Update on the everolimus-eluting coronary stent system: results and implications from the SPIRIT clinical trial program

Drug-eluting stents (DES) have had a major impact in interventional cardiology. Compared to bare metal stents, they significantly reduce restenosis and the need for target vessel revascularization. Four DES are available in the US, the first-generation sirolimus-eluting (Cypher®) and paclitaxel-eluting (Taxus®) stents and later approved second-generation everolimus-eluting (Xience V®) and zotarolimus-eluting (Endeavor®) stents. The Xience V stent was approved on the basis of clinical efficacy and safety data from 3 studies in the SPIRIT clinical trial program. Within this trial series, the Xience V was superior to its bare metal stent counterpart, the Vision® stent, and noninferior to the paclitaxel-eluting stent for target vessel failure at 9 months. This review provides a comprehensive assessment of the data derived from both the pre- and post-approval randomized controlled trials and registry studies of Xience V that comprise the SPIRIT clinical trial program including recently published mid-term outcomes. The implications of the results in terms of interventional practice will be discussed

1,2,3-Trifluoro­benzene

In the title compound, C6H3F3, weak electrostatic and dispersive forces between C(δ+)—F(δ−) and H(δ+)—C(δ−) groups are at the borderline of the hydrogen-bond phenomenon and are poorly directional and further deformed in the presence of π–π stacking inter­actions. The mol­ecule lies on a twofold rotation axis. In the crystal structure, one-dimensional tapes are formed via two anti­dromic C—H⋯F hydrogen bonds. These tapes are, in turn, connected into corrugated two-dimensional sheets by bifurcated C—H⋯F hydrogen bonds. Packing in the third dimension is furnished by π–π stacking inter­actions with a centroid–centroid distance of 3.6362 (14) Å

1,3-Difluoro­benzene

The weak electrostatic and dispersive forces between C(δ+)—F(δ−) and H(δ+)—C(δ−) are at the borderline of the hydrogen-bond phenomenon and are poorly directional and further deformed in the presence of other dominant inter­actions, e.g. C—H⋯π. The title compound, C6H4F2, Z′ = 2, forms one-dimensional tapes along two homodromic C—H⋯F hydrogen bonds. The one-dimensional tapes are connected into corrugated two-dimensional sheets by further bi- or trifrucated C—H⋯F hydrogen bonds. Packing in the third dimension is controlled by C—H⋯π inter­actions

Role of Elastic Projectile-Electron Scattering in Double Ionization of Helium by Fast Proton Impact

We present a systematic study of atomic four-body fragmentation dynamics. To this end we have measured a variety of multiple differential double ionization cross sections for 6 MeV p+He collisions. The data are compared to a first-order calculation with correlated electrons and to a simulation representing a second-order process, with some experimental results seemingly in favor of the first, others in agreement with the second approach. This apparent conflict can be resolved by accounting for elastic scattering between the projectile and one electron already promoted to the continuum through electron-electron correlation in the first-order process

Structural basis for bending of organic crystals

Bending is observed in organic crystals when the packing is anisotropic in such a way that strong and weak interaction patterns occur in nearly perpendicular directions

Systematic Analysis of Double-Ionization Dynamics Based on Four-Body Dalitz Plots

We report on an experimental and theoretical systematic study of double ionization of helium by ion impact in terms of four-particle Dalitz plots. Several collision systems covering abroad range of perturbation parameters η (projectile charge to speed ratio) were investigated. With increasing η we observe a systematic trend from features, characteristic to correlated double-ionization mechanisms, to signatures of higher-order processes not requiring electron-electron correlations [the mechanism called two-step-two projectile-electron interaction (TS-2)]. The data for the largest η can qualitatively be amazingly well described by a simple model only including the TS-2 mechanism

Ultra-low temperature structure determination of a Mn12 single-molecule magnet and the interplay between lattice solvent and structural disorder

We have determined the ultra-low temperature crystal structure of the archetypal single-molecule magnet (SMM) [Mn12O12(O2CMe)16(H2O)4]·4H2O·2MeCO2H (1) at 2 K, by using a combination of single-crystal X-ray and single-crystal neutron diffraction. This is the first structural study of any SMM in the same temperature regime where slow magnetic relaxation occurs. We reveal an additional hydrogen bonding interaction between the {Mn12} cluster and its solvent of crystallisation, which shows how the lattice solvent transmits disorder to the acetate ligands in the {Mn12} complex. Unusual quantum properties observed in 1 have long been attributed to disorder. Hence, we studied the desolvation products of 1, in order to understand precisely the influence of lattice solvent on the structure of the cluster. We present two new axially symmetric structures corresponding to different levels of desolvation of 1, [Mn12O12(O2CMe)16(H2O)4]·4H2O (2) and [Mn12O12(O2CMe)16(H2O)4] (3). In 2, removal of acetic acid of crystallisation largely resolves positional disorder in the affected acetate ligands, whereas removal of lattice water molecules further resolves the acetate ligand disorder in 3. Due to the absence of acetic acid of crystallisation, both 2 and 3 have true, unbroken S4 symmetry, showing for the first time that it is possible to prepare fully axial Mn12–acetate analogues from 1, via single-crystal to single-crystal transformations

pERK, pAKT and p53 as tissue biomarkers in erlotinib-treated patients with advanced pancreatic cancer: a translational subgroup analysis from AIO-PK0104

