The VGAM Package for Categorical Data Analysis

Classical categorical regression models such as the multinomial logit and proportional odds models are shown to be readily handled by the vector generalized linear and additive model (VGLM/VGAM) framework. Additionally, there are natural extensions, such as reduced-rank VGLMs for dimension reduction, and allowing covariates that have values specific to each linear/additive predictor, e.g., for consumer choice modeling. This article describes some of the framework behind the VGAM R package, its usage and implementation details.

Fossa Navicularis Strictures Due to 22F Catheters Used in Robotic Radical Prostatectomy

Background and objectivesFossa navicularis strictures following radical prostatectomy are reported infrequently. We recently experienced a series of fossa strictures following robot-assisted laparoscopic radical prostatectomy. Fossa strictures are usually procedure-induced, arising from urethral trauma or infection; catheter size has not been reported as a factor. We describe herein our experience to determine and prevent fossa navicularis stricture development.MethodsFrom June 2002 until February 2005, 248 patients underwent robot-assisted laparoscopic prostatectomy with the da Vinci surgical system at our institution. Fossa strictures were diagnosed based on acute onset of obstructive voiding symptoms, IPSS and flow pattern changes, and bougie calibration. During our series, we switched from an 18F to a 22F catheter to avoid inadvertent stapling of the urethra when dividing the dorsal venous complex. All patients had an 18F catheter placed after the anastomosis for 1 week. Parameters were evaluated using Fisher's exact test and the Student t test for means.ResultsThe 18F catheter group (n=117) developed 1 fossa stricture, whereas the 22F catheter group (n=131) developed 9 fossa strictures (P=0.02). The fossa stricture rate in the 18F group was 0.9% versus 6.9% in the 22F group. The 2 groups had no differences in age, body mass index, cardiovascular disease, International Prostate Symptom Score, urinary bother score, SHIM score, preoperative PSA, operative time, estimated blood loss, cautery use, prostate size, or catheterization time.ConclusionsUsing a larger urethral catheter size during intraoperative dissection appears to increase the risk 8-fold for fossa stricture as compared with the 18F catheter. The pneumoperitoneum and prolonged extreme Trendelenberg position could potentially contribute to local urethral ischemia

Osteocyte dysfunction promotes osteoarthritis through MMP13-dependent suppression of subchondral bone homeostasis.

Osteoarthritis (OA), long considered a primary disorder of articular cartilage, is commonly associated with subchondral bone sclerosis. However, the cellular mechanisms responsible for changes to subchondral bone in OA, and the extent to which these changes are drivers of or a secondary reaction to cartilage degeneration, remain unclear. In knee joints from human patients with end-stage OA, we found evidence of profound defects in osteocyte function. Suppression of osteocyte perilacunar/canalicular remodeling (PLR) was most severe in the medial compartment of OA subchondral bone, with lower protease expression, diminished canalicular networks, and disorganized and hypermineralized extracellular matrix. As a step toward evaluating the causality of PLR suppression in OA, we ablated the PLR enzyme MMP13 in osteocytes while leaving chondrocytic MMP13 intact, using Cre recombinase driven by the 9.6-kb DMP1 promoter. Not only did osteocytic MMP13 deficiency suppress PLR in cortical and subchondral bone, but it also compromised cartilage. Even in the absence of injury, osteocytic MMP13 deficiency was sufficient to reduce cartilage proteoglycan content, change chondrocyte production of collagen II, aggrecan, and MMP13, and increase the incidence of cartilage lesions, consistent with early OA. Thus, in humans and mice, defects in PLR coincide with cartilage defects. Osteocyte-derived MMP13 emerges as a critical regulator of cartilage homeostasis, likely via its effects on PLR. Together, these findings implicate osteocytes in bone-cartilage crosstalk in the joint and suggest a causal role for suppressed perilacunar/canalicular remodeling in osteoarthritis

Principles and principals: Do customer stewardship and agency control compete or complement when shaping frontline employee behavior?

This article introduces customer stewardship control (CSC) to the marketing field. This concept represents a frontline employee's felt ownership of and moral responsibility for customers' overall welfare. In two studies, the authors show that CSC is a more encompassing construct than customer orientation, which reflects a frontline employee's focus on meeting customers' needs. They provide evidence that the former is more potent in shaping in- and extra-role employee behaviors. Moreover, they highlight how CSC operates in conjunction with an organization's agency control system: Stewardship's positive influence on in- and extra-role behavior is weaker in the presence of high agency control. They offer actionable advice about how to solve the resulting managerial control dilemma. Finally, the authors show that CSC depends on drivers that reside at the individual level (employee relatedness), the team level (team competence), or both levels of aggregation (employee and team autonomy). These findings show how to effectively design a frontline employee's work environment to ensure optimal frontline performance

RNA-binding protein CPEB1 remodels host and viral RNA landscapes.

