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Background: Artificial daylight photodynamic therapy (ADL-PDT) is an alternative, all-year applicable, nearly painless treatment approach for actinic keratoses (AK) with comparable effectiveness to daylight or conventional PDT. At the time this study was initiated, methyl aminolevulinate (MAL) was the only photosensitizer approved for ADL-PDT in Germany., Objective: To gain comprehensive insights into the practicability of MAL-ADL-PDT in patients with AK using different artificial daylight sources under real-world conditions., Methods: This prospective, non-interventional, multicenter study (ArtLight, NCT05725213) enrolled patients with Olsen grade 1 or 2 AK on the face and scalp in Germany. Patients were treated with MAL-ADL-PDT (160mg/g MAL cream). The primary outcome measure was the practicability of MAL-ADL-PDT assessed as rate of resolved AK lesions in the focus area (10x10 cm area within the treatment area). Secondary outcomes included treatment-associated pain (numeric rating scale, NRS-11), Actinic Keratosis Area and Severity Index (AKASI), total lesion count over time, skin preparation, safety, overall assessment of effectiveness, tolerability, adherence, and patient satisfaction., Results: In total, 224 patients (median age: 75.0 years (range 50-91), 85.3% male, 62.5% AK Olsen grade 2, 55.4% treatment-naïve) were included and treated with MAL-ADL-PDT. Three months after treatment, lesion counts were reduced in the focus area by 71% (p<0.001) indicating practicability of the treatment. Nearly all patients (93.3%) experienced none or mild pain during PDT (NRS score 0-3). Median AKASI decreased from 6.2 at baseline to 3.4 at month 3 (95% CI 2.4-3.0; p<0.001). The majority of investigators (82.8%) and patients (80.0%) were satisfied with the treatment. No new safety signals were reported., Conclusions: The clinical practicability of MAL-ADL-PDT was demonstrated under real-world conditions by effective lesion reduction and predominantly none to mild procedural pain. Thus, MAL-ADL-PDT is a convenient way for healthcare professionals to deliver PDT treatment to patients with AK located on the face and scalp., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Background: The use of assays detecting cytomegalovirus (CMV)-specific T cell-mediated immunity may individualize the duration of antiviral prophylaxis after transplantation., Methods: In this randomized trial, kidney and liver transplant recipients from 6 centers in Switzerland were enrolled if they were CMV-seronegative with seropositive donors or CMV-seropositive receiving antithymocyte globulins. Patients were randomized to a duration of antiviral prophylaxis based on immune monitoring (intervention) or a fixed duration (control). Patients in the control group were planned to receive 180 days (CMV-seronegative) or 90 days (CMV-seropositive) of valganciclovir. Patients were assessed monthly with a CMV ELISpot assay (T-Track CMV); prophylaxis in the intervention group was stopped if the assay was positive. The co-primary outcomes were the proportion of patients with clinically significant CMV infection and reduction in days of prophylaxis. Between-group differences were adjusted for CMV serostatus., Results: Overall, 193 patients were randomized (92 in the immune-monitoring group and 101 in the control group), of whom 185 had evaluation of the primary outcome (87 and 98 patients). CMV infection occurred in 26 of 87 (adjusted percentage, 30.9%) in the immune-monitoring group and in 32 of 98 (adjusted percentage, 31.1%) in the control group (adjusted risk difference, -0.1; 95% confidence interval [CI], -13.0% to 12.7%; P = .064). The duration of prophylaxis was shorter in the immune-monitoring group (adjusted difference, -26.0 days; 95%, CI, -41.1 to -10.8 days; P < .001)., Conclusions: Immune monitoring resulted in a significant reduction of antiviral prophylaxis, but we were unable to establish noninferiority of this approach on the co-primary outcome of CMV infection., Clinical Trials Registration: NCT02538172., Competing Interests: Potential conflicts of interest. O. M. reports research grants from Lophius Biosciences (acquired by Mikrogen), the Novartis Foundation, and the Swiss Transplant Cohort Study; participation on a data and safety monitoring board for Syneos and in advisory boards of MSD, Biotest, and Takeda; and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Takeda, paid to their institution. H. H. H. reports grants from Moderna paid to their institution; consulting fees from AiCuris, Allovir, Moderna, VeraTX, and Roche; and honoraria from VeraTX, Takeda, Biotest, and Gilead. P. J. reports serving as an unpaid member of the steering group of a trial funded by Terumo and research grants to their institution from Appili Therapeutics. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: People with human immunodeficiency virus type 1 (HIV-1) (PWH) are frequently coinfected with Mycobacterium tuberculosis (MTB) and at risk for progressing from asymptomatic latent TB infection (LTBI) to active tuberculosis (TB). LTBI testing and preventive treatment (TB specific prevention) are recommended, but its efficacy in low transmission settings is unclear., Methods: We included PWH enrolled from 1988 to 2022 in the Swiss HIV Cohort study (SHCS). The outcome, incident TB, was defined as TB ≥6 months after SHCS inclusion. We assessed its risk factors using a time-updated hazard regression, modeled the potential impact of modifiable factors on TB incidence, performed mediation analysis to assess underlying causes of time trends, and evaluated preventive measures., Results: In 21 528 PWH, LTBI prevalence declined from 15.1% in 2001% to 4.6% in 2021. Incident TB declined from 90.8 cases/1000 person-years in 1989 to 0.1 in 2021. A positive LTBI test showed a higher risk for incident TB (hazard ratio [HR] 9.8, 5.8-16.5) but only 10.5% of PWH with incident TB were tested positive. Preventive treatment reduced the risk in LTBI test positive PWH for active TB (relative risk reduction, 28.1%, absolute risk reduction 0.9%). On population level, the increase of CD4 T-cells and reduction of HIV viral load were the main driver of TB decrease., Conclusions: TB specific prevention is effective in selected patient groups. On a population level, control of HIV-1 remains the most important factor for incident TB reduction. Accurate identification of PWH at highest risk for TB is an unmet clinical need., Competing Interests: Potential conflicts of interest . A. C. received grants from Merck Sharp & Dohme (MSD), ViiV Healthcare, and Gilead Sciences for unrelated research. R. D. K. received grants from Gilead Sciences and National Institutes of Health (NIH) for unrelated research. D. L. B. received honoraria for working on the advisory board of Gilead Sciences, Merck, ViiV, Pfizer, and AstraZeneca. D. L. B. received honoraria for presentations from Gilead Sciences and Merck. E. B. received grants from MSD for unrelated research. E. B. received payments for travel reimbursement from ViiV, MSD, Gilead Sciences, Pfizer, and Abbvie. E. B. received honoraria for working on the advisory board of ViiV, MSD, Pfizer, Gilead Sciences, AstraZeneca, and Ely Lilly. H. H. H. received honoraria for working on the advisory board of AiCuris, Merck, Vera Dx, and Molecular Partners. H. H. H. received honoraria for presentations from Merck, Gilead Sciences, Biotest, and Vera Dx. J. N. received honoraria for presentations from Oxford Immunotec and ViiV. H. F. G. received honoraria for working on the advisory board of Gilead Sciences, Merck, ViiV, Janssen, Johnson and Johnson, Novartis, and GlaxoSmithKline (GSK). H. F. G. received payments for travel reimbursements from Gilead Sciences. H. F. G. received grants from NIH, Yvonne Jacob Foundation, and Gilead Sciences. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Understanding the drivers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission is crucial for control policies, but evidence of transmission rates in different settings remains limited., Methods: We conducted a systematic review to estimate secondary attack rates (SARs) and observed reproduction numbers (Robs) in different settings exploring differences by age, symptom status, and duration of exposure. To account for additional study heterogeneity, we employed a beta-binomial model to pool SARs across studies and a negative-binomial model to estimate Robs., Results: Households showed the highest transmission rates, with a pooled SAR of 21.1% (95% confidence interval [CI]:17.4-24.8). SARs were significantly higher where the duration of household exposure exceeded 5 days compared with exposure of ≤5 days. SARs related to contacts at social events with family and friends were higher than those for low-risk casual contacts (5.9% vs 1.2%). Estimates of SARs and Robs for asymptomatic index cases were approximately one-seventh, and for presymptomatic two-thirds of those for symptomatic index cases. We found some evidence for reduced transmission potential both from and to individuals younger than 20 years of age in the household context, which is more limited when examining all settings., Conclusions: Our results suggest that exposure in settings with familiar contacts increases SARS-CoV-2 transmission potential. Additionally, the differences observed in transmissibility by index case symptom status and duration of exposure have important implications for control strategies, such as contact tracing, testing, and rapid isolation of cases. There were limited data to explore transmission patterns in workplaces, schools, and care homes, highlighting the need for further research in such settings., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)

