Assessment of panobacumab as adjunctive immunotherapy for the treatment of nosocomial Pseudomonas aeruginosa pneumonia.

The fully human anti-lipopolysaccharide (LPS) immunoglobulin M (IgM) monoclonal antibody panobacumab was developed as an adjunctive immunotherapy for the treatment of O11 serotype Pseudomonas aeruginosa infections. We evaluated the potential clinical efficacy of panobacumab in the treatment of nosocomial pneumonia. We performed a post-hoc analysis of a multicenter phase IIa trial (NCT00851435) designed to prospectively evaluate the safety and pharmacokinetics of panobacumab. Patients treated with panobacumab (n = 17), including 13 patients receiving the full treatment (three doses of 1.2 mg/kg), were compared to 14 patients who did not receive the antibody. Overall, the 17 patients receiving panobacumab were more ill. They were an average of 72 years old [interquartile range (IQR): 64-79] versus an average of 50 years old (IQR: 30-73) (p = 0.024) and had Acute Physiology and Chronic Health Evaluation II (APACHE II) scores of 17 (IQR: 16-22) versus 15 (IQR: 10-19) (p = 0.043). Adjunctive immunotherapy resulted in an improved clinical outcome in the group receiving the full three-course panobacumab treatment, with a resolution rate of 85 % (11/13) versus 64 % (9/14) (p = 0.048). The Kaplan-Meier survival curve showed a statistically significantly shorter time to clinical resolution in this group of patients (8.0 [IQR: 7.0-11.5] versus 18.5 [IQR: 8-30] days in those who did not receive the antibody; p = 0.004). Panobacumab adjunctive immunotherapy may improve clinical outcome in a shorter time if patients receive the full treatment (three doses). These preliminary results suggest that passive immunotherapy targeting LPS may be a complementary strategy for the treatment of nosocomial O11 P. aeruginosa pneumonia

A muon-track reconstruction exploiting stochastic losses for large-scale Cherenkov detectors

IceCube is a cubic-kilometer Cherenkov telescope operating at the South Pole. The main goal of IceCube is the detection of astrophysical neutrinos and the identification of their sources. High-energy muon neutrinos are observed via the secondary muons produced in charge current interactions with nuclei in the ice. Currently, the best performing muon track directional reconstruction is based on a maximum likelihood method using the arrival time distribution of Cherenkov photons registered by the experiment\u27s photomultipliers. A known systematic shortcoming of the prevailing method is to assume a continuous energy loss along the muon track. However at energies >1 TeV the light yield from muons is dominated by stochastic showers. This paper discusses a generalized ansatz where the expected arrival time distribution is parametrized by a stochastic muon energy loss pattern. This more realistic parametrization of the loss profile leads to an improvement of the muon angular resolution of up to 20% for through-going tracks and up to a factor 2 for starting tracks over existing algorithms. Additionally, the procedure to estimate the directional reconstruction uncertainty has been improved to be more robust against numerical errors

IMPLEMENTASI PEMBERIAN GANTI KERUGIAN LAYANAN PAKET DI PT TIKI JALUR NUGRAHA EKAKURIR (JNE) CABANG SURAKARTA DITINJAU DARI UNDANG-UNDANG NOMOR 38 TAHUN 2009 TENTANG POS

