A prospective observational study of mycophenolate mofetil treatment in progressive diffuse cutaneous systemic sclerosis of recent onset.

OBJECTIVE: A prospective observational study of mycophenolate mofetil (MMF) treatment in patients with diffuse progressive cutaneous systemic sclerosis (SSc) of recent onset. METHODS: Twenty-five previously untreated consecutive patients with recent-onset (\u3c 24 mo) diffuse progressive cutaneous SSc received MMF as the only disease-modifying therapy. Modified Rodnan skin score (mRSS) and affected body surface area (BSA) were compared from initiation of MMF to study end. Pulmonary function tests performed at the same institution before therapy and at study end were available in 15 patients. Histopathology and real-time PCR assessment of fibrosis-related gene expression were performed before and after treatment in skin biopsies from 3 patients. RESULTS: At 18.2 ± 8.73 months of MMF therapy (median 2000 mg/day) the mRSS decreased from 24.56 ± 8.62 to 14.52 ± 10.9 (p = 0.0004) and the affected BSA from 36% ± 16% to 14% ± 13.3% (p = 0.00001). Pulmonary function tests remained stable from initiation of MMF to the end of the study. Skin histopathology showed a remarkable reduction in accumulation of fibrotic tissue. Real-time PCR of skin biopsies demonstrated a marked decrease in expression of fibrosis-related genes. CONCLUSION: Patients with diffuse progressive cutaneous SSc of recent onset treated with MMF experienced marked improvement in skin involvement and stabilization of pulmonary function. Skin biopsies from 3 patients demonstrated histopathological improvement and decreased expression of fibrosis-related genes

Hamiltonian analysis of subcritical stochastic epidemic dynamics

We extend a technique of approximation of the long-term behavior of a supercritical stochastic epidemic model, using the WKB approximation and a Hamiltonian phase space, to the subcritical case. The limiting behavior of the model and approximation are qualitatively different in the subcritical case, requiring a novel analysis of the limiting behavior of the Hamiltonian system away from its deterministic subsystem. This yields a novel, general technique of approximation of the quasistationary distribution of stochastic epidemic and birth-death models, and may lead to techniques for analysis of these models beyond the quasistationary distribution. For a classic SIS model, the approximation found for the quasistationary distribution is very similar to published approximations but not identical. For a birth-death process without depletion of susceptibles, the approximation is exact. Dynamics on the phase plane similar to those predicted by the Hamiltonian analysis are demonstrated in cross-sectional data from trachoma treatment trials in Ethiopia, in which declining prevalences are consistent with subcritical epidemic dynamics

Engaging Older Youth: Program and City-Level Strategies to Support Sustained Participation in Out-of-School Time

With support from The Wallace Foundation, the Harvard Family Research Project and P/PV conducted a study of almost 200 out-of-school-time (OST) programs in six cities to better understand how they promote sustained participation among older youth.The resulting data indicated that two of the most important practices distinguishing high-retention programs were: ample leadership opportunities for youth and high levels of staff efforts to keep informed about participants' lives outside the programs. The study also compares and contrasts effective practices for middle school- versus high school-aged youth, noting the shortcomings of "one-size-fits-all" strategies. Finally, Engaging Older Youth details the influence of city-level OST initiatives on programs and identifies the types of city-level services that likely support participation

Quenching star formation: Insights from the local main sequence

The so-called star-forming main sequence of galaxies is the apparent tight relationship between the star formation rate and stellar mass of a galaxy. Many studies exclude galaxies which are not strictly ‘star forming’ from the main sequence, because they do not lie on the same tight relation. Using local galaxies in the Sloan Digital Sky Survey, we have classified galaxies according to their emission line ratios, and studied their location on the star formation rate–stellar mass plane. We find that galaxies form a sequence from the ‘blue cloud’ galaxies which are actively forming stars, through a combination of composite, Seyfert, and low-ionization nuclear emission-line region galaxies, ending as ‘red-and-dead’ galaxies. The sequence supports an evolutionary pathway for galaxies in which star formation quenching by active galactic nuclei plays a key rol

Evaluation of 4 Outcomes Measures in Microtia Treatment: Exposures, Infections, Aesthetics, and Psychosocial Ramifications.

