A phase II study of potentiation of pembrolizumab with binimetinib and bevacizumab in refractory microsatellite stable colorectal cancer.

PURPOSE: In this single-institution phase II investigator-initiated study we assessed the ability of MAPK and VEGF pathway blockade to overcome resistance to immunotherapy in microsatellite stable metastatic colorectal cancer (MSS mCRC). PATIENTS AND METHODS: Patients with MSS, BRAF wild-type mCRC who progressed on ≥2 prior lines of therapy received pembrolizumab, binimetinib, and bevacizumab until disease progression or unacceptable toxicity. After a safety run-in, patients were randomized to a 7-day run-in of binimetinib or simultaneous initiation of all study drugs, to explore whether MEK inhibition may increase tumor immunogenicity. The primary endpoint was objective response rate in all patients combined (ORR, by RECIST v1.1). RESULTS: Fifty patients received study drug treatment; 54% were male with median age 55 years (range 31-79). The primary endpoint, ORR, was 12.0% (95% confidence interval [CI] 4.5-24.3%), which was not statistically different than the historical control data of 5% (p=0.038, exceeding pre-specified threshold of 0.025). The disease control rate was 70.0% (95% CI 55.4-82.1%), median progression-free survival 5.9 months (95% CI 4.2-8.7 months), and median overall survival 9.3 months (95% CI 6.7-12.2 months). No difference in efficacy was observed between the randomized cohorts. Grade 3 and 4 adverse events were observed in 56% and 8% of patients, respectively; the most common were rash (12%) and increased aspartate aminotransferase (12%). CONCLUSION: Pembrolizumab, binimetinib, and bevacizumab failed to meet its primary endpoint of higher ORR compared to historical control data, demonstrated a high disease control rate, and demonstrated acceptable tolerability in refractory MSS mCRC.

A Phase Ib Expansion Cohort Evaluating Aurora A Kinase Inhibitor Alisertib and Dual TORC1/2 Inhibitor Sapanisertib in Patients with Advanced Solid Tumors.

BACKGROUND: This study further evaluated the safety and efficacy of the combination of alisertib and sapanisertib in an expansion cohort of patients, including a subset of patients with refractory pancreatic adenocarcinoma, with further evaluation of the pharmacodynamic characteristics of combination therapy. METHODS: Twenty patients with refractory solid tumors and 11 patients with pancreatic adenocarcinoma were treated at the recommended phase 2 dose of alisertib and sapanisertib. Adverse events and disease response were assessed. Patients in the expansion cohort were treated with a 7-day lead-in of either alisertib or sapanisertib prior to combination therapy, with tumor tissue biopsy and serial functional imaging performed for correlative analysis. RESULTS: Toxicity across treatment groups was overall similar to prior studies. One partial response to treatment was observed in a patient with ER positive breast cancer, and a patient with pancreatic cancer experienced prolonged stable disease. In an additional cohort of pancreatic cancer patients, treatment response was modest. Correlative analysis revealed variability in markers of apoptosis and immune cell infiltrate according to lead-in therapy and response. CONCLUSIONS: Dual targeting of Aurora A kinase and mTOR resulted in marginal clinical benefit in a population of patients with refractory solid tumors, including pancreatic adenocarcinoma, though individual patients experienced significant response to therapy. Correlatives indicate apoptotic response and tumor immune cell infiltrate may affect clinical outcomes.

Higher testosterone is associated with higher HDL-cholesterol and lower triglyceride concentrations in older women: an observational study.

OBJECTIVE: This study aimed to determine whether concentrations of testosterone and its main precursor after menopause, dehydroepiandrosterone (DHEA), are associated with lipoproteins and other lipids in community-dwelling older women. METHODS: The Sex Hormones in Older Women (SHOW) study was an observational study of 6358 Australian women, aged at least 70 years, with no prior major adverse cardiovascular event who had sex hormones measured by liquid chromatography-tandem mass spectrometry. Associations between hormones and lipids were examined using multilinear regression adjusted for potential confounders. RESULTS: The cross-sectional analyses included 3231 participants, median age 74.0 (interquartile range 71.7-77.9) years. Compared with concentrations in the lowest quartile (Q1), testosterone concentrations in the highest quartiles (Q3 and Q4) were positively associated with high-density lipoprotein cholesterol (HDL-C) (p = 0.002 and p < 0.001, respectively) while Q4 testosterone concentrations were positively associated with total cholesterol (p = 0.038). Q2, Q3 and Q4 testosterone concentrations were significantly inversely associated with triglycerides (TG) (p = 0.024, p = 0.003 and p < 0.001, respectively). For DHEA, Q4 concentrations was positively associated with non-HDL-C (p = 0.024). CONCLUSIONS: In older women, higher endogenous testosterone concentrations are significantly associated with higher HDL-C and lower TG, indicating a less atherogenic profile. These findings suggest a neutral, or potentially protective, cardiovascular disease effect of testosterone in older women.

