bluuebunny/crossref_metadata_2025 huggingface dataset:
Preparation of hierarchical porous carbon with high capacitance
Authors: Guan Yuming , Mu Jingbo , Che Hongwei , Zhang Xiaoliang , Zhang Zhixiao
Published: April 2018

Purpose

The purpose of this study is to design carbon electrode materials for high performance electric double-layer capacitors (EDLCs) with pores that are large enough and have suitable pore size distribution for the electrolyte to access completely to improve EDLCs’ electrochemical performance.

Design/methodology/approach

This study develop an improved traditional KOH activation method, and a series of micro-meso hierarchical porous carbons have been successfully prepared from phenol formaldehyde resin by combining polyethylene glycol (PEG) and conventional KOH activation.

Findings

As evidenced by N2 adsorption/desorption tests, the obtained samples present Types IV and I-IV hybrid shape isotherms compared with KOH-activated resin (typical of Type I). The sample AC2-7-1, which the addition quantity of PEG is 25 per cent PF (weight ration) activated at 700? For 1 h is considered as the optimum preparation condition. It exhibits the highest specific capacitance value of 240 F/g in 30 wt% KOH aqueous electrolytes because of its higher specific surface area (2085 m2/g), greater pore volume (1.08 cm3/g) and the maximum mesoporosity (43 per cent). In addition, the capacity decay of this material is only 3.1 per cent after 1000 cycles.

Originality/value

The materials that are rich in micropores and mesopores show great potential in EDLC capacitors, particularly for applications where high power output and good high-frequency capacitive performances are required.
Elevated atmospheric carbon dioxide concentrations promote ant tending of aphids
Authors: Kremer Jenni M. M. , Nooten Sabine S. , Cook James M. , Ryalls James M. W. , Barton Craig V. M. , Johnson Scott N.
Published: April 2018

Animal mutualisms, which involve beneficial interactions between individuals of different species, are common in nature. Insect–insect mutualism, for example, is widely regarded as a keystone ecological interaction. Some mutualisms are anticipated to be modified by climate change, but the focus has largely been on plant–microbe and plant–animal mutualisms rather than those between animals.

Ant–aphid mutualisms, whereby ants tend aphids to harvest their honeydew excretions and, in return, provide protection for the aphids, are widespread. The mutualism is heavily influenced by the quality and quantity of honeydew produced by aphids, which is directly affected by host plant quality. As predicted increases in concentrations of atmospheric carbon dioxide (eCO2) are widely reported to affect plant nutritional chemistry, this may also alter honeydew quality and hence the nature of ant–aphid mutualisms.

Using glasshouse chambers and field‐based open‐top chambers, we determined the effect ofeCO2on the growth and nutritional quality (foliar amino acids) of lucerne (Medicago sativa). We determined how cowpea aphid (Aphis craccivora) populations and honeydew production were impacted when feeding on such plants and how this affected the tending behaviour of ants (Iridomyrmexsp.).

eCO2stimulated plant growth but decreased concentrations of foliar amino acids by 29% and 14% on aphid‐infested plants and aphid‐free plants, respectively. Despite the deterioration in host plant quality undereCO2, aphids maintained performance and populations were unchanged byeCO2. Aphids induced higher concentrations of amino acids (glutamine, asparagine, glutamic acid and aspartic acid) important for endosymbiont‐mediated synthesis of essential amino acids. Aphids feeding undereCO2also produced over three times more honeydew than aphids feeding under ambientCO2, suggesting they were imbibing more phloem sap ateCO2. The frequency of ant tending of aphids more than doubled in response toeCO2.

To our knowledge, this is the first study to demonstrate the effects of atmospheric change on an ant–aphid mutualism. In particular, these results highlight how impending changes to concentrations of atmosphericCO2may alter mutualistic behaviour between animals. These could include positive impacts, as reported here, shifts from mutualism to antagonism, partner switches and mutualism abandonment.
Effects of the Kv7 voltage‐activated potassium channel inhibitor linopirdine in rat models of haemorrhagic shock
Authors: Nassoiy Sean P. , Babu Favin S. , LaPorte Heather M. , Byron Kenneth L. , Majetschak Matthias
Published: April 2018

Recently, we demonstrated that Kv7 voltage‐activated potassium channel inhibitors reduce fluid resuscitation requirements in short‐term rat models of haemorrhagic shock. The aim of the present study was to further delineate the therapeutic potential and side effect profile of the Kv7 channel blocker linopirdine in various rat models of severe haemorrhagic shock over clinically relevant time periods. Intravenous administration of linopirdine, either before (1 or 3 mg/kg) or after (3 mg/kg) a 40% blood volume haemorrhage, did not affect blood pressure and survival in lethal haemorrhage models without fluid resuscitation. A single bolus of linopirdine (3 mg/kg) at the beginning of fluid resuscitation after haemorrhagic shock transiently reduced early fluid requirements in spontaneously breathing animals that were resuscitated for 3.5 hours. When mechanically ventilated rats were resuscitated after haemorrhagic shock with normal saline (NS) or with linopirdine‐supplemented (10, 25 or 50 μg/mL) NS for 4.5 hours, linopirdine significantly and dose‐dependently reduced fluid requirements by 14%, 45% and 55%, respectively. Lung and colon wet/dry weight ratios were reduced with linopirdine (25/50 μg/mL). There was no evidence for toxicity or adverse effects based on measurements of routine laboratory parameters and inflammation markers in plasma and tissue homogenates. Our findings support the concept that linopirdine‐supplementation of resuscitation fluids is a safe and effective approach to reduce fluid requirements and tissue oedema formation during resuscitation from haemorrhagic shock.
How do parents’ educational fields affect the choice of educational field?
Authors: Helland Håvard , Wiborg Øyvind N.
Published: April 2018

