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.     

Pattern classification of kinematic and kinetic running data to distinguish gender,shod/barefoot and injury groups with feature ranking

The identification of differences between groups is often important in biomechanics. This paper presents group classification tasks using kinetic and kinematic data from a prospective running injury study. Groups composed of gender, of shod/barefoot running and of runners who developed patellofemoral pain syndrome (PFPS) during the study, and asymptotic runners were classified.

The features computed from the biomechanical data were deliberately chosen to be generic. Therefore, they were suited for different biomechanical measurements and classification tasks without adaptation to the input signals. Feature ranking was applied to reveal the relevance of each feature to the classification task.

Data from 80 runners were analysed for gender and shod/barefoot classification, while 12 runners were investigated in the injury classification task. Gender groups could be differentiated with 84.7%, shod/barefoot running with 98.3%, and PFPS with 100% classification rate. For the latter group, one single variable could be identified that alone allowed discrimination.     

Patients' & Healthcare Professionals' Values Regarding True- & False-Positive Diagnosis when Colorectal Cancer Screening by CT Colonography: Discrete Choice Experiment

Purpose

To establish the relative weighting given by patients and healthcare professionals to gains in diagnostic sensitivity versus loss of specificity when using CT colonography (CTC) for colorectal cancer screening.

Materials and Methods

Following ethical approval and informed consent, 75 patients and 50 healthcare professionals undertook a discrete choice experiment in which they chose between “standard” CTC and “enhanced” CTC that raised diagnostic sensitivity 10% for either cancer or polyps in exchange for varying levels of specificity. We established the relative increase in false-positive diagnoses participants traded for an increase in true-positive diagnoses.

Results

Data from 122 participants were analysed. There were 30 (25%) non-traders for the cancer scenario and 20 (16%) for the polyp scenario. For cancer, the 10% gain in sensitivity was traded up to a median 45% (IQR 25 to >85) drop in specificity, equating to 2250 (IQR 1250 to >4250) additional false-positives per additional true-positive cancer, at 0.2% prevalence. For polyps, the figure was 15% (IQR 7.5 to 55), equating to 6 (IQR 3 to 22) additional false-positives per additional true-positive polyp, at 25% prevalence. Tipping points were significantly higher for patients than professionals for both cancer (85 vs 25, p<0.001) and polyps (55 vs 15, p<0.001). Patients were willing to pay significantly more for increased sensitivity for cancer (p = 0.021).

Conclusion

When screening for colorectal cancer, patients and professionals believe gains in true-positive diagnoses are worth much more than the negative consequences of a corresponding rise in false-positives. Evaluation of screening tests should account for this.     

Invasive interactions: can Argentine ants indirectly increase the reproductive output of a weed?

The direct and indirect interactions of invasive ants with plants, insect herbivores, and Hemiptera are complex. While ant and Hemiptera interactions with native plants have been well studied, the effects of invasive ant–scale insect mutualisms on the reproductive output of invasive weeds have not. The study system consisted of Argentine ants (Linepithema humile), boneseed (Chrysanthemoides monilifera monilifera), and sap-sucking scale insects (Hemiptera: Saissetia oleae and Parasaissetia nigra), all of which are invasive in New Zealand. We examined the direct and indirect effects of Argentine ants on scale insects and other invertebrates (especially herbivores) and on plant reproductive output. Argentine ants spent one-third of their time specifically associated with scale insects in tending behaviours. The invertebrate community was significantly different between uninfested and infested plants, with fewer predators and herbivores on ant-infested plants. Herbivore damage was significantly reduced on plants with Argentine ants, but sooty mould colonisation was greater where ants were present. Herbivore damage increased when ants were excluded from plants. Boneseed plants infested with Argentine ants produced significantly more fruits than plants without ants. The increase in reproductive output in the presence of ants may be due to increased pollination as the result of pollinators being forced to relocate frequently to avoid attack by ants, resulting in an increase in pollen transfer and higher fruit/seed set. The consequences of Argentine ant invasion can be varied; not only does their invasion have consequences for maintaining biodiversity, ant invasion may also affect weed and pest management strategies.     

A New Small-Bodied Azhdarchoid Pterosaur from the Lower Cretaceous of England and Its Implications for Pterosaur Anatomy,Diversity and Phylogeny

Background

Pterosaurs have been known from the Cretaceous sediments of the Isle of Wight (southern England, United Kingdom) since 1870. We describe the three-dimensional pelvic girdle and associated vertebrae of a small near-adult pterodactyloid from the Atherfield Clay Formation (lower Aptian, Lower Cretaceous). Despite acknowledged variation in the pterosaur pelvis, previous studies have not adequately sampled or incorporated pelvic characters into phylogenetic analyses.

