Sheep in a Grotto

Many first-generation college students undergo feelings of inadequacy in what is known as impostor syndrome. This piece of fiction is born from such feelings of identity confusion and formation. The story functions as a written snapshot of an otherwise normal teenager whose life is threatened by a sexual assault; she faces and overcomes trauma at the cusp of her coming of age. Brooks\u27 tale incorporates a raw focus upon the protagonist\u27s ability to persevere and thrive in the face of violence. Ultimately, this text transcends a single character\u27s journey into womanhood to reflect a message of hope and growth

The type I interferon signature in leukocyte subsets from peripheral blood of patients with early arthritis: a major contribution by granulocytes

The type I interferon (IFN) signature in rheumatoid arthritis (RA) has shown clinical relevance in relation to disease onset and therapeutic response. Identification of the cell type(s) contributing to this IFN signature could provide insight into the signature's functional consequences. The aim of this study was to investigate the contribution of peripheral leukocyte subsets to the IFN signature in early arthritis. Blood was collected from 26 patients with early arthritis and lysed directly or separated into peripheral blood mononuclear cells (PBMCs) and polymorphonuclear granulocytes (PMNs). PBMCs were sorted into CD4(+) T cells, CD8(+) T cells, CD19(+) B cells, and CD14(+) monocytes by flow cytometry. Messenger RNA expression of three interferon response genes (IRGs RSAD2, IFI44L, and MX1) and type I interferon receptors (IFNAR1 and IFNAR2) was determined in whole blood and blood cell subsets by quantitative polymerase chain reaction. IRG expression was averaged to calculate an IFN score for each sample. Patients were designated "IFN(high)" (n = 8) or "IFN(low)" (n = 18) on the basis of an IFN score cutoff in whole peripheral blood from healthy control subjects. The difference in IFN score between IFN(high) and IFN(low) patients was remarkably large for the PMN fraction (mean 25-fold) compared with the other subsets (mean 6- to 9-fold), indicating that PMNs are the main inducers of IRGs. Moreover, the relative contribution of the PMN fraction to the whole-blood IFN score was threefold higher than expected from its abundance in blood (p = 0.008), whereas it was three- to sixfold lower for the other subsets (p ≤ 0.063), implying that the PMNs are most sensitive to IFN signaling. Concordantly, IFNAR1 and IFNAR2 were upregulated compared with healthy controls selectively in patient PMNs (p ≤ 0.0077) but not in PBMCs. PMNs are the main contributors to the whole-blood type I IFN signature in patients with early arthritis, which seems due to increased sensitivity of these cells to type I IFN signaling. Considering the well-established role of neutrophils in the pathology of arthritis, this suggests a role of type I IFN activity in the disease as wel

Long term time variability of cosmic rays and possible relevance to the development of life on Earth

An analysis is made of the manner in which the cosmic ray intensity at Earth has varied over its existence and its possible relevance to both the origin and the evolution of life. Much of the analysis relates to the 'high energy' cosmic rays ($E>10^{14}eV;=0.1PeV$) and their variability due to the changing proximity of the solar system to supernova remnants which are generally believed to be responsible for most cosmic rays up to PeV energies. It is pointed out that, on a statistical basis, there will have been considerable variations in the likely 100 My between the Earth's biosphere reaching reasonable stability and the onset of very elementary life. Interestingly, there is the increasingly strong possibility that PeV cosmic rays are responsible for the initiation of terrestrial lightning strokes and the possibility arises of considerable increases in the frequency of lightnings and thereby the formation of some of the complex molecules which are the 'building blocks of life'. Attention is also given to the well known generation of the oxides of nitrogen by lightning strokes which are poisonous to animal life but helpful to plant growth; here, too, the violent swings of cosmic ray intensities may have had relevance to evolutionary changes. A particular variant of the cosmic ray acceleration model, put forward by us, predicts an increase in lightning rate in the past and this has been sought in Korean historical records. Finally, the time dependence of the overall cosmic ray intensity, which manifests itself mainly at sub-10 GeV energies, has been examined. The relevance of cosmic rays to the 'global electrical circuit' points to the importance of this concept.Comment: 18 pages, 5 figures, accepted by 'Surveys in Geophysics

