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Background Drug coated balloons (DCBs) in Europe are mainly used in restenotic lesions as endorsed by the European Society of Cardiology, with a class IA recommendation. However, some of the recent data suggest, it can also be considered in a subset of denovo lesions, especially in small vessels. Most DCBs used, are coated with Paclitaxcel. There is no data on the efficacy of Sirolimus in DCBs, the drug of choice in drug eluting stents. In this study, we report outcomes from the use of a Sirolimus coated balloon (SCB) in de novo small-vessel coronary lesions, from a single high yield centre. Methods A retrospective analysis was conducted on all patients treated with an SCB between March 2018 and October 2020. Follow-up was achieved with clinic visits, telephone calls and admission records. The outcomes measured include cardiac death, target-vessel myocardial-infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, target-vessel MI and TLR). Results During the study period, 279-patients (with 332-lesions) with de novo lesions were treated with an SCB. The mean age of patients was 65±12 years, 219 (79%) were male, 36% (n=100) had diabetes, 16% (n=45) had chronic kidney disease and 61% were in the setting of acute coronary syndrome (n=169). Predilatation was performed in 96% (320-lesions). Bailout stenting (with DES) was required in 5% of lesions (n=18) of which 16 were due to dissections and 2 were due to recoil >30% following DCB use. The mean diameter and length of DCBs were 2.35 mm and 26 mm respectively. During a median follow-up of 584-days (19-months) cardiac death was reported in 8 patients (3%). Target vessel MI was in 3% (n=9), TLR per lesion was 8% (n=26) and the MACE rate was 11% (n=31). There were no documented cases of acute vessel closure. Conclusion The long-term outcome from the first ever study on sirolimus eluting balloons in de novo small vessel lesions appears promising with low rates of hard endpoints, and acceptable repeat rates of TLR despite a complex group of patients (50% ACS, 36% diabetics and 19% CKD) and lesion subsets (small vessel and diffuse disease). Implanting stents in these subsets renders them vulnerable to restenosis, making treatment challenging and resulting in high rates of recurrence. Funding Acknowledgement Type of funding sources: None.

Aims The use of scoring balloon prior to drug coated balloon has been proven to be effective in restenotic lesions. However, their effect in de novo lesions has not been tested. Logic tells that the use of scoring balloons should enhance the drug uptake into the vessel wall. In this study, we evaluated this concept of scoring balloon prior to DCB in de novo lesions and compared to those who were treated with a conventional approach (semi-compliant and/or non-compliant balloons). Methods and results We evaluated all de novo lesions treated with DCB between March 2018 and October 2020 at our centre. The results are reported as cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, target vessel MI and TLR). During the study period 348 patients with de novo lesions were treated with DCB. Of those, 49 were predilated with scoring balloon prior to use of DCB and the remaining 299 were predilated with non-scoring balloons (semi-compliant and/or non-compliant). The majority of the baseline characteristics had no statistically significant differences (table 1), with the exception of the mean diameter of the lesions were larger in the scoring balloon group than non-scoring balloon group: 2.7±0.5 vs. 2.49±0.4; p=0.003 and mean length of lesions were longer in the non-scoring balloon group: 26±8.8 vs. 23±7.7; p=0.02. During the median follow-up of 660 days, clinical outcomes between the scoring and non-scoring balloons were; cardiac death: 0 vs. 8 (3%); p=0.5, TVMI: 2 (4%) vs. 8 (3%); p=0.9, TLR: 3 (6%) vs. 25 (8.4%); p=0.8, MACE: 4 (8%) vs. 34 (11%) p=0.7 Conclusion There were no differences in the clinical outcomes between the two groups indicating that use of scoring balloon prior to DCB may not offer additional benefit, although this needs to be confirmed in a larger patient group. Funding Acknowledgement Type of funding sources: None.

Introduction Use of drug coated balloons (DCBs) in coronary intervention is escalating and the guidelines recommend its use in restenotic lesions. However, recent data suggest it can also be considered in a subset of denovo lesions especially; small vessels, ostium of an important side-branch and in patients unable to tolerate dual antiplatelet therapy for a prolonged period. Most DCBs used elute Paclitaxcel, but there is no data on Sirolimus eluting DCB, which is the drug of choice in currently available drug eluting stents. In this study, we report outcomes from the use of a Sirolimus coated balloon (SCB) in de novo coronary lesions. Methods We retrospectively analysed all patients treated with an SCB between April and December 2018. Results are reported as cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR), target vessel revascularisation (TVR) and MACE (combination of cardiac death, target vessel MI and TLR). Results During the study period, 351 patients (with 414 lesions) with de novo lesions were treated with an SCB. The mean age of patients was 65.6±11.5 years, 275 (78%) were male and 39% (n=212) had diabetes. Most lesions treated were in the LAD/diagonal system (n=173, 42%). Predilatation was performed in 98% (405 lesions). Bailout stenting (with a drug eluting stent) was required in 7% lesions (n=30), of which 11 were due to dissections and 19 were due to recoil >50% following DCB use. The mean diameter and length of DCBs were 2.47 mm and 26 mm respectively. During a median follow-up of 322-days (11-months) cardiac death was reported in 8 patients (2.3%). Target vessel MI was in 3%; n=10, TLR and TVR per lesion were 8% (n=34) and 9% (n=37) respectively. The MACE rate was 11%. There were no documented cases of acute vessel closure. Conclusion The mid-term outcome from the first ever study on sirolimus coated balloons in de novo lesions appears promising with low rates of hard endpoints with no documented cases of acute vessel closure. The MACE rates appear promising, although we need longer follow-up which is ongoing and we will be able to report outcomes from even longer follow-up during the presentation. Funding Acknowledgement Type of funding sources: None.

