Containers have emerged as a more portable and efficient solution than virtual machines for cloud infrastructure providing both a flexible way to build and deploy applications. The quality of ...service, security, performance, energy consumption, among others, are essential aspects of their deployment, management, and orchestration. Inappropriate resource allocation can lead to resource contention, entailing reduced performance, poor energy efficiency, and other potentially damaging effects. In this paper, we present a set of online job allocation strategies to optimize quality of service, energy savings, and completion time, considering contention for shared on-chip resources. We consider the job allocation as the multilevel dynamic bin-packing problem that provides a lightweight runtime solution that minimizes contention and energy consumption while maximizing utilization. The proposed strategies are based on two and three levels of scheduling policies with container selection, capacity distribution, and contention-aware allocation. The energy model considers joint execution of applications of different types on shared resources generalized by the job concentration paradigm. We provide an experimental analysis of eighty-six scheduling heuristics with scientific workloads of memory and CPU-intensive jobs. The proposed techniques outperform classical solutions in terms of quality of service, energy savings, and completion time by 21.73-43.44%, 44.06-92.11%, and 16.38-24.17%, respectively, leading to a cost-efficient resource allocation for cloud infrastructures.
ATLAS evaluated the efficacy and safety of the PARP inhibitor rucaparib in patients with previously treated locally advanced/unresectable or metastatic urothelial carcinoma (UC).
Patients with UC ...were enrolled independent of tumor homologous recombination deficiency (HRD) status and received rucaparib 600 mg BID. The primary endpoint was investigator-assessed objective response rate (RECIST v1.1) in the intent-to-treat and HRD-positive (loss of genome-wide heterozygosity ≥10%) populations. Key secondary endpoints were progression-free survival (PFS) and safety. Disease control rate (DCR) was defined post-hoc as the proportion of patients with a confirmed complete or partial response (PR), or stable disease lasting ≥16 weeks.
Of 97 enrolled patients, 20 (20.6%) were HRD-positive, 30 (30.9%) HRD-negative, and 47 (48.5%) HRD-indeterminate. Among 95 evaluable patients, there were no confirmed responses. However, reductions in the sum of target lesions were observed, including 6 (6.3%) patients with unconfirmed PR. DCR was 11.6%; median PFS was 1.8 months (95% CI, 1.6-1.9). No relationship was observed between HRD status and efficacy endpoints. Median treatment duration was 1.8 months (range, 0.1-10.1). Most frequent any-grade treatment-emergent adverse events were asthenia/fatigue (57.7%), nausea (42.3%), and anemia (36.1%). Of 64 patients with data from tumor tissue samples, 10 (15.6%) had a deleterious alteration in a DNA damage repair pathway gene, including four with a deleterious BRCA1 or BRCA2 alteration.
Rucaparib did not show significant activity in unselected patients with advanced UC regardless of HRD status. The safety profile was consistent with that observed in patients with ovarian or prostate cancer.
This trial was registered in ClinicalTrials.gov (NCT03397394). Date of registration: 12 January 2018. This trial was registered in EudraCT (2017-004166-10).
Fungal pathogens are the main causal agents of postharvest diseases of fruits and vegetables. To prevent this problem and avoid the use of harmful chemical fungicides, safer and greener alternatives ...have been sought. One of these alternatives is the use of plant-growth-promoting bacteria (PGPB). In this study, we evaluated in vitro four well-known PGPB strains (Pseudomonas fluorescens UM270, Bacillus toyonensis COPE52, Bacillus sp. E25, and Bacillus thuringiensis CR71) for their biocontrol potential against nineteen postharvest fungal pathogens. In vivo assays were also performed, and bacterial cells were inoculated on harvested strawberries and grapes with the pathogens Botrytis cinerea, Alternaria alternata, and Fusarium brachygibbosum to evaluate loss of firmness and disease incidence. Our results show that the four strains antagonized fungi in direct and indirect confrontation assays. Stronger antagonism was observed by the action of diffusible metabolites (DMs) compared to volatile organic compound (VOC) activity. All PGPB significantly improved the fruit firmness and reduced disease incidence caused by the fungal pathogens tested. However, strain UM270 showed excellent biocontrol activity, reducing the disease incidence of Fusarium brachygibbosum, Botrytis cinerea, and Alternaria alternata on strawberry fruits by 60%, 55%, and 65%, respectively. Diffusible antifungals and VOCs such as 2,4-diacetyl phloroglucinol, siderophores, auxins, fengycins, and N, N-dimethyl-hexadecyl amine, among others, might be responsible for the beneficial activities observed. These results suggest excellent biocontrol activities to inhibit postharvest pathogenic fungi and improve harvested fruit quality.
Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second lines. Vinflunine is the only treatment approved in this ...setting by the European Medicines Agency and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy versus vinflunine.
This is a multicenter, randomized, open-label, phase II/III study, following a Simon’s optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II. ECOG Performance Status, anaemia and liver metastases were stratification factors. Primary objectives were overall response rate for the phase II and overall survival for the phase III.
Seventy patients were included in the phase II across 19 institutions in Europe. Baseline characteristics were well balanced between the two arms. Three patients (13%) obtained a partial response on cabazitaxel (95% CI 2.7–32.4) and six patients (30%) in the vinflunine arm (95% CI 11.9–54.3). Median progression-free survival for cabazitaxel was 1.9 versus 2.9months for vinflunine (P=0.039). The study did not proceed to phase III since the futility analysis showed a lack of efficacy of cabazitaxel. A trend for overall survival benefit was found favouring vinflunine (median 7.6 versus 5.5months). Grade 3- to 4-related adverse events were seen in 41% patients with no difference between the two arms.
