Clinical Outcomes, Costs, and Cost-effectiveness of Strategies for Adults Experiencing Sheltered Homelessness During the COVID-19 Pandemic

Importance: Approximately 356 000 people stay in homeless shelters nightly in the United States. They have high risk of contracting coronavirus disease 2019 (COVID-19). / Objective: To assess the estimated clinical outcomes, costs, and cost-effectiveness associated with strategies for COVID-19 management among adults experiencing sheltered homelessness. / Design, Setting, and Participants: This decision analytic model used a simulated cohort of 2258 adults residing in homeless shelters in Boston, Massachusetts. Cohort characteristics and costs were adapted from Boston Health Care for the Homeless Program. Disease progression, transmission, and outcomes data were taken from published literature and national databases. Surging, growing, and slowing epidemics (effective reproduction numbers [Re], 2.6, 1.3, and 0.9, respectively) were examined. Costs were from a health care sector perspective, and the time horizon was 4 months, from April to August 2020. / Exposures: Daily symptom screening with polymerase chain reaction (PCR) testing of individuals with positive symptom screening results, universal PCR testing every 2 weeks, hospital-based COVID-19 care, alternative care sites (ACSs) for mild or moderate COVID-19, and temporary housing were each compared with no intervention. / Main Outcomes and Measures: Cumulative infections and hospital-days, costs to the health care sector (US dollars), and cost-effectiveness, as incremental cost per case of COVID-19 prevented. / Results: The simulated population of 2258 sheltered homeless adults had a mean (SD) age of 42.6 (9.04) years. Compared with no intervention, daily symptom screening with ACSs for pending tests or confirmed COVID-19 and mild or moderate disease was associated with 37% fewer infections (1954 vs 1239) and 46% lower costs ($6.10 million vs$3.27 million) at an Re of 2.6, 75% fewer infections (538 vs 137) and 72% lower costs ($1.46 million vs$0.41 million) at an Re of 1.3, and 51% fewer infections (174 vs 85) and 51% lower costs ($0.54 million vs$0.26 million) at an Re of 0.9. Adding PCR testing every 2 weeks was associated with a further decrease in infections; incremental cost per case prevented was $1000 at an Re of 2.6,$27 000 at an Re of 1.3, and $71 000 at an Re of 0.9. Temporary housing with PCR every 2 weeks was most effective but substantially more expensive than other options. Compared with no intervention, temporary housing with PCR every 2 weeks was associated with 81$39.12 million) at an Re of 2.6, 82% fewer infections (95) and 2568% higher costs ($38.97 million) at an Re of 1.3, and 59$38.94 million) at an Re of 0.9. Results were sensitive to cost and sensitivity of PCR and ACS efficacy in preventing transmission. / Conclusions and Relevance: In this modeling study of simulated adults living in homeless shelters, daily symptom screening and ACSs were associated with fewer severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections and decreased costs compared with no intervention. In a modeled surging epidemic, adding universal PCR testing every 2 weeks was associated with further decrease in SARS-CoV-2 infections at modest incremental cost and should be considered during future surges

Primary non Hodgkin's lymphoma of the lacrimal sac

<p>Abstract</p> <p>Background</p> <p>Primary Non Hodgkin's Lymphoma (NHL) of the lacrimal sac is rare.</p> <p>Methods</p> <p>The clinical features of a 78 year old female who presented with epiphora and swelling of the left lacrimal sac are described.</p> <p>Results</p> <p>Computerised tomography showed a mass involving the left lacrimal sac. Histopathological examination revealed a diffuse large B cell NHL. Immunohistological examination demonstrated B cell origin. Chemotherapy could not be administered due to co morbid conditions. The patient was treated with radiotherapy to a dose of 45 Gy in 25 fractions. Patient is disease free and on follow up after 36 months.</p> <p>Conclusion</p> <p>Primary radiotherapy is a treatment option with curative potential for localized NHL of the lacrimal sac and may be considered in patients who cannot tolerate appropriate chemotherapy.</p

Extracellular Matrix Aggregates from Differentiating Embryoid Bodies as a Scaffold to Support ESC Proliferation and Differentiation

