text:
Randomized trial of three rapamycin-eluting stents with different coating strategies for the reduction of coronary restenosis
Aims The objective of this study was to assess the non-inferiority, in terms of anti-restenotic efficacy, of both biodegradable-polymer (BP) and polymer-free (PF) stents compared with permanent-polymer rapamycin-eluting (PP; Cypher) stent.
Methods and results Patients with de novo coronary lesions in native vessels were randomly assigned to receive a BP stent, a PF stent or a PP stent. The primary endpoint was in-stent late lumen loss at follow-up angiogram.
A total of 605 patients were enrolled: 202 patients received BP stents, 202 were treated with PP stents, and 201 received PF stents. Repeat angiography was available for 492 patients (81.3%). Mean late lumen loss at 6–8-month angiographic follow-up was 0.17 ± 0.45 mm in the BP stent group, 0.23 ± 0.46 mm in the PP cohort, and 0.47 ± 0.56 mm in the PF stent group. The BP stent met pre-specified criteria for non-inferiority (P < 0.001), whereas the PF stent did not (P = 0.94). There were no differences in safety outcomes.
Conclusion Both BP and PF stents have a 1-year safety profile similar to that of the PP stent. Whereas the PF stent provided an inferior efficacy, the BP stent is at least as effective as the PP stent in terms of anti-restenotic efficacy.
- Biodegradable
- Coronary restenosis
- Drug-eluting stents
- Polymer
- Rapamycin
Drug-eluting stents (DES) represent a breakthrough technology that has profoundly impacted the treatment of coronary artery disease.1,2 Their working principle consists of the local delivery of pharmacological agents with cytostatic or anti-mitotic properties at the implantation site, which leads to the suppression of neointimal proliferation, the main cause of lumen re-narrowing after stent implantation. Most DES are composed of the stent platform, anti-restenotic agent, and its carrier vehicle, most frequently a polymer, which serves for drug-loading and modification of release kinetics. Several pharmacological agents and different types of polymers, either durable or resorbable, have been employed. A large number of studies including patients with various clinical and angiographic characteristics have shown that DES markedly reduce restenosis risk, which has constituted the major limitation of long-term success of bare metal stents.3–9 The most studied DES are the rapamycin-eluting stent – Cypher - and the paclitaxel-eluting stent – Taxus - both of which use durable polymers. Although their mid-term efficacy has been well-established, there is an ongoing debate on the potential for an increased incidence of late-stent thrombosis,10–13 particularly after discontinuation of thienopyridine therapy, as well as on delayed onset of restenosis or DES "catch-up" phenomenon.14 Based on animal and human pathological data, investigators have linked the above-mentioned concerns to the presence of polymers in DES, which have proinflammatory and thrombogenic potential, and sometimes may induce a hypersensitivity reaction.15–21
Two strategies have been proposed and evaluated to avoid the potential negative influence of durable polymers in DES. One of these consists of the utilization of biodegradable-polymers (BPs) as a means for storage and controlled release of incorporated drugs. Although early work suggested little difference between non-BP and BP in terms of the inflammation response in the acute phase,15 their absorption after the completion of the elution process (typically 6–9 weeks), removes the potential nidus for inflammation and thrombogenicity over the medium to long-term. The first reports have shown promising results with DES using BPs in terms of their anti-restenotic efficacy.22,23 The second strategy consists of the utilization of polymer-free (PF) DES platforms. In this regard, it was recently shown that PF stents eluting rapamycin were effective in reducing neointimal hyperplasia and angiographic restenosis.24–26 At present, there are no data on the relative efficacy of DES which use the same pharmacological agent but differ with respect to the presence or type of polymers used.
We hypothesized that in patients treated with coronary stenting for de novo lesions located in native coronary vessels, rapamycin-eluting stent platforms—both PF and using BP—would have an equivalent effectiveness to the commercially available permanent-polymer (PP) rapamycin-eluting Cypher stent which is the current gold standard for the prevention of restenosis.
Study population and protocol
Patients older than age 18 with ischaemic symptoms or evidence of myocardial ischaemia in the presence of ≥50% de novo stenosis located in native coronary vessels were considered eligible, provided that written, informed consent by the patient or her/his legally authorized representative for participation in the study was obtained. Patients with a target lesion located in the left main stem or in a bypass graft, in-stent restenosis, acute myocardial infarction (MI), cardiogenic shock, malignancies or other co-morbid conditions (e.g. severe liver, renal, and pancreatic disease) with life expectancy <12 months or that may result in protocol non-compliance, known allergy to the study medications (aspirin, clopidogrel, rapamycin, stainless steel), pregnancy (present, suspected or planned), or positive pregnancy test were considered ineligible for the study. The study protocol was approved by the institutional ethics committee responsible for both participating centres, the Deutsches Herzzentrum and the Medizinische Klinik I, Klinikum rechts der Isar, Munich, Germany. All patients gave their written, informed consent for participation in the study.
In each participating centre, allocation to treatment was made by means of sealed, opaque envelopes containing a computer-generated sequence; randomization was performed immediately after decision to proceed with percutaneous coronary intervention (PCI). Patients who met all of the inclusion criteria and none of the exclusion criteria were randomized in the order that they qualified. Patient allocation to each of the three treatment groups was in equal proportions. The three treatment groups were studied concurrently. Time zero was defined as the time of randomization. Patients were considered enrolled in the study at the time of randomization. The same randomly assigned stent had to be implanted in all lesions in those patients who required stenting in multiple lesions and the use of more than one stent per lesion was also allowed. Patients were assigned to receive the BP 0.4% rapamycin stent (180 µg rapamycin/cm2), the PF 2% rapamycin (479 µg rapamycin/cm2) stent, or the PP rapamycin-eluting stent (Cypher stent, Cordis; 140 µg rapamycin/cm2). The stent platform used for the BP and PF arms consists of a premounted, sand-blasted, 316L stainless steel microporous stent and the coating device. A detailed description for creating the micropores and its rationale, as well as the specifics of the coating process involved, have been reported previously.24,27 The BP matrix used in the BP stent arm is completely resorbed within ∼6–9 weeks. The PF stent is coated with rapamycin without employing synthetic polymers. The rapamycin release profile of both the BP and PF stent platforms are shown in Figure 1. The elution characteristics of the PP stent are reported elsewhere.3,16
An oral loading dose of 600 mg clopidogrel was administered to all patients at least 2 h prior to the intervention, regardless of whether the patient was taking clopidogrel prior to admission. During the procedure, patients were given intravenous aspirin, heparin or bivalirudin; glycoprotein IIb/IIIa inhibitor usage was at the discretion of the operators. After the intervention, all patients received 200 mg/day aspirin indefinitely, clopidogrel 150 mg for the first 3 days (or until discharge) followed by 75 mg/day for at least 6 months and other cardiac medications according to the judgment of patient's physician [e.g. ß-blockers, ACE (angiotensin-converting enzyme)-inhibitors, statins, etc.]. After enrolment patients remained in hospital for at least 48 h. Blood samples were drawn every 8 h for the first 24 h after randomization and daily afterwards for the determination of cardiac markers (CK, CK-MB, Troponin T or I) and blood cell counts (haemoglobin, haematocrit, platelet count, white blood cell count). Daily recording of ECG was also performed until discharge. The occurrence of in-hospital bleeding or need for blood product transfusion was also monitored. All patients were evaluated at 1, 9, and 12 months by phone or office visit. Re-hospitalization for repeat coronary angiography was scheduled for 6–8 months.
Data management, endpoints, and definitions
Relevant data were collected and entered into a computer database by specialized personnel of the Clinical Data Management Centre. Clinical events were adjudicated upon by the Clinical Event Adjudication Committee. Patients were blinded to treatment allocation. The interventionalist performing the procedure was blinded to treatment allocation arm if the patient received a BP or PF stent, though not if a PP (Cypher) stent was implanted (due to distinctive packaging of this commercially available stent). Endpoint adjudication and quantitative coronary angiography analysis was fully blinded to randomly assigned stent type.
