bluuebunny/crossref_metadata_2025 huggingface dataset:
Effectiveness of a Pharmacist‐Led Drug Counseling on Enhancing Antihypertensive Adherence and Blood Pressure Control: A Randomized Controlled Trial
Authors: Wong Martin C.S. , Liu Kirin Q.L. , Wang Harry H.X. , Lee Catherine L.S. , Kwan Mandy W.M. , Lee Ken W.S. , Cheung Yu , Lee Gabrielle K.Y. , Morisky Donald E. , Griffiths Sian M.
Published: May 2013

Adherence to antihypertensive medications represents a crucial success factor for optimal blood pressure (BP) control in clinical practice. This study evaluated whether an additional pharmacist‐led medication counseling could achieve better optimal BP control and enhance compliance. In a designated family clinic in a region with similar resident characteristics to Hong Kong, patients taking ≥ one antihypertensive agent with suboptimal compliance were randomly allocated to a brief 3‐minute drug advice (control; n = 161) or pharmacist counseling (intervention; n = 113). The two groups were compared by repeated measure ANOVA at 3‐months and 6‐months with BP control and medication compliance as outcome variables, respectively. The proportions of patients having optimal compliance increased from 0% to 41.1% at 3 months and 61.9% at 6 months (P < 0.001). The proportion of patients having optimal BP control improved from 64.1% at baseline to 74.0% at 3 months and 74.5% at 6 months (P = 0.023). There were no significant differences between the two groups in the changes of BP control and compliance levels. This study implied that even a brief 3‐minute drug advice might lead to improved BP levels among patients on antihypertensive medications in general practice, but did not demonstrate additional effects by pharmacist counseling.
Population Pharmacokinetics of Belimumab Following Intravenous Administration in Patients With Systemic Lupus Erythematosus
Authors: Struemper Herbert , Chen Cecil , Cai Wendy
Published: May 2013

The population pharmacokinetics (PK) of belimumab were characterized in 1,603 patients with systemic lupus erythematosus receiving belimumab 1, 4, 10, or 20 mg/kg doses in Phase 1–3 trials. Belimumab PK were well described with a linear two‐compartment model, with clearance from the central compartment (CL). Belimumab exposure was approximately dose‐proportional. The estimated population terminal half‐life was 19.4 days and steady‐state volume of distribution (Vss) was 5.29 L for the currently approved 10 mg/kg dose used in the Phase 3 trials, with an estimated CL of 215 mL/day. No effects of age, sex, race, disease activity, co‐medications, or baseline characteristics on belimumab PK were found to alter exposure in a manner requiring dose adjustment. An association observed between increasing baseline proteinuria and increasing CL may be clinically relevant in nephropathy with very high proteinuria levels. No evidence of target‐mediated clearance was observed. Clinically relevant effects of body size (increased CL and V1 with increased body weight, and reduced V1 with increased body mass index) have been accounted for in current weight‐normalized belimumab dosing.
In vivo protection of activated Tyr22‐dihydrofolate reductase gene‐modified canine T lymphocytes from methotrexate
Authors: Gori Jennifer L. , Beard Brian C. , Williams Nathaniel P. , Ironside Christina , Swanson Debra , Scott McIvor R. , Kiem Hans‐Peter
Published: May 2013

Background

Nonmyeloablative allogeneic hematopoietic stem cell (HSC) transplantation can cure malignant and nonmalignant diseases affecting the hematopoietic system, such as severe combined immunodeficiencies, aplastic anemia and hemoglobinopathies. Although nonmyeloablative is favored over myeloablative transplantation for many patients, graft rejection remains problematic. One strategy for decreasing rejection is to protect donor activated T cells in the graft from methotrexate (MTX) by genetically modifying the cells to express MTX‐resistant dihydrofolate reductase (Tyr22‐DHFR), leaving the immunosuppressive effects of MTX to act solely on activated host T lymphocytes, shifting the balance to favor allogeneic engraftment.

Methods

To evaluate MTX resistance of Tyr22‐DHFR+ T lymphocytes in vivo, we transplanted dogs with autologous CD34+ cells modified with yellow fluorescent protein (YFP) and DHFR‐green fluorescent protein (GFP) lentivirus vectors. Dogs were then treated with a standard MTX regimen days 1, 3, 6 and 11) following immune activation with a foreign antigen as a surrogate assay to mimic early transplantation.

Results

DHFR‐GFP+ gene marking was maintained in CD3+CD25+ and CD4+ T lymphocytes after MTX treatment, whereas the level of T lymphocytes that expressed only a fluorescent reporter (YFP+) decreased. These data show that Tyr22‐DHFR expression protects T lymphocytes from MTX toxicity in dogs, highlighting a clinically relevant application for preserving donor T lymphocytes during post‐transplantation immunosuppression.

