A bHLH Complex Controls Embryonic Vascular Tissue Establishment and Indeterminate Growth in Arabidopsis

Plants have a remarkable potential for sustained (indeterminate) postembryonic growth. Following their specification in the early embryo, tissue-specific precursor cells first establish tissues and later maintain them postembryonically. The mechanisms underlying these processes are largely unknown. Here we define local control of oriented, periclinal cell division as the mechanism underlying both the establishment and maintenance of vascular tissue. We identify an auxin-regulated basic helix-loop-helix (bHLH) transcription factor dimer as a critical regulator of vascular development. Due to a loss of periclinal divisions, vascular tissue gradually disappears in bHLH-deficient mutants; conversely, ectopic expression is sufficient for triggering periclinal divisions. We show that this dimer operates independently of tissue identity but is restricted to a small vascular domain by integrating overlapping transcription patterns of the interacting bHLH proteins. Our work reveals a common mechanism for tissue establishment and indeterminate vascular development and provides a conceptual framework for developmental control of local cell divisions.

Researchers' roles in knowledge co-production: experience from sustainability research in Kenya, Switzerland, Bolivia and Nepal

Co-production of knowledge between academic and non-academic communities is a prerequisite for research aiming at more sustainable development paths. Sustainability researchers face three challenges in such co-production: (a) addressing power relations; (b) interrelating different perspectives on the issues at stake; and (c) promoting a previously negotiated orientation towards sustainable development. A systematic comparison of four sustainability research projects in Kenya (vulnerability to drought), Switzerland (soil protection), Bolivia and Nepal (conservation vs. development) shows how the researchers intuitively adopted three different roles to face these challenges: the roles of reflective scientist, intermediary, and facilitator of a joint learning process. From this systematized and iterative self-reflection on the roles that a researcher can assume in the indeterminate social space where knowledge is co-produced, we draw conclusions regarding training.

Improved sensitivity of an interferon-gamma release assay (T-SPOT.TB™) in combination with tuberculin skin test for the diagnosis of latent tuberculosis in the presence of HIV co-infection

Background Interferon-gamma release assays (IGRA) are more specific than the tuberculin skin test (TST) for the diagnosis of Mycobacterium tuberculosis infection. Data on sensitivity are controversial in HIV infection. Methods IGRA (T-SPOT.TB) was performed using lymphocytes stored within 6 months before culture-confirmed tuberculosis was diagnosed in HIV-infected individuals in the Swiss HIV Cohort Study. Results 64 individuals (69% males, 45% of non-white ethnicity, median age 35 years (interquartile range [IQR] 31-42), 28% with prior AIDS) were analysed. Median CD4 cell count was 223 cells/μl (IQR 103-339), HIV-RNA was 4.7 log10 copies/mL (IQR 4.3-5.2). T-SPOT.TB resulted positive in 25 patients (39%), negative in 18 (28%) and indeterminate in 21 (33%), corresponding to a sensitivity of 39% (95% CI 27-51%) if all test results were considered, and 58% (95% CI 43-74%) if indeterminate results were excluded. Sensitivity of IGRA was independent of CD4 cell count (p = 0.698). Among 44 individuals with available TST, 22 (50%) had a positive TST. Agreement between TST and IGRA was 57% (kappa = 0.14, p = 0.177), and in 34% (10/29) both tests were positive. Combining TST and IGRA (at least one test positive) resulted in an improved sensitivity of 67% (95% CI 52-81%). In multivariate analysis, older age was associated with negative results of TST and T-SPOT.TB (OR 3.07, 95% CI 1,22-7.74, p = 0.017, per 10 years older). Conclusions T-SPOT.TB and TST have similar sensitivity to detect latent TB in HIV-infected individuals. Combining TST and IGRA may help clinicians to better select HIV-infected individuals with latent tuberculosis who qualify for preventive treatment.

