bluuebunny/crossref_metadata_2025 huggingface dataset:
HER‐2/neu gene amplification in relation to expression of HER2 and HER3 proteins in patients with esophageal adenocarcinoma
Authors: Yoon Harry H. , Sukov William R. , Shi Qian , Sattler Christopher A. , Wiktor Anne E. , Diasio Robert B. , Wu Tsung‐Teh , Jenkins Robert B. , Sinicrope Frank A.
Published: October 2013

BACKGROUND

Human epidermal growth factor receptor 2 (HER2) is a therapeutic target in patients with esophageal adenocarcinoma (EAC), with gene amplification used as a selection criterion for treatment, although to the authors' knowledge the concordance between amplification and HER2 protein expression remains undefined in EAC. Furthermore, the association between HER2 and its interacting partner, human epidermal growth factor receptor 3 (HER3), is unknown yet appears to be of potential therapeutic relevance.

METHODS

Patients with untreated EACs (N = 673) were analyzed for HER2 amplification and polysomy 17 by fluorescence in situ hybridization in parallel with immunohistochemistry (IHC) (IHC scores of 0‐1+, 2+, and 3+). Amplification was defined as HER2/CEP17 ≥ 2. HER3 expression by IHC was analyzed in randomly selected cases (n = 224). IHC and fluorescence in situ hybridization results were compared using least squares linear regression.

RESULTS

Overall, 17% of the EACs (116 of 673 EACs) were HER2‐amplified with an amplification frequency that was highest among IHC3+ cases (89%) and declined among IHC2+ cases (13%) and IHC0 to IHC1+ cases (4%). Among HER2‐amplified cases, the level of amplification increased linearly with HER2 membranous expression (HER2/CEP17 ratio: 7.9 in IHC3+ and 5.5 in IHC2+ vs 2.8 in IHC0 to IHC1+ [P < .0001]), with 14% of amplified tumors demonstrating absent/faint expression (IHC0 to IHC1+). Polysomy 17 was not found to be associated with HER2 expression. Cytoplasmic HER3 expression was detected in 87% of tumors (195 of 224 tumors) and was found to be significantly associated with better differentiation (P < .0001). Stepwise increases in HER3 expression were associated with higher HER2 expression levels (P = .0019).

CONCLUSIONS

Levels of HER2 protein expression and amplification were found to be linearly associated and highly concordant. Among amplified tumors with absent/faint expression, the level of amplification was low. Frequent expression of HER3 suggests its relevance as a therapeutic target, and its significant association with HER2 supports ongoing efforts to inhibit HER2/HER3 in patients with EAC. Cancer 2014;120:415–424. © 2013 American Cancer Society.
Seismic response of 20‐story base‐isolated and fixed‐base reinforced concrete structural wall buildings at a near‐fault site
Authors: Calugaru Vladimir , Panagiotou Marios
Published: October 2013

This paper investigates numerically the seismic response of six seismically base‐isolated (BI) 20‐story reinforced concrete buildings and compares their response to that of a fixed‐base (FB) building with a similar structural system above ground. Located in Berkeley, California, 2 km from the Hayward fault, the buildings are designed with a core wall that provides most of the lateral force resistance above ground. For the BI buildings, the following are investigated: two isolation systems (both implemented below a three‐story basement), isolation periods equal to 4, 5, and 6 s, and two levels of flexural strength of the wall. The first isolation system combines tension‐resistant friction pendulum bearings and nonlinear fluid viscous dampers (NFVDs); the second combines low‐friction tension‐resistant crosslinear bearings, lead‐rubber bearings, and NFVDs. The designs of all buildings satisfy ASCE 7‐10 requirements, except that one component of horizontal excitation, is used in the 2D nonlinear response history analysis. Analysis is performed for a set of ground motions scaled to the design earthquake and to the maximum considered earthquake (MCE). At both the design earthquake and the MCE, the FB building develops large inelastic deformations and shear forces in the wall and large floor accelerations. At the MCE, four of the BI buildings experience nominally elastic response of the wall, with floor accelerations and shear forces being 0.25 to 0.55 times those experienced by the FB building. The response of the FB and four of the BI buildings to four unscaled historical pulse‐like near‐fault ground motions is also studied. Copyright © 2013 John Wiley & Sons, Ltd.
Methylation of serum insulin‐like growth factor‐binding protein 7 promoter in hepatitis B virus‐associated hepatocellular carcinoma
Authors: Li Feng , Fan Yu‐Chen , Gao Shuai , Sun Feng‐Kai , Yang Yang , Wang Kai
Published: October 2013

