An annotated bibliography of materials suitable for use in teaching French in the elementary school

Thesis (Ed.M.)--Boston Universit

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Harnessing the purinergic receptor pathway to develop functional engineered cartilage constructs

Objective: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While this approach can be highly successful, it may be more efficient and effective to harness the known underlying mechanotransduction pathways responsible. With this aim, the purpose of this study was to assess the effect of directly stimulating the purinergic receptor pathway through exogenous adenosine 5\u27-triphosphate (ATP) in absence of externally applied forces. Methods: Isolated bovine articular chondrocytes were seeded in high density, 3D culture and supplemented with varying doses of ATP for up to 4 weeks. The effects on biosynthesis, extracellular matrix accumulation and mechanical properties were then evaluated. Experiments were also conducted to assess whether exogenous ATP elicited any undesirable effects, such as: inflammatory mediator release, matrix turn-over and mineralization. Results: Supplementation with ATP had a profound effect on the growth and maturation of the developed tissue. Exogenous ATP (62.5-250. μM) increased biosynthesis by 80-120%, and when stimulated for a period of 4 weeks resulted in increased matrix accumulation (80% increase in collagen and 60% increase in proteoglycans) and improved mechanical properties (6.5-fold increase in indentation modulus). While exogenous ATP did not stimulate the release of inflammatory mediators or induce mineralization, high doses of ATP (250μM) elicited a 2-fold increase in matrix metalloproteinase-13 expression suggesting the emergence of a catabolic response. Conclusions: Harnessing the ATP-purinergic receptor pathway is a highly effective approach to improve tissue formation and impart functional mechanical properties. However, the dose of ATP needs to be controlled as not to elicit a catabolic response. © 2010 Osteoarthritis Research Society International

Carbon-poor stellar cores as supernova progenitors

Exploring stellar models which ignite carbon off-center (in the mass range of about 1.05 - 1.25 Msun, depending on the carbon mass fraction) we find that they may present an interesting SN I progenitor scenario, since whereas in the standard scenario runaway always takes place at the same density of about 2 X 10^9 gr/cm^3, in our case, due to the small amount of carbon ignited, we get a whole range of densities from 1 X 10^9 up to 6 X 10^9 gr/cm^3. These results could contribute in resolving the emerging recognition that at least some diversity among SNe I exists, since runaway at various central densities is expected to yield various outcomes in terms of the velocities and composition of the ejecta, which should be modeled and compared to observations.Comment: 49 pages, 20 figure

The GUCY2C Tumor Suppressor is the Nexus of a Paracrine Hormone Axis Preventing Radiotherapy-Induced Gastrointestinal (GI) Toxicity

Purpose/Objective: Radiation-induced GI toxicity is the primary dose limitation compromising therapy in cancer patients treated with radiation therapy. GUCY2C is the intestinal receptor for diarrheagenic bacterial enterotoxins and the endogenous paracrine hormones guanylin and uroguanylin. Following genomic insult, cyclic (c)GMP produced by ligand activation of GUCY2C enhances DNA damage sensing and repair in intestinal cells. Here, we show that the GUCY2C-cGMP axis mediates p53-dependent radioprotection of intestinal epithelial cells. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Adverse events in radiation oncology: A case series from wake up safe, the pediatric anesthesia quality improvement initiative

BackgroundRadiation therapy in pediatric patients often requires anesthesia and poses environmental challenges. Monitoring must be done remotely to limit radiation exposure to the provider. Airway access can be limited by masks or frames. Care is often delivered in relatively inaccessible locations in the hospital. While individual institutions have reported their outcomes, this case series aims to review a multicenter registry of significant adverse events and make recommendations for improved care.MethodsWake Up Safe: The Pediatric Quality Improvement Initiative maintains a multisite, voluntary registry of pediatric perianesthetic significant adverse events. This was queried for reports from radiation oncology from January 1, 2010 to May 10, 2018. The database contained 3,379 significant adverse events from approximately 3.3 million anesthetics. All 33 institutions submitted data on a standardized form to a central data repository (Axio Research, Seattle Washington). Prior to each significant adverse events case submission, three anesthesiologists who were not involved in the event analyzed the event using a standardized root cause analysis method to identify the causal or contributing factor(s).ResultsSix significant adverse events were identified. In three, incorrect programming of a propofol infusion resulted in overdose. In case one, the 3â yearâ old female became hypotensive, requiring vasopressors and volume resuscitation. In the second, the 2â yearâ old female experienced airway obstruction and apnea requiring chin lift. In case three, the child suffered no consequences despite a noted overdose of propofol infusion. In case four, a 2â yearâ old female with recent respiratory infection suffered laryngospasm during an unmonitored transport to the recovery area. She developed profound oxygen desaturation with bradycardia treated with succinylcholine and chest compressions. In case five, a 6â yearâ old former premature child suffered laryngospasm at the conclusion of mask creation under general anesthesia with a laryngeal mask airway. The radiation mask delayed recognition of copious secretions. Finally, in case six, a 6â yearâ old undergoing stereotactic radiosurgery in a head halo suffered bronchospasm and unintended extubation during therapy which required multiple attempts at reintubation by multiple providers ultimately requiring cancellation of the treatment and transport to the intensive care unit.ConclusionThere were few radiation oncology significant adverse events, but analysis has led to the identification of several specific opportunities for improvement in pediatric anesthesia for radiation oncology.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148238/1/pan13567_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148238/2/pan13567.pd

