Organically-preserved multicellular eukaryote from the early Ediacaran Nyborg Formation, Arctic Norway.

Eukaryotic multicellularity originated in the Mesoproterozoic Era and evolved multiple times since, yet early multicellular fossils are scarce until the terminal Neoproterozoic and often restricted to cases of exceptional preservation. Here we describe unusual organically-preserved fossils from mudrocks, that provide support for the presence of organisms with differentiated cells (potentially an epithelial layer) in the late Neoproterozoic. Cyathinema digermulense gen. et sp. nov. from the Nyborg Formation, Vestertana Group, Digermulen Peninsula in Arctic Norway, is a new carbonaceous organ-taxon which consists of stacked tubes with cup-shaped ends. It represents parts of a larger organism (multicellular eukaryote or a colony), likely with greater preservation potential than its other elements. Arrangement of open-ended tubes invites comparison with cells of an epithelial layer present in a variety of eukaryotic clades. This tissue may have benefitted the organism in: avoiding overgrowth, limiting fouling, reproduction, or water filtration. C. digermulense shares characteristics with extant and fossil groups including red algae and their fossils, demosponge larvae and putative sponge fossils, colonial protists, and nematophytes. Regardless of its precise affinity, C. digermulense was a complex and likely benthic marine eukaryote exhibiting cellular differentiation, and a rare occurrence of early multicellularity outside of Konservat-Lagerstätten.

Computed tomography examination of the face of Macaca anderssoni (Early Pleistocene, Henan, northern China): Implications for the biogeographic history of Asian macaques.

Macaca anderssoni, a fossil macaque from the Early Pleistocene of northern China, has attracted much attention from researchers in terms of reconstructing the biogeographic history of Asian macaques, while its phylogenetic position remains debatable. In the present study, we evaluated patterns of variation in external and internal craniofacial morphologies among four phylogenetic groups of extant macaques (the fascicularis, sinica, silenus, and sylvanus groups), using computed tomography and multivariate analyses. We also reassessed the holotype of M. anderssoni, a partial cranium preserving the face and palate, to evaluate the phylogenetic group to which M. anderssoni is most closely related. Facial elongation was found to be significantly influenced by size. The particular combination of some allometric and non-allometric shape components was found to reflect phylogenetic relationships; however, these features of M. anderssoni fall intermediate among the four phylogenetic groups, with no typical similarities to any one group. The variations in nasal cavity shape were found to reflect phylogenetic relationships but those of the maxillary sinus did not. Macaca anderssoni has a nasal cavity that is laterally expanded anteriorly and constricted posteriorly, a unique morphology among macaques and shared only with larger members of the sinica group. This unique feature is considered to be a derived condition among macaques, suggesting that M. anderssoni is phylogenetically related to the sinica group (especially M. assamensis, M. thibetana, and M. arctoides) and that the populations of the sinica group were distributed in northern China during the Early Pleistocene. Currently, the populations of the sinica group are not distributed in northern East Asia, while those of the fascicularis group are. Thus, probably due to climatic deterioration in the Late Pleistocene, the former lineage has retreated southward or has become extinct in this region, being replaced by the latter lineage.

Counteractive self-control.

We propose a self-control analysis of the role of availability in valuation. We explored the hypothesis that, when temptation becomes available, counteractive self-control processes render it less valuable. We found evidence for devaluation of available temptation among gym users before they choose to forgo an unhealthy snack rather than after they make their choice (Study 1), and among students evaluating leisure activities when their decision to enroll in an uninteresting class is reversible rather than irreversible (Study 2).

Epstein-Barr virus immune response in high-risk nasopharyngeal carcinoma families in Greenland.

Undifferentiated nasopharyngeal carcinoma is associated with Epstein-Barr virus (EBV) infection. Presence of EBV IgA antibodies is rare among healthy individuals and is used as a marker of nasopharyngeal carcinoma in high-incidence populations. Reasons for EBV IgA seropositivity are unknown, but high EBV IgA levels have been found among unaffected close family members and spouses to nasopharyngeal carcinoma patients in Chinese populations. In Greenland, a nasopharyngeal carcinoma-high-incidence area, we compared EBV serology and viral load in high-risk nasopharyngeal carcinoma family members (N = 20) and controls without nasopharyngeal carcinoma-affected relatives (N = 90). There was no significant difference in EBV viral loads between relatives and controls, and EBV was detected in plasma in 5.0% of relatives and 11.4% of controls. There was no significant difference in EBV serology, but the seroprevalence of EBV viral capsid antigen (VCA) IgA was high in both relatives (25.0%) and controls (20.5%). Compared with anti-VCA IgA-negative, anti-VCA IgA-positive individuals had significantly higher EBV viral loads in peripheral blood mononuclear cells (PBMCs) (P < 0.01). The very high prevalence of anti-VCA IgA indicates that this antibody is unsuitable for nasopharyngeal carcinoma screening among Inuits.

