Several recumbirostran 'microsaurs' are known from early Permian sites across Germany, including the Tambach Formation in Thuringia, central Germany. The only 'microsaur' thus far described from the ...Tambach Formation was the ostodolepid recumbirostran Tambaroter carrolli. However, there is also the documented presence of an undescribed recumbirostran 'microsaur' at the well-known Bromacker locality. The Bromacker locality is highly recognized and best known for its very diverse and extremely well-preserved terrestrial tetrapod assemblage combined with the co-occurrence of an exceptional vertebrate ichnofossil record. Here we describe a second new recumbirostran taxon from the Tambach Formation, which is also the first from the Bromacker locality itself. Phylogenetic analysis indicates that the new taxon, Bromerpeton subcolossus gen. et sp. nov., is a brachystelechid recumbirostran, a group also known elsewhere in Germany. The following features differentiate Bromerpeton from the other members of the clade: the presence of 13 maxillary teeth, narrow postorbitals that do not substantially contribute to the postorbital region of the skull, the frontal does not contribute to the orbital margin, and the presence of five manual digits. This new recumbirostran 'microsaur' further adds to the unique ecosystem that is preserved at the Bromacker locality, granting us a better understanding of what was living underfoot the larger more well-known animals at the locality. Likewise, it expands our understanding of the evolution of recumbirostran 'microsaurs', especially with regards to digit and limb reduction within the clade.
Diarrhea (with or without colitis) is an immune-related adverse event (irAE) associated with ipilimumab. A randomized, double-blind, placebo-controlled, multicenter, multinational phase II trial was ...conducted to determine whether prophylactic budesonide (Entocort EC), a nonabsorbed oral steroid, reduced the rate of grade >or=2 diarrhea in ipilimumab-treated patients with advanced melanoma.
Previously treated and treatment-naïve patients (N = 115) with unresectable stage III or IV melanoma received open-label ipilimumab (10 mg/kg every 3 weeks for four doses) with daily blinded budesonide (group A) or placebo (group B) through week 16. The first scheduled tumor evaluation was at week 12; eligible patients received maintenance treatment starting at week 24. Diarrhea was assessed using Common Terminology Criteria for Adverse Events (CTCAE) 3.0. Patients kept a diary describing their bowel habits.
Budesonide did not affect the rate of grade >or=2 diarrhea, which occurred in 32.7% and 35.0% of patients in groups A and B, respectively. There were no bowel perforations or treatment-related deaths. Best overall response rates were 12.1% in group A and 15.8% in group B, with a median overall survival of 17.7 and 19.3 months, respectively. Within each group, the disease control rate was higher in patients with grade 3 to 4 irAEs than in patients with grade 0 to 2 irAEs, although many patients with grade 1 to 2 irAEs experienced clinical benefit. Novel patterns of response to ipilimumab were observed.
Ipilimumab shows activity in advanced melanoma, with encouraging survival and manageable adverse events. Budesonide should not be used prophylactically for grade >or=2 diarrhea associated with ipilimumab therapy.
Cancer is increasingly being viewed as a stem cell disease, both in its propagation by a minority of cells with stem-cell-like properties and in its possible derivation from normal tissue stem cells. ...But stem cell activity is tightly controlled, raising the question of how normal regulation might be subverted in carcinogenesis. The long-known association between cancer and chronic tissue injury, and the more recently appreciated roles of Hedgehog and Wnt signalling pathways in tissue regeneration, stem cell renewal and cancer growth together suggest that carcinogenesis proceeds by misappropriating homeostatic mechanisms that govern tissue repair and stem cell self-renewal.