Background: The role of pERK, pAKT and p53 as biomarkers in patients with advanced pancreatic cancer has not yet been defined. Methods: Within the phase III study AIO-PK0104 281 patients with advanced pancreatic cancer received an erlotinib-based 1st-line regimen. Archival tissue from 153 patients was available for central immunohistochemistry staining for pERK, pAKT and p53. Within a subgroup analysis, biomarker data were correlated with efficacy endpoints and skin rash using a Cox regression model. Results: Fifty-five out of 153 patients were classified as pERK(low) and 98 patients as pERK(high); median overall survival (OS) was 6.2 months and 5.7 months, respectively (HR 1.29, p = 0.16). When analysing pERK as continuous variable, the pERK score was significantly associated with OS (HR 1.06, 95% CI 1.0-1.12, p = 0.05). Twenty-one of 35 patients were pAKT(low) and 14/35 pAKT(high) with a corresponding median OS of 6.4 months and 6.8 months, respectively (HR 1.03, p = 0.93). Four out of 50 patients had a complete loss of p53 expression, 20 patients a regular expression and 26 patients had tumors with p53 overexpression. The p53 status had no impact on OS (p = 0.91); however, a significant improvement in progression-free survival (PFS) (6.0 vs 1.8 months, HR 0.24, p = 0.02) and a higher rate of skin rash (84% vs 25%, p = 0.02) was observed for patients with a regular p53 expression compared to patients with a complete loss of p53. Conclusion: pERK expression may have an impact on OS in erlotinib-treated patients with advanced pancreatic cancer; p53 should be further investigated for its potential role as a predictive marker for PFS and skin rash

Using smartphone survey and GPS data to inform smoking cessation intervention delivery: Case study

Background: Interest in quitting smoking is common among young adults who smoke, but it can prove challenging. Although evidence-based smoking cessation interventions exist and are effective, a lack of access to these interventions specifically designed for young adults remains a major barrier for this population to successfully quit smoking. Therefore, researchers have begun to develop modern, smartphone-based interventions to deliver smoking cessation messages at the appropriate place and time for an individual. A promising approach is the delivery of interventions using geofences—spatial buffers around high-risk locations for smoking that trigger intervention messages when an individual’s phone enters the perimeter. Despite growth in personalized and ubiquitous smoking cessation interventions, few studies have incorporated spatial methods to optimize intervention delivery using place and time information. Objective: This study demonstrates an exploratory method of generating person-specific geofences around high-risk areas for smoking by presenting 4 case studies using a combination of self-reported smartphone-based surveys and passively tracked location data. The study also examines which geofence construction method could inform a subsequent study design that will automate the process of deploying coping messages when young adults enter geofence boundaries. Methods: Data came from an ecological momentary assessment study with young adult smokers conducted from 2016 to 2017 in the San Francisco Bay area. Participants reported smoking and nonsmoking events through a smartphone app for 30 days, and GPS data was recorded by the app. We sampled 4 cases along ecological momentary assessment compliance quartiles and constructed person-specific geofences around locations with self-reported smoking events for each 3-hour time interval using zones with normalized mean kernel density estimates exceeding 0.7. We assessed the percentage of smoking events captured within geofences constructed for 3 types of zones (census blocks, 500 ft2 fishnet grids, and 1000 ft2 fishnet grids). Descriptive comparisons were made across the 4 cases to better understand the strengths and limitations of each geofence construction method. Results: The number of reported past 30-day smoking events ranged from 12 to 177 for the 4 cases. Each 3-hour geofence for 3 of the 4 cases captured over 50% of smoking events. The 1000 ft2 fishnet grid captured the highest percentage of smoking events compared to census blocks across the 4 cases. Across 3-hour periods except for 3:00 AM-5:59 AM for 1 case, geofences contained an average of 36.4%-100% of smoking events. Findings showed that fishnet grid geofences may capture more smoking events compared to census blocks. Conclusions: Our findings suggest that this geofence construction method can identify high-risk smoking situations by time and place and has potential for generating individually tailored geofences for smoking cessation intervention delivery. In a subsequent smartphone-based smoking cessation intervention study, we plan to use fishnet grid geofences to inform the delivery of intervention messages