Effects of Cochlear Implantation and Steroids on the Aging Guinea Pig Cochlea.

OBJECTIVE: The objective was to determine the effects of older age on hearing preservation after cochlear implantation (CI), and whether steroids improve hearing preservation in older animals. We hypothesized greater hearing preservation would be observed in (1) young animals compared to older animals and (2) older animals receiving steroids compared to no steroids. The secondary objective was to assess levels of fibrosis utilizing optical coherence tomography (OCT). STUDY DESIGN: Experimental Animal Study. SETTING: Laboratory. METHODS: Three groups of guinea pigs: young (YCI; 8.5 ± 0.5 weeks; n = 10), old (OCI; 19.1 ± 1.0 months; n = 9) and old + steroids (OCI+S; 19.1 ± 1.0 months; n = 9) underwent CI. The OCI+S group received a steroid taper over 7 days starting 2 days before surgery to 4 days after. Auditory brainstem response (ABR) measurements were performed preoperatively and postoperatively. OCT imaging was performed to assess cochleae for extent of fibrotic tissue growth in the scala tympani. RESULTS: The YCI group had significantly better hearing preservation as measured by smaller increases in ABR thresholds [mean shift: 2.79 ± 0.66] compared to the OCI group [mean shift = 12.44 ± 5.6]. The OCI+S group had significantly better hearing preservation [2.66 ± 1.50] compared to the OCI group. No significant differences was seen in fibrosis across groups. CONCLUSIONS: Young animals and older animals that received steroids had better hearing after CI than older animals not given steroids, but hearing preservation was not correlated with the level of fibrosis assessed using OCT. This work is the first to investigate differences in hearing preservation by age in an animal model, and supports the protective effects of steroids on hearing preservation in older individuals.

Evidence for Combining Conservative Treatments for Adhesive Capsulitis.

Background: Adhesive capsulitis, also known as frozen shoulder, is a challenge to treat clinically. Common first-line treatment options are suprascapular nerve block (SSNB), intra-articular corticosteroid (IACS) injection, hydrodilatation, and physical therapy. This literature review summarizes each of these conservative treatments and discusses the evidence base for combining treatment options for potential additive benefits to improve patient outcomes (ie, pain, range of motion [ROM], and shoulder function). Methods: The PubMed and Google Scholar databases were searched using the search terms "adhesive capsulitis," "frozen shoulder," "corticosteroids," "physical therapy," "suprascapular nerve block," "hydrodilatation," and "conservative care." Pertinent articles were identified and synthesized to provide a comprehensive review of 4 common conservative treatments for adhesive capsulitis. Results: Combining SSNB with physical therapy and/or IACS injection and combining IACS injection with physical therapy have support in the literature for improving shoulder pain, ROM, and function, while hydrodilatation and physical therapy seem to offer some additive benefits for improving shoulder ROM when used as adjunct treatments for adhesive capsulitis. Conclusion: Adhesive capsulitis remains a challenge to treat clinically with much still unknown regarding treatment optimization. For the foreseeable future, first-line conservative management will continue to be the mainstay of managing adhesive capsulitis. Thus, knowing how to best use and optimize these various options-both individually and in combination-is vital for effective treatment.

Structural optimization of siRNA conjugates for albumin binding achieves effective MCL1-directed cancer therapy.

The high potential of siRNAs to silence oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, divalent lipid-conjugated siRNAs are optimized for in situ binding to albumin to improve pharmacokinetics and tumor delivery. Systematic variation of the siRNA conjugate structure reveals that the location of the linker branching site dictates tendency toward albumin association versus self-assembly, while the lipid hydrophobicity and reversibility of albumin binding also contribute to siRNA intracellular delivery. The lead structure increases tumor siRNA accumulation 12-fold in orthotopic triple negative breast cancer (TNBC) tumors over the parent siRNA. This structure achieves approximately 80% silencing of the anti-apoptotic oncogene MCL1 and yields better survival outcomes in three TNBC models than an MCL-1 small molecule inhibitor. These studies provide new structure-function insights on siRNA-lipid conjugate structures that are intravenously injected, associate in situ with serum albumin, and improve pharmacokinetics and tumor treatment efficacy.

