01% to 0.1% require medical evacuation.1,2 Fortunately, the death rate is low. A number of studies have examined the death rate of their citizens abroad, mostly using national foreign affairs data3–18 or observational studies.19 Unlike many Western countries, there are no data available on the numbers and causes of death of Proteasome function Dutch citizens abroad, even

though countless of Dutch travelers visit destinations outside the Netherlands each year. This lack of information is mostly a result of the absence of a mandatory registration system of Dutch citizens who died abroad. Although the death rate of citizens abroad remains an important indicator of a country’s safety profile, it can—from an alternative point of view—also be Vadimezan solubility dmso considered as the end point of accumulation of personal risk factors, including traveler’s personal health and behavior, which may be preventable to a certain extent. Detailed knowledge on these causes of death of travelers abroad is needed to accurately estimate these health risks. Moreover, this information may also be used as an important feedback tool to improve the quality and focus of our current travel health consultation and preparation. The aim of this study is to provide more insight in the number and causes of death of Dutch citizens abroad in relation to their travel destination. In 2009, we performed a questionnaire-based

survey among all Dutch general physicians. The questionnaire dealt with the following six items: (1) Do you Selleckchem Hydroxychloroquine give pretravel advice and to how many persons? (2) How many of your clients in your practice died abroad in the years 2007 and 2008? (3) What was the country of death? (4) What was the cause of death? (5) What was the age and gender of the deceased?

and (6) Do you have any additional information on the cause of death? All countries were classified in regions, according to the designated six World Health Organization (WHO) regions (available at www.who.int/about/regions/en/). These six regions were the European region including Turkey, Russia, and Greenland; the region of the Americas, both North America and South America; the African region, the whole continent apart from Morocco, Tunisia, Sudan, Somalia, and Egypt; the Eastern Mediterranean region including the Middle East and Morocco, Tunisia, Sudan, Somalia, and Egypt; the Southeast Asian region with also India, Indonesia, Thailand, and Sri Lanka; and the Western Pacific region including countries like China, Japan, Malaysia, New Zealand, and Australia. Demographic data, numbers and causes of deaths, and the countries of death were statistically analyzed using SPSS (v.15.0) software (SPSS Inc., Chicago, IL, USA). The number of Dutch travelers to all countries and regions in the world was obtained from the World Tourist Organization (available at www.e-unwto.org/home/main.mpx).

While the efficacies of the ART regimens modelled

are reported in rates of virological suppression and CD4 benefit, we use the model to project these results over the long term. To achieve stability in estimates, a cohort of 1 000 000 patients is simulated one at a time, from model entry until death. Model outcomes include mean survival time and mean exposure time for all ART regimens. HIV-infected women in the model are at risk for the following HIV-related comorbidities: Pneumocystis jirovecii pneumonia (PCP), Mycobacterium avium complex (MAC), toxoplasmosis, cytomegalovirus (CMV), fungal infections, bacterial infections, invasive cervical selleck cancer and other illnesses (e.g. lymphoma and wasting). Primary and secondary prophylaxis against PCP, toxoplasmosis, and MAC is provided at recommended CD4 thresholds and at efficacy rates reported in the literature [16–24]. ART functions in the model to suppress HIV RNA with a concomitant increase in CD4 cell count as reported in treatment trials from the modern ART era [25–30].

The model allows for numerous sequential drug treatment regimens after failure. However, subsequent Nutlin 3 therapy regimens generally result in diminishing capacity to suppress virus as a result of previous drug exposure and development of resistance. Treatment failure, resulting in a switch to the next available regimen, may occur as a result of either virological failure (defined as a 1-log10 increase in HIV RNA over 2 consecutive months) or immunological failure (defined as a decrease in CD4 cell count over 2 consecutive months). For cases of nucleoside reverse transcriptase inhibitor (NRTI)-related toxicity, the model has the capacity to incorporate a single NRTI switch with an associated quality of life decrement, Methocarbamol without including a switch of

the entire regimen. The model provides six sequential ART regimens to indicate possible treatment sequences for a patient who fails multiple therapies. As a result of the efficacy of the regimens, approximately one-third of simulated patients die of unrelated causes and neither progress through all six regimens nor die as a result of sequential ART failure. If all regimens are exhausted, an optimized background regimen is maintained to capitalize on the independent effect of ART in averting opportunistic infections, despite apparent virological or immunological treatment failure [31]. The WIHS is a longitudinal cohort study of HIV-infected women in six locations in the USA (Bronx/Manhattan, NY; Washington, DC; San Francisco/Bay Area; Los Angeles/Southern California/Hawaii; Chicago, IL; and Brooklyn, NY). Cohort enrolment from October 1994 to November 1995 resulted in the inclusion of 2056 HIV-infected women [32].