Two-year outcomes of radiofrequency device treatment of the nasal valve for nasal airway obstruction.

BACKGROUND: Temperature-controlled radiofrequency (TCRF) device treatment of nasal valve dysfunction (NVD) was superior to a sham procedure control in reducing the symptoms of nasal airway obstruction (NAO) in this randomised controlled trial (RCT). METHODOLOGY: Two-year outcomes for 108 patients actively treated in a prospective, multicenter, patient-blinded RCT were used to determine treatment effect durability and changes in medication/nasal dilator usage. A responder was defined as ≥ 20 reduction in NOSE score or 1 reduction in severity class. RESULTS: The mean (SD) age of patients was 48.5 (12.3) years; 66 (61.1%) women. Baseline NOSE score was 76.3. The 2-year responder rate was 90.4% and NOSE score treatment effect was -41.7; 54.7% improvement. Of 57 patients using medications/nasal dilators at baseline, 45 (78.9%) either stopped all use (33.3%) or stopped/decreased (45.6%) use in >=1 class at 2 years. Concurrent septal deviation, septal swell body, or turbinate enlargement did not significantly affect the odds of exhibiting a NOSE score of ≤ 25 at 2 years. CONCLUSIONS: TCRF device treatment of NVD resulted in significant and sustained improvements in the symptoms of NAO at 2 years, accompanied by a substantial reduction in medication/nasal dilator use.

One Anastomosis Gastric Bypass as Revisional Surgery Following Sleeve Gastrectomy: A Systematic Review and Meta-Analysis.

BACKGROUND: Although sleeve gastrectomy (SG) is the most performed metabolic and bariatric surgery (MBS) worldwide, some patients require conversional procedures due to weight recurrence or late complications. Recently, one-anastomosis gastric bypass (OAGB) gained popularity as a viable option to address those problems. The aim of this meta-analysis is to assess the safety and efficacy of conversional OAGB after primary SG in the management of patients with obesity. METHODS: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to February 2023 by two independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42023403528). RESULTS: From 1,117 studies screened, twenty studies met the eligibility criteria, with a total of 1,057 patients with obesity undergoing conversional OAGB after primary SG. The mean age ranged from 28.2 to 49.5 years, and 744 patients (75.2%) were women. At one year after revisional OAGB, the pooled mean percent excess weight loss (%EWL) was 65.2% (95%CI: 56.9, 73.4, I2 = 97%). The pooled mean %EWL after conversional OAGB was 71.1% (95%CI: 62.2, 80.0, I2 = 90%) at two years and 71.6% (95%CI: 61.0, 82.2, I2 = 50%) at five years. Additionally, resolution rates of diabetes and hypertension were 65.4% (95%CI: 0.522, 0.785, I2 = 65%) and 58.9% (95%CI: 0.415, 0.762, I2 = 89%), respectively. CONCLUSIONS: Our meta-analysis demonstrated OAGB as an effective conversional procedure after primary SG in terms of weight loss and obesity-associated medical problems for selected patients. Despite the promising results, further randomized controlled studies with larger sample sizes and more extended follow-up periods are necessary to determine if the OAGB is the best conversional surgery after SG.

Testosterone and the heart: friend or foe?