Methylation of gene promoter CpG islands is an important early event in hepatocellular carcinoma (HCC), and detection of cell‐free tumor‐specific DNA methylation is becoming a useful noninvasive method for HCC. This study was aimed at determining the diagnostic value of serum insulin‐like growth factor‐binding protein 7 (IGFBP7) promoter methylation in hepatitis B virus‐associated HCC. A total of 217 subjects, including 136 HCC patients, 46 patients with chronic hepatitis B (CHB), and 35 healthy controls (HCs), were included. The methylation status of the serum IGFBP7 gene promoter was determined using methylation‐specific PCR. The frequency of serum IGFBP7 promoter methylation in HCC patients (89/136, 65%) was significantly higher than that in CHB patients (8/46, 17%; X2 = 31.883, P < 0.001) and HCs (5/35, 14%; X2 = 29.429, P < 0.001). Moreover, elevated IGFBP7 methylation frequency was also observed in HCC patients with vascular invasion compared with those without vascular invasion (84 versus 60%, X2 = 6.633, P = 0.010). The sensitivities of serum IGFBP7 methylation and alpha‐fetoprotein (AFP) in detecting HCC were 65 and 57%, respectively. Of note, the combination of IGFBP7 methylation and AFP showed 85% for sensitivity. These results suggest that methylation of the serum IGFBP7 gene promoter may serve as a useful noninvasive biomarker for HCC diagnosis. © 2013 Wiley Periodicals, Inc.
Clinical presentation and differential diagnosis of dementia with Lewy bodies: a review
Authors: Morra L. F. , Donovick P. J.
Published: October 2013

Background

Dementia with Lewy bodies is one of the most prevalent dementia diagnoses. However, differential diagnosis between dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia can still be very difficult given the overlap in neuropathology, clinical presentation, cognitive, and neuroanatomical changes.

Method

A literature review of dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia was conducted using PubMed.

Results and Implications

Accurate diagnosis of dementia with Lewy bodies is crucial in order to more accurately predict the progression of the disease and negative side effects from pharmacological treatment. The differences and similarities between dementia with Lewy bodies, Alzheimer's disease, and Parkinson's disease with dementia are highlighted in order to aid clinicians in differential diagnosis. Copyright © 2013 John Wiley & Sons, Ltd.
Local label learning (LLL) for subcortical structure segmentation: Application to hippocampus segmentation
Authors: Hao Yongfu , Wang Tianyao , Zhang Xinqing , Duan Yunyun , Yu Chunshui , Jiang Tianzi , Fan Yong ,   for the Alzheimer's Disease Neuroimaging Initiative
Published: October 2013

Automatic and reliable segmentation of subcortical structures is an important but difficult task in quantitative brain image analysis. Multi‐atlas based segmentation methods have attracted great interest due to their promising performance. Under the multi‐atlas based segmentation framework, using deformation fields generated for registering atlas images onto a target image to be segmented, labels of the atlases are first propagated to the target image space and then fused to get the target image segmentation based on a label fusion strategy. While many label fusion strategies have been developed, most of these methods adopt predefined weighting models that are not necessarily optimal. In this study, we propose a novel local label learning strategy to estimate the target image's segmentation label using statistical machine learning techniques. In particular, we use a L1‐regularized support vector machine (SVM) with a k nearest neighbor (kNN) based training sample selection strategy to learn a classifier for each of the target image voxel from its neighboring voxels in the atlases based on both image intensity and texture features. Our method has produced segmentation results consistently better than state‐of‐the‐art label fusion methods in validation experiments on hippocampal segmentation of over 100 MR images obtained from publicly available and in‐house datasets. Volumetric analysis has also demonstrated the capability of our method in detecting hippocampal volume changes due to Alzheimer's disease. Hum Brain Mapp 35:2674–2697, 2014. © 2013 Wiley Periodicals, Inc.
Temporal variation of suspended sediment transport in the Koga catchment, North Western Ethiopia and environmental implications
Authors: Yeshaneh Eleni , Eder Alexander , Blöschl Günter
Published: October 2013

Event sediment transport and yield were studied for 45 events in the upstream part of the 260 km2 agricultural Koga catchment that drains to an irrigation reservoir. Discharge and turbidity data were collected over a period of more than a year, accompanied by grab sampling. Turbidity was very well correlated with the sediment concentrations from the samples (r = 0.99), which allowed us to estimate the temporal patterns of sediment concentrations within events. The hysteresis patterns between discharge and sediment concentrations were analysed to provide insight into the different sediment sources. Anticlockwise patterns are the dominant hysteresis patterns in the area, suggesting smaller contributions of suspended sediment from the river channels than from the hillslopes and agricultural areas. Complicated types of hysteresis patterns were mostly observed for long events with multiple peaks. For a given discharge, sediment yields in August and September, when the catchment was almost completely covered with vegetation, were much smaller than during the rest of the rainy season. The hysteresis patterns and timing suggest that the sediment availability from the agricultural areas and hillslopes affects sediment yields more strongly than does peak discharge. Two distinct types of sediment rating curves were observed for the season when the agricultural land was covered with vegetation and when it was not, indicating the dominating contribution of land use/cover to sediment yields in the catchment. The rate of suspended sediment transport in the area was estimated as 25.6 t year−1 ha−1. Copyright © 2013 John Wiley & Sons, Ltd.
Relating pore size variation of poly (ɛ‐caprolactone) scaffolds to molecular weight of porogen and evaluation of scaffold properties after degradation
Authors: Columbus Soumya , Krishnan Lissy K. , Kalliyana Krishnan V.
Published: October 2013