Only 45% of the IL-2 patients who experienced bacterial pneumonia received further dosing cycles of rIL-2 subsequently. The Kaplan–Meier table showing the time to bacterial pneumonia in the IL-2 and control arms

is shown in Figure 2. Overall, as shown in Table 3a, in the multivariate model, baseline risk factors for bacterial pneumonia were older age (HR per 10 years increase in age 1.34; 95% CI 1.14–1.59; P=<0.001), IDU (HR 1.78; 95% CI 1.09–2.90; P=0.02), VL ≥500 HIV-1 RNA copies/mL Selleckchem APO866 (HR 2.02; 95% CI 1.46–2.81; P=<0.001) and history of recurrent bacterial pneumonia as an ADI (HR 5.38; 95% CI 2.86–10.11; P=<0.001). Asian ethnicity was associated with a decreased risk of bacterial pneumonia (HR 0.17; 95% CI 0.05–0.56; P=0.003). In the multivariate analysis of bacterial pneumonia events in the IL-2 arm, the baseline associations were similar to the overall findings, Asian ethnicity was protective (HR 0.10; 95% CI 0.01–0.74; P=0.02);

being older (HR 1.46; 95% CI 1.15–1.85; P=0.002), having detectable plasma VL (HR 2.27; 95% CI 1.45–3.55; P=<0.001) and having a prior history of recurrent bacterial pneumonia (HR 4.46; 95% CI 1.72–11.54; P=0.002) were associated with increased pneumonia risk. However, IDU was not associated with an increased pneumonia risk (HR 1.46; 95% CI 0.72–2.96; P=0.30). Consistent with the overall findings, in control patients, IDU (HR 2.11; 95% CI 1.06–4.20; P=0.03), recurrent bacterial pneumonia (HR 5.61; 95% CI 2.38–13.24; P≤0.001) and detectable plasma VL (HR 1.85; 95% CI 1.13–3.03; INK 128 purchase P=0.01) were associated with a

significantly increased hazard for pneumonia. In contrast to the overall findings, there was only a trend towards decreased risk with Asian ethnicity (HR 0.27; 95% CI 0.06–1.11; P=0.07) and a trend towards increased risk with older age (HR 1.26; 95% CI 0.99–1.61; P=0.06). As shown in Table 3b, higher proximal VL on study (HR for 1 log10 higher VL 1.28; 95% CI 1.11–1.47; P≤0.001) and receipt of rIL-2 within the last 180 days (HR 1.72; 95% CI 1.12–2.65; P=0.01) were predictors of increased risk for a bacterial pneumonia event; higher proximal CD4 cell count 4-Aminobutyrate aminotransferase was associated with decreased risk (HR 0.94; 95% CI 0.89–1.00; P=0.04). When adjusted for baseline predictors (age, IDU, ethnicity and history of recurrent bacterial pneumonia) and time-updated CD4 cell count and VL, the hazards for IL-2 patients cycling within 180 days and ≥180 days of a bacterial pneumonia event were 1.66 (95% CI 1.07–2.60; P=0.02) and 0.98 (95% CI 0.70–1.37; P=0.90), respectively, compared with the control arm. In years 1 and 2 in the IL-2 group, the hazard for bacterial pneumonia when rIL-2 cycling was <30, 30–119 and 120–179 days, compared with receipt ≥180 days previously, was 2.59 (95% CI 0.88–7.62; P=0.08), 1.74 (95% CI 0.70–4.30; P=0.23) and 1.21 (95% CI 0.36–4.04; P=0.75), respectively.

