and control groups. One hundred eighty‐three of 190 completed the intervention and 366 of 380 completed the study. On average, participants drove 140 ± 167 km/wk. Although there was no significant difference between the groups in distance driven per week over 12 months (between‐group difference −5.5 km, 95% confidence interval (CI) = −24.5–13.5 km, p = .57), intervention group participants showed greater readiness to engage in self‐regulatory driving practices, such as reporting avoiding driving at night or at rush hours, than control group participants (odds ratio (OR) = 1.6, 95% CI = 1.1–2.3, P = .02). At 12 months, use of alternate transportation was similar (between‐group difference 0.1, 95% CI = −1.4–1.6, P = .90). Although there was no difference in community participation (between‐group difference −0.1, 95% CI = −0.6–0.3, P = .59), older drivers with low function in the intervention group were 3.1 times as likely to report depressive symptoms (95% CI = 1.04–9.2, P = .04) than those with low function in the control group.

Conclusion

An individualized safe‐transportation program can promote behavior change but did not translate to significant differences in weekly mileage after 12 months. Longer follow‐up may detect changes over time.
An isogenic blood–brain barrier model comprising brain endothelial cells, astrocytes, and neurons derived from human induced pluripotent stem cells
Authors: Canfield Scott G. , Stebbins Matthew J. , Morales Bethsymarie Soto , Asai Shusaku W. , Vatine Gad D. , Svendsen Clive N. , Palecek Sean P. , Shusta Eric V.
Published: December 2016

The blood–brain barrier (BBB) is critical in maintaining a physical and metabolic barrier between the blood and the brain. The BBB consists of brain microvascular endothelial cells (BMECs) that line the brain vasculature and combine with astrocytes, neurons and pericytes to form the neurovascular unit. We hypothesized that astrocytes and neurons generated from human‐induced pluripotent stem cells (iPSCs) could induce BBB phenotypes in iPSC‐derived BMECs, creating a robust multicellular human BBB model. To this end, iPSCs were used to form neural progenitor‐like EZ‐spheres, which were in turn differentiated to neurons and astrocytes, enabling facile neural cell generation. The iPSC‐derived astrocytes and neurons induced barrier tightening in primary rat BMECs indicating their BBB inductive capacity. When co‐cultured with human iPSC‐derived BMECs, the iPSC‐derived neurons and astrocytes significantly elevated trans‐endothelial electrical resistance, reduced passive permeability, and improved tight junction continuity in the BMEC cell population, while p‐glycoprotein efflux transporter activity was unchanged. A physiologically relevant neural cell mixture of one neuron: three astrocytes yielded optimal BMEC induction properties. Finally, an isogenic multicellular BBB model was successfully demonstrated employing BMECs, astrocytes, and neurons from the same donor iPSC source. It is anticipated that such an isogenic facsimile of the human BBB could have applications in furthering understanding the cellular interplay of the neurovascular unit in both healthy and diseased humans.

image

Read the Editorial Highlight for this article on page 843.