Some Recent Developments on Kink Collisions and Related Topics

We review recent works on modeling of dynamics of kinks in 1+1 dimensional $\phi^4$ theory and other related models, like sine-Gordon model or $\phi^6$ theory. We discuss how the spectral structure of small perturbations can affect the dynamics of non-perturbative states, such as kinks or oscillons. We describe different mechanisms, which may lead to the occurrence of the resonant structure in the kink-antikink collisions. We explain the origin of the radiation pressure mechanism, in particular, the appearance of the negative radiation pressure in the $\phi^4$ and $\phi^6$ models. We also show that the process of production of the kink-antikink pairs, induced by radiation is chaotic.Comment: 26 pages, 9 figures; invited chapter to "A dynamical perspective on the {\phi}4 model: Past, present and future", Eds. P.G. Kevrekidis and J. Cuevas-Maraver; Springer book class with svmult.cls include

Disorder-specific functional abnormalities during sustained attention in youth with Attention Deficit Hyperactivity Disorder (ADHD) and with Autism

Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are often comorbid and share behavioural-cognitive abnormalities in sustained attention. A key question is whether this shared cognitive phenotype is based on common or different underlying pathophysiologies. To elucidate this question, we compared 20 boys with ADHD to 20 age and IQ matched ASD and 20 healthy boys using functional magnetic resonance imaging (fMRI) during a parametrically modulated vigilance task with a progressively increasing load of sustained attention. ADHD and ASD boys had significantly reduced activation relative to controls in bilateral striato–thalamic regions, left dorsolateral prefrontal cortex (DLPFC) and superior parietal cortex. Both groups also displayed significantly increased precuneus activation relative to controls. Precuneus was negatively correlated with the DLPFC activation, and progressively more deactivated with increasing attention load in controls, but not patients, suggesting problems with deactivation of a task-related default mode network in both disorders. However, left DLPFC underactivation was significantly more pronounced in ADHD relative to ASD boys, which furthermore was associated with sustained performance measures that were only impaired in ADHD patients. ASD boys, on the other hand, had disorder-specific enhanced cerebellar activation relative to both ADHD and control boys, presumably reflecting compensation. The findings show that ADHD and ASD boys have both shared and disorder-specific abnormalities in brain function during sustained attention. Shared deficits were in fronto–striato–parietal activation and default mode suppression. Differences were a more severe DLPFC dysfunction in ADHD and a disorder-specific fronto–striato–cerebellar dysregulation in ASD

Rapid copper acquisition by developing murine mesothelioma: Decreasing bioavailable copper slows tumor growth, normalizes vessels and promotes T cell infiltration

Copper, an essential trace element acquired through nutrition, is an important co-factor for pro-angiogenic factors including vascular endothelial growth factor (VEGF). Decreasing bioavailable copper has been used as an antiangiogenic and anti-cancer strategy with promising results. However, the role of copper and its potential as a therapy in mesothelioma is not yet well understood. Therefore, we monitored copper levels in progressing murine mesothelioma tumors and analyzed the effects of lowering bioavailable copper. Copper levels in tumors and organs were assayed using atomic absorption spectrophotometry. Mesothelioma tumors rapidly sequestered copper at early stages of development, the copper was then dispersed throughout growing tumor tissues. These data imply that copper uptake may play an important role in early tumor development. Lowering bioavailable copper using the copper chelators, penicillamine, trientine or tetrathiomolybdate, slowed in vivo mesothelioma growth but did not provide any cures similar to using cisplatin chemotherapy or anti-VEGF receptor antibody therapy. The impact of copper lowering on tumor blood vessels and tumor infiltrating T cells was measured using flow cytometry and confocal microscopy. Copper lowering was associated with reduced tumor vessel diameter, reduced endothelial cell proliferation (reduced Ki67 expression) and lower surface ICAM/CD54 expression implying reduced endothelial cell activation, in a process similar to endothelial normalization. Copper lowering was also associated with a CD4+ T cell infiltrate. In conclusion, these data suggest copper lowering is a potentially useful anti-mesothelioma treatment strategy that slows tumor growth to provide a window of opportunity for inclusion of other treatment modalities to improve patient outcomes

Relationship between quality of life and psychopathological profile: data from an observational study in children with ADHD

