bluuebunny/crossref_metadata_2025 huggingface dataset:
N‐Acetyl Cysteine Treatment Restores Early Phase Fracture Healing in Ethanol‐Fed Rats
Authors: Duryee Michael J. , Dusad Anand , Hunter Carlos D. , Kharbanda Kusum K. , Bruenjes Joseph D. , Easterling Karen C. , Siebler Justin C. , Thiele Geoffrey M. , Chakkalakal Dennis A.
Published: April 2018

Background

Fracture healing in alcoholics is delayed and often associated with infections resulting in prolonged rehabilitation. It has been reported that binge drinking of alcohol increases oxidative stress and delays fracture healing in rats, which is prevented by treatment with the antioxidant n‐acetyl cysteine (NAC). Oxidative stress is a significant factor in pathologies of various organs resulting from chronic alcoholism. Therefore, we hypothesize that treatment with NAC reduces oxidative stress and restores fracture healing in chronic alcoholics.

Methods

Rats (10 months old) were pair‐fed the Lieber‐DeCarli ethanol (EtOH) diet or control diet for 16 weeks. A closed fracture was performed and rats allowed to recover for 72 hours. Rats were divided into 4 groups—control, control + NAC, EtOH, and EtOH + NAC—and injected intraperitoneally with 200 mg/kg of NAC daily for 3 days. Serum and bone fracture callus homogenates were collected and assayed for traditional markers of inflammation, oxidative stress, and bone regeneration.

Results

The oxidative stress marker malondialdehyde (MDA) was increased in both serum and bone tissue in EtOH‐fed animals compared to controls. NAC treatment significantly (p < 0.01) reduced MDA to near normal levels and dramatically increased the index of antioxidant efficacy (catalase/MDA ratio) (p < 0.01). Inflammatory markers tumor necrosis factor‐α, interferon‐γ, and interleukin‐6 were significantly decreased in serum and callus following NAC treatment. NAC treatment reduced EtOH‐induced bone resorption as evidenced by significant decreases in C‐telopeptide of type‐I‐collagen levels (p < 0.05) and band‐5 tartrate‐resistant acid phosphatase levels in the tissue (p < 0.001).

Conclusions

Oxidative stress and excessive inflammation are involved in the inhibition of fracture healing by EtOH. In this study, early short‐term treatment of EtOH‐fed animals with the antioxidant NAC reduced oxidative stress and normalized the innate immune response to fracture in the early phase of fracture healing, thereby restoring the normal onset of bone regeneration.
A noninterventional study to monitor patients with diabetic macular oedema starting treatment with ranibizumab (POLARIS)
Authors: Stefanickova Jana , Cunha‐Vaz Jose , Ulbig Michael , Pearce Ian , Fernández‐Vega Sanz Alvaro , Theodossiadis Panagiotis , Kodjikian Laurent , Izmailov Alexander , Muston Dominic , Vassilev Zdravko , Lamotte Benedicte , Tückmantel Claudia , Friedl Sabine , Altemark Andreas , Schwarz Hans‐Jörg , Katz Todd ,   the POLARIS study investigators
Published: April 2018

Purpose

Antivascular endothelial growth factor agents are increasingly used in diabetic macular oedema (DME); however, there are few studies exploring their use in DME in real‐world settings.

Methods

POLARIS was a noninterventional, multicentre study to monitor 12‐month outcomes in patients starting ranibizumab treatment in routine practices. The primary outcome was mean change in visual acuity (VA) from baseline to month 12 (last observation carried forward approach). Other outcomes included mean change in central retinal thickness (CRT) and resource utilization. Visual acuity (VA) outcomes were also stratified by country, baseline visual acuity score (VAS), sex, age and injection frequency.

Results

Outcomes were analysed from all treated patients (n = 804) and from first‐year completers (patients who had a visual acuity assessment at 12 months; n = 568). The mean (SD) baseline VAS was 59.4 (15.9) letters, and the mean change in visual acuity was 4.4 letters (95% confidence interval: 3.3–5.4) at month 12 (study eye; first‐year completers). The mean number of injections (study eye) was 4.9, and the mean number of all visits (any eye) was 10 (58% were injection visits) over 12 months (first‐year completers). The mean (SD) baseline CRT was 410.6 (128.8) μm, and the mean change in CRT was −115.2 μm at month 12 (study eye; first‐year completers). Visual acuity (VA) outcomes were generally comparable across most countries and subgroups and were greatest in patients with the lowest baseline VAS (≤60 letters).

Conclusion

POLARIS showed that real‐world outcomes in DME patients starting treatment with ranibizumab were lower than those observed in clinical studies, in spite of extensive monitoring.
The association among HER2, MET and FOXP3 expression and tumor regression grading in gastric adenocarcinoma
Authors: Neves Filho Eduardo Henrique Cunha , Pires Adriana Pinheiro Bezerra , de Sant'Ana Rosane Oliveira , Rabenhorst Silvia Helena Barem , Hirth Carlos Gustavo , da Cunha Maria Do Perpétuo Socorro Saldanha
Published: April 2018