Methodology/Principal Findings

The new specimen represents the new taxon Vectidraco daisymorrisae gen. et sp. nov., diagnosed by the presence of a concavity posterodorsal to the acetabulum and the form of its postacetabular process on the ilium. Several characters suggest that Vectidraco belongs to Azhdarchoidea. We constructed a pelvis-only phylogenetic analysis to test whether the pterosaur pelvis carries a useful phylogenetic signal. Resolution in recovered trees was poor, but they approximately matched trees recovered from analyses of total evidence. We also added Vectidraco and our pelvic characters to an existing total-evidence matrix for pterosaurs. Both analyses recovered Vectidraco within Azhdarchoidea.

Conclusions/Significance

The Lower Cretaceous strata of western Europe have yielded members of several pterosaur lineages, but Aptian pterosaurs from western Europe are rare. With a pelvis length of 40 mm, the new animal would have had a total length of c. 350 mm, and a wingspan of c. 750 mm. Barremian and Aptian pterodactyloids from western Europe show that small-bodied azhdarchoids lived alongside ornithocheirids and istiodactylids. This assemblage is similar in terms of which lineages are represented to the coeval beds of Liaoning, China; however, the number of species and specimens present at Liaoning is much higher. While the general phylogenetic composition of western European and Chinese communities appear to have been approximately similar, the differences may be due to different palaeoenvironmental and depositional settings. The western Europe pterodactyloid record may therefore be artificially low in diversity due to preservational factors.     

Whether the Weather Drives Patterns of Endemic Amphibian Chytridiomycosis: A Pathogen Proliferation Approach

The pandemic amphibian disease chytridiomycosis often exhibits strong seasonality in both prevalence and disease-associated mortality once it becomes endemic. One hypothesis that could explain this temporal pattern is that simple weather-driven pathogen proliferation (population growth) is a major driver of chytridiomycosis disease dynamics. Despite various elaborations of this hypothesis in the literature for explaining amphibian declines (e.g., the chytrid thermal-optimum hypothesis) it has not been formally tested on infection patterns in the wild. In this study we developed a simple process-based model to simulate the growth of the pathogen Batrachochytrium dendrobatidis (Bd) under varying weather conditions to provide an a priori test of a weather-linked pathogen proliferation hypothesis for endemic chytridiomycosis. We found strong support for several predictions of the proliferation hypothesis when applied to our model species, Litoria pearsoniana, sampled across multiple sites and years: the weather-driven simulations of pathogen growth potential (represented as a growth index in the 30 days prior to sampling; GI₃₀) were positively related to both the prevalence and intensity of Bd infections, which were themselves strongly and positively correlated. In addition, a machine-learning classifier achieved ∼72% success in classifying positive qPCR results when utilising just three informative predictors 1) GI₃₀, 2) frog body size and 3) rain on the day of sampling. Hence, while intrinsic traits of the individuals sampled (species, size, sex) and nuisance sampling variables (rainfall when sampling) influenced infection patterns obtained when sampling via qPCR, our results also strongly suggest that weather-linked pathogen proliferation plays a key role in the infection dynamics of endemic chytridiomycosis in our study system. Predictive applications of the model include surveillance design, outbreak preparedness and response, climate change scenario modelling and the interpretation of historical patterns of amphibian decline.     

Characterization of Dinophysis spp. (Dinophyceae,Dinophysiales) from the mid-Atlantic region of the United States1

Due to the increasing prevalence of Dinophysis spp. and their toxins on every US coast in recent years, the need to identify and monitor for problematic Dinophysis populations has become apparent. Here, we present morphological analyses, using light and scanning electron microscopy, and rDNA sequence analysis, using a ~2-kb sequence of ribosomal ITS1, 5.8S, ITS2, and LSU DNA, of Dinophysis collected in mid-Atlantic estuarine and coastal waters from Virginia to New Jersey to better characterize local populations. In addition, we analyzed for diarrhetic shellfish poisoning (DSP) toxins in water and shellfish samples collected during blooms using liquid-chromatography tandem mass spectrometry and an in vitro protein phosphatase inhibition assay and compared this data to a toxin profile generated from a mid-Atlantic Dinophysis culture. Three distinct morphospecies were documented in mid-Atlantic surface waters: D. acuminata, D. norvegica, and a “small Dinophysis sp.” that was morphologically distinct based on multivariate analysis of morphometric data but was genetically consistent with D. acuminata. While mid-Atlantic D. acuminata could not be distinguished from the other species in the D. acuminata-complex (D. ovum from the Gulf of Mexico and D. sacculus from the western Mediterranean Sea) using the molecular markers chosen, it could be distinguished based on morphometrics. Okadaic acid, dinophysistoxin 1, and pectenotoxin 2 were found in filtered water and shellfish samples during Dinophysis blooms in the mid-Atlantic region, as well as in a locally isolated D. acuminata culture. However, DSP toxins exceeded regulatory guidance concentrations only a few times during the study period and only in noncommercial shellfish samples.     

Localised high-density population of a sea cucumber on a Malaysian coral reef

Coral Reefs - While tropical&nbsp;sea cucumbers are among the most conspicuous mobile invertebrates on coral reefs, information on their population biology and ecology is limited, particularly...