In the case of patients requiring multiple lesion intervention, the same assigned stent had to be implanted at each site. Baseline, post-procedural, and follow-up coronary angiograms were digitally recorded and assessed off-line in the quantitative angiographic core laboratory (Deutsches Herzzentrum ISAR Centre) with an automated edge-detection system (CMS version 7.1, Medis Medical Imaging Systems) by two independent experienced operators unaware of the treatment allocation. All measurements were performed on cineangiograms recorded after the intracoronary administration of nitroglycerin using the same single worst-view projection at all times. The contrast-filled non-tapered catheter tip was used for calibration. Quantitative analysis was performed on both the 'in-stent' and 'in-segment' area (including the stented segment, as well as both 5-mm margins proximal and distal to the stent). Qualitative morphological lesion characteristics were characterized by standard criteria.28
The primary endpoint of the study was in-stent late luminal loss, defined as the difference between the minimal luminal diameter at the end of the procedure and the minimal luminal diameter at follow-up angiography. Secondary endpoints were: in-segment binary angiographic restenosis (defined as diameter stenosis ≥50% in the in-segment area) at follow-up angiography; need for target lesion revascularization (TLR), defined as any revascularization procedure involving the target lesion due to luminal re-narrowing in the presence of symptoms or objective signs of ischaemia; the combined incidence of death or MI; incidence of stent thrombosis. The diagnosis of MI required the presence of new Q-waves on the ECG and/or elevation of creatinine kinase or its MB isoform to at least three times the upper limit of normal in no fewer than two blood samples. Restenosis morphology is categorized as described by Mehran et al.29 Stent thrombosis was classified according to recently agreed Academic Research Consortium criteria.30
Statistical analysis
The objective of the study was to assess the non-inferiority of both BP and PF stents to PP stents. Sample size calculation was based on a margin of non-inferiority for in-stent late luminal loss set at 0.16 mm for both comparisons.31 The assumed common standard deviation (SD) was 0.5 mm. This threshold allowed for the preservation of 80% of reduction in late lumen loss observed previously with rapamycin-eluting stent compared with bare-metal stent.6 With a power of 80% and a one-sided α-level of 0.025 due to two pre-specified comparisons, we estimated that 155 patients in each of the three groups were needed to show the non-inferiority of BP and PF stents. Expecting that up to 20% of patients would not return for follow-up angiography, we aimed to enrol a total of 600 patients (200 in each treatment arm). Sample size calculation was performed with nQuery Advisor (Statistical Solutions, Cork, Ireland) according to the method described by O′Brien and Muller.32 The analysis of primary and secondary endpoints was planned to be performed on an intention-to-treat basis. Although in a non-inferiority design, a per protocol analysis may be considered of equal importance, this issue is not of relevance where cross-over does not occur. The data are presented as means ± SD, or counts or percentages. The non-inferiority hypothesis was tested with EquivTest (Statistical Solutions, Cork, Ireland) according to the methods described by Chow and Liu.33
Baseline characteristics and procedural results
A total of 605 patients were enrolled in this study: 202 patients received the rapamycin stent with BP, 202 were treated with a PP rapamycin stent, and 201 received a PF rapamycin stent. Baseline clinical characteristics are shown in Table 1. Overall 27.4% of patients had diabetes mellitus. In all 712, lesions were treated. Lesion characteristics are shown in Table 2 and are notable for a high proportion of lesions with complex morphology, overall 74.1%. The treatment groups were well matched in terms of lesion and procedural characteristics (Table 3). Implantation of the assigned stent was successful in all patients. Study patient flow chart is shown in Figure 2.
|Overall (n = 605)
|Biodegradable polymer (n = 202)
|Permanent polymer (n = 202)
|Polymer-free (n = 201)
|480 (79.3)
|158 (78.2)
|165 (81.7)
|157 (78.1)
|Age (years), mean ± SD
|66.1 ± 10.7
|66.5 ± 11.6
|65.0 ± 10.7
|66.8 ± 9.70
|27.1 ± 4.0
|27.4 ± 4.1
|26.9 ± 3.9
|27.2 ± 4.2
|166 (27.4)
|58 (28.7)
|53 (26.4)
|55 (27.2)
|410 (67.8)
|145 (71.8)
|130 (64.4)
|135 (67.2)
|Current smoker
|99 (16.4)
|33 (16.3)
|30 (14.9)
|36 (17.8)
|416 (68.8)
|144 (71.3)
|129 (63.9)
|143 (71.1)
|Coronary disease
|Single vessel
|105 (17.4)
|35 (17.3)
|27 (13.4)
|43 (21.4)
|Two vessel
|169 (27.9)
|54 (26.7)
|63 (31.2)
|52 (25.9)
|Three vessel
|331 (54.7)
|113 (56.0)
|112 (55.4)
|106 (52.7)
|Multivessel disease
|500 (82.6)
|167 (82.7)
|175 (86.6)
|158 (78.6)
|Unstable angina
|187 (30.9)
|64 (31.7)
|59 (29.2)
|64 (31.8)
|Previous MI
|199 (32.9)
|65 (32.2)
|68 (33.7)
|66 (32.9)
|Prior bypass surgery
|69 (11.4)
|21 (10.4)
|21 (10.4)
|27 (13.4)
Values shown are number (percentage) unless otherwise indicated.
BMI, body mass index; MI, myocardial infarction.
|Overall (n = 712)
|Biodegradable polymer (n = 239)
|Permanent polymer (n = 242)
|Polymer-free (n = 231)
|EFa (%), mean ± SD
|54.1 ± 12.1
|53.8 ± 11.6
|54.9 ± 11.0
|53.5 ± 13.6
|Target vessel
|306 (43.0)
|110 (46.0)
|104 (43.0)
|92 (39.8)
|190 (26.7)
|53 (22.2)
|69 (28.5)
|68 (29.5)
|216 (30.3)
|76 (31.8)
|69 (28.5)
|71 (30.7)
|185 (26.0)
|55 (23.0)
|73 (30.2)
|58 (25.1)
|Total occlusion
|55 (7.7)
|18 (7.5)
|22 (9.1)
|15 (6.5)
|Complex morphologyb
|528 (74.1)
|170 (71.1)
|186 (77.2)
|172 (74.2)
Values shown are number (percentage) unless otherwise indicated.
EF, ejection fraction; LAD, left anterior descending artery; LCX, left circumflex artery; RCA, right coronary artery.
aData available for 539 (89.5%) of patients.
bDefined as type B2/C by AHA/ACC classification.
|Overall (n = 712)
|Biodegradable polymer (n = 239)
|Permanent polymer (n = 242)
|Polymer-free (n = 231)
|Lesion length
|14.3 ± 6.5
|13.9 ± 7.2
|14.6 ± 7.0
|14.3 ± 5.1
|Reference diameter
|2.75 ± 0.49
|2.74 ± 0.52
|2.75 ± 0.51
|2.75 ± 0.45
|MLD, pre-procedure
|1.11 ± 0.44
|1.06 ± 0.42
|1.13 ± 0.49
|1.13 ± 0.39
|Stenosis, pre-procedure
|59.9 ± 13.2
|61.5 ± 12.8
|59.3 ± 14.5
|58.8 ± 12.1
|Maximum balloon diameter
|3.02 ± 0.49
|3.00 ± 0.51
|3.05 ± 0.52
|3.03 ± 0.42
|Balloon-to-vessel ratio
|1.11 ± 0.09
|1.10 ± 0.08
|1.11 ± 0.10
|1.11 ± 0.10
|MLD, post (in-stent)
|2.55 ± 0.46
|2.51 ± 0.48
|2.56 ± 0.46
|2.59 ± 0.42
|Stenosis, post (in-stent)
|10.7 ± 5.6
|10.9 ± 5.3
|10.2 ± 5.9
|11.0 ± 5.4
|MLD, post (in-segment)
|2.21 ± 0.53
|2.19 ± 0.54
|2.20 ± 0.53
|2.26 ± 0.52
|Stenosis, post (in-segment)
|22.9 ± 10.9
|22.6 ± 11.1
|23.4 ± 10.4
|22.7 ± 11.2
Data are shown as mean ± SD.
MLD, minimal luminal diameter.
Angiographic outcomes
Of 605 patients, 492 re-attended (81.3%) for follow-up angiography. There were no significant differences in follow-up rates between the treatment groups. With respect to the primary endpoint, mean late lumen loss at 6–8-month angiographic follow-up was 0.17 ± 0.45 mm in the cohort who received a BP stent, 0.23 ± 0.46 mm in those receiving a PP stent, and 0.47 ± 0.56 mm in patients treated using a PF stent (Figures 3 and 4). As a consequence, the BP stent met criteria for non-inferiority (P < 0.001), whereas the PF stent did not (P = 0.94) (Figure 5). As we adjusted our significance level for multiple comparisons, a one-sided α-level of 0.0125 may have been more appropriate for this non-inferiority analysis. We did perform a separate analysis of the data using such intervals and found no impact on the overall results (the upper one-sided 98.75% confidence interval for the difference was 0.03 mm for the BP stent and 0.37 mm for the PF stent).
In terms of secondary endpoints, there was a trend towards inferiority in terms of binary angiographic restenosis in-segment with the PF stent compared with the PP stent (Figure 6). This trend was not seen between the BP and PP stents. The distribution of patterns of restenosis observed across treatment arms is included in Table 4.
|Biodegradable polymer (n = 199)
|Permanent polymer (n = 195)
|Polymer-free (n = 183)
|MLD, in-stent (mm)
|2.34 ± 0.66
|2.34 ± 0.63
|2.12 ± 0.64
|MLD, in-segment (mm)
|2.01 ± 0.61
|1.97 ± 0.60
|1.90 ± 0.64
|Stenosis, in-stent (%)
|18.1 ± 17.0
|19.1 ± 17.3
|24.7 ± 19.5
|Stenosis, in-segment (%)
|29.6 ± 15.8
|32.1 ± 16.0
|33.0 ± 18.4
|LLL, in-stent (mm)
|0.17 ± 0.45
|0.23 ± 0.46
|0.47 ± 0.56
|LLL, in-segment (mm)
|0.18 ± 0.48
|0.23 ± 0.52
|0.35 ± 0.54
|Restenosis, in-stent, n (%)
|12 (6.0)
|13 (6.7)
|24 (13.1)
|Restenosis, in-segment, n (%)
|18 (9.0)
|21 (10.8)
|31 (16.9)
|Focal margin
|Focal body
|Diffuse intra-stent
Data are shown as mean ± SD unless otherwise stated.
