The prognostic value of CD3+ tumor-infiltrating lymphocytes for stage II colon cancer according to use of adjuvant chemotherapy: A large single-institution cohort study

BackgroundHigh tumor infiltrating lymphocytes (TILs) density was previously shown to be associated with favorable prognosis for patients with colon cancer (CC). However, the impact of TILs on overall survival (OS) of stage II CC patients who received adjuvant chemotherapy (ADJ) or not (no-ADJ) is unknown. We assessed the prognostic value of CD3+ TILs in stage II CC patients according to whether they had ADJ or not.MethodsPatients treated with curative surgery for stage II CC (2002–2013) were selected from the Santa Maria alle Scotte Hospital registry. TILs at the invasive front, center of tumor, and stroma were determined by immunohistochemistry and manually quantified as the rate of TILs/total tissue areas. High TILs (H-TILs) was defined as >20%. Patients were categorized as high or low TILs (L-TILs) and ADJ or no-ADJ.ResultsOf the 678 patients included, 137 (20%) received ADJ and 541 (80%) did not. The distribution of the 4 groups were: 16% (L-TIL/ADJ), 64% (L-TIL/no-ADJ), 5% (H-TIL/ADJ), 15% (H-TIL/no-ADJ). Compared to H-TILs/no-ADJ, ADJ patients showed a significantly increased OS (P<.01) regardless of the TILs rate whereas L-TILs/no-ADJ had significantly decreased OS and higher risk of death (HR=1.41; 95% CI, 1.06–1.88; P<.0001). On multivariable analysis, the unfavorable prognostic value of L-TILs (vs. H-TILs) for no-ADJ patients was confirmed (HR=1.36; 95% CI 1.02, 1.82; P=.0373).ConclusionLow CD3+ TILs rate was associated with shorter OS in those with stage II colon cancer who did not receive adjuvant therapy. Low CD3+ TILs could be considered an additional risk factor for still ADJ-untreated stage II CC patients, which could facilitate clinical decision making.     

Bone formation rather than inflammation reflects Ankylosing Spondylitis activity on PET-CT: a pilot study

Introduction

Positron Emission Tomography - Computer Tomography (PET-CT) is an interesting imaging technique to visualize Ankylosing Spondylitis (AS) activity using specific PET tracers. Previous studies have shown that the PET tracers [¹⁸F]FDG and [¹¹C](R)PK11195 can target inflammation (synovitis) in rheumatoid arthritis (RA) and may therefore be useful in AS. Another interesting tracer for AS is [¹⁸F]Fluoride, which targets bone formation. In a pilot setting, the potential of PET-CT in imaging AS activity was tested using different tracers, with Magnetic Resonance Imaging (MRI) and conventional radiographs as reference.

Methods

In a stepwise approach different PET tracers were investigated. First, whole body [¹⁸F]FDG and [¹¹C](R)PK11195 PET-CT scans were obtained of ten AS patients fulfilling the modified New York criteria. According to the BASDAI five of these patients had low and five had high disease activity. Secondly, an extra PET-CT scan using [¹⁸F]Fluoride was made of two additional AS patients with high disease activity. MRI scans of the total spine and sacroiliac joints were performed, and conventional radiographs of the total spine and sacroiliac joints were available for all patients. Scans and radiographs were visually scored by two observers blinded for clinical data.

Results

No increased [¹⁸F]FDG and [¹¹C](R)PK11195 uptake was noticed on PET-CT scans of the first 10 patients. In contrast, MRI demonstrated a total of five bone edema lesions in three out of 10 patients. In the two additional AS patients scanned with [¹⁸F]Fluoride PET-CT, [¹⁸F]Fluoride depicted 17 regions with increased uptake in both vertebral column and sacroiliac joints. In contrast, [¹⁸F]FDG depicted only three lesions, with an uptake of five times lower compared to [¹⁸F]Fluoride, and again no [¹¹C](R)PK11195 positive lesions were found. In these two patients, MRI detected nine lesions and six out of nine matched with the anatomical position of [¹⁸F]Fluoride uptake. Conventional radiographs showed structural bony changes in 11 out of 17 [¹⁸F]Fluoride PET positive lesions.