Conclusions

The findings of the present study have implications for the clinical translation of MTX‐resistant T cells to facilitate engraftment of allogeneic cells following nonmyeloablative conditioning and to minimize the risk of rejection. In summary, Tyr22‐DHFR expression in T lymphocytes provides chemoprotection from MTX‐mediated elimination in the context of immune activation in vivo. Copyright © 2013 John Wiley & Sons, Ltd.
Teleseismic magnetic effects (TMDs) of 2011 Tohoku earthquake
Authors: Hao Y. Q. , Xiao Z. , Zhang D. H.
Published: May 2013

Anomalous magnetic variations were observed by ground magnetometers in East Asia area after the 2011 Tohoku earthquake. Some earlier reports showed that the seismo‐magnetic variations have obvious amplitude around the epicenter, we emphasis here that the variations can still be notable at stations 2000–4000 km away from epicenter, and we define it as teleseismic magnetic disturbances (TMDs). TMDs appear about 8 min later after the arrival of seismic Rayleigh waves at teleseismic distances and propagate at a horizontal velocity of 3.9 ± 0.1 km/s. The wave‐like TMDs last for no longer than 10 min and have a main period of 2.1–3.3 min. TMDs are not generated by direct effects of processes in focal area crust or tsunami waves, instead, their properties consist with the Rayleigh wave model of seismo‐ionospheric disturbances. Hence, we conclude that the TMDs are the magnetic manifestation of seismotraveling ionospheric disturbances (STIDs) generated by the interaction between the ionosphere and atmosphere through acoustic waves launched by traveling Rayleigh waves. Our findings contribute to the knowledge of seismo‐electromagnetic effects in the atmosphere‐ionosphere system and further our understanding of couplings between various spheres of the Earth.
Chemical characterization of individual particles and residuals of cloud droplets and ice crystals collected on board research aircraft in the ISDAC 2008 study
Authors: Hiranuma N. , Brooks S. D. , Moffet R. C. , Glen A. , Laskin A. , Gilles M. K. , Liu P. , Macdonald A. M. , Strapp J. W. , McFarquhar G. M.
Published: May 2013

Ambient particles and the dry residuals of mixed‐phase cloud droplets and ice crystals were collected during the Indirect and Semi‐Direct Aerosol Campaign (ISDAC) near Barrow, Alaska, in spring of 2008. The collected particles were analyzed using Computer Controlled Scanning Electron Microscopy with Energy Dispersive X‐ray analysis and Scanning Transmission X‐ray Microscopy coupled with Near Edge X‐ray Absorption Fine Structure spectroscopy to identify physico‐chemical properties that differentiate cloud‐nucleating particles from the total aerosol population. A wide range of individually mixed components was identified in the ambient particles and residuals including organic carbon compounds, inorganics, carbonates, and black carbon. Our results show that cloud droplet residuals differ from the ambient particles in both size and composition, suggesting that both properties may impact the cloud‐nucleating ability of aerosols in mixed‐phase clouds. The percentage of residual particles which contained carbonates (47%) was almost four times higher than those in ambient samples. Residual populations were also enhanced in sea salt and black carbon and reduced in organic compounds relative to the ambient particles. Further, our measurements suggest that chemical processing of aerosols may improve their cloud‐nucleating ability. Comparison of results for various time periods within ISDAC suggests that the number and composition of cloud‐nucleating particles over Alaska can be influenced by episodic events bringing aerosols from both the local vicinity and as far away as Siberia.
Regional mapping of gas uptake by blood and tissue in the human lung using hyperpolarized xenon‐129 MRI
Authors: Qing Kun , Ruppert Kai , Jiang Yun , Mata Jaime F. , Miller G. Wilson , Shim Y. Michael , Wang Chengbo , Ruset Iulian C. , Hersman F. William , Altes Talissa A. , Mugler John P.
Published: May 2013

Purpose

To develop a breathhold acquisition for regional mapping of ventilation and the fractions of hyperpolarized xenon‐129 (Xe129) dissolved in tissue (lung parenchyma and plasma) and red blood cells (RBCs), and to perform an exploratory study to characterize data obtained in human subjects.

Materials and Methods

A three‐dimensional, multi‐echo, radial‐trajectory pulse sequence was developed to obtain ventilation (gaseous Xe129), tissue, and RBC images in healthy subjects, smokers, and asthmatics. Signal ratios (total dissolved Xe129 to gas, tissue‐to‐gas, RBC‐to‐gas, and RBC‐to‐tissue) were calculated from the images for quantitative comparison.

Results

Healthy subjects demonstrated generally uniform values within coronal slices, and a gradient in values along the anterior‐to‐posterior direction. In contrast, images and associated ratio maps in smokers and asthmatics were generally heterogeneous and exhibited values mostly lower than those in healthy subjects. Whole‐lung values of total dissolved Xe129 to gas, tissue‐to‐gas, and RBC‐to‐gas ratios in healthy subjects were significantly larger than those in diseased subjects.

Conclusion

Regional maps of tissue and RBC fractions of dissolved Xe129 were obtained from a short breathhold acquisition, well tolerated by healthy volunteers and subjects with obstructive lung disease. Marked differences were observed in spatial distributions and overall amounts of Xe129 dissolved in tissue and RBCs among healthy subjects, smokers and asthmatics. J. Magn. Reson. Imaging 2014;39:346–359. © 2013 Wiley Periodicals, Inc.
Early Spanish meteorological records (1780–1850)
Authors: Domínguez‐Castro F. , Vaquero J. M. , Rodrigo F. S. , Farrona A. M. M. , Gallego M. C. , García‐Herrera R. , Barriendos M. , Sanchez‐Lorenzo A.
Published: May 2013

ABSTRACT

This article summarizes recent efforts on early instrumental data recovery in Spain conducted under the Salvà‐Sinobas project. We have retrieved and digitized more than 100 000 meteorological observations prior to 1850 in Spain. This data set contains measurements of air temperature, atmospheric pressure, wind direction and state of the atmosphere in 16 places located in Iberia and the Balearic Islands. Most of the observations are made on a daily basis. However, monthly and annual information has also been retrieved. The time coverage of the series is not homogeneous, with the earliest records starting in Seville in 1780. Prior to this work only two series were available in Spain (i.e. Cadiz and Barcelona), so this data set represents a great advance in the early data availability for Spain. Due to the lack of metadata in most of the series, their interpretation must be made with caution. © 2013 Royal Meteorological Society
Arbuscular Mycorrhizal Fungi and Glomalin‐Related Soil Protein as Potential Indicators of Soil Quality in a Recuperation Gradient of the Atlantic Forest in Brazil
Authors: Vasconcellos Rafael L. F. , Bonfim Joice Andrade , Baretta Dilmar , Cardoso Elke J. B. N.
Published: May 2013