This phase II/III second line bladder study comparing cabazitaxel with vinflunine was closed when the phase II showed a lack of efficacy of the cabazitaxel arm. Vinflunine results were consistent with those known previously.
NCT01830231.
Background
The studies IMvigor 210 cohort 2 and IMvigor211 evaluated the efficacy of atezolizumab in patients with locally advanced or metastatic urothelial cancer (mUC) upon progression to ...platinum-based chemotherapy worldwide. Yet, the real impact of this drug in specific geographical regions is unknown.
Materials and methods
We combined individual-level data from the 131 patients recruited in Spain from IMvigor210 cohort 2 and IMvigor211 in a pooled analysis. Efficacy and safety outcomes were assessed in the overall study population and according to PD-L1 expression on tumour-infiltrating immune cells.
Results
Full data were available for 127 patients; 74 (58%) received atezolizumab and 53 (42%) chemotherapy. Atezolizumab patients had a numerically superior median overall survival although not reaching statistical significance (9.2 months vs 7.7 months). No statistically significant differences between arms were observed in overall response rates (20.3% vs 37.0%) or progression-free survival (2.1 months vs 5.3 months). Nonetheless, median duration of response was superior for the immunotherapy arm (non-reached vs 6.4 months;
p
= 0.005). Additionally, among the responders, the 12-month survival rates seemed to favour atezolizumab (66.7% vs 19.9%). When efficacy was analyzed based on PD-L1 expression status, no significant differences were found. Treatment-related adverse events of any grade occurred more frequently in the chemotherapy arm 46/57 (81%) vs 44/74 (59%).
Conclusion
Patients who achieved an objective response on atezolizumab presented a longer median duration of response and numerically superior 12 month survival rates when compared with chemotherapy responders along with a more favorable safety profile. PD-L1 expression did not discriminate patients who might benefit from atezolizumab.
The goal of this article is to provide recommendations about the management of muscle-invasive (MIBC) and metastatic bladder cancer. New molecular subtypes of MIBC are associated with specific ...clinical–pathological characteristics. Radical cystectomy and lymph node dissection are the gold standard for treatment and neoadjuvant chemotherapy with a cisplatin-based combination should be recommended in fit patients. The role of adjuvant chemotherapy in MIBC remains controversial; its use must be considered in patients with high-risk who are able to tolerate a cisplatin-based regimen, and have not received neoadjuvant chemotherapy. Bladder-preserving approaches are reasonable alternatives to cystectomy in selected patients for whom cystectomy is not contemplated either for clinical or personal reasons. Cisplatin-based combination chemotherapy is the standard first-line protocol for metastatic disease. In the case of unfit patients, carboplatin–gemcitabine should be considered the preferred first-line chemotherapy treatment option, while pembrolizumab and atezolizumab can be contemplated for individuals with high PD-L1 expression. In cases of progression after platinum-based therapy, PD-1/PD-L1 inhibitors are standard alternatives. Vinflunine is another option when anti-PD-1/PD-L1 therapy is not possible. There are no data from randomized clinical trials regarding moving on to immuno-oncology agents.
In order to study the importance of background in PIXE spectra to determine elemental concentrations in atmospheric aerosols using artificial neural systems ANS, two independently trained ANS were ...constructed, one which considered as input the net number of counts in the peak, and another which included the background. In the training and validation phases thirty eight spectra of aerosols collected in Santiago, Chile, were used. In both cases the elemental concentration values were similar. This fact was due to the intrinsic characteristic of ANS operating with normalized values of the net and total number of counts under the peaks, something that was verified in the analysis of 172 spectra obtained from aerosols collected in Mexico city. Therefore, networks operating under the mode which include background can reduce time and cost when dealing with large number of samples.
Although sarcomas account for only 1% of all solid tumours, patients with sarcomas comprise a larger proportion of patients entering phase I trials, due to the limited number of registered or active ...drugs for these diseases. To help in patient selection, we evaluated the utility of the predictive Royal Marsden Score which had been derived in carcinoma patients. In addition, we analysed efficacy and toxicity regarding the sarcoma population enrolled in phase I trials.
We used data from a European Database comprising 2182 patients treated in phase I trials in 14 European institutions between 2005 and 2007.
One hundred and seventy-eight patients diagnosed with advanced sarcoma or other mesenchymal tumours were identified and accounted for 217 phase I trial participations during the study period. Histological type, class of drug, number of metastatic sites, high serum lactate dehydrogenase activity (LDH), low albumin and high white blood cell count were independent prognostic factors. Poor performance status (PS), liver metastases and high leucocyte count were associated with increased risk of early death. The class of drug used was the strongest predictor of progression-free survival (PFS) duration, inhibitors of angiogenesis and histone deacetylase giving the best results. Poor PS, high serum LDH and low lymphocyte count correlated with shorter PFS. In this heterogeneous population, PFS with investigational agents appeared comparable with that previously published for patients receiving standard treatments beyond first line.
Prognostic factors in sarcoma patients do not differ from a broader phase I population. Efficacy measures suggest that some patients with sarcoma derive benefit from therapy in this setting which could therefore be considered for patients with no remaining standard therapeutic option.
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