bluuebunny/crossref_metadata_2025 huggingface dataset:
Physical activity and play behaviours in children and young people with intellectual disabilities: A cross-sectional observational study
Authors: Boddy Lynne M. , Downs Samantha J. , Knowles Zoe R. , Fairclough Stuart J.
Published: March 2015

The benefits of physical activity and active play for children and young people are well established. However, there is a lack of physical activity research involving children and young people with intellectual disabilities. This study investigated habitual physical activity and recess play behaviour in 70 5- to 15-year-old participants with intellectual disabilities using objective methods (accelerometers) and systematic observation techniques. Results showed that few children were active enough to benefit their physical health (23% of the cohort). No differences in habitual physical activity, sedentary behaviour, or recess play behaviours were observed between boys and girls. Participants spent most of their recess time alone or playing in small groups, with no participants engaging in large group play. Older participants spent more recess time playing in small groups rather than playing alone and participants with Autistic Spectrum Disorder spent more time engaged in active pursuits and less time standing than non-Autism Spectrum Disorder participants. Positive correlations were observed between time spent alone and physical activity. These findings contrast with those typically observed in a mainstream school setting. In conclusion, interventions designed from formative research are needed to promote physical activity within this population. Implications for school psychologists are discussed.
Self-management training for Chinese obese children at risk for metabolic syndrome: Effectiveness and implications for school health
Authors: Ling Jiying , Anderson Laura M. , Ji Hong
Published: March 2015

This article reviews the results of a school-based self-management intervention for Chinese obese children at risk for metabolic syndrome. Twenty-eight Chinese obese children ( M age = 10 years) and their parents participated in the study. Metabolic syndrome risk factors were measured pre- and post-intervention. The risk factors included Body Mass Index, waist circumstance, systolic blood pressure, diastolic blood pressure, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, High-sensitivity C-reactive Protein, fasting plasma glucose, and fasting blood insulin. After 6 months of school-based self-management intervention, all risk factors with the exception of triglycerides and fasting plasma glucose changed significantly in the healthful direction ( p < 0.01). This pilot study offers promising implications for school interventions that are delivered by school-based practitioners collaborating with parents, teachers, and children. An individualized program based on a self-care and -management framework may have utility as a relatively cost-effective, school-based intervention to improve children’s health.
A randomized controlled design investigating the effects of classroom-based physical activity on children’s fluid intelligence and achievement
Authors: Fedewa Alicia L. , Ahn Soyeon , Erwin Heather , Davis Matthew C.
Published: March 2015

Existing literature shows promising effects of physical activity on children’s cognitive outcomes. This study assessed via a randomized, controlled design whether additional curricular physical activity during the school day resulted in gains for children’s fluid intelligence and standardized achievement outcomes. Participants were children ( N = 460) from four urban schools in the Southeast United States. Schools were randomly assigned to treatment and control conditions. Treatment schools received additional physical activity breaks throughout the school day while control schools maintained a typical schedule without curricular activity breaks. Results from the one-year study show positive effects for children’s mathematics and reading achievement but no differences across treatment and control groups for children’s fluid intelligence scores. Implications for school psychologists in promoting physical activity breaks on a systems-wide level are discussed.
Recommendations for policy and practice of physical education in culturally and linguistically diverse Australian secondary schools based on a two-year prospective cohort study
Authors: Dudley Dean A. , Pearson Phil , Okely Anthony D. , Cotton Wayne G.
Published: March 2015

Physical activity affords a host of physical and cognitive benefits for children. Physical education classes are one such venue where children can reap recommended amounts of physical activity. However, little research has explored evidence-based physical education instruction, particularly in culturally and linguistically diverse schools. No studies to date have provided recommendations for a range of educational stakeholders that serve these students. The Physical Activity in Linguistically Diverse Communities study examined the evidence-based physical education opportunities and barriers at six culturally and linguistically diverse high schools in New South Wales, Australia. This article provides implications and synthesized recommendations based on Phase One (systematic review) and Phase Two (prospective cohort study of students in six schools) of Physical Activity in Linguistically Diverse Communities for school leadership and psychologists targeting policy and practice changes on a systems level.
Living the peace process in reverse: racist violence and British nationalism in Northern Ireland
Authors: McVeigh Robbie
Published: March 2015