This study aimed at surveying arbuscular mycorrhizal fungi (AMF) species and glomalin‐related soil protein (GRSP) to understand their role as presumable biological indicators of soil quality in an undisturbed forest site (NT) and three sites with different management histories, soil textures, and different ages of recovery after reforestation for 20 (R20), 10 (R10) and 5 years (R05). Our objective was to determine how physical, chemical and microbiological soil attributes influence AMF species distribution, total‐GRSP (T‐GRSP) and easily extractable‐GRSP (EE‐GRSP). Glomus and Acaulospora were related to impacted sites, Gigaspora rosea to sites R10 and R20 that have different management histories and soil textures and Glomus geosporum to sites NT and R10, suggesting some influence of texture on its distribution. Scutellospora pellucida and other species were found only in one season. Correlations between EE‐GRSP and T‐GRSP on the one hand and total carbon and nitrogen, dehydrogenase and urease activity, microbial biomass carbon and microbial biomass nitrogen, on the other, reached values of 40–70% and were especially strong in summer. Soil bulk density had a negative and macroporosity a positive effect only on EE‐GRSP, suggesting the necessity to choose either EE‐GRSP or T‐GRSP as biological indicator depending on the soil characteristics and management. This study demonstrates the effect of recovery age, seasonality and other soil attributes on AMF and GRSP distribution and shows that these biological attributes may be used as indicators of soil quality in the Atlantic forest in Brazil. Copyright © 2013 John Wiley & Sons, Ltd.
Microwell Chips for Selection of Bio‐macromolecules that Increase the Differentiation Capacities of Mesenchymal Stem Cells
Authors: Hsu Shan‐hui , Ni Yu‐Hui , Lee Yung‐Chun
Published: May 2013

Microwell chips (25 mm × 25 mm) are fabricated to select proper substrates for growing three‐dimensional (3D) spheroids from mesenchymal stem cells (MSCs). Different bio‐macromolecules and their combinations are immobilized on the chip by air plasma treatment and by polyelectrolyte interaction. Only a small number of MSCs (≈105) are needed for each chip. The expression level of N‐cadherin, a cell‐adhesion molecule, is used as an indicator for cell‐cell interactions. MSC spheroids expressing the highest N‐cadherin level also show the greatest osteogenic potential. The microwell chip may be used as an efficient platform to screen bio‐macromolecules that enhance the differentiation potential of MSCs.
Synthesis and Properties of Poly(p‐phenylene ethynylene)s with Oxidation‐ and Reduction‐Sensitive Moieties
Authors: Schroeter Michael , Behl Marc , Kaiser Christian , Lendlein Andreas
Published: May 2013

The synthesis of redox‐sensitive poly(p‐phenylene ethynylene)s (rsPPEs) bearing protected quinones in their backbone by the Sonogashira coupling reaction is described. The rsPPEs show excellent solubility in toluene, tetrahydrofurane, and chloroform. Cleavage of the protection group of the incorporated quinone moieties enables main‐chain conductive polymers having redox‐sensitive properties to be produced. These redox‐sensitive switches can be reduced and oxidized in solution, as well as in the solid state, accompanied by a change of the photoluminescence values. The processes occurring during oxidation and reduction are analyzed by UV–vis and photoluminescence spectroscopy and lead to a decrease of intensity of 80% during oxidation. Such multifunctional polymers may be useful for redox‐potential changing stimuli in biological systems.

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Heme‐related gene expression signatures of meat intakes in lung cancer tissues
Authors: Lam Tram Kim , Rotunno Melissa , Ryan Brid M. , Pesatori Angela C. , Bertazzi Pier Alberto , Spitz Margaret , Caporaso Neil E. , Landi Maria Teresa
Published: May 2013

Lung cancer causes more deaths worldwide than any other cancer. In addition to cigarette smoking, dietary factors may contribute to lung carcinogenesis. Epidemiologic studies, including the environment and genetics in lung cancer etiology (EAGLE), have reported increased consumption of red/processed meats to be associated with higher risk of lung cancer. Heme–iron toxicity may link meat intake with cancer. We investigated this hypothesis in meat‐related lung carcinogenesis using whole genome expression. We measured genome‐wide expression (HG‐U133A) in 49 tumor and 42 non‐involved fresh frozen lung tissues of 64 adenocarcinoma EAGLE patients. We studied gene expression profiles by high‐versus‐low meat consumption, with and without adjustment by sex, age, and smoking. Threshold for significance was a false discovery rate (FDR) ≤0.15. We studied whether the identified genes played a role in heme–iron related processes by means of manually curated literature search and gene ontology‐based pathway analysis. We found that gene expression of 232 annotated genes in tumor tissue significantly distinguished lung adenocarcinoma cases who consumed above/below the median intake of fresh red meats (FDR = 0.12). Sixty‐three (∼28%) of the 232 identified genes (12 expected by chance, P‐value < 0.001) were involved in heme binding, absorption, transport, and Wnt signaling pathway (e.g., CYPs, TPO, HPX, HFE, SLCs, and WNTs). We also identified several genes involved in lipid metabolism (e.g., NCR1, TNF, and UCP3) and oxidative stress (e.g., TPO, SGK2, and MTHFR) that may be indirectly related to heme‐toxicity. The study's results provide preliminary evidence that heme–iron toxicity might be one underlying mechanism linking fresh red meat intake and lung cancer. © 2013 Wiley Periodicals, Inc.
Defining the Epsilon‐Sarcoglycan (SGCE) Gene Phenotypic Signature in Myoclonus‐Dystonia: A Reappraisal of Genetic Testing Criteria
Authors: Carecchio Miryam , Magliozzi Monia , Copetti Massimiliano , Ferraris Alessandro , Bernardini Laura , Bonetti Monica , Defazio Giovanni , Edwards Mark J. , Torrente Isabella , Pellegrini Fabio , Comi Cristoforo , Bhatia Kailash P. , Valente Enza Maria
Published: May 2013

