Soviet command and control in a historical context

An examination is made of the historical antecedents of present day command and control doctrine in the Soviet Union. The continuity of principal characteristics is demonstrated. The ideological determinants shaping the command and control system are first developed. These include centralism, collective decision-making, unity of command, and redundancy. Practical consequences of these are explored. The functioning of Soviet command and control during World War II is addressed in detail, with emphasis on the uniquely Soviet aspects. Current Soviet command and control concepts are addressed in a general way and linked to historical precedents and ideological precepts. Primary source materials are open Soviet doctrinal and historical publications, in translation.http://archive.org/details/sovietcommandcon00kernCaptain, United States ArmyApproved for public release; distribution is unlimited

Ankle and midtarsal joint quasi-stiffness during walking with added mass

Examination of how the ankle and midtarsal joints modulate stiffness in response to increased force demand will aid understanding of overall limb function and inform the development of bio-inspired assistive and robotic devices. The purpose of this study is to identify how ankle and midtarsal joint quasi-stiffness are affected by added body mass during over-ground walking. Healthy participants walked barefoot over-ground at 1.25 m/s wearing a weighted vest with 0%, 15% and 30% additional body mass. The effect of added mass was investigated on ankle and midtarsal joint range of motion (ROM), peak moment and quasi-stiffness. Joint quasi-stiffness was broken into two phases, dorsiflexion (DF) and plantarflexion (PF), representing approximately linear regions of their moment-angle curve. Added mass significantly increased ankle joint quasi-stiffness in DF (p \u3c 0.001) and PF (p \u3c 0.001), as well as midtarsal joint quasi-stiffness in DF (p \u3c 0.006) and PF (p \u3c 0.001). Notably, the midtarsal joint quasi-stiffness during DF was ~2.5 times higher than that of the ankle joint. The increase in midtarsal quasi-stiffness when walking with added mass could not be explained by the windlass mechanism, as the ROM of the metatarsophalangeal joints was not correlated with midtarsal joint quasi-stiffness (r = −0.142, p = 0.540). The likely source for the quasi-stiffness modulation may be from active foot muscles, however, future research is needed to confirm which anatomical structures (passive or active) contribute to the overall joint quasi-stiffness across locomotor tasks

Effects of KDT501 on Metabolic Parameters in Insulin-Resistant Prediabetic Humans

Context: KDT501 is an isohumulone drug that has demonstrated beneficial effects on metabolic parameters in mice. Objective: This study was intended to examine potential improvements in metabolism in humans. Design and Setting: Changes in carbohydrate and lipid metabolism, along with inflammatory markers, were evaluated in prediabetic humans in a clinical research center. Participants: Nine obese patients participated. All had prediabetes or normal glucose tolerance plus three features of metabolic syndrome. Intervention: All participants were treated with escalating doses of KDT501 to a maximum dose of 1000 mg every 12 hours for a total of 28 days. Outcome Measures: Changes in carbohydrate metabolism were measured with oral glucose tolerance, homeostatic model of insulin resistance, and euglycemic clamp; changes in plasma lipids and response to a lipid tolerance test; and changes in plasma inflammatory markers. Results: The drug was well tolerated. After KDT501 treatment, plasma triglycerides were reduced at 4 hours during a lipid tolerance test. Furthermore, plasma adiponectin and high-molecular-weight adiponectin increased significantly, and plasma tumor necrosis factor-α decreased significantly. There were no significant changes in oral glucose tolerance test results or insulin sensitivity measures. Conclusions: Despite the small sample size and the short duration of therapy, KDT501 administration reduced measures of systemic inflammation and improved postmeal plasma triglyceride levels, which may be beneficial in participants with insulin resistance or metabolic syndrome

The Influence of a KDT501, a Novel Isohumulone, on Adipocyte Function in Humans

Objective: In a phase II clinical trial in nine obese, insulin-resistant humans, we observed that treatment with KDT501, a novel isohumulone drug, increased total and high-molecular weight (HMW) adiponectin in plasma. The objective was to determine whether KDT501 increased adiponectin secretion from subcutaneous white adipose tissue (SC WAT) and the underlying mechanism(s). Methods: Nine obese participants with either prediabetes or with normal glucose tolerance plus three features of metabolic syndrome were part of the study. SC WAT biopsies were performed before and after 28 days of KDT501 treatment in a clinical research setting. In addition, a cold stimulus was used to induce thermogenic gene expression. Adiponectin secretion was measured, and gene expression of 130 genes involved in adipose tissue function was determined. The effect of KDT501 on adipocyte mitochondrial function was analyzed in vitro. Results: SC WAT explants secreted more total and HMW adiponectin after KDT501 treatment (P \u3c 0.05). After KDT501 treatment, a number of genes involved in thermogenesis and lipolysis were induced by cold (P \u3c 0.05). KDT501 also potentiated β-adrenergic signaling (P \u3c 0.001) and enhanced mitochondrial function in adipocytes (P \u3c 0.001). Conclusion: KDT501 induced adiponectin secretion posttranscriptionally and increased gene expression of thermogenic and lipolytic genes in response to cold stimulation. These beneficial effects on SC WAT may be explained by the ability of KDT501 to potentiate β-adrenergic signaling and enhance mitochondrial function in adipocytes. Clinical Trial Registration: https://www.ClinicalTrials.gov, ID number: NCT02444910

The characteristics of cognitive neuroscience tests in a schizophrenia cognition clinical trial: Psychometric properties and correlations with standard measures.

