History of the North Cascades Smokejumper Base

This book provides a brief history of the North Cascades Smokejumper Base, from the origins of smokejumping in the United States to 2002. The initial experiments to test the feasibility of smokejumping in the United States were conducted at the North Cascades base. This history focuses on the development of smokejumping in the United States, providing descriptions of notable events and milestones, as well as individuals important to the history of smokejumping. The book also includes a timeline that extends to 2001, an update to the first edition, and a North Cascades Smokejumper Base roster from 1940-2002.https://dc.ewu.edu/smokejumping_pubs/1003/thumbnail.jp

Designing Accountability Assessments for Teaching

We argue (1) that the domains of externally mandated tests should be transparent to teachers, (2) that test maps can be used to communicate with teachers, and (3) that the most effective test maps express domains in terms of combinations of what students know and can do. We propose a device called a heuristic as the lowest level of specificity in a test map, and criteria to achieve a balance between too much specificity and too much generality in heuristics. Although we focus primarily on summative assessments, we also discuss how a state may use related, teacher-developed formative assessments to foster information-rich classroom environments. Other than item bank structure and sampling, our suggestions would have little impact on how tests are developed or scored, but we believe they would have a large impact on how they are described and used, and ultimately on their effectiveness as agents of instructional reform

U.S. - U.S.S.R. technical exchange program: Smokejumping - rappelling, October 1976

This technical report was prepared by North Cascades Smokejumper Base manager Bill Moody on his detail to the Union of Soviet Socialist Republics on the exchange of information and techniques related to the management of forests in October 1976. The report includes various aspects of wildland fire fighting by use of smokejumping and rappelling, from recruitment to fire suppression. The report is prefaced by a brief summary by Moody about the exchange.https://dc.ewu.edu/smokejumping_pubs/1017/thumbnail.jp

Sustaining Civil Society: Lessons from Five Pooled Funds in Eastern Europe

After 1990, US and European foundations and government agencies invested in a series of Partnerships and Trusts to support civil society in Central and Eastern Europe, the Baltics, the Balkans and the Black Sea regions. Analyzing the long-term impact of these investments is crucial, especially as many politicians across these regions increase their anti-civil society rhetoric. Three long-time US foundation staff look back at the legacy and impact of this funding and derive a series of lessons for practitioners seeking to understand how best to sustain civil societies for the long term

Origin of the thiopyrone CTP-431 “unexpectedly” isolated from the marine sponge Cacospongia mycofijiensis

An intriguing hypothesis that latrunculin A, a well-known natural product, might have undergone transformation into the unprecedented thiopyrone CTP-431 upon long-term storage in methanol is advanced. Thus opening of the hemiacetal of latrunculin A, followed by E1CB elimination, and dehydration would give a polyene that could undergo intramolecular Diels-Alder reaction, followed by methanolysis of the thiazolidinone ring and ring closure by intramolecular thiol addition to an enone. Experimental evidence that the novel thiazolidinone to thiopyrone rearrangement can occur is presented.The marine sponge Cacospongia mycofijiensis, found in the ocean surrounding Fiji, is a source of several polyketide natural products with interesting biological properties,1 including the tubulin binding macrolide fijianolide B (also known as laulimalide),2,3 the HIF1 signal inhibitor mycothiazole,4,5 and the macrolide latrunculins (Figure 1).6 The thiazolidinone-containing latruculins are of mixed polyketide synthesis (PKS) and non-ribosomal peptide synthesis (NRPS) origin, and latrunculin A 1 disrupts microfilament assembly to such an extent that it is the most widely used chemical tool to study actin binding

Aortic calcification and femoral bone density are independently associated with left ventricular mass in patients with chronic kidney disease

Background Vascular calcification and reduced bone density are prevalent in chronic kidney disease and linked to increased cardiovascular risk. The mechanism is unknown. We assessed the relationship between vascular calcification, femoral bone density and left ventricular mass in patients with stage 3 non-diabetic chronic kidney disease in a cross-sectional observational study. Methodology and Principal Findings A total of 120 patients were recruited (54% male, mean age 55±14 years, mean glomerular filtration rate 50±13 ml/min/1.73 m2). Abdominal aortic calcification was assessed using lateral lumbar spine radiography and was present in 48%. Mean femoral Z-score measured using dual energy x-ray absorptiometry was 0.60±1.06. Cardiovascular magnetic resonance imaging was used to determine left ventricular mass. One patient had left ventricular hypertrophy. Subjects with aortic calcification had higher left ventricular mass compared to those without (56±16 vs. 48±12 g/m2, P = 0.002), as did patients with femoral Z-scores below zero (56±15 vs. 49±13 g/m2, P = 0.01). In univariate analysis presence of aortic calcification correlated with left ventricular mass (r = 0.32, P = 0.001); mean femoral Z-score inversely correlated with left ventricular mass (r = −0.28, P = 0.004). In a multivariate regression model that included presence of aortic calcification, mean femoral Z-score, gender and 24-hour systolic blood pressure, 46% of the variability in left ventricular mass was explained (P<0.001). Conclusions In patients with stage 3 non-diabetic chronic kidney disease, lower mean femoral Z-score and presence of aortic calcification are independently associated with increased left ventricular mass. Further research exploring the pathophysiology that underlies these relationships is warranted

Microenvironmental modulation of the developing tumour: an immune-stromal dialogue.

