bluuebunny/crossref_metadata_2025 huggingface dataset:
Chloride intracellular channel 1 participates in migration and invasion of hepatocellular carcinoma by targeting maspin
Authors: Wei Xuyong , Li Jie , Xie Haiyang , Wang Hangxiang , Wang Jianguo , Zhang Xuanyu , Zhuang Runzhou , Lu Di , Ling Qi , Zhou Lin , Xu Xiao , Zheng Shusen
Published: July 2014

Background and Aim

Our previous proteomic research found that chloride intracellular channel 1 (CLIC1) was upregulated in hepatocellular carcinoma (HCC) tissues with portal vein tumor thrombus. The present study aimed to determine the role of CLIC1 in HCC invasion.

Methods

Immunohistochemistry was used to explore protein expression of CLIC1 in 15 cirrhotic tissues and 69 pairs of HCC and paracarcinoma tissues. Small interfering RNA (siRNA) and plasmids were transfected into HepG2 and SMMC7721 cells, and the in vitro function of CLIC1 in these cells were assessed with cell counting kit‐8 assays, cell apoptosis assays, scratch assays, and transwell assays. Microarray analysis was also performed to further explore the candidate genes related to CLIC1.

Results

Our results confirmed that upregulated CLIC1 expression was significantly correlated with vascular invasion (P = 0.034) in HCC tissues. Knockdown of CLIC1 decreased cell viability and the invasive potency of HepG2 cells, whereas CLIC1 overexpression resulted in an opposite effect in SMMC7721 cells. Microarray analysis identified 618 genes that were differentially expressed (fold change ≥ 2, P < 0.05) between HepG2 cells transfected with CLIC1 siRNA and the negative control. Further studies indicate that knockdown of CLIC1 increased maspin expression and reduced vascular endothelial growth factor (VEGF), matrixmetalloproteinase‐2 (MMP2), MMP9, MMP11, and MMP12 expression. In contrast, overexpression of CLIC1 decreased maspin expression and increased VEGF, MMP2, MMP12, and MMP13 expression.

Conclusions

CLIC1 protein expression is significantly correlated with vascular invasion, and the present study suggests a previously unknown mechanism of CLIC1‐mediated control of HCC invasiveness by targeting maspin.
Smoking behaviour modifies IL23r‐associated disease risk in patients with Crohn's disease
Authors: Doecke James D , Simms Lisa A , Zhao Zhen Zhen , Roberts Rebecca L , Fowler Elizabeth V , Croft Anthony , Lin Angela , Huang Ning , Whiteman David C , Florin Timothy H J , Barclay Murray L , Merriman Tony R , Gearry Richard B , Montgomery Grant W , Radford‐Smith Graham L
Published: July 2014

Background and Aim

The etiology of Crohn's disease (CD) implicates both genetic and environmental factors. Smoking behavior is one environmental risk factor to play a role in the development of CD. The study aimed to assess the contribution of the interleukin 23 receptor (IL23R) in determining disease susceptibility in two independent cohorts of CD, and to investigate the interactions between IL23R variants, smoking behavior, and CD‐associated genes, NOD2 and ATG16L1.

Methods

Ten IL23R single‐nucleotide polymorphisms (SNPs) were genotyped in 675 CD cases, and 1255 controls from Brisbane, Australia (dataset 1). Six of these SNPs were genotyped in 318 CD cases and 533 controls from Canterbury, New Zealand (dataset 2). Case–control analysis of genotype and allele frequencies, and haplotype analysis for all SNPs was conducted.

Results

We demonstrate a strong increased CD risk for smokers in both datasets (odds ratio 3.77, 95% confidence interval 2.88–4.94), and an additive interaction between IL23R SNPs and cigarette smoking. Ileal involvement was a consistent marker of strong SNP–CD association (P ≤ 0.001), while the lowest minor allele frequencies for location were found in those with colonic CD (L2). Three haplotype blocks were identified across the 10 IL23R SNPs conferring different risk of CD. Haplotypes conferred no further risk of CD when compared with single SNP analyses.

Conclusion

IL23R gene variants determine CD susceptibility in the Australian and New Zealand population, particularly ileal CD. A strong additive interaction exists between IL23R SNPs and smoking behavior resulting in a dramatic increase in disease risk depending upon specific genetic background.
The immunomodulatory effects of human mesenchymal stem cells on peripheral blood mononuclear cells in ALS patients
Authors: Kwon Min‐Soo , Noh Min‐Young , Oh Ki‐Wook , Cho Kyung‐Ah , Kang Byung‐Yong , Kim Kyung‐Suk , Kim Young‐Seo , Kim Seung H.
Published: July 2014

