bluuebunny/crossref_metadata_2025 huggingface dataset:
Multi‐parametric profiling of renal cell, colorectal, and ovarian cancer identifies tumour‐type‐specific stroma phenotypes and a novel vascular biomarker
Authors: Corvigno Sara , Frödin Magnus , Wisman G Bea A , Nijman Hans W , Van der Zee Ate GJ , Jirström Karin , Nodin Björn , Hrynchyk Ina , Edler David , Ragnhammar Peter , Johansson Martin , Dahlstrand Hanna , Mezheyeuski Artur , Östman Arne
Published: June 2017

A novel set of integrated procedures for quantification of fibroblast‐rich stroma and vascular characteristics has recently been presented allowing discovery of novel perivascular and stromal biomarkers in colorectal, renal cell, and ovarian cancer. In the present study, data obtained through these procedures from clinically well‐annotated collections of these three tumour types have been used to address two novel questions. First, data have been used to investigate if the three tumour types demonstrate significant differences regarding features such as vessel diameter, vessel density, and perivascular marker expression. Second, analyses of the cohorts have been used to explore the prognostic significance of a novel vascular metric, ‘vessel distance inter‐quartile range (IQR)’ that describes intra‐case heterogeneity regarding vessel distribution. The comparisons between the three tumour types demonstrated a set of significant differences. Vessel density of renal cell cancer was statistically significantly higher than in colorectal and ovarian cancer. Vessel diameter was statistically significantly higher in ovarian cancer. Concerning perivascular status, colorectal cancer displayed significantly higher levels of perivascular PDGFR‐β expression than the other two tumour types. Intra‐case heterogeneity of perivascular PDGFR‐β expression was also higher in colorectal cancer. Notably, these fibroblast‐dominated stroma phenotypes matched previously described experimental tumour stroma characteristics, which have been linked to differential sensitivity to anti‐VEGF drugs. High ‘vessel distance IQR’ was significantly associated with poor survival in both renal cell cancer and colorectal cancer. In renal cell cancer, this characteristic also acted as an independent prognostic marker according to multivariate analyses including standard clinico‐pathological characteristics. Explorative subset analyses indicated particularly strong prognostic significance of ‘vessel distance IQR’ in T stage 4 of this cancer type. Together, these analyses identified tumour‐type‐specific vascular‐stroma phenotypes of possible functional significance, and suggest ‘vessel distance IQR’ as a novel prognostic biomarker.
Next‐generation sequencing and clinical outcomes of patients with lung adenocarcinoma treated with stereotactic body radiotherapy
Authors: Cassidy Richard J. , Zhang Xinyan , Patel Pretesh R. , Shelton Joseph W. , Escott Chase E. , Sica Gabriel L. , Rossi Michael R. , Hill Charles E. , Steuer Conor E. , Pillai Rathi N. , Ramalingam Suresh S. , Owonikoko Taofeek K. , Behera Madhusmita , Force Seth D. , Fernandez Felix G. , Curran Walter J. , Higgins Kristin A.
Published: June 2017

BACKGROUND

Genetic aberrations are well characterized in lung adenocarcinomas (LACs) and clinical outcomes have been influenced by targeted therapies in the advanced setting. Stereotactic body radiotherapy (SBRT) is the standard‐of‐care therapy for patients with nonoperable, early‐stage LAC, but to the authors' knowledge, no information is available regarding the impact of genomic changes in these patients. The current study sought to determine the frequency and clinical impact of genetic aberrations in this population.

METHODS

Under an Institutional Review Board‐approved protocol, the records of 242 consecutive patients with early‐stage lung cancers were reviewed; inclusion criteria included LAC histology with an adequate tumor sample for the successful use of next‐generation sequencing and fluorescence in situ hybridization testing. Univariate analysis was performed to identify factors associated with clinical outcomes.

RESULTS

LAC samples from 98 of the 242 patients were reviewed (40.5%), of whom 45 patients (46.0%) had genetic testing. The following mutations were noted: KRAS in 20.0% of samples, BRAF in 2.2% of samples, SMAD family member 4 (SMAD4) in 4.4% of samples, epidermal growth factor receptor (EGFR) in 15.6% of samples, STK1 in 2.2% of samples, tumor protein 53 (TP53) in 15.6% of samples, and phosphatase and tensin homolog (PTEN) in 2.2% of samples. The following gene rearrangements were observed: anaplastic lymphoma kinase (ALK) in 8.9% of samples, RET in 2.2% of samples, and MET amplification in 17.8% of samples. The median total delivered SBRT dose was 50 grays (range, 48‐60 grays) over a median of 5 fractions (range, 3‐8 fractions). The KRAS mutation was associated with worse local control (odds ratio [OR], 3.64; P<.05). MET amplification was associated with worse regional (OR, 4.64; P<.05) and distant (OR, 3.73; P<.05) disease control.