LLL, late luminal loss; MLD, minimal luminal diameter.
Clinical outcomes
There were no significant differences in terms of early safety outcomes. Two patients treated with a PF stent suffered early complications. One patient required repeat PCI and another required surgical revascularization. At 30 days the combined endpoint of death or MI had occurred in three (1.5%), two (1.0%), and four (2.0%) of the patients treated with BP, PP, and PF, respectively.
One-year follow-up was complete for the study cohort (Table 5). There was a clear trend towards an excess of TLR procedures in the PF stent group with 26 cases as opposed to 16 in the PP group and 12 in the BP group. The incidence of death, non-fatal MI, and stent thrombosis was similar across all the three treatment arms (Tables 5 and 6).
|Biodegradable polymer (n = 202)
|Permanent polymer (n = 202)
|Polymer-free (n = 201)
|3 (1.5)
|4 (2.0)
|5 (2.5)
|of which Q-wave
|1 (0.5)
|1 (0.5)
|4 (2.0)
|4 (2.0)
|4 (2.0)
|5 (2.5)
|7 (3.5)
|8 (4.0)
|12 (5.9)
|16 (7.9)
|26 (12.9)
|1 (0.5)
|3 (1.5)
|3 (1.5)
|11 (5.4)
|14 (7.0)
|23 (11.4)
Values shown are number (percentage).
CABG, coronary artery bypass grafting; MI, myocardial infarction; PCI, Percutaneous coronary intervention; TLR, target lesion revascularization.
|Biodegradable polymer (n = 202)
|Permanent polymer (n = 202)
|Polymer-free (n = 201)
|0 (0.0)
|1 (0.5)
|2 (1.0)
|1 (0.5)
|0 (0.0)
|0 (0.0)
|1 (0.5)
|3 (1.5)
|1 (0.5)
|2 (1.0)
|4 (2.0)
|3 (1.5)
Definite: acute coronary syndrome with angiographic or autopsy evidence of thrombus or occlusion, probable: unexplained deaths within 30 days following coronary intervention or acute myocardial infarction involving the target vessel without angiographic confirmation, possible: any unexplained death >30 days post intervention.
In this prospective, randomized trial, we assessed the relative efficacy of PF and BP rapamycin-eluting microporous stents, with standard commercially available PP-based rapamycin stents (Cypher). The study population comprised a cohort of patients with complex coronary lesions (74.1% AHA/ACC type B2/C) and a high prevalence of diabetes mellitus (27.4%). The salient outcomes of our study are that (i) the treatment of complex de novo coronary lesions in native vessels with both BP and PF rapamycin stents is feasible and safe; (ii) in comparison with the PP rapamycin-eluting stent, a BP rapamycin-eluting stent shows equivalent anti-restenotic efficacy in terms of the primary endpoint of in-stent late luminal loss, whereas a PF rapamycin stent is associated with significantly higher luminal loss at follow-up angiography; and (iii) in terms of clinical outcomes, there was a trend towards an excess of TLR procedures at 12 months with the PF platform as compared with the PP platform. This parallels the differences seen in late luminal loss.
Several components of a DES platform contribute to its clinical efficacy, most notably stent design, active drug and the presence and type of polymer. We have previously shown that employing a rapamycin coating on a microporous PF stent platform results in superior clinical and angiographic outcomes than bare metal stent implantation and that a dose response exists up to 2% rapamycin.24,25 Furthermore, when this model was compared against a commercially available paclitaxel-eluting PP stent (Taxus) in a group of patients with similarly complex disease to this current cohort, outcomes were equivalent.26 In this current study, however, this platform proved inferior in terms of anti-restenotic efficacy, when compared with the PP stent. It seems clear that this significant inferiority is due to the use of a superior comparator (PP rapamycin stent) as the late luminal loss in the PF group was almost identical to that observed previously with this stent.26
In terms of choice of active drug for an optimal DES platform there is an accumulating literature suggesting a drug-specific effect in favour of rapamycin. There is well-documented evidence that rapamycin and paclitaxel differ significantly in terms of their anti-restenotic efficacy and cellular and molecular properties.34–37 In addition, a number of meta-analyses have confirmed that a potential safety and efficacy differential may exist in favour of sirolimus-eluting stents when compared with paclitaxel-eluting stents.5,38,39
The significant improvement in anti-restenotic efficacy derived from the delay in rapamycin release associated with the addition of a novel BP is noteworthy. An optimal release kinetic for any anti-restenotic compound used on a DES platform has thus far not been defined. This study is the first to make use of a novel stent coating comprised of a BP combined with a natural resin. Our previous experience with the PF rapamycin stent has shown that two-thirds of the rapamycin is released in the first week after implantation with the remainder eluting over the next 2 weeks. The BP used in this study typically remains in situ for ∼6–9 weeks thereby delaying rapamycin release and enhancing primary stent efficacy. On the other hand, its absence from the vessel wall after this period removes a putative nidus for persistent inflammation and thrombosis. The potential safety implications both in terms of a reduced incidence of late acute stent thrombosis and an obviation of the need for prolonged thienopyridine therapy (and its attendant bleeding risks) are obvious and the concept inherently attractive.40 Previous preliminary experience using a BP on an everolimus-eluting stent was positive.22 Our trial, however, is the first to study a novel BP on this current DES platform and indeed the first to assess efficacy of such a model in a cohort of patients with complex coronary lesions. In this regard, the results were certainly encouraging. The 1-year safety profile, like that of the PF platform, is equivalent to that of the PP stent. Acute luminal gain at the time of index procedure was very well maintained at angiographic follow-up with a late luminal loss of 0.17 ± 0.45 mm comparing very favourably with that of 0.23 ± 0.46 mm seen with the PP. There were no differences in the observed rates of stent thrombosis between the three groups at 1-year follow-up. Whether the absence of PP from the coronary milieu over the mid- to long-term translates into significant differences in clinical outcomes remains to be seen.
Limitations of the study
This trial was not powered to detect differences in delayed clinical outcomes and clinical outcome data must be interpreted with this in mind. At this current time point, follow-up is only available for 1 year. Definitive assessment of the long-term performance of these novel platforms, and indeed of the accruement of potential clinical advantage in terms of a reduction in late thrombotic events, should be the objective of future studies. We should acknowledge the limitation that as we adjusted our significance level for multiple comparisons, a one-sided α of 0.0125 may have been more appropriate for this non-inferiority analysis. We did perform a separate analysis of the data using such significance levels (which we have reported in the results section) and found no impact on the overall results. The analysis of primary and secondary endpoints was planned to be performed on an intention-to-treat basis. We recognize the limitation of absence of angiographic follow-up in 18.3% of patients. Such a limitation is a feature of studies utilizing a primary angiographic endpoint. This is at least in part extenuated by the compatibility of findings from our secondary endpoint analysis, including TLR—an index of clinical restenosis—for which data were available on all patients.
In conclusion, we have demonstrated that in a cohort of patients with complex coronary lesion morphology, the implantation of both novel PF and BP DES platforms is feasible and that the 1-year safety data are similar to that of the Cypher stent. Whereas the PF rapamycin-eluting stent provided an inferior efficacy in terms of the primary endpoint of late luminal loss, the BP-based rapamycin-eluting stent is at least as effective as the Cypher stent. Definitive assessment of performance durability and the accruement of potential clinical advantage associated with the removal of PP from the coronary vessel wall will require further investigation.
Conflict of interest: R.A.B. was supported by a grant from the Irish Board for Training in Cardiovascular Medicine which was sponsored by A. Menarini Pharmaceuticals (Ireland). A.K. reports having received lecture fees from Bristol-Myers, Cordis, Lilly and Sanofi-Aventis. No other conflicts of interest declared.
Study design and analysis were performed by Deutsches Herzzentrum, Munich, and funding was completely industry independent, provided in part by the Bavarian Research Foundation (BFS-ISAR Aktenzeichen AZ: 504/02 and BFS-DES Aktenzeichen AZ: 668/05).
- Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: email@example.com
The above article uses a new reference style being piloted by the EHJ that shall soon be used for all articles.


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Home > Sunglasses > Polo > PH4093 (550213)
PH 4093 is available in 3 additional attractive styles
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Size and availability
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Free outbound and return shipping
30-day money-back guarantee
Low prices
PH4093/550213 Ophthalmic Glasses
PH4093 is a fashion statement, for which sunshine is not necessarily required, because these sunglasses enhance your natural radiance turning night into day. Would another colour not be a better match for your favourite outfit? Check also the other styles of PH4093in our 2015, and 2016 Polo range.
Expressive lines add character to the classical approach, making the glasses a must-have for women. Wearing full rim eyewear, you make it unmistakably clear that you are going the whole hog. The square frame is a classical shape, highlighting the straightforwardness of the personality. Plastic frames like these combine durability and are comfortable to wear. The PH4093 is a very snug fit on the ears and nose. Brown is the perfect alternative for those who find black too high in contrast. Brown flatters the face unobtrusively. Similar to grey, brown lenses don't distort the visual impression as much as other colours do. With all other shades, the eyes take longer to neutralize the colour impression. You can rely on the guaranteed UV400 protection, for all the sunglasses in our shop.