Sports Hernia/Athletic Pubalgia Among Women

© The Author(s) 2018. Background: “Athletic pubalgia,” a term that has gained acceptance over “sports hernia,” is more common in men than women; however, it represents a significant source of morbidity for patients of both sexes. Inconsistent terminology surrounding this entity poses a diagnostic challenge and makes studying the populations at risk difficult. Purpose: To review a case series of women with athletic pubalgia by analyzing their presentations, concomitant pathologies, and surgical outcomes. Study Design: Case series; Level of evidence, 4. Methods: Between 2013 and 2016, 197 patients were seen and evaluated for the diagnosis of athletic pubalgia. Eighteen patients seen during this time were women. All patients received “pubalgia protocol” magnetic resonance imaging and subsequent surgical intervention for their pathologies. Outcomes among 17 women were assessed with a patient questionnaire \u3e1 year after surgery. Results: Of the 17 women, 9 had rectus aponeurotic plate injury only, or pure athletic pubalgia; the remaining 8 had athletic pubalgia in combination with ≥1 inguinal, obturator, and femoral hernias. Regarding female patients in both groups, 88.2% reported that the surgery was a success at follow-up. Conclusion: Surgical repair of athletic pubalgia among women is successful in dramatically reducing pain levels in this important subset of patients

GUCY2C lysosomotropic endocytosis delivers immunotoxin therapy to metastatic colorectal cancer.

The emergence of targeted cancer therapy has been limited by the paucity of determinants which are tumor-specific and generally associated with disease, and have cell dynamics which effectively deploy cytotoxic payloads. Guanylyl cyclase C (GUCY2C) may be ideal for targeting because it is normally expressed only in insulated barrier compartments, including intestine and brain, but over-expressed by systemic metastatic colorectal tumors. Here, we reveal that GUCY2C rapidly internalizes from the cell surface to lysosomes in intestinal and colorectal cancer cells. Endocytosis is independent of ligand binding and receptor activation, and is mediated by clathrin. This mechanism suggests a design for immunotoxins comprising a GUCY2C-directed monoclonal antibody conjugated through a reducible disulfide linkage to ricin A chain, which is activated to a potent cytotoxin in lysosomes. Indeed, this immunotoxin specifically killed GUCY2C-expressing colorectal cancer cells in a lysosomal- and clathrin-dependent fashion. Moreover, this immunotoxin reduced pulmonary tumors \u3e80% (

Supernova 2007bi as a pair-instability explosion

Stars with initial masses 10 M_{solar} < M_{initial} < 100 M_{solar} fuse progressively heavier elements in their centres, up to inert iron. The core then gravitationally collapses to a neutron star or a black hole, leading to an explosion -- an iron-core-collapse supernova (SN). In contrast, extremely massive stars (M_{initial} > 140 M_{solar}), if such exist, have oxygen cores which exceed M_{core} = 50 M_{solar}. There, high temperatures are reached at relatively low densities. Conversion of energetic, pressure-supporting photons into electron-positron pairs occurs prior to oxygen ignition, and leads to a violent contraction that triggers a catastrophic nuclear explosion. Tremendous energies (>~ 10^{52} erg) are released, completely unbinding the star in a pair-instability SN (PISN), with no compact remnant. Transitional objects with 100 M_{solar} < M_{initial} < 140 M_{solar}, which end up as iron-core-collapse supernovae following violent mass ejections, perhaps due to short instances of the pair instability, may have been identified. However, genuine PISNe, perhaps common in the early Universe, have not been observed to date. Here, we present our discovery of SN 2007bi, a luminous, slowly evolving supernova located within a dwarf galaxy (~1% the size of the Milky Way). We measure the exploding core mass to be likely ~100 M_{solar}, in which case theory unambiguously predicts a PISN outcome. We show that >3 M_{solar} of radioactive 56Ni were synthesized, and that our observations are well fit by PISN models. A PISN explosion in the local Universe indicates that nearby dwarf galaxies probably host extremely massive stars, above the apparent Galactic limit, perhaps resulting from star formation processes similar to those that created the first stars in the Universe.Comment: Accepted version of the paper appearing in Nature, 462, 624 (2009), including all supplementary informatio