Examination of prognostic factors in patients undergoing surgery for colorectal perforation: A case controlled study

AbstractObjectiveTo determine if the POSSUM, SOFA, MPI, and SAS scores provide a better measure of severity for patients with prognostic factors undergoing surgery for colorectal perforation.SubjectsFifty-nine patients who underwent surgery between 1996 and 2012.MethodsWe retrospectively reviewed background factors, blood and physiological test results, and intraoperative findings of patients who survived and those who died. We also compared the POSSUM, SOFA, MPI, and SAS scores. Multivariate analysis was performed for factors that were significant by univariate analysis, and selected factors were used to produce a predictive prognostic model.ResultsUnivariate analysis revealed significant differences in age, anticoagulant/steroid administration, serum creatinine level, PF ratio, base excess (BE), chest radiography, pulse rate, and severity of peritoneal soiling. Age, serum creatinine level, pulse rate, and severity of peritoneal soiling were selected for multivariate analysis; only pulse rate was significantly different. There were significant differences between the two groups in POSSUM PS, OSS, SOFA, and MPI scores, and a comparison in terms of the ROC curve showed that our model had the highest peak; the area under the curve was 94.8% compared with 70–80% for the other systems, suggesting that our model is better than those systems.ConclusionsPOSSUM and SOFA are valid methods of evaluating risk from colorectal perforation, but our study revealed addition risk factors: (1) the PF ratio and BE, which are not included in POSSUM; (2) the pulse rate and severity of peritonitis, which are not included in SOFA; and (3) anticoagulant/steroid hormone administration

Application of Benchtop NMR for Metabolomics Study Using Feces of Mice with DSS-Induced Colitis

Nuclear magnetic resonance (NMR)-based metabolomics, which comprehensively measures metabolites in biological systems and investigates their response to various perturbations, is widely used in research to identify biomarkers and investigate the pathogenesis of underlying diseases. However, further applications of high-field superconducting NMR for medical purposes and field research are restricted by its high cost and low accessibility. In this study, we applied a low-field, benchtop NMR spectrometer (60 MHz) employing a permanent magnet to characterize the alterations in the metabolic profile of fecal extracts obtained from dextran sodium sulfate (DSS)-induced ulcerative colitis model mice and compared them with the data acquired from high-field NMR (800 MHz). Nineteen metabolites were assigned to the 60 MHz 1H NMR spectra. Non-targeted multivariate analysis successfully discriminated the DSS-induced group from the healthy control group and showed high comparability with high-field NMR. In addition, the concentration of acetate, identified as a metabolite with characteristic behavior, could be accurately quantified using a generalized Lorentzian curve fitting method based on the 60 MHz NMR spectra.journal articl

Myc-induced nuclear antigen constrains a latent intestinal epithelial cell-intrinsic anthelmintic pathway

<div><p>Expulsion of parasitic gastrointestinal nematodes requires diverse effector mechanisms coordinated by a Th2-type response. The evolutionarily conserved JmjC protein; Myc Induced Nuclear Antigen (Mina) has been shown to repress IL4, a key Th2 cytokine, suggesting Mina may negatively regulate nematode expulsion. Here we report that expulsion of the parasitic nematode <i>Trichuris muris</i> was indeed accelerated in Mina deficient mice. Unexpectedly, this was associated not with an elevated Th2- but rather an impaired Th1-type response. Further reciprocal bone marrow chimera and conditional KO experiments demonstrated that retarded parasite expulsion and a normal Th1-type response both required Mina in intestinal epithelial cells (IECs). Transcriptional profiling experiments in IECs revealed anti-microbial α-defensin peptides to be the major target of Mina-dependent retention of worms in infected mice. In vitro exposure to recombinant α-defensin peptides caused cytotoxic damage to whipworms. These results identify a latent IEC-intrinsic anthelmintic pathway actively constrained by Mina and point to α-defensins as important effectors that together with Mina may be attractive therapeutic targets for the control of nematode infection.</p></div

Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology

Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations

A monoclonal antibody-based sandwich enzyme-linked immunosorbent assay for detection of secreted alpha-defensin