The influence of the NOD Nss1/Idd5 loci on sialadenitis and gene expression in salivary glands of congenic mice.

The nonobese diabetic (NOD) Nss1 and Idd5 loci have been associated with sialadenitis development in mice. In this study the NOD Nss1 and Idd5 loci were backcrossed onto the healthy control strain B10.Q by using the speed congenic breeding strategy, resulting in three congenic strains: B10.Q.Nss1, B10.Q.Nss1/Idd5 heterozygous and B10.Q.Nss1/Idd5 homozygous. We investigated the effects of the Nss1 and Idd5 loci on sialadenitis and gene expression in NOD congenic mice. One submandibular salivary gland from each mouse was used for histological analysis of sialadenitis, whereas the contralateral salivary gland was used for gene expression profiling with the Applied Biosystems Mouse Genome Survey chip v.1.0. The results were validated using quantitative reverse transcriptase PCR. The NOD Nss1 and Idd5 loci had clear influence on the onset and progression of sialadenitis in congenic mice. Double congenic mice exhibited the most severe phenotype. We successfully identified several genes that are located in the NOD congenic regions to be differentially expressed between the congenic strains and the control strain. Several of these were found to be co-regulated, such as Stat1, complement component C1q genes and Tlr12. Also, a vast contingency of interferon-regulated genes (such as Ltb, Irf7 and Irf8) and cytokine and chemokine genes (such as Ccr7 and Ccl19) were differentially expressed between the congenic strains and the control strain. Over-representation of inflammatory signalling pathways was observed among the differentially expressed genes. We have found that the introgression of the NOD loci Nss1 and Idd5 on a healthy background caused sialadenitis in NOD congenic mouse strains, and we propose that genes within these loci are important factors in the pathogenesis. Furthermore, gene expression profiling has revealed several differentially expressed genes within and outside the NOD loci that are similar to genes found to be differentially expressed in patients with Sjögren's syndrome, and as such are interesting candidates for investigation to enhance our understanding of disease mechanisms and to develop future therapies.

Cancer susceptibility in nasopharyngeal carcinoma families--a population-based cohort study.

Undifferentiated nasopharyngeal carcinoma is a result of environmental factors, in particular EBV infection, affecting genetically susceptible individuals. The familial risk of nasopharyngeal carcinoma is among the highest of any malignancy. Whether this susceptibility is restricted to nasopharyngeal carcinoma is unknown as information on the risk of other cancers in relatives is limited. We did a population-based study of the cancer incidence in nasopharyngeal carcinoma families in Greenland, a nasopharyngeal carcinoma-endemic area. Using population-based registers, a cohort of all persons born in Greenland was followed from 1973 to 2002. In this cohort, 134 individuals developed nasopharyngeal carcinoma and their relatives were identified through registers and interviews. Subsequently, the occurrence of cancer was determined by linkage to the population-based cancer register and the risk of cancer in nasopharyngeal carcinoma relatives and nonrelatives compared by relative risks. Among 766 first-degree relatives, the relative risk of nasopharyngeal carcinoma following the family index case was 8.0 [95% confidence interval (95% CI), 4.1-14.0]. Sex and age of the relative or the index case had no modifying effect on the familial risk of nasopharyngeal carcinoma. The relative risks of carcinoma of the salivary glands, 8.4 (95% CI, 2.7-19.5), and uterine cervix, 2.2 (95% CI, 1.1-3.9), were also significantly increased. In families with multiple cases of nasopharyngeal carcinoma, the risk of other cancers than nasopharyngeal carcinoma was further increased. These results indicate that the increased risk of cancer in nasopharyngeal carcinoma families is not restricted to nasopharyngeal carcinoma, but extends to the virally associated cancers of the salivary glands and cervical uteri.

Gene expression profiling of minor salivary glands clearly distinguishes primary Sjögren's syndrome patients from healthy control subjects.