In 1971 British Home Secretary Reginald Maudling suggested that the situation in Northern Ireland amounted to ‘an acceptable level of violence’. During ‘the Troubles’ this became the de facto security policy of successive British governments prepared to countenance a ‘manageable’ level of paramilitary activity. This reality supposedly changed irrevocably with the peace process and the 1997 Good Friday Agreement. Over the last fifteen years, however, Northern Ireland has been dubbed ‘the race hate capital of Europe’ with the ‘targeting of ethnic minorities’ by loyalist paramilitaries characterised as ‘ethnic cleansing’ by the police. The demography of Northern Ireland is changing, with eastern EU and non-white migrant workers arriving, which accentuates the reversing Protestant/Catholic differential and further undermines the ‘Protestant majoritarianism’ on which the state was founded. Alongside ‘flags protests’, racist violence has become one of the principal manifestations of unionist unease. The riposte by the state to racism has been to reach for empty models of ‘hate crime’ and ‘good relations’ alongside a criminal justice policy that appears to find acceptable a certain level of racist violence. Broadly, therefore, the author characterises the experience of people of colour and migrant workers in Northern Ireland as ‘living the peace process in reverse’. He concludes that this reality has profound implications – both for the future of Northern Ireland and for the ways in which we understand the relationship between the state and new forms of British nationalism across the UK.
The Guantánamo-isation of Belgium
Authors: Vervaet Luk
Published: March 2015

Features of the American global war on terror, with its Guantánamo Bay and other secret prisons, where captured detainees are kept outside the national rule of law and international conventions, are being emulated by European democracies, which introduce similar illegal concepts and practices into their penal policies. Now an enthusiastic partner of the US in the war on terror, the Belgian state, fractured internally by the linguistic and regional divide and incapable of finding solutions to the economic crisis, has followed the US in its justice and penal policies. The author charts the erosion of liberal principles within justice policies, from the abandonment of Belgium’s law on universal jurisdiction to the introduction of anti-terror laws and measures; a cooperation agreement with Morocco; and the cavalier attitude to evidence extracted under torture. He examines the significance of the extradition to the US of Tunisian national Nizar Trabelsi. Belgian penal policy has U-turned, especially since the moral panic over child molester and killer Marc Dutroux, and now prisons are massively overcrowded as punishments are ratcheted up. The author argues that the reason for Belgium’s apparent subservience to the US and NATO, and its move to punitive prison policies, lies in its wish to retain its central role within European institutions as it struggles to maintain economic and political stability.
‘Rights’ in the grey area: undocumented border crossers on Lesvos
Authors: Trubeta Sevasti
Published: March 2015

The Aegean island of Lesvos is one of the gateways that refugees and undocumented border crossers use for entering European territory. This study deals with two phenomena related to border crossings on Lesvos: first, the efforts of those arriving to be placed in the status of ‘administrative detention’ in order to receive an expulsion order and then be able to continue their journey; and, second, the activity of the local solidarity network, which initially established an open reception centre for refugees and undocumented immigrants under the umbrella of the civil society, until some activists agreed to put this project under the jurisdiction of the state authorities. In reflecting on these developments, the author addresses two major issues: first, immigration imprisonment as a facet of ‘positive power’ in the Foucauldian sense, and the possible relationship of the latter to grassroots humanitarian commitment; and, second, specific facets of the current paradigm of immigration imprisonment that can help explain why detention may be interpreted as a right by refugees and immigrants. The author argues that the humanitarianism that arises in the interface of surveillance and the provision of care demonstrates post-bureaucratic features; and further, that the strategy pursued by refugees and undocumented immigrants shows how limited their scope is for asserting any rights, given the intensified augmentation of border surveillance worldwide.
Freedom Rides in Palestine: racial segregation and grassroots politics on the bus
Authors: Griffin Maryam S.
Published: March 2015

This article offers an examination of the role of buses in Palestinian protest actions directed at an international audience. These demonstrations occur as part of a post-Oslo strategic shift in which Palestinian resistance has de-prioritised leader-centred negotiations in favour of grassroots mobilisation that directly appeals to international civil society. Given this strategy, the bus is a useful vehicle, both literally and symbolically, for transmitting the message of Palestinian demands for freedom. First, the bus powerfully evokes the triumphs of an earlier generation of activists fighting racial segregation. Second, as a recognisable form of public transportation and mobility, the use of the bus allows Palestinian activists to focus international solidarity on one of the central hardships of occupied life: the denial of the right to freedom of movement, which entrenches the ongoing separation of Palestinians across Palestine.
The ‘knockout game’: moral panic and the politics of white victimhood
Authors: King Mike
Published: March 2015

In the fall of 2013, the ‘knockout game’ – random black-on-white assaults – became the dominant storyline in the US media. Despite no measurable increase in these types of attacks, a moral panic emerged that drew from and amplified numerous previous panics around race and violent crime. While in many ways the ‘knockout game’ is the latest iteration of exaggerated and projected white fears of black violence in the US, the current racial formation is one that increasingly promotes the idea that white Americans are systematically subordinated. In spite of a lack of material evidence to support this claim, media outlets have played a key role in stoking racialised moral panics and normalising what had once been fringe theories of white racial victimhood – to the extent that more than half of white working-class Americans feel they are part of an oppressed racial group.
Fresh Osteochondral Allografts in the Knee
Authors: Gracitelli Guilherme C. , Meric Gokhan , Briggs Dustin T. , Pulido Pamela A. , McCauley Julie C. , Belloti João Carlos , Bugbee William D.
Published: March 2015

Background:

In most treatment algorithms, osteochondral allograft (OCA) transplantation is regarded as an alternative salvage procedure when other, previous reparative treatments have failed.