The major challenge in designing a scaffold for fabricating tissue engineered blood vessels is optimization of its microstructure for supporting uniform cellular in‐growth with good mechanical integrity and degradation kinetics suitable for long‐term implantation. In this study, we have investigated the feasibility of varying the pore size of poly(ɛ‐caprolactone) (PCL) scaffold by altering the molecular weight of porogen and studied the effect of degradation on morphological characteristics and mechanical properties of scaffolds by correlating to the extent of degradation. Scaffolds with two different pore sizes were prepared by solvent casting and particulate leaching where poly(ethylene glycol) (PEG) porogens having two molecular weights (3400 and 8000) were used and subjected toin vitrodegradation in phosphate buffered saline (PBS) upto six months. Microcomputed tomography studies of scaffolds revealed narrower pore size distribution when PEG‐3400 was used as porogen and had 78% pores in the 12–24 µ range, whereas incorporation of PEG‐8000 resulted in broader distribution with only 65% pores in the same range. Degradation resulted in scaffolds with narrower pore size distribution to have better retention of morphological and mechanical characteristics compared to scaffolds with broader distribution. Gravimetric and molecular weight studies also showed that scaffold degradation in both cases was only in initial stages after 6 months and PCL scaffolds had potential to be recommended for vascular tissue engineering applications. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 789–796, 2014.
Methodology of fibroblast and mesenchymal stem cell coating of surgical meshes: A pilot analysis
Authors: Gao Yue , Liu Li‐Jia , Blatnik Jeffrey A. , Krpata David M. , Anderson James M. , Criss Corry N. , Posielski Natasza , Novitsky Yuri W.
Published: October 2013

Coating of various synthetic, absorbable, and biologic meshes with mesenchymal stem cells (MSCs) and fibroblasts was analyzed qualitatively and quantitatively. Five hernia meshes—light weight monofilament polypropylene (Soft Mesh), polyester (Parietex‐TET), polylactide composite (TIGR), heavy weight monofilament polypropylene (Marlex), and porcine dermal collagen (Strattice)—were coated with three cell lines: human dermal fibroblasts (HFs), rat kidney fibroblasts (NRKs), and rat MSCs. Cell densities were determined at different time points. Samples also underwent histology and transmission electron microscopic (TEM) analyses. It required HFs 3 weeks to cover the entire mesh, while only 2 weeks for NRKs and MSCs to do so. MSCs had no preference for any of the meshes and produced the highest cell densities on Parietex and TIGR. Substrate‐preference accounted for the significantly lower fibroblast densities on TIGR than Parietex. Fibroblasts failed to coat Marlex. Strattice, which had the least surface area, generated comparable cell densities to Parietex. Both histology and TEM confirmed cell coating of mesh surface. Various prosthetics can be coated by certain cell strains. Both mesh composition and cell preference dramatically influence the coating process. This methodology provides foundation for novel avenues of modulation of host response to various modern synthetic and biologic meshes. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 102B: 797–805, 2014.
Applications of modern sensors and wireless technology in effective wound management
Authors: Mehmood Nasir , Hariz Alex , Fitridge Robert , Voelcker Nicolas H.
Published: October 2013

The management of chronic wounds has emerged as a major health care challenge during the 21st century consuming, significant portions of health care budgets. Chronic wounds such as diabetic foot ulcers, leg ulcers, and pressure sores have a significant negative impact on the quality of life of affected individuals. Covering wounds with suitable dressings facilitates the healing process and is common practice in wound management plans. However, standard dressings do not provide insights into the status of the wound underneath. Parameters such as moisture, pressure, temperature and pH inside the dressings are indicative of the healing rate, infection, and wound healing phase. But owing to the lack of information available from within the dressings, these are often changed to inspect the wound, disturbing the normal healing process of wounds in addition to causing pain to the patient. Sensors embedded in the dressing would provide clinicians and nurses with important information that would aid in wound care decision making, improve patient comfort, and reduce the frequency of dressing changes. The potential benefits of this enabling technology would be seen in terms of a reduction in hospitalization time and health care cost. Modern sensing technology along with wireless radio frequency communication technology is poised to make significant advances in wound management. This review discusses issues related to the design and implementation of sensor technology and telemetry systems both incorporated in wound dressings to devise an automated wound monitoring technology, and also surveys the literature available on current sensor and wireless telemetry systems. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 102B: 885–895, 2014.
Ectocranial suture fusion in primates: pattern and phylogeny
Authors: Cray James , Cooper Gregory M. , Mooney Mark P. , Siegel Michael I.
Published: October 2013

Patterns of ectocranial suture fusion among Primates are subject to species‐specific variation. In this study, we used Guttman Scaling to compare modal progression of ectocranial suture fusion among Hominidae (Homo, Pan, Gorilla, and Pongo), Hylobates, and Cercopithecidae (Macaca and Papio) groups. Our hypothesis is that suture fusion patterns should reflect their evolutionary relationship. For the lateral‐anterior suture sites there appear to be three major patterns of fusion, one shared by Homo‐Pan‐Gorilla, anterior to posterior; one shared by Pongo and Hylobates, superior to inferior; and one shared by Cercopithecidae, posterior to anterior. For the vault suture pattern, the Hominidae groups reflect the known phylogeny. The data for Hylobates and Cercopithecidae groups is less clear. The vault suture site termination pattern of Papio is similar to that reported for Gorilla and Pongo. Thus, it may be that some suture sites are under larger genetic influence for patterns of fusion, while others are influenced by environmental/biomechanic influences. J. Morphol. 275:342–347, 2014. © 2013 Wiley Periodicals, Inc.
Evaluation of copper desorption characteristics using DTPA and citric acid for wheat (Triticum aestivum L.) rhizosphere of soils amended with sewage sludge
Authors: Reza Motaghian Hamid , Reza Hosseinpur Ali
Published: October 2013

