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"Freeman, Joshua Benjamin"
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American empire : the rise of a global power, the Democratic revolution at home, 1945-2000
A compelling look at the movements and developments that propelled America to world dominance beginning in 1945 and moving through McCarthyism and Vietnam, from the Great Society to Morning in America.
Book
THE TRANSPORT WORKERS UNION IN NEW YORK CITY, 1933-1948
The Transport Workers Union (TWU) was founded in New York City in 1934 to organize mass transit workers. Initiated by the Communist Party (CP), it successfully co-opted pre-existing groups of workers already exploring ways of improving conditions. Its first significant support came from employees working in large groups, primarily shop and powerhouse workers. Among the more scattered operating, station, and maintenance employees, who were heavily Irish, the union benefited from the support of former Irish Republican Army members working in transit. By 1937 the TWU had affiliated with the CIO and won contracts for some 30,000 New York transit workers, an impressive accomplishment in an industry with a half-century record of autocratic management, broken strikes, and defeated unions. Until 1948, the TWU was led by a group close to the CP, which overcame repeated challenges from rival unions and Catholic Church-affiliated dissident groups. Unionization led to a virtual revolution in transit workers' lives, as their intense exploitation and degradation were eased through contractual provisions and union programs. The TWU joined the American Labor Party and brought its members into the institutional structures of the New Deal and the Popular Front, while organizing additional transit, utility, and airline workers throughout the country. In 1940 New York's two largest private transit systems were taken over by the city government and merged with a smaller municipally-run system. The TWU was forced into a prolonged fight to retain its bargaining rights and support on these lines. As a result, it became ever more involved in electoral politics. After World War II, the onset of the Cold War led to a break-up of the center-left milieu in which the TWU had operated. Disagreements over the Henry Wallace campaign and New York Mayor William O'Dwyer's effort to raise the transit fare led to a rift within the TWU leadership. After a bitter faction fight, a group headed by TWU President Michael J. Quill emerged victorious and ousted CP supporters from positions of power. New political and bargaining arrangements were established, effectively ending the first phase of TWU history.
Dissertation
Infectious Complications Following Transrectal Ultrasound—Guided Prostate Biopsy: New Challenges in the Era of Multidrug-Resistant Escherichia coli
Transrectal ultrasound (TRUS)—guided prostate biopsy is currently considered the standard technique for obtaining tissue to make a histological diagnosis of prostatic carcinoma. Infectious complications following TRUS-guided prostate biopsy are well described, and are reportedly increasing in incidence. The role of antibiotic prophylaxis in reducing post—TRUS biopsy infections is now established, and many guidelines suggest that fluoroquinolone antimicrobials are the prophylactic agents of choice. Of note, however, recent reports suggest an emerging association between TRUS biopsy and subsequent infection with fluoroquinolone-resistant Escherichia coli. Against this background, we provide an overview of the epidemiology, prevention, and treatment of infectious complications following TRUS biopsy, in the wider context of increasing global antimicrobial resistance.
Journal Article
Effects of immunomodulatory drugs on depressive symptoms: A mega-analysis of randomized, placebo-controlled clinical trials in inflammatory disorders
Activation of the innate immune system is commonly associated with depression. Immunomodulatory drugs may have efficacy for depressive symptoms that are co-morbidly associated with inflammatory disorders. We report a large-scale re-analysis by standardized procedures (mega-analysis) of patient-level data combined from 18 randomized clinical trials conducted by Janssen or GlaxoSmithKline for one of nine disorders (N = 10,743 participants). Core depressive symptoms (low mood, anhedonia) were measured by the Short Form Survey (SF-36) or the Hospital Anxiety and Depression Scale (HADS), and participants were stratified into high (N = 1921) versus low-depressive strata based on baseline ratings. Placebo-controlled change from baseline after 4–16 weeks of treatment was estimated by the standardized mean difference (SMD) over all trials and for each subgroup of trials targeting one of 7 mechanisms (IL-6, TNF-α, IL-12/23, CD20, COX2, BLγS, p38/MAPK14). Patients in the high depressive stratum showed modest but significant effects on core depressive symptoms (SMD = 0.29, 95% CI [0.12–0.45]) and related SF-36 measures of mental health and vitality. Anti-IL-6 antibodies (SMD = 0.8, 95% CI [0.20–1.41]) and an anti-IL-12/23 antibody (SMD = 0.48, 95% CI [0.26–0.70]) had larger effects on depressive symptoms than other drug classes. Adjustments for physical health outcome marginally attenuated the average treatment effect on depressive symptoms (SMD = 0.20, 95% CI: 0.06–0.35), but more strongly attenuated effects on mental health and vitality. Effects of anti-IL-12/23 remained significant and anti-IL-6 antibodies became a trend after controlling for physical response to treatment. Novel immune-therapeutics can produce antidepressant effects in depressed patients with primary inflammatory disorders that are not entirely explained by treatment-related changes in physical health.
Journal Article
A strategy for cost-effective large language model use at health system-scale
Large language models (LLMs) can optimize clinical workflows; however, the economic and computational challenges of their utilization at the health system scale are underexplored. We evaluated how concatenating queries with multiple clinical notes and tasks simultaneously affects model performance under increasing computational loads. We assessed ten LLMs of different capacities and sizes utilizing real-world patient data. We conducted >300,000 experiments of various task sizes and configurations, measuring accuracy in question-answering and the ability to properly format outputs. Performance deteriorated as the number of questions and notes increased. High-capacity models, like Llama-3–70b, had low failure rates and high accuracies. GPT-4-turbo-128k was similarly resilient across task burdens, but performance deteriorated after 50 tasks at large prompt sizes. After addressing mitigable failures, these two models can concatenate up to 50 simultaneous tasks effectively, with validation on a public medical question-answering dataset. An economic analysis demonstrated up to a 17-fold cost reduction at 50 tasks using concatenation. These results identify the limits of LLMs for effective utilization and highlight avenues for cost-efficiency at the enterprise scale.