If you press the button "order with prescription lenses', our digital dispensing optician will install the lenses in the original tint or as you wish. Your dioptre values are the only thing we require from you.
The model has already been ordered and will shortly be back in stock. If you order now, you will get the reduced price and once the goods arrive, we will send you your new Polo on the same day. And because Edel-Optics is a paradise for bargain hunters, you can get this top model at an incredibly low price. What is labelled as "in the sale" at other online shops, is for us "all-day-everyday" prices.
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Discover safe paths while traveling through different realities! You will switch back and forth between different times to find the special key. When you clear paths in one reality, you will open doors to another. Shape time into the path you desire!
The Suspense II is one of our selected Thinking Games. Also very popular on this website right now are Save the Pig, Candy Crush Pro, Blockoomz 2015 and Gorillaz Tiles.
Report game as broken
Cancel report of broken game


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New Yorker Elliot Madison recently was charged with Hindering Apprehension and other crimes for using Twitter to inform protestors about police movements during anti-G-20 Summit demonstrations in Pittsburgh. Police found Madison and another protestor allegedly directing their comrades via computer in a suburban Pittsburgh hotel room on the first day of the Summit.
As a Reuters freelancer I covered some of the protests, and I'm wondering why police were allowed to hinder my comprehension of what was happening. Their RoboCop-sounding message threatened everyone present with arrest and physical action by officers, and warned:
"No matter what your purpose, you must disperse."
Blasted over a military-issue PA system that was mounted atop an armored police vehicle, the message was serious enough for many journalists to lose enthusiasm for the humid march on G-20 Day One. Just after that day's first protestor-police clashes, a large Wall Street Journal reporter huddled close to a couple in their yard as riot police stormed past.
"They can't arrest you on private property," he said to me.
"We're protecting him," the couple said.
Later, at 5 p.m., after more than two hours of cat-and-mouse between protestors and officers, police again chased protestors—this time, ironically, near Liberty Avenue, in Pittsburgh's Bloomfield section.
"Get out of the street!" a shotgun-armed officer shouted at a CNN journalist near him. She collapsed on her haunches.
I was nervously reporting on the scene, while trying to evade police. Several journalists weren't as lucky and were arrested during the protests. But dodging the cops while trying to work made me wonder how we can hinder or stop reporters from covering news and still have a truly free press.
Police texted each other during the G-20 marches, protestors tweeted one another and reporters texted and phoned their peers while being threatened for doing so. The Internet has changed the political game, but our law officers, and our laws, are slow to reflect the anarchic freedom and immediacy of the Texting Age.
Even so, you can't harass, threaten and arrest journalists for covering news, then say you have a free press. When journalists cannot freely report news happening on the street, those scenes will lack objective eyewitnesses to give the details of what happened. Without journalists covering such incidents, whose job will it be to tell the entire truth about them?


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Import and export users from/to CSV files, supports all WordPress profile data also Cimy User Extra Fields plug-in.
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The Pope
Joye R, June 2015
This is how close you get.
Papal Audience with Pope Benedict XXVI
Maybeth R, April 2011
I took this at the end when everybody had left. If you're patient, you're going to be able to be this close. Photo taken WITHOUT zoom.
Pope Frances up close
Silvia G, September 2016
Pope Francis
Audiencia con el Papa
fede, August 2016
Audiencia con el Papa
Papal Audience
Dennis L, July 2016
Pope Francis I blessing a baby
fontaine de trévi
FAYARD M, June 2016
Fontaine de trévi
Pope Francis 2016
Vicki, June 2016
We were about 30 feet from the pope!


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2 Reviews
Damn good!!!!
This is quite different and delicious. I didn't have chili oil, but I did have some chili-infused vinegar, so I used that in place of the chili oil and rice vinegar. Cooked it in the broiler, not on the grill, and served it with brown rice and broccoli. Family says thanks, and so do I. Good stuff.


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Funeral services for Mr. Lonnie Grady Johnson, 87, the devoted husband of Sarah Burnett Johnson; caring and loving father of El Wanda J. Bradsher (Alfred), Jean J. Shoffner (Lemuel), Sandra J. Brooks (Carlton), Glenda J. Jones and Marilyn Johnson; supportive brother to: Joe Johnson (Mildred), Leon Johnson, "Cedell" Johnson, Dorothy Crutchfield, Barbara Green, Carolyn Stroud (Raymond), Yvonne Johnson and Helen Alston (Jack); loving PaPa to 14 grands, 39 great-grands and 2 great-great-grands; will be held on Saturday, June 11, 2016 from the sanctuary of Burnette Chapel Church of Christ at 1:00pm with the family greeting relatives and friends from 12:30 until 1:00pm. Committal ceremony and the act of Interment will follow the services in the church cemetery.
Mr. Lonnie Grady Johnson
Tony A. Daye Jr
Dateline: Burlington
Name: Mr. Tony A. Daye, Jr.
Age: 21
Date and Place of Death: May 31, 2016 at Cone Health – Alamance Regional
Funeral Arrangements: Funeral services will be conducted on Sunday, June 6, 2016 at 2:00 pm at Sharpe Memorial Chapel with the family visitation from 1:30pm – 2:00pm. Public Viewing will be held on Saturday from 1-9pm.
Interment: North Lawn Cemetery
Mr. Earnest McDade Poteat
Mr. Earnest McDade Poteat was born in August 30, 1922 to the late Mr. John Poteat and the late Louellen Evans Poteat in Caswell County, NC. He departed this life on Friday, May 27, 2016 on the same farm in which he was born 93 years ago. He was preceded in death by his wife Odaris Daye Poteat as well as siblings: Roy Poteat, Willard Poteat, Hulon Poteat, Garland Poteat, Curtis Poteat, Nello Poteat, Philmo Poteat, Nellie Poteat Tyler and Odessa Poteat Rogers.
At an early age he joined Sweet Gum Grove Missionary Baptist Church. He attended the Sweet Gum Elementary School and later went on to the Caswell County Training School. He was drafted into the Army of the United States. During his enlistment he received training in the field of Agriculture. After serving his country, he worked in the industrial field for many years. He was a custodian at Walter Williams High School for several years. He loved farming and gardening. He especially loved his wife Odaris of 60 years as his children, grandchildren and family.
Earnest will be remembered and cherished by his three daughters: Elaine P. Brincefield and Janice P. Moore of Mebane, NC and Cheryl P. Shaw (Luther) of Burlington; two sons: Shelton Poteat (Pattie) and Earnest Glenn Poteat (Daphne) of Mebane; two siblings: W. Clarence Poteat of Philadelphia, Pa. and Clara S. Poteat of the home; a devoted nephew, Hulon Poteat of the home; sister-in-law: M. Frances Poteat of Burlington; 7 grandchildren, 10-great-grandchildren, 2 great-greatgrandchildren and a host of nieces, nephews other relatives and friends.
Mr. Andre' "Dre" Douglas Enoch
Mr. Andre Douglas Enoch age 63 on May 23, 2016, at the Hospice home of Alamance made his transition to be home with his Lord. He is the son to the late Mr. George Thomas Enoch and Mrs. Juanita Morgan Enoch who survives at the home.
Funeral Arrangements: Friday May 27, 2016 at 1 o'clock pm the services will be at Bethseda Baptist Church
Visitation: 12:00 to 1:00 pm on Friday prior to the service at the church. At other times the family will receive visitors at their home on 622 Apple St.
Public Viewing: Thursday rom 1-9 pm at Sharpe Funeral Home.
Burial: North Lawn Cemetery
Mr. Benjamin Franklin Lott
Mr. Benjamin Franklin Lott was born on November 16, 1935 in Ware County Georgia to the late Reverend John Lott and the late Mother Arizona Coleman Lott. He exchanged time for eternity on Friday, May 13, 2016 at the Hospice & Palliative Care Center of Alamance-Caswell.
Our dear and loving husband, father, grandfather and brother loved to garden and do landscaping and; was very good at it. He could beautify any lawn. Ben retired from many years of truck driving. He never lost his excitement talking about big rigs and loved discussing "the road" with family members who were also truckers. He enjoyed westerns, gospel music, fishing and playing the drums. Ben's easy smile and boyish laugh made everyone who met him feel at ease.
Ben was married to the late Jacqueline Sharon Adams Lott for 32 years. To this union 5 children were born: Melvin Adams (Ericka), Donna Adams, Theresa Lott, Andrea Ondieki, and Benjamin Franklin Lott, Jr. After her passing he met Vivian Fleming at Kernodle Senior Center in Burlington, in 2011. Then on December 7, 2012 at Elon First Baptist Church they were happily married. His passing has left a void that only God can fill, however we know that he is resting in God's care.
In addition to his wife Vivian and his children he is also survived by: grandchildren: Shakeilya Adams, Andre Adams Akira Adams, Alaysia Adams, Shaun Adams; siblings: Bishop John Lott (Jeanette), Albert Lott (Celestine), Missionary Geraldine Williams (Louis), Reverend Helen "Lois" McNarr (Reverend Willie McNarr) and Deacon Permmer Lee Lewis (Zack Lewis); his extended family, step-children: Min. Robin Sheppard, Kevin Sheppard (Angela), Deacon Eugene Sheppard (Jennifer), Min. Dawn Sheppard Branch (Glenn), Roahn Sheppard (Kim), Victoria Sheppard, Damon Sheppard (Linda), and Shonnell Sheppard (Holly) and several nieces, nephews other relatives and friends.