A greenhouse experiment was carried out to determine copper (Cu) desorption characteristics in ten bulk and rhizosphere soils (Typic Calcixerepts) amended with sewage sludge (1% w/w) using rhizoboxes. The kinetics of Cu desorption in the bulk and the rhizosphere soils were determined after successive extraction with DTPA‐TEA and 10 mM citric acid in a period of 1 to 504 h at (25 ± 1)°C. The results show that Cu extracted after 504 h using DTPA‐TEA were significantly (P < 1%) lower in the rhizosphere than the bulk soils. However, Cu extracted after 504 h using citric was significantly (P < 1%) higher in the rhizosphere than in the bulk soils. The results illustrated that, on average, citric acid extracted 56% more Cu from the bulk soils than DTPA‐TEA, and citric acid extracted 85% more Cu from the rhizosphere soils than DTPA‐TEA. Desorption kinetics of Cu in the two extractants was well described by power‐function, parabolic diffusion, and first‐order equations. The results show that a 10 mM citric acid extractant may be recommended to determine the kinetics of Cu desorption in calcareous soils amended with sewage sludge.
Striatal dopamine D1‐like receptor binding is unchanged in primary focal dystonia
Authors: Karimi Morvarid , Moerlein Stephen M. , Videen Tom O. , Su Yi , Flores Hubert P. , Perlmutter Joel S.
Published: October 2013

Background: Multiple studies have demonstrated decreases in striatal D2‐like (D2, D3) radioligand binding in primary focal dystonias. Although most investigations have focused on D2‐specific receptors (D2R), a recent study suggests that the decreased D2‐like binding may be due to a D3‐specific (D3R) abnormality. However, only limited data exist on the role of D1‐specific receptors (D1R) and the D1R‐mediated pathways within basal ganglia in dystonia. Metabolic positron emission tomography (PET) data in primary generalized dystonia suggest resting state over activity in the D1R‐mediated direct pathway, leading to excessive disinhibition of motor cortical areas. This work investigated whether striatal D1‐like receptors are affected in primary focal dystonias. Methods: Striatal‐specific (caudate and putamen) binding of the D1‐like radioligand [11C]NNC 112 was measured using PET in 19 patients with primary focal dystonia (cranial, cervical, or arm) and 18 controls. Results: No statistically significant difference was detected in striatal D1‐like binding between the two groups. The study had 91% power to detect a 20% difference, indicating that false‐negative results were unlikely. Conclusions: Because [11C]NNC 112 has high affinity for D1‐like receptors, very low affinity for D2‐like receptors, and minimal sensitivity to endogenous dopamine levels, we conclude that D1‐like receptor binding is not impaired in these primary focal dystonias. © 2013 International Parkinson and Movement Disorder Society
Histone post‐translational modifications in preimplantation mouse embryos and their role in nuclear architecture
Authors: Beaujean Nathalie
Published: October 2013

In mammals, epigenetic modifications are globally rearranged after fertilization, when gametes fuse to form the embryo. While gametes carry special epigenetic signatures and a unique nuclear organization, they attain embryo‐specific patterns after fertilization. This “reprogramming” is promoted by intimate contact between the parental inherited genomes and the oocyte cytoplasm over the first cell cycles of development. Although the mechanisms of this reprogramming remain poorly understood, it appears that the particular epigenetic landscape established after fertilization is essential for further development. This review looks at histone post‐translational modifications, focusing on their functions in chromatin organization and their role in nuclear architecture during mouse embryonic development. Epigenetic changes linked to the use of assisted reproductive technologies are also considered.Mol. Reprod. Dev. 81: 100–112, 2014. © 2013 Wiley Periodicals, Inc.
Noninvasive MRI measurement of the absolute cerebral blood volume–cerebral blood flow relationship during visual stimulation in healthy humans
Authors: Ciris Pelin Aksit , Qiu Maolin , Constable R. Todd
Published: October 2013

Purpose

The relationship between cerebral blood volume (CBV) and cerebral blood flow (CBF) underlies blood oxygenation level–dependent functional MRI signal. This study investigates the potential for improved characterization of the CBV‐CBF relationship in humans, and examines sex effects as well as spatial variations in the CBV‐CBF relationship.

Methods

Healthy subjects were imaged noninvasively at rest and during visual stimulation, constituting the first MRI measurement of the absolute CBV‐CBF relationship in humans with complete coverage of the functional areas of interest.

Results

CBV and CBF estimates were consistent with the literature, and their relationship varied both spatially and with sex. In a region of interest with stimulus‐induced activation in CBV and CBF at a significance level of the P < 0.05, a power function fit resulted in CBV = 2.1 CBF0.32 across all subjects, CBV = 0.8 CBF0.51 in females and CBV = 4.4 CBF0.15 in males. Exponents decreased in both sexes as ROIs were expanded to include less significantly activated regions.