Mutations or exon deletions of the epsilon‐sarcoglycan (SGCE) gene cause myoclonus‐dystonia (M‐D), but a subset of M‐D patients are mutation‐negative and the sensitivity and specificity of current genetic testing criteria are unknown. We screened 46 newly enrolled M‐D patients for SGCE mutations and deletions; moreover, 24 subjects previously testing negative for SGCE mutations underwent gene dosage analysis. In our combined cohorts, we calculated sensitivity, specificity, positive and negative predictive values, and area under the curve of 2 published sets of M‐D diagnostic criteria. A stepwise logistic regression was used to assess which patients' characteristics best discriminated mutation carriers and to calculate a new mutation predictive score (“new score”), which we validated in previously published cohorts. Nine of 46 (19.5%) patients of the new cohort carried SCGE mutations, including 5 novel point mutations and 1 whole‐gene deletion; in the old cohort, 1 patient with a complex phenotype carried a 5.9‐Mb deletion encompassing SGCE. Current diagnostic criteria had a poor ability to discriminate SGCE‐positive from SGCE‐negative patients in our cohort; conversely, age of onset, especially if associated with psychiatric features (as included in the new score), showed the best discriminatory power to individuate SGCE mutation carriers, both in our cohort and in the validation cohort. Our results suggest that young age at onset of motor symptoms, especially in association with psychiatric disturbance, are strongly predictive for SGCE positivity. We suggest performing gene dosage analysis by multiple ligation‐dependent probe amplification (MLPA) to individuate large SGCE deletions that can be responsible for complex phenotypes. © 2013 Movement Disorder Society
4‐Hydroxyderricin and xanthoangelol from Ashitaba (Angelica keiskei) suppress differentiation of preadiopocytes to adipocytes via AMPK and MAPK pathways
Authors: Zhang Tianshun , Sawada Keisuke , Yamamoto Norio , Ashida Hitoshi
Published: May 2013

Scope

Adipocytes differentiation is deeply involved in the onset of obesity. 4‐Hydroxyderricin (4HD) and xanthoangelol (XAG) are the chalcones that are derived from Ashitaba (Angelica keiskei). In this study, we demonstrated the inhibitory effects of these chalcones on adipocytes differentiation.

Methods and results

4HD and XAG suppressed intracellular lipid accumulation by Oil red O staining at 5 μM without cytotoxicity. They inhibited adipocytes differentiation accompanied by down‐expression of adipocyte‐specific transcription factors, CCAAT/enhancer‐binding protein‐β (C/EBP‐β), C/EBP‐α, and peroxisome proliferator‐activated receptor gamma (PPAR‐γ) using RT‐PCR and Western blotting analysis. To obtain insights into the underlying mechanism, the activation of AMP‐activated protein kinase (AMPK) and mitogen‐activated protein kinase pathways was investigated. These two chalcones promoted phosphorylation of AMPK and acetyl CoA carboxylase during differentiation of 3T3‐L1 adipocytes accompanied by a decrease in glycerol‐3‐phosphate acyl transferase‐1 and an increase in carnitine palmitoyltransferase‐1 mRNA expression. These chalcones also promoted phosphorylation of extracellular signal‐regulated kinases and Jun aminoterminal kinases, but not p38. Moreover, the inhibitors for AMPK and extracellular signal‐regulated kinases abolished the chalcones‐caused down‐expression of C/EBP‐β, C/EBP‐α, and PPAR‐γ. Treatment with Jun aminoterminal kinases inhibitor abolished the down‐expression of C/EBP‐α and PPAR‐γ, but not C/EBP‐β.

Conclusion

4HD and XAG inhibit adipocytes differentiation through AMPK and mitogen‐activated protein kinase pathways, resulting in the down‐expression of adipocyte‐specific transcription factors.
Coniothyrione: anatomy of a structure revision
Authors: Martin Gary E. , Buevich Alexei V. , Reibarkh Mikhail , Singh Sheo B. , Ondeyka John G. , Williamson R. Thomas
Published: May 2013

Coniothyrione is a xanthone‐derived antibiotic reported several years ago by researchers at Merck & Co. Inc. Revision of the position of the chloro substitution was recently proposed on the basis of empirical reinterpretation of the carbon chemical shift data and a hypothetical biosynthetic argument without the acquisition of any new spectral data to support the postulated change in substituent location. The originally published HMBC data lead to an equivocal assignment of the structure and do not provide a solid basis of support for either structure. Neural network 13C chemical shift calculations and density functional theory calculations also led to undifferentiated structures. Definitive confirmation of the structure of coniothyrione based on the acquisition and interpretation of 1,1‐ADEQUATE and inverted 1JCC 1,n‐ADEQUATE data is now reported. Copyright © 2013 John Wiley & Sons, Ltd.
Mismatch DNA repair mRNA expression profiles in oral melanin pigmentation lesion and hamartomatous polyp of a child with peutz–jeghers syndrome
Authors: Vageli Dimitra P. , Doukas Sotirios G. , Markou Andreas
Published: May 2013

