Development of enclosed life support system for underground rescue employing a photocatalytic metal oxide thin film to generate oxygen from water and reduce carbon dioxide

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2006.Includes bibliographical references (p. 35-36).Despite major improvements in technology and safety regulations, coal mining continues to be a hazardous industry. Catastrophic accidents, related largely to underground explosions and generation of toxic gases, commonly result in the trapping of miners without oxygen for an extended period of time. As an example, in January 2006, an accident at the Sago Mine in West Virginia trapped 12 coal miners underground for 41 hours and resulted in the deaths of all but one. According to the account of the sole survivor, four of the emergency oxygen sources, or "air packs," failed. While devices capable of supplying oxygen to miners trapped underground exist, these systems are limited by the need for an exogenous gas supply, the large size of the devices, and unreliability. We propose here the design of an enclosed life support system functional for up to 12 hours, which employs photocatalytic mechanisms to generate oxygen from water and provides chemical reduction, or "fixation", of carbon dioxide. Oxygen is generated through a photolytic reaction involving the interaction of UV light and a titanium dioxide thin film, resulting in the generation of oxygen gas at a rate of 0.0507 L 02 / min per m2 of photolytic surface.(cont.) Exhaled carbon dioxide is mechanically segregated from the oxygen and then fixed to a 5 carbon sugar molecule, ribulose, through a mechanism that includes the addition of carbon dioxide and water, the cleavage of the C2-C3 bond, and the ultimate generation of glyceric acid and its unlit. We contend that the system proposed here has the ability to significantly exceed the capacity of current emergency life support systems employed underground, and thereby improve the safety of coal miners and the overall productivity of the coal mining industry.by Meghna S. Trivedi.S.B

Qualitative analysis of shared decision-making for chemoprevention in the primary care setting: provider-related barriers

Background Chemoprevention with anti-estrogens, such as tamoxifen, raloxifene or aromatase inhibitors, have been shown to reduce breast cancer risk in randomized controlled trials; however, uptake among women at high-risk for developing breast cancer remains low. The aim of this study is to identify provider-related barriers to shared decision-making (SDM) for chemoprevention in the primary care setting. Methods Primary care providers (PCPs) and high-risk women eligible for chemoprevention were enrolled in a pilot study and a randomized clinical trial of web-based decision support tools to increase chemoprevention uptake. PCPs included internists, family practitioners, and gynecologists, whereas patients were high-risk women, age 35–75 years, who had a 5-year invasive breast cancer risk ≥ 1.67%, according to the Gail model. Seven clinical encounters of high-risk women and their PCPs who were given access to these decision support tools were included in this study. Audio-recordings of the clinical encounters were transcribed verbatim and analyzed using grounded theory methodology. Results Six primary care providers, of which four were males (mean age 36 [SD 6.5]) and two were females (mean age 39, [SD 11.5]) and seven racially/ethnically diverse high-risk female patients participated in this study. Qualitative analysis revealed three themes: (1) Competing demands during clinical encounters; (2) lack of knowledge among providers about chemoprevention; and (3) limited risk communication during clinical encounters. Conclusions Critical barriers to SDM about chemoprevention were identified among PCPs. Providers need education and resources through decision support tools to engage in risk communication and SDM with their high-risk patients, and to gain confidence in prescribing chemoprevention in the primary care setting

Lessons from the Failure to Complete a Trial of Denosumab in Women With a Pathogenic BRCA1/2 Variant Scheduling Risk-Reducing Salpingo-Oophorectomy

Female carriers of pathogenic/likely pathogenic (P/LP) BRCA1/2 variants are at increased risk of developing breast and ovarian cancer. Currently, the only effective strategy for ovarian cancer risk reduction is risk-reducing bilateral salpingo-oophorectomy (RR-BSO), which carries adverse effects related to early menopause. There is ongoing investigation of inhibition of the RANK ligand (RANKL) with denosumab as a means of chemoprevention for breast cancer in carriers of BRCA1 P/LP variants. Through the NCI Division of Cancer Prevention (DCP) Early Phase Clinical Trials Prevention Consortia, a presurgical pilot study of denosumab was developed in premenopausal carriers of P/LP BRCA1/2 variants scheduled for RR-BSO with the goal of collecting valuable data on the biologic effects of denosumab on gynecologic tissue. The study was terminated early due to the inability to accrue participants. Challenges which impacted the conduct of this study included a study design with highly selective eligibility criteria and requirements and the COVID-19 pandemic. It is critical to reflect on these issues to enhance the successful completion of future prevention studies in individuals with hereditary cancer syndromes

Datopotamab–deruxtecan plus durvalumab in early-stage breast cancer: the sequential multiple assignment randomized I-SPY2.2 phase 2 trial