Cardiovascular disease (CVD) is the leading cause of death in women aged 65 years and older. Sex hormones have been implicated as having a critical role in the evolution of CVD, with the focus mainly on estrogens in women. Available data also indicate that low testosterone blood levels may be detrimental to cardiovascular function in women. At blood concentrations considered normal for premenopausal women, testosterone has favorable effects on blood vessel function (relaxation and contraction), much of which is determined by the endothelial cells that line the inside of blood vessels. Testosterone enhances endothelium-dependent and independent brachial artery vasodilation and has an acute systolic blood pressure-lowering effect in postmenopausal women. Advantageous effects of testosterone in animal models have been seen for myocardial function and cardiac electrical signaling. Human data are mainly limited to observational and mechanistic studies, which mostly demonstrate beneficial effects of testosterone on cardiovascular health. Few studies of testosterone use in women, with cardiovascular endpoints as primary outcomes, have been published.

Evaluation of Long-Term Nutrition Outcomes After Duodenal Switch: A Systematic Review and Meta-Analysis.

BACKGROUND: Biliopancreatic diversion with duodenal switch (BPD-DS) is the most effective and durable metabolic and bariatric surgery to achieve a target weight loss. However, many surgeons are hesitant to adopt BPD-DS due to a lack of training, technical complexity, and long-term nutrition deficiencies. This meta-analysis aimed to investigate long-term nutrition outcomes after primary BPD-DS in the management of obesity. METHODS: Cochrane, Embase, PubMed, Scopus, and Web of Science were searched for articles from their inception to February 2023 by 2 independent reviewers using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) system. The review was registered prospectively with PROSPERO (CRD42023391316). RESULTS: From 834 studies screened, 8 studies met the eligibility criteria, with a total of 3443 patients with obesity undergoing primary BPD-DS. At long-term follow-up (≥5 years), 25.4% of patients had vitamin A deficiency (95% CI: -.012, .520, I2 = 94%), and 57.3% had vitamin D deficiency (95% CI: .059, 1.086, I2 = 86%). Calcium deficiency was observed in 125 patients (22.2%, 95% CI: .061, .383, I2 = 97%), and 69.7% had an abnormal parathyroid hormone level (95% CI: .548, .847, I2 = 78%). Ferritin level was abnormal in 30 patients (29.0%, 95% CI: .099, .481, I2 = 79%). CONCLUSIONS: Despite displaying comparable nutrition-related outcomes to mid-term follow-up, our study demonstrated that BPD-DS could result in a high level of long-term nutrition deficiency after BPD-DS for selected patients. However, further randomized controlled studies with standardized supplementation regimens and improvement in compliance are necessary to evaluate and prevent long-term nutritional deficiencies after BPD-DS.

Volumetric changes in post hemiglossectomy reconstruction with anterolateral thigh free flap versus radial forearm free flap.

The volume of the reconstructed tongue is considered a critical factor for tongue function. Studies investigating the difference in volume loss between the anterolateral thigh free flap (ALTF) and radial forearm free flap (RFFF) used in reconstruction of the tongue after hemiglossectomy are lacking. The aim of this study was to determine whether there is a significant difference in shrinkage between these two flaps. This was a retrospective study of all patients treated for tongue cancer by hemiglossectomy who underwent either ALTF or RFFF reconstruction at the University of Florida College of Medicine between January 2018 and April 2022. Computed tomography scans were used to measure the volumetric changes in the ALTF and RFFF at two time points over a 6-month period. Of the 85 patients assessed, 10 fulfilled the inclusion criteria: five were reconstructed with an ALTF and five with a RFFF. All underwent adjuvant radiotherapy. The mean ALTF percentage shrinkage was 39.6% ± 3.9%, while for the RFFF it was 51.1% ± 6.2% (P = 0.008). Therefore, it is recommended that the difference in volume loss between the two flaps is taken into consideration. It is suggested that in hemiglossectomy cases, the ALTF is made 1.4 times larger than the defect, while the RFFF is made 1.5 times larger.

Can We Miniaturize CT Technology for a Successful Mobile Stroke Unit Roll-Out?

