In "The Production Function and the Theory of Capital, " Joan Robinson (1953-1954 . . . the production function has been a powerful instrument of miseducation. The student of economic theory is taught to write Q ϭ f (L, K ) where L is a quantity of labor, K a quantity of capital and Q a rate of output of commodities. He is instructed to assume all workers alike, and to measure L in man-hours of labor; he is told something about the index-number problem in choosing a unit of output; and then he is hurried on to the next question, in the hope that he will forget to ask in what units K is measured. Before he ever does ask, he has become a professor, and so sloppy habits of thought are handed on from one generation to the next.

Spinal cord injury results in a massive loss of neurons, and thus of function. We recently reported that passive transfer of autoimmune T cells directed against myelin-associated antigens provides acutely damaged spinal cords with effective neuroprotection. The therapeutic time window for the passive transfer of T cells was found to be at least 1 week. Here we show that posttraumatic T cell-based active vaccination is also neuroprotective. Immunization with myelin-associated antigens such as myelin basic protein (MBP) significantly promoted recovery after spinal cord contusion injury in the rat model. To reduce the risk of autoimmune disease while retaining the benefit of the immunization, we vaccinated the rats immediately after severe incomplete spinal cord injury with MBPderived altered peptide ligands. Immunization with these peptides resulted in significant protection from neuronal loss and thus in a reduced extent of paralysis, assessed by an open-field behavioral test. Retrograde labeling of the rubrospinal tracts and magnetic resonance imaging supported the behavioral results. Further optimization of nonpathogenic myelin-derived peptides can be expected to lead the way to the development of an effective therapeutic vaccination protocol as a strategy for the prevention of total paralysis after incomplete spinal cord injury.

Background The spread of a highly pathogenic, novel coronavirus (SARS-CoV-2) has emerged as a once-in-a-century pandemic, having already infected over 63 million people worldwide. Novel therapies are urgently needed. Janus kinase-inhibitors and Type I interferons have emerged as potential antiviral candidates for COVID-19 patients due to their proven efficacy against diseases with excessive cytokine release and their direct antiviral ability against viruses including coronaviruses, respectively. Methods A search of MEDLINE and MedRxiv was conducted by three investigators from inception until July 30th 2020 and included any study type that compared treatment outcomes of humans treated with Janus kinase-inhibitor or Type I interferon against controls. Inclusion necessitated data with clearly indicated risk estimates or those that permitted their back-calculation. Outcomes were synthesized using RevMan. Results Of 733 searched studies, we included four randomized and eleven non-randomized trials. Five of the studies were unpublished. Those who received Janus kinase-inhibitor had significantly reduced odds of mortality (OR, 0.12; 95% CI, 0.03–0.39, p< 0.001) and ICU admission (OR, 0.05; 95% CI, 0.01–0.26, p< 0.001), and had significantly increased odds of hospital discharge (OR, 22.76; 95% CI, 10.68–48.54, p< 0.00001) when compared to standard treatment group. Type I interferon recipients had significantly reduced odds of mortality (OR, 0.19; 95% CI, 0.04–0.85, p< 0.05), and increased odds of discharge bordering significance (OR, 1.89; 95% CI, 1.00–3.59, p=0.05). Conclusions Janus kinase-inhibitor treatment is significantly associated with positive clinical outcomes in terms of mortality, ICU admission, and discharge. Type I interferon treatment is associated with positive clinical outcomes in regard to mortality and discharge. While these data show promise, additional well-conducted RCTs are needed to further elucidate the relationship between clinical outcomes and Janus kinase-inhibitors and Type I interferons in COVID-19 patients.

IntroductionProcalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis.MethodsWe conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection.ResultsPatients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p<0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis.DiscussionThese studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.

In "The Production Function and the Theory of Capital," Joan Robinson (1953-1954 . . . the production function has been a powerful instrument of miseducation. The student of economic theory is taught to write Q 5 f (L, K ) where L is a quantity of labor, K a quantity of capital and Q a rate of output of commodities. He is instructed to assume all workers alike, and to measure L in man-hours of labor; he is told something about the index-number problem in choosing a unit of output; and then he is hurried on to the next question, in the hope that he will forget to ask in what units K is measured. Before he ever does ask, he has become a professor, and so sloppy habits of thought are handed on from one generation to the next.