Telecaregiving for Dementia: A Mapping Review of Technological and Nontechnological Interventions.

BACKGROUND AND OBJECTIVES: Informal (or family) caregivers to older adults with Alzheimer's disease or other related dementias (ADRD) could greatly benefit from innovative telecaregiving systems that support caregiving from a distance. The objective of this review is to better understand (a) who is involved in telecaregiving and their experiences; (b) the interventions currently available to support ADRD telecaregiving; and (c) the outcomes measured to assess the effects of ADRD telecaregiving interventions. RESEARCH DESIGN AND METHODS: A mapping review was conducted by systematically searching MEDLINE, CINAHL, Embase, and PsycINFO for all works published in English from 2002 to 2022. References of included publications were searched to identify additional empirical publications for inclusion. RESULTS: Sixty-one publications (describing 48 studies and 5 nonstudy sources) were included in the review. Currently available information on the demographics, experiences, challenges, and benefits of ADRD telecaregivers is summarized. We found that interventions to support telecaregiving could be classified into 7 categories of technological interventions and 3 categories of nontechnological interventions. Empirical studies on ADRD telecaregiving interventions investigated a variety of outcomes, the most prevalent being user experience. DISCUSSION AND IMPLICATIONS: We conclude that (a) the paucity of literature on telecaregiving does not allow for a comprehensive understanding of the needs and day-to-day activities of ADRD telecaregivers; (b) interventions developed to support ADRD telecaregiving may not fully meet the needs of caregivers or care recipients; and (c) there is insufficient rigorous research establishing the effects of telecaregiving interventions on key ADRD-related outcomes.

Physical Artificial Arterial Pulse System for Development and Testing of PPG-Based Sensors.

A physical system to generate a PPG-mimicking signal was designed and validated using everyday low-cost components to aid in medical sensor design. The pulse waveform was created by driving a working fluid into a silicone tube and changing the pressure within it. The corresponding waveform mimics a PPG signal through an artery, is adaptable, and repeatable. The working fluid is interchangeable allowing for change of blood analyte concentrations for development and testing of PPG-based sensors. The system was validated by black ink water compared to water and air compared to water testing to confirm optical transparency of the tube. The produced PPG signal, pulse rate and pressure change were compared to that seen in subjects. Optical transparency for 660 nm - 1550 nm wavelengths of light was validated with the signal, pulse rate and total compliance matching subject data. Thus, the system can mimic arterial pulses, creating a valid PPG signal that can be detected by PPG-based sensors.Clinical Relevance- Provides a low-cost, adaptable, physical PPG signal generator for research and development of optical medical sensor technologies.

Investigation of Narrow-band NIR LED Spectral Response Towards a Non-invasive Glucose Sensor.

Spectroscopy is utilised extensively in medical sensing technology. Typically, hand-held spectroscopy equipment uses miniature narrow-band light emitting diodes (LEDs) and photodiodes to emit and detect light, respectively. Photodiodes typically absorb light across a wide spectra so measurements can be corrupted by surrounding light. LEDs in the visible spectrum have a narrower spectral response and can be used in place of a traditional photodiode. However, the absorption characteristics of near infrared (NIR) spectrum LEDs is unknown. A discrete, low-cost spectrophotometer was designed to assess spectral response for 8 narrow band NIR LEDs. The normalised and raw spectral response determined the optimum detector for 1050 nm - 1300 nm is the 1450 nm LED, and the optimum detector for 1450 nm - 1650 nm emissions is the 1650 nm LED.Clinical relevance - Understanding the spectral response of narrow-band LEDs in the NIR spectrum will aid development of NIR hand-held spectroscopy medical devices.

