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The WHO recommends molecular characterization of CNS tumors. (Louis et al., 2021, 2016). However, many patients at diagnosis and recurrence, do not have tissue accessible for genomics. Blood-based liquid biopsy tests, provide a non-invasive means to obtain genomic data. Liquid biopsy tests are widely adopted to avoid side effects related to invasive biopsies in other solid tumors. However, for primary brain tumors, most patients have cfDNA concentrations below the Limit-of-Detection (LOD) of the tests. The primary contributor to low yield is the blood-brain barrier (BBB) which prevents free passage of tumor analytes into the circulatory system. BBB opening mediated by Focused Ultrasound (FUS) oscillation of microbubbles (MB) has led to an increase of tumor-derived circulating biomarkers in pre-clinical models and in human GBM (Zhu et al 2018, Meng et al 2021). Cordance Medical is developing a non-invasive, portable FUS platform that can enable clinic-based BBB opening treatments. The Cordance device utilizes three transducer types, a Type 1 transducer for non-invasive BBB opening localization obtains Doppler images of the Circle-of-Willis through the temporal lobe. The Doppler images align to the existing MRI using CoW as the fiducial. An array of Type 2 transducers for BBB opening to generate sufficient acoustic pressure to safely oscillate MBs to open the BBB. Finally, Type 3 transducers for safety monitoring receive echo signals from the MBs. Signals are analyzed for harmonic content which enables safety monitoring. The primary endpoint, we will be examining the Cordance platform's ability to increase the concentration of circulating biomarkers following a safe BBB opening. We will recruit patients with recurrent GBM. Patients will receive a baseline blood draw, a BBB opening treatment with the Cordance device, followed by a blood draw after the treatment. Liquid biopsy tests to be examined include the MSK ACCESS test and tumor-informed ddPCR MRD test.

Background: Cerebral vasospasm is one of the frequent complications that can occur following subarachnoid hemorrhage (SAH). With new protocols in the management of SAH, the combined risk of death and long-term disability have been reduced by about 10% compared with the past. Objective: This work aims to report the latest updates on the vasospasm developing after the SAH in patients in the ICU department. In this short review, we reviewed the latest scientific findings on the mechanisms of vasospasm, and in addition, we considered it necessary to review the literature to report the tools for early diagnosis of vasospasm and the best treatment strategies to prevent the negative outcome in patients admitted to ICU. Aim: The aim of this narrative review is to report the main characteristics of vasospasm, new diagnostic methods, and, especially, more effective treatment of vasospasm. Materials and Methods: The peer-reviewed articles analyzed were selected from PubMed, Google scholar, Embase, and Scopus databases published in the previous 20 years using the keywords "vasospasm", "vasospasm diagnosis", "vasospasm and SAH", "vasospasm treatment", and nontraumatic brain injury. Among the 78 papers identified, 43 articles were selected; after the title - abstract examination and removing the duplicates, only 31 articles were examined. Results: Vasospasm can be classified according to clinical (asymptomatic vs. symptomatic) and diagnostic (angiographic vs. ultrasound) methods. Various procedures such as TCD and CT perfusion are used for early diagnosis and close monitoring of this condition. The treatment of vasospasm consists of both prevention (nimodipine, statitis, and magnesium sulphate) and active treatment (mainly endovascular). Conclusion: As the review shows, vasospasm is a complication of SAH, a complication that is difficult to recognize early and treat with the best outcome. However, with the equipment we have, it has been possible to improve the outcome, even if it is still not ideal, in patients who develop vasospasm. Several studies are in the final stages to improve the outcome of this unfortunately frequent condition.

A major impediment to treatment of brain cancers is the inability to transport drugs across the blood-brain barrier (BBB). The development of an effective, targeted, and non-invasive method to penetrate the BBB to deliver cancer therapeutics is an unmet need in the treatment of brain cancers. Large molecular weight chemo- and immuno-therapies such as doxorubicin and others may be potentially effective against brain cancers if such drugs are sufficiently bioavailable in the brain. Focused ultrasound techniques can safely and transiently open the BBB but current techniques require invasive/intrusive or expensive and high-touch procedures and are not optimal for wide adoption. To address this unmet need, we are developing an innovative technique to non-intrusively, non-invasively and transiently open the BBB in a specified location within the brain using guided ultrasound (US). Our device consists of a proprietary US generator that is controlled by a highly portable system that has a small physical footprint, enabling the US generator and system to be placed in confined spaces such as chemotherapy infusion centers. The US generator is cap-shaped device that is placed on a patient’s head. It includes multiple sets of ultrasound transducers that are distributed within the cap according to the anatomy of the skull. With our proprietary technique, we calculate the position of the cap in relation to the internal anatomy in a real-time manner with a non-intrusive and a non-invasive manner. We have recently concluded an extensive study that resulted in algorithms that can accurately guide the US to various targets within the brain across a spectrum of patients. We also have completed a pilot preclinical study on a large animal demonstrating our ability to open the BBB non-invasively and deposit a drug proxy (gadolinium and Evans Blue). Citation Format: Bhaskar Ramamurthy, Mallika Keralapura, Jack Marshall, Dan Need, Ryan Dittamore, Santosh Kesari, Ekokobe Fonkem. Non-intrusive, non-invasive and patient friendly focused ultrasound device as a delivery vehicle for CNS tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 386.

