Patterns and Prediction of Competing Causes of Mortality in Older Adults Diagnosed with Indolent Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma (NHL) consists of heterogeneous hematological malignancies that are broadly categorized into aggressive or indolent tumor growth groups. In the past two decades, there have been notable increases in the proportion of NHL diagnoses aged >65 and cancer-specific survival with the aging US population and improvements in NHL treatments. These population changes have important implications for non-cancer mortality, particularly for indolent NHL subtypes, which display remitting-relapsing patterns and a slower progression. This dissertation sought to address gaps in knowledge about non-cancer mortality in NHL by providing foundational evidence on: 1) cancer-specific and non-cancer mortality patterns in NHL subtypes and 2) characteristics of indolent NHL patients at greatest risk of non-cancer mortality. We identified adults aged >66 at diagnosis with a first, primary NHL diagnosis from 2004-2011 using a database linking the US Surveillance, Epidemiology, and End Results (SEER) cancer registry with Medicare health insurance claims. Using death certificate data and Fine-Gray competing risks methods, Aim 1 estimated the 5-year cumulative incidence of NHL-specific and non-cancer mortality by prognostic factors (subtype, age, comorbidity level) in 26,809 NHL patients. Among aggressive subtypes, NHL-specific mortality exceeded non-cancer mortality across all ages and comorbidity levels. In indolent subtypes, non-cancer mortality was similar to or exceeded NHL-specific mortality for patients with older ages, higher comorbidity burdens, or specific subtypes. The results support development of tools predicting non-cancer mortality in older indolent NHL patients. In Aim 2, we developed and internally validated risk prediction models for short- and long-term mortality outcomes in 9789 indolent NHL patients. We created 16 elastic net penalized regression models predicting 1- and 5-year all-cause and non-cancer mortality (four models per outcome) in 100 randomly resampled training sets. In 100 validation sets, we compared average performance statistics of the elastic net to those from comorbidity score models. For all outcomes, the elastic net models had a higher discrimination and lower false-positive rate than comorbidity score models. However, differences were not statistically significantly. This project supports development of personalized prediction models integrated into electronic medical records that can inform physicians and patients on non-cancer mortality risk in indolent NHL treatment decision-making.Doctor of Philosoph

3D Self-Localization of Drones using a Single Millimeter-Wave Anchor

We present the design, implementation, and evaluation of MiFly, a self-localization system for autonomous drones that works across indoor and outdoor environments, including low-visibility, dark, and GPS-denied settings. MiFly performs 6DoF self-localization by leveraging a single millimeter-wave (mmWave) anchor in its vicinity - even if that anchor is visually occluded. MmWave signals are used in radar and 5G systems and can operate in the dark and through occlusions. MiFly introduces a new mmWave anchor design and mounts light-weight high-resolution mmWave radars on a drone. By jointly designing the localization algorithms and the novel low-power mmWave anchor hardware (including its polarization and modulation), the drone is capable of high-speed 3D localization. Furthermore, by intelligently fusing the location estimates from its mmWave radars and its IMUs, it can accurately and robustly track its 6DoF trajectory. We implemented and evaluated MiFly on a DJI drone. We demonstrate a median localization error of 7cm and a 90th percentile less than 15cm, even when the anchor is fully occluded (visually) from the drone

Cobalt picolinamide complexes as potential anti-cancer agents

This thesis details the synthesis of cobalt picolinamide complexes with potential chemotherapeutic applications. The anti-cancer, anti-bacterial and anti-fungal activity of these complexes was probed, with lead complexes undergoing further mechanistic investigations. Three series of cobalt picolinamide complex were investigated: cobalt(III) trispicolinamide, cobalt(II) bis-picolinamide and cobalt(III) mixed ligand complexes. Cobalt tris-picolinamide complexes consist of a cobalt(III) ion surrounded by three picolinamide ligands, bound through the pyridyl and amide nitrogen atoms. A minor isomer with different ligand coordination was formed under certain reaction conditions, provided that an electron donating group is present as a substituent on the picolinamide ligand. The formation of cobalt bis-picolinamide complexes was also only successful when electron donating groups were present on the picolinamide ligand. These complexes contain a cobalt(II) ion with two picolinamide ligands and two axial thiocyanate ligands. The cis/trans orientation of the thiocyanate ligands varies dependent upon the position of the picolinamide ligand substituent. Mixed ligand complexes consist of a cobalt(III) ion with two picolinamide ligands and one β-diketonate or ferrocenyl β-diketonate ligand. Complexes were screened for their anti-cancer potential against a number of cell lines. Cobalt bis-picolinamide and mixed ligand complexes were non-toxic. Some cobalt tris-picolinamide complexes displayed cytotoxicity, with the minor isomer displaying greater activity than the analogous major isomer. The two lead complexes were active against cancer cells and cancer stem cells. The mechanism of action is proposed to be inhibition of cell proliferation through interruption of the cell cycle at M phase. The lead complexes did not undergo hydrolysis, in contrast to the mixed ligand complexes containing the ferrocenyl β-diketonate ligand. The lead complexes could also adsorb onto an artificial biomembrane surface, unlike the inactive complexes, implying a correlation between cytotoxicity and cellular uptake. Additionally, cobalt bis-picolinamide complexes displayed antifungal activity against C. albicans, with the thiocyanate ligands essential for activity

