The role of dietary polyphenols in the moderation of the inflammatory response in early stage colorectal cancer

Current focus in colorectal cancer management is on reducing overall mortality by increasing the number of early stage cancers diagnosed and treated with curative intent. Despite the success of screening programmes in down-staging colorectal cancer, interval cancer rates are substantial and other strategies are desirable. Sporadic colorectal cancer is largely associated with lifestyle factors including diet. Polyphenols are phytochemicals ingested as part of a normal diet which are abundant in plant foods including fruits/berries and vegetables. These may exert their anti-carcinogenic effects via the modulation of inflammatory pathways. Key signal transduction pathways are fundamental to the association of inflammation and disease progression including those mediated by NF-κB and STAT, PI3K and COX. Our aim was to examine the evidence for the effect of dietary polyphenols intake on tumour and host inflammatory responses to determine if polyphenols may be effective as part of a dietary intervention. There is good epidemiological evidence of a reduction in colorectal cancer risk from case-control and cohort studies assessing polyphenol intake. It would be premature to suggest a major public health intervention to promote their consumption however, dietary change is safe and feasible, emphasising the need for further investigation of polyphenols and colorectal cancer risk

Counterterrorism Killings and Provisional IRA Bombings, 1970-1998

Counterterrorism strategies involving the killing of terrorists are a prominently used but controversial practice. Proponents argue that such strategies are useful tools for reducing terrorist activity, while critics question their effectiveness. This paper provides empirical insight into this strategy by conducting a series of negative binomial regression and Tobit estimations of the impact of killing Provisional Irish Republican Army (PIRA) terrorists as well as members of the Catholic community on counts of PIRA bombings and targeting activity in Northern Ireland for the period 1970-1998. We consider the impact of discriminate and indiscriminate killings (where only PIRA militants are killed versus those in which both militants and civilians are also killed) on subsequent PIRA IED attacks. Our findings illustrate that while total and discriminate counterterrorism killings have little to no effect on PIRA IED attacks, indiscriminate counterterrorism killings increased PIRA bombings overall and prompted the Provisional IRA to specifically target civilians in IED events. We conclude by discussing the scholarly and policy implications of these findings

Comparison of the prognostic value of measures of the tumor inflammatory cell infiltrate and tumor-associated stroma in patients with primary operable colorectal cancer

The aim of the present study was to compare the clinical utility of two measures of the inflammatory cell infiltrate - a H&E-based assessment of the generalised inflammatory cell infiltrate (the Klintrup-Mäkinen (KM) grade), and an immunohistochemistry-based assessment of combined CD3+ and CD8+ T-cell density (the “Immunoscore”), in conjunction with assessment of the tumor stroma percentage (TSP) in patients undergoing resection of stage I-III colorectal cancer (CRC). 246 patients were identified from a prospectively maintained database of CRC resections in a single surgical unit. Assessment of KM grade and TSP was performed using full H&E sections. CD3+ and CD8+ T-cell density was assessed on full sections and the Immunoscore calculated. KM grade and Immunoscore were strongly associated (P<0.001). KM grade stratified cancer-specific survival (CSS) from 88% to 66% (P=0.002) and Immunoscore from 93% to 61% (P<0.001). Immunoscore further stratified survival of patients independent of KM grade from 94% (high KM, Im4) to 60% (low KM, Im0/1). Furthermore, TSP stratified survival of patients with a weak inflammatory cell infiltrate (low KM: from 75% to 47%; Im0/1: from 71% to 38%, both P<0.001) but not those with a strong inflammatory infiltrate. On multivariate analysis, only Immunoscore (HR 0.44, P<0.001) and TSP (HR 2.04, P<0.001) were independently associated with CSS. These results suggest that the prognostic value of an immunohistochemistry-based assessment of the inflammatory cell infiltrate is superior to H&E-based assessment in patients undergoing resection of stage I-III CRC. Furthermore, assessment of the tumor-associated stroma, using TSP, further improves prediction of outcome

Foreshadowing targeted violence: Assessing leakage of intent by public mass murderers

The idea that identifiable behaviors presage violence is a core concept in the threat assessment literature. Especially meaningful from an operational perspective is “leakage”, which concerns whether offenders intentionally or unintentionally reveal insights into their thoughts or feelings that suggest impending targeted violence. Previous research has generally been limited to assessing the prevalence of leakage in various offender populations. The present study more thoroughly describes leakage in a sample of 115 public mass murderers in the U.S. whose activities took place between 1990 and 2014. We disaggregate leakage into three distinct forms (written statements, verbal statements to the public, verbal statements to family/friends), and examine these in relation to theorized correlates of leakage. The only significant predictor of leakage we found is the presence of a grievance, specifically a grievance against a person or entity, as opposed to a grievance against a category of people or a grievance against an idea, movement or religion. We discuss implications of these results as well as directions for future research

Developing a Phosphorus Fertilizer Training Program for Golf Course Personnel

A new Extension program has been developed in Minnesota to train golf course personnel on managing phosphorus inputs in response to recently passed legislation restricting the use of P fertilizers applied to turfgrass. This article introduces the P legislation passed in Minnesota, describes the curriculum, and discusses survey responses from golf course personnel who have participated in the program. The data presented indicate that respondents found the program either useful or very useful with respect to the day-to-day management of P fertilizers applied to turf

Shooting Alone: The Pre-Attack Experiences and Behaviors of U.S. Solo Mass Murderers with Implications for Threat Assessments

This paper outlines the socio-demographic, developmental, antecedent attack, attack preparation and commission properties of 115 mass murderers between 1990 and 2014. The results indicate that mass murderer attacks are usually the culmination of a complex mix of personal, political and social drivers that crystalize at the same time to drive the individual down the path of violent action. We specifically focus upon areas related to prior criminal engagement, leakage and attack location familiarity. Whether the violence comes to fruition is usually a combination of the availability and vulnerability of suitable targets that suit the heady mix of personal and political grievances and the individual’s capability to engage in an attack from both a psychological and technical capability standpoint. Many individual cases share a mixture of unfortunate personal life circumstances coupled with an intensification of beliefs/grievances that later developed into the idea to engage in violence

The thermal Casimir effect in lipid bilayer tubules

We calculate the thermal Casimir effect for a dielectric tube of radius $R$ and thickness delta formed from a membrane in water. The method uses a field-theoretic approach in the grand canonical ensemble. The leading contribution to the Casimir free energy behaves as -k_BTL kappa_C/R giving rise to an attractive force which tends to contract the tube. We find that kappa_C ~ 0.3 for the case of typical lipid membrane t-tubules. We conclude that except in the case of a very soft membrane this force is insufficient to stabilize such tubes against the bending stress which tends to increase the radius.Comment: 4 pages no figures RevTe