To systematically test whether coinfections spread along the HIV-1 transmission network and whether similarities in HIV-1 genomes predict AIDS-defining illnesses and comorbidities, we analyzed the distribution of these variables on the HIV phylogeny of the densely sampled Swiss HIV Cohort Study. By combining different statistical methods, we could detect, quantify, and explain the clustering of diseases. Infectious conditions such as hepatitis C, but also Kaposi sarcoma, clustered significantly, suggesting transmission of these infections along the HIV-1 transmission network. The clustering of patients with neurocognitive complaints could not be completely explained by the clustering of patients with similar demographic risk factors, which suggests a potential impact of viral genetics. In summary, the consistent and robust signal for coinfections and comorbidities highlights the strong interaction of HIV-1 and other infections and shows the potential of combining phylogenetic methods to identify disease traits that are likely to be related to virus genetic factors., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Background: Scale-up of direct-acting antiviral therapy is expected to abate hepatitis C virus (HCV) incidence among human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). International transmission could influence this process. We classified HCV infections in HIV-positive MSM as either domestically or internationally acquired, and estimated how this classification changed over time., Methods: HCV subtype 1a (the most frequent subtype among MSM) genomes from 99 persons enrolled in the Swiss HIV Cohort Study and diagnosed with replicating HCV infections, were sequenced. Sixty-six of these sequences were from MSM. We inferred maximum-likelihood phylogenetic trees and time trees containing a fragment of the NS5B region of these and 374 circulating strains. We inferred transmission clusters from these trees and used the country composition of such clusters to attribute infections to domestic or international transmission., Results: Of HCV transmissions, 50% to 80% were classified as domestic depending on the classification criterion. Between 2000 and 2007, the fraction attributable to domestic transmission was 54% (range 0-75%). It increased to 85% (range 67%-100%) between 2008 and 2016., Conclusions: International and domestic transmission have played major roles in this epidemic. While international transmission persists, local transmission has established as the main source of infections., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)