Mismatch DNA repair (MMR) mRNA expression analysis was performed on a biopsy of oral mucosa melanin pigmentation lesion, a hamartomatous polyp and peripheral blood derived from a 12‐year‐old child with Peutz–Jeghers Syndrome (PJS). We present a deficient MMR system, in a PJS patient, which demonstrated low mRNA levels of hMSH6 and hPMS2 and an increasing MMR deficiency from the non‐dysplastic lesion to hamartomatous polyp of PJS with a high risk of cancer. Pediatr Blood Cancer 2013;60:E116–E117. © 2013 Wiley Periodicals, Inc.
Depressive‐like history alters persistent pain behavior in rats: Opposite contribution of frontal cortex and amygdala implied
Authors: Qi Wei‐Jing , Wang Wei , Wang Ning , Wang Jin‐Yan , Luo Fei
Published: May 2013

Numerous studies have shown that pain perception is strongly influenced by depression. However, very few studies have examined whether pain perception is altered in the remission period of depression, and what role the fronto‐limbic circuits may play in the behavioral changes associated with remission. Using an unpredictable chronic mild stress (UCMS) animal model of depression, the present study investigated pain‐related behaviors in rats with prior exposure to a UCMS stimulus. The γ‐aminobutyric acid (GABA)A receptor agonist muscimol was microinjected bilaterally into the basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) to examine the modulation of pain by these brain regions in the recovery state. Rats with a depression‐like history displayed increased ongoing pain behavior in the formalin test, although their thermal pain thresholds were unchanged. Intra‐BLA muscimol during the recovery phase dramatically decreased formalin‐induced pain behavior and also significantly increased rats' sucrose preference. By contrast, in the mPFC, muscimol produced the opposite effect, suggesting different, perhaps opposing, roles of the BLA and mPFC in mediating the influence of prior UCMS exposure on pain perception. Taken together, these results demonstrated that a depressive experience may cause long‐term alterations in limbic circuit excitability and thus lead to long‐lasting changes in pain perception.
Maternal cfDNA screening for Down syndrome – a cost sensitivity analysis
Authors: Cuckle Howard , Benn Peter , Pergament Eugene
Published: May 2013

Objective

This study aimed to determine the principal factors contributing to the cost of avoiding a birth with Down syndrome by using cell‐free DNA (cfDNA) to replace conventional screening.

Methods

A range of unit costs were assigned to each item in the screening process. Detection rates were estimated by meta‐analysis and modeling. The marginal cost associated with the detection of additional cases using cfDNA was estimated from the difference in average costs divided by the difference in detection.

Results

The main factor was the unit cost of cfDNA testing. For example, replacing a combined test costing $150 with 3% false‐positive rate and invasive testing at $1000, by cfDNA tests at $2000, $1500, $1000, and $500, the marginal cost is $8.0, $5.8, $3.6, and $1.4m, respectively. Costs were lower when replacing a quadruple test and higher for a 5% false‐positive rate, but the relative importance of cfDNA unit cost was unchanged. A contingent policy whereby 10% to 20% women were selected for cfDNA testing by conventional screening was considerably more cost‐efficient. Costs were sensitive to cfDNA uptake.

Conclusion

Universal cfDNA screening for Down syndrome will only become affordable by public health purchasers if costs fall substantially. Until this happens, the contingent use of cfDNA is recommended. © 2013 John Wiley & Sons, Ltd.
Innovative hypoglycaemia care pathway for admission avoidance: a partnership approach with a local ambulance trust
Authors: James June , Fairfield Jane , De Groot Louise , Jackson Steve
Published: May 2013

In 2010, Leicester City Primary Care Trust commissioned an Intermediate Care Diabetes Service. One aspect of the service plan was to work with the local ambulance trust to gather data around patients using ambulance services for hypoglycaemia, and to provide an advisory service for individuals post ambulance call‐out.

This audit identified 388 diabetic emergency ambulance call‐outs locally (for the period 1 September 2010 to 31 March 2011) including those for hypoglycaemia in the Leicester City area.

The new service commissioned by Leicester City included diabetes specialist nurse assessment within two working days for all hypoglycaemic individuals accessing ambulance services. A care pathway was drawn up and agreed over a series of meetings between the Intermediate Care Diabetes Service and ambulance service leads. Copyright © 2013 John Wiley & Sons. Practical Diabetes 2013; 30(4): 151–153
Audit of clinical practice in the use of incretin mimetic agents for the management of patients with type 2 diabetes
Authors: Dhesi Balraj , Chauhan Hiren , Basu Ansu
Published: May 2013

The objective of this audit was to compare treatment outcomes in patients on dipeptidyl peptidase (DPP)‐4 inhibitors and glucagon‐like peptide‐1 receptor (GLP‐1R) agonists within a hospital clinic setting, and to identify factors that might influence their response to treatment.

We undertook a retrospective audit of 118 consecutive patients who received either a DPP‐4 inhibitor or a GLP‐1R agonist as add‐on to existing oral hypoglycaemic agent therapy. Primary clinical outcomes compared were change in HbA1c and weight. The clinical characteristics of patients who responded with both weight loss and improvement in HbA1c were compared to those who did not.

The results showed that more patients (73.6%) were on a GLP‐1R agonist; 57% of patients on a GLP‐1R agonist lost weight and had improved HbA1c compared to 40% of patients on a DPP‐4 inhibitor. The mean reduction in HbA1c was 8.4mmol/mol with a mean weight loss of 2.6kg. There were good correlations between the initial HbA1c and decline in HbA1c in both treatment groups. In all, 68.3% of patients on additional insulin treatment improved HbA1c while 46.3% improved in terms of both weight and HbA1c. Patients not on insulin responded better to treatment (OR 1.96; p=0.047) with these agents.