Purpose:

To compare the outcomes of a retrospective matched-pair cohort of (1) primary OCA transplantation and (2) OCA transplantation after failure of previous subchondral marrow stimulation.

Study Design:

Cohort study; Level of evidence, 3.

Methods:

An OCA database was used to identify 46 knees that had OCA transplantation performed as a primary treatment (group 1) and 46 knees that underwent OCA transplantation after failure of previous subchondral marrow stimulation (group 2). All patients had a minimum of 2 years’ follow-up. Patients in each group were matched for age (±5 years), diagnosis (osteochondral lesion, degenerative chondral lesion, traumatic chondral injury), and graft size (small, <5 cm2; medium, 5-10 cm2; large, >10 cm2). The groups had similar body mass indexes, sex distributions, and graft locations (femoral condyle, patella, and trochlea. The number and type of further surgeries after the OCA transplantation were assessed; failure was defined as any reoperation resulting in removal of the graft. Functional outcomes were evaluated by use of the modified Merle d’Aubigné-Postel (18-point) scale, International Knee Documentation Committee (IKDC) subjective knee evaluation form, Knee injury and Osteoarthritis Outcomes Score (KOOS), and the Knee Society function (KS-F) scale. Patient satisfaction, according to a 5-point scale from “extremely satisfied” to “dissatisfied,” was recorded at the latest follow-up.

Results:

Eleven of 46 knees (24%) in group 1 had reoperations, compared with 20 of 46 knees (44%) in group 2 ( P = .04). The OCA was classified as a failure in 5 knees (11%) in group 1 and 7 knees (15%) in group 2 ( P = .53). At 10 years of follow-up, survivorship of the graft was 87.4% and 86% in groups 1 and 2, respectively. Both groups showed improvement in pain and function on all subjective scores from preoperatively to the latest follow-up (all P < .001). Results showed that 87% of patients in group 1 and 97% in group 2 were “satisfied” or “extremely satisfied” with the OCA transplantation.

Conclusion:

Favorable results were shown in both groups with significant improvement of functional scores and excellent survivorship. Despite the higher reoperation rate in the previously treated group, previous subchondral marrow stimulation did not adversely affect the survivorship and functional outcome of OCA transplantation.
Dying With Carolyn
Authors: Kortes-Miller Katherine , Jones-Bonofiglio Kristen , Hendrickson Stephanie , Kelley Mary Lou
Published: March 2015

This article examines the development, implementation, and evaluation of a pilot project utilizing high-fidelity simulation (HFS) to improve frontline staff members’ confidence and skills to communicate about death and dying in long-term care homes. The target group was unregulated care providers who provide palliative care for residents and their families. Eighteen participants engaged in the educational intervention and evaluation. Results supported the effectiveness of HFS as an educational tool for unregulated health care providers. Quantitative data showed statistically significant improvements in participants’ self-efficacy scores related to communicating about death and dying and end-of-life care. Qualitative data indicated that the experience was a valuable learning opportunity and helped participants develop insights into their own values, beliefs, and fears providing end-of-life care. HFS is therefore recommended as an innovative training strategy to improve palliative care communication in long-term care homes.
The Safety and Feasibility of Admitting Patients With Intracerebral Hemorrhage to the Step-Down Unit
Authors: Hafeez Shaheryar , Behrouz Réza
Published: March 2015

Background:

Intracerebral hemorrhage (ICH) is a devastating and costly condition. Although the American Heart Association/American Stroke Association recommends admitting patients with ICH to a neurocritical care unit (NCCU), this strategy may accrue unnecessary cost for patients with relatively milder presentation. We conducted a prospective observational study to determine the safety and feasibility of admitting patients with mild ICH directly to a step-down unit (SDU) instead of an NCCU.

Methods:

Consecutive patients with “mild presentation,” defined as a combination of ICH score ≤2, National Institutes of Health Stroke Scale (NIHSS) ≤ 15, and Graeb score ≤2 (if intraventricular hemorrhage was present), were admitted to the SDU. Data were collected on age, gender as well as the initial NIHSS, Glasgow Coma Scale (GCS), ICH, and Graeb scores. Primary end point was any complication or death during hospital stay.

Results:

Twenty patients were admitted to the SDU. No patient was transferred to the NCCU from the SDU. One patient, who eventually died, had respiratory insufficiency due to hospital-acquired pneumonia.