Background: Comprehensive and representative data on resource use are critical for health policy decision making but often lacking for human immunodeficiency virus (HIV) infection. Privacy-preserving probabilistic record linkage of claim and cohort study data may overcome these limitations., Methods: Encrypted dates of birth, sex, study center, and antiretroviral therapy (ART) from the Swiss HIV Cohort Study (SHCS) records for 2012 and 2013 were linked by privacy-preserving probabilistic record linkage with claim data from the largest health insurer covering 15% of the Swiss residential population. We modeled predictors for mean annual costs adjusting for censoring and grouped patients by cluster analysis into 3 risk groups for resource use., Results: The matched subsample of 1196 patients from 9326 SHCS and 2355 claim records was representative for all SHCS patients receiving ART. The corrected mean (standard error) total costs in 2012 and 2013 were $30462 ($582) and $30965 ($629) and mainly accrued in ambulatory care for ART (70% of mean costs). The low-risk group for resource use had mean (standard error) annual costs of $26772 ($536) and $26132 ($589) in 2012 and 2013. In the moderate- and high-risk groups, annual costs for 2012 and 2013 were higher by $3526 (95% confidence interval, $1907-$5144) (13%) and $4327 ($2662-$5992) (17%) and $14026 ($8763-$19289) (52%) and $13567 ($8844-$18288) (52%), respectively., Conclusions: In a representative subsample of patients from linkage of SHCS and claim data, ART was the major cost factor, but patient profiling enabled identification of factors related to higher resource use., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

