Land cover changes across Greenland dominated by a doubling of vegetation in three decades.

Land cover responses to climate change must be quantified for understanding Arctic climate, managing Arctic water resources, maintaining the health and livelihoods of Arctic societies and for sustainable economic development. This need is especially pressing in Greenland, where climate changes are amongst the most pronounced of anywhere in the Arctic. Ice loss from the Greenland Ice Sheet and from glaciers and ice caps has increased since the 1980s and consequently the proglacial parts of Greenland have expanded rapidly. Here we determine proglacial land cover changes at 30 m spatial resolution across Greenland during the last three decades. Besides the vastly decreased ice cover (- 28,707 km2 ± 9767 km2), we find a doubling in total areal coverage of vegetation (111% ± 13%), a quadrupling in wetlands coverage (380% ± 29%), increased meltwater (15% ± 15%), decreased bare bedrock (- 16% ± 4%) and increased coverage of fine unconsolidated sediment (4% ± 13%). We identify that land cover change is strongly associated with the difference in the number of positive degree days, especially above 6 °C between the 1980s and the present day. Contrastingly, absolute temperature increase has a negligible association with land cover change. We explain that these land cover changes represent local rapid and intense geomorphological activity that has profound consequences for land surface albedo, greenhouse gas emissions, landscape stability and sediment delivery, and biogeochemical processes.

Anterior Cervical Discectomy and Fusion Versus Microendoscopic Posterior Cervical Foraminotomy for Unilateral Cervical Radiculopathy: A 1-Year Cost-Utility Analysis.

BACKGROUND: Anterior cervical discectomy and fusion (ACDF) and posterior cervical foraminotomy (PCF) are the most common surgical approaches for medically refractory cervical radiculopathy. Rigorous cost-effectiveness studies comparing ACDF and PCF are lacking. OBJECTIVE: To assess the cost-utility of ACDF vs PCF performed in the ambulatory surgery center setting for Medicare and privately insured patients at 1-year follow-up. METHODS: A total of 323 patients who underwent 1-level ACDF (201) or PCF (122) at a single ambulatory surgery center were compared. Propensity matching generated 110 pairs (220 patients) for analysis. Demographic data, resource utilization, patient-reported outcome measures, and quality-adjusted life-years were assessed. Direct costs (1-year resource use × unit costs based on Medicare national allowable payment amounts) and indirect costs (missed workdays × average US daily wage) were recorded. Incremental cost-effectiveness ratios were calculated. RESULTS: Perioperative safety, 90-day readmission, and 1-year reoperation rates were similar between groups. Both groups experienced significant improvements in all patient-reported outcome measures at 3 months that was maintained at 12 months. The ACDF cohort had a significantly higher preoperative Neck Disability Index and a significantly greater improvement in health-state utility (ie, quality-adjusted life-years gained) at 12 months. ACDF was associated with significantly higher total costs at 1 year for both Medicare ($11 744) and privately insured ($21 228) patients. The incremental cost-effectiveness ratio for ACDF was $184 654 and $333 774 for Medicare and privately insured patients, respectively, reflecting poor cost-utility. CONCLUSION: Single-level ACDF may not be cost-effective in comparison with PCF for surgical management of unilateral cervical radiculopathy.

Evolution of Accredited Pediatric Cardiac Anesthesiology Fellowship Training in the United States: A Step in the Right Direction.

Pediatric cardiac anesthesiology has developed as a subsubspecialty of anesthesiology over the past 70 years. The evolution of this specialty has led to the establishment in 2005 of a dedicated professional society, the Congenital Cardiac Anesthesia Society (CCAS). By 2010, multiple training pathways for pediatric cardiac anesthesia emerged. Eight programs in the United States offered advanced pediatric cardiac anesthesia with variable duration, ranging from 3 to 12 months. Other programs offered a combined fellow/staff position for 1 year. The need for a standardized training pathway was recognized by the Pediatric Anesthesia Leadership Council (PALC) and CCAS in 2014. Specifically, it was recommended that pediatric cardiac anesthesiology be a second, 12-month advanced fellowship following pediatric anesthesia to acquire skills unique from those acquired during a pediatric anesthesia fellowship. This was reiterated in 2018, when specific pediatric cardiac anesthesia training milestones were developed through consensus by the CCAS leadership. However, given the continuous increasing demand for well-trained pediatric cardiac anesthesiologists, it is essential that a supply of comprehensively trained physicians exists. High-quality training programs are therefore necessary to ensure excellent clinical care and enhanced patient safety. Currently, there are 23 programs offering one or more positions for 1-year pediatric cardiac anesthesia fellowship. Due to the diverse curriculum and evaluation process, formalization of the training with accreditation through the Accreditation Council for Graduate Medical Education (ACGME) was the obvious next step. Initial inquiry started in April 2020. The ACGME recognized pediatric cardiac anesthesia as a subsubspecialty in February 2021. The program requirements and milestones for the 1-year fellowship training were developed in 2021 and 2022. This special article reviews the history of pediatric cardiac anesthesia training, the ACGME application process, the development of program requirements and milestones, and implementation.