He was preceded in death by siblings: Banger Lott, Ruthia Anderson.
Funeral Arrangements: On Sunday, May 29, 2016 at 3 o'clock in the afternoon a Memorial service will be held for Benjamin Franklin at Sharpe Memorial Chapel.
Mr. David M. Adams
Mr. David Adams age 89 of 606 N. Fisher St. peacefully made his transition home on May 17, 2016, at the Hospice Home of Alamance-Caswell.
Funeral Arrangements: Funeral services will be held on Tuesday, May 24, 2016 at 2:00 pm at First Baptist Church. Visitation will be held Monday at 6:00 – 7:30 pm at First Baptist Church.
Public Viewing: Monday at Sharpe Funeral Home from 1:00 – 5:00 p.m. The body will lie in state at First Baptist Church from 12:00 – 2:00 pm on Tuesday prior to the service.
Burial: North Lawn Cemetery
Mr. Decatur Louis Fuller
Mr. Decatur Louis Fuller age 66 made his transition on May 17, 2016, from earth to glory. Mr. Fuller leaves to cherish his memory wife Mrs. Margaret Moore Fuller of the home, in Greensboro, NC. Other survivors include his sister Juanita Fuller Strobel (Richard). Mr. Fuller was preceded in death by both parents Mr. Richard Fuller and Mrs. Hazel Herbin Fuller Foster and a brother Levon Fuller.
Funeral Arrangements: Funeral services will be conducted on Monday, May 23, 2016 at 2:00pm at Gibsonville First Baptist Church. The family will greet friends from 1:30pm-2:00 pm prior to the service and at other times the family will be at 1603 Hannaford Rd. Public viewing will be on Sunday from 11am-9 pm at the funeral home.
Interment: Church Cemetery
Mr. Jerry Abney
Mr. Jerry Abney was born on November 4, 1958 to the late Mr. Frank Jr. Abney and the late Mrs. Clara Estelle Culbreathe Abney in Alamance County, North Carolina. After a brief illness, our loving brother and friend transitioned from earth to Glory on Friday, May 13, 2016 at the Cone-Health Alamance Regional Medical Center.
Jerry was a 1977 graduate of Hugh M. Cummings High School and was employed with Phillips Textiles for many years. He was kind and caring individual who would help anyone that he possibly could. He was a devoted member of Mt. Calvary Missionary Baptist Church where he served faithfully as a Trustee. Jerry loved fishing and maintaining a garden of vegetables and flowers. As far as sports were concerned, he enjoyed the St. Louis Rams (now the Los Angeles Rams) and the Los Angeles Lakers. We shall miss his presence here with us, but we know as long as we continue to call his name, he will forever be in our minds and hearts.
Left to cherish his memory and emulate his life are: brothers: Charlie Jr. Abney (Linda) and his twin Terry Abney; an uncle John D. Abney along with other relatives and dear friends.
He was preceded in death by two siblings: George Abney and Frankie Abney.
Funeral Arrangements: Funeral services will be conducted on Saturday, May 21, 2016 at 1:00 pm at Mt. Calvary Missionary Baptist Church. The family will greet friends from 12:30 pm-1:00 pm prior to the service. Public viewing will be on Friday from 1-9 pm at the funeral home.
Interment: North Lawn Cemetery
Mr. Willie Tom Tinnin "Tic-Tock"
Mr. Willie Tom Tinnin better known as "Tic-Tock" was born in Alamance County, NC to the late Mr. Arthur Tinnin and the late Mrs. Lucille Morrow Tinnin. He departed this life on April 20, 2016 at his home surrounded by his loved ones.
He was a graduate of Jordan-Sellars High School and was a longtime cook with Boston's Sandwich Shop and Carolina Sandwich Shop. He was known to be a talented singer.
He leaves to cherish his memories: his wife: Carolyn Jean Thompson Tinnin; children; Terry Tinnin, El Diego Tinnin, Xavier Tinnin (Toni) and Shirazette Tinnin ; sisters: Lillie Mae Tinnin, Catherine Tinnin Compton (Eugene), Peggy T. Faucette (Hulon), Geneva Pennington, Barbara Stone and Margaret Vincent (John); 6 grandchildren and 5 great-grandchildren along with a host of nieces, nephews other relatives and friends.
He now joins his parents, son Samiko Tinnin and siblings: Arthur O. Tinnin, Jr., Odell Tinnin, Othrel Tinnin and Lacy Tinnin what a happy reunion.
Funeral services are scheduled for Wednesday, April 27, 2016 at 1:00 pm with the family greeting relatives and friends from Noon until 1:00pm. The interment will follow the services in North Lawn Cemetery.
Mr. Isaac Henry Boyd
Isaac Henry Boyd was born in Cary, North Carolina on May 11, 1928 to the late Mr. Henry Boyd and the late Mrs. Othalia Webster Boyd. After a period of declining health, April 20, 2016 the arms of our Savior opened and welcomed him to his new home in eternity.
He was married to the love of his life, Mrs. Josie Ward Boyd who preceded him in death. He enjoyed working and providing for his family. In years past, he was a Chef, worked with Heater Well Drilling Company, Steel Mill worker, textile laborer with Burlington Industries and in retirement school system Crossing Guard.
Mr. Boyd was a devoted member of First Baptist Church Apple St. During his membership he was a faithful Usher and enjoyed singing with the Male Chorus. He was devoted to Christian living and desired others to do the same. His desire was for others to live the same way always serve God, love each other and always be ready to forgive.
Remembering him with love are: his children: five children: Vanessa Pennix (Ricky), Sheletha Boyd, Geneva Chandler, Ronald Morrison, Bobby Boyd; 6 grandchildren; 6 great-grandchildren; 3 great-great grandchild; 4 siblings: Preston L. Boyd, Margaret B. Britton, Mazie B. McDuffie, Frances B. Wall; an aunt: Nola Webster; a favorite niece and nephew: Glenda & Vincent Clark; sister-in-law: Mary Boyd a host of nieces, nephews along with several other relatives and dear friends.
He now joins his loving wife Josie, his parents Henry & Othalia; and siblings: Phillip Boyd, Marvin Boyd, Robert Boyd, Carlos Boyd, Viola Boyd and Inez Whitfield what a glorious reunion.
Funeral services will be held on Tuesday, April 26, 2016 at 1:00pm at First Baptist Church Apple St. with the family greeting relatives and friends thirty minutes prior to the services. The interment will follow the services in Mary's Grove Congregational Church Cemetery.


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A sound effect used when expressing sounds generated when whipping or slapping something or someone.
When Atong squeezed the pretty girl's butt, the last sound he heard was a resounding *WAPISH* as her hand made contact with his face.
ronnstein tarafından 7 Ocak 2007, Pazar
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Can you define these popular missing words?
high five
up hi..."wapish"....high five!
high cinco tarafından 22 Şubat 2011, Salı


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Forum indexSony Cyber-shot TalkChange forum
Sony Cyber-shot DSC-W130 review
Started Apr 20, 2008 | User reviews
Shop cameras & lenses ▾
Stephen • Contributing Member • Posts: 731
Sony Cyber-shot DSC-W130 review
Apr 20, 2008 • Review of Sony Cyber-shot DSC-W130
I bought the W130 and did some test shots,IQ excellent pin sharp out of the cam. ISO 400 is very good I feel it make a perfect P&S
LCD should have similar resolution as its bigger brother the W150
So far so good
8 megapixels • 2.5″ screen • 32 – 128 mm (4×)
Announced: Jan 23, 2008
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Fiction » EroticaSub-categories: BDSM | Contemporary | General | Menage/Multiple Partners | Gay Erotica | Women's Erotica | Couples Erotica | Paranormal | Men's Erotica | Romance | Lesbian Erotica | Erotica Anthologies | All sub-categories >>Action/Adventure | BDSM | Comedy/Humor | Contemporary | Couples Erotica | Erotica Anthologies | Gay Erotica | General | Historical | Historical/America | Historical/Ancient | Historical/Gothic | Historical/Greece | Historical/Medieval | Historical/Regency | Interracial | Lesbian Erotica | Literary Erotica | Men's Erotica | Menage/Multiple Partners | MILF | Paranormal | Romance | Sci-Fi Erotica | Suspense/Mystery | Westerns/Cowboys | Women's Erotica | << Top sub-categories
The Ultimate Bad Boy Collection: A Collection Full of Alpha Thugs, Hardcore Gangsters and bdsm by Lily Anderson
Price: $1.50 USD. Words: 41,750. Language: English. Published: May 1, 2016. Categories: Fiction » Erotica » BDSM, Fiction » Erotica » Erotica Anthologies
The Ultimate Bad Boys Erotica Collection: The alpha male erotica collection contains a set of three hardcore bad boy short stories chocked full of dark obsession, raw masculine lust and alpha male domination! Contains: Taken By Obsession Cheating with Him Gangster's Captive Read this collection to quench your dark BDSM Bad Boy Desires!