Assessment of recent HIV-1 infection by a line immunoassay for HIV-1/2 confirmation

BACKGROUND: Knowledge of the number of recent HIV infections is important for epidemiologic surveillance. Over the past decade approaches have been developed to estimate this number by testing HIV-seropositive specimens with assays that discriminate the lower concentration and avidity of HIV antibodies in early infection. We have investigated whether this "recency" information can also be gained from an HIV confirmatory assay. METHODS AND FINDINGS: The ability of a line immunoassay (INNO-LIA HIV I/II Score, Innogenetics) to distinguish recent from older HIV-1 infection was evaluated in comparison with the Calypte HIV-1 BED Incidence enzyme immunoassay (BED-EIA). Both tests were conducted prospectively in all HIV infections newly diagnosed in Switzerland from July 2005 to June 2006. Clinical and laboratory information indicative of recent or older infection was obtained from physicians at the time of HIV diagnosis and used as the reference standard. BED-EIA and various recency algorithms utilizing the antibody reaction to INNO-LIA's five HIV-1 antigen bands were evaluated by logistic regression analysis. A total of 765 HIV-1 infections, 748 (97.8%) with complete test results, were newly diagnosed during the study. A negative or indeterminate HIV antibody assay at diagnosis, symptoms of primary HIV infection, or a negative HIV test during the past 12 mo classified 195 infections (26.1%) as recent (< or = 12 mo). Symptoms of CDC stages B or C classified 161 infections as older (21.5%), and 392 patients with no symptoms remained unclassified. BED-EIA ruled 65% of the 195 recent infections as recent and 80% of the 161 older infections as older. Two INNO-LIA algorithms showed 50% and 40% sensitivity combined with 95% and 99% specificity, respectively. Estimation of recent infection in the entire study population, based on actual results of the three tests and adjusted for a test's sensitivity and specificity, yielded 37% for BED-EIA compared to 35% and 33% for the two INNO-LIA algorithms. Window-based estimation with BED-EIA yielded 41% (95% confidence interval 36%-46%). CONCLUSIONS: Recency information can be extracted from INNO-LIA-based confirmatory testing at no additional costs. This method should improve epidemiologic surveillance in countries that routinely use INNO-LIA for HIV confirmation.

Lipid-poor adenomas on unenhanced CT: does histogram analysis increase sensitivity compared with a mean attenuation threshold?

OBJECTIVE: The purpose of our study was to evaluate the efficacy of CT histogram analysis for further characterization of lipid-poor adenomas on unenhanced CT. MATERIALS AND METHODS: One hundred thirty-two adrenal nodules were identified in 104 patients with lung cancer who underwent PET/CT. Sixty-five nodules were classified as lipid-rich adenomas if they had an unenhanced CT attenuation of less than or equal to 10 H. Thirty-one masses were classified as lipid-poor adenomas if they had an unenhanced CT attenuation greater than 10 H and stability for more than 1 year. Thirty-six masses were classified as lung cancer metastases if they showed rapid growth in 1 year (n = 27) or were biopsy-proven (n = 9). Histogram analysis was performed for all lesions to provide the mean attenuation value and percentage of negative pixels. RESULTS: All lipid-rich adenomas had more than 10% negative pixels; 51.6% of lipid-poor adenomas had more than 10% negative pixels and would have been classified as indeterminate nodules on the basis of mean attenuation alone. None of the metastases had more than 10% negative pixels. Using an unenhanced CT mean attenuation threshold of less than 10 H yielded a sensitivity of 68% and specificity of 100% for the diagnosis of an adenoma. Using an unenhanced CT threshold of more than 10% negative pixels yielded a sensitivity of 84% and specificity of 100% for the diagnosis of an adenoma. CONCLUSION: CT histogram analysis is superior to mean CT attenuation analysis for the evaluation of adrenal nodules and may help decrease referrals for additional imaging or biopsy.