This study examines the links between parental education and students’ choice of field of study in Norwegian higher education. In our interpretation of the results, we suggest a status group perspective that integrates risk aversion models, micro‐class theory, and cultural reproduction schemes. Complete Norwegian register data for all individuals born from 1955 to 1980 allow for a fine‐grained examination of diverse fields of study not attempted in earlier studies. The findings reveal that intergenerational reproduction of educational fields is widespread, but its extent varies across fields of study. The tendency is most pronounced among children of professional, educated parents with masters and higher‐level degrees. Moreover, the analysis shows that students who do not choose the same field as their parents nonetheless tend to choose educational fields close to those of their parents.
The birthweight toll of mining pollution: evidence from the most contaminated mine site in the Andean region
Authors: Arrieta A , Guillen J
Published: April 2018

Objective

To assess the effect of mining pollution on birthweight.

Design

A retrospective before‐and‐after study with an untreated comparison group.

Setting

La Oroya, a mining town in the Peruvian Andes, considered the most contaminated town in the Andean region.

Population

All pregnant women who delivered in the social security healthcare system in years 2005, 2006, 2008 and 2009. A total of 214 983 births records were used, 957 from La Oroya and 214 026 from the rest of the country.

Methods

A difference‐in‐difference estimation is used to assess the effect of mining pollution on birthweight before and after two business policy changes: a partial environmental improvement and a subsequent closure of smelter operations in La Oroya. Birthweight was compared with a group not affected by the environmental changes in La Oroya.

Main outcome measures

Birthweight in grams.

Results

A steep reduction in mining pollution due to the closure of smelter operations in La Oroya showed an increased birthweight of 71.6 g after controlling for socio‐economic and medical characteristics. None of the environmental improvements prior to the closure had a statistically significant effect on birthweight.

Conclusions

Mining pollution in La Oroya had a negative impact on birthweight. Partial environmental improvements were not enough to improve birthweight. Only after the closure of all mining and smelter operations in La Oroya was a significant gain in birthweight shown.

Tweetable abstract

The closure of the most contaminated mine site in the Andean region increased birthweight by 72 g.
Economic development and democracy: An electoral connection
Authors: KNUTSEN CARL HENRIK , GERRING JOHN , SKAANING SVEND‐ERIK , TEORELL JAN , MAGUIRE MATTHEW , COPPEDGE MICHAEL , LINDBERG STAFFAN I.
Published: April 2018

Scholars continue to debate whether economic development affects regime type. This article argues that a clear relationship exists between development and the electoral component of democracy, but not – or at least less so – between development and other components of broader understandings of democracy. This is so because development enhances the power resources of citizens and elections provide a focal point for collective action. The theory is tested with two new datasets – Varieties of Democracy and Lexical Index of Electoral Democracy – that allow us to disaggregate the concept of democracy into meso‐ and micro‐level indicators. Results of these tests corroborate the theory: only election‐centred indicators are robustly associated with economic development. This may help to account for apparent inconsistencies across extant studies and shed light on the mechanisms at work in a much‐studied relationship. Further analysis shows that development affects electoral democracy by reducing electoral fraud, election violence and vote buying.
Rebleeding rate and risk factors in nonsteroidal anti‐inflammatory drug‐induced enteropathy
Authors: Park Junseok , Jeon Seong Ran , Kim Jin‐Oh , Kim Hyun Gun , Lee Tae Hee , Cho Jun‐Hyung , Ko Bong Min , Lee Joon Seong , Lee Moon Sung
Published: April 2018

OBJECTIVE

Limited evidence is available on rebleeding due to nonsteroidal anti‐inflammatory drugs (NSAIDs)‐induced enteropathy. Previous studies have primarily analyzed endoscopic findings. Therefore, there is a need to evaluate their clinical implications for patients. This study aimed to evaluate the rebleeding rate and its related risk factors in patients with NSAIDs‐induced enteropathy.

METHODS

Of 402 patients with obscure gastrointestinal bleeding who were evaluated with capsule endoscopy, 49 were diagnosed with NSAIDs‐induced enteropathy. The clinical characteristics of the patients were retrospectively analyzed. The Charlson comorbidity index was used to stratify the comorbidities. For patients who used additional drugs that influenced their tendency to bleeding, the odds ratio was calculated and used for a quantitative comparison.

RESULTS

The rebleeding rate in patients with NSAIDs‐induced enteropathy was 20.4%, within a mean duration of 23.4 months. Age ≥65 years (hazard ratio [HR] 8.628, 95% confidence interval [CI] 1.152–64.625), no additional use of mucoprotective agents (HR 11.712, 95% CI 1.278–76.098) and the continuation of NSAIDs after the first bleeding episode (HR 9.861, 95% CI 1.395–98.344) were independently related to rebleeding due to NSAIDs‐induced enteropathy. The underlying comorbidities, drug‐related rebleeding risk scores and therapeutic use of proton pump inhibitors were not significantly different (P = 0.209, 0.212 and 0.720, respectively).