We present a new method, CIDER-Seq (Circular DNA Enrichment sequencing) for the unbiased enrichment and long-read sequencing of viral-sized circular DNA molecules. We used CIDER-Seq to produce single-read full-length virus genomes for the first time. CIDER-Seq combines PCR-free virus enrichment with Single Molecule Real Time sequencing and a new sequence de-concatenation algorithm. We apply our technique to produce >1200 full-length, highly accurate geminivirus genomes from RNAi-transgenic and control plants in a field trial in Kenya. Using CIDER-Seq we can demonstrate for the first time that the expression of antiviral double-stranded RNA (dsRNA) in transgenic plants causes a consistent shift in virus populations towards species sharing low homology to the transgene derived dsRNA. Our method and its application in an economically important crop plant opens new possibilities in periodic virus sequence surveillance and accurate profiling of diverse circular DNA elements.

Age-mixing patterns are of key importance for understanding the dynamics of human immunodeficiency virus (HIV)-epidemics and target public health interventions. We use the densely sampled Swiss HIV Cohort Study (SHCS) resistance database to study the age difference at infection in HIV transmission pairs using phylogenetic methods. In addition, we investigate whether the mean age difference of pairs in the phylogenetic tree is influenced by sampling as well as by additional distance thresholds for including pairs. HIV-1 pol -sequences of 11,922 SHCS patients and approximately 240,000 Los Alamos background sequences were used to build a phylogenetic tree. Using this tree, 100 per cent down to 1 per cent of the tips were sampled repeatedly to generate pruned trees ( N  = 500 for each sample proportion), of which pairs of SHCS patients were extracted. The mean of the absolute age differences of the pairs, measured as the absolute difference of the birth years, was analyzed with respect to this sample proportion and a distance criterion for inclusion of the pairs. In addition, the transmission groups men having sex with men (MSM), intravenous drug users (IDU), and heterosexuals (HET) were analyzed separately. Considering the tree with all 11,922 SHCS patients, 2,991 pairs could be extracted, with 954 (31.9 per cent) MSM-pairs, 635 (21.2 per cent) HET-pairs, 414 (13.8 per cent) IDU-pairs, and 352 (11.8 per cent) HET/IDU-pairs. For all transmission groups, the age difference at infection was significantly (P < 0.001) smaller for pairs in the tree compared with randomly assigned pairs, meaning that patients of similar age are more likely to be pairs. The mean age difference in the phylogenetic analysis, using a fixed distance of 0.05, was 9.2, 9.0, 7.3 and 5.6 years for MSM-, HET-, HET/IDU-, and IDU-pairs, respectively. Decreasing the cophenetic distance threshold from 0.05 to 0.01 significantly decreased the mean age difference. Similarly, repeated sampling of 100 per cent down to 1 per cent of the tips revealed an increased age difference at lower sample proportions. HIV-transmission is age-assortative, but the age difference of transmission pairs detected by phylogenetic analyses depends on both sampling proportion and distance criterion. The mean age difference decreases when using more conservative distance thresholds, implying an underestimation of age-assortativity when using liberal distance criteria. Similarly, overestimation of the mean age difference occurs for pairs from sparsely sampled trees, as it is often the case in sub-Saharan Africa.

Pegylated interferon-alpha (pIFN-α) is suggested to lower human immunodeficiency virus type-1 (HIV-1) DNA load in antiretroviral therapy (ART)-treated patients. We studied kinetics of HIV-1 DNA levels in 40 HIV-1/hepatitis C virus (HCV) coinfected patients, treated with pIFN-α for HCV and categorized into 3 groups according to start of ART: chronic HIV-1 infection (n = 22), acute HIV-1 infection (n = 8), no-ART (n = 10). Total HIV-1 DNA levels in 247 peripheral blood mononuclear cell samples were stable before, during, and after pIFN-α treatment in all groups. Our results question the benefit of pIFN-α as an immunotherapeutic agent for reducing the HIV-1 reservoir.

