Introduction Massive transfusions are accompanied by an increased incidence of a particularly aggressive and lethal form of acute lung injury (delayed TRALI) which occurs >24 hours after transfusions. In light of recent reports showing that mtDNA DAMPs are potent pro-inflammatory mediators, and that their abundance in the sera of severely injured or septic patients is predictive of clinical outcomes, we explored the idea that mtDNA DAMPs are present in transfusion products and are associated with the occurrence of delayed TRALI. Methods We prospectively enrolled fourteen consecutive severely injured patients that received greater than three units of blood transfusion products and determined if the total amount of mtDNA DAMPs delivered during transfusion correlated with serum mtDNA DAMPs measured after the last transfusion, and whether the quantity of mtDNA DAMPs in the serum predicted development of ARDS. Results We found detectable levels of mtDNA DAMPs in PRBCs (3±0.4 ng/mL), FFP (213.7± 65 ng/mL), and platelets (94.8±69.2), with the latter two transfusion products containing significant amounts of mtDNA fragments. There was a linear relationship between the mtDNA DAMPs given during transfusion and the serum concentration of mtDNA fragments (R2=0.0.74, p<0.01). The quantity of mtDNA DAMPs in serum measured at 24 hours after transfusion predicted the occurrence of ARDS (9.9±1.4 vs 3.3±0.9, p<0.01). Conclusion These data show that FFP and platelets contain large amounts of extracellular mtDNA, that the amount of mtDNA DAMPs administered during transfusion may be a determinant of serum mtDNA DAMP levels, and that serum levels of mtDNA DAMPs after multiple transfusions may predict the development of ARDS. Collectively, these findings support the idea that mtDNA DAMPs in transfusion products significantly contribute to the incidence of ARDS after massive transfusions. Level of Evidence Level 1. (Prognostic and Diagnostic).

Background: The FDA approved drug granulocyte-colony stimulating factor (G-CSF) displays anti-apoptotic and immunomodulatory properties with neurogenesis and angiogenic functions. It is known to demonstrate neuroprotective mechanisms against ischemic global stroke. Autophagy is a method for the degradation of intracellular components and in particular, unrestrained autophagy may lead to uncontrolled digestion of affected neurons as well as neuronal death in cerebral ischemia. Mitochondrial dynamics is vital for the regulation of cell survival and death after cerebral ischemia and an early upstream event in neuronal death is mitochondrial fission. We examined the pro-survival mechanisms of G-CSF against apoptosis resulting from autophagy, mitochondrial stress and endoplasmic reticulum (ER) stress. Methods: Male Swiss Webster mice (20 weeks of age) were subjected to bilateral common carotid artery occlusion (BCAO) for 30 min. After occlusion, mice were injected with G-CSF (50 μg/kg) subcutaneously for 4 days. Behavioral analysis was carried out using the corner test and locomotor activity test before animals were sacrificed on day 4 or day 7. Key proteins in ER stress, autophagy and mitochondrial stress induced apoptosis were analyzed by immunoblotting.Results: G-CSF improved neurological deficits and improved behavioral performance on corner and locomotor test. G-CSF binds to G-CSF receptors and its activation leads to upregulation of Akt phosphorylation (P-Akt) which in turn decreases levels of the ER stress sensor, GRP 78 and expression of proteins involved in ER stress apoptosis pathway; ATF6, ATF4, eIF2α, XBP1, Caspase 12 and CHOP. G-CSF treatment significantly decreased Beclin-1, an autophagy marker, and decreased mitochondrial stress biomarkers DRP1 and P53. G-CSF also up-regulated the mitochondrial fusion protein, OPA1 and anti-apoptotic protein Bcl-2 while down-regulating the pro-apoptotic proteins Bax, Bak and PUMA. Conclusions: G-CSF is an endogenous ligand in the CNS that has a dual activity that is beneficial both in reducing acute neuronal degeneration and adding to long-term plasticity after cerebral ischemia. G-CSF treatment exerts neuroprotective effects on damaged neurons through the suppression of the ER stress and mitochondrial stress and maintains cellular homeostasis by decreasing pro-apoptotic proteins and increasing of anti-apoptotic proteins.

Critical Human Geography' is an international series which provides a critical examination and extension of the concepts and consequences of work in human geography and the allied social sciences and humanities. The volumes are written by scholars currently engaged in substantive research, so that, wherever possible, the discussions are empirically grounded as well as theoretically informed. Existing studies and the traditions from which they derive are carefully described and located in their historically specific context, but the series at the same time introduces and explores new ideas and insights from the human sciences as a whole. The series is thus not intended as a collection of synthetic reviews, but rather as a cluster of considered arguments which are accessible enough to engage geographers at all levels in the development of geography. The series therefore reflects the continuing methodological and philosophical diversity of the subject, and its books are united only by their common commitment to the prosecution of a genuinely human geography.