Conclusion:

Admission of ICH patients with mild symptoms to the SDU is safe and feasible. Larger prospective studies are needed to define the specific criteria for admission.
Attitude Toward Ambiguity
Authors: Lauriola Marco , Foschi Renato , Mosca Oriana , Weller Joshua
Published: March 2015

Two studies were conducted to examine the factor structure of attitude toward ambiguity, a broad personality construct that refers to personal reactions to perceived ambiguous stimuli in a variety of context and situations. Using samples from two countries, Study 1 mapped the hierarchical structure of 133 items from seven tolerance–intolerance of ambiguity scales ( N = 360, Italy; N = 306, United States). Three major factors—Discomfort with Ambiguity, Moral Absolutism/Splitting, and Need for Complexity and Novelty—were recovered in each country with high replicability coefficients across samples. In Study 2 ( N = 405, Italian community sample; N =366, English native speakers sample), we carried out a confirmatory analysis on selected factor markers. A bifactor model had an acceptable fit for each sample and reached the construct-level invariance for general and group factors. Convergent validity with related traits was assessed in both studies. We conclude that attitude toward ambiguity can be best represented a multidimensional construct involving affective (Discomfort with Ambiguity), cognitive (Moral Absolutism/Splitting), and epistemic (Need for Complexity and Novelty) components.
Flatfoot in School-Age Children
Authors: Sadeghi-Demneh Ebrahim , Jafarian Fahimehsadat , Melvin Jonathan M. A. , Azadinia Fatemeh , Shamsi Fatemeh , Jafarpishe Mohamad
Published: March 2015

Background. Flatfoot has been shown to cause abnormal stresses on the foot and lower extremity. The altered mechanical stresses on these structures can aggravate the foot deformity. Screening of the flatfoot and its associated factors helps detect underlying risks influencing the stresses on the foot. The purpose of this study was to analyze the structure of the medial foot arch and investigate its associated factors in students, aged 7 to 14 years. Methods. Multistage cluster sampling was used and each cluster included 2 other random sampling levels. A total of 667 Iranian school children were recruited and their feet were bilaterally evaluated using a static footprint while standing in a fully weightbearing position. The footprint, an observational measurement, and a questionnaire were used for the foot assessment. Results. The prevalence of flatfoot was 17.1% in the population studied. There was no gender difference but the prevalence of flatfoot did decrease with age. The significant differences were observed in the prevalence of flatfoot between normal-weight, overweight, and obese groups (P < .01); more overweight participants had flatter feet. Conclusion. This study demonstrated that development of the longitudinal plantar arch in school-age children is influenced by age and weight. Age and weight were the primary predictive factors of flatfoot.

Levels of Evidence: Prognostic, Level IV: Case series
Non‐coeliac gluten sensitivity: piecing the puzzle together
Authors: Biesiekierski Jessica R , Iven Julie
Published: March 2015

The avoidance of wheat‐ and gluten‐containing products is a worldwide phenomenon. While coeliac disease is well‐established, much remains unknown about whether gluten can be a trigger of gastrointestinal and/or extra‐intestinal symptoms in patients without coeliac disease. In this article, we discuss the latest scientific evidence and our current understanding for the possible mechanisms of this largely ambiguous group, termed ‘non‐coeliac gluten sensitive’ (NCGS). We can conclude that NCGS should be regarded as an independent disease outside of coeliac disease and wheat allergy, and that the number of patients affected is likely to be limited. Many questions remain unanswered and it needs to be verified whether the elimination of dietary gluten alone is sufficient for the control of symptoms, and to understand the overlap with other components of wheat.
Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study
Authors: Tikk Kaja , Sookthai Disorn , Fortner Renée T , Johnson Theron , Rinaldi Sabina , Romieu Isabelle , Tjønneland Anne , Olsen Anja , Overvad Kim , Clavel-Chapelon Françoise , Baglietto Laura , Boeing Heiner , Trichopoulou Antonia , Lagiou Pagona , Trichopoulos Dimitrios , Masala Giovanna , Krogh Vittorio , Tumino Rosario , Ricceri Fulvio , Mattiello Amalia , Agudo Antonio , Menéndez Virginia , Sánchez María-José , Amiano Pilar , Chirlaque Maria-Dolores , Barricarte Aurelio , Bueno-de-Mesquita HBas , Monninkhof Evelyn M , Onland-Moret N Charlotte , Andresson Anne , Sund Malin , Weiderpass Elisabete , Khaw Kay-Tee , Key Timothy J , Travis Ruth C , Merritt Melissa A , Riboli Elio , Dossus Laure , Kaaks Rudolf
Published: March 2015

Introduction

The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

Methods

We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.

Results

We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2 = 1.35 (95% CI 1.04-1.76), Ptrend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet = 0.98) or baseline HT use (Phet = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend = 0.06 vs Ptrend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (Ptrend = 0.01 vs Ptrend = 0.63; Phet = 0.04) and among nulliparous women compared to parous women (Ptrend = 0.03 vs Ptrend = 0.15; Phet = 0.07).

