New Paleocene skeletons and the relationship of plesiadapiforms to crown-clade primates.

Plesiadapiforms are central to studies of the origin and evolution of primates and other euarchontan mammals (tree shrews and flying lemurs). We report results from a comprehensive cladistic analysis using cranial, postcranial, and dental evidence including data from recently discovered Paleocene plesiadapiform skeletons (Ignacius clarkforkensis sp. nov.

Ranibizumab combined with verteporfin photodynamic therapy in neovascular age-related macular degeneration: year 1 results of the FOCUS Study.

Objective: To investigate the safety and efficacy of intravitreal ranibizumab treatment combined with verteporfin photodynamic therapy (PDT) in patients with predominantly classic choroidal neovascularization secondary to age-related macular degeneration.

Methods: In this 2-year, phase I/II, multicenter, randomized, single-masked, controlled study, patients received monthly ranibizumab (0.5 mg) (n = 106) or sham (n = 56) injections.

Significance of the arthroscopic meniscal flounce sign: a prospective study.

Background: The meniscal flounce sign is a fold in the free, nonanchored inner edge of the medial meniscus that can be noted during routine arthroscopy of the knee.

Hypothesis: The meniscal flounce sign can be a significant indicator of the presence or absence of medial meniscus injury.

Study Design: Cohort study (diagnosis); Level of evidence, 4.

Development of a deployment course for graduating military internal medicine residents.

Graduates of military internal medicine residency programs are required to have the necessary knowledge and skills to function as internists, military physicians, and military medical leaders. The global war on terrorism has increased the role internists are playing in combat theaters as they fill multiple different military medical positions including battalion, brigade, and division surgeons as well as physicians in echelon I, II, and III medical facilities. Along with general internists, internal medicine subspecialists, pediatricians, and family physicians also fill these roles.

Ranibizumab for neovascular age-related macular degeneration.

Background: Ranibizumab--a recombinant, humanized, monoclonal antibody Fab that neutralizes all active forms of vascular endothelial growth factor A--has been evaluated for the treatment of neovascular age-related macular degeneration.

Methods: In this multicenter, 2-year, double-blind, sham-controlled study, we randomly assigned patients with age-related macular degeneration with either minimally classic or occult (with no classic lesions) choroidal neovascularization to receive 24 monthly intravitreal injections of ranibizumab (either 0.3 mg or 0.

Anatomic reconstruction of the lateral ligament complex of the ankle using a gracilis autograft.

Many techniques have been described for surgical management of lateral ankle instability. Anatomic repair and nonanatomic reconstruction have higher recurrence rates, and may be complicated by ankle stiffness. Anatomic reconstruction should be considered in stabilization for deficiencies of the lateral ankle ligament complex, as the initial construct is stronger while maintaining normal ankle mechanics.

Complementation rescue of Pdx1 null phenotype demonstrates distinct roles of proximal and distal cis-regulatory sequences in pancreatic and duodenal expression.

The unique, well-demarcated expression domain of Pdx1 within the posterior foregut suggests that investigating its transcriptional regulation will provide insight into mechanisms that regionally pattern the endoderm. Previous phylogenetic comparison identified conserved noncoding regions that stimulate transcriptional activity selectively in cultured pancreatic beta cells. Characterization of these regulatory elements is helping to dissect the transcription factor networks that operate within beta cells, which is important for understanding the etiology of beta cell dysfunction and diabetes, as well as for developing methods to produce beta cells in vitro for cell-based therapies.

Churg-Strauss syndrome in children: a clinical and pathologic review.

Churg-Strauss syndrome is a vasculitis accompanied by asthma and eosinophilia. It is generally considered a disease of adults; occurrence in children has been reported infrequently. Here we report 2 pediatric patients with Churg-Strauss syndrome manifesting with prominent pulmonary involvement.

Scale-free foraging by primates emerges from their interaction with a complex environment.

Scale-free foraging patterns are widespread among animals. These may be the outcome of an optimal searching strategy to find scarce, randomly distributed resources, but a less explored alternative is that this behaviour may result from the interaction of foraging animals with a particular distribution of resources. We introduce a simple foraging model where individual primates follow mental maps and choose their displacements according to a maximum efficiency criterion, in a spatially disordered environment containing many trees with a heterogeneous size distribution.

Ectopic pancreas formation in Hes1 -knockout mice reveals plasticity of endodermal progenitors of the gut, bile duct, and pancreas.

Ectopic pancreas is a developmental anomaly occasionally found in humans. Hes1, a main effector of Notch signaling, regulates the fate and differentiation of many cell types during development. To gain insights into the role of the Notch pathway in pancreatic fate determination, we combined the use of Hes1-knockout mice and lineage tracing employing the Cre/loxP system to specifically mark pancreatic precursor cells and their progeny in Ptf1a-cre and Rosa26 reporter mice.

Stable expression of shRNAs in human CD34+ progenitor cells can avoid induction of interferon responses to siRNAs in vitro.

RNA interference occurs when cytoplasmic small interfering RNAs (siRNAs) enter the RNA-induced silencing complex and one strand guides cleavage of the target RNA by the Argonaute 2 protein. A significant concern when applying siRNAs or expressing small hairpin RNAs (shRNAs) in human cells is activation of the interferon (IFN) response. Synthetic siRNAs harboring certain motifs can induce an immune response when delivered to mouse and human immune cells such as peripheral blood mononuclear cells, monocytes, plasmacytoid dendritic cells (pDCs) and nonplasmacytoid dendritic cells (mDCs).

Outcomes associated with ganciclovir implants in patients with AIDS-related cytomegalovirus retinitis.

