Bringing Attention to Lesser-known Bone Remodeling Pathways

Osteoporosis, a disease of low bone mass, places individuals at enhanced risk for fracture, disability, and death. In the USA, hospitalizations for osteoporotic fractures exceed those for heart attack, stroke, and breast cancer and, by 2025, the number of fractures due to osteoporosis is expected to rise to nearly three million in the USA alone. Pharmacological treatments for osteoporosis are aimed at stabilizing or increasing bone mass. However, there are significant drawbacks to current pharmacological options, particularly for long-term management of this chronic condition. Moreover, the drug development pipeline is relatively bereft of new strategies. Consequently, there is an urgent and unmet need for developing new strategies and targets for treating osteoporosis. Casual observation led us to hypothesize that much of the bone remodeling research literature focused on relatively few molecular pathways. This led us to perform bibliometric analyses to determine the relative popularity of bone remodeling pathways in publications and US National Institutes of Health funding of the last 10 years. In this review article, we discuss these findings and highlight several less-examined signaling pathways that may hold promise for future therapies

Superficial Ulnar Artery with High Bifurcation of the Brachial Artery and its Clinical Significance

Although the variations in brachial artery branching patterns are commonly observed, only 3.75% exhibit a high ulnar artery variation1. An even fewer number present with a bilateral superficial ulnar artery, as was reported by Fadel and Amonoo-Kuofi2. The compounding variations of a high bifurcation of the brachial artery and a superficial ulnar artery may be asymptomatic, but demonstrate important clinical significance in relation to accidental intra-arterial injections, errors in blood pressure readings, as well as orthopedic, plastic and vascular surgeries of the upper limbs1. This study aims to expand upon previous literature and provide additional insight to the field of clinical anatomy, while educating physicians of the possible presentations and potentially severe risks associated with these variations

Global Hamiltonian dynamics on singular symplectic manifolds

In this thesis, we study the Reeb and Hamiltonian dynamics on singular symplectic and contact manifolds. Those structures are motivated by singularities coming from classical mechanics and fluid dynamics. We start by studying generalized contact structures where the non-integrability condition fails on a hypersurface, the critical hypersurface. Those structures, called $b$-contact structures, arise from hypersurfaces in $b$-symplectic manifolds that have been previously studied extensively in the past. Formerly, this odd-dimensional counterpart to $b$-symplectic geometry has been neglected in the existing vast literature. Examples are given and local normal forms are proved. The local geometry of those manifolds is examined using the language of Jacobi manifolds, which provides an adequate set-up and leads to understanding the geometric structure on the critical hypersurface. We further consider other types of singularities in contact geometry, as for instance higher order singularities, called $b^m$-contact forms, or singularities of folded type. Obstructions to the existence of those structures are studied and the topology of $b^m$-contact manifolds is related to the existence of convex contact hypersurfaces and further relations to smooth contact structures are described using the desingularization technique. We continue examining the dynamical properties of the Reeb vector field associated to a given $b^m$-contact form. The relation of those structures to celestial mechanics underlines the relevance for existence results of periodic orbits of the Hamiltonian vector field in the $b^m$-symplectic setting and Reeb vector fields for $b^m$-contact manifolds. In this light, we prove that in dimension $3$, there are always infinitely many periodic Reeb orbits on the critical surface, but describe examples without periodic orbits away from it in any dimension. We prove that there are traps for this vector field and discuss possible extensions to prove the existence of plugs. We will see that in the case of overtwisted disks away from the critical hypersurface and some additional conditions, Weinstein conjecture holds: more precisely there exists either a periodic Reeb orbit away from the critical hypersurface or a $1$-parametric family in the neighbourhood of it. The mentioned results shed new light towards a singular version for this conjecture. The obtained results are applied to the particular case of the restricted planar circular three body problem, where we prove that after the McGehee change, there are infinitely many non-trivial periodic orbits at the manifold at infinity for positive energy values.En esta tesis, estudiamos la dinámica de Reeb y Hamiltoniana en variedades simplécticas y de contacto con singularidades. El estudio de estas variedades está motivado por singularidades que tienen su origen en la mecánica clásica y la dinámica de fluidos. Empezamos estudiando una generalización de las estructuras de contacto, en la cual la condición de no integrabilidad falla en una hipersuperficie, llamada la hipersuperficie crítica. Estas estructuras geométricas, llamadas estructuras de $b$-contacto, surgen de hipersuperficies en variedades $b$-simplécticas, estudiadas en el pasado. Hasta el momento, este equivalente de dimensión impar de la geometría $b$-simpléctica ha sido desatendido en la literatura existente. Después de los primeros ejemplos, probamos la existencia de formas locales. Estudiamos la geometría local de estas variedades usando el lenguaje de variedades de Jacobi, que resultan ser técnicas adecuadas para entender la estructura geométrica en la hipersuperficie crítica. Consideramos también singularidades de orden superior, formas de $b^m$-contacto, y singularidades de tipo folded. Continuamos con el estudio de las obstrucciones a la existencia de estas estructuras y relacionamos la topología de variedades de $b^m$-contacto con la existencia de hipersuperficies convexas. Describimos relaciones entre formas de $b^m$-contacto y formas de contacto diferenciables usando técnicas de desingularización. Examinamos las propiedades del campo de Reeb asociado a una forma de $b^m$-contacto dada. La relación de estas estructuras con la mecánica celeste pone en relieve la importancia del estudio de órbitas periódicas de este campo vectorial. Comprobamos que, en dimensión $3$, el campo de Reeb en la hipersuperficie crítica admite infinitas órbitas periódicas. Sin embargo, describimos ejemplos sin órbitas periódicas fuera de la hipersuperficie crítica en cualquier dimensión. Comprobamos la existencia de traps y discutimos la posible existencia de plugs. En el caso de un disco \emph{overtwisted} fuera de la hipersuperficie se satisface la conjetura de Weinstein: en concreto, o bien existe una órbita periódica de Reeb fuera de la hipersuperficie de contacto o bien existe una familia de órbitas periódicas en un entorno de la hipersuperficie. Estos resultados sugieren una versión singular de dicha conjetura. Aplicamos los resultados obtenidos al caso del problema de los tres cuerpos restringido circular: comprobamos que después del cambio de coordenadas de McGehee, existen infinitas órbitas periódicas en la variedad en el infinito para valores positivos de la energía.Postprint (published version