In a previous study, we reported that intrathecal injection of mesenchymal stem cells (MSCs) slowed disease progression in G93A mutant superoxide dismutase1 transgenic mice. In this study, we found that intrathecal MSC administration vastly increased the infiltration of peripheral immune cells into the spinal cord of Amyotrophic lateral sclerosis (ALS) mice (G93A mutant superoxide dismutase1 transgenic). Thus, we investigated the immunomodulatory effect of MSCs on peripheral blood mononuclear cells (PBMCs) in ALS patients, focusing on regulatory T lymphocytes (Treg; CD4+/CD25high/FoxP3+) and the mRNA expression of several cytokines (IFN‐γ, TNF‐α, IL‐17, IL‐4, IL‐10, IL‐13, and TGF‐β). Peripheral blood samples were obtained from nine healthy controls (HC) and sixteen patients who were diagnosed with definite or probable ALS. Isolated PBMCs from the blood samples of all subjects were co‐cultured with MSCs for 24 or 72 h. Based on a fluorescence‐activated cell sorting analysis, we found that co‐culture with MSCs increased the Treg/total T‐lymphocyte ratio in the PBMCs from both groups according to the co‐culture duration. Co‐culture of PBMCs with MSCs for 24 h led to elevated mRNA levels of IFN‐γ and IL‐10 in the PBMCs from both groups. However, after co‐culturing for 72 h, although the IFN‐γ mRNA level had returned to the basal level in co‐cultured HC PBMCs, the IFN‐γ mRNA level in co‐cultured ALS PBMCs remained elevated. Additionally, the levels of IL‐4 and TGF‐β were markedly elevated, along with Gata3 mRNA, a Th2 transcription factor mRNA, in both HC and ALS PBMCs co‐cultured for 72 h. The elevated expression of these cytokines in the co‐culture supernatant was confirmed via ELISA. Furthermore, we found that the increased mRNA level of indoleamine 2,3‐dioxygenase (IDO) in the co‐cultured MSCs was correlated with the increase in Treg induction. These findings of Treg induction and increased anti‐inflammatory cytokine expression in co‐cultured ALS PBMCs provide indirect evidence that MSCs may play a role in the immunomodulation of inflammatory responses when MSC therapy is targeted to ALS patients.

image

We propose the following mechanism for the effect of mesenchymal stem cells (MSCs) administered intrathecally in amyotrophic lateral sclerosis (ALS): MSCs increase infiltration of peripheral immune cells into CNS and skew the infiltrated immune cells toward regulatory T lymphocytes (Treg) and Th2 lymphocytes. Treg and Th2 secret anti‐inflammatory cytokines such as IL‐4, IL‐10, and TGF‐β. A series of immunomodulatory mechanism provides a new strategy for ALS treatment.
A distinct subfraction of Aβ is responsible for the high‐affinity Pittsburgh compound B‐binding site in Alzheimer's disease brain
Authors: Matveev Sergey V. , Spielmann Hans Peter , Metts Brittney M. , Chen Jing , Onono Fredrick , Zhu Haining , Scheff Stephen W. , Walker Lary C. , LeVine Harry
Published: July 2014

The positron emission tomography (PET) ligand 11C‐labeled Pittsburgh compound B (PIB) is used to image β‐amyloid (Aβ) deposits in the brains of living subjects with the intent of detecting early stages of Alzheimer's disease (AD). However, deposits of human‐sequence Aβ in amyloid precursor protein transgenic mice and non‐human primates bind very little PIB. The high stoichiometry of PIB:Aβ binding in human AD suggests that the PIB‐binding site may represent a particularly pathogenic entity and/or report local pathologic conditions. In this study, 3H‐PIB was employed to track purification of the PIB‐binding site in > 90% yield from frontal cortical tissue of autopsy‐diagnosed AD subjects. The purified PIB‐binding site comprises a distinct, highly insoluble subfraction of the Aβ in AD brain with low buoyant density because of the sodium dodecyl sulfate‐resistant association with a limited subset of brain proteins and lipids with physical properties similar to lipid rafts and to a ganglioside:Aβ complex in AD and Down syndrome brain. Both the protein and lipid components are required for PIB binding. Elucidation of human‐specific biological components and pathways will be important in guiding improvement of the animal models for AD and in identifying new potential therapeutic avenues.

image

A lipid‐associated subpopulation of Aβ accounts for the high‐affinity binding of Pittsburgh compound B (PIB) in Alzheimer's disease brain. Mass spectrometry of the isolated PIB‐binding site from frontal cortex identified Aβ peptides and a set of plaque‐associated proteins in AD but not age‐matched normal brain. The PIB‐binding site may represent a particularly pathogenic entity and/or report local pathologic conditions.
HOW TO MEASURE THE ECONOMIC IMPACT OF VECTOR‐BORNE DISEASES AT COUNTRY LEVEL
Authors: Basili Marcello , Belloc Filippo
Published: July 2014

Vector‐borne diseases (VBDs) are widespread in less developed countries and reemerging in developed ones. Available economic studies agree that VBDs have significant effects on countries' economic outcomes, and affirm that a systematic evaluation of such effects is crucial for the efficient allocation of resources to health‐related priorities. This paper provides a comparative assessment of available methodologies for measuring the economic impact of VBDs at national level. We review both macroeconometric and micro‐based approaches, and examine advantages and disadvantages of current methods. We conclude by suggesting possible areas for future research.
‘Vitamin D and cognition in older adults’: updated international recommendations
Authors: Annweiler C. , Dursun E. , Féron F. , Gezen‐Ak D. , Kalueff A. V. , Littlejohns T. , Llewellyn D. J. , Millet P. , Scott T. , Tucker K. L. , Yilmazer S. , Beauchet O.
Published: July 2014

Background

Hypovitaminosis D, a condition that is highly prevalent in older adults aged 65 years and above, is associated with brain changes and dementia. Given the rapidly accumulating and complex contribution of the literature in the field of vitamin D and cognition, clear guidance is needed for researchers and clinicians.

