Quadrotor UAV Interface and Localization Design

MIT Lincoln Laboratory has expressed growing interest in projects involving quadrotor Unmanned Aerial Vehicles (UAVs). Our tasks were to develop a system providing computerized remote control of the provided UAV, as well as to develop a high-accuracy localization system. We integrated the UAV\u27s control system with standard Robot Operating System (ROS) software tools. We measured the reliability of the control system, and determined performance characteristics. We found our control scheme to be usable pending minor improvements. To enable localization, we explored machine vision, ultimately altering the Augmented Reality library ARToolKit to interface with ROS. After several tests, we determined that ARToolKit is not currently a feasible alternative to standard localization techniques

The Virtual Choir

The purpose of this project was to continue the ongoing research into the development of a virtual choir with adaptive real-time tempo adjustment. A system was developed which provided the means for a user to adjust the tempo of a multi-track choral recording of the Thomas Tallis piece Spem in Alium in real-time, during playback. An intermediate version was presented at the American Choral Directors Association Eastern Division conference in Philadelphia, PA, and feedback was collected

Association is not causation: treatment effects cannot be estimated from observational data in heart failure

Aims: Treatment ‘effects’ are often inferred from non-randomized and observational studies. These studies have inherent biases and limitations, which may make therapeutic inferences based on their results unreliable. We compared the conflicting findings of these studies to those of prospective randomized controlled trials (RCTs) in relation to pharmacological treatments for heart failure (HF). Methods and results: We searched Medline and Embase to identify studies of the association between non-randomized drug therapy and all-cause mortality in patients with HF until 31 December 2017. The treatments of interest were: angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, mineralocorticoid receptor antagonists (MRAs), statins, and digoxin. We compared the findings of these observational studies with those of relevant RCTs. We identified 92 publications, reporting 94 non-randomized studies, describing 158 estimates of the ‘effect’ of the six treatments of interest on all-cause mortality, i.e. some studies examined more than one treatment and/or HF phenotype. These six treatments had been tested in 25 RCTs. For example, two pivotal RCTs showed that MRAs reduced mortality in patients with HF with reduced ejection fraction. However, only one of 12 non-randomized studies found that MRAs were of benefit, with 10 finding a neutral effect, and one a harmful effect. Conclusion: This comprehensive comparison of studies of non-randomized data with the findings of RCTs in HF shows that it is not possible to make reliable therapeutic inferences from observational associations. While trials undoubtedly leave gaps in evidence and enrol selected participants, they clearly remain the best guide to the treatment of patients

Quadrotor UAV Interface and Localization Design

Our project\u27s task was to assist Lincoln Laboratory in preparation for the future automation of a quadrotor UAV system. We created an interface between the quadrotor and ROS to allow for computerized-control of the UAV. Tests of our system indicated that our solution could be feasible with further research. In the next phase of the projects, we created a localization system automate take-off and landing in future mission environments by altering the augmented reality library, ARToolKit, to work with ROS. We performed accuracy, range, update rate, lighting, and tag occlusion tests on our modified code to determine its viability in real-world conditions. We concluded that our current system would not be a feasible due to inconsistencies in tag-detection, but that it merits further research

Structured Estimation of Heterogeneous Time Series

How best to model structurally heterogeneous processes is a foundational question in the social, health and behavioral sciences. Recently, Fisher et al., (2022) introduced the multi-VAR approach for simultaneously estimating multiple-subject multivariate time series characterized by common and individualizing features using penalized estimation. This approach differs from many popular modeling approaches for multiple-subject time series in that qualitative and quantitative differences in a large number of individual dynamics are well-accommodated. The current work extends the multi-VAR framework to include new adaptive weighting schemes that greatly improve estimation performance. In a small set of simulation studies we compare adaptive multi-VAR with these new penalty weights to common alternative estimators in terms of path recovery and bias. Furthermore, we provide toy examples and code demonstrating the utility of multi-VAR under different heterogeneity regimes using the multivar package for R (Fisher, 2022)

Transcatheter interatrial shunt device for the treatment of heart failure with preserved ejection fraction (REDUCE LAP-HF I [Reduce Elevated Left Atrial Pressure in Patients With Heart Failure]): A phase 2, randomized, sham-controlled trial