Steelhead (Oncorhynchus mykiss) populations have declined dramatically in many parts of their range in North America, most critically in Southern California, where these anadromous trout are now classified as ‘Endangered’ under the United States Endangered Species Act. The widespread introduction of hatchery rainbow trout, the domesticated freshwater resident form of the species O. mykiss, is one factor threatening the long-term persistence of native steelhead and other trout populations. To identify where native fish of coastal steelhead lineage remained, we performed a population genetic analysis of microsatellite and SNP genotypes from O. mykiss populations at the extreme southern end of their range in Southern California, USA and Baja California, Mexico. In the northern part of this region, nearly all populations appeared to be primarily descendants of native coastal steelhead. However, in the southern, more urbanized part of this region, the majority of the sampled populations were derived primarily from hatchery trout, indicating either complete replacement of native fish or a strong signal of introgression overlaying native ancestry. Nevertheless, these genetically introgressed populations represent potentially critical genetic resources for the continued persistence of viable networks of O. mykiss populations, given the limited native ancestry uncovered in this region and the importance of genetic variation in adaptation. This study elucidates the geographic distribution of native trout populations in this region, and serves as a baseline for evaluating the impacts of hatchery trout on native O. mykiss populations and the success of steelhead conservation and recovery efforts.

Using the phenomenography method, interviews with patients and practitioners were undertaken to explore their understanding of 'health that is more than the absence of disease'. The question was challenging and stimulating for all interviewees. A few were unable to conceptualise this positive definition of health, some perceived it as an optimum end-state, whereas others saw it as an ongoing process. Many positive attributes of health and its influencers were identified. The more advanced understandings of this concept were of a holistic, multidimensional, expansive state where the all dimensions of health are interdependent and positively reinforcing. The results affirmed that wellness is more than psychological wellbeing, 'happiness' and life satisfaction. Optimum physical and cognitive capacities along with spiritual, social and occupational wellness were equally as important. 'Energy and vitality' were sufficiently emphasised by patients and some practitioners to support the inclusion of the principles of vitalism in any discussion about health.

Abstract In producing the Northeast Butterly Pool crude oil it was necessary to pump sand consolidating agents into the formation, treat with large amounts of emulsion breaker, blend with high gravity crude, heat in the stock tanks as well as the heaters, and blend additionally as the oil entered the pipeline. Steam jets and drains installed in heaters and two trucks equipped with sand buckets, working 24 hours a day, were necessary to separate the produced sand from the oil and remove it from the area. Despite these problems, over 2,500,000 bbl of oil have been produced in less than 10 years from a reservoir covering 185 surface acres. Introduction The Northeast Butterly Pool, located in Garvin County, Okla., approximately 3 miles northwest of the town of Davis, is unique in several respects. It is the purpose of this paper to share the knowledge gained in combatting the many adverse conditions present in the pool. The possibility that the solutions arrived at in exploiting this reservoir might aid in the development of future pools, which would otherwise be abandoned as non-commercial, has been an added stimulus in the writing of this case history. History of Development The discovery well of the Northeast Butterly Pool, the W. M. Butterly No.1, was completed on Dec. 20, 1945, at a total depth of 4,422 ft and with a plugged back total depth of 4,109 ft. Producing through perforations opposite the Oil Creek sand formation, Ordovician age, the initial potential, pumping, was 240 B/D of 13° API gravity oil, with a bottom bole pressure of 2,500 psia. With one rig in use the field underwent orderly development on 10-acre spacing with five wells drilled in 1946, four in 1947, two in 1948, and one in 1949. Of the 13 wells drilled, one was a dry hole and one was plugged and abandoned during completion due to mechanical difficulties. An offset, 50 ft west of the latter, was drilled as the eleventh producing well in the pool.