OBJECTIVE: To identify gene expression signatures in minor salivary glands (MSGs) from patients with primary Sjogren's syndrome (SS). METHODS: A 16K complementary DNA microarray was used to generate gene expression profiles in MSGs obtained from 10 patients with primary SS and 10 control subjects. The data were analyzed by 2 different strategies, one strict primary analysis and one subanalysis that allowed for inclusion of genes with no signal in more than 3 samples from each group. The results were validated by quantitative reverse transcriptase-polymerase chain reaction techniques. RESULTS: We found a distinct difference in gene expression levels in MSGs, enabling a simple class prediction method to correctly classify 19 of the 20 samples as either patient or control, based on the top 5 differentially expressed genes. The 50 most differentially expressed genes in the primary SS group compared with the control group were all up-regulated, and a clear pattern of genes involved in chronic inflammation was found. CXCL13 and CD3D were expressed in >/=90% of primary SS patients and in

Living in a group dwelling: how do residents spend their time in a psychiatric group dwelling?

The aim of the study was to investigate how residents at psychiatric group dwellings spend their time. The study consisted of two parts: questionnaires and an observation survey. It included all the staff at two municipal psychiatric group dwellings where the residents were primarily diagnosed as having long-term schizophrenia. This study indicated that, even if the dwellings had a creative climate, there was a negative process in terms of nurses' well-being with a high level of depersonalisation. The residents who displayed a predominant picture of negative symptoms were left alone for 84% of the day, and 29.5% of this could be explained by their illness. The remainder of the residents' time alone remains unexplained.

Standardization of prostate brachytherapy treatment plans.

PURPOSE: Whereas custom-designed plans are the norm for prostate brachytherapy, the relationship between linear prostate dimensions and volume calls into question the routine need for customized treatment planning. With the goal of streamlining the treatment-planning process, we have compared the treatment margins (TMs) achieved with one standard plan applied to patients with a wide range of prostate volumes. METHODS AND MATERIALS: Preimplant transrectal ultrasound (TRUS) images of 50 unselected University of Washington patients with T1-T2 cancer and a prostate volume between 20 cc and 50 cc were studied. Patients were arbitrarily grouped into categories of 20-30 cc, 30-40 cc, and 40-50 cc. A standard 19-needle plan was devised for patients in the 30- to 40-cc range, using an arbitrary minimum margin of 5 mm around the gross tumor volume (GTV), making use of inverse planning technology to achieve 100% coverage of the target volume with accentuation of dose at the periphery and sparing of the central region. The idealized plan was applied to each patient's TRUS study. The distances (TMs) between the prostatic edge (GTV) and treated volume (TV) were determined perpendicular to the prostatic margin. RESULTS: Averaged over the entire patient group, the ratio of thickness to width was 1.4, whereas the ratio of length to width was 1.3. These values were fairly constant over the range of volumes, emphasizing that the prostate retains its general shape as volume increases. The idealized standard plan was overlaid on the ultrasound images of the 17 patients in the 30- to 40-cc group and the V100, the percentage of target volume receiving 100% or more of the prescription dose, was 98% or greater for 15 of the 17 patients. The lateral and posterior TMs fell within a narrow range, most being within 2 mm of the idealized 5-mm TM. To estimate whether a 10-cc volume-interval stratification was reasonable, the standard plan generated from the 30- to 40-cc prostate model was applied to 5 patients each from the 20- to 30-cc group and the 40- to 50-cc group. Using the standard plan designed for the 30- to 40-cc group, the TMs were closer to 10 mm than to 5 mm for the smaller volume glands and too small for the larger volume ones, assuming an ideal margin of 5 mm. CONCLUSION: The application of standardized plans to prostate brachytherapy is feasible. Stratifying the volume in 10-cc intervals appears to be adequate, suggesting that the majority of cases appropriate for treatment with brachytherapy might be treated with three standard plans. While the authors believe that the use of a limited number of standard treatment plans is feasible, practical, and medically acceptable, it should be emphasized that the use of a standard plan should always be previewed by computer-aided application to the particular patient's planning images.

Inverse treatment planning for Gamma Knife radiosurgery.