Paneth cells at the base of small intestinal crypts secrete alpha-defensins, which contribute to innate immunity and shape composition of enteric microbiota. Efforts to establish a relationship between secreted alpha-defensins and disease have been hampered by a lack of sensitive assays to quantify luminal alpha-defensins. Here we report on a highly sensitive sandwich enzyme-linked immunosorbent assay (ELISA) for the mouse Paneth cell alpha-defensin cryptdin-4 (Crp4) in varied sources, including luminal contents rinsed from stomach to distal colon and fecal pellets. One pair of monoclonal antibodies (mAbs), selected from 10 rat hybridomas secreting Crp4-specific mAbs, was optimized for Crp4 detection and specificity in the sandwich ELISA. In CD1 mice, luminal Crp4 levels increased gradually from 6.8 +/- 5.2 ng/ml in proximal small intestine to 54.3 +/- 10.3 ng/ml in distal small intestine, and the peptide was detected in colonic lumen and feces. Secreted Crp4 was reduced significantly in feces of IL10 null mice, a model of inflammatory bowel disease (IBD) when compared with wild-type controls. This Crp4 sandwich ELISA enables accurate determinations of luminal alpha-defensins as biomarkers of Paneth cell function and enteric integrity in diverse disease states such as IBD, infectious disease, graft versus host disease, and obesity in association with dysbiosis of the intestinal microbiota. (C) 2013 Elsevier Inc. All rights reserved

Gang Violence in the "Balance:" A Triadic Analysis of Rivalries and Allies

The very existence and purpose of street gangs is predicated on having an external threat or enemy. It is also recognized that gangs form allies as well as rivals with other gangs. The fact that gangs are embedded in an intricate structure of both positive (ally) and negative (rivalry) relationships has rarely been explored in terms of understanding the levels and the patterns of gang violence. In this paper, we use structural balance theory along with its applications in the international relations literature to examine whether certain triadic structures in which two rival gangs i and j are related to a third gang with either an ally or rival relationship is linked to the levels of violence that i will inflict upon j. We analyze the data on inter-gang relations and violent incidents among the gangs in Long Beach, CA using multiple regression quadratic assignment procedure (MRQAP). Our results indicate that the actual violent incidents between two rival gangs are not only the product of their feuding relationships but also the third gangs and the nature of their relationship with the two gangs. The results can potentially contribute to the formulation of effective strategy to manage gang violence and allocate law enforcement resources to gang conflicts that are likely to escalate

Redemption in the Presence of Widespread Criminal Background Checks

Recent advances in information technology and growing concerns about employer liability have combined to increase the demand for criminal background checks. Also, since over 14 million arrests are made each year, many individuals will have criminal history records. As a result, many individuals who have redeemed by avoiding involvement in crime and are seeking employment will be haunted by the record of a crime committed a long time ago, a record that may well indicate a low probability of future crime risk. It is known that the probability of recidivism declines with time "clean" since a last arrest, so that there is some T* such that someone with no arrest for T* years is of no greater risk than any demographically similar counterpart. The problem is that we have very little information on the appropriate value of T*, and how that value varies with the crime type of the earlier event (C1) and the offender’s age at that event (A1). This paper estimates the degree to which a past criminal record loses its relevance in terms of its ability to predict future offending. Data obtained from a state criminal-history repository allow us to estimate the hazard of rearrest. This paper looks for its intersection with the demographically appropriate age-crime curve, representing the risk of arrest for the general population. The findings of this research can contribute to the development of relevancy guidelines for the users of background-checking services and for policy makers interested in enhancing employment opportunities in developing regulations regarding the dissemination of such records

Bactericidal Activity of Mouse α-Defensin, Cryptdin-4 Predominantly Affects Noncommensal Bacteria

Mouse Paneth cell α-defensins, termed cryptdins, are secreted into the intestinal lumen, exert microbicidal activity and contribute to intestinal innate immunity. Among them, cryptdin-4 (Crp4) has the most potent microbicidal activity. In the intestinal lumen, commensal bacteria colonize and elicit beneficial effects to the host. However, the effects of Crp4 against commensal bacteria are poorly understood. Thus, we investigated the bactericidal activities of Crp4 against commensal bacteria compared to non-commensal bacteria. Oxidized Crp4 showed only minimal or no bactericidal activity against 8 out of 12 commensal bacterial species, including Bifidobacterium bifidum and Lactobacillus Casei. We further addressed a role of the conserved disulfide bonds of Crp4 by analyzing reduced Crp4 (r-Crp4). r-Crp4 demonstrated significantly greater bactericidal activities against 7 of 12 commensal bacteria than did oxidized Crp4. Oxidized Crp4 and r-Crp4 elicited equivalently potent bactericidal activities against 11 of 11 non-commensal bacteria tested such as Salmonella enterica serovar Typhimurium, and 5 of 12 commensal bacteria. Furthermore, when r-Crp4 was exposed to a processing enzyme of cryptdins, MMP-7, r-Crp4 was degraded and bactericidal activities disappeared. These findings suggest that Crp4 has selective bactericidal activities against intestinal microbiota and that the activities are dependent on the disulfide bonds