Successful establishment of a tumour relies on a cascade of interactions between cancer cells and stromal cells within an evolving microenvironment. Both immune and nonimmune cellular components are key factors in this process, and the individual players may change their role from tumour elimination to tumour promotion as the microenvironment develops. While the tumour-stroma crosstalk present in an established tumour is well-studied, aspects in the early tumour or premalignant microenvironment have received less attention. This is in part due to the challenges in studying this process in the clinic or in mouse models. Here, we review the key anti- and pro-tumour factors in the early microenvironment and discuss how understanding this process may be exploited in the clinic

Effects of outer hair cell loss on the frequency selectivity of the patas monkey auditory system

This report describes a study that took advantage of the unique reactivity of the patas monkey (Erythrocebus patas) to dihydrostreptomycin-sulfate (DHSM) to investigate the effects of selective outer hair cell (OHC) lesions on psychophysical tuning curves (PTC). Four patas monkeys were trained using operant reinforcement techniques to perform forward masking PTCs at frequencies of 500 Hz, 2, 4, and 8 kHz, at 10 dB SL. Steady and pulsed-tone thresholds were also measured from 63 Hz to 40 kHz in half-octave steps. The animals were given daily i.m. injections of DHSM at 20 mg/kg per day until shifts in absolute threshold at 16 kHz exceeded 10 dB, at which time the drug was discontinued. Initial changes in PTC shape included elevations in the tip region associated with the increase in threshold and no elevation or a hypersensitivity of the low-frequency tail region. In general, threshold and therefore PTC tip elevations of at least 40 dB were required before any increase in the low-frequency tail became evident. Following completion of psychophysical testing, animals were sacrificed and cytochochleograms were determined. At frequencies corresponding to regions of complete OHC loss and complete IHC retention a lack of selectivity was evident and PTCs closely resemble low-pass filters. This residual low-pass tuning is similar to that seen in VIIIth nerve fibers in ears devoid of OHCs and in basilar membrane transfer functions from traumatized ears. PTCs taken at frequencies corresponding to areas with no loss of receptors showed no systematic changes in sensitivity or selectivity. Because toss of normal OHC function results in greater than a 50-dB toss in sensitivity, as well as a detuned PTC, these findings strongly support the suggestion that the role of the OHC system is to increase the sensitivity and selectivity of the auditory system.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/26889/1/0000455.pd

Disruption of CD47-SIRPα signaling restores inflammatory function in tumor-associated myeloid-derived suppressor cells

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous immune population with diverse immunosuppressive functions in solid tumors. Here, we explored the role of the tumor microenvironment in regulating MDSC differentiation and immunosuppressive properties via signal-regulatory protein alpha (SIRPα)/CD47 signaling. In a murine melanoma model, we observed progressive increases in monocytic MDSCs and monocyte-derived dendritic cells that exhibited potent T cell-suppressive capabilities. These adaptations could be recapitulated in vitro by exposing hematopoietic stem cells to tumor-derived factors. Engagement of CD47 with SIRPα on myeloid cells reduced their phagocytic capability, enhanced expression of immune checkpoints, increased reactive oxygen species production, and suppressed T cell proliferation. Perturbation of SIRPα signaling restored phagocytosis and antigen presentation by MDSCs, which was accompanied by renewed T cell activity and delayed tumor growth in multiple solid cancers. These data highlight that therapeutically targeting myeloid functions in combination with immune checkpoint inhibitors could enhance anti-tumor immunity

Effect of beta‐blockade on mortality in patients with cardiac amyloidosis:A systematic review and meta‐analysis

Aims: The efficacy of beta‐blockers in cardiac amyloidosis (CA) is unclear, and concerns persist that neurohormonal blockade could worsen symptoms of heart failure. We aimed to assess whether beta‐blocker therapy is associated with improved survival in patients with CA. Methods and results: We conducted a systematic review and meta‐analysis to examine the impact of beta‐blocker therapy on mortality in patients with CA. A search of MEDLINE and EMBASE was performed in August 2023. Data were extracted from observational studies and synthesized with pooling and random effects meta‐analysis. Thirteen studies including 4215 patients with CA were incorporated in this review (3688 transthyretin amyloid cardiomyopathy (ATTR‐CM), 502 light chain amyloid cardiomyopathy (AL‐CM), 25 not specified; age 74.8 ± 5.5 years, 76% male). Over half of the cohort (52%) received beta‐blockers and the rate of beta‐blocker withdrawal was 28%. All‐cause mortality was 33% (range: 13–51%) after a median follow‐up ranging from 13 to 36 months. There was an inverse association between the pooled risk of mortality and the use of beta‐blocker therapy at any time point (RR 0.48, 95% CI 0.29–0.80, I2 = 83%, P = 0.005, seven studies). There was no association between mortality and beta‐blocker use (RR 0.65, 95% CI 0.29–1.47, I2 = 88%, P = 0.30) in the three studies that only included patients with ATTR‐CM. The three studies that included patients with both ATTR‐CM and AL demonstrated an association of beta‐blocker use with reduced mortality (OR 0.43, 95% CI 0.29–0.63, I2 = 4%, P &lt; 0.001). The only study that solely included 53 patients with AL‐CM, demonstrated improved survival among the 53% who were able to tolerate beta‐blocker therapy (RR 0.26, 95% CI 0.08–0.79, P = 0.02). The absence of information on staging of CA is an important limitation of this study. Conclusions: Treatment with beta‐blockers may be associated with a survival benefit in patients with CA, but these findings are subject to selection and survivor biases. Definitive prospective randomized trials of conventional heart failure therapies are needed in CA