Satisfaction with follow-up consultations among younger adults treated for cancer: the role of quality of life and psychological variables

Given increased survival rates and treatment-related late effects, follow-up for cancer survivors is increasingly recommended. However, information about adverse events (e.g. possibility of late effects) may be distressing for the cancer survivor and lead to poor clinic attendance. Survivor satisfaction with appointments and the information provided are important. The Monitoring Process Model provides a theoretical framework to understand how survivors cope with threatening information, and consequences for follow-up care. Our aims were to describe satisfaction with routine follow-up and association between monitoring/blunting and satisfaction with care.

Structural and functional diversity of connexin genes in the mouse and human genome

Gap junctions are clustered channels between contacting cells through which direct intercellular communication via diffusion of ions and metabolites can occur. Two hemichannels, each built up of six connexin protein subunits in the plasma membrane of adjacent cells, can dock to each other to form conduits between cells. We have recently screened mouse and human genomic data bases and have found 19 connexin (Cx) genes in the mouse genome and 20 connexin genes in the human genome. One mouse connexin gene and two human connexin genes do not appear to have orthologs in the other genome. With three exceptions, the characterized connexin genes comprise two exons whereby the complete reading frame is located on the second exon. Targeted ablation of eleven mouse connexin genes revealed basic insights into the functional diversity of the connexin gene family. In addition, the phenotypes of human genetic disorders caused by mutated connexin genes further complement our understanding of connexin functions in the human organism. In this review we compare currently identified connexin genes in both the mouse and human genome and discuss the functions of gap junctions deduced from targeted mouse mutants and human genetic disorders.

Connexin genes in the mouse and human genome

Gap junctions serve for direct intercellular communication by docking of two hemichannels in adjacent cells thereby forming conduits between the cytoplasmic compartments of adjacent cells. Connexin genes code for subunit proteins of gap junction channels and are members of large gene families in mammals. So far, 17 connexin (Cx) genes have been described and characterized in the murine genome. For most of them, orthologues in the human genome have been found (see White and Paul 1999; Manthey et al. 1999; Teubner et al. 2001; Söhl et al. 2001). We have recently performed searches for connexin genes in murine and human gene libraries available at EMBL/Heidelberg, NCBI and the Celera company that have increased the number of identified connexins to 19 in mouse and 20 in humans. For one mouse connexin gene and two human connexin genes we did not find orthologues in the other genome. Here we present a short overview on distinct connexin genes which we found in the mouse and human genome and which may include all members of this gene family, if no further connexin gene will be discovered in the remaining non-sequenced parts (about 1-5%) of the genomes.

A three-dimensional histological atlas of the human basal ganglia. II. Atlas deformation strategy and evaluation in deep brain stimulation for Parkinson disease

OBJECT: The localization of any given target in the brain has become a challenging issue because of the increased use of deep brain stimulation to treat Parkinson disease, dystonia, and nonmotor diseases (for example, Tourette syndrome, obsessive compulsive disorders, and depression). The aim of this study was to develop an automated method of adapting an atlas of the human basal ganglia to the brains of individual patients. METHODS: Magnetic resonance images of the brain specimen were obtained before extraction from the skull and histological processing. Adaptation of the atlas to individual patient anatomy was performed by reshaping the atlas MR images to the images obtained in the individual patient using a hierarchical registration applied to a region of interest centered on the basal ganglia, and then applying the reshaping matrix to the atlas surfaces. RESULTS: Results were evaluated by direct visual inspection of the structures visible on MR images and atlas anatomy, by comparison with electrophysiological intraoperative data, and with previous atlas studies in patients with Parkinson disease. The method was both robust and accurate, never failing to provide an anatomically reliable atlas to patient registration. The registration obtained did not exceed a 1-mm mismatch with the electrophysiological signatures in the region of the subthalamic nucleus. CONCLUSIONS: This registration method applied to the basal ganglia atlas forms a powerful and reliable method for determining deep brain stimulation targets within the basal ganglia of individual patients.