Technology caregiver intervention for Alzheimer's disease (I-CARE): Feasibility and preliminary efficacy of Brain CareNotes.

BACKGROUND: The primary aim of the current pilot study was to examine enrollment rate, data completion, usability, acceptance and use of a mobile telehealth application, Brain CareNotes. A secondary aim was to estimate the application's effect in reducing caregiver burden and behavioral and psychological symptoms related to dementia (BPSD). METHODS: Patient-caregiver dyads (n = 53) were recruited and randomized to intervention and control groups. Assessment of usability, acceptance, BPSD symptoms, and caregiver burden were collected at baseline, 3- and 6-month follow-up. RESULTS: The enrollment rate was acceptable despite pandemic related challenges (53/60 target recruitment sample). Among randomized individuals, there was a retention rate of 85% and data completion was attained for 81.5% of those allocated to usual care and 88.5% of those allocated to Brain CareNotes. Mean caregiver-reported app usability at 6 months was 72.5 (IQR 70.0-90.0) on the System Usability Scale-considered "Good to Excellent"-and user acceptance was reasonable as indicated by 85%-90% of caregivers reporting they would intend to use the app to some degree in the next 6 months, if able. Regarding intervention effect, although differences in outcome measures between the groups were not statistically significant, compared to baseline, we found a reduction of caregiver burden (NPI-Caregiver Distress) of 1.0 at 3 months and 0.7 at 6 months for those in the intervention group. BPSD (NPI Total Score) was also reduced from baseline by 4.0 at 3 months and by 0.5 at 6 months. CONCLUSIONS: Brain CareNotes is a highly scalable, usable and acceptable mobile caregiver intervention. Future studies should focus on testing Brain CareNotes on a larger sample size to examine efficacy of reducing caregiver burden and BPSD.

Seminal Vesicle Treatment for Localized Prostate Cancer Treated with External Beam Radiotherapy.

This study retrospectively reviewed data from men with localized prostate cancer treated with external beam radiotherapy (EBRT). We identified 359 men with localized prostate cancer treated with curative EBRT at the Cross Cancer Institute between 2010-2011. The volume of seminal vesicles (SVs) treated as well as dose values were extracted. These volumes were compared to gold standard contours drawn by a trained expert based on consensus European Society for Radiotherapy and Oncology (ESTRO) contouring guidelines. Patient and tumor characteristics were extracted for these patients. Memorial Sloan Kettering prostate cancer nomogram was used to assign a predicted risk of SV involvement for each patient based on baseline tumor characteristics. In patients with a predicted risk of SV involvement greater than 15% (n = 184), 86.5% (SD = 18.6) of the base of the SVs were treated with EBRT, compared to 66.7% (SD = 32.6) for patients with a predicted risk of SV involvement less than 15% (n = 175, p < 0.0001). Similarly, the mean percentage of proximal and total SV volumes treated with EBRT was 75.6% (SD = 24.4) and 68.7% (SD = 26.0) for patients with a predicted risk of SV involvement of greater than 15%, compared to 50.3% (SD = 31.0, p < 0.0001) and 41.0% (SD = 27.8, p < 0.0001) for patients with a risk of less than 15%. The results indicate that all parts of the SVs are more likely to be contoured in men with >15% risk of SV involvement than those with <15% risk. However, radiation oncologists still contour a high percentage of SVs in men with <15% risk of SV involvement, suggesting that there may be over-treatment of SVs that increases the risk of rectal or bladder toxicity.

Do Radiation Oncology Residents Have a Preferred Radiation Treatment Planning Review Format?

