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Purpose The majority of unconscious patients after cardiac arrest (CA) do not fulfill guideline criteria for a likely poor outcome, their prognosis is considered “indeterminate”. We compared brain injury markers in blood for prediction of good outcome and for identifying false positive predictions of poor outcome as recommended by guidelines. Methods Retrospective analysis of prospectively collected serum samples at 24, 48 and 72 h post arrest within the Target Temperature Management after out-of-hospital cardiac arrest (TTM)-trial. Clinically available markers neuron-specific enolase (NSE) and S100B, and novel markers neurofilament light chain (NFL), total tau, ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP) were analysed. Normal levels with a priori cutoffs specified by reference laboratories or defined from literature were used to predict good outcome (no to moderate disability, Cerebral Performance Category scale 1–2) at 6 months. Results Seven hundred and seventeen patients were included. Normal NFL, tau and GFAP had the highest sensitivities (97.2–98% of poor outcome patients had abnormal serum levels) and NPV (normal levels predicted good outcome in 87–95% of patients). Normal S100B and NSE predicted good outcome with NPV 76–82.2%. Normal NSE correctly identified 67/190 (35.3%) patients with good outcome among those classified as “indeterminate outcome” by guidelines. Five patients with single pathological prognostic findings despite normal biomarkers had good outcome. Conclusion Low levels of brain injury markers in blood are associated with good neurological outcome after CA. Incorporating biomarkers into neuroprognostication may help prevent premature withdrawal of life-sustaining therapy.

The expression of Renal Carcinoma (ERC)/mesothelin is enhanced in a variety of cancers. ERC/mesothelin contributes to cancer progression by modulating cell signals that regulate proliferation and apoptosis. Based on such biological insights, ERC/mesothelin has become a molecular target for the treatment of mesothelioma, pancreatic cancer, and ovarian cancer. Recent studies revealed about 50–60% of colorectal adenocarcinomas also express ERC/mesothelin. Therefore, colorectal cancer can also be a potential target of the treatment using an anti-ERC/mesothelin antibody. We previously demonstrated an anti-tumor effect of anti-ERC antibody 22A31 against mesothelioma. In this study, we investigated the effect of 22A31 on a colorectal adenocarcinoma cell line, HCT116. The cells were xenografted into BALB/c nu/nu mice. All mice were randomly allocated to either an antibody treatment group with 22A31 or isotype-matched control IgG1κ. We compared the volume of subsequent tumors, and tumors were pathologically assessed by immunohistochemistry. Tumors treated with 22A31 were significantly smaller than those treated with IgG1κ and contained significantly fewer mitotic cells with Ki67 staining. We demonstrated that 22A31 exhibited a growth inhibitory property on HCT116. Our results implied that ERC/mesothelin-targeted therapy might be a promising treatment for colorectal cancer.

In adults, expressed in renal cancer (ERC)/mesothelin is exclusively expressed in the mesothelial cells lining the pleural, pericardial, and peritoneal cavities, yet its function under physiological conditions is unknown. To explore this, we studied ERC expression in wild-type (WT) mice at different developmental stages by immunohistochemistry and analyzed the ultrastructure of the mesothelium in WT and Erc-knockout (KO) mice via electron microscopy. Additionally, cardiopulmonary function in adult WT and Erc-KO mice was assessed using echocardiography and the forced oscillation technique (FOT). During embryonic development in WT mice, ERC expression was detected in the epicardium as early as embryonic day (E)12.5 but was absent in the pleura until E18.5. The timing of expression appeared to coincide with the active maturation of these organs, which implied a potential role in cardiopulmonary development. Electron microscopy revealed that microvilli on the mesothelium of Erc-KO mice were immature compared to those of WT mice. Based on these findings, we hypothesized that ERC might contribute to cardiopulmonary function; however, echocardiography and FOT did not reveal any functional differences between WT and Erc-KO mice. This suggests that ERC has limited functional relevance under physiological conditions.

People who are more avoidant of pathogens are more politically conservative, as are nations with greater parasite stress. In the current research, we test two prominent hypotheses that have been proposed as explanations for these relationships. The first, which is an intragroup account, holds that these relationships between pathogens and politics are based on motivations to adhere to local norms, which are sometimes shaped by cultural evolution to have pathogen-neutralizing properties. The second, which is an intergroup account, holds that these same relationships are based on motivations to avoid contact with outgroups, who might pose greater infectious disease threats than ingroup members. Results from a study surveying 11,501 participants across 30 nations are more consistent with the intragroup account than with the intergroup account. National parasite stress relates to traditionalism (an aspect of conservatism especially related to adherence to group norms) but not to social dominance orientation (SDO; an aspect of conservatism especially related to endorsements of intergroup barriers and negativity toward ethnic and racial outgroups). Further, individual differences in pathogen-avoidance motives (i.e., disgust sensitivity) relate more strongly to traditionalism than to SDO within the 30 nations.