Conclusion

Consideration for potential sex‐related differences, as well as regional variations under a range of physiological states, may reconcile some of the variation across literature and advance our understanding of the underlying cerebrovascular physiology. Magn Reson Med 72:864–875, 2014. © 2013 Wiley Periodicals, Inc.
Study of the free surface flow of water–kaolinite mixture by moving particle semi‐implicit (MPS) method
Authors: Xie J. , Tai Y.C. , Jin Y.C.
Published: October 2013

The flow of water–kaolinite mixtures exhibits a non‐Newtonian nature that differs from the flow of Newtonian fluid. The varying viscosities and shear history of non‐Newtonian fluid flows necessitate the use of a rheology model in moving particle semi‐implicit (MPS) for the numerical studies. On the other hand, the Lagrangian method has the advantage of handling free surface flows with large deformation and fragmentation. This study proposes a mesh‐free Lagrangian method, namely, the MPS method, together with a simple rheology model to investigate the non‐Newtonian free surface flows. The rheological parameters required in the rheology model are determined based upon experiments. The proposed method is applied to a water–kaolinite mixture collapse problem and is proved to be capable of reproducing the significant flow features observed in laboratory experiments. Copyright © 2013 John Wiley & Sons, Ltd.
Resistance, Symbolism and the Language of Stateness in Timor‐Leste
Authors: Myrttinen Henri
Published: October 2013

On gaining independence in 2002 after a protracted struggle against Indonesian occupation, the sovereign Timor‐Leste state began to assert its sovereignty in a range of discursive and expressive media. These assertions developed a distinct ‘language of stateness’ that is the focus of this article. This East Timorese expression of state sovereignty draws heavily on the legacy of the Timorese resistance struggle and on a variety of other sources of symbolic power such as flags, buildings, logos, and uniforms. Yet these efforts have been contested by a range of non‐state actors in Timor‐Leste and the shape that this language of stateness has taken now evokes complaints from martial arts groups (MAGs), ritual arts groups (RAGs), and veterans' organisations that seek to ‘become like the state’ themselves, and who also employ a ‘national language of stateness’ in the form of flags, graffiti, and official buildings. While not challenging the idea of an independent East Timorese state per se, these groups question the prerogative of the state to use and define the language of stateness. In this article I explore the way the state and its challengers use ‘languages of stateness’ and how this shapes their ambivalent stance vis‐à‐vis each other, with both sides often drawing upon a discourse of the fulfilment of the millenarian promises that have for a long time been tied to the achievement of independence.
Evaluation of the incidence and risk of hypoglycemic coma associated with selection of basal insulin in the treatment of diabetes: a Finnish register linkage study
Authors: Haukka Jari , Hoti Fabian , Erästö Panu , Saukkonen Tero , Mäkimattila Sari , Korhonen Pasi
Published: October 2013

Objective

Long‐acting basal insulin analogs have demonstrated positive effects on the balance between effective glycemic control and risk of hypoglycemia versus neutral protamine Hagedorn (NPH) insulin in randomized controlled trials. Evidence of severe hypoglycemic risk with insulin detemir, insulin glargine, or NPH insulin is presented from a nationwide retrospective database study.

Research design and methods

Data from hospital and secondary healthcare visits due to hypoglycemic coma from 75 682 insulin‐naïve type 1 or 2 diabetes patients initiating therapy with NPH insulin, insulin glargine, or insulin detemir in Finland between 2000 and 2009 were analyzed. Incidence rates with 95% confidence intervals (CIs) were calculated using Poisson regression. Hazard ratios were estimated using Cox's regression with adjustments for relevant background variables.

Results

The adjusted risk of hospital/secondary healthcare visits due to the first severe hypoglycemic event was 21.7% (95% CI 9.6–32.1%, p < 0.001) lower for insulin detemir and 9.9% (95% CI 1.5–17.6%, p = 0.022) lower for insulin glargine versus NPH insulin. Risk of hypoglycemic coma recurrence was 36.3% (95% CI 8.9–55.5%, p = 0.014) lower for detemir and 9.5% but not significantly (95% CI −10.2 to 25.7%, p = 0.318) lower for glargine versus NPH insulin. Risk of all hypoglycemic coma events was 30.8% (95% CI 16.2–42.8%, p‐value <0.001) lower for detemir and 15.6% (95% CI 5.1–25.0%, p‐value 0.005) lower for glargine versus NPH. Insulin detemir had a significantly lower risk for first (13.1% lower [p = 0.034]), recurrent (29.6% lower [p = 0.021]), and all (17.9% lower [p = 0.016]) severe hypoglycemic events than insulin glargine.

Conclusions

There were considerable differences in risk of hospitalization or secondary healthcare visits due to hypoglycemic coma between basal insulin treatments in real‐life clinical practice. © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
An observational study examining the effect of comorbidity on the rates of persistence and adherence to newly initiated oral anti‐hyperglycaemic agents
Authors: O'Shea Miriam P. , Teeling Mary , Bennett Kathleen
Published: October 2013

Purpose

To examine whether the type of comorbid condition affects medication persistence and adherence in patients initiating oral anti‐hyperglycaemic (OAH) therapy.