ABSTRAK Yusuf Bintang Syaifinuha, E0012414. 2016. IMPLEMENTASI PEMBERIAN GANTI KERUGIAN LAYANAN PAKET DI PT TIKI JALUR NUGRAHA EKAKURIR (JNE) CABANG SURAKARTA DITINJAU DARI UNDANG-UNDANG NOMOR 38 TAHUN 2009 TENTANG POS. Fakultas Hukum Universitas Sebelas Maret Surakarata. Penelitian ini bertujuan untuk mengetahui implementasi pemberian ganti kerugian di PT Tiki Jalur Nugraha Ekakurir (JNE) Cabang Surakarta ditinjau dari UU Pos dan untuk mengetahui cara penyelesaian sengketa yang timbul dari implementasi pemberian ganti kerugian di PT Tiki Jalur Nugraha Ekakurir (JNE) Cabang Surakarta. Metode penelitian yang digunakan dalam penelitian ini adalah deskriptif kualitatif. Jenis penelitian ini adalah penelitian empiris. Data yang digunakan terdiri dari dua data yaitu data primer dan data sekunder. Teknik pengumpulan data adalah dengan metode wawancara dan studi pustaka. Berdasarkan hasil analisis penelitian, dapat diambil kesimpulan bahwa implementasi pemberian ganti kerugian di JNE kurang sesuai dengan Pasal 28 UU Pos karena jenis ganti kerugian hanya untuk kehilangan kiriman dan kerusakan isi kiriman. Pengirim yang mengajukan klaim ganti kerugian harus memenuhi syarat administrasi yang telah ditetapkan oleh JNE. Nilai ganti kerugian yang diberikan JNE adalah 10 kali biaya pengiriman atau sesuai harga barang yang hilang dan/atau rusak jika menggunakan asuransi. JNE memilih upaya hukum diluar pengadilan (nonlitigasi) berupa negosiasi dalam menyelesaikan sengketa yang terjadi dalam implementasi pemberian ganti kerugian. Kata kunci :Perjanjian, Wanprestasi, Implementasi ganti kerugian

Application of a risk-management framework for integration of stromal tumor-infiltrating lymphocytes in clinical trials

Stromal tumor-infiltrating lymphocytes (sTILs) are a potential predictive biomarker for immunotherapy response in metastatic triple-negative breast cancer (TNBC). To incorporate sTILs into clinical trials and diagnostics, reliable assessment is essential. In this review, we propose a new concept, namely the implementation of a risk-management framework that enables the use of sTILs as a stratification factor in clinical trials. We present the design of a biomarker risk-mitigation workflow that can be applied to any biomarker incorporation in clinical trials. We demonstrate the implementation of this concept using sTILs as an integral biomarker in a single-center phase II immunotherapy trial for metastatic TNBC (TONIC trial, NCT02499367), using this workflow to mitigate risks of suboptimal inclusion of sTILs in this specific trial. In this review, we demonstrate that a web-based scoring platform can mitigate potential risk factors when including sTILs in clinical trials, and we argue that this framework can be applied for any future biomarker-driven clinical trial setting

4H-SiC bipolar power diodes realized by ion implantation

International audiencePhysico-chemical and electrical investigations were carried out in 4H-SiC p-type layers created by Aluminum ion implantation at room temperature and high temperature post-implantation annealing. Crystal recovery and dopant preservation after annealing are proved by RBS/C and respectively SIMS measurements. Dopant activation is evaluated by sheet resistance measurements. These results were applied for high voltage bipolar diodes with JTE protection realization

A comparison of warfarin and aspirin for the prevention of recurrent ischemic stroke

Background: Despite the use of antiplatelet agents, usually aspirin, in patients who have had an ischemic stroke, there is still a substantial rate of recurrence. Therefore, we investigated whether warfarin, which is effective and superior to aspirin in the prevention of cardiogenic embolism, would also prove superior in the prevention of recurrent ischemic stroke in patients with a prior noncardioembolic ischemic stroke. Methods: In a multicenter, double-blind, randomized trial, we compared the effect of warfarin (at a dose adjusted to produce an international normalized ratio of 1.4 to 2.8) and that of aspirin (325 mg per day) on the combined primary end point of recurrent ischemic stroke or death from any cause within two years. Results: The two randomized study groups were similar with respect to base-line risk factors. In the intention-to-treat analysis, no significant differences were found between the treatment groups in any of the outcomes measured. The primary end point of death or recurrent ischemic stroke was reached by 196 of 1103 patients assigned to warfarin (17.8 percent) and 176 of 1103 assigned to aspirin (16.0 percent; P=0.25; hazard ratio comparing warfarin with aspirin, 1.13; 95 percent confidence interval, 0.92 to 1.38). The rates of major hemorrhage were low (2.22 per 100 patient-years in the warfarin group and 1.49 per 100 patient-years in the aspirin group). Also, there were no significant treatment-related differences in the frequency of or time to the primary end point or major hemorrhage according to the cause of the initial stroke. Conclusions: Over a two-year period, we found no difference between aspirin and warfarin in the prevention of recurrent ischemic stroke or death or in the rate of major hemorrhage. Consequently, we regard both warfarin and aspirin as reasonable therapeutic alternatives

Annealing Studies of Al-implanted 6H-SiC in an Induction Furnace

International audienc