Conclusions

Our PET-CT data suggest that AS activity is reflected by bone activity (formation) rather than inflammation. The results also show the potential value of PET-CT for imaging AS activity using the bone tracer [¹⁸F]Fluoride. In contrast to active RA, inflammation tracers [¹⁸F]FDG and [¹¹C](R)PK11195 appeared to be less useful for AS imaging.     

The influence of life history milestones and association networks on crop-raiding behavior in male African elephants

Factors that influence learning and the spread of behavior in wild animal populations are important for understanding species responses to changing environments and for species conservation. In populations of wildlife species that come into conflict with humans by raiding cultivated crops, simple models of exposure of individual animals to crops do not entirely explain the prevalence of crop raiding behavior. We investigated the influence of life history milestones using age and association patterns on the probability of being a crop raider among wild free ranging male African elephants; we focused on males because female elephants are not known to raid crops in our study population. We examined several features of an elephant association network; network density, community structure and association based on age similarity since they are known to influence the spread of behaviors in a population. We found that older males were more likely to be raiders than younger males, that males were more likely to be raiders when their closest associates were also raiders, and that males were more likely to be raiders when their second closest associates were raiders older than them. The male association network had sparse associations, a tendency for individuals similar in age and raiding status to associate, and a strong community structure. However, raiders were randomly distributed between communities. These features of the elephant association network may limit the spread of raiding behavior and likely determine the prevalence of raiding behavior in elephant populations. Our results suggest that social learning has a major influence on the acquisition of raiding behavior in younger males whereas life history factors are important drivers of raiding behavior in older males. Further, both life-history and network patterns may influence the acquisition and spread of complex behaviors in animal populations and provide insight on managing human-wildlife conflict.     

Fascioloides magna (Bassi, 1875) in feral swine from southern Texas.

Between 1971 and 1975, Fascioloides magna was found in 46 of 67 (69%) feral swine (Sus scrofa) in southern Texas. Flukes were recovered from swine in areas where F. magna commonly has been recovered from white-tailed deer and cattle. One to 12 flukes were recovered from each infected animal. Their presence was indicated by black hematin pigment on the liver and various other internal organs. Eggs were not detected in the gallbladder or feces of infected animals although mature flukes and eggs were recovered in the livers suggesting that, like cattle, feral swine can be infected but are aberrant hosts for the parasite and do not disseminate eggs.     

Karyometry of infiltrating breast lesions

OBJECTIVE: To characterize nuclei from well-differentiated, moderately differentiated and poorly differentiated lesions of invasive breast cancer by karyometry and to test the hypothesis that these diagnostic categories form homogeneous sets. STUDY DESIGN: Histopathologic sections from 6 cases of well-differentiated, 11 cases of moderately differentiated and 17 cases of poorly differentiated ductal carcinomas were digitally recorded. From each case 100 nuclei were segmented and analyzed by karyometry. A discriminant analysis was performed, and nuclear and lesion signatures were computed. The nonsupervised learning algorithm P-index was applied. A progression curve per diagnostic category based on mean nuclear abnormality and a discriminant function score was derived. RESULTS: The well-differentiated lesions formed a homogeneous set, but both the moderately and poorly differentiated lesions showed 2 significantly different subpopulations with nuclei of substantially different nuclear abnormality and progression. CONCLUSION: The visual histopathologic diagnostic assessment of these lesions was based on an evaluation of both tissue architectural criteria and nuclear criteria. Here, only the pattern of nuclear chromatin was evaluated. Cases belonging to the same diagnostic category as assessed by their differentiation may be further characterized by the extent to which the nuclei deviate from normal. There was substantial case-to-case heterogeneity in these invasive lesions.     

Dosimetry of low-energy neutrons using low-pressure proportional counters

Measurements in nearly monoenergetic beams of 144, 24.5, and 2 keV neutrons and of thermal neutrons have been performed with low-pressure proportional counters. The suitability of a tissue-equivalent proportional counter (TEPC) for dosimetry of low-energy neutrons has been investigated. In contrast to higher neutron energies, the modification of the primary radiation field by the detector wall and the contribution of secondaries produced in the gas are significant. These effects have been investigated by additional measurements with a carbon-walled proportional counter. The various physical processes of neutron interaction with wall and gas of the TEPC have been analyzed, and absorbed dose, kerma, and kerma contributions from the various processes are presented. In addition, dose contributions from contaminating neutrons and photons have been obtained for the calibration fields used. The results have been related to neutron fluence. The comparison with tabulated kerma factors shows excellent agreement, indicating the suitability of the TEPC method for dosimetry of low-energy neutrons.     