CONCLUSIONS

Approximately one‐fifth of patients with NSAIDs‐induced enteropathy showed rebleeding within 2 years. A careful long‐term follow‐up should be offered to elderly patients with NSAIDs‐induced enteropathy who need continuous NSAID treatment without the additional use of mucoprotective medications.
Image‐based management of empiric lung stereotactic body radiotherapy (SBRT) without biopsy: Predictors from a 10‐year single institution experience
Authors: Hasan Shaakir , Colonias Athanasios , Mickus Timothy , VanDeusen Matthew , Wegner Rodney E.
Published: April 2018

Background

There is emerging reliance on clinical imaging for the diagnosis, prognosis, and treatment evaluation of early stage non‐small cell lung cancer (NSCLC) in patients deemed too high risk for biopsy. We report our experience of clinically diagnosed NSCLC treated empirically with stereotactic body radiotherapy (SBRT) to validate the imaging parameters used for management in this high‐risk population.

Methods

We reviewed 101 empiric lung SBRT cases and profiled imaging specifics of computed tomography and positron emission tomography for diagnosis and follow‐up. Secondarily, we identified potential correlates of disease progression with Cox regression multivariate analysis.

Results

Fifty‐seven men and 43 women aged 45–94 (median 76) were treated with a median dose of 48 Gy in four fractions. The median nodule diameter was 1.6 cm (0.6–4.5 cm) and most were spiculated (n = 58), right‐sided (n = 63), and in the upper lobe (n = 68). Median follow‐up and survival rates were 14 and 28 months, respectively. Local control at three years was 94%. Freedom from any progression at one and three years was 85% and 69%, respectively. Toxicity ≥ grade 3 included two grade 3 dyspneas. A pre‐treatment standard uptake value > 4.1 was the only significant predictor of disease progression.

Conclusion

This study illustrates the instrumental role of modern clinical imaging for the effective management of presumed early stage NSCLC treated with empiric lung SBRT. As lung SBRT without tissue confirmation becomes more common, hopefully these assertions can be prospectively validated.
Lifelong reduction in complex IV induces tissue‐specific metabolic effects but does not reduce lifespan or healthspan in mice
Authors: Deepa Sathyaseelan S. , Pharaoh Gavin , Kinter Michael , Diaz Vivian , Fok Wilson C. , Riddle Kaitlyn , Pulliam Daniel , Hill Shauna , Fischer Kathleen E. , Soto Vanessa , Georgescu Constantin , Wren Jonathan D. , Viscomi Carlo , Richardson Arlan , Van Remmen Holly
Published: April 2018

Loss of SURF1, a Complex IV assembly protein, was reported to increase lifespan in mice despite dramatically lower cytochrome oxidase (COX) activity. Consistent with this, our previous studies found advantageous changes in metabolism (reduced adiposity, increased insulin sensitivity, and mitochondrial biogenesis) in Surf1−/− mice. The lack of deleterious phenotypes in Surf1−/− mice is contrary to the hypothesis that mitochondrial dysfunction contributes to aging. We found only a modest (nonsignificant) extension of lifespan (7% median, 16% maximum) and no change in healthspan indices in Surf1−/− vs. Surf1+/+ mice despite substantial decreases in COX activity (22%–87% across tissues). Dietary restriction (DR) increased median lifespan in both Surf1+/+ and Surf1−/− mice (36% and 19%, respectively). We measured gene expression, metabolites, and targeted expression of key metabolic proteins in adipose tissue, liver, and brain in Surf1+/+ and Surf1−/− mice. Gene expression was differentially regulated in a tissue‐specific manner. Many proteins and metabolites are downregulated in Surf1−/− adipose tissue and reversed by DR, while in brain, most metabolites that changed were elevated in Surf1−/− mice. Finally, mitochondrial unfolded protein response (UPRmt)‐associated proteins were not uniformly altered by age or genotype, suggesting the UPRmt is not a key player in aging or in response to reduced COX activity. While the changes in gene expression and metabolism may represent compensatory responses to mitochondrial stress, the important outcome of this study is that lifespan and healthspan are not compromised in Surf1−/− mice, suggesting that not all mitochondrial deficiencies are a critical determinant of lifespan.
Necroptosis increases with age and is reduced by dietary restriction
Authors: Deepa Sathyaseelan S. , Unnikrishnan Archana , Matyi Stephanie , Hadad Niran , Richardson Arlan
Published: April 2018