It was concluded that good metabolic control can be achieved if these agents are used judiciously. The DPP‐4 inhibitors improve HbA1c but are weight neutral, while the GLP‐1R agonists cause both weight loss and improvements in HbA1c. The addition of insulin under specialist supervision can be beneficial. Copyright © 2013 John Wiley & Sons. Practical Diabetes 2013; 30(4): 159–162
Evaluation of the Effect of Blackcurrant Products on Gut Microbiota and on Markers of Risk for Colon Cancer in Humans
Authors: Molan Abdul‐Lateef , Liu Zhuojian , Plimmer Gabriel
Published: May 2013

The purpose of this study was to determine in healthy humans whether First Leaf (FL; composed of blackcurrant extract powder, lactoferrin and lutein) and Cassis Anthomix 30 (CAM30; blackcurrant extract powder) can positively modify the colonic microbiota by enhancing the growth of the beneficial bacteria and inactivating the toxic bacterial enzymes which are known to be involved in colonic carcinogenesis. Thirty healthy adult male and female volunteers were recruited for this study. Fluorescent in situ hybridization was carried out to analyse the populations of fecal microbiota. Consumption of FL and CAM30 led to significant increases (P < 0.0001) in the population sizes of lactobacilli and bifidobacteria whereas the population sizes of Clostridium spp. and Bacteroides spp were decreased significantly (P < 0.0001). In addition, feeding of FL and CAM30 decreases the activity of β‐glucuronidase (bacterial enzyme which is considered to be one of the enzymes that increases risk for colorectal cancer) and significantly decreased (P < 0.05) the fecal pH. In conclusion, the results of this study open up the possibility that consumption of FL and CAM30 can offer various benefits to human health through acting as novel prebiotic agents via increasing the numbers of beneficial bacteria (lactobacilli and bifidobacteria) in the gut. Copyright © 2013 John Wiley & Sons, Ltd.
PATTERNS OF ICHTHYOFAUNAL DISTRIBUTION AND CONNECTIVITY IN NAVIGABLE AND FREE‐FLOWING REACHES OF A MAJOR RIVER SYSTEM: THE ALLEGHENY RIVER IN PENNSYLVANIA
Authors: Argent D. G. , Kimmel W. G.
Published: May 2013

Connectivity throughout large riverine networks is often compromised by lock and dam (L/D) structures designed to facilitate year‐round navigation. The resultant interruption of flow inhibits free passage of aquatic biota potentially isolating mainstem and tributary communities. Our objectives were (i) to evaluate the impact of a series of navigational L/D structures on two targeted fish assemblages (TFAs): large‐bodied (>250 mm total length) pelagic and benthic (darter) communities and (ii) to examine patterns of tributary and mainstem connectivity. We systematically captured fishes utilizing gillnets, benthic trawls and backpack electrofishers from an impounded and a free‐flowing reach extending over 203 km of the Allegheny River in Pennsylvania. Species richness among the large‐bodied targeted fish assemblage was distributed somewhat evenly throughout each pool, peaking near dams and in an undredged pool. Depauperate darter assemblages of low species richness characterized most of the navigable reach with diversity and abundance concentrated in L/D tailrace areas. By contrast, darter communities inhabiting the free‐flowing reach were more diverse, abundant and evenly distributed, indicating the influence of uninterrupted connectivity. Community similarity at mainstem/tributary junctions increased with increasing tributary size with 50% of the mainstem species complement also inhabiting the largest tributary. This study underscores the importance of dams as barriers to ichthyofaunal connectivity, particularly to those benthic fishes which are relatively immobile and habitat specific, and the importance of mainstem/tributary junctions as avenues of riverine connectivity. Copyright © 2013 John Wiley & Sons, Ltd.
Avoiding the Target Language with the Help of Google: Managing Language Choices in Gathering Information for EFL Project Work
Authors: Musk Nigel
Published: May 2013

The integration of translation tools into the Google search engine has led to a huge increase in the visibility and accessibility of such tools, with potentially far‐reaching implications for the English language classroom. Although these translation tools are the focus of this study, using them is in fact only one way in which English language learners can exercise their language preferences, especially when working more autonomously. By acting upon these preferences and opting to read in their first language, learners effectively adopt an avoidance strategy—that of avoiding the target language. This qualitative study highlights several ways in which pupils can and do exercise their language choices in their computer‐assisted project work using (Swedish) Google. More specifically, after mapping out the trajectories of pupils' Internet searches and their gathering of resources, conversation analysis is used to zoom in on key moves that are jointly negotiated at the interface with Google, where different language options are made available and even flagged. By making incremental choices that avoid English (or favour Swedish), the visibility of English can diminish radically, if not altogether. The negative implications of avoidance are discussed as well as the practicalities of solutions using Google itself.
Aquaporin‐4 orthogonal arrays of particles from a physiological and pathophysiological point of view
Authors: Nicchia Grazia Paola , Pisani Francesco , Sparaneo Angelo , Mola Maria Grazia , Basco Davide , Rossi Andrea , Svelto Maria , Frigeri Antonio
Published: May 2013