Although the introduction of the perioperative chemotherapy on the management of gastric cancer has improved patients survival, heterogeneity of clinical outcomes has been evidenced in parallel to different histopathological regression pattern of gastric cancer cells. Thus, this study evaluated the tumor regression grading (TRG) in a series of post‐treatment gastric tumors and its associations with HER2, MET, and FOXP3 expression. Material of 54 gastric cancer samples was available for TRG evaluation and immunohistochemistry. We found that total and subtotal pathologic response were significantly associated to the intestinal subtype (p = 0.04) and that well‐differentiated tumors were significantly correlated with total or partial response (p = 0.019). Although not associated with the TRG, FOXP3 expression in gastric tumors was associated to poorly differentiated tumors (p = 0.03), to the diffuse and mixed subtypes together (p = 0.04) and to the presence of vascular infiltration (p = 0.04), while HER2 overexpression was associated to better differentiated cases (p = 0.04) and to the absence of vascular infiltration (p = 0.02). MET expression, however, showed no association with the analyzed clinicopathological factors. This study highlights the role of tissue differentiation on pathological response to neoadjuvant chemotherapy in gastric cancer and shows no impact between FOXP3, HER2 and MET expression in terms of TRG.
Estimation of concentration of radionuclides in skeletal muscle from blood, based on the data from abandoned animals in Fukushima
Authors: Fukuda Tomokazu
Published: April 2018

The damage caused by the earthquake on 11 March, 2011 resulted in a serious nuclear accident in Japan. Due to the damage to the Fukushima Daiichi Nuclear Power Plant (FNPP), large amounts of radioactive substances were released into the environment. In particular, one of the largest safety concerns is radioactive cesium (134Cs and 137Cs). Due to the FNPP nuclear accident, a 20 km area was restricted from human activity, and various types of domestic animals were left in the zone. We collected the organs and tissues from sacrificed animals to obtain scientific data to evaluate the internal deposition of radioactive compounds. At first, we found there is a strong correlation between blood 137Cs and organ 137Cs with data from 44 cattle, indicating that skeletal muscle is the target organ of deposition of radioactive cesium. Second, we analyzed the relationship between blood 137Cs and muscle 137Cs within relatively lower radioactive concentration, suggesting that estimation of concentration of 137Cs is possible from blood concentration of 137Cs. Finally, we developed computer software to estimate the muscle 137Cs concentration from blood samples. Our study contributes to the food safety of livestock products.
School Location, Social Ties, and Perceived Neighborhood Boundaries
Authors: Burdick–Will Julia
Published: April 2018

Local organizations can serve as landmarks that orient residents’ understanding of space and foster social ties through regular and repeated interaction. Depending on their location, schools can serve as local social anchors or pull families who live in the same neighborhood in different directions. This study examines the extent to which the geographic location of schools shapes how residents view their social and spatial connection to their own residential neighborhood. Specifically, I use GIS, descriptive statistics, and regressions with neighborhood fixed–effects to analyze the Making Connections Survey of 28 low–income neighborhoods in 10 different cities. The results show that residents who have a child attending a school inside their neighborhood report living in a closer–knit community and knowing more of their kids’ friends. Residents also shift their perception of their neighborhoods’ geographic boundaries in the direction of the school their child attends.
Cardiac performance is influenced by rotational changes of position in the transversal plane, both in the horizontal and in the 60̊ head‐up postures
Authors: Kölegård Roger , Da Silva Cristina , Siebenmann Christoph , Keramidas Michail E. , Eiken Ola
Published: April 2018

Background

Echocardiography is usually performed with the subject/patient lying in the left lateral position (LLP), because the acoustic window is better in this than in the supine position (SP). The aim was to investigate cardiac responses to rotational changes of position in the transversal plane, from SP to LLP while horizontal, and from leaning on the back (HUT‐LB) to leaning on the left side (HUT‐LL) while tilted 60° head‐up from the horizontal.

Methods

Healthy men (n = 12) underwent 10‐min HUT provocations. Cardiac variables were measured using two‐dimensional echocardiography, Doppler, tissue Doppler imaging and arterial pressures using a volume‐clamp method.

Results

In horizontal posture, cardiac volumes were smaller in SP than in LLP: end‐diastolic volume (EDV) by 14%, end‐systolic volume (ESV) by 13%, stroke volume (SV) by 14%, and cardiac output (CO) by 16% (P<0·03). In addition, the mitral annular plane systolic excursion (MAPSE) was 11% smaller (P = 0·001) and the left ventricle isovolumic relaxation time (IVRT) 27% longer in SP than in LLP. The ejection fraction, heart rate, arterial pressure and pulmonary ventilation were similar in SP and LLP. During HUT, EDV, SV, CO and MAPSE were smaller, and IVRT was longer, in HUT‐LB than in HUT‐LL, by −19%, −20%, −17%, −18% and +35%, respectively (P<0·04).

Conclusions

Cardiac performance is enhanced in LLP versus SP and in HUT‐LL versus HUT‐LB, which can be attributed to improved venous return, conceivably, wholly or in part, due to increased hydrostatic pressure gradients between the caval veins and the heart in the LLP and HUT‐LL positions.
Refuges and risks: Evaluating the benefits of an expanded MPA network for mobile apex predators
Authors: Daly Ryan , Smale Malcolm J. , Singh Sarika , Anders Darrell , Shivji Mahmood , K. Daly Clare A. , Lea James S. E. , Sousa Lara L. , Wetherbee Bradley M. , Fitzpatrick Richard , Clarke Christopher R. , Sheaves Marcus , Barnett Adam
Published: April 2018

Aim

Concurrently, assessing the effectiveness of marine protected areas and evaluating the degree of risk from humans to key species provide valuable information that can be integrated into conservation management planning. Tiger sharks (Galeocerdo cuvier) are a wide‐ranging ecologically important species subject to various threats. The aim of this study was to identify “hotspots” of tiger shark habitat use in relation to protected areas and potential risks from fishing.