Background: Hepatitis B virus (HBV) has a detrimental effect on human immunodeficiency virus (HIV) natural course, and HBV vaccination is less effective in the HIV infected. We examine the protective effect of dually active antiretroviral therapy (DAART) for HIV/HBV (tenofovir, lamivudine, and emtricitabine) in a large cohort encompassing heterosexuals, men who have sex with men, and intravenous drug users who are HIV infected yet susceptible to HBV, with comprehensive follow-up data about risky behavior and immunological profiles., Methods: We defined an incident HBV infection as the presence of any of HBV serological markers (hepatitis B surface antigen, anti-hepatitis B core antibodies, or HBV DNA) after a negative baseline test result for anti-hepatitis B core antibodies. Patients with positive anti-hepatitis B surface antigen serology were excluded. Cox proportional hazards models were used, with an incident case of HBV infection as the outcome variable., Results: We analyzed 1716 eligible patients from the Swiss HIV Cohort Study with 177 incident HBV cases. DAART was negatively associated with incident HBV infection (hazard ratio [HR], 0.4; 95% confidence interval [CI], .2-.6). This protective association was robust to adjustment (HR, 0.3; 95% CI, .2-.5) for condomless sex, square-root-transformed CD4 cell count, drug use, and patient demographics. Condomless sex (HR, 1.9; 95% CI, 1.4-2.6), being a man who has sex with men (2.7; 1.7-4.2), and being an intravenous drug user (3.8; 2.4-6.1) were all associated with a higher hazard of contracting HBV., Conclusions: Our study suggests that DAART, independently of CD4 cell count and risky behavior, has a potentially strong public health impact, including pre-exposure prophylaxis of HBV coinfection in the HIV infected., (© The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.)

Systemic immune activation, a major determinant of human immunodeficiency virus (HIV) disease progression, is the result of a complex interplay between viral replication, dysregulation of the immune system, and microbial translocation due to gut mucosal damage. Although human genetic variants influencing HIV load have been identified, it is unknown how much the host genetic background contributes to interindividual differences in other determinants of HIV pathogenesis such as gut damage and microbial translocation. Using samples and data from 717 untreated participants in the Swiss HIV Cohort Study and a genome-wide association study design, we searched for human genetic determinants of plasma levels of intestinal fatty acid-binding protein (I-FABP/FABP2), a marker of gut damage, and of soluble CD14 (sCD14), a marker of lipopolysaccharide bioactivity and microbial translocation. We also assessed the correlations between HIV load, sCD14, and I-FABP. Although we found no genome-wide significant determinant of the tested plasma markers, we observed strong associations between sCD14 and both HIV load and I-FABP, shedding new light on the relationships between processes that drive progression of untreated HIV infection., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cassava (Manihot esculenta) is the most important root crop in the tropics, but rapid postharvest physiological deterioration (PPD) of the root is a major constraint to commercial cassava production. We established a reliable method for image-based PPD symptom quantification and used label-free quantitative proteomics to generate an extensive cassava root and PPD proteome. Over 2600 unique proteins were identified in the cassava root, and nearly 300 proteins showed significant abundance regulation during PPD. We identified protein abundance modulation in pathways associated with oxidative stress, phenylpropanoid biosynthesis (including scopoletin), the glutathione cycle, fatty acid α-oxidation, folate transformation, and the sulfate reduction II pathway. Increasing protein abundances and enzymatic activities of glutathione-associated enzymes, including glutathione reductases, glutaredoxins, and glutathione S-transferases, indicated a key role for ascorbate/glutathione cycles. Based on combined proteomics data, enzymatic activities, and lipid peroxidation assays, we identified glutathione peroxidase as a candidate for reducing PPD. Transgenic cassava overexpressing a cytosolic glutathione peroxidase in storage roots showed delayed PPD and reduced lipid peroxidation as well as decreased H 2 O 2 accumulation. Quantitative proteomics data from ethene and phenylpropanoid pathways indicate additional gene candidates to further delay PPD. Cassava root proteomics data are available at www.pep2pro.ethz.ch for easy access and comparison with other proteomics data., (© 2014 American Society of Plant Biologists. All rights reserved.)

