Delayed outpatient follow-up beyond the first 6 weeks after AMI is associated with worse short-term and long-term patient medication adherence. These data support the concept that medication adherence is modifiable via improved care transitions.

Summary How the highly stereotyped morphologies of individual neurons are genetically specified is not well understood. We identify six transcription factors (TFs) expressed in a combinatorial manner in seven post-mitotic adult leg motor neurons (MNs) that are derived from a single neuroblast in Drosophila. Unlike TFs expressed in mitotically active neuroblasts, these TFs do not regulate each other's expression. Removing the activity of a single TF resulted in specific morphological defects, including muscle targeting and dendritic arborization, and in a highly specific walking defect in adult flies. In contrast, when the expression of multiple TFs was modified nearly complete transformations in MN morphologies were generated. These results show that the morphological characteristics of a single neuron are dictated by a combinatorial code of morphology TFs (mTFs). mTFs function at a previously unidentified regulatory tier downstream of factors acting in the NB, but independently of factors that act in terminally differentiated neurons.

SUMMARYAdult Drosophila walk using six multi-jointed legs, each controlled by ~50 leg motoneurons (MNs). Although MNs have stereotyped morphologies, little is known about how they are specified. Here, we describe the function of Hox genes and homothorax (hth), which encodes a Hox co-factor, in Drosophila leg MN development. Removing either Hox or Hth function from a single neuroblast (NB) lineage results in MN apoptosis. A single Hox gene, Antennapedia (Antp), is primarily responsible for MN survival in all three thoracic segments. When cell death is blocked, partially penetrant axon branching errors are observed in Hox mutant MNs. When single MNs are mutant, errors in both dendritic and axon arborizations are observed. Our data also suggest that Antp levels in postmitotic MNs are important for specifying their identities. Thus, in addition to being essential for survival, Hox and hth are required to specify accurate MN morphologies in a level-dependent manner.

Specification of muscle identity in Drosophila is a multistep process: early positional information defines competence groups termed promuscular clusters, from which muscle progenitors are selected, followed by asymmetric division of progenitors into muscle founder cells (FCs). Each FC seeds the formation of an individual muscle with morphological and functional properties that have been proposed to reflect the combination of transcription factors expressed by its founder. However, it is still unclear how early patterning and muscle-specific differentiation are linked. We addressed this question, using Collier (Col; also known as Knot) expression as both a determinant and read-out of DA3 muscle identity. Characterization of the col upstream region driving DA3 muscle specific expression revealed the existence of three separate phases of cis-regulation, correlating with conserved binding sites for different mesodermal transcription factors. Examination of col transcription in col and nautilus (nau) loss-of-function and gainof-function conditions showed that both factors are required for col activation in the 'naïve' myoblasts that fuse with the DA3 FC, thereby ensuring that all DA3 myofibre nuclei express the same identity programme. Together, these results indicate that separate sets of cis-regulatory elements control the expression of identity factors in muscle progenitors and myofibre nuclei and directly support the concept of combinatorial control of muscle identity.

SUMMARYHox transcription factors control many aspects of animal morphogenetic diversity. The segmental pattern of Drosophila larval muscles shows stereotyped variations along the anteroposterior body axis. Each muscle is seeded by a founder cell and the properties specific to each muscle reflect the expression by each founder cell of a specific combination of 'identity' transcription factors. Founder cells originate from asymmetric division of progenitor cells specified at fixed positions. Using the dorsal DA3 muscle lineage as a paradigm, we show here that Hox proteins play a decisive role in establishing the pattern of Drosophila muscles by controlling the expression of identity transcription factors, such as Nautilus and Collier (Col), at the progenitor stage. Highresolution analysis, using newly designed intron-containing reporter genes to detect primary transcripts, shows that the progenitor stage is the key step at which segment-specific information carried by Hox proteins is superimposed on intrasegmental positional information. Differential control of col transcription by the Antennapedia and Ultrabithorax/Abdominal-A paralogs is mediated by separate cis-regulatory modules (CRMs). Hox proteins also control the segment-specific number of myoblasts allocated to the DA3 muscle. We conclude that Hox proteins both regulate and contribute to the combinatorial code of transcription factors that specify muscle identity and act at several steps during the muscle-specification process to generate muscle diversity.