This study empirically examines the role of shocks to macro-uncertainty in shaping the responses of stock market participants to firm-specific earnings news. Specifically, I find that investors place greater weight on bad news following an increase in macro-uncertainty. By contrast, I find that investors place equal weight on both good and bad news following a decrease in macro-uncertainty. Furthermore, my findings show that these effects are more pronounced (1) for firms whose prior returns are more correlated with macro-uncertainty, (2) for firms that experience abnormally low trading volume during the earnings announcement, (3) for firms with relatively lower levels of institutional ownership, and (4) for firms with relatively higher information uncertainty. In sum, these findings provide novel empirical evidence that investors behave in a manner consistent with ambiguity aversion, with the effects strongest among unsophisticated investors.

Cardiopulmonary resuscitation (CPR)-related injuries have not been assessed since the 2015 Resuscitation Guidelines were established. To describe the incidence and severity of CPR-related injuries, and to evaluate the impact of the 2015 European Resuscitation Council (ERC) guidelines on the objective assessment of injuries. This multicenter, retrospective study analyzed autopsy reports of patients who underwent CPR. The most severe injuries were objectively assessed using the Abbreviated Injury Scale (AIS) and all injuries were summarized according to the New Injury Severity Score (NISS). Among 628 autopsy reports analyzed, patient characteristics and case details were distributed as follows: male sex, 71.1%; median age, 67 years; out-of-hospital cardiac arrest, 89.2%; bystander CPR, 56.8%. CPR-related injuries included: rib(s) 94.6%; lung(s), 9.9%; sternum, 62.4%; liver, 2.5%; and spleen, 1.8%. The incidence of bystander-provided CPR and severity of injury were similar to CPR provided only by professionals. There were no difference between mechanical and manual compressions. Females were older (p = 0.0001) and, although the frequency of their injuries was similar to males, they were significantly more severe (p = 0.01). Patients with life-threatening injury exhibited a baseline profile similar to those without injury . The median score (according to AIS) of the most severe injury was 3 and the median of summary of injuries was 13 according to the NISS–low risk of fatal injury. CPR-related injuries occurred frequently, although those that were life-threatening accounted for only 3% of cases. There were no differences between patients who were resuscitated by bystander(s) or by professionals and no differences between mechanical chest devices or manual resuscitation. Compared with a study based on the 2010 guidelines, similar injuries were found, but with more rib fractures, less visceral organ damage, and fewer life-threatening injuries. •The Impact of the 2015 European Resuscitation Council guidelines was evaluated.•Autopsy reports of those who underwent cardiopulmonary resuscitation were analyzed.•Cardiopulmonary resuscitation-related injuries were objectively assessed.•No differences between resuscitation by bystander(s) or compared to professionals.•Compared to the 2010 guidelines, more injuries, but fewer were life-threatening.

IntroductionIn acute obstructive common bile duct (CBD) stones endoscopic retrograde cholangiography for CBD stone removal before cholecystectomy (ChE) (‘ERC-first’) is the gold standard of treatment. Intraoperative antegrade balloon dilatation of the duodenal papilla during ChE with flushing of CBD stones to the duodenum (‘ABD-during-ChE’) may be an alternative ‘one-stop-shop’ treatment option. However, a comparison of outcomes of the ‘ABD-during-ChE’ technique and the’ERC-first’ approach has never been performed.MethodsRetrospective case control matched study of patients suffering from obstructive CBD stones (< 8 mm) without severe pancreatitis or cholangitis that underwent the traditional ‘ERC-first’ approach versus the ‘ABD-during-ChE’ technique. Primary endpoint was the overall Comprehensive Complication Index (CCI®) from diagnosis to complete CBD stone removal and performed ChE.ResultsA total of 70 patients were included (35 patients each in the ‘ERC first’- and ‘ABD-during-ChE’-group). There were no statistical significant differences in terms of demographics and disease specific characteristics between the two study groups. However, there was a not significant difference towards an increased overall CCI® in the ‘ERC-first’ group versus the ‘ABD-during-ChE’ group (14.4 ± 15.4 versus 9.8 ± 11.1, p = 0.225). Of note, six major complications (Clavien-Dindo classification ≥ IIIa) occurred in the ‘ERC-first’ group versus two in the ‘ABD-during-ChE’ group (17% versus 6%, p = 0.136). In addition, significantly more interventions and a longer overall time from diagnosis to complete clearance of bile ducts and performed ChE was found, when comparing the ‘ERC-first’ group and the ‘ABD-during-ChE’ group (3.7 ± 0.8 versus 1.1 ± 0.4, p < 0.001; 160.5 ± 228.6 days versus 12.0 ± 18.0 days, p < 0.001).ConclusionIn patients suffering from acute obstructive CBD stones smaller than 8 mm, compared to the ‘ERC-first’ approach, the ‘ABD-during-ChE’ technique resulted in significantly less interventions and reduced overall treatment time from diagnosis to complete clearance of bile ducts and performed ChE. This comes together with a strong trend of less intervention related complications in the ‘ABD-during-ChE’ group.