Import of nuclear-encoded precursor proteins from the cytosol is an essential step in chloroplast biogenesis that is mediated by protein translocon complexes at the inner and outer envelope membrane (TOC). Toc159 is thought to be the main receptor for photosynthetic proteins, but lacking a large-scale systems approach, this hypothesis has only been tested for a handful of photosynthetic and nonphotosynthetic proteins. To assess Toc159 precursor specificity, we quantitatively analyzed the accumulation of plastid proteins in two mutant lines deficient in this receptor. Parallel genome-wide transcript profiling allowed us to discern the consequences of impaired protein import from systemic transcriptional responses that contribute to the loss of photosynthetic capacity. On this basis, we defined putative Toc159-independent and Toc159-dependent precursor proteins. Many photosynthetic proteins accumulate in Toc159-deficient plastids, and, surprisingly, several distinct metabolic pathways are negatively affected by Toc159 depletion. Lack of Toc159 furthermore affects several proteins that accumulate as unprocessed N-acetylated precursor proteins outside of plastids. Together, our data show an unexpected client protein promiscuity of Toc159 that requires a far more differentiated view of Toc159 receptor function and regulation of plastid protein import, in which cytosolic Met removal followed by N-terminal acetylation of precursors emerges as an additional regulatory step.

pep2pro is a comprehensive proteome analysis database specifically suitable for flexible proteome data analysis. The pep2pro database schema offers solutions to the various challenges of developing a proteome data analysis database and because data integrated in pep2pro are in relational format, it enables flexible and detailed data analysis. The information provided here will facilitate building proteome data analysis databases for other organisms or applications. The capacity of the pep2pro database for the integration and analysis of large proteome datasets was demonstrated by creating the pep2pro dataset, which is an organ-specific characterisation of the Arabidopsis thaliana proteome containing 14 522 identified proteins based on 2.6 million peptide spectrum assignments. This dataset provides evidence of protein expression and reveals organ-specific processes. The high coverage and density of the dataset are essential for protein quantification by normalised spectral counting and allowed us to extract information that is usually not accessible in low-coverage datasets. With this quantitative protein information we analysed organ- and organelle-specific sub-proteomes. In addition we matched spectra to regions in the genome that were not predicted to have protein coding capacity and provide PCR validation for selected revised gene models. Furthermore, we analysed the peptide features that distinguish detected from non-detected peptides and found substantial disagreement between predicted and detected proteotypic peptides, suggesting that large-scale proteomics data are essential for efficient selection of proteotypic peptides in targeted proteomics surveys. The pep2pro dataset is available as a resource for plant systems biology at www.pep2pro.ethz.ch.

Early observers of plant evolution in the Arctic have noted a floristic similarity with temperate alpine regions and a predominance of high ploidy levels. The aim of our study was to survey these and other traits in multiple closely related but independently evolved lineages of Artemisia. Our phylogenetic study was based on 133 taxa using 3'-ETS and ITS, and on data on morphology, karyology, distribution, and ecological preferences. We compared Arctic lineages with sister groups and tested whether patterns were significantly different. We found: (1) Artemisia has independently adapted to Arctic habitats 13-18 times; (2) There were no ecological preferences of putative progenitors that might determine the colonization success in the Arctic, although most sister groups were centered in steppe habitats; (3) Plant height was distinctly reduced in Arctic lineages; (4) Arctic lineages contained no more polyploids than their respective sister groups or taxa from other habitats; (5) Enlarged flower heads have evolved repeatedly, probably for better pollinator attraction. This strategy could be a substitute for polyploidy, which is typical in other Arctic taxa. Stronger pollinator attraction should result in better outcrossing and higher heterozygosity in the offspring, which is among the main effects of polyploidy.

Background and Aims: Germination and establishment of seeds are complex traits affected by a wide range of internal and external influences. The effects of parental temperature preconditioning and temperature during germination on germination and establishment of Arabidopsis thaliana were examined., Methods: Seeds from parental plants grown at 14 and at 22 degrees C were screened for germination (protrusion of radicle) and establishment (greening of cotyledons) at three different temperatures (10, 18 and 26 degrees C). Seventy-three accessions from across the entire distribution range of A. thaliana were included., Key Results: Multifactorial analyses of variances revealed significant differences in the effects of genotypes, preconditioning, temperature treatment, and their interactions on duration of germination and establishment. Reaction norms showed an enormous range of plasticity among the preconditioning and different germination temperatures. Correlations of percentage total germination and establishment after 38 d with the geographical origin of accessions were only significant for 14 degrees C preconditioning but not for 22 degrees C preconditioning. Correlations with temperature and precipitation on the origin of the accessions were mainly found at the lower germination temperatures (10 and 18 degrees C) and were absent at higher germination temperatures (26 degrees C)., Conclusions: Overall, the data show huge variation of germination and establishment among natural accessions of A. thaliana and might serve as a valuable source for further germination and plasticity studies.