Introduction Provisional stenting is the preferred strategy even in true bifurcations, however, to minimise the need for repeat revascularization of side-branches, the use of drug coated balloons has been suggested. Most of the data available in the literature are on Paclitaxel coated balloons, a drug which is almost obsolete in stents due to its cytotoxic properties. There is limited data on Limus coated balloons (SCB), a drug which is the default for all the currently available drug eluting stents. In this study, we explore the clinical outcomes following use of SCB in side-branches during provisional stent technique in true bifurcations. Methods and results We evaluated all de novo lesions treated with DCB for true bifurcations between March 2018 and October 2020 at our centre. The results are reported as cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, target vessel MI and TLR). During the study period 110 patients with de novo lesions were treated with SCB for bifurcation lesions. Of them; 66 were in true bifurcations. The mean age of patients were 66.3±10.7 years, 75% (n=50) were male, 40 (61%) were in the setting of acute coronary syndrome, 52% (n=34) had diabetes and 32% (n=21) had CKD. Pre-dilatation was performed in all cases and none of them needed bailout stenting. Small vessels ( During a median follow-up of 729 days (2-years); there were no cardiac deaths, TVMI occurred in one case (2%), TLR in 3% (n=2) and the overall MACE rate was 3% (n=2). There were no documented cases of acute vessel closure Conclusion The results from long term follow-up with this relatively new technology of DCB in treatment of side-branch in true bifurcation is encouraging. We have demonstrated low rates of hard endpoints, TLR and MACE rates despite complex group of patients (61% ACS, 52% diabetics and 32% CKD). These results are encouraging, but going forward, we need more data from larger patient trials. In the meanwhile our data should instil confidence to adopt this technology in clinical practice. Funding Acknowledgement Type of funding sources: None.

Background Drug coated balloons (DCBs) in Europe are mainly used in restenotic lesions as endorsed by the European Society of Cardiology, with a class IA recommendation. However, some of the recent data suggest, it can also be considered in a subset of denovo lesions, especially in small vessels. Most DCBs used are coated with Paclitaxcel. There is no data on the efficacy of Sirolimus in DCBs, the drug of choice in drug eluting stents. In this study, we report outcomes from the use of a Sirolimus coated balloon (SCB) in de novo small-vessel coronary lesions, from a single high yield centre. Methods A retrospective analysis was conducted on all patients treated with an SCB between March 2018 and October 2020. Follow-up was achieved with clinic visits, telephone calls and admission records. The outcomes measured include cardiac death, target-vessel myocardial-infarction, target lesion revascularisation and MACE (combination of cardiac death, target-vessel MI and TLR). Results During the study period, 279-patients (with 332-lesions) with de novo lesions were treated with an SCB. The mean age of patients was 65 ± 12 years, 219 (79%) were male, 36% (n=100) had diabetes, 16% (n=45) had chronic kidney disease and 61% were in the setting of acute coronary syndrome (n=169). Predilatation was performed in 96% (320-lesions). Bailout stenting (with DES) was required in 5% lesions (n=18) and of which 16 were due to dissections and 2 were due to recoil >30% following DCB use. The mean diameter and length of DCBs were 2.35 mm and 26 mm respectively. During a median follow-up of 584-days (19-months) cardiac death was reported in 8 patients (3%). Target vessel MI was in 3% (n=9), TLR per lesion was 8% (n=26) and the MACE rate was 11% (n=31). There were no documented cases of acute vessel closure. Conclusion The long-term outcome from the first ever study on sirolimus eluting balloon in de novo small vessel lesions appears promising with low rates of hard endpoints, and acceptable repeat rates of TLR despite a complex group of patients (50% ACS, 36% diabetics and 19% CKD) and lesion subsets (small vessel and diffuse disease). Implanting stents in these subsets renders them vulnerable to restenosis, making it difficult to treat, making treatment challenging and resulting in high rates of recurrence. Conflict of Interest None to declare

Background The use of drug coated balloons (DCBs) in coronary intervention is escalating. There are two drugs of choice for coating either DCBs or drug eluting stents: Paclitaxel or Sirolimus. Most available DCBs are coated with Paclitaxcel, due to pre-existing, extensive data that support good clinical outcomes. With drug eluting stents both the literature and hence clinical practice favour Sirolimus over Paclitaxcel. This is due the cytostatic properties and wide therapeutic window of Sirolimus. However, there is very limited data on Sirolimus coated balloons (SCBs). We report a long-term follow-up with this relatively new technology from our centre. Methods A retrospective analysis was conducted on all patients treated with an SCB between March 2018 and October 2020. Follow-up was achieved with clinic visits, telephone calls and admission records. The outcomes measured include cardiac death, target-vessel myocardial-infarction, target lesion revascularisation and MACE (combination of cardiac death, target-vessel MI and TLR). Results 533 patients (690-lesions) with a mean age of 65.4 (range; 37-90) were treated with an SCB. 79% (n=419) were male, 314 (59%) were in the setting of acute coronary syndrome, 40% (n=211) had diabetes and 60% (n=414) had DCB in de-novo lesions. Small vessels accounted for 59% of cases (n=406). Pre-dilatation was performed in 97% (n=670) of cases. Bailout stenting (with a drug eluting stent) was required in 6.5% lesions (n=45), of which 11 were due to dissections and 34 were due to >50% recoil following DCB use. The mean diameter and length of DCBs were 2.8 mm and 26.3 mm respectively. During a median follow-up of 572 days (IQR: 381 - 868); cardiac death occurred in 15 patients (3%). Target vessel MI was in 4%; n=21, TLR per lesion and per patient were 10% (n=72 and n=55 respectively). The overall MACE rate was 12%. There were no documented cases of acute vessel closure. Conclusions The results from long term follow-up with this relatively new technology DCB are encouraging with low rates of hard endpoints and acceptable rates of TLR and MACE despite complex group of patients (59% ACS and 40% diabetics) and lesion subsets (40% restenotic lesions and 59% small vessels). This suggests that SCBs can be used in both restenotic and de novo small vessel lesions with acceptable clinical outcomes. However, in order to further inform clinical practice, more longer-term data on SCBs compared with Paclitaxel coated balloons is needed. Conflict of Interest None to declare