CONCLUSIONS

To the authors' knowledge, the current series is the first to quantify genetic mutations and their association with clinical outcomes in patients with early‐stage LAC treated with SBRT. KRAS mutations were associated with worse local control and MET amplification was associated with worse regional and distant disease control, findings that need to be validated in a prospective setting. Cancer 2017;123:3681–3690. © 2017 American Cancer Society
Prognostic value of event‐free survival at 12 and 24 months and long‐term mortality for non‐Hodgkin follicular lymphoma patients: A study report from the Spanish Lymphoma Oncology Group
Authors: Provencio Mariano , Royuela Ana , Torrente María , Pollán Marina , Gómez‐Codina José , Sabín Pilar , Llanos Marta , Gumá Josep , Quero Cristina , Blasco Ana , Aguiar David , García‐Arroyo Francisco Ramón , Lavernia Javier , Martínez Natividad , Morales Manuel , Saenz‐Cusi Álvaro , Rodríguez Delvys , Calvo Virginia , de la Cruz‐Merino Luis , de la Cruz Miguel Ángel , Rueda Antonio ,   for the Spanish Lymphoma Oncology Group
Published: June 2017

BACKGROUND

Relatively few studies have analyzed the mortality of follicular lymphoma (FL) patients in comparison with a sex‐ and age‐matched general population. This study analyzed the overall survival (OS) of patients with FL and compared their survival with the expected survival of a general population.

METHODS

Patients diagnosed with FL were prospectively enrolled from 1980 to 2013. Standardized mortality ratios (SMRs) were obtained from yearly sex‐ and age‐specific mortality rates in Spain, and OS was compared with age‐ and sex‐matched general population data.

RESULTS

A total of 1074 patients with newly diagnosed FL were enrolled. The median OS was 231 months (95% confidence interval [CI], 195‐267 months). Event‐free survival at 12 months (EFS12) and event‐free survival at 24 months (EFS24) were associated with an increased probability of early death, with an SMR of 10.27 (95% CI, 8.26‐12.77) for EFS12. The overall SMR, including all causes of death, was 2.55 (95% CI, 2.23‐2.92), and it was higher for women (SMR, 3.02; 95% CI, 2.48‐3.67) and young adults (SMR, 6.01; 95% CI, 3.13‐11.55). More than 10 years after the diagnosis, mortality rates for FL patients were lower than those for the general population (SMR, 0.47; 95% CI, 0.28‐0.78). When FL was excluded as a cause of death, the overall SMR was 1.35 (95% CI, 1.11‐1.65) without a statistically significant mortality increase in the >60‐year‐old group in comparison with age‐ and sex‐matched general population data. More than 15% of the patients included in the study (n = 158) had more than 10 years of follow‐up.

CONCLUSIONS

EFS12 and EFS24 predict an early increase in mortality. The long‐term SMR, over the course of 10 years of follow‐up, shows that patients with FL have a risk of dying similar to that of a sex‐ and age‐matched general population. Cancer 2017;123:3709–3716. © 2017 American Cancer Society
Osteoradionecrosis of the mandible in patients with oropharyngeal carcinoma treated with intensity‐modulated radiotherapy
Authors: Caparrotti Francesca , Huang Shao Hui , Lu Lin , Bratman Scott V. , Ringash Jolie , Bayley Andrew , Cho John , Giuliani Meredith , Kim John , Waldron John , Hansen Aaron , Tong Li , Xu Wei , O'Sullivan Brian , Wood Robert , Goldstein David , Hope Andrew
Published: June 2017

BACKGROUND

Osteoradionecrosis (ORN) of the mandible is a late toxicity affecting patients treated with radiotherapy for head and neck malignancies. To the authors' knowledge, ORN has no standardized grading system and its reporting is based on retrospective findings in heterogeneous patient populations. The rate of ORN in the era of intensity‐modulated radiotherapy (IMRT) still is unknown.

METHODS

The authors report the incidence of ORN from prospectively collected data regarding 1196 patients who were diagnosed with squamous cell carcinoma of the oropharynx and treated with curative‐intent IMRT, with or without concomitant systemic treatment, from January 2005 to December 2014. Each case of ORN was graded according to its severity. Clinical and dosimetric comparisons were performed between patients with ORN and a matched control cohort of patients without ORN.

RESULTS

The actuarial rate of ORN of the mandible was 3% at 1 year, 5% at 3 years, and 7% at 5 years. On multivariable analysis, smoking (hazard ratio, 1.9; 95% confidence interval, 1.07‐3.4 [P = .03]) and T classification (hazard ratio, 1.78; 95% confidence interval, 1.02‐3.1 [P = .041]) were found to be statistically significant risk factors. The presence of cardiovascular comorbidities, use of bisphosphonates, and pre‐IMRT dental extractions were found to be different between the matched cohorts. The mandibular volume receiving 50 grays (Gy) (in cm3) and the volume receiving 60 Gy (in cm3) were found to be associated with ORN on multivariable analysis in the matched cohort patients receiving an IMRT regimen of 2 Gy per fraction.

CONCLUSIONS

ORN is relatively uncommon among patients with oropharyngeal carcinoma who are treated with IMRT, but continues to occur beyond 5 years after treatment. Modifiable risk factors that are associated with higher rates of ORN include smoking and the use of bisphosphonates. Minimizing the volumes of the mandible receiving >50 Gy or > 60 Gy also may have an effect on the ORN rate. Cancer 2017;123:3691–3700. © 2017 American Cancer Society
Value and application of trimodality therapy or definitive concurrent chemoradiotherapy in thoracic esophageal squamous cell carcinoma
Authors: Lin Wei‐Cheng , Ding Yi‐Fang , Hsu Han‐Lin , Chang Jer‐Hwa , Yuan Kevin Sheng‐Po , Wu Alexander T. H. , Chow Jyh‐Ming , Chang Chia‐Lun , Chen Shee‐Uan , Wu Szu‐Yuan
Published: June 2017

BACKGROUND

Few large, prospective, randomized studies have investigated the value and optimal application of neoadjuvant chemoradiotherapy followed by surgery (trimodality therapy) or definitive concurrent chemoradiotherapy (CCRT) for patients with thoracic esophageal squamous cell carcinoma (TESCC).