Embryonic stem cells (ESCs) have emerged as potential cell sources for tissue engineering and regeneration owing to its virtually unlimited replicative capacity and the potential to differentiate into a variety of cell types. Current differentiation strategies primarily involve various growth factor/inducer/repressor concoctions with less emphasis on the substrate. Developing biomaterials to promote stem cell proliferation and differentiation could aid in the realization of this goal. Extracellular matrix (ECM) components are important physiological regulators, and can provide cues to direct ESC expansion and differentiation. ECM undergoes constant remodeling with surrounding cells to accommodate specific developmental event. In this study, using ESC derived aggregates called embryoid bodies (EB) as a model, we characterized the biological nature of ECM in EB after exposure to different treatments: spontaneously differentiated and retinoic acid treated (denoted as SPT and RA, respectively). Next, we extracted this treatment-specific ECM by detergent decellularization methods (Triton X-100, DOC and SDS are compared). The resulting EB ECM scaffolds were seeded with undifferentiated ESCs using a novel cell seeding strategy, and the behavior of ESCs was studied. Our results showed that the optimized protocol efficiently removes cells while retaining crucial ECM and biochemical components. Decellularized ECM from SPT EB gave rise to a more favorable microenvironment for promoting ESC attachment, proliferation, and early differentiation, compared to native EB and decellularized ECM from RA EB. These findings suggest that various treatment conditions allow the formulation of unique ESC-ECM derived scaffolds to enhance ESC bioactivities, including proliferation and differentiation for tissue regeneration applications. © 2013 Goh et al

f(R) theories

Over the past decade, f(R) theories have been extensively studied as one of the simplest modifications to General Relativity. In this article we review various applications of f(R) theories to cosmology and gravity - such as inflation, dark energy, local gravity constraints, cosmological perturbations, and spherically symmetric solutions in weak and strong gravitational backgrounds. We present a number of ways to distinguish those theories from General Relativity observationally and experimentally. We also discuss the extension to other modified gravity theories such as Brans-Dicke theory and Gauss-Bonnet gravity, and address models that can satisfy both cosmological and local gravity constraints.Comment: 156 pages, 14 figures, Invited review article in Living Reviews in Relativity, Published version, Comments are welcom

Real-Life Evidence for Tedizolid Phosphate in the Treatment of Cellulitis and Wound Infections: A Case Series

Introduction Tedizolid phosphate 200 mg, once daily for 6 days, has recently been approved for the treatment of patients with acute bacterial skin and skin structure infections (ABSSSIs) in several countries; however, clinical experience in real-life settings is currently limited. Here, we report on the use of tedizolid with an extended treatment duration for complex and severe ABSSSIs in real-world clinical settings. Methods Two patients with cellulitis and two patients with surgical site infection (SSI), aged 26–60 years, were treated with tedizolid phosphate 200 mg, intravenous/oral (IV/PO) or IV only, once daily at four different institutions. Results Two morbidly obese patients had non-necrotizing, non-purulent severe cellulitis, which were complicated by sepsis or systemic inflammatory response syndrome plus myositis. One female patient failed on first-line empiric therapy with IV cefalotin, clindamycin and imipenem (3–4 days), and was switched to IV/PO tedizolid (7 + 5 days). One male patient received IV clindamycin plus IV/PO tedizolid (5 + 5 days), but clindamycin was discontinued on Day 3 due to an adverse event. For both patients, clinical signs and symptoms improved within 72 h, and laboratory results were normalized by Days 7 and 8, respectively. Two other patients (one obese, diabetic female with chronic hepatitis and chronic obstructive pulmonary disease) had complicated SSIs occurring 10 days after hernia repair with mesh or 3 months after spinal fusion surgery with metal implant. First patient with previous methicillin-resistant Staphylococcus aureus (MRSA) bacteremia received a 7-day tedizolid IV course empirically. The second patient with culture-confirmed MRSA infection received a 14-day IV course. Both patients responded within 72 h, and local and systemic signs normalized by end of treatment. There were no reports of thrombocytopenia. Conclusion Tedizolid phosphate 200 mg for 7–14 days was a favored treatment option for patients with severe/complex ABSSSIs, and was effective following previous treatment failure or in late-onset infections

Quality-sensitive foraging by a robot swarm through virtual pheromone trails

Large swarms of simple autonomous robots can be employed to find objects clustered at random locations, and transport them to a central depot. This solution offers system parallelisation through concurrent environment exploration and object collection by several robots, but it also introduces the challenge of robot coordination. Inspired by ants’ foraging behaviour, we successfully tackle robot swarm coordination through indirect stigmergic communication in the form of virtual pheromone trails. We design and implement a robot swarm composed of up to 100 Kilobots using the recent technology Augmented Reality for Kilobots (ARK). Using pheromone trails, our memoryless robots rediscover object sources that have been located previously. The emerging collective dynamics show a throughput inversely proportional to the source distance. We assume environments with multiple sources, each providing objects of different qualities, and we investigate how the robot swarm balances the quality-distance trade-off by using quality-sensitive pheromone trails. To our knowledge this work represents the largest robotic experiment in stigmergic foraging, and is the first complete demonstration of ARK, showcasing the set of unique functionalities it provides