Mortality from stroke remains high in Australia, especially for patients located outside the metropolitan cities. This is because they have limited access to specialized stroke facilities for optimal stroke treatment. Mobile stroke units have the capability to take CT scanners out to the patient however current CT commercial scanner designs are large and heavy. As such, this paper aims to design and develop a lightweight CT scanner for use in a mobile stroke unit (either road-based or air-based ambulance) to bring healthcare solution to patients in the rural and remote areas. We used the engineering design optimization approach to redesign and reduce the weight of the existing CT scanner with without compromised it structural performance. We managed to reduce the weight the CT scanner by three-fold while reducing design costs by allowing numerous simulations to be performed using computer software to achieve our design goals. The results are not only useful to optimize CT scanner structure to retrofit on a mobile stroke unit, but also bring the medical device solution to the market and support scalable solution to the larger community. Such an advance will allow for improved equity in healthcare whereby patients can be treated irrespective of location.

The 2023 Practitioner's Toolkit for Managing Menopause.

OBJECTIVE: The Practitioner's Toolkit for Managing the Menopause, developed in 2014, provided an accessible desk-top tool for health-care practitioners caring for women at midlife. To ensure the Toolkit algorithms and supporting information reflect current best practice, the Toolkit has been revised in accordance with the published literature. METHODS: A systematic search for guidelines, position and consensus statements pertaining to the menopause and published after 2014 was undertaken, and key recommendations extracted from the Clinical Practice Guidelines determined to be the most robust by formal evaluation. The peer-reviewed literature was further searched for identified information gaps. RESULTS: The revised Toolkit provides algorithms that guide the clinical assessment and care of women relevant to menopause. Included are the reasons why women present, information that should be ascertained, issues that may influence shared decision-making and algorithms that assist with determination of menopausal status, menopause hormone therapy (MHT) and non-hormonal treatment options for symptom relief. As clear guidelines regarding when MHT might be indicated to prevent bone loss and subsequent osteoporosis in asymptomatic women were found to be lacking, the Toolkit has been expanded to support shared decision-making regarding bone health. CONCLUSIONS: The 2023 Toolkit and supporting document provide accessible desk-top information to support health-care providers caring for women at midlife.The Toolkit has been endorsed by the International Menopause Society, Australasian Menopause Society, British Menopause Society, Endocrine Society of Australia and Jean hailes for Women's Health.

Biosorption of rare earth elements from luminophores by G. sulphuraria (Cyanidiophytina, Rhodophyta).

Lanthanides are indispensable constituents of modern technologies and are often challenging to acquire from natural resources. The demand for REEs is so high that there is a clear need to develop efficient and eco-friendly recycling methods. In the present study, freeze-dried biomass of the polyextremophile Galdieria sulphuraria was employed to recover REEs from spent fluorescent lamps (FL) luminophores by pretreating the freeze-dried biomass with an acid solution to favour ion exchange and enhance the binding sites on the cell surface available for the metal ions. Lanthanides were extracted from the luminophores using sulfuric acid solutions according to standardised procedures, and the effect of biosorbent dosage (0.5-5 mg/ml) and biosorption time (5-60 min) were evaluated. The content of individual REEs in the luminophores and the resulting algal biomass were determined using inductively coupled plasma mass spectrometry (ICP-MS). The most abundant REE in the luminophores was yttrium (287.42 mg/g dm, 91.60% of all REEs), followed by europium (20.98 mg/g, 6.69%); cerium, gadolinium, terbium and lanthanum was in trace. The best biosorption performances were achieved after 5 min and at the lowest biosorbent dosage (0.5 mg/mL). The highest total metal amount corresponded to 41.61 mg/g dried mass, and yttrium was the most adsorbed metal (34.59 mg/g dm, 82.88%), followed by cerium (4.01 mg/g); all other metals were less than 2 mg/g. The rapidity of the biosorption process and the low biosorbent dosage required confirmed this microalga as a promising material for creating an eco-sustainable protocol for recycling REEs.

The association between gut microbiome and growth in infants with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF. METHODS: Infants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups. RESULTS: Infants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing. CONCLUSIONS: In infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation.

Identification of candidate novel production variants on the Bos taurus chromosome X.