In an era of increasing virtual communication, we aimed to investigate current formats used by radiation oncology residents for reviewing radiation treatment plans with attendings, preferences for formats, and reasons contributing to preferences. Residents enrolled in Canadian radiation oncology programs received questionnaires examining training level, typical review formats, preferred format, and reasons for preference. Analysis excluded PGY-1s due to insufficient exposure. Fifty-two residents participated. National response rate was 55%. Overall, hybrid review was the most used format (77%). Virtual review was the most preferred format (44%). Preference for virtual review was most common among junior residents (57%), while in-person review was most preferred by senior residents (45.4%). Few residents typically use their preferred format (35%). Reasons for preference varied between groups in convenience (p < 0.01), interactivity (p < 0.01), and teaching quality (p = 0.04). The persistence of e-learning suggests that virtual treatment planning education will continue to some degree. Junior residents prefer virtual review, while a clearly preferred review format was less apparent among senior residents. Preferences are multifactorial, and the trends seen in reasons for preference between formats may reflect advantages inherent to each. Progress is still needed in optimizing treatment planning education, as suggested by few residents using their preferred format. Residents and staff should collectively decide which educational format for treatment planning best meets educational needs.

Structural Optimization of siRNA Conjugates for Albumin Binding Achieves Effective MCL1-Targeted Cancer Therapy.

The high potential for therapeutic application of siRNAs to silence traditionally undruggable oncogenic drivers remains largely untapped due to the challenges of tumor cell delivery. Here, siRNAs were optimized for in situ binding to albumin through C18 lipid modifications to improve pharmacokinetics and tumor delivery. Systematic variation of siRNA conjugates revealed a lead structure with divalent C18 lipids each linked through three repeats of hexaethylene glycol connected by phosphorothioate bonds. Importantly, we discovered that locating the branch site of the divalent lipid structure proximally (adjacent to the RNA) rather than at a more distal site (after the linker segment) promotes association with albumin, while minimizing self-assembly and lipoprotein association. Comparison to higher albumin affinity (diacid) lipid variants and siRNA directly conjugated to albumin underscored the importance of conjugate hydrophobicity and reversibility of albumin binding for siRNA delivery and bioactivity in tumors. The lead conjugate increased tumor siRNA accumulation 12-fold in orthotopic mouse models of triple negative breast cancer over the parent siRNA. When applied for silencing of the anti-apoptotic oncogene MCL-1, this structure achieved approximately 80% MCL1 silencing in orthotopic breast tumors. Furthermore, application of the lead conjugate structure to target MCL1 yielded better survival outcomes in three independent, orthotopic, triple negative breast cancer models than an MCL1 small molecule inhibitor. These studies provide new structure-function insights on optimally leveraging siRNA-lipid conjugate structures that associate in situ with plasma albumin for molecular-targeted cancer therapy.

Rate of Endothelial Cell Loss and Graft Survival in Descemet Membrane Endothelial Keratoplasty in Eyes Requiring a Rebubble.

PURPOSE: We aimed to compare the rate of 6-month endothelial cell loss (ECL) and 6-month graft survival in eyes that did not require a postoperative rebubble with eyes that did require a postoperative rebubble after Descemet membrane endothelial keratoplasty (DMEK) surgery. METHODS: A consecutive series of DMEK surgeries performed from September 2013 to March 2020 was retrospectively analyzed. Eyes that did not require a rebubble for graft detachment were compared with eyes with 1 rebubble and eyes with 2 or more rebubbles for 6-month ECL and graft survival. A subanalysis of the rebubble rate for different indications for transplantation was also performed. RESULTS: One thousand two hundred ninety-eight eyes were included in this study. The 6-month ECL for eyes with no rebubbles, 1 rebubble, and ≥2 rebubbles was 29.3% ± 16.2% (n = 793), 36.4% ± 18.6% (n = 97, P = 0.001), and 50.1% ± 19.6% (n = 28, P < 0.001), respectively. The 6-month graft survival rate for eyes with no rebubbles, 1 rebubble, and ≥2 rebubbles was 99.5%, 97.8% ( P = 0.035), and 81.8% ( P < 0.001), respectively. When compared to the rebubble rate for DMEK for Fuchs dystrophy (156/1165 eyes = 13.4%), the rebubble rates were statistically higher for DMEK for failed penetrating keratoplasty (28.5%, P = 0.021) and pseudophakic bullous keratopathy (28.0%, P = 0.036). CONCLUSIONS: Eyes undergoing any rebubble procedure in the postoperative period after DMEK have an increased risk of endothelial cell loss and graft failure at 6 months postoperative. DMEK in eyes for failed penetrating keratoplasty and failed DMEK had the highest rebubble rate, with the former reaching statistical significance.