Highlights • Limited data on intra-stent CTO. • We explored the long-term outcomes in patients undergoing PCI to intra-stent CTO. • Acceptable rates of hard endpoints (cardiac death; 5.8%, TVMI; 4%). • High rates of TLR (45.6%). • PCI should only be undertaken if symptomatic or if there is inducible ischaemia. • If PCI is undertaken, DCB and DES should be considered over POBA., Background Angioplasty for ISR remains a challenge with relatively high rates of recurrence. Although there is a plethora of data on ISR, there is relatively less data on intra-stent-CTO. In this study, we explore the long-term clinical outcomes following angioplasty to intra-stent CTO and study the differences in clinical outcomes between three treatment-arms: POBA vs. DES vs. DCB. Methods and results We evaluated all patients who underwent PCI to intra-stent CTO between 2011 and 2017. The endpoints used were: cardiac-death, TVMI, TLR, TVR, and MACE. During the study period, 403-patients with a mean age of 69.2 years had successful PCI to intra-stent CTO. 50% were diabetic, 38% had CKD and 32% had left ventricular dysfunction. 93% of cases were stable angina. 22% (n = 88) received only POBA, 28% (n = 113) received DCB and 50% (n = 202) received DES. During the median follow-up of 48-months, cardiac-death occurred in 5.8% (n = 23), TVMI in 4% (n = 16), TLR in 45.6% (n = 182), TVR in 48.7% (n = 194) and MACE of 46%. There were no differences in the hard endpoints between the 3treatment arms. However, the TLR and overall MACE were better in DCB and DES-groups as compared to POBA (TLR: 33%vs.42%vs.49%; p = 0.06); MACE (34% vs. 45% vs. 52%; p = 0.05). Conclusion This is the first study that has focussed on the outcomes following angioplasty to intra-stent CTOs with a very long-term follow-up. The hard endpoints were low, although the TLR rates were high. In regards to treatment strategy, the DCB and DES provide relatively better outcomes than POBA.

Introduction Bailout stenting post-Paclitaxcel drug coated balloon use (DCB) is done with Limus eluting stent as we don’t use Paclitaxcel eluting stent anymore. However, when using Sirolimus DCB, bailout stenting is done with Limus eluting stent, but this raises the issue of drug toxicity with double dose of Limus to the vessel wall. In this study, we evaluate all patients treated with Limus DCB that required bailout stenting for safety and clinical outcomes. Methods and Results We evaluated all patients who were treated with MagicTouch Sirolimus eluting DCB (Concept Medical limited, India) March 2018-June 2019. Bailout stenting per lesion were identified and studied for endpoints which included cardiac death, target vessel MI, stent thrombosis, target lesion revascularisation and MACE. Between the study period; 406 patients (477-lesions) with a mean age of 66 ± 11.2 years (range; 37-90) were treated with MagicTouch DCB. Bailout stenting was required in 39 lesions (8%) and of which 22 were due to dissections and 17 were due to >50% recoil following DCB use. During a median follow-up of 302 days; there were no cases of cardiac death, 1-case of target vessel MI (2.6%) and 3-cases (7%) of TLR. The MACE rate was 7%. There were no cases of stent thrombosis as per the ARC definition. Conclusion One of the highlighting features of our study is low-rates of bailout stenting (9%). This may be due to our criteria of not stenting mild dissections (unless they are flow limiting) and not to expect stent like results. The outcomes in the bailout stenting group is excellent with very low hard clinical endpoints indicating there may not be any toxic effect from double dose of Limus drug (DCB + DES). Conflict of Interest None