Truth-Functional and Penumbral Intuitions

Two of the main intuitions that underlie the phenomenon of vagueness are the truth-functional and the penumbral intuitions. After presenting and contrasting them, I will put forward Tappenden's gappy approach to vagueness (which takes into account the truth-functional intuition). I will contrast Tappenden's view with another of the theories of vagueness that see it as a semantic phenomenon: Supervaluationism (which takes into account the penumbral intuition). Then I will analyze some objections to Tappenden's approach and some objections to Supervaluationism. Finally, I will present my own worries about Tappenden's account

Developing an In Vitro Model of CKD-MBD Induced αKlotho Suppression

Chronic Kidney Disease (CKD) affects approximately 1 in 10 Americans. Diabetic nephropathy is also associated with the development of chronic kidney disease-mineral bone disorder (CKD-MBD). CKD-MBD disrupts the normal bone-kidney endocrine axis responsible for regulating mineral metabolism, and hyperphosphatemia develops in late stage disease. Important clinical hallmarks of the CKD-MBD progression include elevated bioactive Fibroblast growth factor-23 (FGF23) and suppression of FGF23’s co-receptor, αKlotho (αKL). In healthy individuals the hormone FGF23, primarily produced by bone, and aKL aid in maintaining normal phosphate and vitamin D homeostasis. It is currently unknown what drives the suppression of αKL expression, however increasing αKL expression in CKD-MBD models is being investigated as a novel therapeutic. Our study sought to develop a novel in vitro model of one of the clinical hallmarks of the progression of CKD-MBD, αKL suppression, to investigate both possible stimuli of its repression and downstream signaling events. The Human Embryonic Kidney (HEK) cell line was used to determine if changes in fluid shear stress, similar to those that occur in diabetic nephropathy, could lead to reduced αKL expression. HEK cells were plated and exposed to oscillatory fluid shear stress (OFSS) for intervals between 0-60 min to examine protein expression or 0-2 hours to assess gene expression. HEK cells were sensitive to mechanical stimulation as pathways including increased ERK phosphorylation occurred in response to OFSS. In response to longer bouts of OFSS αKL expression was significantly (p\u3c0.05) reduced. Dramatic changes in fluid shear stress may serve as a stimulus for reduced αKL expression in CKD-MBD. Further studies are underway to investigate downstream signaling events related to αKL suppression. Understanding both the stimuli of αKL suppression and related downstream signaling events could provide novel therapeutic targets for the treatment of CKD-MBD