Aquaporin‐4 (AQP4) is the neuromuscular water channel that is also expressed at the basolateral membranes of other cell types in kidney, stomach, and lung. In skeletal muscle, AQP4 is found at the sarcolemma of fast‐twitch fibers and its function is strictly correlated with the glycolytic metabolism. In the central nervous system, AQP4 is expressed at the basolateral membranes of ependymal cells, and is highly concentrated at the glial end‐foot processes surrounding blood vessels and forming the glia limitans, as well as at the nonend‐foot glial processes of the granule cell layer in the cerebellum. AQP4 plasma membrane organization is different from other aquaporins (AQPs). AQP4 is expressed as two major polypeptides called M1 and M23. These two isoforms form heterotetramers appearing in the plasma membrane as intramembrane particles (IMPs) observable by freeze‐fracture electron microscopy. Such tetrameric organization is common to all other AQPs. In the case of AQP4, however, multiple IMPs further aggregate to form structures called orthogonal arrays of particles (OAPs). The relative abundance of M23 and M1 in vivo is the major determinant for the formation of OAPs of different sizes. The function of AQP4 aggregation into OAPs under normal conditions is still not completely understood. Interestingly, there are several reports indicating that OAPs are involved in different neuromuscular diseases. In particular, the OAP‐related diseases that have attracted more attention are Duchenne muscular distrophy and, more recently, neuromyelitis optica, the two pathological conditions in which OAPs are involved in completely different ways. WIREs Membr Transp Signal 2013, 2:143–154. doi: 10.1002/wmts.86

Conflict of interest: The authors have declared no conflicts of interest for this article.

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Synthesis and Single Crystal X‐ray Structures of Cationic Zinc β‐Diketiminate Complexes
Authors: Scheiper Christoph , Schulz Stephan , Wölper Christoph , Bläser Dieter , Roll Joachim
Published: May 2013

The cationic zinc complex [L1Zn][Al(OC(CF3)3)4] (1) (L1 = {[(2,4,6‐Me3–C6H2)NC(Me)]2CH}) bearing a weakly coordinating aluminate anion was obtained from reaction of L1ZnCl with Li[Al(OC(CF3)3)4]. In addition, base‐stabilized zinc cations [L1/2Zn(base)2][X] (2–5) (L2 = {[(2,6‐iPr2–C6H3)NC(Me)]2CH}; X = [Al(OC(CF3)3)4], [B(C6F5)4]) containing weakly coordinating anions and different Lewis bases (dimethylaminopyridine (dmap), tert‐butylpyridine (tBuPy)) were synthesized and structurally characterized. Moreover, the solid‐state structures of L1ZnMe (6) and the neutral base‐stabilized complexes tBuPy‐Zn(Cl)L1 (7) and base‐Zn(Me)L2 (base = dmap 8, tBuPy 9) are reported and compared with those of 2–5. Preliminary studies showed that 1 is catalytically activity in lactide polymerization at 160 °C.
Two-Higgs-doublet models and enhanced rates for a 125 GeV Higgs
Authors: Drozd Aleksandra , Grzadkowski Bohdan , Gunion John F. , Jiang Yun
Published: May 2013

Abstract

We examine the level of enhancement that can be achieved in the ZZ and γγ channels for a two-Higgs-doublet model Higgs boson (either the light h or the heavy H) with mass near 125 GeV after imposing all constraints from LEP data, B physics, precision electroweak data, vacuum stability, unitarity and perturbativity. The latter constraints restrict substantially the possibilities for enhancing the gg → h → γγ or gg → H → γγ signal relative to that for the SM Higgs, h
SM. Further, we find that a large enhancement of the gg → h → γγ or gg → H → γγ signal in Type II models is possible only if the gg → h → ZZ or gg → H → ZZ mode is even more enhanced, a situation disfavored by current data. In contrast, in the Type I model one can achieve enhanced rates in the γγ final state for the h while having the ZZ mode at or below the SM rate — the largest [gg → h → γγ]/[gg → h
SMγγ] ratio found is of order ~ 1.3 when the two Higgs doublet vacuum expectation ratio is tan β = 4 or 20 and the charged Higgs boson has its minimal LEP-allowed value of m

H± = 90 GeV.
Perfect periodic scheduling for three basic cycles
Authors: Kim Eun-Seok , Glass Celia A.
Published: May 2013

Periodic scheduling has many attractions for wireless telecommunications. It offers energy saving where equipment can be turned off between transmissions, and high-quality reception through the elimination of jitter, caused by irregularity of reception. However, perfect periodic schedules, in which each (of

$$n$$

n

) client is serviced at regular, prespecified intervals, are notoriously difficult to construct. The problem is known to be NP-hard even when service times are identical. This paper focuses on cases of up to three distinct periodicities, with unit service times. Our contribution is to derive a

$$O(n^4)$$

O
(

n

4

)

test for the existence of a feasible schedule, and a method of constructing a feasible schedule if one exists, for the given combination of client periodicities. We also indicate why schedules with a higher number of periodicities are unlikely to be useful in practice. This methodology can be used to support perfect periodic scheduling in a wide range in real world settings, including machine maintenance service, wireless mesh networks and various other telecommunication networks transmitting packet size data.
Helicobacter pylori secretes the chaperonin GroEL (HSP60), which binds iron
Authors: González‐López Marco Antonio , Velázquez‐Guadarrama Norma , Romero‐Espejel María Elena , de Jesús Olivares‐Trejo José
Published: May 2013