Methods

International experts met at an invitational summit on ‘Vitamin D and Cognition in Older Adults’. Based on previous reports and expert opinion, the task force focused on key questions relating to the role of vitamin D in Alzheimer's disease and related disorders. Each question was discussed and voted using a Delphi‐like approach.

Results

The experts reached an agreement that hypovitaminosis D increases the risk of cognitive decline and dementia in older adults and may alter the clinical presentation as a consequence of related comorbidities; however, at present, vitamin D level should not be used as a diagnostic or prognostic biomarker of Alzheimer's disease due to lack of specificity and insufficient evidence. This population should be screened for hypovitaminosis D because of its high prevalence and should receive supplementation, if necessary; but this advice was not specific to cognition. During the debate, the possibility of ‘critical periods’ during which vitamin D may have its greatest impact on the brain was addressed; whether hypovitaminosis D influences cognition actively through deleterious effects and/or passively by loss of neuroprotection was also considered.

Conclusions

The international task force agreed on five overarching principles related to vitamin D and cognition in older adults. Several areas of uncertainty remain, and it will be necessary to revise the proposed recommendations as new findings become available.
Nonresident Father Involvement With Children and Divorced Women's Likelihood of Remarriage
Authors: McNamee Catherine B. , Amato Paul , King Valarie
Published: July 2014

Although remarriage is a relatively common transition, little is known about how nonresident fathers affect divorced mothers' entry into remarriage. Using the 1979–2010 rounds of the National Longitudinal Study of Youth 1979, the authors examined the likelihood of remarriage for divorced mothers (N = 882) by nonresident father contact with children and payment of child support. The findings suggest that maternal remarriage is positively associated with nonresident father contact but not related to receiving child support.
Parents' Relationship Quality and Children's Behavior in Stable Married and Cohabiting Families
Authors: Goldberg Julia S. , Carlson Marcia J.
Published: July 2014

Although an extensive literature has shown that family structure is linked with child well‐being, less well understood is how the dynamics within families affect children, in particular the extent to which positive mother–father relationship quality is linked with children's outcomes. In this study the authors used data from the Fragile Families and Child Wellbeing Study (N = 773) to examine how couple supportiveness in stable coresident families is related to children's externalizing and internalizing behavioral problems over ages 3 through 9. Using latent growth curve and fixed effects models, they found that parents' greater supportiveness has a slight association with lower levels of children's behavioral problems. Using cross‐lagged structural equation models to examine the direction of the association, they also found some evidence that parents' relationship quality and children's behavioral problems are reciprocally related. Overall, this study suggests that more positive couple interactions are beneficial for children residing with both of their biological parents.
Parenting in Relation to School Dropout Through Student Engagement: A Longitudinal Study
Authors: Blondal Kristjana S. , Adalbjarnardottir Sigrun
Published: July 2014

Dropping out of school generally has negative consequences for both individuals and society, and the decision to do so has been described as a crucial developmental task of adolescence. This longitudinal study examined the contribution of parenting practices to students' completion of upper secondary school through their school engagement. Icelandic youth (N = 835, 54% female) were followed from age 14 to 22. Analyses using structural equation modeling revealed that adolescents (age 14) with more authoritative parents (high acceptance, supervision, and psychological autonomy granting) were more likely to have graduated at age 22 compared to adolescents with less authoritative parents. Moreover, the level of student engagement at age 15 partly mediated the relationship between authoritative parenting and educational status. These findings emphasize the importance of quality parent–child relationships to enhance adolescents' school engagement, which in turn reduces the risk of school dropout.
Single Motherhood, Living Arrangements, and Time With Children in Japan
Authors: Raymo James M. , Park Hyunjoon , Iwasawa Miho , Zhou Yanfei
Published: July 2014

The authors examined relationships between single parenthood and mothers' time with children in Japan. Using data from the 2011 National Survey of Households with Children (N = 1,926), they first demonstrate that time spent with children and the frequency of shared dinners are significantly lower for single mothers than for their married counterparts. For single mothers living alone, less time with children reflects long work hours and work‐related stress. Single mothers coresiding with parents spend less time with children and eat dinner together less frequently than either married mothers or their unmarried counterparts not living with parents, net of (grand)parental support, work hours, income, and stress. The findings suggest that rising divorce rates and associated growth in single‐mother families may have a detrimental impact on parents' time with children in Japan and that the relatively high prevalence of intergenerational coresidence among single mothers may do little to temper this impact.
Dynamic Family System Trajectories From Pregnancy to Child's First Year
Authors: Lindblom Jallu , Flykt Marjo , Tolvanen Asko , Vänskä Mervi , Tiitinen Aila , Tulppala Maija , Punamäki Raija‐Leena
Published: July 2014