Location

Southwest Indian Ocean, east coast of South Africa and Mozambique.

Methods

Satellite tags were fitted to 26 tiger sharks. A subset of 19 sharks with an average period at liberty of 197 (SD = 110) days were analysed using hotspot analysis to identify areas of core habitat use. The spatial and temporal overlap of significant hotspots with current and planned marine protected areas as well as risks from fishing and culling was then calculated.

Results

There was a 5.97% spatial overlap between tiger shark hotspots and marine protected areas, which would increase significantly (p < .05) to 24.36% with the expansion of planned protected areas in South Africa and could be as high as 41.43% if Mozambique similarly expanded neighbouring protected area boundaries. Tiger sharks remained largely coastal, but only showed a spatial overlap of 5.12% with shark culling nets in South Africa. Only three sharks undertook open ocean migrations during which they were more likely to interact with longline fisheries in the region.

Main conclusions

This study demonstrates how spatial information can be used to assess the overlap between marine protected areas and the core habitats of top marine predators and highlights how congruent transnational conservation management can improve the effectiveness of protected areas. Core habitat use of marine apex predators may also be indicative of productive habitats, and therefore, predators such as tiger sharks could act as surrogate species for identifying key habitats to prioritize for conservation planning.
Comparative effectiveness of hand scaling by undergraduate dental students following a two‐week pre‐clinical training course
Authors: Gartenmann S. J. , Hofer D. , Wiedemeier D. , Sahrmann P. , Attin T. , Schmidlin P. R.
Published: April 2018

Background

The Bologna reform resulted in a drastic restructuring of pre‐clinical training courses at the University of Zurich. The aim of this study was to assess student pre‐clinical scaling/root planning skills after just 8.5 hours of manual training.

Material and Methods

Three consecutive classes of dental students (n = 41; n = 34; n = 48) were tasked with removing lacquer concrement from the maxillary left canine on a typodont using Gracey and universal (Deppeler M23A) curettes. At baseline (prior to instruction), a timed five‐minute session of scaling/root planning was undertaken. The second scaling/root planning session was held immediately following training. Eight experienced dental hygienists and eight lay people served as positive and negative controls, using the same instruments and time limit, respectively. Instrumented teeth were collected, scanned and planimetrically analysed for the percentage of tooth surface cleaned. Statistical analyses were performed to assess the dental students’ improvement after the training (Wilcoxon signed‐rank test) and to compare it to that of laypeople and dental hygienists (Kruskal–Wallis rank sum test followed by Conover's post hoc test).

Results

At baseline, the dental students’ mean scaling scores of the cleaned surfaces were not significantly different than those of laypeople (29.8%, 31.0%, 42% vs 27.9%). However, after 8.5 hours of manual training, the students’ ability to clean the maxillary tooth improved significantly and they achieved mean removal values of 61.7%, 79.5% and 76% compared to the 67.4% (P < .001) of the experienced dental hygienists (Tables Tables and). There were no statistically significant differences between the scores achieved by students after training and those achieved by experienced dental hygienists.

Conclusion

A shortened pre‐clinical training time was sufficient for students to acquire the basic scaling/root planning skills needed in preparation for clinical training. Further research is needed to identify ways to help students consistently reach highest skill levels.
Sameness and selfhood: The efficiency of constitutional identities in EU law
Authors: Sterck Julien
Published: April 2018

This article enquires into the formal dimension of constitutional identity by focusing not on what it consists of but on how it is expressed in the different discursive practices developed by constitutional courts. Contrasting constitutional identity as sameness and constitutional identity as selfhood shows that domestic courts can favour either a substantive determination of core constitutional features or a performative approach where the reflexive ability to define oneself prevails. Such a choice conditions the judicial strategies developed in the interactions with the Court of Justice, and their effectiveness. From this perspective, the accommodation in EU law, in light of the respect for Member States' national identity affirmed in Article 4(2) TEU, of these domestic identity claims rooted in the supremacy of the Constitution, depends less on what is asked for than on how it is asked for.
Toward understanding the contribution of waterbodies to the methane emissions of a permafrost landscape on a regional scale—A case study from the Mackenzie Delta, Canada
Authors: Kohnert Katrin , Juhls Bennet , Muster Sina , Antonova Sofia , Serafimovich Andrei , Metzger Stefan , Hartmann Jörg , Sachs Torsten
Published: April 2018

Waterbodies in the arctic permafrost zone are considered a major source of the greenhouse gas methane (CH4) in addition to CH4 emissions from arctic wetlands. However, the spatio‐temporal variability of CH4 fluxes from waterbodies complicates spatial extrapolation of CH4 measurements from single waterbodies. Therefore, their contribution to the CH4 budget of the arctic permafrost zone is not yet well understood. Using the example of two study areas of 1,000 km² each in the Mackenzie Delta, Canada, we approach this issue (i) by analyzing correlations on the landscape scale between numerous waterbodies and CH4 fluxes and (ii) by analyzing the influence of the spatial resolution of CH4 flux data on the detected relationships. A CH4 flux map with a resolution of 100 m was derived from two aircraft eddy‐covariance campaigns in the summers of 2012 and 2013. We combined the CH4 flux map with high spatial resolution (2.5 m) waterbody maps from the Permafrost Region Pond and Lake Database and classified the waterbody depth based on Sentinel‐1 SAR backscatter data. Subsequently, we reduced the resolution of the CH4 flux map to analyze if different spatial resolutions of CH4 flux data affected the detectability of relationships between waterbody coverage, number, depth, or size and the CH4 flux. We did not find consistent correlations between waterbody characteristics and the CH4 flux in the two study areas across the different resolutions. Our results indicate that waterbodies in permafrost landscapes, even if they seem to be emission hot spots on an individual basis or contain zones of above average emissions, do currently not necessarily translate into significant CH4 emission hot spots on a regional scale, but their role might change in a warmer climate.
Association between pancreatic fat and incidence of metabolic syndrome: a 5‐year Japanese cohort study
Authors: Yamazaki Hajime , Tauchi Shinichi , Kimachi Miho , Dohke Mitsuru , Hanawa Nagisa , Kodama Yoshihisa , Katanuma Akio , Yamamoto Yosuke , Fukuma Shingo , Fukuhara Shunichi
Published: April 2018