Ecology of an Isolated Muskrat Population During Regional Population Declines

Evidence indicating a decline in Ondatra zibethicus (Muskrat) populations in the United States during the past 40 years has led to speculation regarding factors influencing Muskrat survival. In order to understand population dynamics and survival, it is important to first define the ecology of local populations. We investigated the dwelling structure use, movements, home range, and survival of radio-tagged Muskrats (n = 14) in an urban wetland complex in central Pennsylvania. We used locations collected from intensive radio-telemetry monitoring to determine number of lodging structures used, hourly movement, and size and percent area overlap of home ranges. Muskrats shared an average of 9 lodging structures, and on average, 68% of a Muskrat’s home range overlapped home ranges of other Muskrats. We used 4 home-range estimators (kernel density estimator [KDE]href, KDEad hoc, KDEplug-in, and local convex hull estimator) to assess the ability of each estimator to represent Muskrat home ranges. The KDEplug-in that constrained the estimate of home range to habitat boundaries provided the most appropriate home-range size for Muskrats in a linear–non-linear habitat matrix. We also calculated overwinter survival estimates using known-fate models. Our top model indicated a positive effect of the average weekly precipitation on survival, with an overwinter survival estimate of 0.59 (SE = 0.16). The main cause of Muskrat mortality was predation by Neovison vison (American Mink; n = 6). The small sample size and uncertainty surrounding our model selection led to weak estimates of survival; however, our model suggests that snowfall may be an important factor in Muskrat survival. Our study provides novel data on Muskrat ecology in Pennsylvania as well as preliminary evidence for future investigations of factors affecting Muskrat survival during the winter months

Swaddling Infants

Swaddling infants has been known to provide them comfort when transitioning from the womb to the world. There has been an ongoing debate of whether or not this intervention is as helpful as we have known it to be in the past. We have performed a systematic literature review to answer the question: In infants, what are the effects of swaddling on sleeping practices and comfort? We studied peer-reviewed articles and have gathered information related to answering our research question. Some research has shown that swaddling is no longer in use due to the risks it presents with. We developed a practice protocol to address the effect that swaddling has on infants. The impact of this research is to determine if swaddling is beneficial regarding the sleeping practices and comfort of infants

Should vascular wall F-18-FDG uptake be adjusted for the extent of atherosclerotic burden?

Vascular wall 18F-FDG uptake is often used as a surrogate marker of atherosclerotic plaque inflammation. A potential caveat is that vascular wall 18F-FDG uptake is higher simply because more atherosclerosis is present. To determine if the degree of inflammation is high or low relative to the extent of atherosclerosis, vascular wall 18F-FDG uptake may require statistical adjustment for a non-inflammatory marker reflecting the extent of atherosclerosis, e.g. calcification. Adjustments is probably needed if (1) vascular wall 18F-FDG uptake correlates sufficiently strongly with arterial calcification and (2) adjustment for extent of calcification affects determinants of vascular 18F-FDG uptake. This study addresses these questions. 18F-FDG PET/low-dose-CT scans of 99 patients were used. Cardiovascular risk factors were assessed and PET/CT scans were analysed for standardized 18F-FDG uptake values and calcification. ANOVA was used to establish the association between vascular 18F-FDG uptake and calcification. Multiple linear regression (with and without calcification as independent variable) was used to show whether determinants of vascular 18F-FDG uptake were affected by the degree of calcification. 18F-FDG uptake was related to increased calcification in the aortic arch, descending and abdominal aorta. However, 18F-FDG uptake showed considerable overlap between categories of calcification. Age and body mass index were main determinants of vascular 18F-FDG uptake. In multiple regression analyses, most standardized beta coefficients of these determinants were not affected by adjustment for the degree of calcification. Although vascular 18F-FDG uptake is related to total atherosclerotic burden, as reflected by vascular calcification, the association is weak and unlikely to affect the identification of determinants of atherosclerotic inflammation implicating no need for adjustment in future studies

Spontaneous Repolarization Alternans Causes VT/VF Rearrest That Is Suppressed by Preserving Gap Junctions

Background: Ventricular tachycardia (VT)/ventricular fibrillation (VF) rearrest after successful resuscitation is common, and survival is poor. A mechanism of VT/VF, as demonstrated in ex vivo studies, is when repolarization alternans becomes spatially discordant (DIS ALT), which can be enhanced by impaired gap junctions (GJs). However, in vivo spontaneous DIS ALT–induced VT/VF has never been demonstrated, and the effects of GJ on DIS ALT and VT/VF rearrest are unknown. Objectives: This study aimed to determine whether spontaneous VT/VF rearrest induced by DIS ALT occurs in vivo, and if it can be suppressed by preserving Cx43-mediated GJ coupling and/or connectivity. Methods: We used an in vivo porcine model of resuscitation from ischemia-induced cardiac arrest combined with ex vivo optical mapping in porcine left ventricular wedge preparations. Results: In vivo, DIS ALT frequently preceded VT/VF and paralleled its incidence at normal (37°C, n = 9) and mild hypothermia (33°C, n = 8) temperatures. Maintaining GJs in vivo with rotigaptide (n = 10) reduced DIS ALT and VT/VF incidence, especially during mild hypothermia, by 90% and 60%, respectively (P \u3c 0.001; P \u3c 0.013). Ex vivo, both rotigaptide (n = 5) and αCT11 (n = 7), a Cx43 mimetic peptide that promotes GJ connectivity, significantly reduced DIS ALT by 60% and 100%, respectively (P \u3c 0.05; P \u3c 0.005), and this reduction was associated with reduced intrinsic heterogeneities of action potential duration rather than changes in conduction velocity restitution. Conclusions: These results provide the strongest in vivo evidence to date suggesting a causal relationship between spontaneous DIS ALT and VT/VF in a clinically realistic scenario. Furthermore, our results suggest that preserving GJs during resuscitation can suppress VT/VF rearrest