Methods

The Irish Health Services Executive pharmacy claims database was used to identify a cohort of incident OAH therapy users (anatomical therapeutic chemical A10B), ≥25 years, between June 2009 and December 2010. Persistence and adherence were examined at 6 and 12 months post‐therapy initiation. Comorbidity was ascertained using modified versions of the RxRisk and RxRisk‐V indices and classified as either concordant or discordant with diabetes. Adjusted odds ratios (ORs) and 95% confidence intervals (95%CIs) were determined in relation to comorbidity using logistic regression analysis, adjusting for age, gender and type of OAH prescribed.

Results

In the study cohort (n = 21 280), persistence was 74.0% and 62.6% and adherence was 70.0% and 66.7% for all OAHs at 6 and 12 months, respectively. Patients with only concordant comorbidity were significantly more likely to be persistent at 6 (OR 1.45, 95%CI 1.28, 1.65) and 12 months (OR 1.22, 95%CI 1.09, 1.38). Patients with only discordant comorbidity were significantly less likely to be persistent at 6 (OR 0.40, 95%CI 0.35, 0.46) and 12 months (OR 0.43 95%CI 0.38, 0.50) (p < 0.0001). Results were similar for adherence.

Conclusion

The study suggests that the persistence and adherence of OAH therapy in incident users are affected by the type of comorbidity present; this may help in identifying effective interventions aimed at optimising medication use. Copyright © 2013 John Wiley & Sons, Ltd.
Validity of smoking prevalence estimates from primary care electronic health records compared with national population survey data for England, 2007 to 2011
Authors: Booth Helen P. , Prevost A. Toby , Gulliford Martin C.
Published: October 2013

Purpose

Primary care electronic health records (EHRs) are increasingly used as a resource for epidemiological research. Cigarette smoking is an important variable in many epidemiological studies. We evaluated the validity of smoking records in primary care EHRs by comparing estimates for smoking prevalence from primary care EHRs with national health survey data.

Methods

Data were analysed for adults over 30 years of age from the Clinical Practice Research Datalink (CPRD) in comparison with data from the Health Survey for England between 2007 and 2011. Electronic health records in the CPRD were searched for records of smoking status and smoking cessation treatment. Annual age‐ and sex‐standardised prevalence of current‐, non‐ and former smoking were calculated, and compared with equivalent data from the Health Survey for England (HSE).

Results

The difference between estimates of current smoking in CPRD and HSE was generally <1% from 2007 to 2011. In 2011, the prevalence of current smoking in men was: CPRD 24.3%, HSE 24.2%. The mean difference was 0.1% (95% confidence interval −1.5 to 1.7%). In women, current smoking prevalence was CPRD 20.3%, HSE 19.0%; mean difference 1.3% (0.0 to 2.6%). Estimates for former smoking were lower in CPRD than HSE for men (CPRD 26.7%, HSE 31.3%) and women (CPRD 22.9%, HSE 25.0%).

Conclusions

Prevalence estimates for current smoking, and non‐smoking, from primary care EHRs are similar to those from nationally representative surveys, but former smoking may be under‐recorded. © 2013 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
Synthesis and characterization of poly (styrene‐b‐[(butadiene)1−x‐(ethylene‐co‐butylene)x] ‐b‐styrene) star‐like molecular polymers produced by partial hydrogenation of SBS
Authors: Xicohtencatl‐Serrano Hugo , García‐Leiner Manuel , Cabrera‐Ortiz Armando , Herrera‐Nájera Rafael
Published: October 2013

This article reports the synthesis and characterization of four arm star‐shaped poly(styrene‐b‐[(butadiene)1−x‐(ethylene‐co‐butylene)x]‐b‐styrene) (SBEBS) copolymers. A series of SBEBS copolymers with different compositions of the elastomeric block were produced by hydrogenating a given poly(styrene‐b‐butadiene‐b‐styrene) (SBS) copolymer using a catalyst prepared from bis(η5‐cyclopentadienyl)titanium(IV) dichloride and n‐butyllithium. The characterization was accomplished by proton nuclear magnetic resonance spectroscopy (1H NMR), infrared spectroscopy (FTIR), gel permeation chromatography (GPC), differential scanning calorimetry (DSC), dynamic mechanical analysis (DMA), and thermogravimetric analysis (TGA). The results indicate that there is a selective saturation of the polybutadiene block over the polystyrene block; this selectivity was determined by the Ti/Li molar ratio and the concentration of Ti. It was observed that the saturation rate of the 1,2‐vinyl was higher than that of the 1,4‐trans and 1,4‐cis poly(butadiene)‐b isomers. The DSC and DMA results indicate that the degree of hydrogenation had a profound effect on the polymer's relaxation behavior. All samples exhibited a biphasic system behavior with two distinct transitions corresponding to the elastomeric and polystyrene blocks. SBEBS copolymers with higher saturation levels (>33%) exhibited a crystalline character. The TGA results indicated a characteristic weight loss temperature in all samples, with slightly higher thermal degradation stabilities in the materials with higher degrees of saturation. POLYM. ENG. SCI., 54:2332–2344, 2014. © 2013 Society of Plastics Engineers
Production of Cationic Nanogels with Potential Use in Controlled Drug Delivery
Authors: Pikabea Aintzane , Ramos Jose , Forcada Jacqueline
Published: October 2013