Prospective, intraindividual comparison of MRI versus MDCT for endoleak detection after endovascular repair of abdominal aortic aneurysms

This study compares MRI and MDCT for endoleak detection after endovascular repair of abdominal aortic aneurysms (EVAR). Forty-three patients with previous EVAR underwent both MRI (2D T1-FFE unenhanced and contrast-enhanced; 3D triphasic contrast-enhanced) and 16-slice MDCT (unenhanced and biphasic contrast-enhanced) within 1 week of each other for endoleak detection. MRI was performed by using a high-relaxivity contrast medium (gadobenate dimeglumine, MultiHance). Two blinded, independent observers evaluated MRI and MDCT separately. Consensus reading of MRI and MDCT studies was defined as reference standard. Sensitivity, specificity, and accuracy were calculated and Cohen's k statistics were used to estimate agreement between readers. Twenty endoleaks were detected in 18 patients at consensus reading (12 type II and 8 indeterminate endoleaks). Sensitivity, specificity, and accuracy for endoleak detection were 100%, 92%, and 96%, respectively, for reader 1 (95%, 81%, 87% for reader 2) for MRI and 55%, 100%, and 80% for reader 1 (60%, 100%, 82% for reader 2) for MDCT. Interobserver agreement was excellent for MDCT (k = 0.96) and good for MRI (k = 0.81). MRI with the use of a high-relaxivity contrast agent is significantly superior in the detection of endoleaks after EVAR compared with MDCT. MRI may therefore become the preferred technique for patient follow-up after EVAR.

Comparison of interferon-gamma release assay versus tuberculin skin test for tuberculosis screening in inflammatory bowel disease

OBJECTIVES: Reactivation of latent tuberculosis (TB) in inflammatory bowel disease (IBD) patients treated with antitumor necrosis factor-alpha medication is a serious problem. Currently, TB screening includes chest x-rays and a tuberculin skin test (TST). The interferon-gamma release assay (IGRA) QuantiFERON-TB Gold In-Tube (QFT-G-IT) shows better specificity for diagnosing TB than the skin test. This study evaluates the two test methods among IBD patients. METHODS: Both TST and IGRA were performed on 212 subjects (114 Crohn's disease, 44 ulcerative colitis, 10 indeterminate colitis, 44 controls). RESULTS: Eighty-one percent of IBD patients were under immunosuppressive therapy; 71% of all subjects were vaccinated with Bacille Calmette Guérin; 18% of IBD patients and 43% of controls tested positive with the skin test (P < 0.0001). Vaccinated controls tested positive more often with the skin test (52%) than did vaccinated IBD patients (23%) (P = 0.011). Significantly fewer immunosuppressed patients tested positive with the skin test than did patients not receiving therapy (P = 0.007); 8% of patients tested positive with the QFT-G-IT test (14/168) compared to 9% (4/44) of controls. Test agreement was significantly higher in the controls (P = 0.044) compared to the IBD group. CONCLUSIONS: Agreement between the two test methods is poor in IBD patients. In contrast to the QFT-G-IT test, the TST is negatively influenced by immunosuppressive medication and vaccination status, and should thus be replaced by the IGRA for TB screening in immunosuppressed patients having IBD.

Novel screening tools for latent tuberculosis: time to leave an old friend?

PURPOSE OF REVIEW: Therapeutic inhibition of tumour necrosis factor-alpha strongly increases the risk of reactivation in latent tuberculosis infection. Recent blood tests based on antigen-specific T cell response and measuring production of interferon-gamma, so called interferon-gamma release assays (IGRAs), are promising novel tools to identify infected patients. The performance of diagnostic testing for latent tuberculosis infection in patients with rheumatic diseases will be discussed. RECENT FINDINGS: In patients with rheumatoid arthritis, IGRAs are more sensitive and more specific than traditional tuberculin skin testing. They are unaffected by Bacillus-Calmette-Guérin vaccination and most nontuberculous mycobacteria. Most comparative studies show a better performance of the IGRAs than tuberculin skin testing in terms of a higher specificity. The rate of indeterminate results may be affected by glucocorticoids and the underlying disease but appears independent of disease-modifying antirheumatic drugs. Despite using identical Mycobacterium tuberculosis antigens, the two commercially available tests show differences in clinical performance. SUMMARY: The current information about the performance of the tuberculin skin testing and the IGRAs in the detection of latent tuberculosis infection in patients with rheumatic diseases strongly suggest a clinically relevant advantage of the IGRAs. Their use will help to reduce overuse and underuse of preventive treatment in tumour necrosis factor inhibition.