Purpose: To investigate complications associated with ganciclovir implants used to treat AIDS-related cytomegalovirus (CMV) retinitis, and to identify factors that predict poor outcomes.

Design: Retrospective chart review.

Participants: Consecutive patients with AIDS-related CMV retinitis from 3 clinical facilities who underwent implantation procedures during the period January 1, 1995 through December 31, 2001.

Targeted deletion of a cis-regulatory region reveals differential gene dosage requirements for Pdx1 in foregut organ differentiation and pancreas formation.

Pdx1 (IPF-1 in humans, which is altered in MODY-4) is essential for pancreas development and mature beta-cell function. Pdx1 is expressed dynamically within the developing foregut, but how its expression characteristics are linked to the various steps of organ specification, differentiation, and function is unknown. Deletion of a conserved enhancer region (Area I-II-III) from Pdx1 produced a hypomorphic allele (Pdx1(DeltaI-II-III)) with altered timing and level of expression, which was studied in combination with wild-type and protein-null alleles.

Transient floral change and rapid global warming at the Paleocene-Eocene boundary.

Rapid global warming of 5 degrees to 10 degrees C during the Paleocene-Eocene Thermal Maximum (PETM) coincided with major turnover in vertebrate faunas, but previous studies have found little floral change. Plant fossils discovered in Wyoming, United States, show that PETM floras were a mixture of native and migrant lineages and that plant range shifts were large and rapid (occurring within 10,000 years). Floral composition and leaf shape and size suggest that climate warmed by approximately 5 degrees C during the PETM and that precipitation was low early in the event and increased later.

S6 kinase 2 potentiates interleukin-3-driven cell proliferation.

Interleukin-3 (IL-3) mediates hematopoietic cell survival and proliferation via several signaling pathways such as the Janus kinase/signal transducer and activator of transcription pathway, mitogen-activated protein kinase (MAPK) pathway, and phosphoinositide-3 kinase (PI-3K) pathway. Mammalian target of rapamycin (mTOR) is one of the downstream targets of the PI-3K pathway, and it plays an important role in hematopoiesis and immune cell function. To better elucidate how mTOR mediates proliferation signals from IL-3, we assessed the role of S6 kinase 2 (S6K2), one of the downstream targets of mTOR, in IL-3 signaling.

Verteporfin therapy of subfoveal minimally classic choroidal neovascularization in age-related macular degeneration: 2-year results of a randomized clinical trial.

Objective: To compare the treatment effect and safety of photodynamic therapy with verteporfin using a standard (SF) or reduced (RF) light fluence rate with that of placebo therapy in patients with subfoveal minimally classic choroidal neovascularization (CNV) with age-related macular degeneration.

Design: Phase 2, multicenter, double-masked, placebo-controlled, randomized clinical trial.

Setting: Nineteen ophthalmology practices in North America and Europe.

Human monoclonal antibodies to Pseudomonas aeruginosa alginate that protect against infection by both mucoid and nonmucoid strains.

Two fully human mAbs specific for epitopes dependent on intact carboxylate groups on the C6 carbon of the mannuronic acid components of Pseudomonas aeruginosa alginate were found to promote phagocytic killing of both mucoid and nonmucoid strains as well as protection against both types of strains in a mouse model of acute pneumonia. The specificity of the mAbs for alginate was determined by ELISA and killing assays. Some strains of P.

Efficacy of verteporfin photodynamic therapy on laser-induced choroidal neovascularization and the ancillary effect on diabetic microvasculopathy.

Purpose: To demonstrate the efficacy of photodynamic therapy (PDT) in treating choroidal neovascularization (CNV) induced by laser photocoagulation for diabetic macular edema and its ancillary effect on surrounding diabetic microvascular abnormalities.

Methods: A retrospective interventional case series study in a clinical practice setting of four patients with proliferative diabetic retinopathy and clinically significant macular edema who had developed classic CNV in proximity to the area of previous laser photocoagulation. The lesions were treated with verteporfin PDT and followed with serial fluorescein angiography.

Numerical study of domain coarsening in anisotropic stripe patterns.

We study the coarsening of two-dimensional smectic polycrystals characterized by grains of oblique stripes with only two possible orientations. For this purpose, an anisotropic Swift-Hohenberg equation is solved. For quenches close enough to the onset of stripe formation, the average domain size increases with time as t(1/2).

Comparison of the dimensional accuracy of injection-molded denture base materials to that of conventional pressure-pack acrylic resin.

Purpose: This study compared the linear dimensional changes of 3 injection-molded denture base materials to that of conventionally processed polymethylmethacrylate (PMMA) resin.

Materials And Methods: An impression of an aluminum maxillary edentulous arch was made with a condensation silicone impression material (Denture Elasticon) to fabricate a gypsum master cast that was replicated as a silicone mold. A maxillary complete denture with acrylic teeth was waxed to full contour on the master cast and replicated to make 40 wax dentures.

Chronic central serous chorioretinopathy: photodynamic therapy.

Purpose: To demonstrate, using optical coherence and fluorescien angiography, the efficacy of photodynamic therapy in treating chronic central serous chorioretinopathy.

Design: Interventional case series.

Methods: A retrospective study in a clinical practice setting of four patients (five eyes) with chronic central serous chorioretinopathy.

Arthroscopic versus open treatment of anterior shoulder instability.

Open repair is the accepted mainstay of treatment for anterior shoulder instability, and consistently good clinical results have been reported in the literature. With the development of newer arthroscopic imbrication techniques, however, arthroscopy may eventually provide equivalent long-term efficacy.