Mastered by the CEO by Opal Carew
Series: Mastered By, #4. Price: $2.99 USD. Words: 25,110. Language: English. Published: April 5, 2016 by Edge of Ecstasy. Categories: Fiction » Romance » Erotic, Fiction » Erotica » BDSM
From New York Times and USA Today Bestselling Author Opal Carew comes another sizzling BDSM erotic romance in the Mastered By series. Rachel knows her job is in trouble when her ex-lover and boss takes over her company. Is she willing to totally submit to him—in every way—in order to prove she'll no longer fight his every decision?
Butterfly Effect by Jill Elaine Hughes
Price: $2.99 USD. Words: 90,610. Language: English. Published: February 22, 2016. Categories: Fiction » Romance » Suspense, Fiction » Erotica » Suspense/Mystery
When we last left Nancy Delaney and Nancy Rostovich, they were on the run from violent criminal overlords in the former Soviet Union. Our hero Peter Rostovich is an elusive, enigmatic international artist/playboy, originally from the Ukraine, who may or may not have ties to the Russian/Ukrainian mafia. FIFTY SHADES meets John Le Carre.
Sissified for Science 1 & 2 (Sissification Feminization Short & Novella Bundle) by Aurora Sparks
Price: $2.99 USD. Words: 39,980. Language: English. Published: February 1, 2016. Categories: Fiction » Erotica » Menage/Multiple Partners, Fiction » Erotica » Gay Erotica
For the first time, readers can get Aurora Sparks's bestselling sissy hypno short, Sissified for Science, and its two-part, novella-length sequel in a single convenient package, for one low price!
Stories of Nasreddin: 納斯雷金的故事(ESL/EFL 英漢對照繁體版) by Qiliang Feng
Series: 百萬英語閱讀計劃叢書(英漢對照中級英語讀物繁體版)第一輯. Price: $2.99 USD. Words: 26,190. Language: Chinese (traditional). Published: January 7, 2016. Categories: Fiction » Erotica » Comedy/Humor, Nonfiction » Language Instruction » English as a second language
本書是"百萬英語閱讀計劃"叢書——英漢對照中級英語系列讀物第I輯之10,適合已掌握1500基本英語辭彙的讀者閱讀。百萬英語閱讀計劃(Million-Word Reading Project, MWRP)是專門為將英語作為外語的學習者(EFL learners)設計的英語閱讀提高計劃,讀者對象爲已掌握1500基本英語詞彙的讀者(相當於初級英語水準),通過2年、每天約15分鐘的閱讀能達到中級英語水準,掌握3000多單詞和大量的短語,熟練掌握英語的各種句子結構,並能閱讀一般英語原著。
Femdom Wife Trio: Three Sexy Stories! by Aurora Sparks
Price: $2.99 USD. Words: 23,210. Language: English. Published: October 19, 2015. Categories: Fiction » Erotica » Menage/Multiple Partners, Fiction » Erotica » BDSM
In the Femdom Wife Trio, you'll find these three stories: Hypnotized, Sissified, Hogtied & Humiliated by My Wife! Transformed & Humiliated by My Wife! Cold-Cocked & Cuckolded Plus a free bonus gender transformation/BDSM short, More Than (S)he Bargained For!
Mastered By My Guardian by Opal Carew
Series: Mastered By, #3. Price: $2.99 USD. Words: 24,660. Language: English. Published: September 20, 2015 by Edge of Ecstasy. Categories: Fiction » Romance » Erotic, Fiction » Erotica » BDSM
A hot new BDSM story in the MASTERED BY series from NYT Bestselling Author Opal Carew. Chelsea spent the past ten years rebelling against Zane's control as her guardian. But when she experiences his potent masculine domination she finds the reality of being with Zane far exceeds her fantasies… leaving her wanting more. Can she surrender to this forbidden love and be mastered by her guardian?
Bound by the Burglar by Natasha Stevens
Series: Bound by the Burglar. Price: $2.99 USD. Words: 25,980. Language: English. Published: February 26, 2015. Categories: Fiction » Erotica » Suspense/Mystery, Fiction » Romance » Suspense
Elena is an underwear model and trophy wife with a dark past. Joshua is a former NAVY Seal with a dark present; he is now a burglar who robs the homes of the wealthy. The two of them are thrown together in a devil's bargain of lust, blackmail and robbery, in a plan to steal a fortune in gold. But some very dangerous individuals are after the gold, also...
Naughty Bits: Eight Stories of Erotica by Natasha Stevens
Price: Free! Words: 35,520. Language: English. Published: February 8, 2014. Categories: Fiction » Erotica » BDSM, Fiction » Erotica » Contemporary
Natahsa Stevens is one of the hottest voices in dark and taboo erotica and this collection contains eight of her hottest stories, all previously published. Older men and younger women, humiliation and blackmail, naughty girls and alpha males, spanking and bondage and hot sex, these stories will take you to the limit ... and then cross over.
Haunted Romance by Douglas Daech
Price: $2.99 USD. Words: 30,200. Language: English. Published: September 8, 2013. Categories: Fiction » Romance » Paranormal, Fiction » Erotica » Paranormal(5.00 from 1 review)
Thirty years ago two high school seniors competed for a trophy, a scholarship and a girl. One of them ended up dead and the other won all three treasures. Now follow the story of Tori Clark, a girl haunted by the spirit of the murdered boy. Tori is asked to expose the murderer and bring justice to the thirty year old cold case. But something unexpected happens along the way.
And One Makes Three by Suzanne Rock
Series: Carnal Coeds, Book 2. Price: $2.99 USD. Words: 28,530. Language: English. Published: June 24, 2013. Categories: Fiction » Erotica » Menage/Multiple Partners, Fiction » Romance » Erotic
When Gabe catches his girlfriend, Becca, checking out the local lifeguard, he sees an opportunity to live out his deepest, darkest fantasy. He confronts the handsome stranger and they form an instant, carnal connection. Now Gabe must convince Becca that their troubled relationship needs sexual healing that only the sexy lifeguard can provide.
Domino Effect by Jill Elaine Hughes
Price: $2.99 USD. Words: 111,240. Language: English. Published: March 24, 2013. Categories: Fiction » Erotica » BDSM, Fiction » Coming of age
DOMINO EFFECT An erotic thriller "Fifty Shades meets John Le Carre"


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Ratings for Dr. William Carlson
Agree all positive comments about Dr. Carlson. He's a great doctor, and is helping me through my prostate cancer.
the best doctor ever...i have been treated by him for prostate issues... and after procedure his follow up was amazing...he is so down to earth.would highly recomend him... front end staff are also very helpful..
My husband continuesnto seemdr. And will for some time. Honest straight forward even if it is not what you want to here. Being honest and forward help understand the issues at hand
This Doctor made me feel comfortable right from the start. He is friendly, down to earth & even has a sense of humour. A far cry from many other Doctors I have seen. Even Deb his Office Assistant was pleasant & friendly. Highly recommended - you're in good hands. :)
Dr. Carlson is a #10. Knowledgeable and informs you in layman's terms so you understand the situations. Top-notch all rounded Dr. who is always on time. I would suggest every General GP would refer their patients to him. - His office staff are very efficient and always call you back immediately.
The most informative knowledgeable - straight to the point-understanding and caring individual with a great personality... I trust him.
Doctor Carlson makes you feel like you are in good hands by what he does and the experience he provides. Meticulous, great staff, great doctor.
Great Dr wonderful personality , extremely good with young children.
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I am a 93 year old prostate cancer survivor, (6/10 Gleason Scale, stage 2TB) treated 14 years ago via 33 radiation exposures (= 6600 cGy) at Vancouver Cancer Centre. This was before we had the Victoria facility available to we Van Islanders. I have recently suffered an extremely sore penis despite a month long application of meds prescribed by our family Dr., who finally referred me to Dr. Carlson, who soon saw me & promptly cured me!. He greeted my wife & I warmly & treated us with kindly respect. He showed sincere empathy & compassion. He has a gentle sense of humour & after explaining that the cause of my problem was 'radiation', said: "But 'radiation' has enabled you to live long enough to complain about its 'side effects'! Thank you Dr. Carlson, I am feeling better every day!
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The TEN-T Guidelines defined a stringent methodology for the eligibility and priorities of transport infrastructure. During the past year, the Commission, member states and infrastructure managers have jointly worked on corridor work plans that are to identify the priority projects with the highest European added value that should thus be the first recipients of EU funding. However, under the EFSI, any European transport project independent of location and mode of transport can receive funding. This shifts the logic away from the carefully chosen transport priorities of the CEF and TEN-T.
Therefore, the reallocation of financial resources from the CEF budget to the EFSI is much more than an attempt to attract new private resources to projects of European economic and social added value. It is, rather, a policy change that must be assessed thoroughly: other projects will be promoted instead of the ones which were identified as a priority by CEF, at the same time cutting the EU spending capacity for grants to projects of the TEN-T network.
Moreover, the EFSI does not ring-fence money for any particular type of investments. Different sectors ranging from energy, to education and health will be competing for financing. The money transferred from the CEF could thus end up being absorbed by other sectors if these are better able to present mature projects with clear revenue streams.
We therefore ask the decision makers in the EU institutions to take into account the concerns of the undersigned, and to ensure that the money dedicated to transport infrastructure in the Multiannual Financial Framework and the Connecting Europe Facility continues to serve the transport objectives defined in the TEN-T Guidelines.