In comparison to batteries of standard neuropsychological tests, cognitive neuroscience tests may offer a more specific assessment of discrete neurobiological processes that may be aberrant in schizophrenia. However, more information regarding psychometric properties and correlations with standard neuropsychological tests and functional measures is warranted to establish their validity as treatment outcome measures. The N-back and AX-Continuous Performance Task (AX-CPT) are two promising cognitive neuroscience tests designed to measure specific components of working memory and contextual processing respectively. In the current study, we report the psychometric properties of multiple outcome measures from these two tests as well as their correlations with standard neuropsychological measures and functional capacity measures. The results suggest that while the AX-CPT and N-back display favorable psychometric properties, they do not exhibit greater sensitivity or specificity with functional measures than standard neurocognitive tests

In Vitro Characterization of a Nineteenth-Century Therapy for Smallpox

In the nineteenth century, smallpox ravaged through the United States and Canada. At this time, a botanical preparation, derived from the carnivorous plant Sarracenia purpurea, was proclaimed as being a successful therapy for smallpox infections. The work described characterizes the antipoxvirus activity associated with this botanical extract against vaccinia virus, monkeypox virus and variola virus, the causative agent of smallpox. Our work demonstrates the in vitro characterization of Sarracenia purpurea as the first effective inhibitor of poxvirus replication at the level of early viral transcription. With the renewed threat of poxvirus-related infections, our results indicate Sarracenia purpurea may act as another defensive measure against Orthopoxvirus infections

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways

Purpose: Immune-related cutaneous adverse events (ircAEs) occur in ≥50% of patients treated with checkpoint inhibitors (CPI), but mechanisms are poorly understood. Experimental Design: Phenotyping/biomarker analyses were conducted in 200 patients on CPIs (139 with ircAEs, 61 without, control) to characterize their clinical presentation and immunologic endotypes. Cytokines were evaluated in skin biopsies, skin tape strip (STS) extracts and plasma using real-time PCR and Meso Scale Discovery multiplex cytokine assays. Results: Eight ircAE phenotypes were identified: pruritus (26%), maculopapular rash (MPR; 21%), eczema (19%), lichenoid (11%), urticaria (8%), psoriasiform (6%), vitiligo (5%), and bullous dermatitis (4%). All phenotypes showed skin lymphocyte and eosinophil infiltrates. Skin biopsy PCR revealed the highest increase in IFN-gamma mRNA in patients with lichenoid (p<0.0001) and psoriasiform dermatitis (p<0.01) as compared to patients without ircAEs, while the highest IL-13 mRNA levels were detected in the eczema (p<0.0001, compared to control). IL-17A mRNA was selectively increased in psoriasiform (p<0.001), lichenoid (p<0.0001), bullous dermatitis (p<0.05) and MPR (p<0.001), compared to control. Distinct cytokine profiles were confirmed in STS and plasma. Analysis determined increased skin/plasma IL-4 cytokine in pruritus, skin IL-13 in eczema, plasma IL-5 and IL-31 in eczema and urticaria, and mixed-cytokine pathways in MPR. Broad inhibition via corticosteroids or type 2-cytokine targeted inhibition resulted in clinical benefit in these ircAEs. In contrast, significant skin upregulation of type 1/type 17 pathways was found in psoriasiform, lichenoid, bullous dermatitis, and type 1 activation in vitiligo. Conclusions: Distinct immunologic ircAE endotypes suggest actionable targets for precision medicine-based interventions

Expanding the stdpopsim species catalog, and lessons learned for realistic genome simulations

Simulation is a key tool in population genetics for both methods development and empirical research, but producing simulations that recapitulate the main features of genomic datasets remains a major obstacle. Today, more realistic simulations are possible thanks to large increases in the quantity and quality of available genetic data, and the sophistication of inference and simulation software. However, implementing these simulations still requires substantial time and specialized knowledge. These challenges are especially pronounced for simulating genomes for species that are not well-studied, since it is not always clear what information is required to produce simulations with a level of realism sufficient to confidently answer a given question. The community-developed framework stdpopsim seeks to lower this barrier by facilitating the simulation of complex population genetic models using up-to-date information. The initial version of stdpopsim focused on establishing this framework using six well-characterized model species (Adrion et al., 2020). Here, we report on major improvements made in the new release of stdpopsim (version 0.2), which includes a significant expansion of the species catalog and substantial additions to simulation capabilities. Features added to improve the realism of the simulated genomes include non-crossover recombination and provision of species-specific genomic annotations. Through community-driven efforts, we expanded the number of species in the catalog more than threefold and broadened coverage across the tree of life. During the process of expanding the catalog, we have identified common sticking points and developed the best practices for setting up genome-scale simulations. We describe the input data required for generating a realistic simulation, suggest good practices for obtaining the relevant information from the literature, and discuss common pitfalls and major considerations. These improvements to stdpopsim aim to further promote the use of realistic whole-genome population genetic simulations, especially in non-model organisms, making them available, transparent, and accessible to everyone