Family systems reorganize during transitional periods, such as the birth of a new child. Longitudinal research, however, on family dynamics during the transition to parenthood is lacking. Accordingly, the authors aimed to identify family system trajectories from pregnancy to the child's first birthday and to examine their contextual predictors. Both parents (N = 702) reported autonomy and intimacy in marital (wife‐to‐husband, husband‐to‐wife) and parenting (mother‐to‐child, father‐to‐child) relations during pregnancy and at child's ages of 2 months and 12 months. Finite mixture modeling revealed 7 unique family system trajectories: (a) Cohesive (35%), (b) Disengaged (5%), (c) Enmeshed Declining (6%), (d) Enmeshed Quadratic (5%), (e) Authoritarian (14%), (f) Escalating Crisis (4%), and (g) Discrepant (15%) families. Parental education in interaction with duration of partnership and parity predicted family trajectory membership. The study demonstrates how different family types reorganize during the transition to parenthood; this includes decline, growth, and stability in autonomy and intimacy.
His and Hers: Economic Factors and Relationship Quality in Germany
Authors: Hardie Jessica Halliday , Geist Claudia , Lucas Amy
Published: July 2014

Research has linked economic factors to relationship quality in the United States, primarily using cross‐sectional data. In the current study, 2 waves of the Panel Analysis of Intimate Relationships and Family Dynamics data (n = 2,937) were used to test the gendered association between economic factors and relationship satisfaction among young German couples. In contrast to U.S.‐based studies, the findings showed striking gender differences in the association between economic factors and relationship satisfaction for Germans. In cross‐sectional models, women's relationship satisfaction was positively associated with receiving government economic support, and men's satisfaction was positively associated with poverty status and negatively associated with being a breadwinner. Longitudinal models revealed that changes in poverty status are associated with women's satisfaction, but men's satisfaction remains tied to their role as family provider. These unexpected results suggest that men's satisfaction is positively associated with a more equal division of labor market activity between partners.
Derivation and Evaluation of Thresholds for Core and Tissue at Risk of Infarction Using CT Perfusion
Authors: McVerry Ferghal , Dani Krishna Ashok , MacDougall Niall J.J. , MacLeod Mary Joan , Wardlaw Joanna , Muir Keith W
Published: July 2014

BACKGROUND AND PURPOSE

Computed tomography perfusion provides information on tissue viability according to proposed thresholds. We evaluated thresholds for ischemic core and tissue at risk and subsequently tested their accuracy in independent datasets.

MATERIALS AND METHODS

Tissue at risk was evaluated in patients with persistent arterial occlusions, and ischemic core thresholds in patients with recanalization and major clinical improvement. Scans were randomly allocated to derivation or validation groups for tissue at risk and core analysis. Optimum thresholds using mean transit time (MTT), cerebral blood flow (CBF), cerebral blood volume, and delay time (DT) were assessed.

RESULTS

Absolute MTT, relative MTT and DT were best derived predictors of tissue at risk with thresholds of ≥7 seconds, ≥125%, and ≥2 seconds respectively. DT ≥ 2 seconds was the best predictor in the validation dataset (95% agreement levels = −44 to +30 mL, Bias = −6.9). Absolute and relative MTT were the best derived predictors of infarct volume in the core group (8 seconds and 125% respectively) but relative CBF of ≤45% performed best in the core validation dataset.

CONCLUSIONS

Time‐based perfusion thresholds perform well as predictors of tissue at risk of infarction with DT the best predictor. Relative CBF was the best predictor of ischemic core. Evaluation in larger populations is needed to confirm the performance of tissue viability thresholds.
Changes in the species and functional trait composition of the seed bank during semi‐natural grassland assembly: seed bank disassembly or ecological palimpsest?
Authors: Helsen Kenny , Hermy Martin , Honnay Olivier
Published: July 2014

Question

Unlike above‐ground plant community assembly, the processes that govern assembly of the soil seed bank following severe habitat disturbance are poorly understood. Two hypotheses have been put forward in this context: (1) the ‘ecological palimpsest hypothesis’ assumes a gradual accumulation of species in the seed bank; and (2) the ‘community disassembly hypothesis’ assumes a gradual deterministic loss of species from the seed bank. Here, we investigated which hypothesis is applicable to the seed bank assembly of semi‐natural grasslands, following forest clearance. Furthermore, we asked whether seed bank community divergence occurred at the species and at the functional trait level.

Location

Restored and ancient (old) calcareous grasslands in south Belgium.

Methods

The species composition of 106 seed bank samples from three restoration age classes were obtained through a germination experiment. Community‐weighted means were calculated for 26 functional traits. We evaluated changes in species and functional composition with increasing grassland age. Differentiation in species and trait composition was compared between age groups. Finally, we tested for the occurrence of nestedness of the seed bank communities according to age.

Results

Seed bank species richness decreased with time since restoration, at the trait level reflected by the replacement of traits associated with generalist therophytes by traits typical for chamaephytes and grassland specialists. Whereas species differentiation remained relatively constant, trait differentiation decreased with time since restoration. The seed bank composition of old grasslands was a nested subset of that of young grasslands.