Chromosome X is often excluded from bovine genetic studies due to complications caused by the sex specific nature of the chromosome. As chromosome X is the second largest cattle chromosome and makes up approximately 6% of the female genome, finding ways to include chromosome X in dairy genetic studies is important. Using female animals and treating chromosome X as an autosome, we performed X chromosome inclusive genome-wide association studies in the selective breeding environment of the New Zealand dairy industry, aiming to identify chromosome X variants associated with milk production traits. We report on the findings of these genome-wide association studies and their potential effect within the dairy industry. We identify missense mutations in the MOSPD1 and CCDC160 genes that are associated with decreased milk volume and protein production and increased fat production. Both of these mutations are exonic SNP that are more prevalent in the Jersey breed than in Holstein-Friesians. Of the 2 candidates proposed it is likely that only one is causal, though we have not been able to identify which is more likely.

The Rate of Medial Ulnar Collateral Ligament Repair Is Increasing While Reconstruction Remains the Most Common Procedure Overall Among Early-Career Orthopaedic Surgeons.

Purpose: To determine the practice patterns and complication rates in medial ulnar collateral ligament (MUCL) repair versus reconstruction procedures performed by early-career orthopaedic surgeons each year between 2010 and 2020, stratified by fellowship training and concomitant procedures performed, during their 6-month American Board of Orthopaedic Surgery (ABOS) Case List collection period. Methods: The ABOS database was queried for MUCL reconstruction and MUCL repair procedures reported by ABOS Part II Oral Examination examinees from 2010 to 2020. Surgeon fellowship training background, patient demographics, procedural diagnosis codes, complications, and concomitant procedures were recorded for each case. Differences between overall procedure rates and the associated complications reported were examined. Data regarding the specific injury pathology and other patient-specific characteristics for each case were not available. Results: In total, 187 primary procedures performed to address isolated MUCL injuries were reported. Of those, 83% (n = 155) were reconstructions and 17% (n = 32) were repairs. The annual percentage of MUCL repair increased from 10% (1/10) in 2010 to 38% (8/21) in 2020 (linear regression; R2 = 0.56, P < .05). The cumulative complication rate for MUCL reconstruction (11.6%) was significantly lower than for MUCL repair (25%) from 2010 to 2020 (P < .05). This remained true among subsets of cases from Orthopaedic Sports Medicine, Shoulder & Elbow, and or Hand Surgery fellowship-trained examinees, although only statistically significant in the Hand Surgery subset. Reported complication rates were not significantly different among cases in which concurrent ulnar nerve neuroplasty and/or transposition or concurrent elbow arthroscopy were performed. Conclusions: Among cases reported by ABOS Part II Oral Examination examinees from 2010 to 2020, there was an increasing rate of MUCL repair whereas MUCL reconstruction remained more common overall. Interestingly, the overall complication rates were significantly lower for MUCL reconstruction than for MUCL repair both in isolation and when concurrent procedures were performed. Level of Evidence: Level III, retrospective cohort study.

Extended postoperative venous thromboembolism prophylaxis after bariatric surgery: a comparison of existing risk-stratification tools and 5-year MBSAQIP analysis.

BACKGROUND: Venous thromboembolism (VTE) is a leading cause of 30-day mortality after metabolic and bariatric surgery (MBS). Multiple predictive tools exist for VTE risk assessment and extended VTE chemoprophylaxis determination. OBJECTIVE: To review existing risk-stratification tools and compare their predictive abilities. SETTING: MBSAQIP database. METHODS: Retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was performed (2015-2019) for primary minimally invasive MBS cases. VTE clinical factors and risk-assessment tools were evaluated: body mass index threshold of 50 kg/m2, Caprini risk-assessment model, and 3 bariatric-specific tools: the Cleveland Clinic VTE risk tool, the Michigan Bariatric Surgery Collaborative tool, and BariClot. MBS patients were deemed high risk based on criteria from each tool and further assessed for sensitivity, specificity, and positive predictive value. RESULTS: Overall, 709,304 patients were identified with a .37% VTE rate. Bariatric-specific tools included multiple predictors: procedure, age, race, gender, operative time, length of stay, heart failure, and dyspnea at rest; operative time was the only variable common to all. The body mass index cutoff and Caprini risk-assessment model had higher sensitivity but lower specificity when compared with the Michigan Bariatric Surgery Collaborative and BariClot tools. While the sensitivity of the tools varied widely and was overall low, the Cleveland Clinic tool had the highest sensitivity. The bariatric-specific tools would have recommended extended prophylaxis for 1.1%-15.6% of patients. CONCLUSIONS: Existing MBS VTE risk-assessment tools differ widely for inclusion variables, high-risk definition, and predictive performance. Further research and registry inclusion of all significant risk factors are needed to determine the optimal risk-stratified approach for predicting VTE events and determining the need for extended prophylaxis.