Conclusions

Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
Identifying candidate drivers of alcohol dependence-induced excessive drinking by assembly and interrogation of brain-specific regulatory networks
Authors: Repunte-Canonigo Vez , Shin William , Vendruscolo Leandro F , Lefebvre Celine , van der Stap Lena , Kawamura Tomoya , Schlosburg Joel E , Alvarez Mariano , Koob George F , Califano Andrea , Sanna Pietro Paolo
Published: March 2015

Background

A systems biology approach based on the assembly and interrogation of gene regulatory networks, or interactomes, was used to study neuroadaptation processes associated with the transition to alcohol dependence at the molecular level.

Results

Using a rat model of dependent and non-dependent alcohol self-administration, we reverse engineered a global transcriptional regulatory network during protracted abstinence, a period when relapse rates are highest. We then interrogated the network to identify master regulator genes that mechanistically regulate brain region-specific signatures associated with dependent and non-dependent alcohol self-administration. Among these, the gene coding for the glucocorticoid receptor was independently identified as a master regulator in multiple brain regions, including the medial prefrontal cortex, nucleus accumbens, central nucleus of the amygdala, and ventral tegmental area, consistent with the view that brain reward and stress systems are dysregulated during protracted abstinence. Administration of the glucocorticoid antagonist mifepristone in either the nucleus accumbens or ventral tegmental area selectively decreased dependent, excessive, alcohol self-administration in rats but had no effect on non-dependent, moderate, alcohol self-administration.

Conclusions

Our study suggests that assembly and analysis of regulatory networks is an effective strategy for the identification of key regulators of long-term neuroplastic changes within specific brain regions that play a functional role in alcohol dependence. More specifically, our results support a key role for regulatory networks downstream of the glucocorticoid receptor in excessive alcohol drinking during protracted alcohol abstinence.
Characterization of the immunophenotypes and antigenomes of colorectal cancers reveals distinct tumor escape mechanisms and novel targets for immunotherapy
Authors: Angelova Mihaela , Charoentong Pornpimol , Hackl Hubert , Fischer Maria L , Snajder Rene , Krogsdam Anne M , Waldner Maximilian J , Bindea Gabriela , Mlecnik Bernhard , Galon Jerome , Trajanoski Zlatko
Published: March 2015

Background

While large-scale cancer genomic projects are comprehensively characterizing the mutational spectrum of various cancers, so far little attention has been devoted to either define the antigenicity of these mutations or to characterize the immune responses they elicit. Here we present a strategy to characterize the immunophenotypes and the antigen-ome of human colorectal cancer.

Results

We apply our strategy to a large colorectal cancer cohort (n = 598) and show that subpopulations of tumor-infiltrating lymphocytes are associated with distinct molecular phenotypes. The characterization of the antigenome shows that a large number of cancer-germline antigens are expressed in all patients. In contrast, neo-antigens are rarely shared between patients, indicating that cancer vaccination requires individualized strategy. Analysis of the genetic basis of the tumors reveals distinct tumor escape mechanisms for the patient subgroups. Hypermutated tumors are depleted of immunosuppressive cells and show upregulation of immunoinhibitory molecules. Non-hypermutated tumors are enriched with immunosuppressive cells, and the expression of immunoinhibitors and MHC molecules is downregulated. Reconstruction of the interaction network of tumor-infiltrating lymphocytes and immunomodulatory molecules followed by a validation with 11 independent cohorts (n = 1,945) identifies BCMA as a novel druggable target. Finally, linear regression modeling identifies major determinants of tumor immunogenicity, which include well-characterized modulators as well as a novel candidate, CCR8, which is then tested in an orthologous immunodeficient mouse model.

Conclusions

The immunophenotypes of the tumors and the cancer antigenome remain widely unexplored, and our findings represent a step toward the development of personalized cancer immunotherapies.
An approach for determining and measuring network hierarchy applied to comparing the phosphorylome and the regulome
Authors: Cheng Chao , Andrews Erik , Yan Koon-Kiu , Ung Matthew , Wang Daifeng , Gerstein Mark
Published: March 2015

Many biological networks naturally form a hierarchy with a preponderance of downward information flow. In this study, we define a score to quantify the degree of hierarchy in a network and develop a simulated-annealing algorithm to maximize the hierarchical score globally over a network. We apply our algorithm to determine the hierarchical structure of the phosphorylome in detail and investigate the correlation between its hierarchy and kinase properties. We also compare it to the regulatory network, finding that the phosphorylome is more hierarchical than the regulome.
High-resolution genomic analysis: the tumor-immune interface comes into focus
Authors: Havel Jonathan J , Chan Timothy A
Published: March 2015

A genomic analysis of heterogeneous colorectal tumor samples has uncovered interactions between immunophenotype and various aspects of tumor biology, with implications for informing the choice of immunotherapies for specific patients and guiding the design of personalized neoantigen-based vaccines.