Necroptosis is a newly identified programmed cell death pathway that is highly proinflammatory due to the release of cellular components that promote inflammation. To determine whether necroptosis might play a role in inflammaging, we studied the effect of age and dietary restriction (DR) on necroptosis in the epididymal white adipose tissue (eWAT), a major source of proinflammatory cytokines. Phosphorylated MLKL and RIPK3, markers of necroptosis, were increased 2.7‐ and 1.9‐fold, respectively, in eWAT of old mice compared to adult mice, and DR reduced P‐MLKL and P‐RIPK3 to levels similar to adult mice. An increase in the expression of RIPK1 (1.6‐fold) and MLKL (2.7‐fold), not RIPK3, was also observed in eWAT of old mice, which was reduced by DR in old mice. The increase in necroptosis was paralleled by an increase in 14 inflammatory cytokines, including the pro‐inflammatory cytokines IL‐6 (3.9‐fold), TNF‐α (4.7‐fold), and IL‐1β (5.1‐fold)], and 11 chemokines in old mice. DR attenuated the expression of IL‐6, TNF‐α, and IL‐1β as well as 85% of the other cytokines/chemokines induced with age. In contrast, inguinal WAT (iWAT), which is less inflammatory, did not show any significant increase with age in the levels of P‐MLKL and MLKL or inflammatory cytokines/chemokines. Because the changes in biomarkers of necroptosis in eWAT with age and DR paralleled the changes in the expression of pro‐inflammatory cytokines, our data support the possibility that necroptosis might play a role in increased chronic inflammation observed with age.
Likelihood Ratios for the Emergency Physician
Authors: Peng Paul , Coyle Andrew
Published: April 2018

The concept of likelihood ratios was introduced more than 40 years ago, yet this powerful metric has still not seen wider application or discussion in the medical decision‐making process. There is concern that clinicians‐in‐training are still being taught an oversimplified approach to diagnostic test performance and have limited exposure to likelihood ratios. Even for those familiar with likelihood ratios, they might perceive them as mathematically cumbersome in application, if not difficult to determine for a particular disease process. This article takes a conceptual approach to likelihood ratios and applies them to two clinical settings: 1) severe intracranial injury after minor head trauma and 2) suspected pulmonary embolism with shortness of breath. Likelihood ratios are the most appropriate metric for efficient rational clinical examination and can prevent unnecessary and wasteful treatments and procedures.
“And Poland is filed away with Samothrace”: Australian Responses to Poland's June 1956 Crisis
Authors: Rudzinski Adrian , Korobacz Victor
Published: April 2018

The suppression of Poznan June 1956 workers’ rebellion (Poznanski Czerwiec) by Polish authorities prompted immediate Australia‐wide demonstrations and protests by Polish émigrés who were supported by friends and allies in the Catholic Church and the Australian anti‐communist movement. Nation‐wide demonstrations in Australia and subsequent approaches by émigré Poles and supporters required a disinterested Australian government to develop a position on Poznan June events. Pressure on the Australian government for a response, potentially disruptive to its foreign policies, was applied only by elements within the Australian political scene that posed little threat to its future. Poznan June ‘56's effect on Australia takes place within the particular nature of Australian domestic politics where the June events were used to fan the flames of bitter rivalry within the labour movement by a strident anti‐communist faction seeking to restructure the Australian Labor Party in a manner consistent with its ideological predilections. In taking up the anti‐communist cause of the Polish émigrés, the Australian anti‐communist leadership claimed a moral high‐ground, but lacked sufficient commitment to use their considerable parliamentary advantage to pressure the Australian government to adopt a more muscular position towards Poland's government.
IL‐10 polymorphisms and T‐cell subsets could affect the clinical presentation and outcome of childhood immune thrombocytopenia in Egyptian population
Authors: Soliman Mohamed A. , Helwa Mohamed A. , Fath‐Allah Samar K. , El‐Hawy Mahmoud A. , Badr Hassan S. , Barseem Naglaa Fathy
Published: April 2018

The aim is to study IL‐10 polymorphisms and IL‐10 level and assess their relation to T‐cell subsets in childhood immune thrombocytopenia (ITP). In all, 40 (25 acute, 15 chronic) ITP child patients were investigated at time of presentation, compared to 15 healthy, age‐ and gender‐matched controls and followed up for 1 year to determine chronic cases. Studying the effect of IL‐10 promoter polymorphism was done by PCR‐RFLP, IL‐10 level was determined by ELISA, natural killer cells and T‐cell subsets were evaluated by flow cytometry. Subjects with IL‐10 promoter (1082 AA and 592 AA) genotypes had lower IL‐10 levels and had lower CD4%, higher CD8%, lower CD4/CD8 ratio and lower T‐reg%. IL‐10 polymorphisms had no effect on NK%. IL‐10 serum levels and IL‐10 promoter polymorphic genotype frequencies are not different between ITP cases and controls; however, in ITP patients, IL‐10 promoter (1082 AA and 592 AA) genotypes and associated lower CD4, higher CD8, lower CD4/CD8 ratio is associated with more severe thrombocytopenia at presentation and had a poorer response to first‐line treatment. Patients with lower T‐reg cells had a higher tendency to develop chronic ITP. IL‐10 level and polymorphisms as well as disturbed T‐cell subsets percentages are demonstrable effectors of immune dysfunction in ITP and can affect the presentation and outcome of childhood ITP.
B7‐H3 expression and its correlation with clinicopathologic features, angiogenesis, and prognosis in intrahepatic cholangiocarcinoma
Authors: Cheng Rui , Chen Yongqin , Zhou Haohui , Wang Bi , Du Qiang , Chen Yanling
Published: April 2018

