Practical Understanding of Cancer Model Identifiability in Clinical Applications.

Mathematical models are a core component in the foundation of cancer theory and have been developed as clinical tools in precision medicine. Modeling studies for clinical applications often assume an individual's characteristics can be represented as parameters in a model and are used to explain, predict, and optimize treatment outcomes. However, this approach relies on the identifiability of the underlying mathematical models. In this study, we build on the framework of an observing-system simulation experiment to study the identifiability of several models of cancer growth, focusing on the prognostic parameters of each model. Our results demonstrate that the frequency of data collection, the types of data, such as cancer proxy, and the accuracy of measurements all play crucial roles in determining the identifiability of the model. We also found that highly accurate data can allow for reasonably accurate estimates of some parameters, which may be the key to achieving model identifiability in practice. As more complex models required more data for identification, our results support the idea of using models with a clear mechanism that tracks disease progression in clinical settings. For such a model, the subset of model parameters associated with disease progression naturally minimizes the required data for model identifiability.

Massive MCA stroke requiring alteplase followed by thrombectomy in a 34-year-old female with alport syndrome.

34-year-old-female with a medical history significant for Alport's syndrome, chronic kidney disease on dialysis, and hypertension, was brought to the emergency department for sudden onset aphasia and facial droop that began 30 min prior to arrival. She denied a history of prior strokes, recent illness, or fever. The vital signs on arrival as follows: blood pressure 151/71 mmHg, temperature of 98.4F, pulse of 77 beats/min, and respirations of 16 breaths/min. Upon examination, she appeared in mild distress with a left sided facial droop, right sided hemiparesis, and expressive aphasia, only answering to yes/no. Neurological examination revealed: expressive aphasia, intact sensation throughout the face and bilateral extremities, no effort in the right arm against gravity, some effort against gravity of the right leg, left arm and left leg had muscle strength of 5/5. Patient had an NIH stroke scale of 8. The remainder of the exam was unremarkable. Radiographic imaging with CT revealed no intracranial hemorrhage (Fig. 1) and the patient was given alteplase (tPA) injection 5.6 mg within 1 h of her arrival to the Emergency Department. After administration of tPA a CT perfusion scan was performed (Fig. 2). Imaging demonstrated decreased cerebral blood flow and prolonged mean transit time within the majority of the left middle cerebral artery territory, sparing the basal ganglia. This indicated a left middle cerebral artery M1 occlusion. Neurosurgery was consulted and the patient underwent thrombectomy. Her hospital course was complicated by hemorrhagic transformation (HT) on hospital day 2. The patient underwent MRI that showed a large left MCA distribution acute infarction with focal reperfusion hemorrhage and parenchymal hematoma measuring approximately 3 cm in each dimension (Fig. 3). This finding prompted emergent decompression and hemicraniectomy on day 2 of hospitalization. The patient was discharged on hospital day 17 to a rehab center.

Smooth muscle specific overexpression of p22phox potentiates carotid artery wall thickening in response to injury.

We hypothesized that transgenic mice overexpressing the p22(phox) subunit of the NADPH oxidase selectively in smooth muscle (Tg(p22smc)) would exhibit an exacerbated response to transluminal carotid injury compared to wild-type mice. To examine the role of reactive oxygen species (ROS) as a mediator of vascular injury, the injury response was quantified by measuring wall thickness (WT) and cross-sectional wall area (CSWA) of the injured and noninjured arteries in both Tg(p22smc) and wild-type animals at days 3, 7, and 14 after injury. Akt, p38 MAPK, and Src activation were evaluated at the same time points using Western blotting. WT and CSWA following injury were significantly greater in Tg(p22smc) mice at both 7 and 14 days after injury while noninjured contralateral carotids were similar between groups. Apocynin treatment attenuated the injury response in both groups and rendered the response similar between Tg(p22smc) mice and wild-type mice. Following injury, carotid arteries from Tg(p22smc) mice demonstrated elevated activation of Akt at day 3, while p38 MAPK and Src activation was elevated at day 7 compared to wild-type mice. Both increased activation and temporal regulation of these signaling pathways may contribute to enhanced vascular growth in response to injury in this transgenic model of elevated vascular ROS.

A preconcentrator coupled to a GC/FTMS: advantages of self-chemical ionization, mass measurement accuracy, and high mass resolving power for GC applications.

Coupling of a cryogenic preconcentrator (PC) to a gas chromatograph/Fourier transform ion cyclotron resonance mass spectrometer (GC/FT-ICR MS) is reported. To demonstrate the analytical capabilities of the PC/GC/FT-ICR MS, headspace samples containing volatile organic compounds (VOCs) emitted from detached pine tree twigs were analyzed. Sub-ppm mass measurement accuracy (MMA) for highly resolved (m/Deltam(50%) > 150 k) terpene ions was achieved. Direct PC/GC/FT-ICR MS analyses revealed that detached twigs from pine trees emit acetone, camphor, and four detectable hydrocarbon isomers with C(10)H(16) empirical formula. The unknown analytes were identified based on accurate mass measurement and their mass spectral appearances. Authentic samples were used to confirm initially unknown identifications. Self-chemical-ionization (SCI) reactions furnished an additional dimension for rapid isomer differentiation of GC eluents in real time.