Evaluation of parking-related financial toxicity associated with cancer treatments in Western Canada.

INTRODUCTION/BACKGROUND: Patients and their caregivers incur numerous out-of-pocket costs while receiving oncologic treatments. These expenses are often overlooked by clinicians, even in countries with publicly funded healthcare systems. Parking fees are one such category of expenses that contribute to financial toxicity in cancer care. Patients with cancer often have protracted treatment courses, especially if they are receiving external beam radiation therapy. It is not clear if cancer center parking fees influence city-specific indices such as city-specific cost of living. The aim of this study was to evaluate cancer center parking fees in Western Canada and to elucidate any correlation between daily cost of parking and the city-specific indices. METHODS: This was a cross sectional study conducted from February 1st, 2022, to March 1st, 2022. An online search was undertaken to obtain the publicly available parking information for the regional and community cancer centers in the provinces of British Columbia, Alberta, Manitoba, and Saskatchewan. Telephone calls were made with parking offices or switchboards to obtain this information for the cancer centers that did not have online information on parking. Cancer center address transit scores, median city household income, and city-specific cost of living scores were obtained online for the cities where the cancer centers were located. Pearson correlation and a zero-inflated negative binomial model were used for statistical analysis. RESULTS: Data was collected from 115 community and regional cancer centers distributed across the 4 provinces. The median hourly parking fee across all provinces was 2.00 Canadian Dollars (CAD) (Interquartile range (IQR), 0-4.25), whereas the median daily cost of parking was 9.50 CAD (IQR, 0-13.13). The median cancer center address transit score was 41.00 (IQR, 12.00-50.50). There was a statistically significant (p=0.029) positive correlation between the daily cost of parking and city cost of living. The correlation coefficient between the two variables was 0.412. Furthermore, there was a statistically significant (p<0.001) positive correlation between daily cost of parking and cancer center address transit score. The correlation coefficient between the two variables was 0.676. In addition, there was a strong negative correlation between the cancer center address transit score and the presence of free parking with a correlation coefficient of -0.613 (p<0.001). There was a nonsignificant (p=0.88) negative correlation between cost of living and the presence of free parking with a correlation coefficient of -0.028. DISCUSSION: The results of this study demonstrate that daily cost of parking for community and regional cancer centers in Western Canada significantly influences city-specific cost of living and cancer center address transit scores to a varying degree. This demonstrates that the influence of parking fees on patients with cancer is multilayered with significant direct and indirect effects. This can contribute to loss of wage and added financial burden on patients and their caregivers in higher-cost provinces. The presence of free parking at community and regional cancer centers had a statistically significant negative correlation with the cancer center address transit score. This suggests that cities with more free parking also have less robust public transit systems. Conversely, the presence of an extensive public transit system leads to a lower likelihood of free parking being available at cancer centers. CONCLUSION: The presence of a strong public healthcare system does not necessarily address all aspects of cancer-related financial toxicity. There is strong evidence of both positive and negative correlations between city specific indices and cancer center parking fees in Western Canada. Policy makers and stakeholders should be cognizant of this interplay between the various city specific indices and parking fees for patients with cancer. Policies on provincial and federal levels should be implemented to address this increasingly problematic burden on oncologic patients.

Hundred-meter Gb/s deep ultraviolet wireless communications using AlGaN micro-LEDs.