Helicobacter pylori is a bacterium that can use multiple iron sources. However, it is unknown whether this bacterium secretes molecules such as siderophores or haemophores to scavenge iron. Here, we report the first secreted iron‐binding protein of H. pylori, which we purified by haem‐affinity chromatography. Mass spectrometry analysis revealed its identity as chaperonin (HpGroEL). When we compared HpGroEL with EcGroEL from Escherichia coli, they were homologous, showing 60% similarity. Additionally, purified cytoplasmic HpGroEL could also bind iron. Perhaps H. pylori secretes HpGroEL to maintain the appropriate folding of extracellular proteins and to bind iron.
Inorganic pyrophosphatases: One substrate, three mechanisms
Authors: Kajander Tommi , Kellosalo Juho , Goldman Adrian
Published: May 2013

Soluble inorganic pyrophosphatases (PPases) catalyse an essential reaction, the hydrolysis of pyrophosphate to inorganic phosphate. In addition, an evolutionarily ancient family of membrane‐integral pyrophosphatases couple this hydrolysis to Na+ and/or H+ pumping, and so recycle some of the free energy from the pyrophosphate. The structures of the H+‐pumping mung bean PPase and the Na+‐pumping Thermotoga maritima PPase solved last year revealed an entirely novel membrane protein containing 16 transmembrane helices. The hydrolytic centre, well above the membrane, is linked by a charged “coupling funnel” to the ionic gate about 20 Å away. By comparing the active sites, fluoride inhibition data and the various models for ion transport, we conclude that membrane‐integral PPases probably use binding of pyrophosphate to drive pumping.
Non‐coding RNAs in DNA damage and repair
Authors: Sharma Vivek , Misteli Tom
Published: May 2013

Non‐coding RNAs (ncRNAs) are increasingly recognized as central players in diverse biological processes. Upon DNA damage, the DNA damage response (DDR) elicits a complex signaling cascade, which includes the induction of multiple ncRNA species. Recent studies indicate that DNA‐damage induced ncRNAs contribute to regulation of cell cycle, apoptosis and DNA repair, and thus play a key role in maintaining genome stability. This review summarizes the emerging role of ncRNAs in DNA damage and repair.
Conformational dynamics in phosphoglycerate kinase, an open and shut case?
Authors: Bowler Matthew W.
Published: May 2013

Domain motions are essential to many catalytic mechanisms in enzymes but they are often difficult to study. X‐ray crystal structures can provide molecular details of snapshots of catalysis but many states important in the cycle remain inaccessible using this technique. Phosphoglycerate kinase (PGK) undergoes large domain movements in order to catalyse the production of ATP. PGK is the enzyme responsible for the first ATP generating step of glycolysis and has been implicated in oncogenesis and the in vivo activation of l‐nucleoside pro‐drugs effective against retroviruses. Its mechanism requires considerable hinge bending to bring the substrates into proximity in order for phosphoryl transfer to occur. The enzyme has been the subject of intense study for decades but new crystal structures, methods in solution scattering and modelling techniques are throwing light on the dynamics of catalysis of this archetypal kinase. Here, I argue that Brownian forces acting on the protein are the dominant factor in the catalytic cycle and that the enzyme has evolved measures to harness this force for efficient catalysis.
Key role of lipids in heat stress management
Authors: Balogh Gábor , Péter Mária , Glatz Attila , Gombos Imre , Török Zsolt , Horváth Ibolya , Harwood John L. , Vígh László
Published: May 2013

Heat stress is a common and, therefore, an important environmental impact on cells and organisms. While much attention has been paid to severe heat stress, moderate temperature elevations are also important. Here we discuss temperature sensing and how responses to heat stress are not necessarily dependent on denatured proteins. Indeed, it is clear that membrane lipids have a pivotal function. Details of membrane lipid changes and the associated production of signalling metabolites are described and suggestions made as to how the interconnected signalling network could be modified for helpful intervention in disease.
Copper chaperones. The concept of conformational control in the metabolism of copper
Authors: Palumaa Peep
Published: May 2013

Copper chaperones compose a specific class of proteins assuring safe handling and specific delivery of potentially harmful copper ions to a variety of essential copper proteins. Copper chaperones are structurally heterogeneous and can exist in multiple metal‐loaded as well as oligomeric forms. Moreover, many copper chaperones can exist in various oxidative states and participate in redox catalysis, connected with their functioning. This review is focused on the analysis of the structural and functional properties of copper chaperones and their partners, which allowed us to define specific regulatory principles in copper metabolism connected with copper‐induced conformational control of copper proteins.
Independent voices, social insight, and action: An analysis of a social action project
Authors: Epstein Shira Eve
Published: May 2013

Social action projects provide opportunities for students to practice civic skills by learning about pressing social issues and taking action to address them. So to explore the texture of such projects, this paper illustrates how the pedagogy guiding them can support students to experience their agency as individuals, develop their knowledge of their broader social contexts, and provide opportunities for action. While the value of a relationship between individual agency, social knowledge, and action are richly described in theoretical texts, this paper shows how such principles are extended in one social action project that unfolded in an eighth grade class. Through the use of qualitative methods, I documented and analyzed the project. I share my analysis so to bring teachers and students’ lived experiences with social action projects to light. The paper concludes with recommendations for educators when envisioning and enacting social action projects.
Preparing effective history teachers: The assessment gap
Authors: Brown Sarah Drake
Published: May 2013

This case study examines a teaching candidate's completion of a major assessment project, including his approach to lesson planning and assessment design, the creation of rubrics, and the crafting of narratives to analyze his students’ work. Qualitative data analysis suggests that this beginning teacher, who excelled in planning and teaching for historical thinking, needed additional support in honing his skills with respect to discipline-based assessment. In his analysis of students’ work and his reflection on the assessments, the teaching candidate retreated to generalist stances that made no references to thinking historically. The teaching candidate demonstrated an ability to design discipline-based assessments and an inability to use a discipline-based framework to assess and describe his students’ work.