Whole genome methylation array analysis reveals new aspects in Balkan endemic nephropathy etiology

Background Balkan endemic nephropathy (BEN) represents a chronic progressive interstitial nephritis in striking correlation with uroepithelial tumours of the upper urinary tract. The disease has endemic distribution in the Danube river regions in several Balkan countries. DNA methylation is a primary epigenetic modification that is involved in major processes such as cancer, genomic imprinting, gene silencing, etc. The significance of CpG island methylation status in normal development, cell differentiation and gene expression is widely recognized, although still stays poorly understood. Methods We performed whole genome DNA methylation array analysis on DNA pool samples from peripheral blood from 159 affected individuals and 170 healthy individuals. This technique allowed us to determine the methylation status of 27 627 CpG islands throughout the whole genome in healthy controls and BEN patients. Thus we obtained the methylation profile of BEN patients from Bulgarian and Serbian endemic regions. Results Using specifically developed software we compared the methylation profiles of BEN patients and corresponding controls and revealed the differently methylated regions. We then compared the DMRs between all patient-control pairs to determine common changes in the epigenetic profiles. SEC61G, IL17RA, HDAC11 proved to be differently methylated throughout all patient-control pairs. The CpG islands of all 3 genes were hypomethylated compared to controls. This suggests that dysregulation of these genes involved in immunological response could be a common mechanism in BEN pathogenesis in both endemic regions and in both genders. Conclusion Our data propose a new hypothesis that immunologic dysregulation has a place in BEN etiopathogenesis. Keywords: Epigenetics; Whole genome array analysis; Balkan endemic nephropathy

Draft Genome Sequence of the Virulent Avibacterium paragallinarum Serotype A Strain JF4211 and Identification of Two Toxins

Avibacterium paragallinarum is an important pathogen of chicken livestock causing infectious coryza. Here, we report the draft genome sequence of the virulent A. paragallinarum serotype A strain JF4211 (2.8 Mbp and G+C content of 41%) and the two toxin operons discovered from the annotation of the genome.

Draft Genome Sequence of the Virulent Clostridium chauvoei Reference Strain JF4335

Clostridium chauvoei is the etiological agent of blackleg, a disease of cattle and sheep with high mortality rates, causing severe economic losses in livestock production. Here, we report the draft genome sequence of the virulent C. chauvoei strain JF4335 (2.8 Mbp and 28% G+C content) and the annotation of the genome.

Complete Genome Sequence of Treponema paraluiscuniculi, Strain Cuniculi A: The Loss of Infectivity to Humans Is Associated with Genome Decay.

Treponema paraluiscuniculi is the causative agent of rabbit venereal spirochetosis. It is not infectious to humans, although its genome structure is very closely related to other pathogenic Treponema species including Treponema pallidum subspecies pallidum, the etiological agent of syphilis. In this study, the genome sequence of Treponema paraluiscuniculi, strain Cuniculi A, was determined by a combination of several high-throughput sequencing strategies. Whereas the overall size (1,133,390 bp), arrangement, and gene content of the Cuniculi A genome closely resembled those of the T. pallidum genome, the T. paraluiscuniculi genome contained a markedly higher number of pseudogenes and gene fragments (51). In addition to pseudogenes, 33 divergent genes were also found in the T. paraluiscuniculi genome. A set of 32 (out of 84) affected genes encoded proteins of known or predicted function in the Nichols genome. These proteins included virulence factors, gene regulators and components of DNA repair and recombination. The majority (52 or 61.9%) of the Cuniculi A pseudogenes and divergent genes were of unknown function. Our results indicate that T. paraluiscuniculi has evolved from a T. pallidum-like ancestor and adapted to a specialized host-associated niche (rabbits) during loss of infectivity to humans. The genes that are inactivated or altered in T. paraluiscuniculi are candidates for virulence factors important in the infectivity and pathogenesis of T. pallidum subspecies.

The Oxytricha trifallax macronuclear genome: a complex eukaryotic genome with 16,000 tiny chromosomes.

