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BackgroundSevere trauma induces a widespread response of the immune system. This “genomic storm” can lead to poor outcomes, including Multiple Organ Dysfunction Syndrome (MODS). MODS carries a high mortality and morbidity rate and adversely affects long-term health outcomes. Contemporary management of MODS is entirely supportive, and no specific therapeutics have been shown to be effective in reducing incidence or severity. The pathogenesis of MODS remains unclear, and several models are proposed, such as excessive inflammation, a second-hit insult, or an imbalance between pro- and anti-inflammatory pathways. We postulated that the hyperacute window after trauma may hold the key to understanding how the genomic storm is initiated and may lead to a new understanding of the pathogenesis of MODS.Methods and findingsWe performed whole blood transcriptome and flow cytometry analyses on a total of 70 critically injured patients (Injury Severity Score [ISS] ≥ 25) at The Royal London Hospital in the hyperacute time period within 2 hours of injury. We compared transcriptome findings in 36 critically injured patients with those of 6 patients with minor injuries (ISS ≤ 4). We then performed flow cytometry analyses in 34 critically injured patients and compared findings with those of 9 healthy volunteers. Immediately after injury, only 1,239 gene transcripts (4%) were differentially expressed in critically injured patients. By 24 hours after injury, 6,294 transcripts (21%) were differentially expressed compared to the hyperacute window. Only 202 (16%) genes differentially expressed in the hyperacute window were still expressed in the same direction at 24 hours postinjury. Pathway analysis showed principally up-regulation of pattern recognition and innate inflammatory pathways, with down-regulation of adaptive responses. Immune deconvolution, flow cytometry, and modular analysis suggested a central role for neutrophils and Natural Killer (NK) cells, with underexpression of T- and B cell responses.In the transcriptome cohort, 20 critically injured patients later developed MODS. Compared with the 16 patients who did not develop MODS (NoMODS), maximal differential expression was seen within the hyperacute window. In MODS versus NoMODS, 363 genes were differentially expressed on admission, compared to only 33 at 24 hours postinjury. MODS transcripts differentially expressed in the hyperacute window showed enrichment among diseases and biological functions associated with cell survival and organismal death rather than inflammatory pathways. There was differential up-regulation of NK cell signalling pathways and markers in patients who would later develop MODS, with down-regulation of neutrophil deconvolution markers. This study is limited by its sample size, precluding more detailed analyses of drivers of the hyperacute response and different MODS phenotypes, and requires validation in other critically injured cohorts.ConclusionsIn this study, we showed how the hyperacute postinjury time window contained a focused, specific signat...

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We use panel data for 50 states during the 1960-2000 period to examine the deterrent effect of capital punishment, using the moratorium as a ''judicial experiment.'' We compare murder rates immediately before and after changes in states' death penalty laws, drawing on cross-state variations in the timing and duration of the moratorium. The regression analysis supplementing the beforeand-after comparisons disentangles the effect of lifting the moratorium on murder from the effect of actual executions on murder. Results suggest that capital punishment has a deterrent effect, and that executions have a distinct effect which compounds the deterrent effect of merely (re)instating the death penalty. The finding is robust across 96 regression models. (JEL C1, K1)

I examine two important questions in the capital punishment literature: what kinds of murders are deterred and what effect does the length of the death row wait have on deterrence? I use monthly murder and execution data that measure deterrence more precisely than the annual data of most capital punishment studies. Results from least squares and negative binomial estimations indicate that capital punishment does deter: each execution results in, on average, three fewer murders. In addition, capital punishment deters murders previously believed to be undeterrable: crimes of passion and murders by intimates. Moreover, murders of both African-American and white victims decrease after executions, which suggests that capital punishment benefits people of all races. However, longer waits on death row before execution lessen the deterrence. Specifically, one less murder is committed for every 2.75-year reduction in death row waits. Thus, recent legislation to shorten the wait should strengthen capital punishment's deterrent effect.