A long-term extension trial reported a case of lymphoma in a

patient treated with tofacitinib, but the rate of lymphoproliferative disease was consistent with the rate seen in all patients with RA, including those treated with biologics.[28] Similarly, occurrences of basal cell cancer, non-Hodgkin’s lymphoma, stomach adenocarcinoma, http://www.selleckchem.com/products/BKM-120.html breast mucinous adenocarcinoma and bone squamous cell carcinoma were reported in phase 3 trials.[31] Further investigation has pooled phase 2 and 3 data to reflect 5651 patient-years of tofacitinib treatment. The most common malignancies reported were lung and breast cancer. Three cases of lymphoma were identified. The incidence for all malignancies (excluding non-melanoma skin cancer) is consistent with that of RA patients taking traditional small-molecule DMARDs and biologic agents.[33] Laboratory abnormalities were observed with tofacitinib treatment. Neutrophil levels decreased and studies showed suppressed hemoglobin selleck products levels (contrary to the rise in hemoglobin typically seen with biologic therapy). Since JAK2 is integral in the signaling of erythropoietin and colony stimulating factors, these

cytopenias are felt to be a consequence of JAK2 inhibition.[28] Notably, low density lipoprotein (LDL) and high DL (HDL) levels increased in tofacitinib study groups. While analyses of phase 3 trials and long-term open label extension studies have not demonstrated an increased risk of cardiovascular events compared

to control RA patients, it may be too soon to conclude that these changes in lipid levels are inconsequential.[34] Small, but statistically significant elevations in serum creatinine and infrequent increases in serum transaminase levels were also demonstrated. While long-term trials of tofacitinib are still ongoing, the available data regarding the safety profile of tofacitinib is encouraging and in keeping with the safety profile seen in biologic therapy. Additional JAK inhibitors are under clinical investigation Fossariinae in RA (Table 5). Baricitinib (INCBO28050) is a selective inhibitor of JAK1 and JAK2. Baricitinib is similar to ruxolitinib in its inhibition of JAK1 and JAK2. Ruxolitinib was the first JAK inhibitor approved by the United States FDA in November of 2011 for treatment of myelofibrosis. Phase 2a trials for ruxolitinib in RA demonstrated significantly improved ACR response criteria, spurring on further investigation of baricitinib.[35] In preclinical trials of baricitinib, inhibition of JAK1 and JAK2 interfered with signaling of inflammatory cytokines such as IL-6 and IL-23.[36] Indeed, baricitinib was found to be effective in several rodent models of inflammatory arthritis without evidence of immunosuppression. The risk of bone marrow suppression expected with JAK1 and JAK2 inhibition was avoided by using periodic and incomplete inhibition.

The remaining patients had undergone one or several treatment changes. The majority of these treatment changes (49%) were made rationally (e.g. because of suspected treatment failure or drug toxicity), in 12% of the cases the treatment changes were irrational (e.g. because of cost or interrupted drug supplies) and 17% of the changes involved treatment interruption (often because of cost or interrupted drug supplies) (Table 2). CDC stage and self-reported adherence levels were not significantly correlated to resistance, whereas CD4 cell counts and plasma HIV RNA levels were selleck chemicals llc significantly correlated to resistance. However, it should

be pointed out that these CD4 and HIV RNA levels frequently were not obtained concomitantly with the resistance test and often not even while the patient was JQ1 on the same therapy as when the resistance test was carried out. Multiple logistic regression was used to identify variables that were independently associated with the presence of genotypic resistance. The final model includes as categorical variables: route of infection, start of therapy within the national treatment programme (yes/no) and type of virological failure (virological, immunological or clinical). Number of treatment changes and years on therapy were included as continuous variables. Age (adult vs. child) was

not included as a variable because it largely overlapped with route of infection. CD4 cell counts and HIV RNA were not included because results were not available for all patients and often were obtained long before the sample used for resistance testing. The multivariable analysis identified the following variables as independently associated with resistance: type of treatment failure [virological failure (OR=1) vs. immunological failure (OR=0.11; 95% CI 0.030–0.43) vs. clinical failure (OR=0.037; 95% CI 0.0063–0.22)]; route of transmission (OR=42.8; 95% CI 3.73–491); Loperamide and years on therapy (OR=1.81;

95% CI 1.11–2.93). This indicates that VL testing was needed to correctly identify patients with treatment failure attributable to resistance. As shown in Table 3, genotypes predicted to have reduced susceptibility to at least one NRTI were observed in 98 of 138 patients (71%; 95% CI 63–78%); to at least one NNRTI in 96 patients (70%; 95% CI 61–77%); and to at least one PI in 51 patients (37%; 95% CI 29–45%). Dual and triple class resistance was very common. Thus, triple-class drug resistance was documented in 37 of the 138 study subjects (27%; 95% CI 20–35%) and dual-class drug resistance was detected in 59 patients (43%; 95% CI 34–51%), whereas only 16 (12%; 95% CI 7–18) of the patients showed single-class resistance.

