Distortion and regulation characterization of a Mapham inverter

Output voltage Total Harmonic Distortion (THD) of a 20kHz, 6kVA Mapham resonant inverter is characterized as a function of its switching-to-resonant frequency ratio, f sub s/f sub r, using the EASY5 engineering analysis system. EASY5 circuit simulation results are compared with hardware test results to verify the accuracy of the simulations. The effects of load on the THD versus f sub s/f sub r ratio is investigated for resistive, leading, and lagging power factor load impedances. The effect of the series output capacitor on the Mapham inverter output voltage distortion and inherent load regulation is characterized under loads of various power factors and magnitudes. An optimum series capacitor value which improves the inherent load regulation to better than 3 percent is identified. The optimum series capacitor value is different than the value predicted from a modeled frequency domain analysis. An explanation is proposed which takes into account the conduction overlap in the inductor pairs during steady-state inverter operation, which decreases the effective inductance of a Mapham inverter. A fault protection and current limit method is discussed which allows the Mapham inverter to operate into a short circuit, even when the inverter resonant circuit becomes overdamped

Realization of Coherent Optically Dense Media via Buffer-Gas Cooling

We demonstrate that buffer-gas cooling combined with laser ablation can be used to create coherent optical media with high optical depth and low Doppler broadening that offers metastable states with low collisional and motional decoherence. Demonstration of this generic technique opens pathways to coherent optics with a large variety of atoms and molecules. We use helium buffer gas to cool 87Rb atoms to below 7 K and slow atom diffusion to the walls. Electromagnetically induced transparency (EIT) in this medium allows for 50% transmission in a medium with initial OD >70 and for slow pulse propagation with large delay-bandwidth products. In the high-OD regime, we observe high-contrast spectrum oscillations due to efficient four-wave mixing.Comment: 4 pages, 4 figures. V2: modified title, abstract, introduction, conclusion; added references; improved theoretical fit in figure 3(b); shortened slow light theory description; clarified simplicity of apparatus. Final version as published in Phys. Rev.

Surgical results of the Lung Cancer Mutation Consortium 3 trial: A phase II multicenter single-arm study to investigate the efficacy and safety of atezolizumab as neoadjuvant therapy in patients with stages IB-select IIIB resectable non-small cell lung cancer

OBJECTIVE: Multimodality treatment for resectable non-small cell lung cancer has long remained at a therapeutic plateau. Immune checkpoint inhibitors are highly effective in advanced non-small cell lung cancer and promising preoperatively in small clinical trials for resectable non-small cell lung cancer. This large multicenter trial tested the safety and efficacy of neoadjuvant atezolizumab and surgery. METHODS: Patients with stage IB to select IIIB resectable non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0/1 were eligible. Patients received atezolizumab 1200 mg intravenously every 3 weeks for 2 cycles or less followed by resection. The primary end point was major pathological response in patients without EGFR/ALK+ alterations. Pre- and post-treatment computed tomography, positron emission tomography, pulmonary function tests, and biospecimens were obtained. Adverse events were recorded by Common Terminology Criteria for Adverse Events v.4.0. RESULTS: From April 2017 to February 2020, 181 patients were entered in the study. Baseline characteristics were mean age, 65.1 years; female, 93 of 181 (51%); nonsquamous histology, 112 of 181 (62%); and clinical stages IIB to IIIB, 147 of 181 (81%). In patients without EGFR/ALK alterations who underwent surgery, the major pathological response rate was 20% (29/143; 95% confidence interval, 14-28) and the pathological complete response rate was 6% (8/143; 95% confidence interval, 2-11). There were no grade 4/5 treatment-related adverse events preoperatively. Of 159 patients (87.8%) undergoing surgery, 145 (91%) had pathologic complete resection. There were 5 (3%) intraoperative complications, no intraoperative deaths, and 2 postoperative deaths within 90 days, 1 treatment related. Median disease-free and overall survival have not been reached. CONCLUSIONS: Neoadjuvant atezolizumab in resectable stage IB to IIIB non-small cell lung cancer was well tolerated, yielded a 20% major pathological response rate, and allowed safe, complete surgical resection. These results strongly support the further development of immune checkpoint inhibitors as preoperative therapy in locally advanced non-small cell lung cancer

Neoadjuvant atezolizumab for resectable non-small cell lung cancer: An open-label, single-arm phase II trial

In an ongoing, open-label, single-arm phase II study ( NCT02927301 ), 181 patients with untreated, resectable, stage IB-IIIB non-small cell lung cancer received two doses of neoadjuvant atezolizumab monotherapy. The primary end point was major pathological response (MPR; ≤10% viable malignant cells) in resected tumors without EGFR or ALK alterations. Of the 143 patients in the primary end point analysis, the MPR was 20% (95% confidence interval, 14-28%). With a minimum duration of follow-up of 3 years, the 3-year survival rate of 80% was encouraging. The most common adverse events during the neoadjuvant phase were fatigue (39%, 71 of 181) and procedural pain (29%, 53 of 181), along with expected immune-related toxicities; there were no unexpected safety signals. In exploratory analyses, MPR was predicted using the pre-treatment peripheral blood immunophenotype based on 14 immune cell subsets. Immune cell subsets predictive of MPR in the peripheral blood were also identified in the tumor microenvironment and were associated with MPR. This study of neoadjuvant atezolizumab in a large cohort of patients with resectable non-small cell lung cancer was safe and met its primary end point of MPR ≥ 15%. Data from this single-arm, non-randomized trial suggest that profiles of innate immune cells in pre-treatment peripheral blood may predict pathological response after neoadjuvant atezolizumab, but additional studies are needed to determine whether these profiles can inform patient selection and new therapeutic approaches