Different plant plastid types contain a distinct protein complement for specialized functions and metabolic activities. plprot was established as a plastid proteome database to provide information about the proteomes of chloroplasts, etioplasts and undifferentiated plastids. The current version of plprot features 2,043 protein entries and consists of two modules. Module one contains a BLAST search option and provides comparative information on the proteomes of different plastid types. The second module contains four searchable databases, three for each individual plastid type and one comprehensive composite database that provides the results of plastid proteome analyses from different laboratories. plprot is accessible at http://www.plprot.ethz.ch.

The evolution of the realized climatic niche in the genus Arabidopsis was studied using an almost complete phylogenetic tree based on DNA sequences of the ribosomal internal transcribed spacers. The realized climatic niche (climate space) was determined by the intersections of the distribution ranges of the taxa with climate data and is presented in temperature/precipitation diagrams. A positive correlation exists between the climate spaces of the taxa and their range sizes. The diagrams revealed a core climate; that is, a climate space in which all taxa co-exist. This core climate is almost identical to the most parsimonious reconstruction of the genus' ancestral climate space and may be considered an ancestral state of these characters. Mapping the evolutionary changes occurring in the realized climatic space on the phylogenetic tree from the core climate proved to be the most parsimonious procedure. The character complex is homoplastic; that is, many parallel evolutionary events have occurred in the subclades. With the exception of A. thaliana, which is sister to the other species of the genus and occupies a very large climate space, the late-diverged taxa of the other subclades experienced great evolutionary changes whereas the realized climate space of the taxa that diverged earlier resembles the core climate. The latter also show some parallel contractions in the climate space. It is hypothesized that the diversification of Arabidopsis may have started from small to midsized ranges in a temperate climate.

Aim: Sub-threshold stimulation (STS) applied during atrioventricular nodal re-entrant tachycardia (AVNRT) of the common (slow-fast) type has been shown to effectively characterise target sites suitable for slow pathway (SP) ablation but has not been investigated in the setting of fast-slow and slow-slow variants., Methods and Results: Seventeen consecutive patients (52+/-16 years, 12 female) with sustained uncommon type AVNRT (fast-slow: n = 13, slow-slow: n = 4) were investigated. Mapping of the SP was started postero-septally close to the coronary sinus ostium and continued toward mid-septal sites, if required. Target sites for STS were selected according to established criteria including the recording of the earliest retrograde atrial activation during AVNRT. Long duration (5 s) constant current STS during AVNRT variants was performed in a stepwise manner (max 5 mA) at each site eligible for SP ablation until termination or capture occurred. Radiofrequency current (RFC) was delivered following successful STS termination of tachycardia (65 degrees C, 60 s) and exclusion of catheter dislodgement. Uncommon AVNRT with a mean cycle length of 405+/-70 ms was induced without spontaneous termination in all patients. Interruption of AVNRT variants due to selective STS-induced block of the retrograde (n = 12) or anterograde (n =2) SP occurred without capture in 14/17 (82%) patients. This was exclusively observed at sites with successful subsequent RFC application. AVNRT was rendered non-inducible in all patients after a median of 1 (1-11) RFC pulses without complications., Conclusions: Uncommon AVNRT can be interrupted by STS delivered at subsequently successful target sites for SP ablation in most patients (82%). The high positive and negative concordance between the effects of STS and following RFC application indicates that STS-mapping is also useful in the setting of AVNRT variants.

A retrospective analysis of hospitalizations due to infection in 175 injection drug users was performed for the 3 years before and the period during their participation in an injection opiate maintenance program (mean duration during program, 2.6 years). Skin infections were the main reason for hospitalization. The injection opiate maintenance program did not reduce the incidence of infection leading to hospitalization among the injection drug users studied.