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Background Global ischemia is the resulting effect of a cardiopulmonary arrest (CPA). Presently there is no effective treatment to address neurological deficits in patients who survived a CPA. Granulocyte-colony stimulating factor is a growth factor (G-CSF) with a plethora of beneficial effects, including neuroprotection. Clinical application of human G-CSF (hG-CSF) is limited due to its plasma half-life of 4 h. Therefore, novel approaches need to be investigated that would (1) enable prolonged manifestation of hG-CSF and (2) demonstrate G-CSF efficacy from studying the underlying protective mechanisms of hG-CSF. In our previous work, we used the self-complementary adeno-associated virus (stereotype2: scAAV2) as a vector to transfect the hG-CSF gene into the global ischemic brain of a mouse. As an extension of that work, we now seek to elucidate the protective mechanisms of hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia. Method A single drop of either AAV-CMV-hG-CSF or AAV-CMV-GFP was dropped into the conjunctival sac of the Swiss Webster mouse’s left eye, 30–60 min after bilateral common artery occlusion (BCAO). The efficacy of the expressed hG-CSF gene product was analyzed by monitoring the expression levels of endoplasmic reticulum stress (ER), mitochondrial dynamics and autophagic proteins over 4- and 7-days post-BCAO in vulnerable brain regions including the striatum, overlying cortex (frontal brain regions) and the hippocampus (middle brain regions). Statistical analysis was performed using mostly One-Way Analysis of variance (ANOVA), except for behavioral analysis, which used Repeated Measures Two-Way ANOVA, post hoc analysis was performed using the Tukey test. Results Several biomarkers that facilitated cellular death, including CHOP and GRP78 (ER stress) DRP1 (mitochondrial dynamics) and Beclin 1, p62 and LC3-ll (autophagy) were significantly downregulated by hG-CSF gene transfer. hG-CSF gene therapy also significantly upregulated antiapoptotic Bcl2 while downregulating pro-apoptotic Bax. The beneficial effects of hG-CSF gene therapy resulted in an overall improvement in functional behavior. Conclusion Taken together, this study has substantiated the approach of sustaining the protein expression of hG-CSF by eye drop administration of the hG-CSF gene. In addition, the study has validated the efficacy of using hG-CSF gene therapy against endoplasmic reticulum induced stress, mitochondrial dynamics and autophagy in global ischemia.

The spatial distribution of phytoplankton can be difficult to assess in shallow, productive aquatic systems due to frequent algal blooms, high turbidity and sediment-resuspension events. We conducted a study to assess the distribution of suspended particles in Lake Okeechobee, Florida, utilizing both Landsat (1974-75) or Advanced Very High Resolution Radiometer (AVHRR) (1987) satellite remote sensing. Surface water samples were collected by helicopter to determine in situ chlorophyll-a and turbidity levels at 20 stations on four dates in 1974-75 and six dates in 1987. Remotely sensed reflectance values agreed well with in situ particle densities at the 20 in-lake stations (average R 2 : Landsat = 0.81, AVHRR = 0.53) and independent, synoptic boat mapping of algal blooms (r 2 = 0.79, P < 0.01). Basin-wide maps of chlorophyll and turbidity, as well as additional spatial sampling, both indicated that these parameters are not necessarily coupled in Lake Okeechobee. Our data concur with the hypothesis that the spatial distributions of chlorophyll and turbidity are shaped by different forces. The highest concentrations of chlorophyll occurred in the vicinity of tributary nutrient inputs at the lake's perimeter, while turbidity increased towards the center of the lake, reflecting predominant water circulation patterns.

Conspiracy theories about COVID-19 have proliferated during the global pandemic, and their rapid spread among certain groups inthe population has important implications for policy attitudes (e.g., motivation to engage in social distancing and willingness to vaccinate). Using survey data from two waves of a nationally representative, longitudinal study of life in lockdown in the UK (N = 1,406), we analyze the factors associated with belief in three theories related to COVID-19, namely that it 1) originated in a meat market in Wuhan, China, 2) was developed in a lab in Wuhan, China, and 3) is caused by 5G mobile networks. Using a dual-factor model, we test how cognitive ability and motivations affect susceptibility to misinformation. Our findings suggest that motivational and political dispositions, as well as the sources from which people derive COVID-19 related information, are strongly associated with belief in conspiracy theories about the virus, though these predictors vary among conspiracies. Belief in the Chinese lab conspiracy is associated with right-wing authoritarianism (RWA), social dominance orientation (SDO) and a preference for tabloid newspapers, while belief in the 5G network origin story is associated with social dominance orientation and a tendency to derive information on COVID-19 from social media. Moreover, we find that motivational factors like RWA and SDO have larger effect sizes than COVID-19 related anxiety, a desire for certainty, cognitive reasoning ability, or even general conspiracy ideation (in the case of 5G belief). These findings suggest that efforts to mitigate the potential damage caused by conspiracy theories, for example, by increasing education and awareness, may be inadequate because they miss a larger story, namely the role that politically motivated reasoning plays in making individuals susceptible to misinformation, and the propagation of conspiracies through networks and channels that reinforce these inaccurate worldviews.

TX 75083-3836, U.S.A., fax 01-972-952-9435. AbstractAccording to the OSHA database for the period from 1997 through 2003, one fatality occurred every 10 days in the U.S. upstream (E&P) oil and gas industry. To determine trends and provide insights into the safety failures, as well as potential interventions to eliminate the high frequency of fatal incidents, the seven years of OSHA data were reviewed. This data encompasses over 250 fatalities from the four principal SIC categories that comprise the onshore upstream oil & gas exploration and production industry. Data were sorted initially by region, well drilling or field servicing, rig type, and event. Further analysis was conducted by a diverse team of industry professionals, including representatives from operating companies, well drilling and servicing companies, and industry trade associations. Particular focus was directed at accident type, equipment type and well site location in an attempt to identify causal factors from the limited incident descriptions contained in the OSHA database.The resulting analysis showed nearly half of all fatalities (47%) resulted from "struck by" incidents; fires and explosions accounted for 16% while falls from heights accounted for another 14% of the fatalities. Fatality incident rates from year to year were strongly correlated to overall upstream industry activity level as represented by the U.S. rig count.This fatality data review provides oil and gas industry operating managers, safety professionals, trade associations and others a road map for targeted improvement programs and priorities for reducing onshore oil field-related fatalities.