Background and Aim

Previous cross‐sectional studies showed that pancreatic fat was associated with metabolic syndrome. However, no longitudinal study has evaluated whether people with high pancreatic fat are likely to develop future metabolic syndrome. This study investigated the association between baseline pancreatic fat and metabolic syndrome incidence.

Methods

In 2008–2009, 320 participants without metabolic syndrome underwent health checks, which included unenhanced computed tomography, and were followed up annually for 4–5 years. Baseline pancreatic fat amounts were evaluated using a histologically validated method that measured differences between pancreas and spleen attenuations on computed tomography. The participants were divided into low (reference), intermediate, and high pancreatic fat groups based on pancreas and spleen attenuation tertiles. Metabolic syndrome incidence was evaluated annually over a median follow‐up period of 4.99 (interquartile range, 4.88–5.05) years, in accordance with the 2009 harmonized criteria. Risk ratios (RRs) for the association between baseline pancreatic fat amounts and metabolic syndrome incidence were estimated using Poisson regression models adjusted for age, sex, body mass index, liver fat, pre‐metabolic syndrome, cigarette use, alcohol use, and physical activity.

Results

Metabolic syndrome incidence was 30.6% (98/320). Pancreatic fat was associated with an increased incidence of metabolic syndrome, based on a univariate analysis (RRs [95% confidence interval], 3.14 [1.74–5.67] and 3.96 [2.23–7.03] in the intermediate and high pancreatic fat groups, respectively). The association remained statistically significant in the multivariate analysis (RR [95% confidence interval], 2.04 [1.14–3.64] and 2.30 [1.28–4.14] for the same groups, respectively).

Conclusions

Pancreatic fat predicts the future risk of metabolic syndrome.
Integration of pharmacokinetic–pharmacodynamic for dose optimization of doxycycline againstHaemophilus parasuisin pigs
Authors: Zhang L. , Li Y. , Wang Y. , Sajid A. , Ahmed S. , Li X.
Published: April 2018

The aims of this study were to establish optimal doses of doxycycline (dox) againstHaemophilus parasuison the basis of pharmacokinetic–pharmacodynamic (PK‐PD) integration modeling. The infected model was established by intranasal inoculation of organism in pigs and confirmed by clinical signs, blood biochemistry, and microscopic examinations. The recommended dose (20 mg/kg b.w.) was administered in pigs through intramuscular routes forPKstudies. The area under the concentration 0‐ to 24‐hr curve (AUC0–24), elimination half‐life (T½ke), and mean residence time (MRT) of dox in healthy andH. parasuis‐infected pigs were 55.51 ± 5.72 versus 57.10 ± 4.89 μg·hr/ml, 8.28 ± 0.91 versus 9.80 ± 2.38 hr, and 8.43 ± 0.27 versus 8.79 ± 0.18 hr, respectively. The minimal inhibitory concentration (MIC) of dox against 40H. parasuisisolates was conducted through broth microdilution method, the correspondingMIC50andMIC90were 0.25 and 1 μg/ml, respectively. The Ex vivo growth inhibition data suggested that dox exhibited a concentration‐dependent killing mechanism. Based on the observedAUC24 hr/MICvalues by modelingPK‐PDdata inH. parasuis‐infected pigs, the doses predicted to obtain bacteriostatic, bactericidal, and elimination effects forH. parasuisover 24 hr were 5.25, 8.55, and 10.37 mg/kg for the 50% target attainment rate (TAR), and 7.26, 13.82, and 18.17 mg/kg for 90%TAR, respectively. This study provided a more optimized alternative for clinical use and demonstrated that the dosage 20 mg/kg of dox by intramuscular administration could have an effective bactericidal activity againstH. parasuis.
Use of cast antlers to assess antler size variation in red deer populations: effects of mast seeding, climate and population features in Mediterranean environments
Authors: Peláez M. , Perea R. , Díaz M. , San Miguel A. , Rodríguez‐Vigal C. , Côté S. D.
Published: April 2018