Paternal inheritance of growth in fish pursuing alternative reproductive tactics

In species with indeterminate growth, age-related size variation of reproductive competitors within each sex is often high. This selects for divergence in reproductive tactics of same-sex competitors, particularly in males. Where alternative tactics are fixed for life, the causality of tactic choice is often unclear. In the African cichlid Lamprologus callipterus, large nest males collect and present empty snail shells to females that use these shells for egg deposition and brood care. Small dwarf males attempt to fertilize eggs by entering shells in which females are spawning. The bourgeois nest males exceed parasitic dwarf males in size by nearly two orders of magnitude, which is likely to result from greatly diverging growth patterns. Here, we ask whether growth patterns are heritable in this species, or whether and to which extent they are determined by environmental factors. Standardized breeding experiments using unrelated offspring and maternal half-sibs revealed highly divergent growth patterns of male young sired by nest or dwarf males, whereas the growth of female offspring of both male types did not differ. As expected, food had a significant modifying effect on growth, but neither the quantity of breeding substrate in the environment nor ambient temperature affected growth. None of the environmental factors tested influenced the choice of male life histories. We conclude that in L. callipterus growth rates of bourgeois and parasitic males are paternally inherited, and that male and female growth is phenotypically plastic to only a small degree.

Infection of cattle with Border disease virus by sheep on communal alpine pastures

The purpose of this study was to investigate whether sheep grazing communal alpine pastures with cattle can transmit Border disease virus (BDV) to cattle. A total of 1170 sheep and 923 cattle were tested for BDV using RT-PCR (sheep) and for pestivirus antibodies using an ELISA (cattle), respectively, before being moved to one of 4 pastures (A, B, C and D). Eight sheep from pasture C were viraemic. 396 of 923 cattle examined before the pasture season were seronegative. The latter were re-examined after the pasture season and 99 were seropositive or indeterminate. Antibody specificity was determined in 25 of these using a serum neutralization test (SNT). BDV infection was confirmed in 10 cattle and was considered likely in 8 others. BVDV infection was confirmed in 4 cattle and considered likely in 3 after pasturing. The study has shown that the transmission of BDV from sheep to cattle is possible on communal alpine pastures.

Investigation of border disease and bovine virus diarrhoea in sheep from 76 mixed cattle and sheep farms in eastern Switzerland

The purpose of this study was to examine the occurrence of sheep persistently infected with Border disease virus (BDV) on 76 mixed cattle and sheep farms and whether seroconversion to BDV infection occurred in cattle of these farms. Seroprevalence of BDV and bovine viral disease virus (BVDV) infection in sheep was also investigated. Quantitative RT-PCR for pestivirus detection and an ELISA to detect pestivirus antibodies were used in 2'384 and 2'291 ovine blood samples, respectively. Another 27 seropositive sheep from ten flocks underwent serum neutralization testing to differentiate between BDV and BVDV antibodies. A BDV titre that was at least four times higher than the BVDV titre was interpreted as the result of BDV infection. Titres against BVDV were interpreted in an analogous fashion. All examined sheep were pestivirus-negative, 310 sheep were seropositive, 119 had an indeterminate titre and 1'862 were seronegative. The flock seroprevalence ranged from 0.0 to 73.9 %. Three of the 27 flocks that underwent serum neutralization testing were interpreted as BDV-infected because of 6 sheep with higher BDV titres, and 6 flocks were interpreted as BVDV-infected because of 14 sheep with higher BVDV titres.

Gender differences in paediatric patients of the swiss inflammatory bowel disease cohort study.