We demonstrate the use of deep ultraviolet (DUV) micro-light-emitting diodes (LEDs) for long-distance line-of-sight optical wireless communications. With a single 285 nm-emitting micro-LED, we have respectively achieved data rates greater than 6.5 Gb/s at a distance of 10 m and 4 Gb/s at 60 m. Moreover, we obtained >1 Gb/s data rates at a distance of 116 m. To our knowledge, these results are the highest data rates at such distances thus far reported using DUV micro-LEDs and the first demonstration of Gb/s communication at >100 m using any micro-LED-based transmitter.

Tumor Volume Predicts for Pathologic Complete Response in Rectal Cancer Patients Treated With Neoadjuvant Chemoradiation.

OBJECTIVES: Nonoperative management (NOM) of locally advanced rectal cancer is an emerging approach allowing patients to preserve their anal sphincter. Identifying clinical factors associated with pathologic complete response (pCR) is essential for physicians and patients considering NOM. MATERIALS AND METHODS: In total, 412 locally advanced rectal cancer patients were included in this retrospective analysis. Tumor volumes were derived from pretreatment MRI. Clinical parameters such as tumor volume, stage, and location were analyzed by univariate and multivariate analysis, against pCR. A receiver operator characteristic curve was generated to identify a tumor volume cut-off with the highest clinically relevant Youden index for predicting pCR. RESULTS: Seventy-five of 412 patients (18%) achieved pCR. A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR. On regression analysis, a tumor volume >37.3 cm 3 was associated with a greater than 78% probability of not achieving pCR. On multivariate analysis, a GTV <37.3 cm 3 [odds ratio (OR)=3.7, P <0.0001] was significantly associated with an increased pCR rate, whereas tumor length > 4.85 cm was associated with pCR on univariate (OR=3.03, P <0.01) but not on multivariate analysis (OR=1.45, P =0.261). Other clinical parameters did not impact pCR rates. CONCLUSIONS: A tumor volume threshold of 37.3 cm 3 was identified as predictive for pCR in locally advanced rectal cancer patients receiving neoadjuvant chemoradiation. Tumors above this volume threshold corresponded to a greater than 78% probability of not achieving pCR. This information will be helpful at diagnosis for clinicians who are considering potential candidates for NOM.

Putative COVID-19 therapies imatinib, lopinavir, ritonavir, and ivermectin cause hair cell damage: A targeted screen in the zebrafish lateral line.

The biomedical community is rapidly developing COVID-19 drugs to bring much-need therapies to market, with over 900 drugs and drug combinations currently in clinical trials. While this pace of drug development is necessary, the risk of producing therapies with significant side-effects is also increased. One likely side-effect of some COVID-19 drugs is hearing loss, yet hearing is not assessed during preclinical development or clinical trials. We used the zebrafish lateral line, an established model for drug-induced sensory hair cell damage, to assess the ototoxic potential of seven drugs in clinical trials for treatment of COVID-19. We found that ivermectin, lopinavir, imatinib, and ritonavir were significantly toxic to lateral line hair cells. By contrast, the approved COVID-19 therapies dexamethasone and remdesivir did not cause damage. We also did not observe damage from the antibiotic azithromycin. Neither lopinavir nor ritonavir altered the number of pre-synaptic ribbons per surviving hair cell, while there was an increase in ribbons following imatinib or ivermectin exposure. Damage from lopinavir, imatinib, and ivermectin was specific to hair cells, with no overall cytotoxicity noted following TUNEL labeling. Ritonavir may be generally cytotoxic, as determined by an increase in the number of TUNEL-positive non-hair cells following ritonavir exposure. Pharmacological inhibition of the mechanotransduction (MET) channel attenuated damage caused by lopinavir and ritonavir but did not alter imatinib or ivermectin toxicity. These results suggest that lopinavir and ritonavir may enter hair cells through the MET channel, similar to known ototoxins such as aminoglycoside antibiotics. Finally, we asked if ivermectin was ototoxic to rats in vivo. While ivermectin is not recommended by the FDA for treating COVID-19, many people have chosen to take ivermectin without a doctor's guidance, often with serious side-effects. Rats received daily subcutaneous injections for 10 days with a clinically relevant ivermectin dose (0.2 mg/kg). In contrast to our zebrafish assays, ivermectin did not cause ototoxicity in rats. Our research suggests that some drugs in clinical trials for COVID-19 may be ototoxic. This work can help identify drugs with the fewest side-effects and determine which therapies warrant audiometric monitoring.