Sequential adaptive trial designs can help accomplish the goals of personalized medicine, optimizing outcomes and avoiding unnecessary toxicity. Here we describe the results of incorporating a promising antibody-drug conjugate, datopotamab-deruxtecan (Dato-DXd) in combination with programmed cell death-ligand 1 inhibitor, durvalumab, as the first sequence of therapy in the I-SPY2.2 phase 2 neoadjuvant sequential multiple assignment randomization trial for high-risk stage 2/3 breast cancer. The trial includes three blocks of treatment, with initial randomization to different experimental agent(s) (block A), followed by a taxane-based regimen tailored to tumor subtype (block B), followed by doxorubicin-cyclophosphamide (block C). Subtype-specific algorithms based on magnetic resonance imaging volume change and core biopsy guide treatment redirection after each block, including the option of early surgical resection in patients predicted to have a high likelihood of pathologic complete response, which is the primary endpoint assessed when resection occurs. There are two primary efficacy analyses: after block A and across all blocks for six prespecified HER2-negative subtypes (defined by hormone receptor status and/or response-predictive subtypes). In total, 106 patients were treated with Dato-DXd/durvalumab in block A. In the immune-positive subtype, Dato-DXd/durvalumab exceeded the prespecified threshold for success (graduated) after block A; and across all blocks, pathologic complete response rates were equivalent to the rate expected for the standard of care (79%), but 54% achieved that result after Dato-DXd/durvalumab alone (block A) and 92% without doxorubicin-cyclophosphamide (after blocks A + B). The treatment strategy across all blocks graduated in the hormone-negative/immune-negative subtype. No new toxicities were observed. Stomatitis was the most common side effect in block A. No patients receiving block A treatment alone had adrenal insufficiency. Dato-DXd/durvalumab is a promising therapy combination that can eliminate standard chemotherapy in many patients, particularly the immune-positive subtype.ClinicalTrials.gov registration: NCT01042379

Effects of neoadjuvant chemotherapy on the contralateral non-tumor-bearing breast assessed by diffuse optical tomography

Background The purpose of this study is to evaluate whether the changes in optically derived parameters acquired with a diffuse optical tomography breast imager system (DOTBIS) in the contralateral non-tumor-bearing breast in patients administered neoadjuvant chemotherapy (NAC) for breast cancer are associated with pathologic complete response (pCR). Methods In this retrospective evaluation of 105 patients with stage II–III breast cancer, oxy-hemoglobin (ctO2Hb) from the contralateral non-tumor-bearing breast was collected and analyzed at different time points during NAC. The earliest monitoring imaging time point was after 2–3 weeks receiving taxane. Longitudinal data were analyzed using linear mixed-effects modeling to evaluate the contralateral breast ctO2Hb changes across chemotherapy when corrected for pCR status, age, and BMI. Results Patients who achieved pCR to NAC had an overall decrease of 3.88 μM for ctO2Hb (95% CI, 1.39 to 6.37 μM), p = .004, after 2–3 weeks. On the other hand, non-pCR subjects had a non-significant mean reduction of 0.14 μM (95% CI, − 1.30 to 1.58 μM), p > .05. Mixed-effect model results indicated a statistically significant negative relationship of ctO2Hb levels with BMI and age. Conclusions This study demonstrates that the contralateral normal breast tissue assessed by DOTBIS is modifiable after NAC, with changes associated with pCR after only 2–3 weeks of chemotherapy

Making National Cancer Institute–Designated Comprehensive Cancer Center Knowledge Accessible to Community Oncologists via an Online Tumor Board: Longitudinal Observational Study

BackgroundExpert knowledge is often shared among multidisciplinary academic teams at tumor boards (TBs) across the country, but these conversations exist in silos and do not reach the wider oncology community. ObjectiveUsing an oncologist-only question and answer (Q&A) website, we sought to document expert insights from TBs at National Cancer Institute–designated Comprehensive Cancer Centers (NCI-CCCs) to provide educational benefits to the oncology community. MethodsWe designed a process with the NCI-CCCs to document and share discussions from the TBs focused on areas of practice variation on theMednet, an interactive Q&A website of over 13,000 US oncologists. The faculty translated the TB discussions into concise, non–case-based Q&As on theMednet. Answers were peer reviewed and disseminated in email newsletters to registered oncologists. Reach and engagement were measured. Following each Q&A, a survey question asked how the TB Q&As impacted the readers’ practice. ResultsA total of 23 breast, thoracic, gastrointestinal, and genitourinary programs from 16 NCI-CCC sites participated. Between December 2016 and July 2021, the faculty highlighted 368 questions from their TBs. Q&As were viewed 147,661 times by 7381 oncologists at 3515 institutions from all 50 states. A total of 277 (75%) Q&As were viewed every month. Of the 1063 responses to a survey question on how the Q&A affected clinicians’ practices, 646 (61%) reported that it confirmed their current practice, 163 (20%) indicated that a Q&A would change their future practice, and 214 (15%) reported learning something new. ConclusionsThrough an online Q&A platform, academics at the NCI-CCCs share knowledge outside the walls of academia with oncologists across the United States. Access to up-to-date expert knowledge can reassure clinicians’ practices, significantly impact patient care in community practices, and be a source of new knowledge and education