Fundamental understanding of the factors influencing cervid antler size, development and investment has been traditionally drawn from harvest data. However, depending on the hunting tactic, harvest data may not represent a random sample of the population leading to possible inferential biases. Cast antlers may represent an alternative, cost‐effective and non‐invasive method. We used 4756 red deer (Cervus elaphus L.) cast antlers collected during a 10‐year period to evaluate the relationship between annual antler gross score and three key environmental components that determine habitat quality and resource availability in Mediterranean systems: (1) population traits (density and male age structure), (2) acorn yield and (3) a proxy of plant productivity [Real Bioclimatic Index(RBI)]. Population traits and acorn yield were measured before antler formation (autumn/winter) whereasRBIwas calculated before (autumn/winter) and during (spring) antler formation. Population traits explained the highest amount of variance in antler score, followed by acorn yield and springRBI, while no effect was found for autumn/winterRBI. Antler gross score was negatively related to population density but positively associated with acorn yield, springRBIand male age structure. Interestingly, a significant interaction between population traits and acorn yield suggests a disproportional effect of population traits on antler size during non‐mast years (poor acorn crops), whereas no significant population effect was observed during mast years. Similarly, we found a positive effect of springRBIon antlers when density was medium or low and/or age structure was balanced or older. These findings have important ecological implications in environments with high inter‐annual resources variability where high population densities lead to strong intraspecific competition during years of low food availability (e.g. during non‐mast years or drier springs), producing large antler size variation. Finally, although cast antlers reflect changes in environmental conditions we do not recommend their use unless reliable data on age structure is available.
Efficacy and safety of mirabegron, a β3‐adrenoceptor agonist, in patients with detrusor hyperactivity and impaired contractility
Authors: Lee Cheng‐Ling , Kuo Hann‐Chorng
Published: April 2018

Objective

We examined the efficacy and safety of mirabegron in elderly patients with urodynamic detrusor hyperactivity with impaired contractility (DHIC).

Methods

Patients diagnosed with DHIC received daily dose of mirabegron (25mg). Subjective symptom scores, uroflowmetry data, and adverse events (AEs) were recorded for all patients at baseline and after 1, 3, and 6 months treatment. Comparisons were made for each patient individually and between patients with detrusor overactivity (DO).

Results

Of the 65 patients enrolled in the study, 25 had DHIC and 40 had DO (mean [± SD] age 79.3 ± 9.6 and 75.6 ± 10.7 years, respectively). At the 6‐month follow‐up, significant (P < .05) improvement was seen compared with baseline in both the DHIC and DO groups in terms of OAB symptom scores (4.72 ± 3.05 vs. 6.88 ± 4.06 and 4.50 ± 2.99 vs. 6.70 ± 3.60, respectively), urgency severity score (1.90 ± 2.00 vs. 3.35 ± 1.13 and 1.58 ± 1.93 vs. 3.00 ± 1.65, respectively), and global response assessment (1.80 ± 1.41 and 1.73 ± 1.34, respectively). In the DHIC group, post‐void residual (PVR) volume decreased from 153 ± 52.7 mL at baseline to 85.8 ± 90.1 mL at 6th month (P < .05) and voiding efficiency improved from 40.0 ± 20.7% to 62.6 ± 28.3% (P < .05). Common AEs included dry mouth and dizziness, yet 16% of DHIC patients developed PVR >180 mL.

Conclusion

Mirabegron was an effective treatment option in elderly patients with urodynamic DO and DHIC in the present study. The AEs reported were mild and infrequent.
Zinc isotope fractionation during grain filling of wheat and a comparison of zinc and cadmium isotope ratios in identical soil–plant systems
Authors: Wiggenhauser Matthias , Bigalke Moritz , Imseng Martin , Keller Armin , Archer Corey , Wilcke Wolfgang , Frossard Emmanuel
Published: April 2018

Remobilization of zinc (Zn) from shoot to grain contributes significantly to Zn grain concentrations and thereby to food quality. On the other hand, strong accumulation of cadmium (Cd) in grain is detrimental for food quality.

Zinc concentrations and isotope ratios were measured in wheat shoots (Triticum aestivum) at different growth stages to elucidate Zn pathways and processes in the shoot during grain filling.

Zinc mass significantly decreased while heavy Zn isotopes accumulated in straw during grain filling (Δ66Znfull maturity–flowering = 0.21–0.31‰). Three quarters of the Zn mass in the shoot moved to the grains, which were enriched in light Zn isotopes relative to the straw (Δ66Zngrain–straw −0.21 to −0.31‰).

Light Zn isotopes accumulated in phloem sinks while heavy isotopes were retained in phloem sources likely because of apoplastic retention and compartmentalization. Unlike for Zn, an accumulation of heavy Cd isotopes in grains has previously been shown. The opposing isotope fractionation of Zn and Cd might be caused by distinct affinities of Zn and Cd to oxygen, nitrogen, and sulfur ligands. Thus, combined Zn and Cd isotope analysis provides a novel tool to study biochemical processes that separate these elements in plants.
Unity in diversity: structural and functional insights into the ancient partnerships between plants and fungi
Authors: Field Katie J. , Pressel Silvia
Published: April 2018

ContentsSummary996I.Introduction996II.An ancient, and diverse, symbiosis998III.Structural diversity in ancient plant–fungal partnerships1000IV.Mycorrhizal unity in host plant nutrition1002V.Plant‐to‐fungus carbon transfer1003VI.From individuals to networks1003VII.Diverse responses of mycorrhizal functioning to dynamic environments1006VIII.Summary of future research direction1007Acknowledgements1006References1006