An Invitation to Singular Symplectic Geometry

In this paper we analyze in detail a collection of motivating examples to consider $b^m$-symplectic forms and folded-type symplectic structures. In particular, we provide models in Celestial Mechanics for every $b^m$-symplectic structure. At the end of the paper, we introduce the odd-dimensional analogue to $b$-symplectic manifolds: $b$-contact manifolds.Comment: 14 pages, 1 figur

OMS International ARC2004 -006 - Finding Aid

https://place.asburyseminary.edu/findingaids/1027/thumbnail.jp

Elaboració de materials basats en el treball dels Bombers

Aquest treball és una proposta d’activitats que treballen continguts específics de 1er, 2on i 3er d’ESO a través del treball dels bombers i l’estudi d’aquests continguts en una visita al propis parcs. Aquesta proposta té l’origen en la detecció d’una falta de motivació i interès de l’alumnat en l’assignatura de Tecnologia, la qual millora amb les activitats més manipulatives. A més, també es percep una creixent desvinculació entre els continguts explicats a l’aula i la realitat tecnològica que envolta l’alumnat, de manera que es traslladen les activitats proposades a un context més social i tecnològic com són els bombers. Així doncs, aquest seguit d’activitats es poden portar a terme en els parcs de bombers i són fàcilment combinables amb altres activitats en el propi institut. A més, cada activitat es concreta dins un nivell d’ESO i es relaciona directament amb els continguts, objectius i competències bàsiques que marca el currículum per cada curs. Això fa que es faciliti, al professorat, la concreció d’aquestes activitats proposades en la programació que més li interessi, convertint-se, d’alguna manera, en un recurs més. Un recurs més que es veu incrementat pel fet de que hi hagi més activitats proposades que les que es poden dur a terme en un dia, possibilitant que el professorat pugui escollir quines s’adeqüen més als seus interessos. A més a més, aquestes activitats proposades són d’àmbit molt pràctic i localitzades en un context atractiu per l’alumnat. Aquest fet, ens pot incrementar les nostres perspectives d’èxit ja que l’alumnat mostrarà molt més interès per els continguts ensenyats. En tercer i últim lloc, cal destacar l’activitat de síntesi amb el geocaching. Aquesta activitat-recurs basat en el joc de pistes, tot i que s’hagi emmarcat només en l’àmbit de bombers, obra un camp de possibilitats per tal d’aplicarla com a activitat de síntesi o bé com a activitat independent que pot incrementar la motivació de l’alumnat. Á més, porta implícit l’ús d’un aparell tecnològic que està revolucionant la societat actual i que no se’l té prou en compte, el GPS. En síntesi, les activitats aquí proposades són una proposta de recurs que intenten fer una aproximació del món de les emergències i el mon educatiu, alhora que serveixen per fer l’aprenentatge més engrescador i significatiu

Comparison of Pregnancy Complication Rates: Does Opioid Agonist Pharmacotherapy Make A Difference?

Background: Over the past decade, the prevalence of opioid use disorder (OUD) in pregnant patients has increased by 131% with an associated increase in pregnancy complications. Opioid agonist pharmacotherapy (OAP) with methadone or buprenorphine is recommended by ACOG for the management of OUD. The objectives of our study are to compare the incidence of pregnancy complications among patients who at the time of their delivery used OAP, OAP plus any additional substance (OAP+), illicit or prescribed opioids, and no opioids. Methods: We conducted a retrospective cohort study at Berkshire Medical Center in Pittsfield, MA, between January 1, 2018, through December 31, 2020, to compare the incidence of nine pregnancy complications in patients who at the time of their delivery were using OAP, OAP+, illicit or prescribed opioids, and no opioids. The data was analyzed with Chi-squared tests and a Bonferroni correction of the p-value was used to adjust for comparison of the rates. The significance level used was p ≤ 0.025. Results: There were 1979 deliveries during the 3-year study period with a total complication incidence of 23%. The complication incidence was 11% for OAP, 15% for OAP+, 42% for illicit or prescribed opioids, and 24% for no opioids. The incidence of complications in the OAP group was significantly lower than the incidence in the no opioids group (11% vs 24%, p = 0.01). There was no significant difference in the comparisons between other groups. Discussion: Our study investigated nine pregnancy complications; no other single study included all of these complications. Patients who used OAP had a significantly lower incidence of pregnancy complications compared to those who used no opioids. A multisite cohort study showed a low incidence of placental abruption in patients using methadone (3%), which was a similar outcome to the MOTHER study (2.3%) and our study (1.4%). The results of this research could assist providers in counseling their patients on the use of OAP in pregnancy