METHODS

The authors analyzed data from patients with TESCC in the Taiwan Cancer Registry database. To compare their outcomes, patients with TESCC were enrolled and categorized into the following groups according to treatment modality: group 1, those who underwent surgery alone; group 2, those who received trimodality therapy; and group 3, those who received definitive CCRT. Group 1 was used as the control arm for investigating the risk of mortality after treatment.

RESULTS

In total, 3522 patients who had TESCC without distant metastasis were enrolled. Multivariate Cox regression analysis indicated that a Charlson comorbidity index score ≥3, American Joint Committee on Cancer stage ≥IIA, earlier year of diagnosis, alcohol consumption, cigarette smoking, and definitive CCRT were significant, independent predictors of a poor prognosis. After adjustment for confounders, adjusted hazard ratios and 95% confidence intervals (CIs) for overall mortality in patients with clinical stage I, IIA, IIB, IIIA, IIIB, and IIIC TESCC were 2.01 (95% CI, 0.44‐6.18), 1.65 (95% CI, 0.99‐2.70), 1.48 (95% CI, 0.91‐2.42), 0.66 (95% CI, 1.08‐1.14), 0.39 (95% CI, 0.26‐0.57), and 0.44 (95% CI, 0.24‐0.83), respectively, in group 2; and 2.06 (95% CI, 1.18‐3.59), 2.65 (95% CI, 1.76‐4.00), 2.25 (95% CI, 1.49‐3.39), 1.34 (95% CI, 0.79‐2.28), 0.82 (95% CI, 0.57‐1.17), and 0.93 (95% CI, 0.51‐1.71), respectively, in group 3.

CONCLUSIONS

Trimodality therapy may be beneficial for the survival of patients with advanced‐stage (IIIA‐IIIC) TESCC, and CCRT might be an alternative to surgery alone in these patients. Cancer 2017;123:3904‐15. © 2017 American Cancer Society.
Elevated risk of human papillomavirus‐related second cancers in survivors of anal canal cancer
Authors: Nelson Rebecca A. , Lai Lily L.
Published: June 2017

BACKGROUND

Over the last decade, the causal link between human papillomavirus (HPV) infection and squamous cell carcinoma of the anus (SCCA) has been well described. Because HPV infection in one site is often associated with other sites of infection, it then follows that patients with SCCA may have an increased risk of additional HPV‐related cancers. Identifying and targeting at‐risk sites through cancer screening and surveillance may help to guide best practices. The current study sought to ascertain sites and risk of HPV‐related second primary malignancies (SPMs) in survivors of SCCA.

METHODS

Using population‐based data from 1992 through 2012, the authors identified patients with SCCA and determined their risk of HPV‐related SPMs, including anal, oral, and genital cancers. Standardized incidence ratios (SIRs), defined as observed to expected cases, were calculated to determine excess risk.

RESULTS

Of 10,537 patients with SCCA, 416 developed HPV‐related SPMs, which corresponded to an overall SIR of 21.5 (99% confidence interval [99% CI], 19.0‐24.2). Men were found to have a higher SIR (35.8; 99% CI, 30.7‐41.6) compared with women (12.8; 99% CI, 10.4‐15.5). SIRs for a second SCCA were markedly higher in men (127.5; 99% CI, 108.1‐149.2) compared with women (47.0; 99% CI, 34.7‐62.1), whereas SIRs for oral cavity and pharyngeal cancers were elevated in men (3.1; 99% CI, 1.5‐5.7) and women (4.4; 99% CI, 1.5‐9.7). SIRs for sex‐specific sites also were elevated, with male genital cancers having an SIR of 19.6 (99% CI, 8.7‐37.6) and female genital cancers an SIR of 8.3 (99% CI, 6.1‐11.0).

CONCLUSIONS

Patients with index SCCA are at an increased risk of subsequent HPV‐related SPMs. The elevated risk is most striking in patients with second primary SCCAs; however, the risk of second cancers also appears to be increased in other HPV‐related sites. Cancer 2017;123:4013‐21. © 2017 American Cancer Society.
Post‐fine‐needle aspiration biopsy communication and the integrated and standardized cytopathology report
Authors: Pitman Martha B. , Black‐Schaffer W. Stephen
Published: June 2017