Mycorrhizal symbiosis is an ancient and widespread mutualism between plants and fungi that facilitated plant terrestrialisation > 500 million years ago, with key roles in ecosystem functioning at multiple scales. Central to the symbiosis is the bidirectional exchange of plant‐fixed carbon for fungal‐acquired nutrients. Within this unifying role of mycorrhizas, considerable diversity in structure and function reflects the diversity of the partners involved. Early diverging plants form mutualisms not only with arbuscular mycorrhizal Glomeromycotina fungi, but also with poorly characterised Mucoromycotina, which may also colonise the roots of ‘higher’ plants as fine root endophytes. Functional diversity in these symbioses depends on both fungal and plant life histories and is influenced by the environment. Recent studies have highlighted the roles of lipids/fatty acids in plant‐to‐fungus carbon transport and potential contributions of Glomeromycotina fungi to plant nitrogen nutrition. Together with emerging appreciation of mycorrhizal networks as multi‐species resource‐sharing systems, these insights are broadening our views on mycorrhizas and their roles in nutrient cycling. It is crucial that the diverse array of biotic and abiotic factors that together shape the dynamics of carbon‐for‐nutrient exchange between plants and fungi are integrated, in addition to embracing the unfolding and potentially key role of Mucoromycotina fungi in these processes.
Sequence variation in the bolting time regulator BTC1 changes the life cycle regime in sugar beet
Authors: Höft Nadine , Dally Nadine , Jung Christian
Published: April 2018

In beet production, flowering is an undesirable trait which drastically reduces yield. BOLTING TIME CONTROL 1 (BTC1) and BvBBX19 are major floral regulators in beet. Their proteins have been suggested to interact to jointly regulate their downstream targets BvFT1 and BvFT2. Annual and biennial BTC1 haplotypes differ by six non‐synonymous SNPs and a large insertion in the promoter of the biennial btc1 allele. We describe a new BTC1 allele which displays three nucleotide polymorphisms in the coding sequence and an 8‐bp insertion in the promoter region compared to the annual BTC1d allele. The protein lacks a low‐complexity region, which likely alters its suggested ability to bind BvBBX19. Our findings demonstrate that little sequence variation in BTC1 is sufficient to turn an annual into a biennial genotype. Our results shed new light on the evolution of cultivated beets, and the identified btc1l allele offers new possibilities to breed winter beets.
Temperature related instability of a naturally induced cytoplasmic male sterility in industrial chicory (Cichorium intybus L.)
Authors: Van der Veken Jeroen , Vandermoere Stany , Maudoux Olivier , Notté Christine , Eeckhaut Tom , Baert Joost , Werbrouck Stefaan , Van Huylenbroeck Johan
Published: April 2018

Natural alloplasmic cytoplasmic male sterile (CMS) clones of industrial chicory were obtained after crossing wild chicory with selected breeding lines. We investigated the CMS stability of 10 clones in various environmental growing conditions. CMS was stable under cool growing conditions in most of them. Fertility restoration, based on pollen production scores, was observed in all clones after a period of hot temperatures. The early flower bud stage was sensitive, resulting in fertile flowers 12–17 days after exposure to high temperatures. Experiments under controlled growing conditions at 15°C demonstrated that a heat shock of 2 days at 25 or 30°C was sufficient to restore fertility. Sterile flowers were formed when plants were again grown at lower temperatures. Significant differences between individual clones were observed, indicating the potential of genetic selection to obtain stable CMS parent lines.
Coexistence of glandular papilloma and sclerosing pneumocytoma in the bronchiole
Authors: Kitawaki Yuko , Fujishima Fumiyoshi , Taniuchi Shinji , Saito Ryoko , Nakamura Yasuhiro , Sato Ryoko , Aoyama Yayoi , Onodera Yoshiaki , Inoshita Naoko , Matsuda Yasushi , Watanabe Mika , Sasano Hironobu
Published: April 2018

Both glandular papilloma (GP) and sclerosing pneumocytoma (SP) are rare tumors in the lung. We herein report an extremely rare case of coexistence of these two uncommon tumors. The patient was a 40‐year‐old Japanese woman with no chief complaint. A solitary nodule of the lung was detected using chest computed tomography. The transbronchial biopsy revealed that the tumor histologically corresponded to GP. The patient subsequently underwent partial resection of the right upper lobe. Histological examination of the resected specimens further revealed that the mass contained two different and independent elements and displayed typically histological features of GP and SP. Molecular analysis further revealed the presence of BRAF V600E and AKT1 E17K mutations in GP, whereas only AKT1 mutation was detected in SP. To our knowledge, this is the first case of coexistence of GP and SP in the bronchiole harboring common AKT1 mutation and different BRAF V600E mutational status.
The rate of sedimentation from turbulent suspension: An experimental model with application to pyroclastic density currents and discussion on the grain‐size dependence of flow runout
Authors: Dellino Pierfrancesco , Dioguardi Fabio , Doronzo Domenico M. , Mele Daniela
Published: April 2018

Large‐scale experiments generating ground‐hugging multiphase flows were carried out with the aim of modelling the rate of sedimentation, of pyroclastic density currents. The current was initiated by the impact on the ground of a dense gas‐particle fountain issuing from a vertical conduit. On impact, a thick massive deposit was formed. The grain size of the massive deposit was almost identical to that of the mixture feeding the fountain, suggesting that similar layers formed at the impact of a natural volcanic fountain should be representative of the parent grain‐size distribution of the eruption. The flow evolved laterally into a turbulent suspension current that sedimented a thin, tractive layer. A good correlation was found between the ratio of transported/sedimented load and the normalized Rouse number of the turbulent current. A model of the sedimentation rate was developed, which shows a relationship between grain size and flow runout. A current fed with coarser particles has a higher sedimentation rate, a larger grain‐size selectivity and runs shorter than a current fed with finer particles. Application of the model to pyroclastic deposits of Vesuvius and Campi Flegrei of Southern Italy resulted in sedimentation rates falling inside the range of experiments and allowed definition of the duration of pyroclastic density currents which add important information on the hazard of such dangerous flows. The model could possibly be extended, in the future, to other geological density currents as, for example, turbidity currents.
English, super‐diversity, and identity in the State of Qatar
Authors: Hillman Sara , Ocampo Eibenschutz Emilio
Published: April 2018