Introduction Sub-optimal stent expansion due to coronary calcification augments the risk of restenosis and stent thrombosis. Calcium modification is generally achieved by rotational atherectomy or specialized balloons (scoring and cutting balloons), which carries risk of complications. Intravascular lithotripsy (IVL) appears safe and also aids in cracking deep seated adventitial calcium. Although, there are reported studies on this novel technology, there is a lack of real-world data. In this study, we report the experience from 4 centres that undertake high-volume complex coronary interventions. Methods We enrolled all patients treated with IVL between September 2018 and October 2019 at 4 centres (1 in UK and 3 in Italy). Procedural success and complication were assessed. The clinical outcomes evaluated were; cardiovascular death, target vessel MI (TVMI), target lesion revascularisation (TLR) and MACE (composite of cardiovascular death, TVMI and TLR). Results During the study period, 100 lesions (in 94 patients) with a mean age of 71±9.7 years (range;30 - 88) were treated using IVL. 70% (n=70) were male, 85% (n=80) had hypertension, 51% (n=48) had diabetes and 20% (n=19) had chronic kidney disease. Acute coronary syndromes accounted for 40% of patients (n=38). De-novo lesions accounted for 66% of cases (n=66) and the remaining 34% (n=34) were restenotic lesions. Left anterior descending artery (56%) accounted for most cases followed by right coronary artery (22%), left circumflex artery (21%), left main (17%) and saphenous vein grafts (3%) procedures. Upfront use of IVL occurred in 18% of cases whilst the rest were bail-out procedures due to inadequate pre-dilatation with conventional balloons. Adjuvant rotational atherectomy (Rota-tripsy) was used in 10 cases (10%) prior to the use of IVL. The mean diameter of IVL balloon was 3.3 ± 0.5mm. Intravascular imaging (IVUS) was used in 19% of cases. Procedural success was achieved in 100% of cases with a complication rate of 2% (2-cases of coronary perforation and one of them resulted in in-hospital mortality). During the median follow-up of 150 days, there were no clinical events including cardiac death, TVMI and TLR. Conclusion Initial experience and short-term clinical follow-up from IVL use appears safe and effective PCI strategy for dealing with calcified coronary lesions. A high success rate was observed with low event rates and procedural complications. We are enrolling more patients from other centres as part of a larger multi-centre registry and will be able to report this with higher numbers and longer follow-up at BCS 2020. Conflict of Interest nil

Aims The bailout stenting post-drug coated balloon (DCB) is performed with second generation drug eluting stents (DES). For paclitaxel DCBs (PCB), it will result in delivery of 2 different drugs to the vessel wall (Paclitaxel from DCB + Limus from DES), on the contrary for sirolimus DCBs (SCB) it will result in double dose of a same drug (Limus from DCB + Limus from DES). In this study, we study the differences in the clinical outcomes between the two groups (PCB + Limus stent vs. SCB + Limus stent) assessing for either a synergistic or a toxic-effects. Methods and Results We evaluated patients treated with DCB between January 2016 and June 2019 at our centre. Results are reported as death, cardiac death, target vessel myocardial infarction (TVMI), target lesion revascularisation (TLR) and MACE (combination of cardiac death, TVMI and TLR). During the study period; 890 lesions (766-patients) were treated with DCB. Of them; 433 were treated with PCB and 477 with SCB. Total of 81-lesions (9%) needed bailout stenting for either dissection and/or recoil of >50%. This included; 42-lesions in PCB group and 39-lesions in SCB group. There were no significant differences in the baseline characteristics between the two groups. During the median follow-up period of 18-months, the clinical outcomes between PCB and SCB group were; death: 3 (7%) vs. 0; p=0.3, cardiac death: 2 (5%) vs. 0; p=0.5, TVMI: 0 vs. 1 (2.6%); p=0.4, TLR: 1 (2.4%) vs. 3 (7.7%); p=0.5, MACE: 3 (7%) vs. 3 (7.7%); p=0.7. There were no reported cases of stent thrombosis in either group. Conclusions The bailout stenting rate was relatively low in our group (9%) as compared to previously published studies. No significant differences were observed between the two-bailout stenting groups, although numerically PCB + limus stent group had lower rates of TLR, but had higher mortality rates as compared to SCB + limus stent, implying potential synergistic effect, but maybe at the cost of toxicity? This needs to be confirmed with larger patient group with multi-centre experience. Conflict of Interest None

Background Use of drug coated balloons (DCBs) in coronary intervention is escalating. There is a plethora of data on Paclitaxcel-DCB. However, when it comes of stents, Limus-drugs are preferred over Paclitaxel. There is very limited data on Sirolimus coated balloons (SCB). MagicTouch-SCB (Concept Medical, FL) elutes Sirolimus via nano-technology and have been used in our centers since March 2018. We report a mid-term follow-up with this relatively novel-technology. Methods and results We retrospectively analyzed all patients treated with MagicTouch-SCB between March-2018 and February-2019. Results are reported as cardiac-death, target-vessel myocardial-infarction (TVMI), target lesion revascularization (TLR) and Major Adverse Cardiac Events (MACE). During the study period, 288-patients (373-lesions) with a mean age of 65.8 were treated with MagicTouch-SCB. 84% (n = 241) were male, 155 (54%) were in the setting of acute coronary syndrome, 38% (n = 110) had diabetes and 62% (n = 233) were in de-novo lesions. Most lesions treated were in the LAD/diagonal-system (n = 170; 46%). Pre-dilatation was performed in 92% (n = 345) of cases. Bailout stenting was required in 9% lesions (n = 35). The mean diameter and length of SCBs were 2.64 ± 0.56 mm and 24 ± 8.9 mm respectively. During a median follow-up of 363 days (IQR: 278-435), cardiac death and TVMI occurred in 5-patients (1.7%) and 10-patients (3.4%) respectively, TLR per-lesion was 12%. The MACE rate was 10%. There were no documented cases of acute vessel closure. Conclusions The results from mid-term follow-up with this relatively new technology SCB is encouraging with a low rates of hard endpoints and acceptable MACE rates despite complex group of patients and lesion subsets.