Communication between cytopathologists and patients and their care team is a critical component of accurate and timely patient management. The most important single means of communication for the cytopathologist is through the cytopathology report. Implementation of standardized terminology schemes and structured, templated reporting facilitates the ability of the cytopathologist to provide a comprehensive and integrated report. Cytopathology has been among the pathology subspecialties that have led the way in developing standardized reporting, beginning with the 1954 Papanicolaou classification scheme for cervical‐vaginal cytology and continuing through the Bethesda systems for gynecological cytology and several nongynecological cytology systems. The effective reporting of cytopathology necessarily becomes more complex as it addresses increasingly sophisticated management options, requiring the integration of information from a broader range of sources. In addition to the complexity of information inputs, a wider spectrum of consumers of these reports is emerging, from patients themselves to primary care providers to subspecialized disease management experts. Both these factors require that the reporting cytopathologist provide the integration and interpretation necessary to translate diverse forms of information into meaningful and actionable reports that will inform the care team while enabling the patient to meaningfully participate in his or her own care. To achieve such broad and focused communications will require first the development of standardized and integrated reports and ultimately the involvement of cytopathologists in the development of the clinical informatics needed to treat all these items of information as structured data elements with flexible reporting operators to address the full range of patient and patient care needs. Cancer Cytopathol 2017;125(6 suppl):486‐93. © 2017 American Cancer Society.
Neuronal distribution of tyramine and the tyramine receptor AmTAR1 in the honeybee brain
Authors: Thamm Markus , Scholl Christina , Reim Tina , Grübel Kornelia , Möller Karin , Rössler Wolfgang , Scheiner Ricarda
Published: June 2017

Tyramine is an important neurotransmitter, neuromodulator, and neurohormone in insects. In honeybees, it is assumed to have functions in modulating sensory responsiveness and controlling motor behavior. Tyramine can bind to two characterized receptors in honeybees, both of which are coupled to intracellular cAMP pathways. How tyramine acts on neuronal, cellular and circuit levels is unclear. We investigated the spatial brain expression of the tyramine receptor AmTAR1 using a specific antibody. This antibody detects a membrane protein of the expected molecular weight in western blot analysis. In honeybee brains, it labels different structures which process sensory information. Labeling along the antennal nerve, in projections of the dorsal lobe and in the gnathal ganglion suggest that tyramine receptors are involved in modulating gustatory and tactile perception. Furthermore, the ellipsoid body of the central complex and giant synapses in the lateral complex show AmTAR1‐like immunoreactivity (AmTAR1‐IR), suggesting a role of this receptor in modulating sky‐compass information and/or higher sensor‐motor control. Additionally, intense signals derive from the mushroom bodies, higher‐order integration centers for olfactory, visual, gustatory and tactile information. To investigate whether AmTAR1‐expressing brain structures are in vicinity to tyramine releasing sites, a specific tyramine antibody was applied. Tyramine‐like labeling was observed in AmTAR1‐IR positive structures, although it was sometimes weak and we did not always find a direct match of ligand and receptor. Moreover, tyramine‐like immunoreactivity was also found in brain regions without AmTAR1‐IR (optic lobes, antennal lobes), indicating that other tyramine‐specific receptors may be expressed there.
Computing in Verotoxin
Authors: Adamatzky Andrew
Published: June 2017

We develop an excitable automata model of a protein verotoxin and demonstrate that logic gates and circuits are realised in the model via interacting patterns of excitation. By sampling potential input pairs of nodes, we calculate frequencies of logic gates which occurred in the verotoxin model for various parameters of node excitation rules. We show that overall the gates can be arranged in the following hierarchy of descending frequencies: AND>OR>AND‐NOT>XOR. We demonstrate realisations of one‐bit half‐adder and controlled‐not gates and estimate memory capacity of the verotoxin molecule.
Using Voltammetry to Measure the Relative Hydrogen‐Bonding Strengths of Pyridine and Its Derivatives in Acetonitrile
Authors: Tessensohn Malcolm E. , Koh Yu Rong , Lim Sihao , Hirao Hajime , Webster Richard D.
Published: June 2017

The voltammetric behavior of 2,3,5,6‐tetramethyl‐1,4‐phenylenediamine was found to be able to differentiate the hydrogen acceptor abilities of electroinactive pyridine compounds in acetonitrile. Weak and strong hydrogen acceptors were distinguished through the onset of a third oxidation process that came about at sub‐stoichiometric amounts of strong hydrogen acceptors, but not in the presence of weak hydrogen acceptors. This additional oxidation reaction occurred at a potential between the two 1 e−‐oxidation reactions that phenylenediamines typically undergo (i.e. EPox(1)<EPox(3)<EPox(2), with EPox(1) and EPox(2) representing the electrochemical conversion of the neutral phenylenediamine into the radical cation and thereafter to the quinonediimine dication) as well as at the expense of the second electrochemical reaction. EPox(2) and EPox(3) were observed to shift towards less positive potentials with increasing concentrations of weak or strong hydrogen acceptors, respectively, whereas EPox(1) remained virtually unaffected. This allows the electrochemical parameters ΔEPox(1, 2)=|EPox(1)−EPox(2)| and ΔEPox(1, 3)=|EPox(1)−EPox(3)| to be employed as measures of the hydrogen‐bonding strengths within each category, to which they were found to be highly reproducible and responsive to steric, electronic, inductive, and mesomeric effects. The electrochemical findings concur with available aqueous pKa data of the protonated pyridine compounds but were, however, in poor agreement with results obtained by density functional theory calculations.
Does the severity of psychopathology of Italian students receiving counselling services increase over time? A 5‐year analysis and a comparison with a clinical and non‐clinical sample
Authors: Strepparava Maria Grazia , Bani Marco , Zorzi Federico , Mazza Umberto , Barile Francesca , Rezzonico Giorgio
Published: June 2017