The discovery and increased understanding of the complex interactions regulating the immune system have contributed to the pharmacologic activation of antitumor immunity. The activity of effector ...cells, such as T and NK cells, is regulated by an array of activating and attenuating receptors and ligands. Agents that target these molecules can modulate immune responses by exerting antagonistic or agonistic effects. Several T- or NK-cell modulators have entered clinical trials, and two have been approved for use. Ipilimumab (Yervoy®, Bristol-Myers Squibb) and nivolumab (OPDIVO, Ono Pharmaceutical Co., Ltd./Bristol-Myers Squibb) were approved for the treatment of metastatic melanoma, in March 2011 in the United States, and in July 2014 in Japan, respectively. The clinical activity of these two antibodies has not been limited to tumor types considered sensitive to immunotherapy, and promising activity has been reported in other solid and hematologic tumors. Clinical development of ipilimumab and nivolumab has presented unique challenges in terms of safety and efficacy, requiring the establishment of new evaluation criteria for adverse events and antitumor effects. Guidelines intended to help oncologists properly manage treatment in view of these non-traditional features have been implemented. The introduction of this new modality of cancer treatment, which is meant to integrate with or replace the current standards of care, requires additional efforts in terms of optimization of treatment administration, identification of biomarkers and application of new clinical trial designs. The availability of immune modulators with different mechanisms of action offers the opportunity to establish immunological combinations as new standards of care.
Prostate cancer aggressiveness and appropriate therapy are routinely determined following biopsy sampling. Current clinical and pathologic parameters are insufficient for accurate risk prediction ...leading primarily to overtreatment and also missed opportunities for curative therapy.
An 8-biomarker proteomic assay for intact tissue biopsies predictive of prostate pathology was defined in a study of 381 patient biopsies with matched prostatectomy specimens. A second blinded study of 276 cases validated this assay's ability to distinguish "favorable" versus "nonfavorable" pathology independently and relative to current risk classification systems National Comprehensive Cancer Network (NCCN and D'Amico).
A favorable biomarker risk score of ≤0.33, and a nonfavorable risk score of >0.80 (possible range between 0 and 1) were defined on "false-negative" and "false-positive" rates of 10% and 5%, respectively. At a risk score ≤0.33, predictive values for favorable pathology in very low-risk and low-risk NCCN and low-risk D'Amico groups were 95%, 81.5%, and 87.2%, respectively, higher than for these current risk classification groups themselves (80.3%, 63.8%, and 70.6%, respectively). The predictive value for nonfavorable pathology was 76.9% at biomarker risk scores >0.8 across all risk groups. Increased biomarker risk scores correlated with decreased frequency of favorable cases across all risk groups. The validation study met its two coprimary endpoints, separating favorable from nonfavorable pathology (AUC, 0.68; P < 0.0001; OR, 20.9) and GS-6 versus non-GS-6 pathology (AUC, 0.65; P < 0.0001; OR, 12.95).
The 8-biomarker assay provided individualized, independent prognostic information relative to current risk stratification systems, and may improve the precision of clinical decision making following prostate biopsy.
The present paper focuses on a sensitivity analysis of Sentinel-1 backscattering signatures from oil palm canopies cultivated in Gabon, Africa. We employed one Sentinel-1 image per year during the ...2015–2021 period creating two separated time series for both the wet and dry seasons. The first images were almost simultaneously acquired to the initial growth stage of oil palm plants. The VH and VV backscattering signatures were analysed in terms of their corresponding statistics for each date and compared to the ones corresponding to tropical forests. The times series for the wet season showed that, in a time interval of 2–3 years after oil palm plantation, the VV/VH ratio in oil palm parcels increases above the one for forests. Backscattering and VV/VH ratio time series for the dry season exhibit similar patterns as for the wet season but with a more stable behaviour. The separability of oil palm and forest classes was also quantitatively addressed by means of the Jeffries–Matusita distance, which seems to point to the C-band VV/VH ratio as a potential candidate for discrimination between oil palms and natural forests, although further analysis must still be carried out. In addition, issues related to the effect of the number of samples in this particular scenario were also analysed. Overall, the outcomes presented here can contribute to the understanding of the radar signatures from this scenario and to potentially improve the accuracy of mapping techniques for this type of ecosystems by using remote sensing. Nevertheless, further research is still to be done as no classification method was performed due to the lack of the required geocoded reference map. In particular, a statistical assessment of the radar signatures should be carried out to statistically characterise the observed trends.
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