Introduction Drug development for neurodegenerative diseases such as Friedreich’s ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. Methods 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich’s Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. Discussion Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression. Clinical trial registration ClinicalTrails.gov Identifier: NCT04349514 .
The purpose of this chapter is to summarize the results of antenna and radome technology which are of particular interest for antenna stealth. Shape is everything when it comes to both the active and passive signatures of antennas and radomes. Once the shape is right then things such as element pattern, amplitude weighting, thickness, and edge treatment become important. First, the relationship between the radiation pattern (beamwidth, side-lobes, etc.) and the current distribution across the antenna aperture is discussed. This is followed by descriptions of the various types of antennas which have been applied to radar and datalinks, including reflectors, lenses, and arrays. Several methods of pattern synthesis are discussed. The effect of broadband signals and errors in the aperture distribution on the radiation and RCS patterns is also considered. This chapter covers both the active and passive signatures of antennas and radomes. The chapter concludes with brief discussions of radome and antenna near field interaction.
Cytomegalovirus (CMV) enterocolitis is an infection often associated with significant immunosuppression We report a case of CMV ileitis in a healthy male who subsequently was diagnosed with Crohn's disease. Guidance for treatment of active CMV disease prior to initiation of biologic therapy is lacking in the current medical literature, outside of chemotherapy guidelines. A 43-year-old African American male was referred to the Gastroenterology clinic for a 12-month history of alternating diarrhea and constipation and newly decreased stool caliber. Colonoscopy was unable to be initially performed due to a significant anal stricture. Exam under anesthesia demonstrated a functional narrowing of the anus as well as two large ulcers of the posterior anal canal. Biopsies demonstrated granuloma formation along with positive staining for CMV. Repeat colonoscopy demonstrated extensive circumferential ulcerations and inflammation of the terminal ileum (TI) with endoscopically normal colon. Biopsies from the TI demonstrated chronic ileitis with positive CMV staining. MRE confirmed extent of newly diagnosed Crohn's disease and he underwent a 21-day course of valganciclovir prior to initiation of biologic therapy. CMV ileitis is rare in young, immunocompetent patients without significant co-morbidities such as diabetes or end-stage kidney disease. Current medical literature is limited in guidance regarding treatment of active CMV disease prior to initiation of biologic therapy; existing guidelines only relate to treatment prior to chemotherapy. NCCN guidelines recommend screening and treatment of CMV infection prior to immunosuppressive treatments due to the risk of disseminated CMV after starting chemotherapy. Disseminated CMV can be a significant complication of biologic therapy and we should consider anti-viral therapy prior to initiation.2054_A Figure 1. 20x CMV…: H&E stain of an anal biopsy at 200x magnification demonstrates loose granulomatous inflammation and a characteristic CMV inclusion (arrow).2054_B Figure 2. 40x CMV…: Immunohistochemistry for CMV demonstrates scattered positive cells (dark brown).2054_C Figure 3. Endoscopic view of terminal ileum demonstrating extensive circumferential ulcerations and inflammation
Regional pituitary blood flow has been studied in adult female Fischer 344 rats by [14C]iodoantipyrine autoradiography. A general mathematical solution has been derived to allow the calculation of blood flow in the second compartment of a portal system and the proportion of blood "shunted" through the first compartment without exposure to tissue uptake from a knowledge of (a) the volume ratios of the two compartments, (b) the tissue tracer uptakes of the two compartments, and (c) the arterial tracer concentration with respect to time of a freely diffusible tracer. Significant diffusion limitation and/or arteriovenous shunting has been demonstrated in the neurohypophysis, suggesting that the majority of incoming blood is "shunted" unchanged to the adenohypophysis. The mean value of the shunt is 89% (range of 84-93%) for the median eminence and lies between 72% (range of 52-82%) and 73% (range of 59-81%) for the posterior pituitary. Neurohypophysial flow rates of 1.20 (range of 0.99-1.55) ml g-1 min-1 for the median eminence and 1.68 (range of 0.83-3.53) ml g-1 min-1 for the posterior pituitary were measured. These values represent "tissue-available" (nonshunted) flow; estimated mean total (shunted plus nonshunted) neurohypophysial flow rates were 11.7 (range of 9.5-17.5) ml g-1 min-1 for the median eminence and 6.1 (range of 3.1-8.9) ml g-1 min-1 (minimum) for the posterior pituitary. Adenohypophysial blood flow is heterogeneous. In the long portal territory, the flow rate was 1.18 (range of 0.95-1.75) ml g-1 min-1 but short portal territory flow calculation is complicated by an unquantifiable nonportal venous drainage; using the natural limits of zero and 100% gives a minimum adenohypophysial flow rate of 1.42 (range of 0.76-2.07) ml g-1 min-1 and a maximum value of 1.97 (range of 1.03-2.82) ml g-1 min-1.
Aortic dissection is a rare cause of death in young adults, which may be caused by acquired or congenital factors. We present the case of a 21-year-old man who died as a result of spontaneous aortic dissection and cardiac tamponade. At autopsy, signs of Marfan syndrome were evident both grossly and microscopically. Hodgkin lymphoma was also discovered, though was noncontributory to death. We review the causes of aortic dissection in young individuals, with a focus on the key differentiating features of predisposing inheritable connective tissue disorders. Given the implications for surviving family members, it is the obligation of the diligent forensic pathologist to be aware of these conditions, such that families may be alerted to the need for genetic counseling.