An inverse treatment planning system for Gamma Knife radiosurgery has been developed using nonlinear programming techniques. The system optimizes the shot sizes, locations, and weights for Gamma Knife treatments. In the patient's prescription, the user can specify both the maximum number of shots of radiation and a minimum isodose line that must surround the entire treatment volume. After satisfying all of the constraints included in the prescription, the system maximizes the conformity of the dose distribution. This automated approach to treatment planning has been applied retrospectively to a series of patient cases, and each optimized plan has been compared to the corresponding manual plan produced by an experienced user. The results demonstrate that this tool can often improve the tumor dose homogeneity while using fewer shots than were included in the original plan. Therefore, inverse treatment planning should improve both the quality and the efficiency of Gamma Knife treatments.

Postoperative endoscopic retrograde high dose-rate brachytherapy for cholangiocarcinoma.

Cholangiocarcinoma typically presents with disease unlikely to be completely resected, and prognosis remains poor. Improvements in imaging, endoscopy, and stenting have given rise to renewed interest in brachytherapy. Several recent retrospective series suggest a benefit to intraluminal brachytherapy, most commonly delivered by the transhepatic route. We describe a case in which brachytherapy was delivered via the nasobiliary route to address positive margins at the common bile duct stump. A custom catheter was manufactured to make the procedure feasible. Pertinent literature is reviewed, which supports the view that these malignancies benefit from high doses of radiation, if this can be achieved respecting normal tissue tolerance.

Preservation of visual fields after peri-sellar gamma-knife radiosurgery.

Radiosurgical treatment of pituitary and peri-sellar tumors has become an increasingly utilized modality as an alternative to conventional radiotherapy and surgery. Such radiosurgery results in a relatively high dose of radiation to the optic chiasm. The clinical data establishing safe single-fraction doses to the chiasm is immature, although taken together previous literature suggests a recommended maximal dose of 8 Gy. Optic neuropathy, when it occurs, tends to take place within 2 years of treatment. We evaluated the visual fields of 20 sequential patients that received significant doses to the optic chiasm by Gamma-knife radiosurgery. There were 17 cases of pituitary adenoma and 3 cases of meningioma, and two patients refused follow-up testing. Preoperative visual field and cranial nerve examinations were done prior to radiosurgery and in follow-up, with a median follow-up of 24 months. There were no cases of quantitative visual field deficit induced by treatment. No patients developed symptomatic visual deterioration. Radiat. Oncol. Invest. 90:343-350, 2000. 2000 Wiley-Liss, Inc.

Tomographic convolutional dosimetry of interstitial brachytherapy implants.

A method for approximation of the dose distribution generated by an interstitial brachytherapy implant is introduced. The method employs convolution of raw tomographic data, as a measurement of attenuation of CT pencil beams by the metallic substrate and casing of radioactive seeds. A convolution kernel is introduced in the algorithm for CT image reconstruction such that the tomographic computation results in an approximation of absorbed dose. Error estimates are discussed, and limitations of the method and the domain of validity are discussed. Equivalence with a technique of employing convolution methods to the CT image itself is demonstrated. Calibration and testing on phantom implants is underway.

Delayed expression of hpS2 and prolonged expression of CIP1/WAF1/SDI1 in human tumour cells irradiated with X-rays, fission neutrons or 1 GeV/nucleon Fe ions.

PURPOSE: Differences in gene expression underlie the phenotypic differences between irradiated and unirradiated cells. The goal was to identify late-transcribed genes following irradiations differing in quality, and to determine the RBE of 1 GeV/n Fe ions. MATERIALS AND METHODS: Clonogenic assay was used to determine the RBE of Fe ions. Differential hybridization to cDNA target clones was used to detect differences in expression of corresponding genes in mRNA samples isolated from MCF7 cells irradiated with iso-survival doses of Fe ions (0 or 2.5 Gy) or fission neutrons (0 or 1.2 Gy) 7 days earlier. Northern analysis was used to confirm differential expression of cDNA-specific mRNA and to examine expression kinetics up to 2 weeks after irradiation. RESULTS: Fe ion RBE values were between 2.2 and 2.6 in the lines examined. Two of 17 differentially expressed cDNA clones were characterized. hpS2 mRNA was elevated from 1 to 14 days after irradiation, whereas CIP1/WAF1/SDI1 remained elevated from 3 h to 14 days after irradiation. Induction of hpS2 mRNA by irradiation was independent of p53, whereas induction of CIP1/WAF1/SDI1 was observed only in wild-type p53 lines. CONCLUSIONS: A set of coordinately regulated genes, some of which are independent of p53, is associated with change in gene expression during the first 2 weeks post-irradiation.