Over 30% of all endoscopic retrograde cholangiography procedures in the US are associated with biliary stone extraction, and over 10–15% of these cases are noted to be complex or difficult. The aim of this review is to define the characteristics of difficult common bile duct stones and provide an algorithmic therapeutic approach to these difficult cases. We describe additional special clinical circumstances in which difficult biliary stones are identified and provide additional management strategies to aid endoscopic stone extraction efforts.

ERC/mesothelin is expressed in mesothelioma and other malignancies. The ERC/mesothelin gene (MSLN) encodes a 71-kDa precursor protein, which is cleaved to yield 31-kDa N-terminal (N-ERC/mesothelin) and 40-kDa C-terminal (C-ERC/mesothelin) proteins. N-ERC/mesothelin is a soluble protein and has been reported to be a diagnostic serum marker of mesothelioma and ovarian cancer. Gastric cancer tissue also expresses C-ERC/mesothelin, but the significance of serum N-ERC levels for diagnosing gastric cancer has not yet been studied. We examined the latter issue in the present study as well as C-ERC/mesothelin expression in human gastric cancer tissues and cell lines. We immunohistochemically examined C-ERC/mesothelin expression in tissue samples from 50 cases of gastric cancer, and we also assessed the C-ERC/mesothelin expression in 6 gastric cancer cell lines (MKN-1, MKN-7, MKN-74, NUGC-3, NUGC-4 and TMK-1) using reverse transcription-polymerase chain reaction, flow cytometry, immunohistochemistry and immunoblotting. We also examined the N-ERC/mesothelin concentrations in the supernatants of cultured cells and in the sera of gastric cancer patients using an enzyme-linked immunosorbent assay (ELISA). N-ERC/mesothelin was detected in the supernatants of 3 gastric cancer cell lines (MKN-1, NUGC-4 and TMK-1) by ELISA, but its concentration in the sera of gastric cancer patients was almost same as that observed in the sera of the normal controls. In the gastric cancer tissues, C-ERC/mesothelin expression was associated with lymphatic invasion. N-ERC/mesothelin was secreted into the supernatants of gastric cancer cell lines, but does not appear to be a useful serum marker of gastric cancer.

Well-focused and accurately scaled high-resolution inverse synthetic aperture radar (ISAR) images provide a sound basis for feature extraction and target recognition. This paper proposes a novel high-resolution ISAR imaging algorithm, namely modified joint range spatial-variant autofocus and azimuth scaling algorithm (MJAAS). After motion compensation, the shift of the equivalent rotational center (ERC) of the target destroys the linear relationship between the azimuth chirp rates (ACR) of echo signals and the range coordinates of scattering points, thereby leading to the failure of azimuth scaling. Accordingly, a new joint equivalent rotational center position and effective rotational velocity (JERCP-ERV) signal model is established, serving as the basis of MJAAS. By recourse to the Davidon-Fletcher-Powell (DFP) algorithm, MJAAS can jointly estimate the ERCP and ERV by solving a minimum entropy optimization problem, so as to simultaneously achieve accurate azimuth scaling and range spatial-variant autofocus, which further improves the image focusing performance. MJAAS is not restricted by the modes of motion errors (coherent or non-coherent) and the motion compensation methods, so it can be widely applied to real data with the advantages of strong practicality and high accuracy. Extensive experimental results based on both simulated and real data are provided to corroborate the effectiveness of the proposed algorithm.