Comprehensive assessment during palliative radiotherapy consultation optimizes supportive care for patients with advanced breast cancer.

PURPOSE: Palliative radiotherapy (PRT) in advanced cancer improves symptom control and quality of life. PRT consultations take place in various clinical settings, including through dedicated rapid access clinics. We examined holistic assessment and PRT delivery by consultation setting. METHODS: We analyzed patients with breast cancer who died (01/04/2013-31/03/2014), after at least one lifetime PRT consultation. Data abstracted included Karnofsky Performance Status (KPS), Edmonton Symptom Assessment System Revised (ESAS-r) ratings, and PRT timelines. Descriptive statistics, t tests of proportions, independent t tests, and chi-square tests were calculated. RESULTS: One hundred thirty patients were assessed for PRT over 224 consults, 28/224 (12.5%) in the rapid access clinic. In non-rapid access versus rapid access visits, KPS was documented in 30.1% versus 89.3%, and medication history in 53.6% versus 96.4%, respectively (both p < 0.0001). Baseline ESAS-r scores were available for 67.9% of rapid access visits, versus no non-rapid access visit. Rapid access consults had a higher proportion of subsequent supportive care referrals (46.4% versus 8.2%; p < 0.0001). Same day PRT start occurred in 37% of rapid access versus 23.4% of non-rapid access visits (p = 0.13). CONCLUSIONS: Assessment for PRT by a dedicated multidisciplinary team provides a comprehensive picture of patient needs and streamlines PRT delivery, essential to personalizing supportive care.

Palliative radiotherapy delivery by a dedicated multidisciplinary team facilitates early integration of palliative care: A secondary analysis of routinely collected health data.

BACKGROUND: Early integration of Specialist Palliative Care (SPC) with oncological care improves quality of life (QOL) of patients with advanced cancer; however, patients tend to access SPC late in their disease trajectory, if at all. Routine referral of all patients to SPC would quickly overwhelm available resources, suggesting a need for widespread accessibility of generalist PC competencies. This has been increasingly facilitated by dedicated palliative radiotherapy (PRT) clinics, such as the multidisciplinary Palliative Radiation Oncology (PRO) program at the Cross Cancer Institute (CCI). Our objectives were to estimate the proportion of patients dying with breast cancer seen in consultation for PRT, and the interaction between PRT delivery and SPC referral. METHODS: This secondary analysis of routinely collected health data examined female adults with breast cancer who died between 04/01/2013 and 03/31/2014, and had advanced disease while under the care of a CCI oncologist. Alberta Cancer Registry, electronic medical records, and Edmonton Zone Palliative Care Program data were linked. During the study period, referrals for SPC, and setting of assessment for PRT, were at the attending physicians' discretion. Clinical data were abstracted including summaries of intervals between PRT and SPC consultations, as well as from consults to death. Kaplan-Meier survival estimates, independent samples median tests, t tests of proportions, independent t tests and Chi-square tests compared groups. RESULTS: Of 194 patients, median age at cancer diagnosis was 59 years (range 24-95yrs), median one-way distance from the CCI was 18.8km, and overall median survival (MS) was 4.4 years. 130/194 (67.0%) and 110/194 (56.7%) were assessed for PRT and by SPC respectively; 22/194 (11.3%) saw neither prior to death. Median time between first PRT consultation and death was 11.7 months (interquartile range 3.7-22.2 mos). Median time between first SPC consult and death was 2.9 mos (IQR 1-6.2 mos). 65.6% of those who never had PRT ultimately required SPC involvement, versus 52.3% of those receiving PRT. Of the 68/130 who had both, 91.2% were seen for PRT first, a median of 7.9 mos prior to seeing SPC. Patients who had SPC consultation without previous PRT were seen by PC a median 1.5 mos prior to death (IQR 0.6-4.9 mos). Patients seen for PRT outside of the PRO clinic had SPC consultation a median of 3.3 mos before death (IQR 1.2-6.2 mos), versus those seen by the PRO clinic team, who were referred a median of 6.2 mos prior (IQR 2.4-8.1 mos). CONCLUSIONS: Fewer advanced breast cancer patients who received PRT ultimately required SPC consultation, but those who did were referred earlier in their disease course, especially if PRT assessment and delivery had taken place in the setting of a dedicated multidisciplinary team.