Host and virus interactions occurring at the post-transcriptional level are critical for infection but remain poorly understood. Here, we performed comprehensive transcriptome-wide analyses revealing that human cytomegalovirus (HCMV) infection results in widespread alternative splicing (AS), shortening of 3' untranslated regions (3' UTRs) and lengthening of poly(A)-tails in host gene transcripts. We found that the host RNA-binding protein CPEB1 was highly induced after infection, and ectopic expression of CPEB1 in noninfected cells recapitulated infection-related post-transcriptional changes. CPEB1 was also required for poly(A)-tail lengthening of viral RNAs important for productive infection. Strikingly, depletion of CPEB1 reversed infection-related cytopathology and post-transcriptional changes, and decreased productive HCMV titers. Host RNA processing was also altered in herpes simplex virus-2 (HSV-2)-infected cells, thereby indicating that this phenomenon might be a common occurrence during herpesvirus infections. We anticipate that our work may serve as a starting point for therapeutic targeting of host RNA-binding proteins in herpesvirus infections

A Detailed Observational Analysis of V1324 Sco, the Most Gamma-Ray Luminous Classical Nova to Date

It has recently been discovered that some, if not all, classical novae emit GeV gamma rays during outburst, but the mechanisms involved in the production of the gamma rays are still not well understood. We present here a comprehensive multi-wavelength dataset---from radio to X-rays---for the most gamma-ray luminous classical nova to-date, V1324 Sco. Using this dataset, we show that V1324 Sco is a canonical dusty Fe-II type nova, with a maximum ejecta velocity of 2600 km s$^{-1}$ and an ejecta mass of few $\times 10^{-5}$ M$_{\odot}$. There is also evidence for complex shock interactions, including a double-peaked radio light curve which shows high brightness temperatures at early times. To explore why V1324~Sco was so gamma-ray luminous, we present a model of the nova ejecta featuring strong internal shocks, and find that higher gamma-ray luminosities result from higher ejecta velocities and/or mass-loss rates. Comparison of V1324~Sco with other gamma-ray detected novae does not show clear signatures of either, and we conclude that a larger sample of similarly well-observed novae is needed to understand the origin and variation of gamma rays in novae.Comment: 26 pages, 13 figure

Supramolecular chemistry enables vat photopolymerization 3D printing of novel water-soluble tablets

Vat photopolymerization has garnered interest from pharmaceutical researchers for the fabrication of personalised medicines, especially for drugs that require high precision dosing or are heat labile. However, the 3D printed structures created thus far have been insoluble, limiting printable dosage forms to sustained-release systems or drug-eluting medical devices which do not require dissolution of the printed matrix. Resins that produce water-soluble structures will enable more versatile drug release profiles and expand potential applications. To achieve this, instead of employing cross-linking chemistry to fabricate matrices, supramolecular chemistry may be used to impart dynamic interaction between polymer chains. In this study, water-soluble drug-loaded printlets (3D printed tablets) are fabricated via digital light processing (DLP) 3DP for the first time. Six formulations with varying ratios of an electrolyte acrylate monomer, [2-(acryloyloxy)ethyl]trimethylammonium chloride (TMAEA), and a co-monomer, 1-vinyl-2-pyrrolidone (NVP), were prepared to produce paracetamol-loaded printlets. 1H NMR spectroscopy analysis confirmed the integration of TMAEA and NVP in the polymer, and residual TMAEA monomers were found to be present only in trace amounts (0.71 - 1.37 %w/w). The apparent molecular mass of the photopolymerised polymer was found to exceed 300,000 Da with hydrodynamic radii of 15 - 20 nm, estimated based on 1H DOSY NMR measurements The loaded paracetamol was completely released from the printlets between 45 minutes to 5 hours. In vivo single-dose acute toxicity studies in rats suggest that the printlets did not cause any tissue damage. The findings reported in this study represent a significant step towards the adoption of vat photopolymerization-based 3DP to produce personalised medicines

Expansion of a single transposable element family is associated with genome-size increase and radiation in the genus Hydra

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.Transposable elements are one of the major contributors to genome-size differences in metazoans. Despite this, relatively little is known about the evolutionary patterns of element expansions and the element families involved. Here we report a broad genomic sampling within the genus Hydra, a freshwater cnidarian at the focal point of diverse research in regeneration, symbiosis, biogeography, and aging. We find that the genome of Hydra is the result of an expansion event involving long interspersed nuclear elements and in particular a single family of the chicken repeat 1 (CR1) class. This expansion is unique to a subgroup of the genus Hydra, the brown hydras, and is absent in the green hydra, which has a repeat landscape similar to that of other cnidarians. These features of the genome make Hydra attractive for studies of transposon-driven genome expansions and speciation