Please see related article: http://dx.doi.org/10.1186/s13059-015-0620-6
Single-cell analysis of lung adenocarcinoma cell lines reveals diverse expression patterns of individual cells invoked by a molecular target drug treatment
Authors: Suzuki Ayako , Matsushima Koutatsu , Makinoshima Hideki , Sugano Sumio , Kohno Takashi , Tsuchihara Katsuya , Suzuki Yutaka
Published: March 2015

Background

To understand the heterogeneous behaviors of individual cancer cells, it is essential to investigate gene expression levels as well as their divergence between different individual cells. Recent advances in next-generation sequencing-related technologies have enabled us to conduct a single-cell RNA-Seq analysis of a series of lung adenocarcinoma cell lines.

Results

We analyze a total of 336 single-cell RNA-Seq libraries from seven cell lines. The results are highly robust regarding both average expression levels and the relative gene expression differences between individual cells. Gene expression diversity is characteristic depending on genes and pathways. Analyses of individual cells treated with the multi-tyrosine kinase inhibitor vandetanib reveal that, while the ribosomal genes and many other so-called house-keeping genes reduce their relative expression diversity during the drug treatment, the genes that are directly targeted by vandetanib, the EGFR and RET genes, remain constant. Rigid transcriptional control of these genes may not allow plastic changes of their expression with the drug treatment or during the cellular acquisition of drug resistance. Additionally, we find that the gene expression patterns of cancer-related genes are sometimes more diverse than expected based on the founder cells. Furthermore, we find that this diversity is occasionally latent in a normal state and initially becomes apparent after the drug treatment.

Conclusions

Characteristic patterns in gene expression divergence, which would not be revealed by transcriptome analysis of bulk cells, may also play important roles when cells acquire drug resistance, perhaps by providing a cellular reservoir for gene expression programs.
Associations between host gene expression, the mucosal microbiome, and clinical outcome in the pelvic pouch of patients with inflammatory bowel disease
Authors: Morgan Xochitl C , Kabakchiev Boyko , Waldron Levi , Tyler Andrea D , Tickle Timothy L , Milgrom Raquel , Stempak Joanne M , Gevers Dirk , Xavier Ramnik J , Silverberg Mark S , Huttenhower Curtis
Published: March 2015

Background

Pouchitis is common after ileal pouch-anal anastomosis (IPAA) surgery for ulcerative colitis (UC). Similar to inflammatory bowel disease (IBD), both host genetics and the microbiota are implicated in its pathogenesis. We use the IPAA model of IBD to associate mucosal host gene expression with mucosal microbiomes and clinical outcomes. We analyze host transcriptomic data and 16S rRNA gene sequencing data from paired biopsies from IPAA patients with UC and familial adenomatous polyposis. To achieve power for a genome-wide microbiome-transcriptome association study, we use principal component analysis for transcript and clade reduction, and identify significant co-variation between clades and transcripts.

Results

Host transcripts co-vary primarily with biopsy location and inflammation, while microbes co-vary primarily with antibiotic use. Transcript-microbe associations are surprisingly modest, but the most strongly microbially-associated host transcript pattern is enriched for complement cascade genes and for the interleukin-12 pathway. Activation of these host processes is inversely correlated with Sutterella, Akkermansia, Bifidobacteria, and Roseburia abundance, and positively correlated with Escherichia abundance.

Conclusions

This study quantifies the effects of inflammation, antibiotic use, and biopsy location upon the microbiome and host transcriptome during pouchitis. Understanding these effects is essential for basic biological insights as well as for well-designed and adequately-powered studies. Additionally, our study provides a method for profiling host-microbe interactions with appropriate statistical power using high-throughput sequencing, and suggests that cross-sectional changes in gut epithelial transcription are not a major component of the host-microbiome regulatory interface during pouchitis.
ClinSeK: a targeted variant characterization framework for clinical sequencing
Authors: Zhou Wanding , Zhao Hao , Chong Zechen , Mark Routbort J , Eterovic Agda K , Meric-Bernstam Funda , Chen Ken
Published: March 2015

Applying genomics to patient care demands sensitive, unambiguous and rapid characterization of a known set of clinically relevant variants in patients’ samples, an objective substantially different from the standard discovery process, in which every base in every sequenced read must be examined. Further, the approach must be sufficiently robust as to be able to detect multiple and potentially rare variants from heterogeneous samples. To meet this critical objective, we developed a novel variant characterization framework, ClinSeK, which performs targeted analysis of relevant reads from high-throughput sequencing data. ClinSeK is designed for efficient targeted short read alignment and is capable of characterizing a wide spectrum of genetic variants from single nucleotide variation to large-scale genomic rearrangement breakpoints. Applying ClinSeK to over a thousand cancer patients demonstrated substantively better performance, in terms of accuracy, runtime and disk storage, for clinical applications than existing variant discovery tools. ClinSeK is freely available for academic use at http://bioinformatics.mdanderson.org/main/clinsek.
The gut microbiome in cardio-metabolic health
Authors: Hansen Tue H , Gøbel Rikke J , Hansen Torben , Pedersen Oluf
Published: March 2015