Between January 2004 and October 2004, 600 individuals

were randomized: 300 to the active nevirapine group (N) and 300 to the active abacavir group (A). selleck Baseline characteristics were broadly similar (Table 1). A total of 563 participants (94%) completed 48 weeks (286 in A and 277 in N); 25 (4%) died (nine in A and16 in N) and 12 (2%) were lost to follow-up (five in A and seven in N). The randomized drug had been substituted/stopped in 21 participants (7%) receiving abacavir vs. 34 participants (11%) receiving nevirapine by 48 weeks/last follow-up (exact P=0.09). The majority had substituted abacavir/nevirapine with tenofovir DF for adverse events (five in A and 12 in N; mostly suspected hypersensitivity while on the blinded drug), or to start anti-tuberculosis treatment

as per protocol (five in A and 17 in N), or for personal reasons (one in A). The remainder had stopped ART for adverse events (two in A and one in N) or personal reasons Selleck LBH589 (one in A and three in N), or changed to the opposite drug for pregnancy (one in A) or adverse events (two in A) or in error when unblinded at 24 weeks (four in A and one in N). Fifty-one participants (8%) had substituted stavudine for zidovudine, mostly for anaemia/neutropenia (25 in A and 26 in N). In the abacavir group, 94.8% of person-time spent under follow-up to 48 weeks was spent on abacavir+lamivudine+zidovudine/stavudine compared with 91.1% on nevirapine+lamivudine+zidovudine/stavudine in the nevirapine

group. Adherence by 4-weekly self-reported questionnaire was similar in the abacavir and nevirapine groups, with means of 3.7%vs. 2.6%, respectively, reporting missing pills in the last 4 days (P=0.32), and 14.5%vs. 13.4%, respectively, in the last 28 days (P=0.70). To 48 weeks, there was a consistent trend towards clinical superiority of abacavir over nevirapine in terms of HIV-related events (Fig. 1). Nine participants in the abacavir group vs. 16 in the nevirapine group had died (HR 0.55; 95% CI 0.24–1.25; P=0.15) and 20 vs. SPTBN5 32, respectively, had experienced a new or recurrent WHO stage 4 event or died (HR 0.60; 95% CI 0.34–1.05; P=0.07). The first new or recurrent WHO stage 4 events were oesophageal candidiasis (four in A and six in N), extrapulmonary tuberculosis (two in A and five in N), cryptococcus (two in A and four in N), Pneumocystis carinii pneumonia (two in A and one in N), herpes simplex (two in A and one in N), toxoplasmosis (one in A and one in N), Kaposi sarcoma (two in N), HIV wasting (one in N), and cryptosporidia (one in N); and 18 participants (seven in A and 11 in N) died without a new or recurrent WHO 4 event being identified after ART initiation. Forty-eight participants in the abacavir group vs. 68 in the nevirapine group experienced a new or recurrent WHO stage 3 or 4 event or died (HR=0.67; 95% CI 0.46–0.96; P=0.03).

The JIA patients recruited in this study had relatively low levels of disease activity. It could be postulated GSI-IX purchase that had patients with more active/severe disease been targeted, that the levels of maternal stress would have exceeded those seen in eczema and enteral feeding. The paper by Lederberg and Golbach[18] referenced in our paper regarding maternal stress in mothers of deaf children suggested mothers of deaf children do not feel a high level of parenting stress.

Stress levels were comparable to normative data. In this study they used another tool (Questionnaire on Resources and Stress [QRS-F]) to measure maternal stress in addition to PSI. By the QRS-F tool mothers of deaf children did express more stress. Most of the patients involved in the study had been enrolled in early intervention programs, which may have helped to reduce stress levels. Patients with JIA in the Australian setting are often not as well supported as those with deafness for which established structures of support are in place. The paper by Powers et al.,[19] which reported on parenting stress in young children Autophagy Compound Library cell assay with diabetes, looked more

specifically at parental stress in response to mealtime behavioral problems. In their paper the level of parental stress measured by PSI Total Stress score was higher in parents of diabetics (218.1) when compared to a control group (195.5) recruited in the study. Thus the Powers et al. paper did not use the established normative data for PSI Total Stress score, which others[14] and us have used as a comparator. In fact if we Decitabine were to use the lower 195.5 score rather than 222 it would further strengthen the findings of increased stress in the mothers of children with JIA and further highlights the need for intervention in parents of children with chronic illness, as it appears