Background The incidence of bailout stenting post-drug coated balloon use (DCB) in the literature has been more than 10%; ranging up-to 21% in Bello trial and this variation could be due to the different criteria used to consider bailout stenting and may also reflect aggressive pre-dilatation. Our eyes are trained to expect stent like result and anything less is considered sub-optimal and this could be one of the reasons for high incidence of bailout stenting. The current recommendation is to use drug eluting stent (DES) for bailout stenting and hence raising in the possibility of drug toxicity or maybe even synergistic effect from combination of Paclitaxel (DCB) and limus (DES). Aim We have evaluated the incidence and outcomes of patients needing bailout stenting in our centre. Methods and results We evaluated all patients who were treated with DCB between January 2016-August 2017. Bailout stenting per lesion were identified and studied for endpoints which included cardiac death, target vessel MI, stent thrombosis, target lesion revascularization and target vessel revascularisation. Between the study period; 468 lesions (in 364 patients) were treated with paclitaxel DCB (Sequent Please, B Braun, Germany). Bailout stenting was required in 23 lesions (4.9%) and of which 12 (52%) was for flow limiting dissections (type C or more) and the remaining 11 was for recoil of more than 50%. Majority of the lesions were de novo (18; 78%). All bailout stenting was performed with third generation limus eluting stents. During a median follow-up of 18.14 months; range; 7–33 months, there was no cardiac death and target vessel MI occurred in 1 patient (4.3%), TLR and TVR were in 3 lesions (13%). MACE rate (combination of cardiac death, target vessel MI and TVR) was 13%. There were no cases of stent thrombosis as per the ARC definition. Conclusion One of the highlighting features of our study is very low-rates of bailout stenting. This may be due to our criteria of not stenting mild dissections (unless they are flow limiting) and also to accepting recoil of up-to 50% post-DCB use. The outcome in bailout stenting group is acceptable especially with hard endpoints (cardiac death, target vessel MI and stent thrombosis) although TLR and TVR rates were higher indicating synergistic effect of paclitaxel and limus may not offer additional benefits.

Bailout stenting post–paclitaxel drug-coated balloon use (DCB) is done with a limus-eluting stent, as we no longer use the paclitaxel-eluting stent. However, when using sirolimus DCB, bailout stenting is done with a limus-eluting stent, but this raises the issue of drug toxicity with a double dose

Use of drug-coated balloon (DCB) in de novo lesions is usually preferred in small vessels, and the recently reported Basket small 2 trial showed that DCBs were noninferior to second-generation DES. All the available data DCBs in de novo lesions have been extrapolated from paclitaxel-eluting balloons

Use of drug-coated balloons (DCBs) in coronary intervention is escalating. Most available DCBs elute paclitaxel, and there is a plethora of data on them. However, we prefer limus-eluting over paclitaxel-eluting stents. There is very limited data on sirolimus-eluting DCBs. MagicTouch (Concept Medical

In this paper, a method is introduced for approximating the likelihood for the unknown parameters of a state space model. The approximation converges to the true likelihood as the simulation size goes to infinity. In addition, the approximating likelihood is continuous as a function of the unknown parameters under rather general conditions. The approach advocated is fast and robust, and it avoids many of the pitfalls associated with current techniques based upon importance sampling. We assess the performance of the method by considering a linear state space model, comparing the results with the Kalman filter, which delivers the true likelihood. We also apply the method to a non-Gaussian state space model, the stochastic volatility model, finding that the approach is efficient and effective. Applications to continuous time finance models and latent panel data models are considered. Two different multivariate approaches are proposed. The neoclassical growth model is considered as an application.

Background Studies which have attempted to assess the predictive potential of socio-environmental risk factors for psychosis have used such a variety of datasets and methodologies. As a result, it is not possible for policy-makers to understand how different models compare, or might inform evidence-based policy-making. Thus, the cumulative predictive potential of non-genetic risk factors for psychosis has not yet been studied systematically. An important question which has not been considered previously is whether correlation structure between multivariate risks can be detrimental to the goal of prediction, particularly across different populations. Model fitting to locally-relevant correlation structures can limit the generalizability of a prediction model. Copulas are mathematical functions which allow the joint risk function of two or more correlated variables to be modelled in spite of this inherent bias. The copula approach is a foundation methodology with applications in the fields of finance, insurance and banking, where it is used for risk-management purposes. This study examines the impact of copulas on the stability of prediction power for psychosis across different populations. Methods The data used in this work comes from work package 2 (WP2) (entitled “Functional Enviromics”) of The European Union (EU)-funded European Network Study of Gene-Environment Interactions (EUGEI). The total dataset available consists of 1180 cases of first episode psychosis (ICD10 diagnostic criteria F20-F29 or F30-F33) and 1528 healthy controls recruited by 16 centres across 6 countries (United Kingdom, Holland, Spain, France, Italy, Brazil). We sought to compare the predictive performance of copulas against that of summary risk scores for formulating disease risk for a common set of socio-environmental risk factors. The copula methodology allows joint risks to be modelled as a distribution whilst summary scores convey the number of risk factors encountered by an individual, weighted by literature-derived odds ratios for association. Gaussian copula with non-Gaussian marginal distributions were used to capture the correlation structure of 9 discrete variables in total. These incorporated: Lifetime Cannabis Use, frequency of Cannabis Use, Household discord, severity of psychological abuse, severity of physical abuse, severity of sexual abuse, severity of bullying, number of adverse adult life events and intrusive adult life events. We applied a fully Bayesian approach which uses Markov Chain Monte Carlo to simulate latent variables from multivariate ordered probit model and also estimate the threshold parameters and parameters from copula model. The resulting joint distribution (a copula) mapped the relationship between cumulative exposure to these factors and risk of psychosis. Results A proportion of subjects were withheld from the copula, so that the performance of the finished function could be evaluated on unseen data. The performance of the 2 prediction methods was compared within and between recruitment centres and are conveyed in terms of: • Sensitivity and false positive rates (The area under the Receiver Operating Characteristic curve) • Percentage of variance explained (Nagelkerke R2) • Calibration (whether predicted risks were correct) • Discrimination (whether high risk subjects could be distinguished from low risk ones) • Reclassification (model behaviour close to specific thresholds) Discussion The application of the copula methodology to the multi-centre EUGEI dataset provides us with the opportunity to tackle a major limitation of the summary scoring approach which is the default method for aggregating risks across most areas of health research.