Conclusions

Our results suggest that the ‘community disassembly hypothesis’ is applicable to the community assembly of semi‐natural grasslands. Directly following forest clearance, a diverse seed bank is formed, followed by a gradual net loss of species. Surprisingly, this species loss is not governed by seed persistence traits but by functional changes in the above‐ground community. This disassembly process results in one deterministic end state at the trait level, but not at the species level.
A role for matrix remodelling proteins in invasive and malignant meningiomas
Authors: Jalali Shahrzad , Singh Sanjay , Agnihotri Sameer , Wataya Takafumi , Salehi Fatemeh , Alkins R. , Burrell Kelly , Navab Roya , Croul Sidney , Aldape Kenneth , Zadeh Gelareh
Published: July 2014

Aims

Meningiomas are one of the most common brain tumours in adults. Invasive and malignant meningiomas present a significant therapeutic challenge due to high recurrence rates and invasion into surrounding bone, brain, neural and soft tissues. Understanding the molecular mechanism of invasion could help in designing novel therapeutic approaches in order to prevent the need for repeat surgery, decrease morbidity and improve patient survival. The aim of this study was to identify the key factors and underlying mechanisms which govern invasive properties of meningiomas.

Methods

Formalin‐fixed paraffin‐embedded (FFPE) as well as frozen tumour tissues from bone‐invasive, non‐invasive and malignant meningiomas were used for RNA microarray, quantitative real‐time PCR or Western blot analyses. Malignant meningioma cell lines (F5) were subject to MMP16 downregulation or overexpression and used for in vitro and in vivo functional assays. Subdural xenograft meningioma tumours were generated to study the invasion of tumour cells into brain parenchyma using cell lines with altered MMP16 expression.

Results

We establish that the expression level of MMP16 was significantly elevated in both bone‐invasive and brain invasive meningiomas. Gain‐ and loss‐of‐function experiments indicated a role for MMP16 in meningioma cell movement, invasion and tumour cell growth. Furthermore, MMP16 was shown to positively regulate MMP2, suggesting this mechanism may modulate meningioma invasion in invasive meningiomas.

Conclusions

Overall, the results support a role for MMP16 in promoting invasive properties of the meningioma tumours. Further studies to explore the potential value for clinical use of matrix metalloproteinases inhibitors are warranted.
Deterioration, improvement of kidney function over time and determinants in the Cape Town Bellville South cohort
Authors: Matsha Tandi E , Soita David J , Hassan Shafick M , Erasmus Rajiv T , Kengne Andre P
Published: July 2014

Aim

The aim of the present study was to assess the trajectories of glomerular filtration rate (GFR) and determinants of change during a 3‐year period in free‐living mixed‐ancestry South Africans.

Methods

In all 320 (78.1% women) adults, aged 56.2 years, from Cape Town were examined in 2008 and 2011. Estimated glomerular filtration rate (eGFR) was based on the Modification of Diet in Renal Disease model; and staging of eGFR used the National Kidney Foundation's classification.

Results

Mean eGFR (mL/min per 1.73 m2) was 68.6 at baseline and eGFR stages were: >90 (9.4%), 60–90 (58.7%), 30–60 (28.1%) and <30 (0.9%). eGFR increased by 8 mL/min during follow‐up, reflecting variable trajectories by baseline eGFR stages, sex, hypertension and glucose tolerance (all P‐interaction ≤0.012). Movements across eGFR stages during follow‐up favoured improvement in 113 participants (35.3%), and worsened in 23 (7.2%). In adjusted multinomial logistic regressions, men had a 72% (43–86%) lower chance of improvement, while each mmHg higher systolic blood pressure conferred a 7% (3–11%) risk of deterioration. Equivalent for each 1% HbA1c was 30% (8–56%). Participants with glucose intolerance had 102% (3–297%) higher chances of improvement than diabetics.

Conclusion

Variable trajectories of eGFR with time were observed in this cohort, reflecting the effects of modifiable risk factors such as hypertension and dysglycaemia.
Factors limiting and facilitating changes in caring for the intensive care unit patients' relatives
Authors: Zaforteza Concha , García‐Mozo Ana , Amorós Sylvia M , Pérez Eva , Maqueda Mónica , Delgado Joaquina
Published: July 2014

ABSTRACT

Aim

To explore how the intensive care unit (ICU) context influenced receptivity to change in clinical practice, in order to improve the care offered to patients' relatives.

Background

Families of critically ill patients have unmet needs that are not being addressed. Lack of attention to these needs is related more to the ICU context than to a lack of scientific evidence.

Design

Participatory action research (PAR), a qualitative study conducted in a Spanish ICU.

Method

Eleven participants agreed to represent their teams in all scheduled group discussions. Field diaries were kept by the principal investigator and discussion participants, and five in‐depth interviews were conducted. Content analysis was performed.

Results

Four factors limited change: (1) Not acknowledging the legitimacy of scientific evidence regarding the families of critically ill patients. (2) Imbalanced power relationships between the members of multidisciplinary teams. (3) Lack of nurse participation in the information flows. (4) The organization of time and physical space in the unit. Three factors facilitated change: (1) A sense of individual and shared commitment. (2) Leadership in day‐to‐day matters. (3) A process based on reflection.

Conclusions

PAR can lead to change in clinical practice, although the process is complex and requires substantial input of time and energy. Contextual factors limiting this change were structural whereas facilitating factors were circumstantial and depended upon individuals' characteristics. Professionals working at the bedside are capable of identifying, developing and introducing changes to the context in which they work.