Although ADHD significantly affects the quality of life (QoL) of patients and their families, QoL in children with ADHD has rarely been investigated in association with psychopathological profile, and the relationship remains unclear. The open-label OBSEER study evaluated the effectiveness and tolerability of Equasym XL®, a modified-release methylphenidate, in routine care of children and adolescents (aged 6–17 years) with ADHD. At baseline, questionnaires assessing psychopathological profile (Strengths and Difficulties Questionnaire, SDQ; parental ratings) and QoL (KINDL; parent, child or adolescent versions) were completed; QoL was reassessed at final visit. We analysed the relationship between psychopathology and parent/patient-rated QoL in ADHD at baseline. Data from 721 consecutively referred children and adolescents were analysed. QoL was similarly low from parent and self-ratings and independent of severity on the SDQ subscale hyperactivity/inattention. Self-ratings indicated that additional conduct disorder was associated with further reduction in QoL. Similarly, children with high scores from parent and adolescent ratings on the SDQ subscale conduct problems had reduced QoL on some KINDL subscales. Adolescents with ADHD not receiving medication at baseline reported lower QoL than those already on medication. Results show that children and adolescents with ADHD have low QoL, independent of core symptom severity. Additional conduct problems may further impact QoL negatively, while ADHD medication use may show a trend towards improved QoL. Not all psychopathological problems associated with ADHD affect QoL similarly. As parents appear to have a less critical view of QoL compared with children’s self-ratings, both parent and child ratings should be included in clinical assessments

Time dependent ethnic convergence in colorectal cancer survival in hawaii

BACKGROUND: Although colorectal cancer death rates have been declining, this trend is not consistent across all ethnic groups. Biological, environmental, behavioral and socioeconomic explanations exist, but the reason for this discrepancy remains inconclusive. We examined the hypothesis that improved cancer screening across all ethnic groups will reduce ethnic differences in colorectal cancer survival. METHODS: Through the Hawaii Tumor Registry 16,424 patients diagnosed with colorectal cancer were identified during the years 1960–2000. Cox regression analyses were performed for each of three cohorts stratified by ethnicity (Caucasian, Japanese, Hawaiian, Filipino, and Chinese). The models included stage of diagnosis, year of diagnosis, age, and sex as predictors of survival. RESULTS: Mortality rates improved significantly for all ethnic groups. Moreover, with the exception of Hawaiians, rates for all ethnic groups converged over time. Persistently lower survival for Hawaiians appeared linked with more cancer treatment. CONCLUSION: Ethnic disparities in colorectal cancer mortality rates appear primarily the result of differential utilization of health care. If modern screening procedures can be provided equally to all ethnic groups, ethnic outcome differences can be virtually eliminated

Quorum Sensing Regulation of the Two hcp Alleles in Vibrio cholerae O1 Strains

BACKGROUND: The type VI secretion system (T6SS) has emerged as a protein secretion system important to several gram-negative bacterial species. One of the common components of the system is Hcp, initially described as a hemolysin co-regulated protein in a serotype O17 strain of Vibrio cholerae. Homologs to V. cholerae hcp genes have been found in all characterized type VI secretion systems and they are present also in the serotype O1 strains of V. cholerae that are the cause of cholera diseases but seemed to have non-functional T6SS. METHODOLOGY/PRINCIPAL FINDINGS: The serotype O1 V. cholerae strain A1552 was shown to express detectable levels of Hcp as determined by immunoblot analyses using polyclonal anti-Hcp antiserum. We found that the expression of Hcp was growth phase dependent. The levels of Hcp in quorum sensing deficient mutants of V. cholerae were compared with the levels in wild type V. cholerae O1 strain A1552. The expression of Hcp was positively and negatively regulated by the quorum sensing regulators HapR and LuxO, respectively. In addition, we observed that expression of Hcp was dependent on the cAMP-CRP global transcriptional regulatory complex and required the RpoN sigma factor. CONCLUSION/SIGNIFICANCE: Our results show that serotype O1 strains of V. cholerae do express Hcp which is regarded as one of the important T6SS components and is one of the secreted substrates in non-O1 non-O139 V. cholerae isolates. We found that expression of Hcp was strictly regulated by the quorum sensing system in the V. cholerae O1 strain. In addition, the expression of Hcp required the alternative sigma factor RpoN and the cAMP-CRP global regulatory complex. Interestingly, the environmental isolates of V. cholerae O1 strains that showed higher levels of the HapR quorum sensing regulator in comparison with our laboratory standard serotype O1 strain A1552 where also expressing higher levels of Hcp