This study was designed to explore the expression of B7‐H3 in human intrahepatic cholangiocarcinoma (ICC) and its association with the clinicopathologic factors. In the current study, the expression of B7‐H3 in 45 patients with intrahepatic cholangiocarcinoma and 8 patients with hepatolithiasis was analyzed by immunohistochemistry, which revealed that B7‐H3 was not expressed in hepatolithiatic tissues, but positively expressed in 57.8% (26/45) of the ICC cases. The expression of B7‐H3 was significantly associated with lymph node metastases and venous invasion. A positive correlation was also observed between the expression of B7‐H3 and MVD, an index for tumor angiogenesis. Further survival analysis indicated that patients with B7‐H3 negative expression had higher overall survival (OS) and cancer‐specific survival (CSS) rates than those with B7‐H3 positive expression. Multivariate analysis revealed that B7‐H3 expression was an independent prognostic indicator for poor OS and CSS of ICC patients. Our results suggest that B7‐H3 may be a valuable biomarker in determining tumor progression and prognosis of intrahepatic cholangiocarcinoma. It is also a potential target for antivascular therapy of ICC.
Bacterial biofilms: a possible mechanism for chronic infection in patients with lumbar disc herniation – a prospective proof‐of‐concept study using fluorescence in situ hybridization
Authors: Ohrt‐Nissen Søren , Fritz Blaine G. , Walbom Jonas , Kragh Kasper N. , Bjarnsholt Thomas , Dahl Benny , Manniche Claus
Published: April 2018

A relationship has been suggested between lumbar disc herniation (LDH) and chronic bacterial infection frequently involving Propionibacterium acnes, which is known to cause chronic infection through the formation of biofilm aggregates. The objective of the study was to assess whether a disc infection involving biofilm formation is present in patients with LDH. A total of 51 LDH patients and 14 controls were included. Bacterial DNA was detected by real‐time polymerase chain reaction (PCR) in 16/51 samples in the LDH group and 7/14 controls (p = 0.215). Sequencing identified bacteria in 9/16 and 6/7 PCR positive samples in the LDH and control groups, respectively. All samples were stained using fluorescence in situ hybridization (FISH) and examined by confocal laser scanning microscopy. Microscopy demonstrated tissue‐embedded bacterial aggregates with host inflammatory cells in 7/51 LDH patients and no controls. The presence of both bacterial aggregates and inflammatory cells suggests a chronic infection in a subset of LDH patients. The finding of bacterial 16S rDNA in both LDH and control disc tissue highlights the importance of microscopic observation to discriminate infection vs contamination. Our findings may have therapeutic implications, as the treatment of biofilm infections is different and more challenging than traditional infections.
Cannabis, from plant to pill
Authors: Grof Christopher P. L.
Published: April 2018

The therapeutic application of cannabis is attracting substantial public and clinical interest. The cannabis plant has been described as a veritable ‘treasure trove’, producing more than 100 different cannabinoids, although the focus to date has been on the psychoactive molecule delta‐9‐tetraydrocannabinol (THC) and cannabidiol (CBD). Other numerous secondary metabolites of cannabis, the terpenes, some of which share the common intermediary geranyl diphosphate (GPP) with the cannabinoids, are hypothesized to contribute synergistically to their therapeutic benefits, an attribute that has been described as the ‘entourage effect’. The effective delivery of such a complex multicomponent pharmaceutical relies upon the stable genetic background and standardized growth of the plant material, particularly if the raw botanical product in the form of the dried pistillate inflorescence (flos) is the source. Following supercritical CO2 extraction of the inflorescence (and possibly bracts), the secondary metabolites can be blended to provide a specific ratio of major cannabinoids (THC : CBD) or individual cannabinoids can be isolated, purified and supplied as the pharmaceutical. Intensive breeding strategies will provide novel cultivars of cannabis possessing elevated levels of specific cannabinoids or other secondary metabolites.
Therapeutic Drug Monitoring of Teicoplanin in Haematological Malignancy Patients with Febrile Neutropenia and Optimizing Dosage Regimens
Authors: Hu Sasa , Wang Taotao , You Haisheng , Wei Shuangyu , Song Hongjuan , Zhang Tao , Zhang Di , Dong Yalin
Published: April 2018

This study used high‐performance liquid chromatography to measure 202 teicoplanin plasma trough concentrations (Cmin) in 114 haematological malignancy patients with febrile neutropenia. Patients were divided into two groups according to the mean initial dose (MID) over the first 3 days of treatment: (i) MID = 533.33 mg/day (loading dose group, 400 mg q12h for three doses followed by 400 mg qd, n = 62) and (ii) MID < 533.33 mg/day (unloaded or underloaded group, n = 52). During the first 3 days after treatment, the overall Cmin was higher in group 1 than in group 2 (10.96 ± 5.44 mg/L versus 6.31 ± 3.73 mg/L, mean ± S.D.; p = 0.002), as was the qualifying rate of Cmin > 10 mg/L (54.5% versus 11.1%, p = 0.001), and the probability of Cmin < 5 mg/L was lower in group 1 than in group 2 (13.6% versus 40.7%, p = 0.037). After 3 days, the average Cmin and qualifying rates did not differ significantly between the two groups, and the average Cmin was <10 mg/L in both groups. Binary logistic regression analysis revealed that creatinine clearance (p = 0.004) and MID (p = 0.010) could affect Cmin during the first 3 days of treatment and that age (p = 0.022) only could affect Cmin after 3 days. In conclusion, it is necessary to apply loading dose to achieve teicoplanin Cmin > 10 mg/L rapidly and, from a pharmacokinetic/pharmacodynamic perspective, 600 mg is recommended as loading and maintenance dose for these patients when AUC24/minimum inhibitory concentration > 345.
SATB2 targeted by methylated miR‐34c‐5p suppresses proliferation and metastasis attenuating the epithelial‐mesenchymal transition in colorectal cancer
Authors: Gu Jingfeng , Wang Guiqi , Liu Haixia , Xiong Chaohui
Published: April 2018

Objectives

SATB2 has been shown to be markedly reduced in colorectal cancer (CRC) tissues relative to paired normal controls; however, the mechanism behind remains not well understood. To investigate why SATB2 was down‐regulated in CRC, we attempted to analyse it from the angle of miRNA‐mRNA modulation.