BackgroundIn craniofacial microsomia, microtia and canal atresia pose formidable reconstructive challenges. We review our institutional experience in treating microtia and atresia to identify variables associated with 4 outcomes measures: complications, surgical revisions, aesthetic outcomes, and psychosocial function.MethodsCraniofacial microsomia patients treated at the University of California Los Angeles Craniofacial Clinic between 2008 and 2014 greater than 13 years of age (n = 68) were reviewed for microtia and atresia treatment and outcomes.ResultsIn total, 91.2% of patients diagnosed with craniofacial microsomia presented with microtia, affecting 75 ears. Both a male and right-sided predominance were observed. Fifty-six patients (90.3%) underwent autologous external ear reconstruction at an average age of 8.5 years. Age, type of incision, and size of cartilage framework did not predict total number of surgeries or complications. Severity of ear anomalies correlated with increased number of surgeries (P < 0.001) and decreased aesthetic outcomes (P < 0.001) but not complications. In total, 87.1% of patients with microtia had documented hearing loss, of which the majority were conductive and 18.5% were mixed sensorineural and conductive. Hearing deficits were addressed in 70.4% of patients with external hearing aids, bone anchored hearing aids, or canaloplasty. Of all variables, improvement of psychosocial function was correlated only to hearing loss treatment of any type (P = 0.01).ConclusionsOn evaluation of surgical and patient characteristics, severity of microtia predicted the total number of surgical revisions performed and aesthetic ratings. In addition, we found that the only factor that correlated with improved patient and parent-reported psychosocial outcomes was treatment of hearing loss

Pleistocene till provenance in east Yorkshire:Reconstructing ice flow of the British North Sea Lobe

The ice flow path and dynamic behaviour of the British-Irish Ice Sheet has been subject to renewed interest and controversy in recent years. Early studies in eastern England argued for interaction with Fennoscandian ice onshore in Britain, instigating re-examination of the sedimentology and provenance of many Pleistocene till successions. These studies instead supported an exclusively British provenance, and are used to predict southward advance of a broadly coast-parallel North Sea Lobe. Quantitative lithological and palynological analysis of the Pleistocene till succession in Holderness, East Yorkshire, however, remains to be carried out. We examined the lithologically diverse Skipsea Till in order to reconstruct ice flow pathways to the Holderness coast during the Pleistocene, thereby constraining which areas of substrate were subglacially eroded and entrained prior to deposition. The till yields a diverse range of soft, low-durability and uniquely British allochthonous material, including Permian Magnesian Limestone, Carboniferous limestone and coal, and Carboniferous pollen and spore assemblages that would be unlikely to survive polyphase reworking. Ice extended southwards through southern Scotland, incorporating material in north-east England, north-east Yorkshire and the western margin of the North Sea Basin (NSB), supporting a recurrent ice flow pathway for the eastern margin of the British-Irish Ice Sheet during the Mid to Late Pleistocene

Effects of gut chemistry in marine bivalves on the assimilation of metals from ingested sediment particles

Bioavailability and uptake of trace metals by benthic animals are often assumed to be limited by authigenic sulfide minerals because of their low metal solubilities and reactivities under sedimentary conditions. However, digestive processes and gut conditions such as Eh, pH, and enzyme or surfactant activity, can affect the release of ingested metals in the gut and control uptake. In a series of laboratory experiments with the deposit-feeding clam, Macoma balthica and the suspension-feeding mussel, Mytilus edulis, we assessed assimilation efficiencies (AE) of radioisotopes of Ag, Cd and Co associated with acid-volatile sulfide (AVS), iron oxide (re-oxidized AVS), and reduced and oxidized natural sediment. To evaluate controls on AE, we measured the gut passage time (GPT) of ingested particles, gut Eh, pH, and extraction of Ag, Cd, and Co from particles into gut juice. In general, the overall trends of AEs and metal extraction were Co \u3e Cd ≥ Ag. AEs, metal extraction, and GPTs were higher in M. balthica than in M. edulis in most cases. M. balthica tended overall to take up metals more readily from oxidized than reduced natural sediment, whereas M. edulis did the opposite for Co and Cd. AEs of metals in reoxidized AVS (Fe-oxides) were generally similar to oxic sediment (Ag being the exception for M. edulis). In M. balthica, there was no significant difference in AEs from AVS and Fe-oxide particles for Cd (14 -20%) or Co (27-35%), but AEs for Ag from AVS particles were greater in large clams (28%) than small clams (15%). There were generally poor correlations between AEs of metals and metal release in gut juice. Low pH and moderate reducing conditions facilitated dissolution of AVS- and iron oxide-bound metal in the guts of both animals. The GPTs (64 h) for Co associated with AVS particles in M. edulis were an order of magnitude greater than for Ag and Cd, or for Co associated with other particle types. Overall, no single mechanism appears to control metal AE in marine bivalves and in vitro studies of metal dissolution in gut juice do not completely mimic the complex digestive processes operating in vivo, and thus cannot fully explain metal assimilation in these animals