The diversity of Drosophila muscles correlates with the expression of combinations of identity transcription factors (iTFs) in muscle progenitors. Here, we address the question of when and how a combinatorial code is translated into muscle specific properties, by studying the roles of the Collier and Nautilus iTFs that are expressed in partly overlapping subsets of muscle progenitors. We show that the three dorso-lateral (DL) progenitors which express Nautilus and Collier are specified in a fixed temporal sequence and that each expresses additionally other, distinct iTFs. Removal of Collier leads to changes in expression of some of these iTFs and mis-orientation of several DL muscles, including the dorsal acute DA3 muscle which adopts a DA2 morphology. Detailed analysis of this transformation revealed the existence of two steps in the attachment of elongating muscles to specific tendon cells: transient attachment to alternate tendon cells, followed by a resolution step selecting the final sites. The multiple cases of triangular-shaped muscles observed in col mutant embryos indicate that transient binding of elongating muscle to exploratory sites could be a general feature of the developing musculature. In nau mutants, the DA3 muscle randomly adopts the attachment sites of the DA3 or DO5 muscles that derive from the same progenitor, resulting in a DA3, DO5-like or bifid DA3-DO5 orientation. In addition, nau mutant embryos display thinner muscle fibres. Together, our data show that the sequence of expression and combinatorial activities of Col and Nau control the pattern and morphology of DL muscles.

SUMMARYThe LIM-homeodomain transcription factor Tailup/Islet1 (Tup) is a key component of cardiogenesis in Drosophila and vertebrates. We report here an additional major role for Drosophila Tup in specifying dorsal muscles. Tup is expressed in the four dorsal muscle progenitors (PCs) and tup-null embryos display a severely disorganized dorsal musculature, including a transformation of the dorsal DA2 into dorsolateral DA3 muscle. This transformation is reciprocal to the DA3 to DA2 transformation observed in collier (col) mutants. The DA2 PC, which gives rise to the DA2 muscle and to an adult muscle precursor, is selected from a cluster of myoblasts transiently expressing both Tinman (Tin) and Col. The activation of tup by Tin in the DA2 PC is required to repress col transcription and establish DA2 identity. The transient, partial overlap between Tin and Col expression provides a window of opportunity to distinguish between DA2 and DA3 muscle identities. The function of Tup in the DA2 PC illustrates how single cell precision can be reached in cell specification when temporal dynamics are combined with positional information. The contributions of Tin, Tup and Col to patterning Drosophila dorsal muscles bring novel parallels with chordate pharyngeal muscle development.

COPDOriginal Research tion (PCI) for revascularization. Although patients with COPD currently make up almost 10% of patients undergoing PCI, 7 limited data reveal an increased risk of mortality. [7][8] Potential factors associated with this A mong the 10 most common causes of death in the United States, COPD is the only one that is increasing in frequency. 1 Independent of smoking status, patients with COPD are at increased risk for cardiovascular disease. 2 Additionally, the presence of coronary artery disease in these patients is associated with increased mortality and decreased quality of life. 3 Management of coronary artery disease in patients with chronic COPD can present therapeutic challenges. Given that COPD is associated with higher risk for adverse events after coronary artery bypass graft surgery (CABG), 4-6 patients with COPD may be preferentially referred for percutaneous coronary intervenBackground: Previous studies have demonstrated that patients with COPD are at higher risk for death after percutaneous coronary intervention (PCI), but other clinical outcomes and possible associations with adverse events have not been described. Methods: Using waves 1 through 5 (1999-2006) of the National Heart, Lung, and Blood Institute Dynamic Registry, patients with COPD (n 5 860) and without COPD (n 5 10,048) were compared. Baseline demographics, angiographic characteristics, and in-hospital and 1-year adverse events were compared. Results: Patients with COPD were older (mean age 66.8 vs 63.2 years, P , .001), more likely to be women, and more likely to have a history of diabetes, prior myocardial infarction, peripheral arterial disease, renal disease, and smoking. Patients with COPD also had a lower mean ejection fraction (49.1% vs 53.0%, P , .001) and a greater mean number of signifi cant lesions (3.2 vs 3.0, P 5 .006). Rates of in-hospital death (2.2% vs 1.1%, P 5 .003) and major entry site complications (6.6% vs 4.2%, P , .001) were higher in pulmonary patients. At discharge, pulmonary patients were signifi cantly less likely to be prescribed aspirin (92.4% vs 95.3%, P , .001), b -blockers (55.7% vs 76.2%, P , .001), and statins (60.0% vs 66.8%, P , .001). After adjustment, patients with COPD had signifi cantly increased risk of death (hazard ratio [HR] 5 1.30, 95% CI 5 1.01-1.67) and repeat revascularization (HR 5 1.22, 95% CI 5 1.02-1.46) at 1 year, compared with patients without COPD. Conclusions: COPD is associated with higher mortality rates and repeat revascularization within 1 year after PCI. These higher rates of adverse outcomes may be associated with lower rates of guidelinerecommended class 1 medications prescribed at discharge. CHEST 2011; 140(3):604-610Abbreviations: CABG 5 coronary artery bypass graft surgery; CHF 5 congestive heart failure; HR 5 hazard ratio; MACE 5 major adverse cardiac event; MI 5 myocardial infarction; NHLBI 5 National Heart, Lung, and Blood Institute; PCI 5 percutaneous coronary intervention