Dual‐stimuli‐responsive nanogel particles based on poly(2‐(diethylamino)ethyl) methacrylate (PDEAEMA) cross‐linked with ethylene glycol dimethacrylate (EGDMA) are prepared via batch emulsion polymerization. An in‐depth study of their swelling behavior is carried out, which presents a dual‐dependent thermo‐ and pH‐sensitivity tunable with the ionic strength. The study reveals that nanogel particles undergo a unique transition from a swollen state to a collapsed state at physiological conditions. Such systems presenting tunable sensitivity and synthesized using biocompatible components could be suitable for applications in the field of controlled drug or gene delivery.
Study of the bipolar resistive‐switching behaviors in Pt/GdOx/TaNx structure for RRAM application
Authors: Zhou Qigang , Zhai Jiwei
Published: October 2013

The bipolar resistive switching (RS) behaviors in Pt (top)/GdOx/TaNx (bottom) memory cells were investigated systematically for RRAM applications. Compared to that of the memory cells in Pt/GdOx/Pt structure showing unipolar switching behaviors, the memory cells in Pt/GdOx/TaNx structure with bipolar switching behaviors show better switching properties, such as better switching reliability, enhanced cycling endurance, improved low resistive state value and more uniform RS parameters. The composition and chemical bonding states of the prepared GdOx and TaNx films were analyzed by X‐ray photoelectron spectroscopy to elucidate the underlying resistive switching mechanisms for Pt/GdOx/TaNx structures. The results show that both the oxygen vacancies in the GdOx film and the interfacial TaON layer formed between the dielectric GdOx film and the TaNx bottom electrode play important roles in the RS performance improvement.
High‐current AlGaN/GaN high electron mobility transistors achieved by selective‐area growth via plasma‐assisted molecular beam epitaxy
Authors: Pang Liang , Krein Philip , Kim Ki‐Won , Lee Jung‐Hee , Kim Kyekyoon (Kevin)
Published: October 2013

We report on AlGaN/GaN high electron mobility transistors (HEMTs) for high current operation achieved by selective area growth (SAG) technique based on plasma‐assisted molecular beam epitaxy (PAMBE). Significant improvement in DC characteristics of the multiple‐gate‐finger HEMTs was demonstrated when SAG was employed. Furthermore, when group of HEMTs were interconnected, the resulted large‐periphery device, with the total gate width of 5.2 mm, exhibited a maximum current of 1.75 A and an on‐state resistance of 4.76 mΩ cm2, showing the efficacy of PAMBE‐SAG to fabricate GaN‐based HEMTs for high‐power applications.
Scientizing and Cooking: Helping Middle‐School Learners Develop Scientific Dispositions
Authors: CLEGG TAMARA , KOLODNER JANET
Published: October 2013

We aim to understand how to help young people recognize the value of science in their lives and take initiative to see the world in scientific ways. Our approach has been to designlife‐relevantscience‐learning programs that engage middle‐school learners in science through pursuit of personally meaningful goals. In this paper, we analyze the case studies of two focal learners in the Kitchen Science Investigators life‐relevant, science‐learning program. Our analysis highlights ways to design life‐relevant science‐learning programs to help learners connect science to their everyday lives in meaningful ways. Our findings point to the ways in which learners' dispositions develop, which have implications for the design of programming and learning environments to promote the development of scientific dispositions.
Influence of surface properties on the interfacial adhesion in carbon fiber/epoxy composites
Authors: Li Zhaorui , Wu Shuai , Zhao Zhen , Xu Lianghua
Published: October 2013

A polyacrylonitrile‐based carbon fiber was electrochemically oxidized in an aqueous ammonium bicarbonate solution with current density of up to 2.76 A/m2 at room temperature. X‐ray photoelectron spectroscopy revealed that the oxygen content increased with increasing current density before approaching saturation. The increase can be divided into two regions, the rapid increase region (0–1.78 A/m2) and a plateau region (1.78–2.76 A/m2). The surface chemistry analysis showed that the interlaminar shear strength (ILSS) value of the carbon fiber/epoxy composite could be improved by 24.7%. The carbon structure was examined using Raman spectroscopy in terms of order/disorder in the graphite structure and the results indicated that the relative percentage of graphite carbon in the form of sp2 hybridization increased above a current density of 1.39 A/m2. The increasing non‐polar graphite carbon on the carbon fiber surface decreased the surface energy. As a result, both the surface free energy () and its polar component () decreased when current density increased above 1.78 A/m2. The ILSS value had no direct relationship with the nature and surface density of the oxygen‐containing functional groups nor with the carbon structure. It is the surface free energy (), especially the polar component (), which played a critical role in affecting the interfacial adhesion of carbon fiber/epoxy composites. The ILSS value changed with increasing current density and could be divided into three distinct regions, as chemical interaction region (I), anchor force region (II) and matrix damage region (III). Copyright © 2013 John Wiley & Sons, Ltd.
Systematic review and meta‐analysis of performance of second‐trimester nasal bone assessment in detection of fetuses with Down syndrome
Authors: Moreno‐Cid M. , Rubio‐Lorente A. , Rodríguez M. J. , Bueno‐Pacheco G. , Tenías J. M. , Román‐Ortiz C. , Arias Á.
Published: October 2013

Objective

To review systematically the literature on diagnostic tests and performance of second‐trimester sonographic assessment of nasal bone (NB) in identifying fetuses affected by Down syndrome.