With the prevalence of cardio-metabolic disorders reaching pandemic proportions, the search for modifiable causative factors has intensified. One such potential factor is the vast microbial community inhabiting the human gastrointestinal tract, the gut microbiota. For the past decade evidence has accumulated showing the association of distinct changes in gut microbiota composition and function with obesity, type 2 diabetes and cardiovascular disease. Although causality in humans and the pathophysiological mechanisms involved have yet to be decisively established, several studies have demonstrated that the gut microbiota, as an environmental factor influencing the metabolic state of the host, is readily modifiable through a variety of interventions. In this review we provide an overview of the development of the gut microbiome and its compositional and functional changes in relation to cardio-metabolic disorders, and give an update on recent progress in how this could be exploited in microbiota-based therapeutics.
Are mesenchymal stromal cells immune cells?
Authors: Hoogduijn Martin J
Published: March 2015

Mesenchymal stromal cells (MSCs) are considered to be promising agents for the treatment of immunological disease. Although originally identified as precursor cells for mesenchymal lineages, in vitro studies have demonstrated that MSCs possess diverse immune regulatory capacities. Pre-clinical models have shown beneficial effects of MSCs in multiple immunological diseases and a number of phase 1/2 clinical trials carried out so far have reported signs of immune modulation after MSC infusion. These data indicate that MSCs play a central role in the immune response. This raises the academic question whether MSCs are immune cells or whether they are tissue precursor cells with immunoregulatory capacity. Correct understanding of the immunological properties and origin of MSCs will aid in the appropriate and safe use of the cells for clinical therapy. In this review the whole spectrum of immunological properties of MSCs is discussed with the aim of determining the position of MSCs in the immune system.
Cumulative impact of health deficits, social vulnerabilities, and protective factors on cognitive dynamics in late life: a multistate modeling approach
Authors: Armstrong Joshua J , Mitnitski Arnold , Andrew Melissa K , Launer Lenore J , White Lon R , Rockwood Kenneth
Published: March 2015

Introduction

Many factors influence late-life cognitive changes, and evaluating their joint impact is challenging. Typical approaches focus on average decline and a small number of factors. We used multistate transition models and index variables to look at changes in cognition in relation to frailty (accumulation of health deficits), social vulnerability, and protective factors in the Honolulu-Asia Aging Study (HAAS).

Methods

The HAAS is a prospective cohort study of 3,845 men of Japanese descent, aged 71 to 93 years at baseline. Cognitive function was measured using the Cognitive Abilities Screening Instrument (CASI). Baseline index variables were constructed of health deficits (frailty), social vulnerabilities, and protective factors. The chances of improvement/stability/decline in cognitive function and death were simultaneously estimated using multistate transition modeling for 3- and 6-year transitions from baseline.

Results

On average, CASI scores declined by 5.3 points (standard deviation (SD) = 10.0) over 3 years and 9.5 points (SD = 13.9) over 6 years. After adjusting for education and age, baseline frailty was associated with an increased risk of cognitive decline at 3 years (β = 0.18, 95% confidence interval (CI), 0.08 to 0.29) and 6 years (β = 0.40, 95% CI, 0.27 to 0.54). The social vulnerability index was associated with 3-year changes (β = 0.16, 95% CI, 0.09 to 0.23) and 6-year changes (β = 0.14, 95% CI, 0.05 to 0.24) in CASI scores. The protective index was associated with reductions in cognitive decline over the two intervals (3-year: β = −0.16, 95% CI, −0.24 to −0.09; 6-year: β = −0.21, 95% CI, −0.31 to –0.11,).

Conclusions

Research on cognition in late life needs to consider overall health, the accumulation of protective factors, and the dynamics of cognitive change. Index variables and multistate transition models can enhance understanding of the multifactorial nature of late-life changes in cognition.
Effects of norepinephrine on tissue perfusion in a sheep model of intra-abdominal hypertension
Authors: Ferrara Gonzalo , Kanoore Edul Vanina S , Caminos Eguillor Juan F , Martins Enrique , Canullán Carlos , Canales Héctor S , Ince Can , Estenssoro Elisa , Dubin Arnaldo
Published: March 2015

Background

The aim of the study was to describe the effects of intra-abdominal hypertension (IAH) on regional and microcirculatory intestinal blood flow, renal blood flow, and urine output, as well as their response to increases in blood pressure induced by norepinephrine.

Methods

This was a pilot, controlled study, performed in an animal research laboratory. Twenty-four anesthetized and mechanically ventilated sheep were studied. We measured systemic hemodynamics, superior mesenteric and renal blood flow, villi microcirculation, intramucosal-arterial PCO2, urine output, and intra-abdominal pressure. IAH (20 mm Hg) was generated by intraperitoneal instillation of warmed saline. After 1 h of IAH, sheep were randomized to IAH control (n = 8) or IAH norepinephrine (n = 8) groups, for 1 h. In this last group, mean arterial pressure was increased about 20 mm Hg with norepinephrine. A sham group (n = 8) was also studied. Fluids were administered to prevent decreases in cardiac output. Differences between groups were analyzed with two-way repeated measures of analysis of variance (ANOVA).