Psychological problems—from the most minor such as exams anxiety to the more severe such as personality disorders—are not rare in young adults. University Counselling Services often present the only opportunity for undergraduates to meet health professionals and to be confronted with their difficulties in a non‐clinical setting or—in cases of more severe psychopathology—to be referred to mental health services. Recent research attests to the increasing severity of psychological problems among undergraduate and graduate university students. The question necessarily arises as to whether this trend is replicated in the general population being referred to mental health services and, if such is the case, whether there are differences between the two populations. This paper analyses the change in the severity of self‐reported symptoms in a sample of 194 students attending a University Counselling Service over a course of 5 years (2010–2014). Clinical severity was assessed in both groups by Symptoms Check List 90‐Revised, Clinical Outcome in Routine Evaluation‐Outcome Measure, and Emotion Regulation Questionnaire scores. Results show a substantial stability in severity level across time, and a comparison with an age‐matched sample of patients referred to a public hospital clinical psychology service shows overlapping data with respect to disease severity level. As the mental health of university students is an important public health issue, the implications for the organization and structure of university counselling services and the connection with public mental health hospital centres are discussed.
A multi‐wing butterfly chaotic system and its implementation
Authors: Ma Junpeng , Wang Lidan , Duan Shukai , Xu Yaming
Published: June 2017

It has been a common brief that the principle for generating multi‐wing attractor from a Lorenz‐like chaotic system is to construct an even symmetric function for the system. In this pursuit, research effort on exploring the possibility of using non‐even symmetric function is scant, if any. This paper attempts to reveal the intrinsic relation between such a system function and its generated multi‐wing attractor in a chaotic system. It will be shown that a rather simple asymmetric function applying to the Shimizu–Morioka system can indeed generate a multi‐wing butterfly chaotic attractor. Then, some basic properties, compound structure, bifurcation diagram, Lyapunov exponent spectrum, and dynamical analysis of the new chaotic system are investigated in detail. Finally, an electronic circuit is designed and its experimental results are presented, which well match the numerical simulation results, thereby verifying the feasibility of the new method. Copyright © 2017 John Wiley & Sons, Ltd.
Antiestrogenic Activity of Triptolide in Human Breast Cancer Cells MCF‐7 and Immature Female Mouse
Authors: Tang Yi , Wang Jun , Cheng Jinghua , Wang Lijun
Published: June 2017

Preclinical Research

To investigate the antiestrogenic activity of triptolide in human breast cancer cell line MCF‐7 and immature female C57BL/6 mouse. The effects of triptolide on cell proliferation, cell cycle, and the expression of estrogen receptor alpha (ERα) and progesterone receptor (PR) were examined in MCF‐7 cells. In vivo antiestrogenic effects of triptolide were observed after cotreatment of mice with E2 and triptolide for 4 days. Triptolide dose‐ and time‐dependently inhibited cell growth in untreated or E2‐treated MCF‐7 cells, which was associated with increased S phase arrest. Furthermore, triptolide down regulated the expression of ERα and PR in cells. The expression of ERα and PR in combined group of triptolide with E2 was much higher than that of triptolide alone. Triptolide decreased the E2‐induced uterine weight in mice, while triptolide alone had no effect. Triptolide treatment (90 μg/kg) resulted in extensive degeneration and necrosis of uterine epithelial cells, whereas the same concentration of triptolide in combination with E2 caused morphologic changes in epithelial cells from simple columnar to ellipse, without destruction. Triptolide showed antiestrogenic activity in vitro and in vivo, and the down regulation of ERα and PR expression may be its underlying mechanisms. Drug Dev Res 78 : 164‐169, 2017. © 2017 Wiley Periodicals, Inc.
Cultural entrainment of motor skill development: Learning to write hiragana in Japanese primary school
Authors: Nonaka Tetsushi
Published: June 2017

The aim of the present study was to examine how the social norms shared in a classroom environment influence the development of movement dynamics of handwriting of children who participate in the environment. To look into this issue, the following aspects of the entire period of classroom learning of hiragana letters in Japanese 1st graders who had just entered primary school were studied: First, the structure of classroom events and the specific types of interaction and learning within such environment were described. Second, in the experiment involving 6‐year‐old children who participated in the class, writing movements of children and their changes over the period of hiragana education were analyzed for each stroke composing letters. It was found that writing movement of children became differentiated in a manner specific to the different types of stroke endings, to which children were systematically encouraged to attend in the classroom. The results provide a detailed description of the process of how dynamics of fine motor movement of children is modulated by the social norms of a populated, classroom environment in a non‐Latin alphabet writing system.
HPA axis linkage in parent–child dyads: Effects of parent sex, autism spectrum diagnosis, and dyadic relationship behavior
Authors: Saxbe Darby E. , Golan Ofer , Ostfeld‐Etzion Sharon , Hirschler‐Guttenberg Yael , Zagoory‐Sharon Orna , Feldman Ruth
Published: June 2017

Families of preschoolers participated in two dyadic home visits, once with mother (56 dyads) and once with father (59 dyads). Each member of the dyad provided three cortisol samples and participated in several interaction tasks that were behaviorally coded. Approximately half of the children had been diagnosed with autism spectrum disorders (ASD), whereas half were typically developing (TD).