Materials and methods

SATB2 expression was detected in CRC tissues using immunohistochemistry and verified using real‐time PCR on mRNA level, followed by analysis of clinicopathological significance of its expression. Metastatic variation of CRC cells was evaluated both in vivo and in vitro. To find out the potential miRNA that directly regulate the SATB2, luciferase reporter assay was performed following the bioinformatic prediction.

Results

SATB2 was confirmed to be closely linked with the metastasis and shorter overall survival of CRC in our own cases. Silencing of SATB2 was shown to be able to promote the metastatic ability of CRC cells in vivo, enhancing the epithelial‐mesenchymal transition (EMT). Mechanistically, miR‐34c‐5p was identified to be a novel miRNA that can directly modulate the SATB2. It turned out that the promoter of miR‐34c‐5p was methylated, which leads to the repression of miR‐34c‐5p in CRC. Treatment with 5‐Aza‐dC can reasonably and significantly restore the level of miR‐34c‐5p in CRC cells relative to control, thereby down‐regulating the SATB2.

Conclusions

Together, our study revealed that SATB2 targeted by methylated miR‐34c‐5p can suppress the metastasis, weakening the EMT in CRC.
How Should Colleges Treat Multiple Admissions Test Scores?
Authors: Mattern Krista , Radunzel Justine , Bertling Maria , Ho Andrew D.
Published: April 2018

The percentage of students retaking college admissions tests is rising. Researchers and college admissions offices currently use a variety of methods for summarizing these multiple scores. Testing organizations such as ACT and the College Board, interested in validity evidence like correlations with first‐year grade point average (FYGPA), often use the most recent test score available. In contrast, institutions report using a variety of composite scoring methods for applicants with multiple test records, including averaging and taking the maximum subtest score across test occasions (“superscoring”). We compare four scoring methods on two criteria. First, we compare correlations between scores and FYGPA by scoring method. We find them similar (). Second, we compare the extent to which test scores differentially predict FYGPA by scoring method and number of retakes. We find that retakes account for additional variance beyond standardized achievement and positively predict FYGPA across all scoring methods. Superscoring minimizes this differential prediction—although it may seem that superscoring should inflate scores across retakes, this inflation is “true” in that it accounts for the positive effects of retaking for predicting FYGPA. Future research should identity factors related to retesting and consider how they should be used in college admissions.
The CGRP Pathway in Migraine as a Viable Target for Therapies
Authors: Edvinsson Lars
Published: April 2018

The neuropeptide calcitonin gene‐related peptide is well established as a key player in the pathogenesis of migraine. Clinical studies show calcitonin gene‐related peptide levels correlate with migraine attacks, and decreases in this neuropeptide can indicate antimigraine therapy effectiveness. Research has revealed a wide distribution of expression sites for calcitonin gene‐related peptide in the central and peripheral nervous system. Of these, the calcitonin gene‐related peptide receptor, which binds calcitonin gene‐related peptide with high affinity, has attracted growing interest as a viable target for antimigraine therapies. An incentive to pursue such research is the continuing unmet medical need of patients. Triptans have offered some clinical benefit, but many patients do not respond and these drugs have important safety considerations. Initial calcitonin gene‐related peptide‐focused research led to development of the “gepant” small‐molecule calcitonin gene‐related peptide receptor blockers. Positive efficacy reports concerning the gepants have been tempered by safety findings which led to the discontinuation of some of these agents. Currently, there is considerable excitement regarding monoclonal antibodies against calcitonin gene‐related peptide (eptinezumab, galcanezumab, fremanezumab) and the calcitonin gene‐related peptide receptor (erenumab). To date, these monoclonal antibodies have shown promising efficacy in clinical trials, with no major safety concerns. If ongoing long‐term studies show that their efficacy can be maintained, this may herald a new era for effective antimigraine therapies.
The bigger picture: young children's perception of fatness in the context of other physical differences
Authors: Charsley J. S. , Collins S. C. , Hill A. J.
Published: April 2018

Background

Negative obesity stereotypes and anti‐fat attitudes have been observed in children from age three. It is uncertain whether this is specific to fatness or generalizable to other visible differences.

Objectives

To determine whether young children base decisions about qualities in others and friendship choices more on fatness than other visible differences between people.

Methods

Using a personal construct theory approach, 85 children (mean age 5.7, 42 girls) completed a simple repertory grid. The children were asked about differences (constructs) between four illustrations (elements) that showed children as healthy weight, fat, the opposite gender and in a wheelchair. Children were also asked about friendship with the illustrated children and self‐image preferences. Their answers were grouped using thematic analysis.