Results

After 2 h of IAH, abdominal perfusion pressure decreased in IAH control group compared to IAH norepinephrine and sham groups (49 ± 11, 73 ± 11, and 86 ± 15 mm Hg, P < 0.0001). There were no differences in superior mesenteric artery blood flow, intramucosal-arterial PCO2, and villi microcirculation among groups. Renal blood flow (49 ± 30, 32 ± 24, and 102 ± 45 mL.min−1.kg−1, P < 0.0001) and urinary output (0.3 ± 0.1, 0.2 ± 0.2, and 1.0 ± 0.6 mL.h−1.kg−1, P < 0.0001) were decreased in IAH control and IAH norepinephrine groups, compared to the sham group.

Conclusions

In this experimental model of IAH, the gut and the kidney had contrasting responses: While intestinal blood flow and villi microcirculation remained unchanged, renal perfusion and urine output were severely compromised.
A study of balloon type, system constraint and artery constitutive model used in finite element simulation of stent deployment
Authors: Schiavone A , Zhao L G
Published: March 2015

Background

Finite element is an effective tool to simulate stent expansion inside stenotic arteries, which provides an insightful understanding of the biomechanical behaviour of the whole stent-artery system during the procedure. The choice of balloon type, system constraint and artery constitutive model plays an important role in finite element simulation of stent deployment.

Methods

Commercial finite element package ABAQUS was used to model the expansion of Xience stent inside a diseased artery with 40% stenosis. The arterial wall, consisting of intima, media and adventitia layers, and the stenotic plaque were described by different hyperelastic models. Both folded and rubber balloons were considered and inflated with a linearly increasing pressure of 1.4 MPa. Simulations were also carried out by considering free, partially and fully constrained arteries.

Results

Folded balloon produces sustained stent expansion under a lower pressure when compared to rubber balloon, leading to increased stress level and enhanced final expansion for the system. Fully constrained artery reduces the stent expansion when compared to free and partially constrained arteries, due to the increased recoiling effect. Stress in the artery-plaque system has higher magnitude for stent expansion in a free artery due to more severe stretch. Calcified plaque limits stent expansion considerably when compared to hypocellular plaque. The negligence of the second stretch invariant in the strain energy potential leads to the disappearance of saturation behaviour during stent expansion. The use of anisotropic artery model reduces the system expansion at peak pressure when compared to the isotropic model, but with an increased final diameter due to reduced recoiling effect. The stress distribution in the artery-plaque system is also different for different combinations of artery and plaque constitutive models.

Conclusions

Folded balloon should be used in the simulation of stent deployment, with the artery partially constrained using spring elements with a proper stiffness constant. The blood vessel should be modelled as a three-layer structure using a hyperelastic potential that considers both the first and second stretch invariants as well as the anisotropy. The composition of the plaque also has to be considered due to its major effect on stent deployment.
Body-wave reconstruction from ambient seismic noise correlations in an underground mine
Authors: Olivier Gerrit , Brenguier Florent , Campillo Michel , Lynch Richard , Roux Philippe
Published: March 2015

The reconstruction of seismic Green’s functions from correlations of ambient seismic noise has recently developed as a promising approach for exploring the earth’s interiors without the requirement of costly active seismic sources. This approach is widely used for imaging the crust at a kilometer scale. However, few studies report noise-based Green’s function reconstruction at smaller scales in industrial environments. We have investigated the possibility of constructing seismic Green’s functions between sensors in an active underground mine (Garpenberg, Sweden) by crosscorrelating seismic noise generated by mining activities. We have determined with realistic numerical simulations that the mining excavations in an underground mine lead to a regime of strong scattering, which is favorable for constructing seismic Green’s functions by crosscorrelating seismic noise. One month of continuous data was recorded by 18 seismic sensors located more than 1 km below surface. A variety of broadband (10–3000 Hz) seismic sources were present, but the seismic wavefields are directional and often monochromatic, so that the conditions for constructing Green’s functions by crosscorrelating ambient seismic noise were not ideal (isotropic illumination and spectrally white). We developed a stacking scheme that dismissed data during periods when the seismic noise was dominated by monochromatic signals or when noise sources were not in stationary phase locations. Estimates of the seismic Green’s functions were retrieved for a broad frequency range (20–400 Hz) for almost all of the correlation pairs when we used the selective stacking scheme. We used the direct body waves present at low frequencies (less than 100 Hz) in the reconstructed seismic Green’s functions to invert for the 3D S-wave velocity structure of the mine. Our results revealed the existence of a high-velocity zone and a low-velocity zone that corresponded with known ore bodies.