ObjectivesThis research was designed to assess the effect of type 2 diabetes mellitus (T2DM) on myocardial glucose utilization in patients with heart failure secondary to coronary artery disease.BackgroundPatients with T2DM and coronary artery disease have an increased morbidity and mortality compared with patients with coronary artery disease without diabetes that may relate to a reduction in the ability of the myocardium to utilize glucose.MethodsMyocardial blood flow and glucose utilization were assessed during a hyperinsulinemic clamp by 18F-flurodeoxyglucose and positron emission tomography in 54 patients (19 with T2DM) with multivessel coronary artery disease and heart failure. In a subgroup of 18 patients, myocardial biopsies were obtained during coronary bypass surgery to assess glucose transporter (GLUT4) distribution and protein concentration, and compared with myocardium from transplant donor hearts.ResultsMyocardial blood flow was similar in patients without diabetes and those with T2DM. Myocardial glucose utilization was lower in patients with T2DM (0.34 ± 0.16 vs. 0.47 ± 0.24 μmol·min−1·g−1, p = 0.0002) despite comparable plasma insulin concentrations and a higher blood glucose concentration. Extraction of glucose by the myocardium was reduced in patients with T2DM (7.1 ± 3.1% vs. 13.5 ± 5.2%, p < 0.01). Myocardial GLUT4 protein was similar in patients with and without T2DM (p = 0.75).ConclusionsPatients with coronary artery disease and heart failure exhibit myocardial insulin resistance, and this is greater in those with T2DM. This may limit the ability of the myocardium in patients with T2DM to withstand ischemia and may contribute to the increased cardiovascular morbidity and mortality in such patients.

A Gaussian copula regression model gives a tractable way of handling a multivariate regression when some of the marginal distributions are non-Gaussian. Our paper presents a general Bayesian approach for estimating a Gaussian copula model that can handle any combination of discrete and continuous marginals, and generalises Gaussian graphical models to the Gaussian copula framework. Posterior inference is carried out using a novel and efficient simulation method. The methods in the paper are applied to simulated and real data.

This paper extends recent ideas for constructing classes of stationary autoregressive processes of order 1. A Gibbs sampler representation of such processes is extended in a straightforward way to introduce new processes. These maintain a linear expectation property which provides a simple exponential form for the autocorrelation function.

New data are presented on the performance of thick film multilayer microwave components in the frequency range 30–40 GHz. It was seen that the performance of a novel microwave DC block has been enhanced through the use of broadside coupling between conductors in a multilayer structure. Very good results have shown that low loss and wideband performance at low mm-wave frequencies can be achieved through direct thick film printing. The effects of the properties of the materials employed are discussed in the context of minimum cost structures.

Here we present a novel method for modeling stationary time series. Our approach is to construct the model with a specified marginal family and build the dependence structure around it. We show that the resulting time series is linear with a simple autocorrelation structure. We construct models that parallel existing structures, namely state-space models, autoregressive conditional heteroscedasticity (ARCH) models, and generalized ARCH models. We use Bayesian techniques to estimate the resulting models. We also demonstrate that the models perform well compared with competing methods for the applications considered, count models and volatility models.

This paper examines the potential use of low cost materials and processes to produce thick film structures at low microwave frequencies. It examines empirically the upper frequency limits for the use of simple design techniques as a function of substrate thickness. It concludes that satisfactory results can be obtained using low cost methods up to about 12 GHz for 1 mm 96% alumina substrates and 16 GHz for 0.63 mm substrates. These are the most commonly available thick film substrate thicknesses. A low permittivity protective layer is desirable to maintain reliability.

To evaluate the potential of a continuous telemetry system linking rural ambulances to a coronary care unit to reduce call to thrombolysis times.This prospective randomised controlled trial recruited patients using the 999 ambulance service in a rural area of the UK with signs or symptoms of coronary heart disease. Subjects were assigned to receive either standard paramedic treatment or transmission of 12 lead ECG, blood pressure, pulse oximetry, and relevant medical history to a general hospital coronary care unit. Cardiology senior house officers then determined each patient's suitability for pre-hospital thrombolysis time, and transmitted this decision back to the ambulance. This was documented as the potential thrombolysis, although no thrombolytic agents were administered by paramedics. The between groups difference in time to potential thrombolysis (intervention group) and actual thrombolysis (controls) was compared. The proportion of intervention group subjects ultimately receiving thrombolysis in hospital was compared with that recommended for pre-hospital thrombolysis.The potential reduction in call to treatment time for telemetry patients recommended for pre-hospital thrombolysis was 55 minutes (p = 0.022). Following hospital admission,21/213 of the telemetry patients were thrombolysed (10%, 95% confidence interval (CI) 6% to 15%). Of these patients, 3/21 received a recommendation for thrombolysis in the ambulance (14%, 95% CI 3.1% to 36.3%). The sensitivity and specificity of the telemetry system in detecting patients requiring thrombolysis was 13.6 and 99.5% respectively. Errors were made in the pre-hospital treatment recommendations for two patients.Continuous telemetry systems may significantly reduce call to treatment times for patients recommended for pre-hospital thrombolysis in a rural setting. However, this benefit must be balanced against the very small proportion of eligible patients identified as suitable for pre-hospital thrombolysis. This limitation may be due to communications problems, the criteria used to identify eligible patients, or the seniority of physicians tasked with making treatment decisions.