Utilizing Simulation to Evaluate Robotic Skill Acquisition and Learning Decay.

BACKGROUND: We aim to evaluate how new robotic skills are acquired and retained by having participants train and retest using exercises on the robotic platform. We hypothesized that participants with a 3-month break from the robotic platform will have less learning decay and increased retention compared with those with a 6-month break. METHODS: This was a prospective randomized trial in which participants voluntarily enrolled and completed an initial training phase to reach proficiency in 9 robot simulator exercises. They were then instructed to refrain from practicing until they retested either 3 or 6 months later. This study was completed at an academic medical center within the general surgery department. Participants were medical students, and junior-level residents with minimal experience in robotic surgery were enrolled. A total of 27 enrolled, and 13 participants completed the study due to attrition. RESULTS: Overall, intragroup analysis revealed that participants performed better in their retest phase compared with their initial training in terms of attempts to reach proficiency, time for completion, penalty score, and overall score. Specifically, during the first attempt in the retesting phase, the 3-month group did not deviate far from their final attempt in the training phase, whereas the 6-month group experienced significantly worse time to complete and overall score in interrupted suturing {[-4 (-18 to 20) seconds vs. 109 (55 to 118) seconds, P =0.02] [-1.3 (-8 to 1.9) vs. -18.9 (-19.5 to (-15.0)], P =0.04} and 3-arm relay {[3 (-4 to 23) seconds vs. 43 (30 to 50) seconds, P =0.02] [0.4 (-4.6 to 3.1) vs. -24.8 (-30.6 to (-20.3)], P =0.01] exercises. In addition, the 6-month group had a significant increase in penalty score in retesting compared with the 3-month group, which performed similarly to their training phase [3.3 (2.7 to 3.3) vs. 0 (-0.8 to 1.7), P =0.03]. CONCLUSIONS: This study identified statistically significant differences in learning decay, skills retention, and proficiency between 3-month and 6-month retesting intervals on a robotic simulation platform.

Singlet Molecular Oxygen: from COIL Lasers to Photodynamic Cancer Therapy.

Translation of experimental techniques from one scientific discipline to another is often difficult but rewarding. Knowledge gained from the new area can lead to long lasting and fruitful collaborations with concomitant development of new ideas and studies. In this Review Article, we describe how early work on the chemically pumped atomic iodine laser (COIL) led to the development of a key diagnostic for a promising cancer treatment known as photodynamic therapy (PDT). The highly metastable excited state of molecular oxygen, a1Δg, also known as singlet oxygen, is the link between these disparate fields. It powers the COIL laser and is the active species that kills cancer cells during PDT. We describe the fundamentals of both COIL and PDT and trace the development path of an ultrasensitive dosimeter for singlet oxygen. The path from COIL lasers to cancer research was relatively long and required medical and engineering expertise from numerous collaborations. As we show below, the knowledge gained in the COIL research, combined with these extensive collaborations, has resulted in our being able to show a strong correlation between cancer cell death and the singlet oxygen measured during PDT treatments of mice. This progress is a key step in the eventual development of a singlet oxygen dosimeter that could be used to guide PDT treatments and improve outcomes.

If you build it, will they come? Is test site availability a root cause of geographic disparities in COVID-19 testing?

OBJECTIVES: The purpose of this study was to examine the relationship between test site availability and testing rate within the context of social determinants of health. STUDY DESIGN: A retrospective ecological investigation was conducted using statewide COVID-19 testing data between March 2020 and December 2021. METHODS: Ordinary least squares and geographically weighted regression were used to estimate state and ZIP code level associations between testing rate and testing sites per capita, adjusting for neighbourhood-level confounders. RESULTS: The findings indicate that site availability is positively associated with the ZIP code level testing rate and that this association is amplified in communities of greater economic deprivation. In addition, economic deprivation is a key factor for consideration when examining ethnic differences in testing in medically underserved states. CONCLUSION: The study findings could be used to guide the delivery of testing facilities in resource-constrained states.