In a multilevel model, father's cortisol level at each timepoint predicted child cortisol. Father–child linkage was stronger in dyads that showed less reciprocity, in which fathers showed less sensitivity, and in which children showed less self‐regulation and more withdrawal. Cortisol levels were not significantly correlated in mother–child dyads, and there was a trend toward moderation by ASD diagnosis, such that linkage was greater in TD children. Mother–child linkage was stronger in dyads that showed less behavioral coordination and less sensitivity. HPA axis linkage may be stronger in less behaviorally attuned dyads.
A risk‐score model for predicting risk of type 2 diabetes mellitus in a rural Chinese adult population: A cohort study with a 6‐year follow‐up
Authors: Zhang Hongyan , Wang Chongjian , Ren Yongcheng , Wang Bingyuan , Yang Xiangyu , Zhao Yang , Han Chengyi , Zhou Junmei , Zhang Lu , Qi Minjie , Zhai Yujia , Pang Chao , Yin Lei , Zhao Jingzhi , Hu Dongsheng , Zhang Ming
Published: June 2017

Background

Several prediction tools have been developed to identify people with type 2 diabetes mellitus (T2DM) and to quantify the probability of developing T2DM. However, most of the risk models were constructed based on cross‐sectional studies and tea‐drinking was not included.

Methods

A total of 15 768 participants without known T2DM were followed up from 2007‐2008 to 2013‐2014; 12 654 were randomly assigned to the derivation dataset and 3114 to the validation dataset. We constructed a risk‐score model for T2DM by using a Cox proportional‐hazards model. Risk scores were calculated by multiplying β by 10 in the derivation cohort and were verified in the validation dataset. The model's accuracy was assessed by the area under the receiver operating characteristic curve (AUC).

Results

Predictors for T2DM risk in the derivation dataset were drinking tea frequently, body mass index ≥28.0 kg/m2, waist to height ratio ≥ 0.5, triglycerides level 1.70 to 2.25 and ≥2.26 mmol/L, and fasting plasma glucose 5.6 to 6.0 and ≥6.1 mmol/L. The corresponding scores were −2, 7, 7, 4, 6, 11, and 25, respectively. The sensitivity, specificity, and AUC (95% confidence interval) for this full model were 69.63%, 75.56%, and 0.791 (0.783‐0.799), respectively. The ability of the non‐invasive models to predict T2DM was not superior to that of the full model. With the validation dataset, the predictive performance was better for our full model than the Framingham risk‐score model (AUC 0.731 vs 0.525, P < .001).

Conclusions

Our risk‐score model has fair efficacy for predicting 6‐year risk of T2DM in a rural adult Chinese population.
Intensive insulin therapy combined with metformin is associated with reduction in both glucose variability and nocturnal hypoglycaemia in patients with type 2 diabetes
Authors: Zhang Yifei , Zhao Zhiyun , Wang Shujie , Zhu Wei , Jiang Yiran , Sun Shouyue , Chen Chen , Wang Kai , Mu Liangshan , Cao Jinyi , Zhou Yingxia , Gu Weiqiong , Hong Jie , Wang Weiqing , Ning Guang
Published: June 2017

Background

The effect on glucose variability in patients with intensive insulin therapy has not been fully understood. This observational study investigated the different glucose variability and hypoglycaemia patterns in type 2 diabetes patients treated with continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) with or without metformin administration.

Methods

During hospitalization, a total of 501 patients with poor glycaemic control and in initial treatment with either CSII alone (n = 187), CSII + Metformin (n = 81), MDI alone (n = 146), or MDI + Metformin (n = 87) were involved in the final analysis. Data obtained from continuous glucose monitoring were used to assess blood glucose fluctuation and nocturnal hypoglycaemia.

Results

Among the 4 groups, no difference was found in mean blood glucose levels. Results in parameters reflecting glucose fluctuation: continuous overlapping net glycaemic action in CSII + Metformin and mean amplitude of glycaemic excursions in MDI + Metformin were significantly lower than those in either CSII alone or MDI alone, respectively, even after adjustment (P = .031 and .006). Frequency of nocturnal hypoglycaemia was significantly decreased in CSII + Metformin as compared with CSII alone (0.6% vs 1.8%) and in MDI + Metformin as compared with MDI alone (1.6% vs 2.3%), with the highest frequency observed in MDI alone and the lowest in CSII + Metformin (all between group P < .001). Consistent results were obtained in between‐group comparisons for hypoglycaemia duration. Subgroup analysis matched with baseline body mass index, and glycated haemoglobin and fasting blood glucose further confirmed these findings.

Conclusion

Metformin added to initial CSII or MDI therapy is associated with a reduction in both glucose fluctuation and nocturnal hypoglycaemic risk in patients with type 2 diabetes.
Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study
Authors: Laaksonen Jaakko , Taipale Tuukka , Seppälä Ilkka , Raitoharju Emma , Mononen Nina , Lyytikäinen Leo‐Pekka , Waldenberger Melanie , Illig Thomas , Hutri‐Kähönen Nina , Rönnemaa Tapani , Juonala Markus , Viikari Jorma , Kähönen Mika , Raitakari Olli , Lehtimäki Terho
Published: June 2017

Background

Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PRD) and without dyslipidaemia (PR0) and compared these to nonprediabetic controls without dyslipidaemia (C0).

Methods

The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years. Genome‐wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes.