Methods

A search of studies involving screening tests for NB evaluation and measurements was carried out in the main international bibliographic databases (MEDLINE, EMBASE and CINAHL). Those considered to be relevant were then subjected to critical reading, following Critical Appraisal Skills Programme (CASP) criteria, by at least three independent observers. All data were extracted and tabulated by two independent investigators. A statistical synthesis of sensitivity, specificity and likelihood ratios was performed using specific software (Meta‐DiSc).

Results

From an initial list of 852 articles referring to ultrasound markers for Down syndrome, 207 relevant papers were selected. Following exclusions, 21 studies were included in the quantitative synthesis. The pooled estimates of positive and negative likelihood ratios were 40.08 (95% CI, 18.10–88.76) and 0.71 (95% CI, 0.64–0.79), respectively, for absent NB and 15.15 (95% CI, 8.15–28.16) and 0.47 (95% CI, 0.34–0.64), respectively, for hypoplastic NB. No relevant differences were found between the various means of defining nasal hypoplasia (multiples of the median (MoM) or percentiles). The biparietal diameter/nasal bone length (BPD/NBL) ratio showed somewhat higher sensitivity but lower specificity with a threshold effect.

Conclusions

NB absence or hypoplasia show high specificity and low but acceptable sensitivity in identifying fetuses with Down syndrome. Screening performance is better with NB measurements as a function of MoM or percentiles rather than as the BPD/NBL ratio. Classification of women into various risk groups for Down syndrome does not affect diagnostic performance. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd
Provably correct derivation of algorithms using FermaT
Authors: Ward Martin , Zedan Hussein
Published: October 2013

The transformational programming method of algorithm derivation starts with a formal specification of the result to be achieved, plus some informal ideas as to what techniques will be used in the implementation. The formal specification is then transformed into an implementation, by means of correctness-preserving refinement and transformation steps, guided by the informal ideas. The transformation process will typically include the following stages: (1) Formal specification (2) Elaboration of the specification, (3) Divide and conquer to handle the general case (4) Recursion introduction, (5) Recursion removal, if an iterative solution is desired, (6) Optimisation, if required. At any stage in the process, sub-specifications can be extracted and transformed separately. The main difference between this approach and the invariant based programming approach (and similar stepwise refinement methods) is that loops can be introduced and manipulated while maintaining program correctness and with no need to derive loop invariants. Another difference is that at every stage in the process we are working with a correct program: there is never any need for a separate “verification” step. These factors help to ensure that the method is capable of scaling up to the development of large and complex software systems. The method is applied to the derivation of a complex linked list algorithm and produces code which is over twice as fast as the code written by Donald Knuth to solve the same problem.
An Objective Evaluation of a Multi‐Component, Competitive, Selection Process for Admitting Surgeons into Higher Surgical Training in a National Setting
Authors: Gallagher Anthony G. , O’Sullivan Gerald C. , Neary Paul C. , Carroll Sean M. , Leonard Gerald , Bunting Brendan P. , Traynor Oscar
Published: October 2013

Background

Changing work practices make it imperative that surgery selects candidates for training who demonstrate the spectrum of abilities that best facilitate learning and development of attributes that, by the end of their training, approximate the characteristics of a consultant surgeon.

Aims

The aim of our study was to determine the relative merits of components of a program used for competitive selection of trainees into higher surgical training (HST) in general surgery.

Methods

Applicants (N = 98, males 69, mean age 31 years [range 29–40]) to the Royal College of Surgeons in Ireland program for HST in general surgery between 2006 and 2008 were assessed. Clinical, basic surgical training, logbook, research performance, and reference scores were evaluated. A total of 51 candidates were shortlisted and completed a further objective assessment of their technical skills and interview performances.

Results

Shortlisted candidates performed better (p < 0.003) on all assessed parameters. Compared with candidates who were not selected for HST, those who were selected (N = 31) significantly outperformed on individual assessments and overall (p < 0.0001). Logistic regression analysis showed that clinical, technical skills, and research assessments, but not interview, predicted (92.2 %) HST selection outcomes.

Conclusions

Candidates selected for the national HST program in Ireland consistently outperformed those who were not. The assessments reliably and consistently distinguished between candidates, and all of the assessed parameters (except interview) contributed to a highly predictive selection model. This is the largest reported dataset from an objective, transparent, and fair assessment program for selection of the next generation of surgeons.
European Regional Populations: Current Trends, Future Pathways, and Policy Options
Authors: Rees Philip , van der Gaag Nicole , de Beer Joop , Heins Frank
Published: October 2013

Europe is currently experiencing an ageing population and slowing population growth of both the total and working-age populations. These trends are likely to continue. Even though population ageing will affect all European regions, different regions will be affected in different ways. Even under favorable conditions, 35–40 % of all NUTS2 regions will face a labor force decline. If economic conditions are poor, some regions may continue to grow, but 55–70 % of the regions will see a labor force decline by 10 % or more. In most regions of Eastern Europe, the labor force may decrease by more than 30 %. To keep regions prosperous (maintaining competitiveness) and to avoid worse inequality (maintaining cohesion), policy-makers must find ways to cope with these challenges through new fiscal and social policies, though policies directly affecting demographic and migratory trends may also be needed.