Relevance to clinical practice

Knowing these factors and sharing the experience of a successful change process can help others design processes appropriate to their site.
Suppression of collagen‐induced arthritis by oral administration of transgenic rice seeds expressing altered peptide ligands of type II collagen
Authors: Iizuka Mana , Wakasa Yuhya , Tsuboi Hiroto , Asashima Hiromitsu , Hirota Tomoya , Kondo Yuya , Matsumoto Isao , Takaiwa Fumio , Sumida Takayuki
Published: July 2014

Rheumatoid arthritis (RA) is an autoimmune disease associated with the recognition of self proteins secluded in arthritic joints. We previously reported that altered peptide ligands (APLs) of type II collagen (CII256‐271) suppress the development of collagen‐induced arthritis (CIA). In this study, we generated transgenic rice expressing CII256‐271 and APL6 contained in fusion proteins with the rice storage protein glutelin in the seed endosperm. These transgene products successfully and stably accumulated at high levels (7–24 mg/g seeds) in protein storage vacuoles (PB‐II) of mature seeds. We examined the efficacy of these transgenic rice seeds by performing oral administration of the seeds to CIA model mice that had been immunized with CII. Treatment with APL6 transgenic rice for 14 days significantly inhibited the development of arthritis (based on clinical score) and delayed disease onset during the early phase of arthritis. These effects were mediated by the induction of IL‐10 from CD4+ CD25− T cells against CII antigen in splenocytes and inguinal lymph nodes (iLNs), and treatment of APL had no effect on the production of IFN‐γ, IL‐17, IL‐2 or Foxp3+ Treg cells. These findings suggest that abnormal immune suppressive mechanisms are involved in the therapeutic effect of rice‐based oral vaccine expressing high levels of APLs of type II collagen on the autoimmune disease CIA, suggesting that the seed‐based mucosal vaccine against CIA functions via a unique mechanism.
Clinical course and prognostic factors of pulmonary aspergilloma
Authors: Lee Jung‐Kyu , Lee Yeon Joo , Park Sung Soo , Park Jong Sun , Cho Young‐Jae , Park Young Sik , Yoon Ho Il , Lee Choon‐Taek , Lee Jae Ho
Published: July 2014

Background and objective

There is limited data on size change during natural progression of pulmonary aspergilloma. We aimed at elucidating the clinical course and prognosis of aspergilloma according to its size change.

Methods

A multicentre retrospective observational study was performed in 143 adult pulmonary aspergilloma patients with serial chest computed tomography images. The clinical course and risk of haemoptysis according to the size change of the cavity or mass of aspergillomas was evaluated.

Results

Median follow‐up duration was 5.1 years. The size of aspergillomas changed in 39.2% of study subjects. Decreased and increased volumes of aspergilloma were observed in 13.3% and 25.9%, respectively. Patients with decreased volume had significantly higher C‐reactive protein, and more severe bronchiectasis and tuberculosis‐destroyed lung. Clinically significant haemoptysis occurred in 50.3% of patients and was significantly associated with the cavity and mass volume of aspergilloma, but not the extent of volume change. A mean cavity diameter of more than 22 mm and a mass diameter of more than 18 mm increased the risk of clinically significant haemoptysis.

Conclusions

A significant portion of pulmonary aspergilloma changed size in our population. The prevalence of clinically significant haemoptysis was associated with absolute size of cavity and mass of aspergilloma.
Assessing Risk Factors in the Organic Control System: Evidence from Inspection Data in Italy
Authors: Zanoli Raffaele , Gambelli Danilo , Solfanelli Francesco
Published: July 2014

Certification is an essential feature in organic farming, and it is based on inspections to verify compliance with respect to European Council Regulation—EC Reg. No 834/2007. A risk‐based approach to noncompliance that alerts the control bodies to activate planning inspections would contribute to a more efficient and cost‐effective certification system. An analysis of factors that can affect the probability of noncompliance in organic farming has thus been developed. This article examines the application of zero‐inflated count data models to farm‐level panel data from inspection results and sanctions obtained from the Ethical and Environmental Certification Institute, one of the main control bodies in Italy. We tested many a priori hypotheses related to the risk of noncompliance. We find evidence of an important role for past noncompliant behavior in predicting future noncompliance, while farm size and the occurrence of livestock also have roles in an increased probability of noncompliance. We conclude the article proposing that an efficient risk‐based inspection system should be designed, weighting up the known probability of occurrence of a given noncompliance according to the severity of its impact.
Inequality of Income and Consumption in the U.S.: Measuring the Trends in Inequality from 1984 to 2011 for the Same Individuals
Authors: Fisher Jonathan , Johnson David S. , Smeeding Timothy M.
Published: July 2014

This paper examines the distribution of income and consumption in the U.S. using one dataset that obtains measures of both income and consumption from the same set of individuals. We develop a set of inequality measures that show the increase in inequality during the past 27 years using the 1984–2011 Consumer Expenditure Survey. We find that the trends in income and consumption inequality are similar between 1984 and 2006, and diverge during and after the Great Recession. For the entire 27‐year period we find that consumption inequality increases almost as much as does income inequality.
Inferences on Relative Failure Rates in Stratified Mark-Specific Proportional Hazards Models with Missing Marks, with Application to Human Immunodeficiency Virus Vaccine Efficacy Trials
Authors: Gilbert Peter B. , Sun Yanqing
Published: July 2014