Background -In non-randomized, open-label studies, a transcatheter interatrial shunt device (IASD, Corvia Medical) was associated with lower pulmonary capillary wedge pressure (PCWP), less symptoms, and greater quality of life and exercise capacity in patients with heart failure (HF) and mid-range or preserved ejection fraction (EF ≥ 40%). We conducted the first randomized, sham-controlled trial to evaluate the IASD in HF with EF ≥ 40%. Methods -REDUCE LAP-HF I was a phase 2, randomized, parallel-group, blinded multicenter trial in patients with New York Heart Association (NYHA) class III or ambulatory class IV HF, EF ≥ 40%, exercise PCWP ≥ 25 mmHg, and PCWP-right atrial pressure gradient ≥ 5 mmHg. Participants were randomized (1:1) to the IASD vs. a sham procedure (femoral venous access with intracardiac echocardiography but no IASD placement). The participants and investigators assessing the participants during follow-up were blinded to treatment assignment. The primary effectiveness endpoint was exercise PCWP at 1 month. The primary safety endpoint was major adverse cardiac, cerebrovascular, and renal events (MACCRE) at 1 month. PCWP during exercise was compared between treatment groups using a mixed effects repeated measures model analysis of covariance that included data from all available stages of exercise. Results -A total of 94 patients were enrolled, of which n=44 met inclusion/exclusion criteria and were randomized to the IASD (n=22) and control (n=22) groups. Mean age was 70±9 years and 50% were female. At 1 month, the IASD resulted in a greater reduction in PCWP compared to sham-control (P=0.028 accounting for all stages of exercise). Peak PCWP decreased by 3.5±6.4 mmHg in the treatment group vs. 0.5±5.0 mmHg in the control group (P=0.14). There were no peri-procedural or 1-month MACCRE in the IASD group and 1 event (worsening renal function) in the control group (P=1.0). Conclusions -In patients with HF and EF ≥ 40%, IASD treatment reduces PCWP during exercise. Whether this mechanistic effect will translate into sustained improvements in symptoms and outcomes requires further evaluation. Clinical Trial Registration -URL: http://clinicaltrials.gov. Unique identifier: NCT02600234

The pseudokinase MLKL mediates programmed hepatocellular necrosis independently of RIPK3 during hepatitis

Although necrosis and necroinflammation are central features of many liver diseases, the role of programmed necrosis in the context of inflammation-dependent hepatocellular death remains to be fully determined. Here, we have demonstrated that the pseudokinase mixed lineage kinase domain-like protein (MLKL), which plays a key role in the execution of receptor interacting protein (RIP) lcinase-dependent necroptosis, is upregulated and activated in human autoimmune hepatitis and in a murine model of inflammation-dependent hepatitis. Using genetic and pharmacologic approaches, we determined that hepatocellular necrosis in experimental hepatitis is driven by an MLKL-dependent pathway that occurs independently of RIPK3. Moreover, we have provided evidence that the cytotoxic activity of the proinflammatory cytokine IFN-gamma in hepatic inflammation is strongly connected to induction of MLKL expression via activation of the transcription factor STAT1. In summary, our results reveal a pathway for MLKL-dependent programmed necrosis that is executed in the absence of RIPK3 and potentially drives the pathogenesis of severe liver diseases

The effectiveness, safety and cost-effectiveness of cytisine versus varenicline for smoking cessation in an Australian population: a study protocol for a randomized controlled non-inferiority trial

Smoking cessation medications are effective but often underutilised because of costs and side effects. Cytisine is a plant-based smoking cessation medication with over 50 years of use in Central and Eastern Europe. While cytisine has been found to be well-tolerated and more effective than nicotine replacement therapy, direct comparison with varenicline have not been conducted. This study evaluates the effectiveness, safety and cost-effectiveness of cytisine compared with varenicline.Two arm, parallel group, randomised, non-inferiority trial, with allocation concealment and blinded outcome assessment.Australian population-based study.Adult daily smokers (N=1266) interested in quitting will be recruited through advertisements and Quitline telephone-based cessation support services.Eligible participants will be randomised (1:1 ratio) to receive either cytisine capsules (25-day supply) or varenicline tablets (12-week supply), prescribed in accordance with the manufacturer's recommended dosing regimen. The medication will be mailed to each participant's nominated residential address. All participants will also be offered standard Quitline behavioural support (up to six 10-12 minute sessions).Assessments will be undertaken by telephone at baseline, 4- and 7-months post-randomisation. Participants will also be contacted twice (two and four weeks post-randomisation) to ascertain adverse events, treatment adherence and smoking status. The primary outcome will be self-reported 6-month continuous abstinence from smoking, verified by carbon monoxide at 7-month follow-up. We will also evaluate the relative safety and cost-effectiveness of cytisine compared with varenicline. Secondary outcomes will include self-reported continuous and 7-day point prevalence abstinence and cigarette consumption at each follow-up interview.If cytisine is as effective as varenicline, its lower cost and natural plant-based composition may make it an acceptable and affordable smoking cessation medication that could save millions of lives worldwide