(1) The completion of the TEN-T network requires about € 550 billion until 2020 out of which some €215 billion can be referred to the removal of the main bottlenecks (Transport White Paper 2011, page 14).
The signatories:
EFIP Director Kathrin Obst joining the European Commission (DG Move)
Brussels, 20.01.2015
EFIP Director Kathrin Obst will be leaving EFIP in March to take up a new position with the EU's civil service. Kathrin will be joining the European Commission, DG Move, to work on rail policy. "She provided an excellent job in promoting the key role of inland ports of connecting transport modes and developing multimodal logistics", the President of EFIP, Hans-Peter Hadorn, said. EFIP is very grateful to Kathrin Obst for her efficient work and wish her a successful continuation of her career in the world of transport.
The transport priorities of the Latvian Presidency
Brussels, 12.01.2015
On 1 January, Latvia took over the six-months rotating presidency of the Council of the European Union from Italy. Latvia will focus on three priorities during its Presidency: 1) facilitation of EU competiveness as a key to economic growth and jobs; 2) full exploitation of the digital potential of the European economy; 3) reinforcing the role of the European Union in the world. In addition, the Latvian Presidency wishes to ensure that the Council contributes to the implementation of the European Council's five-year Strategic Agenda in the areas of protection of citizens, an Energy Union with a forward-looking climate policy, and a Union of freedom, security and justice.
According to the Latvian Presidency's programme, The EU's inland waterway transport sector is an important catalyst for the future development of the EU internal market and a more sustainable and effective transport network. In the next six months, the Presidency will start working on the revised proposal laying down technical requirements for inland waterway vessels.
As regards land transport, strengthening the European railway network will be a distinctive part of the Presidency. Progress on the Fourth Railway Package is instrumental for the development of the single EU transport area, which contributes to a more competitive and modern public transport infrastructure across the EU. The Presidency will continue the discussions on all parts of the package. The Presidency will work to finalise negotiations with the European Parliament on the technical pillar based on substantial progress that has been achieved during previous presidencies. In order to achieve further progress on the remaining elements of the package, discussions started by the Italian Presidency will be continued.
The Presidency will also formalise the agreement reached on the weights and dimensions proposal.
In order to highlight the importance of TEN-T, the Presidency will initiate ministerial discussions focusing on the development, implementation and financing of the TEN-T transport network infrastructure. This will be also an opportunity to look at the practical implementation of the Investment plan for Europe in the field of transport.
Finally, maritime transport is and will be an important long-term contributor to Europe's economy and the quality of life of the European people. The Presidency will strive to secure the right international environment for maritime transport and intends to promote all the initiatives facilitating growth and enhancing competitive European shipping. As regards the ports sector, once the European Parliament has adopted its first reading position, the Presidency may seek further progress on the Commission's proposal to establish a framework for market access to port services and the financial transparency of ports.
The next Transport, Telecommunications and Energy Council (TTE) will take place in March (5-13) and June (8-11).
The official website of the Latvian Presidency is: http://eu2015.lv/
Port Authority Vukovar joins European Federation of Inland Ports (EFIP)
Brussels, 16.12.2014
The port of Vukovar is located on 1335rkm right bank of the Danube and is identified as a TEN-T core network port on the Rhine-Danube corridor. Its navigability class provides access 365 days a year to all types of vessels. Direct vicinity of the Croatian road corridor Vc and the rail-road corridor X reflect the significance of the port for the region.
Within the port area, which encompasses 26 ha of space, port activities are carried out by four concessionaires that provide transhipment of all kinds of commodities including liquid and dry bulk, general cargo and heavy cargo. Besides transhipment services, port operators in the port of Vukovar also provide warehousing services offering 3000 m2 capacity of closed warehouse, 12000 m3 of warehouse for liquid cargo and 48.000 t of silo capacity for grain.
In 2007, the Port Authority Vukovar initiated a project of reconstruction and modernization called Port of Vukovar-New Port East. Project preparation including main design was supported by the EU within the Instrument for Pre-Accession Assistance Programme (IPA) 2007-2013 and encompasses documentation for:
The European Federation of Inland Ports (EFIP) brings together more than 200 inland ports and port authorities in now 18 countries in the European Union, Switzerland and Ukraine. Since 1994, EFIP has been the voice of the inland ports in Europe.
Božana Matoš, Managing Director of the Port Authority Vukovar said: "Port Authority Vukovar is honoured to become a member of European Federation of Inland Ports and we hope to be a worthy partner of this respected organization."
Transport ministers pledge to implement Fairway Rehabilitation and Maintenance Master Plan for the Danube and its Tributaries – Sector asks for swift action
Brussels, 04.12.2014
The current lack of fairway maintenance on the Danube is a pressing issue for the inland waterway sector and the industry using it. The failure to maintain the Danube and its navigable tributaries threatens the safe and cost-efficient navigability of the river with disastrous consequences for the barge and port sector and affected client industries. Moreover, unreliable infrastructure conditions deter potential customers from transporting their goods by inland waterway in the first place. Providing quality infrastructure and legal certainty will kick-start private investment in innovative and cost-effective services with positive effects for economic development in Europe.
The Master Plan was developed in the framework of the EU Strategy for the Danube Region (EUSDR). It identifies critical maintenance locations which currently limit the navigability of the Danube and analyses the underlying issues and the financial needs required to resolve them.
Ministers agreed to establish national roadmaps which identify individual actions, responsibilities, funding resources and intermediate milestones for the implementation of these measures and to communicate these roadmaps by 30 June 2015 to the relevant coordinating bodies. They further confirmed their intention to allocate the necessary national budgets as referred to in the Master Plan and stressed the importance of making use of EU co-financing opportunities.
The Conclusions were signed by Austria, Bulgaria, Croatia, Germany, Moldova, Romania, Bosnia and Herzegovina, Slovakia and Ukraine. The undersigning associations regret that Hungary and Serbia did not yet sign the Conclusions, but welcome the positive attitude towards the activity expressed by both countries.
The majority of investments are needed for dredging equipment, fairway marking and riverbed surveying. Investments are to be carried out in full compliance with EU environmental legislation, thus ensuring respect for biodiversity and integrated water management.
Undersigning organisations:
Inland Navigation Europe (INE) is the European platform of national & regional waterway managers and promotion bureaux, established in 2000 with the support of the European Commission. INE sees major opportunities to contribute to long-term strategies for sustainable transportation by moving more goods by water in EU regions and cities with accessible and navigable rivers and canals. INE is a neutral platform without commercial interests.
The European Barge Union (EBU) represents the majority of the inland navigation industry in Europe. Its members are the national associations of barge owners and barge operators of meanwhile 9 leading European inland navigation countries. EBU's main objective is to represent the interests of the inland shipping industry at a European and international level and to contribute to the development of a sustainable and efficient European transport system.
European Skippers' Organisation (ESO) is the voice of the European private inland shipping entrepreneurs in Belgium, Germany, France, Poland and The Netherlands since 1975.
Pro Danube International (PDI) acts as network of private businesses vis-à-vis policy makers, media and general public to promote better infrastructure and services which result in a more intensive use of the environmentally friendly inland waterway. Pro Danube International defines and carries out policy actions as well as projects to achieve this goal.
The National Company "Maritime Ports Administration" SA Constanţa (MPA SA Constanţa) is a joint stock company subordinated to the Ministry of Transport, being assigned to develop activities of national public interest in its capacity of port administration. MPA SA Constanţa fulfils the administrative function for Constanţa, Midia, Mangalia maritime ports and the Tomis marina.


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David Liam Kyle/NBAE via Getty Images
Boston Celtics vs Cleveland Cavaliers - Game 2 - (Cavs lead 1-0)
8:00 PM ET, May 3, 2010 -- Quicken Loans Arena, Cleveland, OH -- TNT
The Cavaliers took Game 1, which is good news for them. They are 8-0 all-time in best-of-7 series when winning the first game (7-0 with LeBron James). Cleveland has won six straight and 13 of its last 14 home-playoff games dating back to 2008 Conference Semis. Boston has lost six-straight playoff games at Cleveland. The game turned after Mo Williams threw down a one-hander over Paul Pierce, before finishing with 20 points. Cleveland is 5-1 when Mo Williams scores 20+ in a playoff game. How important is Game 2? Well, Boston has lost six straight best-of-7 series when trailing 2-0 and is 1-7 all-time when facing such a deficit.
Game Preview: Celtics vs Cavaliers
Harry Gossage/NBAE/Getty Images
San Antonio Spurs vs Phoenix Suns - Game 1
10:30 PM ET, May 3, 2010 -- US Airways Center, Phoenix, AZ -- TNT
The Suns advance to the Conference Semifinals for the first time since 2007, where they will meet the Spurs (who eliminated them in 2007). The Spurs have advanced to the Conference Semis in 11 of Tim Duncan's 13 seasons in the league. This will be the 10th time these teams have met in the last 19 postseasons. In the last 20 postseasons, no other matchup has occurred more than seven times. Amare Stoudemire has a 24.6-point playoff average against the Spurs. Not including his rookie season of 2003, Amare's average jumps to 28.8. This regular season, as Phoenix won two of three from the Spurs, Stoudemire averaged 32.7 points and 11.3 rebounds.