Results

Pathways for cholesterol synthesis, interleukin‐12‐mediated signalling events, and downstream signalling in naïve CD8+ T‐cells were upregulated in the PR0 group in comparison with controls (C0). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T‐cell signalling and interleukin‐12‐mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR0 and PRD) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PRD group was compared with the C0 group. Five genes in the PR0 group and 1 in the PRD group were significantly differentially expressed in comparison with the C0 group.

Conclusions

Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined.
Lazarus ecology: Recovering the distribution and migratory patterns of the extinct Carolina parakeet
Authors: Burgio Kevin R. , Carlson Colin J. , Tingley Morgan W.
Published: June 2017

The study of the ecology and natural history of species has traditionally ceased when a species goes extinct, despite the benefit to current and future generations of potential findings. We used the extinct Carolina parakeet as a case study to develop a framework investigating the distributional limits, subspecific variation, and migratory habits of this species as a means to recover important information about recently extinct species. We united historical accounts with museum collections to develop an exhaustive, comprehensive database of every known occurrence of this once iconic species. With these data, we combined species distribution models and ordinal niche comparisons to confront multiple conjectured hypotheses about the parakeet's ecology with empirical data on where and when this species occurred. Our results demonstrate that the Carolina parakeet's range was likely much smaller than previously believed, that the eastern and western subspecies occupied different climatic niches with broad geographical separation, and that the western subspecies was likely a seasonal migrant while the eastern subspecies was not. This study highlights the novelty and importance of collecting occurrence data from published observations on extinct species, providing a starting point for future investigations of the factors that drove the Carolina parakeet to extinction. Moreover, the recovery of lost autecological knowledge could benefit the conservation of other parrot species currently in decline and would be crucial to the success of potential de‐extinction efforts for the Carolina parakeet.
Blue‐to‐Green Delayed Fluorescence of 2‐Aminoisophthalic Acid Diesters Dispersed in Polymer Film
Authors: Shimizu Masaki , Nakatani Masaki
Published: June 2017

We have synthesized ten 2‐aminoisophthalic acid diesters from commercially available dimethyl 2‐bromoisophthalate. The diesters in 2‐methyltetrahydrofuran were found to be non‐emissive or faintly fluorescent (Φ = 0.04–0.08) at room temperature, whereas each ester in its powder form exhibits fluorescence in the blue to green spectral region with a luminescence efficiency superior to that in solution. DFT calculations revealed that luminescence occurs from the lowest singlet excited state generated by intramolecular charge transfer from the amino moiety to the isophthalate core. Time‐dependent DFT calculations suggest that the energy gap between the S1 and T1 states is very small, which allows reverse intersystem crossing leading to delayed fluorescence emission. Indeed, the diesters dispersed in poly(methyl methacrylate) (PMMA) films exhibit luminescence consisting of two components, the lifetimes of which are in the order of nano‐ and microseconds, respectively. The luminescence spectra of the PMMA films in air completely overlap with those recorded under vacuum, which indicates that the long‐lived emission can be assigned to delayed fluorescence.
Electropolymerization of Metallophthalocyanines Carrying Redox Active Metal Centers and their Electrochemical Pesticide Sensing Application
Authors: Keleş Turgut , Akyüz Duygu , Biyiklioglu Zekeriya , Koca Atıf
Published: June 2017

In this study, modified electrodes were constructed with the electropolymerization of metallophthalocyanines (MPcs) carrying redox active metal cations and electropolymerizable substituents. Then these electrodes were tested as selective and sensitive electrochemical pesticide sensors. Incorporation of the redox active Co(II) (CoPc(MOR‐NAF)), Cl–Mn(III) (MnPc(MOR‐NAF)), and Ti(IV)O (TiOPc(MOR‐NAF)) metal cations into Pc cavity increased the redox activity of Pc ring. Moreover, redox active and electropolymerizable 5‐{[(1E)‐(4‐morpholin‐4‐ylphenyl)methylene]amino}‐1‐naphthoxy substituents (MOR‐NAF) on the Pc ring triggered coating of the complexes on the electrode surface with the electropolymerization reactions. Therefore, modified electrodes GCE/MPc(MOR‐NAF) were constructed with the electropolymerizations of MPcs. These electrodes illustrated reasonable redox activity and conductivity for the potential applications in different fields of the electrochemical technologies. Pesticide sensing measurements indicated that changing the metal center of the complexes significantly altered their sensing activities. Among the complexes, GCE/CoPc(MOR‐NAF) electrode behaved as the most sensitive and selective electrode and it sensed the parathion with good selectivity and sensitivity. GCE/CoPc(MOR‐NAF) electrode showed a wider linear range (0.075‐5.75 μmoldm−3) and smaller LOD (0.025 μmoldm−3) and higher sensitivity (3.46 Acm−2M−1) for the parathion sensing. Although GCE/TiOPc(MOR‐NAF) electrode also sensed the parathion with a high sensitivity, its selectivity was poor and the linear range of this sensing was very narrow. Differently GCE/Cl–MnPc(MOR‐NAF) electrode only sensed eserine with reasonably sensitivity.
Isatin Analysis Using Flow Injection Analysis with Amperometric Detection – Comparison of Tetrahedral Amorphous Carbon and Diamond Electrode Performance
Authors: Jarošová Romana , Sanchez Simon , Haubold Lars , Swain Greg M.
Published: June 2017