to alleviate stress. The literature including Caning et al.[12] regarding outcomes of mothers of children with chronic disease generally agrees that disease severity is not related to psychological outcome. There was not a significant association between current disease activity and maternal stress levels in this study. The overall disease activity was not high with low mean active joint counts, CHAQ scores indicating mild disease activity and low mean physician global assessments. However, half of the patients were taking a disease-modifying anti-rheumatic drug (DMARD) and one-fifth a biologic DMARD, which would suggest that at some point in time the disease activity in at least some of the patients included had been greater. The low levels of disease activity seen in this study were not surprising. Current treatment practices for JIA and all the inflammatory arthritides in general aim for remission and even low levels of disease activity are not accepted. The mothers in this study were recruited at any stage of their child’s disease course.

98) among those who started in the recent period, compared with the early period. HIF inhibitor Patients who had a previous history of injecting drug use (IDU) (of whom 65% had been enrolled in the early period) had almost a threefold increased risk of discontinuation because of poor adherence compared with those who were infected with HIV by heterosexual intercourse (ARH

2.85; 95% CI 1.89–4.30, P<.0001). Female gender (ARH 1.42, 95% CI 1.07–1.89 vs. male gender; P=0.01) and a higher CD4 cell count at baseline (ARH 1.08, 95% CI 1.02–1.14 per 100 cells/μL higher; P=0.002) were independently associated with a higher risk of discontinuation because of poor adherence. We observed a tendency towards a higher rate of discontinuation because of poor adherence in patients younger than 30 years compared with those aged 30–45 years (ARH 1.34, 95% CI 0.97–1.84, P=0.07) (Table 3). The results of the model were similar when we analysed separately patients

who received coformulated boosted PI (72% of those who started a boosted PI) and those Buparlisib cell line who received ritonavir and another PI as a separate drug (data not shown). The Kaplan–Meier estimates of discontinuation by 1 year because of immunovirological and clinical failure were about 60% lower in patients who started HAART recently (3.4%; 95% CI 1.9–4.9%) and in the intermediate period (2.4%; 95% CI 1.3–3.4%) compared with those who started in 1997–1999 (5.5%; 95% CI 4.3–6.6%) (log rank P=0.0013) (Fig. 1). In the multivariable model, we observed a significant decline

in the incidence of discontinuation because of failure in patients who started HAART in 2000–2002 (ARH 0.46, 95% CI 0.26–0.82, P=0.008 vs. 1997–1999) and, surprisingly, comparable rates of discontinuation because of failure between the early and recent periods (ARH 0.81, 95% CI 0.40–1.63, P=0.57). The number of CD4 T cells at HAART initiation showed an independent association with this outcome (ARH 0.88, 95% CI 0.80–0.97, per 100 cells/μL higher; P=0.01) (Table 3). Fifty-seven patients out of 101 (56%) who discontinued because of virological failure had viral load >500 copies/mL at the time of switching, five of 11 (45%) who discontinued because of immunological failure had an increase in CD4 cell count of <10% from the pre-therapy value, and six of 14 (43%) categorized as having Thalidomide clinical failure had an AIDS-defining illness at the time of discontinuation. In order to validate the accuracy of the reason for discontinuation given by the clinicians, the analysis with the endpoint immunovirological and clinical failure was repeated only with those patients, and provided results that were very similar to those of the main analysis (Table 4). A significant declining trend with calendar period of HAART initiation was observed in the viral load at switch of patients who discontinued because of virological failure [1.69 log10 copies/mL (95% CI 1.69–2.75 log10 copies/mL) in patients who started HAART in the recent period, 2.37 log10 copies/mL (95% CI 2.00–4.