Expression profiling of human donor lungs to understand primary graft dysfunction after lung transplantation

Lung transplantation is the treatment of choice for end-stage pulmonary diseases. A limited donor supply has resulted in 4000 patients on the waiting list. Currently, 10-20% of donor organs offered for transplantation are deemed suitable under the selection criteria, of which 15-25% fails due to primary graft dysfunction (PGD). This has resulted in increased efforts to search for alternative donor lungs selection criteria. In this study, we attempt to further our understanding of PGD by observing the changes in gene expression across donor lungs that developed PGD versus those that did not. Our second goal is to use a machine learning tool - support vector machine (SVM), to distinguish unsuitable donor lungs from suitable donor lungs, based on the gene expression data. From our analysis, we have obtained transcripts that were involved in signalling, apoptosis and stress-activated pathways. Results also indicate that metallothionein 3 may prevent lungs from developing PGD. Preliminary classification results for distinguishing suitable and unsuitable lungs for transplantation using a SVM were promising. This is the first such attempt to use human lungs used for transplantation and combine the identification of a molecular signature for PGD, with machine learning methods for donor lung prediction

Single-Lung Transplantation in the Setting of Aborted Bilateral Lung Transplantation

Background. The outcome of patients undergoing a single-lung transplant in the setting of an aborted bilateral lung transplant is unclear. Methods. A retrospective review of single lung transplants at an institutional program. Results. Of the 543 lung transplants performed over the last 10 years, 31 (5.7%) were single-lung transplants. Nineteen of 31 (61%) were planned single-lung transplants, while 12/31 (39%) were intraoperatively aborted, double lung transplants converted to single-lung transplants. The aborted and planned groups were similar in age, lung allocation score and NYHA status. The reasons for aborted double lung transplantation were cardiac/hemodynamic instability 4/12 (33%), difficult pneumonectomy 3/12 (25%), size mismatch 4/12(33%), and technical issues 1/12 (8%). The aborted group had higher CPB utilization (5/12 versus 1/19, P = .02), similar ischemic times (260 versus 234 min) and similar incidence of grade 3 primary graft dysfunction (6/12 versus 3/19, P = .13). ECMO was required for graft dysfunction in 2 patients in the aborted group. The one and two-year survival was 84% and 79% in the planned group and 62% and 52% in the aborted group, respectively. Conclusions. Patients undergoing single-lung transplantation in the setting of an aborted bilateral lung transplant may be at a higher risk of worse outcomes

Questioning Classic Patient Classification Techniques in Gait Rehabilitation: Insights from Wearable Haptic Technology

Classifying stroke survivors based on their walking abilities is an important part of the gait rehabilitation process. It can act as powerful indicator of function and prognosis in both the early days after a stroke and long after a survivor receives rehabilitation. This classification often relies solely on walking speed; a quick and easy measure, with only a stopwatch needed. However, walking speed may not be the most accurate way of judging individual’s walking ability. Advances in technology mean we are now in a position where ubiquitous and wearable technologies can be used to elicit much richer measures to characterise gait. In this paper we present a case study from one of our studies, where within a homogenous group of stroke survivors (based on walking speed classification) important differences in individual results and the way they responded to rhythmic haptic cueing were identified during the piloting of a novel gait rehabilitation technique

Role of defensins in the pathogenesis of chronic lung allograft rejection

Chronic rejection predominantly manifested as bronchiolitis obliterans syndrome (BOS), still remains a major problem affecting long-term outcomes in human lung transplantation (LTx). Donor specific antibodies (DSA) and infiltration of neutrophils in the graft have been associated with the development of BOS. This study determines the role of defensins, produced by neutrophils, and its interaction with α-1-antitrypsin (AAT) towards induction of airway inflammation and fibrosis which are characteristic hallmarks of BOS. Bronchoalveolar lavage (BAL) and serum from LTx recipients, BOS+ (n=28), BOS− (n=26) and normal healthy controls (n=24) were analyzed. Our results show that BOS+ LTx recipients had higher α-defensins (HNP1–3) and β-defensin2 HBD2 concentration in BAL and serum compared to BOS-DSA-recipients and normal controls (p=0.03). BOS+ patients had significantly lower serum AAT along with higher circulating concentration of HNP–AAT complexes in BAL (p=0.05). Stimulation of primary small airway epithelial cells (SAECs) with HNPs induced expression of HBD2, adhesion molecules (ICAM and VCAM), cytokines (IL-6, IL-1β, IL-13, IL-8 and MCP-1) and growth-factor (VEGF and EGF). In contrast, anti-inflammatory cytokine, IL-10 expression decreased 2-fold (p=0.002). HNPs mediated SAEC activation was completely abrogated by AAT. In conclusion, our results demonstrates that neutrophil secretory product, α-defensins, stimulate β-defensin production by SAECs causing upregulation of pro-inflammatory and pro-fibrotic signaling molecules. Hence, chronic stimulation of airway epithelial cells by defensins can lead to inflammation and fibrosis the central events in the development of BOS following LTx