Development of Learning Objectives to Guide Enhancement of Chronic Disease Prevention and Management Curricula in Undergraduate Medical Education

Phenomenon: Chronic disease is a leading cause of death and disability in the United States. With an increase in the demand for healthcare and rising costs related to chronic care, physicians need to be better trained to address chronic disease at various stages of illness in a collaborative and cost-effective manner. Specific and measurable learning objectives are key to the design and evaluation of effective training, but there has been no consensus on chronic disease learning objectives appropriate to medical student education. Approach: Wagner’sChronic Care Model (CCM) was selected as a theoretical framework to guide development of an enhanced chronic dis-ease prevention and management (CDPM) curriculum. Findings of a literature review of CDPM competencies, objectives, and topical statements were mapped to each of the six domains of the CCM to understand the breadth of existing learning topics within each domain. At an in-person meeting, medical educators prepared a survey for the modified Delphi approach. Attendees iden-tified 51 possible learning objectives from the literature review mapping, rephrased the CCM domains as competencies, constructed possible CDPM learning objectives for each competency with the goal of reaching multi-institutional consensus on a limited number of CDPM learning objectives that would be feasible for institutions to use to guide enhancement of medical student curricula related to CDPM. After the meeting, the group developed a survey which included 39 learning objectives. In the study phase of the modified Delphi approach, 32 physician CDPM experts and educators completed an online survey to prioritize the top 20 objectives. The next step occurred at a CDPM interest group in-person meeting with the goal of identifying the top 10 objectives. Findings: The CCM domains were reframed as the following competencies for medical student education: patient self-care management, decision support, clinical information systems, community resources, delivery systems and teams, and health system practice and improvement. Eleven CDPM learning objectives were identified within the six competencies that were most important in developing curriculum for medical students. Insights: These learning objectives cut across education on the prevention and management of individual chronic diseases and frame chronic disease care as requiring the health system science competencies identified in the CCM. They are intended to be used in combination with traditional disease-specific pathophysiology and treatment objectives. Additional efforts are needed to identify specific curricular strategies and assessment tools for each learning objective

Evaluation of the Novel Folate Receptor Ligand [18F] Fluoro-PEG-Folate for Macrophage Targeting in a Rat Model of Arthritis.

Introduction Detection of (subclinical) synovitis is relevant for both early diagnosis and monitoring of therapy of rheumatoid arthritis (RA). Previously, the potential of imaging (sub)clinical arthritis was demonstrated by targeting the translocator protein in activated macrophages using (R)-[11C]PK11195 and positron emission tomography (PET). Images, however, also showed significant peri-articular background activity. The folate receptor (FR)-β is a potential alternative target for imaging activated macrophages. Therefore, the PET tracer [18F]fluoro-PEG-folate was synthesized and evaluated in both in vitro and ex vivo studies using a methylated BSA induced arthritis model. Methods [18F]fluoro-PEG-folate was synthesized in a two-step procedure. Relative binding affinities of non-radioactive fluoro-PEG-folate, folic acid and naturally circulating 5-methyltetrahydrofolate (5-Me-THF) to FR were determined using KB cells with high expression of FR. Both in vivo [18F]fluoro-PEG-folate PET and ex vivo tissue distribution studies were performed in arthritic and normal rats and results were compared with those of the established macrophage tracer (R)-[11C]PK11195. Results [18F]fluoro-PEG-folate was synthesized with a purity \u3e97%, a yield of 300 to 1,700 MBq and a specific activity between 40 and 70 GBq/µmol. Relative in vitro binding affinity for FR of F-PEG-folate was 1.8-fold lower than that of folic acid, but 3-fold higher than that of 5-Me-THF. In the rat model, [18F]fluoro-PEG-folate uptake in arthritic knees was increased compared with both contralateral knees and knees of normal rats. Uptake in arthritic knees could be blocked by an excess of glucosamine-folate, consistent with [18F]fluoro-PEG-folate being specifically bound to FR. Arthritic knee-to-bone and arthritic knee-to-blood ratios of [18F]fluoro-PEG-folate were increased compared with those of (R)-[11C]PK11195. Reduction of 5-Me-THF levels in rat plasma to those mimicking human levels increased absolute [18F]fluoro-PEG-folate uptake in arthritic joints, but without improving target-to-background ratios. Conclusions The novel PET tracer [18F]fluoro-PEG-folate, designed to target FR on activated macrophages provided improved contrast in a rat model of arthritis compared with the accepted macrophage tracer (R)-[11C]PK11195. These results warrant further exploration of [18F]fluoro-PEG-folate as a putative PET tracer for imaging (sub)clinical arthritis in RA patients