Electrical potentials were recorded in epochs from 0 to 200 ms after the stimulus. A total of 200 stimulus-related epochs were recorded for each measurement. Latencies and the peak-to-peak amplitude of the N20-P25 response component, which is assumed to be generated in the SI, were measured and compared before and after each intervention. In addition to an analysis of the raw amplitude data, paired-pulse suppression Alectinib was expressed as a ratio of the amplitude (P2/P1) of the second peak (P2) over the amplitude of the first peak (P1) (Fig. 1). Tactile two-point discrimination of the index fingers was assessed using a method of constant stimuli, as described previously

(Godde et al., 2000; Pleger et al., 2001; Dinse et al., 2003b). We used a specifically designed apparatus that allows a standardized and objective form of testing. In brief, seven pairs of rounded needle probes (diameter 200 μm), with separation distances between 0.7 and 2.5 mm in 0.3-mm steps, were used. Each distance Selleck MI-503 was presented eight times in a randomized order, resulting in 64 single trials per session. Subjects were aware that there were single needle-probe

stimuli presented, but not how often they would be presented. As a control, zero distance was tested using only a single needle probe. The number of single-needle presentations was 1/8, i.e. eight presentations in one session. The probes were mounted on a rotatable disc that allowed for rapid switching between distances. To accomplish a uniform and standardized stimulation, the disc was installed in front of a plate that could be moved up and down. The arm and fingers of subjects were fixed on the plate, which was moved up and down by

the experimenter. The down movement was arrested by a stopper at a fixed position above the probes (Fig. 2A). The test finger (index finger, or d2) was held in a hollow containing a small hole (diameter, 15 mm), through which the distal phalanx of the finger came to touch the probes, at approximately the same indentations in each trial. The probes were always presented parallel to the fingertip. Subjects had to decide immediately after touching the probes whether they had the sensation of touching one or two tips, simply by answering ‘one’ or ‘two’. After each session, individual discrimination thresholds were calculated. Sunitinib cell line The summed subject’s responses (‘1’ for one tip and ‘2’ for two tips) were plotted against the tip distance as a psychometric function, and were fitted with a logistic regression method (SPSS version 10.01). Thresholds as a marker for individual tactile performance were defined as the point at which a 50% correct response rate was obtained (Fig. 2B). In addition to analysing the two-point discrimination thresholds, we calculated the signal detection d′ index to control for response bias, which we report together with false alarm and hit rates.

These studies identified the very C-terminal end of TraB forming a wHTH fold as being responsible for clt recognition. Further studies even narrowed down the TRS recognition region to helix α3 of the wHTH fold. Exchange of only 13 aa of TraBpSVH1 against the 13 aa corresponding to helix α3 of TraBpIJ101 switched clt recognition. The chimeric protein was no longer able to bind to the clt of pSVH1 but shifted the clt fragment of pIJ101 (Vogelmann et al., 2011a). Generation of pock structures during Streptomyces conjugation has been interpreted as the result of selleck compound intramycelial plasmid

spreading following the primary DNA transfer from a donor into the recipient (Hopwood & Kieser, 1993; Grohmann et al., 2003). Whereas plasmid transfer from a donor into the recipient requires only TraB, plasmid spreading involves five to seven plasmid-encoded proteins (Spd) in addition

to TraB. This probably reflects the challenge to cross the septal cross-walls. The Spd proteins have no significant similarity to any functionally characterized protein complicating prediction PD0325901 chemical structure of their putative function. Inactivation of a single spd gene reduces the size of the pock structures (Kieser et al., 1982; Kataoka et al., 1994; Servin-Gonzalez et al., 1995; Reuther et al., 2006a). Only few reports address the biochemical characterization of the Spd proteins and their molecular function is more or less unknown. Genetic organization of the spd genes with overlapping stop and start codons, analysis of protein–protein interaction by chemical crosslinking,

bacterial two-hybrid analysis or copurification experiments indicated that the Metalloexopeptidase Spd proteins form a multiprotein complex with TraB (Tiffert et al., 2007) (Thoma, Guezguez and Muth, unpublished). Intramycelial plasmid spreading might also contribute to the stable maintenance of Streptomyces plasmids, because hyphal compartments that have lost a plasmid can recover a plasmid from the neighbouring compartment. In agreement with this hypothesis, a clear effect of spd1 inactivation on stable maintenance of the linear plasmid SLP2 was reported (Hsu & Chen, 2010). Streptomyces plasmids contribute to the evolution and shaping of the chromosome in different ways (Medema et al., 2010). Linear plasmids can recombine with the chromosome. Because the Streptomyces chromosome is normally linear (Lin et al., 1993), this results in the exchange of the ends, creating plasmids that carry chromosomal DNA. These plasmids can be transferred by conjugation to new Streptomyces species, where they can replicate either autonomously or recombine again with the chromosome. But also circular plasmids have been reported to mobilize chromosomal fragments with high efficiency (Kieser et al., 1982; Hopwood & Kieser, 1993).