Analyzing Racial Disparities in Incarceration Sentences Using Data from State Criminal History Repositories

This project is designed to reveal and document the role of criminal history record information in explaining racial disparity in incarceration sentences using official records of several states. This project will not only document the presence and the extent of racial disparity in sentencing, but will also leverage the focus on criminal history data to frame the study in a larger context of direct and collateral consequences of criminal history records. Major Project Activities 1. Data Collection and Curation The project will collect criminal history data from three state criminal history records repositories. This dataset is referred to within the industry as “computerized criminal history” or CCH data. The range of data expected to be collected will be a minimum of 30 years (beginning in 1990). The dataset will include all data needed to address the research questions presented in the Research Methodology section of this proposal. Datasets from the states of Maine, New Jersey and South Carolina have been acquired as of this date although in some cases refreshes of the data are being requested to address all data requirements. Should any state be unable to provide the full dataset required, participation by replacement states will be pursued (see Risk Section below). SEARCH will be primarily responsible for the curation of this data into a standardized and semantically equivalent dataset for research purposes. UMD will assist in data curation tasks. Curation includes completing the standard Extract, Transform and Load (ETL) functionality necessary to acquire and host the data. Curation also includes the standardization of data between the states to ensure semantic equivalency and the ability to perform equivalent analyses. SEARCH’s familiarity and expertise in understanding the data contained in state CCH systems uniquely qualifies it to ensure semantic equivalency of the data to be analyzed. 2. Research and Analysis In collaboration with state criminal history repositories, this project aims to illuminate the role of the criminal history record in explaining racial disparity in incarceration sentences. We will focus primarily on incarceration sentences for two reasons. First, incarceration is one of the most severe forms of punishment, and the fact that minorities are being disproportionately punished by incarceration is one of the most troubling aspect of racial disparity. Second, identifying the presence of racial disparity in incarceration sentences may indicate a lack of racial disparity (or disparity favoring minorities). This way, by directly examining the racial disparity in incarceration sentences, we can gain an understanding of racial disparity in other types of sentences, which is informative. State repositories provide an authoritative source of individual criminal history records, allowing for a comprehensive assessment of the role of criminal history information in sentencing, especially incarceration sentences. Along with the unprecedented growth in incarceration rates from the 1970’s to the turn of the century, there was considerable growth in racial disparity in incarceration rates (National Research Council, 2014). While this racial disparity in incarceration persists today, many have noted that the extent of such disparity actually decreased in the last decade (Beck and Blumstein, 2018; Cullen, 2016; Enders et al., 2019; King and Light, 2019; Kim and Kiesel, 2018; Nellis, 2016). A recent report by the Council on Criminal Justice, however, found that despite the progress in narrowing racial disparity in who is committed to prison, racial disparity has been growing with regard to time served with blacks spending more time in prison than whites across all crime types (Sabol et al., 2019; also Courtney et al., 2017). While this could be due to multiple factors, the report singles out criminal history as a potential contributor of growing racial disparity in time served, and the authors make a case that it deserves further research (see also Weihua, 2019). Criminal history is not only a key factor in sentencing decisions (Roberts, 1997) and one of the two primary factors that make up the presumptive sentences for most sentencing guidelines (Frase 2005), but is also a key consideration in plea bargaining (Kutateladze et al., 2015; Redlich et al., 2016). A better understanding of the racial variation in the creation and application of criminal history over time is a key area of research that can shed light on our existing and future policy efforts to address disparity in the system. The current project’s main analysis builds on the recent work by Kim and Kiesel (2018), which used individual criminal history data from the New York state repository to estimate the amount of racial disparity in the state prison unexplainable with the amount of disparity in arrest. Using the method first introduced by Blumstein (1982), the paper demonstrated that accounting for criminal history as well as crime type reduces the amount of unexplainable racial disparity in prison sentences, as those factors vary across racial groups. While this is an important step toward understanding the role of criminal history in racially disparate sentencing, there are several avenues the current project