Previous investigations have demonstrated local and systemic toxicity of variable severity with parenteral, enteral, and intratracheal SPA administration in animals [34, 35].
In addition to systemic inflammation previous studies including work from our own laboratory have demonstrated local inflammation in the upper airway mucosa of patients with OSA [7] [9].
Moreover, we have demonstrated local PVAT inflammation in AKO mice.
We and others have demonstrated local overexpression of cytoplasmic and extracellular HMGB1 in synovial biopsy specimens in RA and experimental arthritis [ 14, 15].
Reports have demonstrated local existence and production of Epo in the tumor mass in several different cancer types such as hepatocellular carcinoma [ 2, 3], renal cell carcinoma [ 4, 5], gastric carcinoma [ 6], thymic carcinoma [ 7], and lung adenocarcinoma [ 8].
Neurophysiological studies in monkeys have demonstrated local cortical circuits generating precisely timed sequences of nerve cell activation, so-called synfire chains, that may contribute to specific perceptual, cognitive, and behavioral processes (Abeles 1991; Abeles et al. 1993; Prut et al. 1998; Ikegaya et al. 2004).
On the one hand, a number of studies have demonstrated local adaptation and the evolution of tolerance to pollutants such as heavy metals, pesticides, and soot (Macnair 1987; Taylor and Feyereisen 1996; Reznick and Ghalambor 2001; Ownby et al. 2002; Meyer and Di Giulio 2003; Williams and Oleksiak 2008).
Overall, the SMART program has demonstrated that local, long-term, hands-on environmental research in a guided mentorship program can support and sustain the interest of female and URM students, increasing their confidence and enrollment in STEM fields.
Brachytherapy has demonstrated excellent local control of breast cancer at follow-up of up to 6 years post treatment.
Early clinical experience with single dose radiotherapy in oligometastatic human cancers has demonstrated that local control of ∼90% can be achieved with single doses of 22 25 Gy[31].