In this article element-specific mapping using a broad-spectrum laboratory based X-ray source is reported. Element-specific and element-exempt images of silver nitrate and di-hydrated barium chloride have been obtained from raw images collected either side of the K-edges for silver and barium. The informed positioning of filters between the source and sample narrowed the X-ray spectra, thereby enhancing the final images. For barium, samples with a barium area density of less than 8×10 −5 g mm −2 have been analysed. The system used here can be employed for mapping the distribution of elements from the middle of the second row transition metals to the light lanthanides.

Thermal cycling is used as a diagnostic test for electronic equipment. It is particularly severe on solder joints that are under both compressive and tensile strain during a cycle as a result of differential thermal expansion. The electronics industry document IPC-SM-785 addresses this problem and provides means whereby joint failure can be predicted as a function of the type and number of cycles used. The method can be applied to both non-compliant ceramic chips and compliant packages on FR4 board. This paper describes the applicability of SM-785 for both compliant and non-compliant packages. Due to the change in metallurgy of solder at temperatures approaching −20 °C, the approach is restricted to temperatures where near eutectic tin–lead solder is in its non-elastic form. A new approach will be needed when lead-free joining becomes mandatory.

Aims Our aim was to follow changes in myocardial function and physiology in patients awaiting coronary artery bypass surgery (CABG) and relate changes to post-revascularisation functional response. Methods and results In 21 patients with CAD and LV dysfunction, myocardial glucose utilisation (MGU) and blood flow (MBF) were measured with positron emission tomography using F-18-fluorodeoxyglucose and oxygen-15-labelled water. Left ventricular function, MGU, and MBF were re-assessed after one year, immediately prior to CABG. At baseline, dysfunctional myocardium displayed a reduction in MGU, hyperaemic MBF, and coronary vasodilator reserve (CVR) compared to normally functioning muscle. In the year preceding CABG, the overall wall motion score index increased (2.09±0.65 vs. 2.3±0.7, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p=0.0001\) \end{document}) and the LV ejection fraction decreased (30.6±11.1% vs. 27.3±11.5%, \batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepackage{amsfonts} \usepackage{amsmath} \pagestyle{empty} \begin{document} \(p{

First order stationary autoregressive (AR(1)) models are introduced for which there exists a linear relation between the expectations of the observations, and where it is readily possible to arrange the marginal distributions to be other than normal.

To determine if low dose nalbuphine provides an adequate reduction in pain with minimal side effects.Prospective cohort of 115 patients given nalbuphine by paramedics in Wales and the English borders.(1) Mean total dose of nalbuphine administered, change in pain score, time to adequate pain relief (score below four), and change in respiratory rate and systolic blood pressure; (2) proportion of patients continuing to suffer moderate to severe pain on arrival at hospital; (3) incidence of adverse events.Full data were obtained for all patients. The mean total dose of nalbuphine administered was 6.09 mg (range 2.5 to 12.5 mg). This was significantly higher in trauma than ischaemic chest pain patients (7.03 versus 5.13 mg). The mean reduction in pain score was -3.97 (95% CI -4.38 to -3.57, p0.001). The mean time to adequate pain relief (where this was achieved) was 15.7 minutes (95% CI 13.4 to 17.9 minutes). On arrival at hospital 60% of patients (n=69, 95% CI 50.9 to 68.5%) still met ambulance criteria for analgesia (70.7% of trauma patients and 49.1% with ischaemic chest pain). Systolic blood pressure fell by a mean of -3.67 (95% CI -6.76 to -0.58, p=0.02) and respiratory rate increased by a mean of 1.63 (95% CI 1.08 to 2.17, p0.001). Two patients complained of nausea (1.74%, 95% CI 0.5 to 6.0%). No other adverse events were reported.Low dose nalbuphine results in few adverse events, but offers poor pain control for a high proportion of patients.

Crystal growth can be controlled by the incorporation of dopant ions into the lattice and yet the question of how such substituents affect the morphology has not been addressed. This paper describes the forms of calcite (CaCO3) which arise when the growth assay is doped with cobalt. Distinct and specific morphological changes are observed; the calcite crystals adopt a morphology which is dominated by the {01.1} family of faces. These experimental studies paralleled the development of computational methods for the analysis of crystal habit as a function of dopant concentration. In this case, the predicted defect morphology also argued for the dominance of the (01.1) face in the growth form. The appearance of this face was related to the preferential segregation of the dopant ions to the crystal surface. This study confirms the evolution of a robust computational model for the analysis of calcite growth forms under a range of environmental conditions and presages the use of such tools for the predictive development of crystal morphologies in those applications where chemico-physical functionality is linked closely to a specific crystallographic form.