proposes to explore by exploiting the repository data on complete individual criminal history records. First, we will apply the same methodology using other state repository data and aim to replicate the previous findings on racial disparity in the probability of incarceration sentences and the incarceration sentence lengths. Prior work has made it clear that racial disparity in prison and its drivers varies considerably across states (Beck and Blumstein, 2018; Enders et al., 2019; Nellis, 2016). Analyzing the role of criminal history across states could clarify the national picture and also point to more specific policy directions for individual states, through the analysis of state-specific factors such as sentencing guidelines and policy reforms. Furthermore, the use of state repository data will allow us to investigate within-state heterogeneity. The amount of racial disparity in incarceration and the extent to which it is explainable varies across regions within a state (Kim and Kiesel, 2018). Sentencing research has found support for inter-court and inter-county variation in sentencing and such variation can be explained not only by individual- and case-level factors (e.g., criminal history and crime severity), but also by court- and county/community-level factors, such as court size, caseload, and crime rates (Johnson, 2006; Ulmer and Johnson, 2004). The within-state analysis will help understand the role of regional and county factors in generating variation in racial disparity in incarceration sentences. Analyzing the data over the years that saw a steady increase in incarceration, as well as the years that have seen stability in incarceration rates in recent years, will allow us to evaluate policy and legislative reforms intended to reduce prison population as well as racial disparity, including changes to drug laws, mandatory minimums, and bail and pretrial detention. This analysis is state specific. For example, New Jersey passed a legislative reform related to drug-free school zone laws in 2010. The proposed analysis, using the method by Gelbach (2016), will examine the changes in racial disparity associated with these reforms and identify the drivers of the changes (e.g., weight on criminal history). Second, the current project extends the above method (Blumstein, 1982; Kim and Kiesel, 2018) by exploring racial disparity in decision points beyond arrest and sentencing. The existing research on assessing racial disproportionality in incarceration captures the presence of net disparate treatment between arrest and sentencing, but it leaves out the potential disparity in intervening stages, providing an incomplete picture of the drivers of racial disparity in sentencing. There are several interlocking decision points between police arrest and judicial sentencing that can affect disparity, including charge filing, pretrial detention and bail, plea negotiation, and disposition. It is possible, for example, that the process from conviction to incarceration does not differentially treat racial and ethnic minorities, but the racial disparity at sentencing may result from the fact that the process from arrest to conviction disfavors minorities. While a few recent studies examine the cumulative nature of racial disparity in successive decision points up to sentencing (Kutateladze et al., 2014; Wooldredge et al., 2015), this study breaks ground by extending data from over decades across states. Third, the current project explores the structures and rules embedded in the judicial process that can contribute to racially disparate sentencing outcomes. The “modal approach” in the study of race and sentencing tends to use regression models to estimate the coefficients on race variables while controlling for other case and demographic variables (Baumer, 2013). While this approach has been contributing to our efforts to detect “unwarranted disparity” – unwarranted in the sense that it points to the racial difference in sentencing that cannot be explained by legal factors such as offense seriousness, criminal history, weapon use – this approach of trying to explain away unwarranted disparity may inadvertently throw away important information about the sources of racial disparity in sentencing (Bushway and Forst, 2013; Bushway and Piehl, 2011; Kurlychek and Johnson, 2019; MacDonald and Raphael, 2020; Murakawa, 2019). We will unpack “warranted disparity” and examine how the factors and structures, which on their face appear race neutral, could be an important avenue to reduce racial disparity. Among the legal factors, we will pay close attention to type of offense in incarceration sentences. Racial disparity in prison tends to be less explainable for offenses that are more susceptible to judicial discretion, most notably drug offenses (Beck and Blumstein, 2018). It is interesting to note that the recent decline in racial disparity is also most salient for drug offenses (Sabol et al., 2019), suggesting that the scale of incarceration, judicial discretion, and racial disparity are likely intertwined (MacDonald and Raphael, 2020). Fourth, relatedly, we will also examine the racial disparity in the accumulation of criminal history over the life course and how it manifests in incarceration sentence disparity during the eras of rapid prison growth and recent decline. Over the last four decades, the