This article provides a contemporary profile of English, or Englishes thereof, in the State of Qatar, a tiny country undergoing tremendous socio‐cultural transformations. The historical background section contextualizes Qatar's contemporary linguistic ‘super‐diversity’ as a continuity of mobility, integration, and exchange with various communities within and beyond the shores of the Arab/Persian Gulf for centuries. We describe Qatar's present‐day sociolinguistic situation, English language policy initiatives and reforms in the educational context, and take a critical stance toward the common homogenizing view of English and Arabic language in the region, one that precludes a nuanced understanding in terms of wider cultural and linguistic processes taking place and shaping identities in Qatar today.
Debt Servicing and Sectoral Economic Growth in Kenya
Authors: Molonko Brenda , Jagongo Ambrose , Omagwa Job
Published: April 2018

The study objective was toestablish the effect of debt servicing on sectoral economic growth as well as the moderating effect of inflation on the relationship between debt servicing and sectorial economic growth in Kenya. The study employed Auto Regressive Distributed Lag model. Eleven sectors that receive government expenditure were analyzed while adopting positivist philosophy and a causal research design. The Study period covered the year 2006 to the 2015.Secondary data for the study period were collected from Statistical Abstracts of Kenya National Bureau of Statistics and Debt Servicing Reports from Kenya National Treasury. Panel Stationarity Test and Heterogeneity Test were conducted as preliminary tests whereas Hausman Test was carried out to choose efficient estimator from Pooled Mean Group, Dynamic Fixed Effects and Mean Group Estimators. The study established that in the long run, debt servicing has a significant effect on sectoral economic growth. In addition, the study established that inflation has a significant moderating effect on the relationship between debt servicing and Sectoral economic growth in the long run at the significance level of 0.05. The study concluded that debt servicing has a significant effect on sectoral economic growth in Kenya in the long run and no effect in the short run. Additionally, inflation enhances the influence of debt servicing on sectoral economic growth in the long run. The study further confirms that Kenya is not facing a debt overhang problem. The study recommends that if the government must borrow, the loans should be concessional in nature with long term repayment periods. The government should ensure that reasonable levels of inflation are achieved.
Siberian sculpture is among the oldest monumental art
Authors: Curry Andrew
Published: April 2018

The 11,600-year-old Shigir Idol offers an enigmatic glimpse of hunter-gatherers' world view.
The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution
Authors: Briggs James A. , Weinreb Caleb , Wagner Daniel E. , Megason Sean , Peshkin Leonid , Kirschner Marc W. , Klein Allon M.
Published: April 2018

Mapping the vertebrate developmental landscape

As embryos develop, numerous cell types with distinct functions and morphologies arise from pluripotent cells. Three research groups have used single-cell RNA sequencing to analyze the transcriptional changes accompanying development of vertebrate embryos (see the Perspective by Harland). Wagner
et al.
sequenced the transcriptomes of more than 90,000 cells throughout zebrafish development to reveal how cells differentiate during axis patterning, germ layer formation, and early organogenesis. Farrell
et al.
profiled the transcriptomes of tens of thousands of embryonic cells and applied a computational approach to construct a branching tree describing the transcriptional trajectories that lead to 25 distinct zebrafish cell types. The branching tree revealed how cells change their gene expression as they become more and more specialized. Briggs
et al.
examined whole frog embryos, spanning zygotic genome activation through early organogenesis, to map cell states and differentiation across all cell lineages over time. These data and approaches pave the way for the comprehensive reconstruction of transcriptional trajectories during development.

Science
, this issue p.
981
, p.
eaar3131
, p.
eaar5780
; see also p.
967
The November 2017
M
w
5.5 Pohang earthquake: A possible case of induced seismicity in South Korea
Authors: Grigoli F. , Cesca S. , Rinaldi A. P. , Manconi A. , López-Comino J. A. , Clinton J. F. , Westaway R. , Cauzzi C. , Dahm T. , Wiemer S.
Published: April 2018

Triggering quakes in a geothermal space

Enhanced geothermal systems (EGSs) provide a potentially clean and abundant energy source. However, two magnitude-5 earthquakes recently occurred in South Korea during EGS site development. Grigoli
et al.
and Kim
et al.
present seismic and geophysical evidence that may implicate the second of these earthquakes, which occurred in Pohang, as an induced event. The combination of data from a local seismometer network, well logs, satellite observations, teleseismic waveform analysis, and stress modeling leads to the assessment that the earthquake was probably or almost certainly anthropogenically induced. The possibility remains that the earthquake occurred coincidentally at the EGS site location, but the aftershock distribution and other lines of evidence are concerning for future development of this geothermal resource.