Results

The fat, opposite gender and wheelchair‐bound characters were equally chosen by children as different to the standard character. When identifying differences, fatness or body shape was referred to significantly less than gender or being in a wheelchair. Children were more likely to reject an opposite gender character as a friend, or as someone they would like to be, than to reject the fat character. Only one child, themselves overweight, voiced strong anti‐fat attitudes.

Conclusions

Apparent negativity towards fatness is fostered by failure to consider other visible differences and by children's ‘like me’ peer preferences. It was less desirable in the eyes of most 5‐year old girls to be a boy than to be fat. This offers some reassurance to those working to improve children's health literacy in obesity.
Vitamin D during pregnancy and offspring body composition: a prospective cohort study
Authors: Hyde N. K. , Brennan‐Olsen S. L. , Wark J. D. , Hosking S. M. , Holloway‐Kew K. L. , Pasco J. A.
Published: April 2018

Background

Evidence regarding the association between gestational vitamin D status and offspring body composition during childhood is inconsistent. Therefore, we aimed to determine the association between maternal vitamin D and offspring lean and fat mass in the Vitamin D in Pregnancy birth cohort.

Methods

Subjects were mother–child pairs recruited from the Australian‐based Vitamin D in Pregnancy cohort study. Mothers were recruited before 16 weeks' gestation and provided a blood sample at both recruitment and at 28–32 weeks' gestation. Serum vitamin D [25(OH)D] was measured by radioimmunoassay (Tyne and Wear, UK). Offspring lean and fat mass were quantified by using dual‐energy X‐ray absorptiometry (GE Lunar Prodigy, Madison, WI, USA) at 11 years of age.

Results

Median maternal 25(OH)D levels were 55.9 (42.2–73.3) and 56.1 (43.6–73.9) at recruitment and 28–32 weeks' gestation, respectively. Maternal smoking was identified as an effect modifier in the association between maternal vitamin D status at recruitment and offspring body composition. In smokers, but not non‐smokers, serum 25(OH)D status at recruitment was negatively associated with offspring fat mass percentage and positively associated with lean mass (both p < 0.05). There was no association with 25(OH)D status at 28–32 weeks' gestation.

Conclusions

Maternal vitamin D status in early pregnancy, in smokers, is associated with offspring body composition. These important findings warrant confirmation in larger studies and trials.
Is there a deprivation and maternal education gradient to child obesity and moderate‐to‐vigorous physical activity? Findings from the Millennium Cohort Study
Authors: Noonan R. J. , Fairclough S. J.
Published: April 2018

Objective

The primary aim was to examine associations between individual‐level and area‐level measures of socioeconomic status (SES) and different measures of overweight/obesity in 7‐year‐old English children. A secondary aim was to examine associations between individual‐level and area‐level measures of SES and moderate‐to‐vigorous intensity physical activity (MVPA).

Methods

Data were from wave four of the Millennium Cohort Study. Children were classified as normal weight, overweight/obese and centrally obese. MVPA was accelerometer derived. Individual‐level and area‐level SES were defined using self‐reported maternal education and the 2004 English Indices of Multiple Deprivation, respectively. Adjusted linear and multinomial logistic regressions were conducted.

Results

Three thousand seven hundred seventeen children (1890 girls) had complete data. Children in the lowest maternal education group and highest deprivation decile were at greatest risk of overweight and central obesity. MVPA was inversely associated with deprivation, and the most deprived children were most likely to achieve 60 min of daily MVPA.

Conclusions

Individual‐level and area‐level SES were independently related to overweight and central obesity. Higher rates of overweight and central obesity among deprived children are not due to physical inactivity. Further research examining the concurrent effect of diet and MVPA on child weight status by deprivation is warranted.
SjHSP60 induces CD4+CD25+Foxp3+ Tregs via TLR4‐Mal‐drived production of TGF‐β in macrophages
Authors: Zhou Sha , Qi Qianqian , Wang Xiaofan , Zhang Lina , Xu Lei , Dong Liyang , Zhu Jifeng , Li Yalin , Wang Xuefeng , Xu Zhipeng , Liu Feng , Hu Wei , Zhou Liang , Chen Xiaojun , Su Chuan
Published: April 2018

CD4+CD25+Foxp3+ regulatory T cells (Tregs) play a pivotal role in limiting immunopathological damage to host organs after schistosome infection. Transforming growth factor‐β (TGF‐β) is an essential factor for the periphery conversion of CD4+CD25− T cells into CD4+CD25+Foxp3+ Tregs by inducing the key transcription factor Foxp3. Antigen presenting cells (APCs), which highly express TGF‐β, are involved in parasite antigen‐induced Treg conversion in peripheral. However, the mechanisms underlying high TGF‐β induction in APCs by parasite antigens remain to be clarified during schistosome infection. Here, we demonstrated that Schistosoma japonicum stress protein, heat shock protein 60 (SjHSP60), promoted TGF‐β production in macrophages (Mφ). Furthermore, we showed that activation of TLR4‐Mal (MyD88 adaptor‐like protein) signaling by SjHSP60 is necessary for induction of TGF‐β expression in Mφ, which subsequently promoted Treg induction. Our results not only demonstrate a novel mechanism of TGF‐β production in Mφ for inducing Tregs in mice with schistosomiasis, but also allude to the possibility of targeting parasite stress protein for potential therapeutics.
Ranking Forecasts by Stochastic Error Distance, Information and Reliability Measures
Authors: Ardakani Omid M. , Ebrahimi Nader , Soofi Ehsan S.
Published: April 2018