Game Preview: Spurs vs Suns
Brian Babineau/NHLI/Getty Images
Philadelphia Flyers vs Boston Bruins - Game 2 - (Bruins lead 1-0)
7:00 PM ET, May 3, 2010 -- TD Garden, Boston, Massachusetts -- Versus
The Bruins go for a 2-0 lead tonight, and are 20-6 all time in postseason series when up 2-0. Marc Savard, who hadn't played a game since his March 7 concussion, returned to the ice and provided both energy and the game-winning goal Saturday. The Flyers admitted they were sloppy to start Game 1, and will look for a sharper performance tonight, in all three periods. The Flyers went eight days without a game after eliminating the New Jersey Devils in five games. The Bruins had four days off after their six-game victory over the Buffalo Sabres. The rust, if any, should be gone for the Flyers tonight.
Game Preview: Flyers vs Bruins
Bill Smith/Getty Images
Vancouver Canucks vs Chicago Blackhawks - Game 2 - (Canucks lead 1-0)
9:00 PM ET, May 3, 2010 -- United Center, Chicago, Illinois -- Versus
The Blackhawks try to avoid losing back-to-back home playoff games for the first time since 2002 vs Blues (lost 1st round series 4-1) when they face-off against the Canucks tonight. To do so, Chicago needs to figure out Roberto Luongo, something they failed to do in the opener. Despite a storm of shots early on, Luongo made 17 of his 36 saves in the first 20 minutes of play, and denied two power-plays. Vancouver used its speed and depth, getting scoring from all four if its lines to claim Game 1. The Blackhawks also lost the first game of the previous round at home to Nashville before capturing the series in six games.
Game Preview: Canucks vs Blackhawks
Note: The Elias Sports Bureau and ESPN Stats and Information group contributed to this report.


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Get a free sampled drum kit made in a spacecraft test facility
Last November, I went armed with some LOM label microphones to the Netherlands to find out what sounds you could discover in a space research facility. That exploration produced a lot of sounds, and one way to play with them was to transform them into percussion. Now you can download the drum kit I made for your own use, or to create your own instruments.
Making stems ought to be a step in your production workflow
Forget about whether anyone is going to listen to that release, let alone whether you'll make money. Finishing is a beautiful feeling. Something happens when you get to that phase of adjusting the final mix, bouncing for mastering. For many of us, that last step involves a stereo bounce. But I think it's high time to start thinking in terms of stems (both in the lowercase, and the all-caps STEMS Native Instruments is keen for you to use).
In LA, looking to what new tech means for music makers
This week, the eyes of the music world will look at what's new in toys. But how about looking further, to how technology is used? Going deeper to what's happening in live music and music making is the essence of our new series Practice Space. CDM is excited to host a living-room style gathering of musicians and performance artists in the heart of downtown LA, and we hope you'll join us – in person and online.
Celemony Melodyne can now dive into overtones and spectra
Celemony's flagship Melodyne audio editor has long been reaching past the limits of what most people imagine as pitch correction. It was clear the mission of the software was no less than seamlessly transforming audio – shaping sound as directly as you can MIDI notes. Well, now it's gone even further. Now we're not just talking about moving polyphonic notes around. In Melodyne 4, we're talking reaching into the spectra of polyphonic sound material itself. It's like playing God with a recording.
Remembering David Bowie's legacy, in videos
There are artists who are remembered for their cultural impact, for the power of their identities or their musical output. But David Bowie always struck me as one of those few larger-than-life personalities whose sheer force of productivity was staggering itself. From the tiniest details of a stage production to ground-breaking concepts in fashion to an exhaustive approach to studio work, Bowie was king of workaholics. He was a person who made, and made some more. If he had done so in total obscurity and you happened to unearth the output of his imagination, you would be staggered. And everything …
Use a hardware synth like it's a plug-in – in a $60 DAW
With a little setup, you can integrate a hardware synth with Reaper as if it's a software plug-in. Check out the video tutorial from The Reaper Blog to see how. Reaper is a terrific "indie" DAW for the budget-conscious. Just $60 buys you an individual personal license with a bunch of free upgrades. ("Commercial" use is described as anyone making more than $20k a year – plenty of very serious musicians make less than that.)
Link could change how you play music, even without Ableton
You're probably so used to sync being broken that the first time you see Link, you might not believe what's happening. Link began its life as a research project and has turned into a full-fledged product from Ableton. But unlike Push or Live, Link itself isn't something you buy. Instead, it'll be built into software you use, and unlock seemingly magical wireless (or wired) sync. The upshot: the electronic jam session is about to get a whole lot easier. And with a beta out today, that's not some unknown future. It's right now.
Confidence, humanity, and drumming: Kiran Gandhi interview
It's clear right away that Kiran Gandhi is an "always-on artist." We're sitting down with the drummer/singer/electronic musician/businesswoman at Ableton's Loop conference, and as she reflects on the acoustics of the outdoor tent where we're recording, she sings an impromptu recording into her phone. There's even a lyric reminding her to write about tents. The tone is set for our whole conversation: as Kiran longs for a higher-fidelity phone microphone, technology alone can't keep pace with her spontaneity.
Ableton Push 2 meets modular; here's how it works
Digital, analog – whatever. Let's see what happens when Ableton's latest digital hardware, the new Push, meets Eurorack, for a sort of convergence of the stuff electronic musicians are talking about right now. (Don't worry; we aren't going to a round-the-clock all-Ableton format – the Berlin developer is notoriously conservative about spreading out releases, so let's give them this week as a special occasion. And, anyway, there are some tips here relevant to Eurorack users with or without any Ableton products. Plus, you might just like the music.) We stopped by the studio of Berlin-based musician Kaan Bulak. He's an …
Akai MPC Touch is an MPC with a multi-touch screen
MPC lovers, you finally get a piece of hardware with everything in one place: touch, color displays, pads, buttons for workflow access. There's just one catch: you will still need the computer. Ever looked at those beautiful color waveforms on Native Instruments' Traktor and Maschine controller and wished you could touch the screen? Imagined pinching to zoom waveforms and navigate samples, the way you can on an iPad? Well, Akai are the first to do groove-making hardware that combines physical pads and a touchscreen in one unit – no iPads (or Microsoft Surfaces) in sight.


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The need-know about vacationing in Germany
Sep 4, 2012, 8:31 a.m.
A German vacation offers a tourist traveling in Germany the opportunity to visit unique and interesting sites that include medieval cities, historic castles, popular beer halls, and modern cities full of excitement. If you have an upcoming German vacation planned or if you have ever just dreamed of traveling in Germany, there are a few things you need to know to make it your best trip possible.
Unless you are fluent in German, the first thing you may want to consider is downloading a German translator app that allows you to simply say a sentence in English and immediately hear the German translation. You can download the free app from GooglePlay and once you can understand the language a little better, you will be all set to explore and navigate the many interesting sites a German vacation has to offer.
Germany is located directly in the middle of Europe and shares a border with nine European countries. It is an interesting mix of beautiful scenery, exciting nightlife, historic greatness, and fascinating culture; and the perfect German vacation will allow you to catch a glimpse of it all.
According to LonelyPlanet.com, there are several popular cities that those traveling in Germany most often include in their itineraries. These popular German vacation destinations are listed below, along with a few details about what makes them such great places to visit.
5 must see cities to visit during your German vacation
- Berlin -- The capital of Germany, Berlin is a fast paced and energetic city that has become a trendy and cultural melting pot filled with a background rich in history. Popular Berlin landmarks include the Checkpoint Charlie Museum, the Reichstag, the old Berlin Wall, the Holocaust Memorial, and many museums as well as popular German pubs.
- Cologne -- The 4 th largest city in Germany, Cologne is known for its rich culture and dynamic architecture. The city is filled with medieval churches, historic museums, and well attended concert halls. The most popular attraction is the Cologne Cathedral, known as the Dom, which fills the city's skyline with its beauty. Cologne also features chocolate makers, a culture of art, and fun filled beer halls.
- Rügen Island -- This Island is home to about 356 miles of beautiful coastline. The lush surroundings and blue water are included in the Island's national parks and protected nature reserves. Popular with tourists, the resort of Binz as well as the Stubbenkammer, are located in the Jasmund National Park and see many visitors each year.
- Dresden -- A classically beautiful city, Dresden is popular with artists who are inspired by the beautiful views from the Elbe's northern bank. From soaring towers to ancient palaces and historic churches, this unique city offers a magnificent cultural experience. With world class museums and Mediterranean feel, you will want to spend a few days here to soak in its charm.
- Hamburg -- Home to the largest port in Germany, Hamburg is also a booming media capital and the richest city in Germany. Hamburg's rich maritime history makes it a wonderful city to visit. It is a popular town with the young, rich and hip crowd who like an energetic nightlife with lots of activities. Take a popular riverfront sightseeing tour near the Elbe River, see buildings shaped like ocean liners, and enjoy the scenic views and city sights of the beautiful hillside district of Blankenese.
No matter what your idea of the perfect German vacation is, you are sure to find something everyone will enjoy while traveling in Germany. Spend a week or a month and soak in the rich culture this historic country has to offer.
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Go exploring with your better half! European barge tours for the young at heart
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