Science
, this issue p.
1003
, p.
1007
Weighing one protein with light
Authors: Lee Steven F. , Klenerman David
Published: April 2018

A light-scattering method allows rapid measurement of the mass of individual proteins
Regulation of Apolipoprotein E Trafficking by Hepatitis C Virus-Induced Autophagy
Authors: Kim Ja Yeon , Ou Jing-hsiung James
Published: April 2018

Hepatitis C virus (HCV) is one of the most important human pathogens. Its virion is associated with apolipoprotein E (ApoE), which enhances its infectivity. HCV induces autophagy to enhance its replication. In this report, we demonstrate that autophagy plays an important role in the trafficking of ApoE in HCV-infected cells. This leads to the degradation of ApoE by autophagy. However, if the autophagic protein degradation is inhibited, ApoE is stabilized and colocalized with autophagosomes. This leads to its enhanced colocalization with the HCV E2 envelope protein and increased production of infectious progeny viral particles. If autophagy is inhibited by suppressing the expression of ATG7, a gene essential for the formation of autophagosomes, the colocalization of ApoE with E2 is reduced, resulting in the reduction of progeny viral titers. These results indicate an important role of autophagy in the transport of ApoE to promote the production of infectious HCV particles.
A novel combined approach using a Penumbra catheter and balloon catheter for cerebral venous sinus thrombosis
Authors: Matsuda Yoshikazu , Owai Yoshihiro , Kakishita Koji , Nakao Naoyuki
Published: April 2018

Cerebral venous sinus thrombosis is sometimes fatal. We describe a case of sinus thrombosis in a 43-year-old woman presenting with generalized seizure, delirium, and a 2 week history of headache and nausea. The patient underwent mechanical thrombectomy using a novel combined approach, in which a Shouryu HR balloon catheter (Kaneka) was anchored in the right transverse sinus (TS), sigmoid sinus (SS), and superior sagittal sinus (SSS), while a Penumbra 5 MAX ACE (Penumbra) catheter was moved back and forth between the right TS, SS, and SSS. Additionally, back and forth movement of the inflated balloon with aspiration—the so-called ‘dental floss technique’—was performed. Partial recanalization was eventually obtained. Follow-up angiography on postoperative day 7 showed a dramatic improvement in venous outflow. The patient was transferred to a rehabilitation hospital on postoperative day 42. We describe our combined approach using aspiration, and Penumbra and balloon catheters, to achieve mechanical thrombectomy for sinus thrombosis.
Improving rates of implantable cardioverter defibrillator deactivation in end-of-life care
Authors: Javaid MR , Squirrell Suzanne , Farooqi Fahad
Published: April 2018

Implantable cardioverter defibrillators (ICDs) save lives in selected patients at risk of sudden cardiac death. However, in patents suffering with terminal illness, ICD therapy could pose a risk of unnecessary futile shocks which could lead to undignified discomfort in their final days of life. National guidelines advise that patients approaching the end of their natural life should be offered a compassionate choice of having their defibrillator deactivated. Following an actual clinical incident involving a patient receiving avoidable ICD shocks in his final hours, we identified shortcomings in communication and gaps in knowledge about ICD management in end-of-life care. We developed a quality improvement programme targeting training and educational support to general physicians and nurses at our large District General Hospital. A series of interventions were delivered including Grand Round presentation, departmental seminars and publicity posters. In parallel, we introduced a local protocol for implementing ICD deactivation which was published on our intranet for Trust-wide accessibility. Following interventions, we examined the clinical notes of each end-of-life care patient who died with an ICD in situ over a 6-month observation period and recorded the proportion who received consent-guided ICD deactivation versus died with an active ICD in situ because no deactivation discussion had been offered. Before our interventions in 2015, 0 out of 10 eligible patients (0%) received consent-guided ICD deactivation. Six months into our campaign to encourage healthcare workers to undertake advance care planning discussion in 2016, 7 out of 13 eligible patients (54%) received consent-guided ICD deactivation and no patients received shocks in their final month of life. This programme was successful in raising awareness of this emerging issue, improving physician knowledge and delivering patient choice as well as contributing to safe and compassionate end-of-life care.
Plasma cytokines and risk of coronary heart disease in the PROCARDIS study
Authors: Clarke Robert , Valdes-Marquez Elsa , Hill Michael , Gordon Joanne , Farrall Martin , Hamsten Anders , Watkins Hugh , Hopewell Jemma C
Published: April 2018

Objective

The aims of the study were to examine the associations of plasma levels of five cytokines (interleukin (IL)-6, IL-5, interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-6 receptor (IL-6R)) and C reactive protein (CRP) with risk of coronary heart disease (CHD).

Methods

In a case–control study of 931 CHD cases and 974 controls, logistic regression was used to estimate the OR and 95% CI of CHD for extreme thirds of biomarkers after adjustment for established risk factors. Sensitivity analyses were conducted in non-statin and in non-aspirin users.

Results

Plasma levels of CRP were moderately correlated with IL-6 (r=0.45) in controls, but more weakly correlated with other cytokines. Likewise, all other cytokines were only weakly correlated with each other. After adjustment for established risk factors, the ORs (95% CI) for CHD comparing extreme thirds of cytokine levels (defined in controls) were 2.53 (1.86 to 3.43) for IL-6, 1.46 (1.11 to 1.93) for IL-5 and 1.46 (1.09 to 1.95) for IFN-γ, respectively. However, neither TNF-α, IL-6R nor CRP was significantly associated with CHD. After further adjustment for the associated cytokines, only IL-5 (1.34; 1.00 to 1.80) and IL-6 (2.39; 1.73 to 3.30) remained significantly associated with CHD. The risk associations of cytokines in non-users of statins or aspirin were comparable with the overall population.

Conclusions

This study confirmed the importance of IL-6 as the most strongly associated cytokine with CHD risk, but also demonstrated novel and independent associations of IL-5 with CHD that warrant further investigation using larger panels of cytokines.