The stochastic error distance (SED) introduced by Diebold and Shin () ranks forecast models by divergence between distributions of the errors of the actual and perfect forecast models. The basic SED is defined by the variation distance and provides a representation of the mean absolute error, but by basing ranking on the entire error distribution and divergence, the SED moves beyond the traditional forecast evaluations. First, we establish connections between ranking forecast models by the SED, error entropy and some partial orderings of distributions. Then, we introduce the notion of excess error for forecast errors of magnitudes larger than a tolerance threshold and give the SED representation of the mean excess error (MEE). As a function of the threshold, the MEE is a local risk measure. With the distribution of the absolute error as a prior for the threshold, its Bayes risk is the entropy functional of the survival function, which is a known measure in the information theory and reliability. Notions and results are illustrated using various distributions for the error. The empirical versions of SED, MEE and its Bayes risk are compared with the mean squared error in ranking regression and autoregressive integrated moving average models for forecasting bond risk premia.
Process evaluation of implementing Protected Mealtimes under clinical trial conditions
Authors: Porter Judi , Ottrey Ella
Published: April 2018

Aim

To evaluate the implementation of Protected Mealtimes and contrast the findings with implementation fidelity.

Background

Protected Mealtimes is a systems approach developed to address the issue of malnutrition in hospitalized patients. Previous studies have used a pre‐–post study design, with no high‐quality trials previously undertaken to measure the effect of the intervention.

Design

A prospective, stepped‐wedge cluster randomized controlled trial was undertaken October–November 2015. This process evaluation was conducted using qualitative and quantitative methods to explain discrepancies between expected and observed clinical trial outcomes.

Methods

Qualitative data were collected using focus groups with the healthcare team and contrasted with fidelity data. Quantitative data were collected using attendance lists, audits and observations and analysed descriptively. Concept‐driven coding was undertaken using a framework derived from studies citing the Theoretical Domains Framework.

Findings

Staff training in the trial protocol was viewed positively, however, not all staff attended. Staff were generally enthusiastic about Protected Mealtimes with many programme aspects successfully implemented. Limited staffing resources, particularly of nursing staff, hindered implementation. The presence of trial observers affected staff morale by increasing feelings of stress and anxiety.

Conclusion

Process data allowed challenges for the implementation of Protected Mealtimes under clinical trial conditions to be described. Given our inability to implement the trial protocol fully due to the complexity of the mealtime environment and the lack of efficacy on nutritional intake, alternative approaches should be considered to resolve the problem of hospital malnutrition.
Task‐related fMRI in hemiplegic cerebral palsy—A systematic review
Authors: Gaberova Katerina , Pacheva Iliyana , Ivanov Ivan
Published: April 2018

Rationale

Functional magnetic resonance imaging (fMRI) is used widely to study reorganization after early brain injuries. Unilateral cerebral palsy (UCP) is an appealing model for studying brain plasticity by fMRI.

Aim

To summarize the results of task‐related fMRI studies in UCP in order to get better understanding of the mechanism of neuroplasticity of the developing brain and its reorganization potential and better translation of this knowledge to clinical practice.

Methods

A systematic search was conducted on the PubMed database by keywords: “cerebral palsy”, “congenital hemiparesis”, “unilateral”, “Magnetic resonance imaging” , “fMRI”, “reorganization”, and “plasticity” The exclusion criteria were as follows: case reports; reviews; studies exploring non‐UCP patients; and studies with results of rehabilitation.

Results

We found 7 articles investigated sensory tasks; 9 studies—motor tasks; 12 studies—speech tasks. Ipsilesional reorganization is dominant in sensory tasks (in 74/77 patients), contralesional—in only 3/77. In motor tasks, bilateral activation is found in 64/83, only contralesional—in 11/83, and only ipsilesional—8/83. Speech perception is bilateral in 35/51, only or dominantly ipsilesional (left‐sided) in 8/51, and dominantly contralesional (right‐sided) in 8/51. Speech production is only or dominantly contralesional (right‐sided) in 88/130, bilateral—26/130, and only or dominantly ipsilesional (left‐sided)—in 16/130.

Discussion

The sensory system is the most “rigid” to reorganization probably due to absence of ipsilateral (contralesional) primary somatosensory representation. The motor system is more “flexible” due to ipsilateral (contralesional) motor pathways. The speech perception and production show greater flexibility resulting in more bilateral or contralateral activation.

Conclusions

The models of reorganization are variable, depending on the development and function of each neural system and the extent and timing of the damage. The plasticity patterns may guide therapeutic intervention and prognostics, thus proving the fruitiness of the translational approach in neurosciences.
How Friedman and Schwartz Became Monetarists
Authors: LOTHIAN JAMES R. , TAVLAS GEORGE S.
Published: April 2018

During the early‐1940s, both Milton Friedman and Anna Schwartz downplayed the role of money in the economy. By the mid‐1950s, they had not only become what later were called monetarists, but the findings from their joint work defined monetarism. The key factor underlying the change in their views was what they learned from their study of U.S. historical experience, especially their empirical confirmation of the Fed's role in the Great Depression. Here, the influence of Clark Warburton on Friedman's thinking loomed large. We document Friedman's advocacy of the constant‐money‐growth rule as an outgrowth of his and Schwartz's empirical research.