Assessment of Physiological Responses During Field Science Task Performance: Feasibility and Future Needs.

OBJECTIVE: By understanding the physiological demands of different types of tasks that will be performed during extravehicular activity (EVA) on Mars, human performance safety risks can be mitigated. In addition, such understanding can assist in planning EVAs with an appropriate balance of human health and safety with scientific mission return. BACKGROUND: This paper describes the results of a study of technical feasibility performed within a Mars human research analog, with participants conducting scientifically relevant planetary science sample analysis and return tasks in two distinct field locations. METHODS: The authors collected heart rate, respiration rate, and heart rate variability (HRV) data, using commercial off-the-shelf hardware and software from study participants as they performed field science tasks within a concept of operations for a Mars science return human expedition mission. These data were remotely monitored, shared in real time, and later analyzed to identify different responses to different tasks in order to determine if there were any predictable or consistent patterns among participants. RESULTS: It was ultimately determined that, while differences exist between responses to tasks, they are highly subject to multiple sources of individual variability, dynamics of evolving field science tasks, and demands of a demanding physical environment. Further, distributional analyses of participants do not support parametric statistical analysis techniques. CONCLUSION: The authors conclude that the physiology of individual astronauts should be extensively studied and modeled to support individualized automated monitoring tools for each crew member that is sent to Mars. Application: Physiological monitoring for specialized populations will require significant individual-level analysis, baselining, and bootstrap statistical methods to enable appropriate human performance determinations.

Exploiting the fundamentals of biological organization for the advancement of biofabrication.

The field of biofabrication continues to progress, offering higher levels of spatial control, reproducibility, and functionality. However, we remain far from recapitulating what nature has achieved. Biological systems such as tissues and organs are assembled from the bottom-up through coordinated supramolecular and cellular processes that result in their remarkable structures and functionalities. In this perspective, we propose that incorporating such biological assembling mechanisms within fabrication techniques, offers an opportunity to push the boundaries of biofabrication. We dissect these mechanisms into distinct biological organization principles (BOPs) including self-assembly, compartmentalization, diffusion-reaction, disorder-to-order transitions, and out-of-equilibrium processes. We highlight recent work demonstrating the viability and potential of these approaches to enhance scalability, reproducibility, vascularization, and biomimicry; as well as current challenges to overcome.

Society for Palliative Radiation Oncology: Report from the Ninth Annual Meeting (2022).

The Society for Palliative Radiation Oncology (SPRO) is an international group of clinicians whose primary aim is to advance the field of palliative radiation oncology by promoting evidence-based palliative radiation therapy and excellence in primary palliative care through research, education, collaboration, and patient advocacy. SPRO held its 9th Annual Meeting on October 23, 2022 in association with the American Society for Radiation Oncology (ASTRO) 64th Annual Meeting. Accomplishments and goals from the previous year were discussed and newly appointed officers were announced. Dr. Dirk Rades from the University of Lubeck in Germany gave the keynote address, reviewing critical trials and evidence for the use of stereotactic body radiotherapy (SBRT) in the palliative and oligometastatic settings. Recipients of the Lifetime Service Award and the Rising Star Award were announced and presented. This Meeting Report summarizes the proceedings of SPRO's 9th Annual Meeting.