Classification of ductal carcinoma in situ by gene expression profiling

INTRODUCTION: Ductal carcinoma in situ (DCIS) is characterised by the intraductal proliferation of malignant epithelial cells. Several histological classification systems have been developed, but assessing the histological type/grade of DCIS lesions is still challenging, making treatment decisions based on these features difficult. To obtain insight in the molecular basis of the development of different types of DCIS and its progression to invasive breast cancer, we have studied differences in gene expression between different types of DCIS and between DCIS and invasive breast carcinomas. METHODS: Gene expression profiling using microarray analysis has been performed on 40 in situ and 40 invasive breast cancer cases. RESULTS: DCIS cases were classified as well- (n = 6), intermediately (n = 18), and poorly (n = 14) differentiated type. Of the 40 invasive breast cancer samples, five samples were grade I, 11 samples were grade II, and 24 samples were grade III. Using two-dimensional hierarchical clustering, the basal-like type, ERB-B2 type, and the luminal-type tumours originally described for invasive breast cancer could also be identified in DCIS. CONCLUSION: Using supervised classification, we identified a gene expression classifier of 35 genes, which differed between DCIS and invasive breast cancer; a classifier of 43 genes could be identified separating between well- and poorly differentiated DCIS samples

Why caretakers bypass Primary Health Care facilities for child care - a case from rural Tanzania

<p>Abstract</p> <p>Background</p> <p>Research on health care utilization in low income countries suggests that patients frequently bypass PHC facilities in favour of higher-level hospitals - despite substantial additional time and financial costs. There are limited number of studies focusing on user's experiences at such facilities and reasons for bypassing them. This study aimed to identify factors associated with bypassing PHC facilities among caretakers seeking care for their underfive children and to explore experiences at such facilities among those who utilize them.</p> <p>Methods</p> <p>The study employed a mixed-method approach consisting of an interviewer administered questionnaires and in-depth interviews among selected care-takers seeking care for their underfive children at Korogwe and Muheza district hospitals in north-eastern Tanzania.</p> <p>Results</p> <p>The questionnaire survey included 560 caretakers. Of these 30 in-depth interviews were conducted. Fifty nine percent (206/348) of caretakers had not utilized their nearer PHC facilities during the index child's sickness episode. The reasons given for bypassing PHC facilities were lack of possibilities for diagnostic facilities (42.2%), lack of drugs (15.5%), closed health facility (10.2%), poor services (9.7%) and lack of skilled health workers (3.4%). In a regression model, the frequency of bypassing a PHC facility for child care increased significantly with decreasing travel time to the district hospital, shorter duration of symptoms and low disease severity.</p> <p>Findings from the in-depth interviews revealed how the lack of quality services at PHC facilities caused delays in accessing appropriate care and how the experiences of inadequate care caused users to lose trust in them.</p> <p>Conclusion</p> <p>The observation that people are willing to travel long distances to get better quality services calls for health policies that prioritize quality of care before quantity. In a situation with limited resources, utilizing available resources to improve quality of care at available facilities could be more appropriate for improving access to health care than increasing the number of facilities. This would also improve equity in health care access since the poor who can not afford travelling costs will then get access to quality services at their nearer PHC facilities.</p

Transcriptome-wide association study reveals candidate causal genes for lung cancer.

We have recently completed the largest GWAS on lung cancer including 29,266 cases and 56,450 controls of European descent. The goal of our study has been to integrate the complete GWAS results with a large-scale expression quantitative trait loci (eQTL) mapping study in human lung tissues (n = 1,038) to identify candidate causal genes for lung cancer. We performed transcriptome-wide association study (TWAS) for lung cancer overall, by histology (adenocarcinoma, squamous cell carcinoma and small cell lung cancer) and smoking subgroups (never- and ever-smokers). We performed replication analysis using lung data from the Genotype-Tissue Expression (GTEx) project. DNA damage assays were performed in human lung fibroblasts for selected TWAS genes. As expected, the main TWAS signal for all histological subtypes and ever-smokers was on chromosome 15q25. The gene most strongly associated with lung cancer at this locus using the TWAS approach was IREB2 (pTWAS = 1.09E-99), where lower predicted expression increased lung cancer risk. A new lung adenocarcinoma susceptibility locus was revealed on 9p13.3 and associated with higher predicted expression of AQP3 (pTWAS = 3.72E-6). Among the 45 previously described lung cancer GWAS loci, we mapped candidate target gene for 17 of them. The association AQP3-adenocarcinoma on 9p13.3 was replicated using GTEx (pTWAS = 6.55E-5). Consistent with the effect of risk alleles on gene expression levels, IREB2 knockdown and AQP3 overproduction promote endogenous DNA damage. These findings indicate genes whose expression in lung tissue directly influences lung cancer risk