Occurrence and performance of the aspen blotch miner,Phyllonorycter salicifoliella,on three host-tree species

Summary Larvae of the aspen blotch miner, Phyllonorycter salicifoliella Chambers (Lepidoptera: Gracillariidae), feed within leaves of three host-tree species in north-central Minnesota, USA. Far more individuals occur on Populus tremuloides than on P. balsamifera or P. grandidentata. We tested whether this pattern of host use reflected variable performance among alternative hosts by examining survivorship, sources of mortality, pupal mass, feeding efficiency, and development time of miners on each tree species. We also determined foliar water, nitrogen, condensed tannin, and phenolic glycoside content of host trees to test if host-tree chemical attributes were responsible for differences in performance. There was no significant difference in egg-to-adult survival among miners on different hosts, although dominant sources of mortality did vary. Miners on P. grandidentata suffered less parasitism and more predation than those on the other hosts, even though most parasitoid species attacked miners on all hosts. The other performance parameters varied among host species, but not in a consistent pattern. Pupal mass was greatest on P. tremuloides and P. balsamifera, the hosts with comparatively high foliar nitrogen and low phenolic glycoside concentrations. However, feeding efficiency was greatest and development time shortest for miners on P. grandidentata. Thus, pupal mass was the only index of performance maximized on P. tremuloides, the most commonly used host. Infrequent occurrence of Phyllonorycter salicifoliella on P. grandidentata results in part from phenological differences between this and the other host species. Low oviposition rates on P. balsamifera are correlated with low abundance of this host at the study site and a phenolic glycoside profile different from that of the other host species.     

Biocontrol evaluation of extracts and a major component,clusianone, from Clusia fluminensis Planch. & Triana against Aedes aegypti

Studies evaluated the effects of hexanic extracts from the fruits and flowers ofClusia fluminensis and the main component of the flower extract, a purified benzophenone (clusianone), against Aedes aegypti. The treatment of larvae with the crude fruit or flower extracts from C. fluminensis did not affect the survival ofAe. aegypti (50 mg/L), however, the flower extracts significantly delayed development of Ae. aegypti. In contrast, the clusianone (50 mg/L) isolate from the flower extract, representing 54.85% of this sample composition, showed a highly significant inhibition of survival, killing 93.3% of the larvae and completely blocking development of Ae. aegypti. The results showed, for the first time, high activity of clusianone against Ae. aegypti that both killed and inhibited mosquito development. Therefore, clusianone has potential for development as a biopesticide for controlling insect vectors of tropical diseases. Future work will elucidate the mode of action of clusianone isolated from C. fluminensis.     

Allele-specific gene expression in a wild nonhuman primate population

Natural populations hold enormous potential for evolutionary genetic studies, especially when phenotypic, genetic and environmental data are all available on the same individuals. However, untangling the genotype-phenotype relationship in natural populations remains a major challenge. Here, we describe results of an investigation of one class of phenotype, allele-specific gene expression (ASGE), in the well-studied natural population of baboons of the Amboseli basin, Kenya. ASGE measurements identify cases in which one allele of a gene is overexpressed relative to the alternative allele of the same gene, within individuals, thus providing a control for background genetic and environmental effects. Here, we characterize the incidence of ASGE in the Amboseli baboon population, focusing on the genetic and environmental contributions to ASGE in a set of eleven genes involved in immunity and defence. Within this set, we identify evidence for common ASGE in four genes. We also present examples of two relationships between cis-regulatory genetic variants and the ASGE phenotype. Finally, we identify one case in which this relationship is influenced by a novel gene-environment interaction. Specifically, the dominance rank of an individual's mother during its early life (an aspect of that individual's social environment) influences the expression of the gene CCL5 via an interaction with cis-regulatory genetic variation. These results illustrate how environmental and ecological data can be integrated into evolutionary genetic studies of functional variation in natural populations. They also highlight the potential importance of early life environmental variation in shaping the genetic architecture of complex traits in wild mammals.