Killer to cure: Expression and production costs calculation of tobacco plant-made cancer-immune checkpoint inhibitors.

Immune checkpoint inhibitors (ICIs) have achieved huge clinical success. However, many still have limited response rates, and are prohibitively costly. There is a need for effective and affordable ICIs, as well as local manufacturing capacity to improve accessibility, especially to low-to-middle income countries (LMICs). Here, we have successfully expressed three key ICIs (anti-PD-1 Nivolumab, anti-NKG2A Monalizumab, and anti-LAG-3 Relatimab) transiently in Nicotiana benthamiana and Nicotiana tabacum plants. The ICIs were expressed with a combination of different Fc regions and glycosylation profiles. They were characterized in terms of protein accumulation levels, target cell binding, binding to human neonatal Fc receptors (hFcRn), human complement component C1q (hC1q) and various Fcγ receptors, as well as protein recovery during purification at 100 mg- and kg-scale. It was found that all ICIs bound to the expected target cells. Furthermore, the recovery during purification, as well as Fcγ receptor binding, can be altered depending on the Fc region used and the glycosylation profiles. This opens the possibility of using these two parameters to fine-tune the ICIs for desired effector functions. A scenario-based production cost model was also generated based on two production scenarios in hypothetical high- and low-income countries. We have shown that the product accumulation and recovery of plant production platforms were as competitive as mammalian cell-based platforms. This highlights the potential of plants to deliver ICIs that are more affordable and accessible to a widespread market, including LMICs.

Financial Implications of Enhanced Recovery After Surgery Protocols in Microsurgical Breast Reconstruction.

INTRODUCTION: Surgical advancements in breast reconstruction have allowed a shift toward optimizing patient-reported outcomes and efficiency measures. The enhanced recovery after surgery (ERAS) protocol has been instrumental in improving outcomes, but the effect of these protocols on health care spending has not been examined. This study aims to assess the effect of ERAS protocols on the length of hospital stay and costs associated with microsurgical breast reconstruction. METHODS: In 2018, the authors implemented an ERAS protocol for patients undergoing microsurgical breast reconstruction that included perioperative procedures involving patient education and care. Subjects included patients who underwent deep inferior epigastric perforator flap breast reconstruction at the authors' institution between 2016 and 2019. Data were gathered from the electronic medical record and the hospital system's finance department, and patients were divided into pre-ERAS and ERAS cohorts. A 2-sample t test was used for statistical analysis. RESULTS: The study included 269 patients with no statistically significant differences in demographic data between the cohorts. The average length of hospitalization was 3.46 days for the pre-ERAS group and 2.45 days for the ERAS group ( P = 0.000). In a linear regression, the ERAS protocol predicted a 1.04-day decrease in the length of stay ( P = 0.000). Overall, total direct cost decreased by 7.5% with the ERAS protocol. CONCLUSION: The rising cost of health care presents a challenge for providers to reduce the cost burden placed on our health system while providing the highest-quality care. This study demonstrates that the use of standardized ERAS protocols can achieve this 2-fold goal.

Anterior Cervical Discectomy and Fusion in the Ambulatory Surgery Center Versus Inpatient Setting: One-Year Cost-Utility Analysis.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: Assess the cost-utility of anterior cervical discectomy and fusion (ACDF) performed in the ambulatory surgery center (ASC) versus inpatient hospital setting for Medicare and privately insured patients at one-year follow-up. SUMMARY OF BACKGROUND DATA: Outpatient ACDF has gained popularity due to improved safety and reduced costs. Formal cost-utility studies for ambulatory versus inpatient ACDF are lacking, precluding an accurate assessment of cost-effectiveness. MATERIALS AND METHODS: A total of 6504 patients enrolled in the Quality Outcomes Database (QOD) undergoing one-level to two-level ACDF at a single ASC (520) or the inpatient hospital setting (5984) were compared. Propensity matching generated 748 patients for analysis (374 per cohort). Demographic data, resource utilization, patient-reported outcome measures, and quality-adjusted life-years (QALYs) were assessed. Direct costs (1-year resource use×unit costs based on Medicare national allowable payment amounts) and indirect costs (missed workdays×average US daily wage) were recorded. Incremental cost-effectiveness ratios were calculated. RESULTS: Complication rates and improvements in patient-reported outcome measures and QALYs were similar between groups. Ambulatory ACDF was associated with significantly lower total costs at 1 year for Medicare ($5879.46) and privately insured ($12,873.97) patients, respectively. The incremental cost-effectiveness ratios for inpatient ACDF was $3,674,662 and $8,046,231 for Medicare and privately insured patients, respectively, reflecting unacceptably poor cost-utility. CONCLUSION: Inpatient ACDF is associated with significant increases in total costs compared to the ASC setting without a safety, outcome, or QALY benefit. The ASC setting is a dominant option from a health economy perspective for first-time one-l to two-level ACDF in select patients compared to the inpatient hospital setting.