Cardiac Arrest Caused by an Acute Intrathoracic Gastric Volvulus Treated With Percutaneous Gastrostomy

During cardiopulmonary resuscitation, one of the first priorities after establishing basic and advanced life support is to identify the cause of the arrest. We present a rare case of cardiac arrest due to a decreased venous return from mediastinal shift caused by a paraesophageal hernia with an incarcerated thoracic gastric volvulus, which was treated by percutaneous gastrostomy

Association between muscle thickness, fat-free mass and malnutrition in patients with copd: an exploratory study

Rationale: Malnutrition is a common problem in patients with Chronic Obstructive Pulmonary Disease (COPD). Whereas estimation of fat-free muscle mass index (FFMi) with bio-electrical impedance is often used, less is known about muscle thickness measured with ultrasound (US) as a parameter for malnutrition. Moreover, it has been suggested that in this population, loss of muscle mass is characterized by loss of the lower body muscles rather than of the upper body muscles.1 Therefore, we explored the association between FFMi, muscle thickness of the biceps brachii (BB) and the rectus femoris (RF), and malnutrition in patients with COPD. Methods: Patients were assessed at the start of a pulmonary rehabilitation program. Malnutrition was assessed with the Scored Patient-Generated Subjective Global Assessment (PG-SGA). Malnutrition was defined as PG-SGA Stage B or C. FFMi (kg/m²) was estimated with bio-electrical impedance analysis BIA 101® (Akern), using the Rutten equation. Muscle thickness (mm) of the BB and the RF was measured with the handheld BodyMetrix® device (Intelametrix). Univariate and multivariate logistic regression analyses were performed to analyse associations between FFMi and muscle thickness for BB and RF, and malnutrition. Multivariate analysis corrected for sex, age, and GOLD-stage. Odds ratios (OR) and 95% confidence intervals (CI) were presented. A p-level of <0.05 was considered significant. Results: In total, 27 COPD patients (age 64±8.1 years; female 60%, GOLD-stage 3, interquartile range=3-4, BMI 27±6.6 kg/m2) were included in the analyses. In the univariate analysis, FFMi (p=0.014; OR=0.70, 95%CI: -0.12—0.15), RF thickness (p=0.021; OR=0.79, 95%CI: -0.09—0.01), and BB thickness (p=0.006; OR=0.83, 95%CI: -0.06—0.01) were all significantly associated with malnutrition. In the multivariate analysis, FFMi (p=0.031; OR=0.59, 95%CI: -0.18—0.01) and BB thickness (p=0.017; OR=0.73, 95%CI:-0.09—0.01) were significantly associated with malnutrition. None of the co-variables were significantly associated with malnutrition. Conclusion: In this relatively small sample of patients with severe COPD, low FFMi and low BB muscle thickness were both robustly associated with increased odds of being malnourished. BB muscle thickness measured with US may provide added value to the toolbox for nutritional assessment. The results of this exploratory study suggest that upper body muscles may reflect nutritional status more closely than lower body muscles. Reference: 1 Shrikrishna D, Patel M, Tanner RJ, Seymour JM, Connolly BA, Puthucheary ZA, et al. Quadriceps wasting and physical inactivity in patients with COPD. Eur Respir J. 2012;40(5):1115–22.

Implementation of MenACWY vaccination because of ongoing increase in serogroup W invasive meningococcal disease, the Netherlands, 2018.

The annual incidence rate of serogroup W invasive meningococcal disease in the Netherlands increased from < 0.05/100,000 (n < 10) before 2015 to 0.5/100,000 (n = 80) in 2017. Most isolates (94%) belong to clonal complex 11. The incidence rate is highest among  < 5 year-olds and 15-24 year-olds. The case fatality rate was 12% (17/138) in 2015-2017. From May 2018, MenACWY vaccination replaces MenC vaccination at age 14 months and from October 2018, 13-14 year-olds are offered MenACWY vaccination