The macronuclear genome of the ciliate Oxytricha trifallax displays an extreme and unique eukaryotic genome architecture with extensive genomic variation. During sexual genome development, the expressed, somatic macronuclear genome is whittled down to the genic portion of a small fraction (∼5%) of its precursor "silent" germline micronuclear genome by a process of "unscrambling" and fragmentation. The tiny macronuclear "nanochromosomes" typically encode single, protein-coding genes (a small portion, 10%, encode 2-8 genes), have minimal noncoding regions, and are differentially amplified to an average of ∼2,000 copies. We report the high-quality genome assembly of ∼16,000 complete nanochromosomes (∼50 Mb haploid genome size) that vary from 469 bp to 66 kb long (mean ∼3.2 kb) and encode ∼18,500 genes. Alternative DNA fragmentation processes ∼10% of the nanochromosomes into multiple isoforms that usually encode complete genes. Nucleotide diversity in the macronucleus is very high (SNP heterozygosity is ∼4.0%), suggesting that Oxytricha trifallax may have one of the largest known effective population sizes of eukaryotes. Comparison to other ciliates with nonscrambled genomes and long macronuclear chromosomes (on the order of 100 kb) suggests several candidate proteins that could be involved in genome rearrangement, including domesticated MULE and IS1595-like DDE transposases. The assembly of the highly fragmented Oxytricha macronuclear genome is the first completed genome with such an unusual architecture. This genome sequence provides tantalizing glimpses into novel molecular biology and evolution. For example, Oxytricha maintains tens of millions of telomeres per cell and has also evolved an intriguing expansion of telomere end-binding proteins. In conjunction with the micronuclear genome in progress, the O. trifallax macronuclear genome will provide an invaluable resource for investigating programmed genome rearrangements, complementing studies of rearrangements arising during evolution and disease.

The impact of cancer on the population of Salvador-Bahia, Brazil

The impact of cancer on the population of Salvador-Bahia, Brazil was studied using mortality data available from the Brazilian National Bureau of Vital Statistics. Average annual site, age, and gender specific and adjusted cancer mortality rates were determined for the years 1977-83 and contrasted with United States cancer mortality rates for the year of 1977. The accuracy of the cancer mortality rates generated by this research was determined by comparing the underlying causes of death as coded on death certificates to pathology reports and to hospital diagnosis of a sample of 966 deaths occurring in Salvador during the year of 1983. To further explore the information available on the death certificate, a population based decedent case control study was used to determine the relationship between type of occupation (proxy for exposure) and mortality by cancer sites known to be occupationally related.^ The rates in Salvador for cancer of the stomach, oral cavity, and biliary passages are, on average, two fold higher than the U.S. rates.^ The death certificate was found to be accurate for 65 percent of the 485 cancer deaths studied. Thirty five histologically confirmed cancer deaths were found in a random sample of 481 deaths from other causes. This means that, approximately 700 more deaths may be lost among the remainder 10,073 death certificates stating a cause other than cancer.^ In addition, despite the known limitations of decedent case-control studies, cancers of the oral cavity OR = 2.44, CI = 1.17-5.09, stomach OR = 2.31, CI = 1.18-4.52, liver OR = 4.06, CI = 1.27-12.99, bladder OR = 6.77, CI = 1.5-30.67, and lymphoma OR = 2.55, CI = 1.04-6.25 had elevated point estimates, for different age strata indicating an association between these cancers and occupations that led to exposure to petroleum and its derivates. ^

Performance of jet substructure techniques for large-ℝ jets in proton-proton collisions at sqrts = 7 TeV using the ATLAS detector

This paper presents the application of a variety of techniques to study jet substructure. The performance of various modified jet algorithms, or jet grooming techniques, for several jet types and event topologies is investigated for jets with transverse momentum larger than 300 GeV. Properties of jets subjected to the mass-drop filtering, trimming, and pruning algorithms are found to have reduced sensitivity to multiple proton-proton interactions, are more stable at high luminosity and improve the physics potential of searches for heavy boosted objects. Studies of the expected discrimination power of jet mass and jet substructure observables in searches for new physics are also presented. Event samples enriched in boosted W and Z bosons and top-quark pairs are used to study both the individual jet invariant mass scales and the efficacy of algorithms to tag boosted hadronic objects. The analyses presented use the full 2011 ATLAS dataset, corresponding to an integrated luminosity of 4.7 +/- 0.1 /fb from proton-proton collisions produced by the Large Hadron Collider at a center-of-mass energy of sqrt(s) = 7 TeV.

Socio-economic atlas of Kenya: Depicting the national population census by county and sub-location

The Socio-Economic Atlas of Kenya is the first of its kind to offer high-resolution spatial depictions and analyses of data collected in the 2009 Kenya Population and Housing Census . The combination of geographic and socio-eco - nomic data enables policymakers at all levels, development experts, and other interested readers to gain a spatial understanding of dynamics affecting Kenya. Where is the informal economic sector most prominent? Which areas have adequate water and sanitation? Where is population growth being slowed effectively? How do education levels vary throughout the country? And where are poverty rates lowest? Answers to questions such as these, grouped into seven broad themes, are visually illustrated on high-resolution maps. By supplying precise information at the sub-location level and summarizing it at the county level, the atlas facilitates better planning that accounts for local contexts and needs. It is a valuable decision-support tool for government institutions at different administrative levels, educational institutions, and others. Three organizations – two in Kenya and one in Switzerland – worked together to create the atlas: the Kenya National Bureau of Statistics (KNBS), the Nanyuki-based Centre for Training and Integrated Research in ASAL Development (CETRAD), and the Centre for Development and Environment (CDE) at the University of Bern. Close cooperation between KNBS, CETRAD, and CDE maximized synergies and knowledge exchange.