The paper develops hypothesis testing procedures for the stratified mark-specific proportional hazards model in the presence of missing marks. The motivating application is preventive human immunodeficiency virus (HIV) vaccine efficacy trials, where the mark is the genetic distance of an infecting HIV sequence to an HIV sequence represented inside the vaccine. The test statistics are constructed on the basis of two-stage efficient estimators, which utilize auxiliary predictors of the missing marks. The asymptotic properties and finite sample performances of the testing procedures are investigated, demonstrating double robustness and effectiveness of the predictive auxiliaries to recover efficiency. The methods are applied to the RV144 vaccine trial.
Global Permutation Tests for Multivariate Ordinal Data: Alternatives, Test Statistics and The Null Dilemma
Authors: Jelizarow Monika , Cieza Alarcos , Mansmann Ulrich
Published: July 2014

We discuss two-sample global permutation tests for sets of multivariate ordinal data in possibly high dimensional set-ups, motivated by the analysis of data collected by means of the World Health Organization's ‘International classification of functioning, disability and health’. The tests do not require any modelling of the multivariate dependence structure. Specifically, we consider testing for marginal inhomogeneity and direction-independent marginal order. As opposed to max-T-tests, which are known to have good power against alternatives with few strong individual effects, the tests proposed have good power against alternatives with many weak individual effects. Permutation tests are valid only if the two multivariate distributions are identical under the null hypothesis. By means of simulations, we examine the practical effect of violations of this exchangeability condition. Our simulations suggest that theoretically invalid permutation tests can still be ‘practically valid’. In particular, they suggest that the degree of the permutation procedure's failure may be considered as a function of the difference in group-specific covariance matrices, the proportion between group sizes, the number of variables in the set, the test statistic used and the number of levels per variable.
A Bayesian Dose Finding Design for Clinical Trials Combining a Cytotoxic Agent with a Molecularly Targeted Agent
Authors: Riviere M.-K. , Yuan Y. , Dubois F. , Zohar S.
Published: July 2014

Novel molecularly targeted agents (MTAs) have emerged as valuable alternatives or complements to traditional cytotoxic agents in the treatment of cancer. Clinicians are combining cytotoxic agents with MTAs in a single trial to achieve treatment synergism and better outcomes for patients. An important feature of such combinational trials is that, unlike the efficacy of the cytotoxic agent, that of the MTA may initially increase at low dose levels and then approximately plateau at higher dose levels as MTA saturation levels are reached. Therefore, the goal of the trial is to find the optimal dose combination that yields the highest efficacy with the lowest toxicity and meanwhile satisfies a certain safety requirement. We propose a Bayesian phase I–II design to find the optimal dose combination. We model toxicity by using a logistic regression and propose a novel proportional hazard model for efficacy, which accounts for the plateau in the MTA dose–efficacy curve. We evaluate the operating characteristics of the proposed design through simulation studies under various practical scenarios. The results show that the design proposed performs well and selects the optimal dose combination with high probability.
Managing Some Motorised Recreational Boating Challenges in South African Estuaries: A Case Study at the Kromme River Estuary
Authors: Lee Deborah Ellen , Hosking Stephen Gerald , Du Preez Mario
Published: July 2014

Estuaries in South Africa face negative crowding effects with respect to motorised boat use because of competing demand. This paper proposes this be managed through user charges and that the setting of these charges be informed by applying a choice experiment to estimate user preferences for reduced motorised boat congestion on the Kromme River Estuary, Eastern Cape. The application of this method led the paper to deduce that users are willing to pay an additional supplementary charge of R548 per annum during peak periods (only) in order to experience a decrease in negative crowding effects.
Antennal heart morphology supports relationship of Zoraptera with polyneopteran insects
Authors: WIPFLER BENJAMIN , PASS GÜNTHER
Published: July 2014

The antennal hearts of the zorapteran Zorotypus hubbardi and of two psocopteran species (Caecilius sp., Embidopsocus sp.) are described in detail and compared to those of other insects. In Zorotypus, the ampullae of this organ are located dorsally of the antennal base. They are attached to the frontal cuticle of the head capsule and laterally suspended by two delicate bands of connective tissue. The associated muscles comprise a well‐developed M. interampullaris and a M. ampulloaortica, which together act as dilators of the ampullae. The connected antennal vessel has a very thin wall and is uniform along its entire length. In the two studied psocopterans the ampullae are likewise connected to the head capsule and have two additional elastic bands. In Caecilius sp. the anterior band is muscular, while in Embidopsocus sp. it is the posterior one. The psocopteran antennal hearts have no additional musculature. Antennal hearts with a musculature configuration resembling that of Zoraptera are known only from Dictyoptera, Phasmatodea and some orthopterans. This condition thus might be a synapomorphy of a polyneopteran subgroup including Zoraptera.
Evaluating a program to increase blood donation among racial and ethnic minority communities in New York City
Authors: Frye Victoria , Caltabiano Melinda , Kessler Debra A. , Schaffler Harvey , Reboza Mark , Hillyer Christopher D. , Shaz Beth H.
Published: July 2014

Background

Individuals with sickle cell disease (SCD), thalassemia, and leukemia often require frequent transfusion and run the risk of red blood cell (RBC) alloimmunization. To prevent alloimmunization or when alloimmunization is present, phenotype‐matched and antigen‐negative RBCs are transfused. To increase the probability of a phenotypic match, donors and recipients should share the same racial and/or ethnic background. Because the majority of patients with SCD are of African and Hispanic or Latino descent, a donor base of racial and ethnic minority donors providing an adequate supply of antigen‐negative RBC units that can be phenotypically matched is required to meet the needs of frequently transfused patients.