One-year outcomes after transcatheter insertion of an interatrial shunt device for the management of heart failure with preserved ejection fraction

Background—Heart failure with preserved ejection fraction has a complex pathophysiology and remains a therapeutic challenge. Elevated left atrial pressure, particularly during exercise, is a key contributor to morbidity and mortality. Preliminary analyses have demonstrated that a novel interatrial septal shunt device that allows shunting to reduce the left atrial pressure provides clinical and hemodynamic benefit at 6 months. Given the chronicity of heart failure with preserved ejection fraction, evidence of longer-term benefit is required. Methods and Results—Patients (n=64) with left ventricular ejection fraction ≥40%, New York Heart Association class II–IV, elevated pulmonary capillary wedge pressure (≥15 mm Hg at rest or ≥25 mm Hg during supine bicycle exercise) participated in the open-label study of the interatrial septal shunt device. One year after interatrial septal shunt device implantation, there were sustained improvements in New York Heart Association class (P<0.001), quality of life (Minnesota Living with Heart Failure score, P<0.001), and 6-minute walk distance (P<0.01). Echocardiography showed a small, stable reduction in left ventricular end-diastolic volume index (P<0.001), with a concomitant small stable increase in the right ventricular end-diastolic volume index (P<0.001). Invasive hemodynamic studies performed in a subset of patients demonstrated a sustained reduction in the workload corrected exercise pulmonary capillary wedge pressure (P<0.01). Survival at 1 year was 95%, and there was no evidence of device-related complications. Conclusions—These results provide evidence of safety and sustained clinical benefit in heart failure with preserved ejection fraction patients 1 year after interatrial septal shunt device implantation. Randomized, blinded studies are underway to confirm these observations

Obesity-induced insulin resistance in human skeletal muscle is characterised by defective activation of p42/p44 MAP kinase

Insulin resistance (IR), an impaired cellular, tissue and whole body response to insulin, is a major pathophysiological defect of type 2 diabetes mellitus. Although IR is closely associated with obesity, the identity of the molecular defect(s) underlying obesity-induced IR in skeletal muscle remains controversial; reduced post-receptor signalling of the insulin receptor substrate 1 (IRS1) adaptor protein and downstream effectors such as protein kinase B (PKB) have previously been implicated. We examined expression and/or activation of a number of components of the insulin-signalling cascade in skeletal muscle of 22 healthy young men (with body mass index (BMI) range, 20–37 kg/m2). Whole body insulin sensitivity (M value) and body composition was determined by the hyperinsulinaemic (40 mU. min−1.m−2.), euglycaemic clamp and by dual energy X-ray absorptiometry (DEXA) respectively. Skeletal muscle (vastus lateralis) biopsies were taken before and after one hour of hyperinsulinaemia and the muscle insulin signalling proteins examined by western blot and immunoprecipitation assay. There was a strong inverse relationship between M-value and BMI. The most striking abnormality was significantly reduced insulin-induced activation of p42/44 MAP kinase, measured by specific assay, in the volunteers with poor insulin sensitivity. However, there was no relationship between individuals' BMI or M-value and protein expression/phosphorylation of IRS1, PKB, or p42/44 MAP kinase protein, under basal or hyperinsulinaemic conditions. In the few individuals with poor insulin sensitivity but preserved p42/44 MAP kinase activation, other signalling defects were evident. These findings implicate defective p42/44 MAP kinase signalling as a potential contributor to obesity-related IR in a non-diabetic population, although clearly multiple signalling defects underlie obesity associated IR