Isatin is an endogenous indole compound in humans and rodents that has a wide range of biological activity. In rat models, isatin concentrations have been shown to increase in the heart, brain, blood plasma, and urine with stress. Studies on patients suffering from Parkinson's disease have indicated a correlation between progress of the disease and urinary output of the molecule. Isatin is electrochemically active and can therefore be detected with electrochemical techniques. In this work, we compared the performance of a nitrogen‐incorporated tetrahedral amorphous carbon (ta‐C:N) and a boron‐doped nanocrystalline diamond thin‐film electrode for the oxidative detection of this biomolecule using flow injection analysis with amperometric detection. The measurements were performed in 0.1 phosphate buffer pH 7.2. The ta‐C:N electrode, like boron‐doped nanocrystalline diamond, exhibits some excellent properties for electroanalytical measurements including (i) low background current and noise, (ii) microstructural stability at positive detection potentials, and (iii) good activity for a wide range of bioanalytes without conventional surface pretreatment. The results reveal that both electrodes exhibit a linear dynamic range from 100 to 0.1 μmol L−1, a short‐term response variability 3–4 % RSD (30 injections), a sensitivity of 18 mA M‐1, and a limit of detection (S/N=3) of 1.0×10−7 mol L−1 (14 ng mL−1 or 2.5 fmol).
Building Evaluation Capacity to Address Problems of Equity
Authors: Carden Fred
Published: June 2017

The issue of equity is receiving increasing attention not only in health but in other areas of social development. It is often a highly charged and emotional conversation. This chapter argues that with better capacity to evaluate for equity, evaluators can make a significant contribution to clarifying the issues in the debate and, through that, to addressing inequities. Evidence is never the only element in a debate—politics and emotion always play important roles—but the absence of solid evidence fosters even stronger polarization of the debate. This chapter addresses a gap in our capacity to evaluate for equity so that evidence can make a central contribution to this debate. Building on the challenges to measurement in the equity space, the chapter identifies the process and systems thinking skills that are needed to complement our evaluation methods skills.
Lessons from Chile's Use of System‐Level Theory of Change to Implement a Policy Redesign Process to Address Health Inequities
Authors: Solar Orielle , Frenz Patricia
Published: June 2017

To reduce health inequities, Chile´s Ministry of Health embarked on an ambitious process to implement policy redesign involving six public health programs that used a system‐level theory of change. The process brought together a large and diverse group of national and local actors from within and outside the health sector organized in a network of program nodes, who worked together on well‐defined tasks over the course of a year with high‐level political and technical support. The tasks were part of a coconstructed stepwise assessment methodology, based on understanding and testing program theory and uncovering theories of inequities, drawing on realistic evaluation approaches, the social determinants of health framework, and models of effective program coverage. Almost simultaneously, the program nodes proposed new program theories to address equities with an implementation strategy, which necessarily engaged other sectors and community actors. This chapter highlights some of the lessons to explain the success of Chile´s redesign process: (a) the diversity of knowledge and experiences across nodes enriched and enabled system‐level change, (b) the key distinction between theory of change and theory of inequities required to address inequities, and (c) the long‐lasting transformative capital for institutional change of training a network of agents for change.
Equity Is Not an Intervention: Implications of Evaluation—Reflections from India
Authors: Hay Katherine
Published: June 2017

Like most of the world, China, India, and Chile—the three countries discussed in this volume—are all characterized by increasing inequity. Equity is not the primary goal driving core policies and programs, and equity is often knowingly and readily sacrificed for other goals. In such a context, is it reasonable to expect that interventions generated from systems that perpetuate and deepen inequities, and do not challenge those systems and outcomes, will lead to equity? Is it reasonable to expect further that evaluation of such interventions will enhance equity? This chapter suggests that it is reasonable, but only if such evaluations are understood and framed as intentional disruptions to systems perpetuating inequities. Taking India as an example, the chapter lays out the persistence of health inequities in India and discusses implications and possible solutions emerging from seeing program and other evaluations as an opportunity to disrupt program, organizational, or system ecologies that perpetuate inequities. The chapter sees no conflict between, and argues for, models of evaluation that are both rigorous and transformative.
Study on different finite difference methods at skin interface for burn prediction in protective clothing evaluation
Authors: Zhai L. , Camenzind M. , Li J. , Rossi R. M.
Published: June 2017

For protective clothing evaluation by using the flame engulfment method, a skin burn injury model is required to predict burn degree of the covered skin. By applying finite difference methods, 2 numerical methods are compared. One is based on equivalent heat intensity; the other is based on the law of conservation of energy. In this study, skin temperature rise is compared between these 2 methods by using homogeneous skin properties as well as the analytical solutions. Differences between these 2 methods in application of measured heat exposure tests data are also explored. The results show that assuming equivalent heat intensity at the skin layer interfaces overestimates severity of burn injury. Burn injury time is sensitive to the investigated numerical methods, especially for third‐degree burns. The differences of the 2 methods can be reduced by optimization of the grid size using the test cases described in ASTM F1930. A detailed description of requirements regarding applicable numerical methods in future revisions of the relevant standards is recommended. The finite difference model applied in this paper can act as an effective tool to predict temperature distribution in the skin as well as predict burn injury for evaluation of thermal protective clothing.