proportion of the population with criminal records (arrest, felony conviction, incarceration) increased with considerable racial differences (Brame et al., 2012; Brame et al., 2014; Pettit and Western, 2004; Shannon et al., 2017). Furthermore, the increasing probability of incarceration during the era of mass incarceration was driven in part by the increase in the average defendant’s criminal record (King, 2019). Given that judicial discretion can lead to disproportionate punishment for those with more extensive criminal history (Bushway and Piehl, 2001; MacDonald and Raphael, 2020), examining racial disparity in criminal history accumulation will illuminate how race can exert direct and indirect influences on incarceration sentences. Lastly, beyond the single dimensionality of race, we will explore the intersectionality of race, gender, age, and legal factors. Given that prior work has demonstrated differential impacts of these intersections on sentence severity (Spohn and Sample, 2013; Steen et al., 2005; Steffensmeier et al., 1998), a better understanding of racial disparity in incarceration sentences and its drivers and trends will benefit from closely examining the circumstances under which race matters. We will work closely with state criminal history repositories to access pertinent subsets of data from their criminal history databases. This collaboration will allow us to not only extract the cohorts of individuals sentenced in particular years to link their sentences to their criminal history records, but also to examine the accumulation of criminal history within the broader context of racial disparity trends. To date, SEARCH has received criminal history data from Maine, New Jersey, and South Carolina. Other states have recently agreed to provide criminal history data to SEARCH in support of broader research efforts and, to the extent possible, data from these jurisdictions will augment our research here. 3. Workshop This project will not only document the presence and the extent of racial disparity in sentencing, but it will also leverage the focus on CCH in a broader context of direct and collateral consequences associated with criminal history records. Criminal records can hinder access to employment, housing, education, and other opportunities (Kirk and Wakefield, 2018; Pager, 2008), but the use of criminal records in the criminal justice system that can trap people in the system and prevent (re)integration should be critically examined. From risk assessment for pre-trial services, probation, and parole supervision to sentencing decisionmaking, those with prior records systematically receive harsher punishment and continue to be entangled with the criminal justice system (Hannah-Moffat, 2013; Harcourt, 2007; Murakawa, 2019). To the extent that racial disparity exists in the accumulation of criminal history, that disparity could perpetuate and manifest itself in the disproportionate representation of racial minorities in incarceration sentences. We will engage with stakeholders to inform them about the sources and conditions of racial disparity in sentencing and incarceration. We will also discuss potential remedies, which may include record clearing mechanisms, but also how criminal history is used formally and informally across criminal justice decision points. Findings from this project can help develop policy changes to reduce racial disparity and fully understand the intended and potentially unintended impacts of such changes through mechanisms such as racial impact statements. In collaboration with Arnold Ventures, SEARCH will host a workshop to review our research and to explore the operational and policy implications of our findings. The objective of the workshop is to leverage research findings in developing policy briefs and program recommendations. Project staff will draft 2-3 policy briefs for consideration and to stimulate discussion at the workshop. Project staff will also facilitate discussion of publication and dissemination strategies to reach the broadest national audience. The workshop will include invited community advocates, stakeholders working on reducing limiting barriers, state criminal history records repository directors, justice practitioners, and policy subject matter experts. Our preference is to organize the workshop as a day-long, in-person event in Washington, D.C., to foster an open and dynamic dialogue among workshop participants. On-line, virtual meeting options will also be considered, however, if existing public health and safety conditions and travel restrictions persist. 4. Policy Briefs/Reports/Dissemination/Social Media Channels In addition to research papers submitted for publication in peer-reviewed journals, op-ed articles, and presentations at professional and academic conferences, the project team will also draft 2-3 policy briefs for review and discussion at the workshop. Following the workshop, the policy briefs will be revised and expanded, as needed, and circulated via the dissemination strategy and social media channels by SEARCH, and provided to workshop participants, community advocates, and other stakeholders for their dissemination. SEARCH will also feature the research and policy briefs in SEARCH Membership Group meetings and in dedicated workshops during the next Symposium on Justice Information Technology, Policy, and Research