Study Design and Methods

The New York Blood Center began the PreciseMatch program in 2005 to increase donations among African American and Hispanic/Latino donors by 150 incremental units per month. To evaluate the program, we conducted a systematic analysis of program documentation, focus group results, and collections data by race and ethnicity over time.

Results

The program achieved 75% of the operationalized goal of a 150‐unit‐per‐month increase; 75% of donors were first‐time donors, with deferral rates at new drives as high as 50%. Significant time and effort was involved in cultivating the community connections that facilitated new drives.

Conclusions

Although PreciseMatch fell short of targets, it served as a foundation for relationships with diverse communities. Further research is needed to understand better how to increase minority donation using existing infrastructure and in the face of market pressures to collect blood as efficiently as possible.
Stochastic Optimal Motion Planning for the Attitude Kinematics of a Rigid Body With Non-Gaussian Uncertainties
Authors: Lee Taeyoung
Published: July 2014

This paper investigates global uncertainty propagation and stochastic motion planning for the attitude kinematics of a rigid body. The Fokker–Planck equation on the special orthogonal group is numerically solved via noncommutative harmonic analysis to propagate a probability density function along flows of the attitude kinematics. Based on this, a stochastic optimal control problem is formulated to rotate a rigid body while avoiding obstacles within uncertain environments in an optimal fashion. The proposed intrinsic, geometric formulation does not require the common assumption that uncertainties are Gaussian or localized. It can be also applied to complex rotational maneuvers of a rigid body without singularities in a unified way. The desirable properties are illustrated by numerical examples.
Flow Induced Energy Losses in the Exhaust Port of an Internal Combustion Engine
Authors: Wang Yue , Semlitsch Bernhard , Mihaescu Mihai , Fuchs Laszlo
Published: July 2014

A numerical study of the flow in the exhaust port geometry of a Scania heavy-duty diesel engine is performed using the large eddy simulation (LES) and an unsteady Reynolds-Averaged Navier–Stokes (URANS) simulation approach. The calculations are performed at fixed valve positions and stationary boundary conditions to mimic the setup of an air flow bench experiment, which is commonly used to acquire input data for one-dimensional engine simulations. The numerical results are validated against available experimental data. The complex three-dimensional (3D) flow structures generated in the flow field are qualitatively assessed through visualization and analyzed by statistical means. For low valve lifts, the major source of kinetic energy losses occurs in the proximity of the valve. Flow separation occurs immediately downstream of the valve seat. Strong helical flow structures are observed in the exhaust manifold, which are caused due an interaction of the exhaust port streams in the port geometry.
Effects of System Rotation on Vortical Structure in Wall Turbulence
Authors: Iida Oaki
Published: July 2014

Direct numerical simulations (DNSs) of rotating turbulent Poiseuille flows are performed to study the effects of both cyclonic and anticyclonic system rotation on the kinematics of the quasi-streamwise vortices. By using the second invariant of the deformation tensor, a number of streamwise vortices are detected and averaged in the wall vicinity where the intense sweep motion, i.e., the inrush motion of high-speed fluid toward the wall, is related to the quasi-streamwise vortices. The effects of the system rotation on the angle of vortex axis are clearly observed as studied in longitudinal vortices of the homogeneous shear flow. Moreover, by calculating the probability of the emergence of the counterclockwise vortices (CCVs) around a clockwise vortex (CV), we find that with increase in the anticyclonic system rotation, the probability increases and decreases in the ejection and sweep sides of a CV, respectively. In contrast, cyclonic system rotation attenuates CCVs in both sides of a CV, though it increases at the top of the CV. This distribution of CCVs is found to affect sweep motion related to the quasi-streamwise vortices.
A Three-Dimensional Curved Beam Element for Helical Components Modeling
Authors: Provasi Rodrigo , Martins Clóvis de Arruda
Published: July 2014

The structural behavior of flexible pipes and umbilical cables is difficult to model due to their complex construction that includes components of different materials, shapes, and functions. Also, it is difficult to model due to the nonlinear interaction between those components, which includes contacts, gaps, and friction. To model a flexible pipe or umbilical cable, one can rely on analytical or numerical approaches. Analytical models need a large set of simplifying hypotheses. Numerical models, like classical finite elements models, require large meshes and have great difficulties to converge. But one can take profit of the particular characteristics of a specific component and develop a custom-made finite element that represents its structural behavior, a so-called finite macro-element. Adopting this approach, in a previous work, it was developed a cylindrical macro-element with orthotropic behavior, to model the plastic layers of a flexible pipe or umbilical cable. This paper presents a three-dimensional (3D) curved beam element, built to model a helical metallic component, which takes into account the effects of curvature and tortuosity of that kind of component. This is accomplished by using a strong coupling between displacements and assuming that the twist and shear strains vary linearly within the element, to avoid the shear lock phenomenon. The complete formulation of this element is presented. Results obtained with this formulation are also presented and compared to those obtained by a classical finite element modeling tool, with good agreement.