PURPOSE Gender differences in paediatric patients with inflammatory bowel disease (IBD) are frequently reported as a secondary outcome and the results are divergent. To assess gender differences by analysing data collected within the Swiss IBD cohort study database since 2008, related to children with IBD, using the Montreal classification for a systematic approach. METHODS Data on gender, age, anthropometrics, disease location at diagnosis, disease behaviour, and therapy of 196 patients, 105 with Crohn's disease (CD) and 91 with ulcerative or indeterminate colitis (UC/IC) were retrieved and analysed. RESULTS THE CRUDE GENDER RATIO (MALE : female) of patients with CD diagnosed at <10 years of age was 2.57, the adjusted ratio was 2.42, and in patients with UC/IC it was 0.68 and 0.64 respectively. The non-adjusted gender ratio of patients diagnosed at ≥10 years was 1.58 for CD and 0.88 for UC/IC. Boys with UC/IC diagnosed <10 years of age had a longer diagnostic delay, and in girls diagnosed with UC/IC >10 years a more important use of azathioprine was observed. No other gender difference was found after analysis of age, disease location and behaviour at diagnosis, duration of disease, familial occurrence of IBD, prevalence of extra-intestinal manifestations, complications, and requirement for surgery. CONCLUSION CD in children <10 years affects predominantly boys with a sex ratio of 2.57; the impact of sex-hormones on the development of CD in pre-pubertal male patients should be investigated.

The phylogenetic position of the Dura Language of Nepal

The precise phylogenetic propinquity of Dura within the Tibeto-Burman or Trans-Himalayan language family has hitherto been indeterminate. In the absence of compelling comparative evidence, the language has previously been assigned to a subgroup in its own right within the linguistic phylum as a whole. Meanwhile, the Dura language is effectively extinct, although attempts at revival may be undertaken by well-intentioned members of Dura ethnicity. On the basis of a comprehensive study and analysis of all of the extant Dura language material, the phylogenetic position of the language within the family will be clarified. Comparative evidence from the Dura lexicon, its nominal and verbal morphology as well as from syntactic and phonological properties is adduced to determine the phylogenetic position of Dura. Moreover, this result will help explain some of the sociocultural realities associated with the Dura language community in Lamjung, Nepal

Chronological Order of Appearance of Extraintestinal Manifestations Relative to the Time of IBD Diagnosis in the Swiss Inflammatory Bowel Disease Cohort.

BACKGROUND Data evaluating the chronological order of appearance of extraintestinal manifestations (EIMs) relative to the time of inflammatory bowel disease (IBD) diagnosis is currently lacking. We aimed to assess the type, frequency, and chronological order of appearance of EIMs in patients with IBD. METHODS Data from the Swiss Inflammatory Bowel Disease Cohort Study were analyzed. RESULTS The data on 1249 patients were analyzed (49.8% female, median age: 40 [interquartile range, 30-51 yr], 735 [58.8%] with Crohn's disease, 483 [38.7%] with ulcerative colitis, and 31 [2.5%] with indeterminate colitis). A total of 366 patients presented with EIMs (29.3%). Of those, 63.4% presented with 1, 26.5% with 2, 4.9% with 3, 2.5% with 4, and 2.7% with 5 EIMs during their lifetime. Patients presented with the following diseases as first EIMs: peripheral arthritis 70.0%, aphthous stomatitis 21.6%, axial arthropathy/ankylosing spondylitis 16.4%, uveitis 13.7%, erythema nodosum 12.6%, primary sclerosing cholangitis 6.6%, pyoderma gangrenosum 4.9%, and psoriasis 2.7%. In 25.8% of cases, patients presented with their first EIM before IBD was diagnosed (median time 5 mo before IBD diagnosis: range, 0-25 mo), and in 74.2% of cases, the first EIM manifested itself after IBD diagnosis (median: 92 mo; range, 29-183 mo). CONCLUSIONS In one quarter of patients with IBD, EIMs appeared before the time of IBD diagnosis. Occurrence of EIMs should prompt physicians to look for potential underlying IBD.