The molecular signature of the stroma response in prostate cancer-induced osteoblastic bone metastasis highlights expansion of hematopoietic and prostate epithelial stem cell niches

The reciprocal interaction between cancer cells and the tissue-specific stroma is critical for primary and metastatic tumor growth progression. Prostate cancer cells colonize preferentially bone (osteotropism), where they alter the physiological balance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption, and elicit prevalently an osteoblastic response (osteoinduction). The molecular cues provided by osteoblasts for the survival and growth of bone metastatic prostate cancer cells are largely unknown. We exploited the sufficient divergence between human and mouse RNA sequences together with redefinition of highly species-specific gene arrays by computer-aided and experimental exclusion of cross-hybridizing oligonucleotide probes. This strategy allowed the dissection of the stroma (mouse) from the cancer cell (human) transcriptome in bone metastasis xenograft models of human osteoinductive prostate cancer cells (VCaP and C4-2B). As a result, we generated the osteoblastic bone metastasis-associated stroma transcriptome (OB-BMST). Subtraction of genes shared by inflammation, wound healing and desmoplastic responses, and by the tissue type-independent stroma responses to a variety of non-osteotropic and osteotropic primary cancers generated a curated gene signature ("Core" OB-BMST) putatively representing the bone marrow/bone-specific stroma response to prostate cancer-induced, osteoblastic bone metastasis. The expression pattern of three representative Core OB-BMST genes (PTN, EPHA3 and FSCN1) seems to confirm the bone specificity of this response. A robust induction of genes involved in osteogenesis and angiogenesis dominates both the OB-BMST and Core OB-BMST. This translates in an amplification of hematopoietic and, remarkably, prostate epithelial stem cell niche components that may function as a self-reinforcing bone metastatic niche providing a growth support specific for osteoinductive prostate cancer cells. The induction of this combinatorial stem cell niche is a novel mechanism that may also explain cancer cell osteotropism and local interference with hematopoiesis (myelophthisis). Accordingly, these stem cell niche components may represent innovative therapeutic targets and/or serum biomarkers in osteoblastic bone metastasis.

Complete Genome Sequence of Bovine Pestivirus Strain PG-2, a Second Member of the Tentative Pestivirus Species Giraffe

We report the complete genome sequence of bovine pestivirus strain PG-2. The sequence data from this virus showed that PG-2 is closely related to the giraffe pestivirus strain H138. PG-2 and H138 belong to one pestivirus species that should be considered an approved member of the genus Pestivirus.

Measurement of Higgs boson production in the diphoton decay channel in pp collisions at center-of-mass energies of 7 and 8 TeV with the ATLAS detector

A measurement of the production processes of the recently discovered Higgs boson is performed in the two-photon final state using 4.5  fb −1 of proton-proton collisions data at s √ =7  TeV and 20.3  fb −1 at s √ =8  TeV collected by the ATLAS detector at the Large Hadron Collider. The number of observed Higgs boson decays to diphotons divided by the corresponding Standard Model prediction, called the signal strength, is found to be μ=1.17±0.27 at the value of the Higgs boson mass measured by ATLAS, m H =125.4  GeV . The analysis is optimized to measure the signal strengths for individual Higgs boson production processes at this value of m H . They are found to be μ ggF =1.32±0.38 , μ VBF =0.8±0.7 , μ WH =1.0±1.6 , μ ZH =0.1 +3.7 −0.1 , and μ tt ¯ H =1.6 +2.7 −1.8 , for Higgs boson production through gluon fusion, vector-boson fusion, and in association with a W or Z boson or a top-quark pair, respectively. Compared with the previously published ATLAS analysis, the results reported here also benefit from a new energy calibration procedure for photons and the subsequent reduction of the systematic uncertainty on the diphoton mass resolution. No significant deviations from the predictions of the Standard Model are found.