In this article, we present a previously unreported morphology of bacterially precipitated calcite (determined using XRD, FTIR, and SAED) occurring subaqueously in Weebubbie Cave. Observations using FESEM and TEM revealed spindle-shaped crystals with curved {hk.O} faces lying parallel to the c-axis. Calcite precipitated under conditions designed to mimic the inorganic solution chemistry of the cave revealed a different morphology. These differences between the crystals suggest that the formation of the cave crystals is a consequence of biologically activity.

It is theoretically possible to calculate electrical losses in conductors at high frequencies using standard microstrip equations. To do this it is necessary to know the length, width and surface roughness of sample tracks. The sheet resistance at d.c. is replaced with a new term, surface resistance which is the bulk resistivity divided by the skin depth at the frequency under consideration. The paper looks at the relationship between these predictions and measured results. A wide range of commercial thick film conductors has had its physical properties measured and a comparison made with the figures for idealized structures. The paper contains a discussion on the differences between real and ideal materials. It was seen that the predictions were close to the measured results at lower frequencies, but that there was divergence as the frequency approached 15–20 GHz. For low-cost applications it is generally considered that economically viable conductors will be unsuitable for microwave applications. However, the paper discusses whether some of the lesser used conductors, such as fritted silver, could have an application in low-cost microwave devices, for example alarm systems. © 2001 Kluwer Academic Publishers

This paper describes the fabrication and test of a new low cost thick film system using base metals. The resistor pastes were developed using non-precious metal oxides and contain molybdenum trioxide and other additives. The conductors are either silver or nickel. The dielectrics contain barium oxide, but, unlike ruthenium based resistors, on related dielectrics, there is very little difference in resistor behavior on alumina from that on the dielectrics investigated. Long term stability tests show that the new resistor family, while less stable than those based on ruthenium, is suitable for many low cost applications. Results suggest that high temperature ageing tends to minimize contact effects and that they are compatible with both silver and nickel terminations.

This paper examines the influence of the materials on the electrical properties of conductors for both high speed MCM structures and microstrip applications. Calculated figures for attenuation in microstrip lines are compared with published results. It is seen that the nature and physical structure as well as the geometrical shape of a conductor track all strongly influence the microwave performance. However, it is also clear that real materials have been developed for these applications which closely approach the behavior predicted for ideal conductors. It is proposed that microwave performance can be predicted by modelling the d.c. conductor materials and extrapolating to high frequencies.

In this paper we obtain a closed form expression for the convergence rate of the Gibbs sampler applied to the unobserved states of a first-order autoregression plus noise model. The rate is expressed in terms of the parameters of the model, which are regarded as fixed. For the case where the unconditional mean of the states is a parameter of interest we provide evidence that a 'centred' parameterization of a state space model is preferable for the performance of the Gibbs sampler. These two results provide guidance when the Gaussianity or linearity of the state space form is lost. We illustrate this by examining the performance of a Markov chain Monte Carlo sampler for the stochastic volatility model.

This paper assesses the impact of changes in union density on the male structure in the United Kingdom over the 1980s. Using four separate data sets, the authors estimate the kernel density of hourly wages for men. Counterfactual densities are then generated to predict how the distribution of wages has changed over time because of the decline in union membership. They find that approximately 20 percent of the increase in the variance of log wages over the period can be attributed to changes in unionization. The effect is particularly strong in the latter part of the period. The authors also present disaggregated estimates of the impact of declining unionization. Their results are robust across all the data sets the authors examine and similar results are obtained if union coverage is used rather than union membership. Copyright 1998 by Blackwell Publishing Ltd

SUMMARY In this paper we provide methods for estimating non-Gaussian time series models. These techniques rely on Markov chain Monte Carlo to carry out simulation smoothing and Bayesian posterior analysis of parameters, and on importance sampling to estimate the likelihood function for classical inference. The time series structure of the models is used to ensure that our simulation algorithms are efficient.

In 1901 excavations by the German Archaeological Institute in the Lower Agora of pergamon uncovered an inscribed Hellenistic law laying out the duties and powers of the city astynomoi, a board of magistrates whose responsibilities included care for both city and suburban streets, city blocks and their party walls, water channels, fountains, and cisterns. The inscription provides a wealth of information about Hellenistic city planning and maintenance, as well as offering insights into the legal and procedural framework in which a variety of polis officials, citizens, and slaves operated. Keywords: city; legal history; urban history

Particle learning provides a simulation-based approach to sequential Bayesian computation. To sample from a posterior distribution of interest we use an essential state vector together with a predictive and propagation rule to build a resampling-sampling framework. Predictive inference and sequential Bayes factors are a direct by-product. Our approach provides a simple yet powerful framework for the construction of sequential posterior sampling strategies for a variety of commonly used models.

This article provides a description of time series methods that emphasize modern macroeconomics and finance. It discusses a variety of posterior simulation algorithms and illustrates their use in a range of models. This article introduces the state space framework and explains the main ideas behind filtering, smoothing, and likelihood computation. It also mentions the particle filter as a general approach for estimating state space models and gives a brief discussion of its methods. The particle filter is a very useful tool in the Bayesian analysis of the kinds of complicated nonlinear state space models that are increasingly being used in macroeconomics. It also deals with conditionally Gaussian state space models and non-Gaussian state space models. A discussion of the advantages and disadvantages of each algorithm is provided in this article. This aims to help with the use of these methods in empirical work.