Journal Article
Prefrontal Dopaminergic and Enkephalinergic Synaptic Accommodation in HIV-associated Neurocognitive Disorders and Encephalitis
Changes in synapse structure occur in frontal neocortex with HIV encephalitis (HIVE) and may contribute to HIV-associated neurocognitive disorders (HAND). A postmortem survey was conducted to determine if mRNAs involved in synaptic transmission are perturbed in dorsolateral prefrontal cortex (DLPFC) in subjects with HIVE or HAND. Expression of the opioid neurotransmitter preproenkephalin mRNA (
PENK
) was significantly decreased in a sampling of 446 brain specimens from HIV-1 infected people compared to 67 HIV negative subjects. Decreased DLPFC
PENK
was most evident in subjects with HIVE and/or increased expression of interferon regulatory factor 1 mRNA (
IRF1
). Type 2 dopamine receptor mRNA (
DRD2L
) was decreased significantly, but not in the same set of subjects with
PENK
dysregulation.
DRD2L
downregulation occurred primarily in the subjects without HIVE or neurocognitive impairment. Subjects with neurocognitive impairment often failed to significantly downregulate
DRD2L
and had abnormally high
IRF1
expression. Conclusion: Dysregulation of synaptic preproenkephalin and
DRD2L
in frontal neocortex can occur with and without neurocognitive impairment in HIV-infected people. Downregulation of
DRD2L
in the prefrontal cortex was associated with more favorable neuropsychological and neuropathological outcomes; the failure to downregulate
DRD2L
was significantly less favorable.
PENK
downregulation was related neuropathologically to HIVE, but was not related to neuropsychological outcome independently. Emulating endogenous synaptic plasticity pharmacodynamically could enhance synaptic accommodation and improve neuropsychological and neuropathological outcomes in HIV/AIDS.
Journal Article
An organ-on-chip model of pulmonary arterial hypertension identifies a BMPR2-SOX17-prostacyclin signalling axis
Pulmonary arterial hypertension (PAH) is an unmet clinical need. The lack of models of human disease is a key obstacle to drug development. We present a biomimetic model of pulmonary arterial endothelial-smooth muscle cell interactions in PAH, combining natural and induced bone morphogenetic protein receptor 2 (BMPR2) dysfunction with hypoxia to induce smooth muscle activation and proliferation, which is responsive to drug treatment. BMPR2- and oxygenation-specific changes in endothelial and smooth muscle gene expression, consistent with observations made in genomic and biochemical studies of PAH, enable insights into underlying disease pathways and mechanisms of drug response. The model captures key changes in the pulmonary endothelial phenotype that are essential for the induction of SMC remodelling, including a BMPR2-SOX17-prostacyclin signalling axis and offers an easily accessible approach for researchers to study pulmonary vascular remodelling and advance drug development in PAH.
A biomimetic inducible model of pulmonary arterial hypertension (PAH) is presented, combining natural and induced BMPR2 dysfunction with hypoxia in lung endothelial cells and blood-derived PAH cells to induce smooth muscle activation & proliferation.
Journal Article
Mechanical and Thermal Properties of Calcined Clay Mixed with Agrowaste Char for Sustainable Building Applications
This paper presents a combined experimental and computational result on the mechanical and thermal properties of calcined clay‐agrowaste char composites for sustainable building applications. The calcined clays were characterized for their structural, microstructural, mechanical, and thermal properties after they were mixed with 5 wt%, 10 wt%, 15 wt%, and 20 wt% of agrowaste char of varying sources (i.e., coconut, palm kernel, and acacia). Analytical and finite element analyses were used to predict and also confirm the experimentally determined results. The results show that increasing char fractions increases the thermal energy properties but reduces the mechanical properties. For the compressive strength results, it was noted that the palm kernel char composite recorded the highest compressive strength (∼4.60 MPa) followed by coconut char (∼4.23 MPa) and acacia char composites (∼4.14 MPa). The optical micrographs show uniform distribution of the char in the clay/cement matrix. The analytical and finite element analysis predictions show that the sample with microcracks recorded appreciable fracture toughness (∼38.2 MPa/mm
−0.5
) and slow rate of energy release during fracture. The implications of the results are discussed to elaborate on the role calcined clays and agrowaste chars plays on the thermal and mechanical properties for a sustainable building materials industry.
Journal Article
Sequential Earthquake Damage Assessment Incorporating Optimized sUAV Remote Sensing at Pescara del Tronto
A sequence of large earthquakes in central Italy ranging in moment magnitudes (Mw) from 4.2 to 6.5 caused significant damage to many small towns in the area. After each earthquake in 2016 (24 August and 26 October), automated small unmanned aerial vehicles (sUAV) acquired valuable imagery data for post-hazard reconnaissance in the mountain village of Pescara del Tronto, and were applied to 3D reconstruction using Structure-from-Motion (SfM). In July 2018, the site was again monitored to obtain additional imagery data capturing changes since the last visit following the 30 October 2016 Earthquake. A genetic-based mission-planning algorithm that delivers optimal viewpoints and path planning was field tested and reduced the required photos for 3D reconstruction by 9.1%. The optimized 3D model provides a better understanding of the current conditions of the village, when compared to the nadir models, by containing fewer holes on angled surfaces, including an additional 17% surface area, and with a comparable ground-sampling distance (GSD) of ≈2.4 cm/px (≈1.5 cm/px when adjusted for camera pixel density). The resulting three time-lapse models provide valuable metrics for ground motion, progression of damage, resilience of the village, and the recovery progress over a span of two years.
Journal Article