Measurement of the Bottom-Strange Meson Mixing Phase in the Full CDF Data Set

We report a measurement of the bottom-strange meson mixing phase \beta_s using the time evolution of B0_s -> J/\psi (->\mu+\mu-) \phi (-> K+ K-) decays in which the quark-flavor content of the bottom-strange meson is identified at production. This measurement uses the full data set of proton-antiproton collisions at sqrt(s)= 1.96 TeV collected by the Collider Detector experiment at the Fermilab Tevatron, corresponding to 9.6 fb-1 of integrated luminosity. We report confidence regions in the two-dimensional space of \beta_s and the B0_s decay-width difference \Delta\Gamma_s, and measure \beta_s in [-\pi/2, -1.51] U [-0.06, 0.30] U [1.26, \pi/2] at the 68% confidence level, in agreement with the standard model expectation. Assuming the standard model value of \beta_s, we also determine \Delta\Gamma_s = 0.068 +- 0.026 (stat) +- 0.009 (syst) ps-1 and the mean B0_s lifetime, \tau_s = 1.528 +- 0.019 (stat) +- 0.009 (syst) ps, which are consistent and competitive with determinations by other experiments.Comment: 8 pages, 2 figures, Phys. Rev. Lett 109, 171802 (2012

Filamin A Binds to CCR2B and Regulates Its Internalization

The chemokine (C-C motif) receptor 2B (CCR2B) is one of the two isoforms of the receptor for monocyte chemoattractant protein-1 (CCL2), the major chemoattractant for monocytes, involved in an array of chronic inflammatory diseases. Employing the yeast two-hybrid system, we identified the actin-binding protein filamin A (FLNa) as a protein that associates with the carboxyl-terminal tail of CCR2B. Co-immunoprecipitation experiments and in vitro pull down assays demonstrated that FLNa binds constitutively to CCR2B. The colocalization of endogenous CCR2B and filamin A was detected at the surface and in internalized vesicles of THP-1 cells. In addition, CCR2B and FLNa were colocalized in lamellipodia structures of CCR2B-expressing A7 cells. Expression of the receptor in filamin-deficient M2 cells together with siRNA experiments knocking down FLNa in HEK293 cells, demonstrated that lack of FLNa delays the internalization of the receptor. Furthermore, depletion of FLNa in THP-1 monocytes by RNA interference reduced the migration of cells in response to MCP-1. Therefore, FLNa emerges as an important protein for controlling the internalization and spatial localization of the CCR2B receptor in different dynamic membrane structures

Filamins Regulate Cell Spreading and Initiation of Cell Migration

Mammalian filamins (FLNs) are a family of three large actin-binding proteins. FLNa, the founding member of the family, was implicated in migration by cell biological analyses and the identification of FLNA mutations in the neuronal migration disorder periventricular heterotopia. However, recent knockout studies have questioned the relevance of FLNa to cell migration. Here we have used shRNA-mediated knockdown of FLNa, FLNb or FLNa and FLNb, or, alternatively, acute proteasomal degradation of all three FLNs, to generate FLN-deficient cells and assess their ability to migrate. We report that loss of FLNa or FLNb has little effect on migration but that knockdown of FLNa and FLNb, or proteolysis of all three FLNs, impairs migration. The observed defect is primarily a deficiency in initiation of motility rather than a problem with maintenance of locomotion speed. FLN-deficient cells are also impaired in spreading. Re-expression of full length FLNa, but not re-expression of a mutated FLNa lacking immunoglobulin domains 19 to 21, reverts both the spreading and the inhibition of initiation of migration

Airway Microbiota and Pathogen Abundance in Age-Stratified Cystic Fibrosis Patients

Bacterial communities in the airways of cystic fibrosis (CF) patients are, as in other ecological niches, influenced by autogenic and allogenic factors. However, our understanding of microbial colonization in younger versus older CF airways and the association with pulmonary function is rudimentary at best. Using a phylogenetic microarray, we examine the airway microbiota in age stratified CF patients ranging from neonates (9 months) to adults (72 years). From a cohort of clinically stable patients, we demonstrate that older CF patients who exhibit poorer pulmonary function possess more uneven, phylogenetically-clustered airway communities, compared to younger patients. Using longitudinal samples collected form a subset of these patients a pattern of initial bacterial community diversification was observed in younger patients compared with a progressive loss of diversity over time in older patients. We describe in detail the distinct bacterial community profiles associated with young and old CF patients with a particular focus on the differences between respective “early” and “late” colonizing organisms. Finally we assess the influence of Cystic Fibrosis Transmembrane Regulator (CFTR) mutation on bacterial abundance and identify genotype-specific communities involving members of the Pseudomonadaceae, Xanthomonadaceae, Moraxellaceae and Enterobacteriaceae amongst others. Data presented here provides insights into the CF airway microbiota, including initial diversification events in younger patients and establishment of specialized communities of pathogens associated with poor pulmonary function in older patient populations