Demand and cross-price elasticity of cocaine and social contact in a free-operant procedure of nonexclusive choice.

Research examining the social determinants of addiction has advanced significantly with the recent development of preclinical models of drug use and the social environment. These models reveal that drug use and social contact compete with one another for behavioral expression in discrete-trial choice procedures using concurrent schedules of reinforcement. The purpose of this study was to determine how concurrent access to cocaine and a social partner influences the demand for each alternative under free-operant conditions in which responding maintained by each reinforcer is independent and nonexclusive of the other. To this end, male rats were trained under a free-operant, concurrent schedule of reinforcement in which responding maintained by cocaine and access to a social partner operated independently of one another. Measures of economic demand (e.g., intensity, Omax, cross-price elasticity) were determined by manipulating the response requirement (i.e., fixed ratio value) across sessions. Tests were conducted in which the social partner was either treated or not treated with cocaine to determine whether the intoxication state of the partner influenced demand. The principal findings of this study are (1) demand for a cocaine-treated partner is greater than demand for a cocaine-free partner, (2) demand for cocaine is greater in the presence of a cocaine-treated partner than a cocaine-free partner, and (3) concurrent access to cocaine decreases demand for social contact. Notably, measures of cross-price elasticity indicated that social contact is a robust economic substitute for cocaine.

Estimation of the Number of Scans Required per Hard-to-Clean Location and Establishing the Limit of Quantification of a Partial Least Squares Calibration Model When the FTIR Is Used for Pharmaceutical Cleaning Verification.

This study aims to identify two critical components required for pharmaceutical cleaning verification when an FTIR is used: (a) the number of scans required per hard-to-clean location, and (b) the limit of quantification (LOQ) of the FTIR instrument when measuring the surface contamination. The current practice in pharmaceutical manufacturing does not require multiple samples as it is standard practice to collect a single swab sample from a 25 × 25 cm area from a difficult-to-reach area of the manufacturing equipment. However, since the FTIR will only scan a tiny portion of the surface compared to the swab, a sufficient number of samples (data points) are required to provide enough confidence to ensure that the measurement results are close to the true value with a maximum degree of certainty. Similarly, calculating the LOQ for a linear regression could be straightforward. However, complexity arises when the experimental data are complex; in this case, the complexity arises due to the nature of the measurement and the lack of the defined peak in the pre-processed spectra. Therefore, this study uses the practical approach of calculating the sample size and the LOQ.

Trends in treatment costs of U.S. emergency department visits.

BACKGROUND: Spending on emergency department (ED) services in recent years has increased faster than spending in any other area of healthcare. Analyzing growth rates of ED treatment costs by patient and hospital attributes may illuminate ways to reduce overall hospital cost growth. Prior studies have examined changes in ED visit charges and expenditures over time, but little research has focused on changes in ED treatment costs. METHODS: We analyzed trends in ED treatment costs by applying the Healthcare Cost and Utilization Project (HCUP) Cost-to-Charge Ratios for ED Files to the 2012-2019 HCUP Nationwide Emergency Department Sample. Specifically, we estimated treatment cost per ED visit, mean and total costs by patient and hospital characteristics, and compound annual growth rate in costs and patient volumes. RESULTS: During 2012-2019, ED treatment costs increased from $54 billion to $88 billion, a 5.4% annual growth rate-with 4.4 percentage points attributable to higher treatment cost per visit. Growth rates varied by patient and hospital attribute. CONCLUSIONS: By highlighting overall ED cost trends, as well as specific segments of the delivery system with the most rapidly increasing costs, this study provides important information for policymakers and hospital decisionmakers.

Risk Assessment of Norovirus Illness from Consumption of Raw Oysters in the United States and in Canada.

Human norovirus (NoV) is the leading cause of foodborne illness in the United States and Canada. Bivalve molluscan shellfish is one commodity commonly identified as being a vector of NoV. Bivalve molluscan shellfish are grown in waters that may be affected by contamination events, tend to bioaccumulate viruses, and are frequently eaten raw. In an effort to better assess the elements that contribute to potential risk of NoV infection and illness from consumption of bivalve molluscan shellfish, the U.S. Department of Health and Human Services/Food and Drug Administration (FDA), Health Canada (HC), the Canadian Food Inspection Agency (CFIA), and Environment and Climate Change Canada (ECCC) collaborated to conduct a quantitative risk assessment for NoV in bivalve molluscan shellfish, notably oysters. This study describes the model and scenarios developed and results obtained to assess the risk of NoV infection and illness from consumption of raw oysters harvested from a quasi-steady-state situation. Among the many factors that influence the risk of NoV illness for raw oyster consumers, the concentrations of NoV in the influent (raw, untreated) and effluent (treated) of wastewater treatment plants (WWTP) were identified to be the most important. Thus, mitigation and control strategies that limit the influence from human waste (WWTP outfalls) in oyster growing areas have a major influence on the risk of illness from consumption of those oysters.

Cheap and Commonplace: Making the Case for BCG and γδ T Cells in COVID-19.

Antigen-specific vaccines developed for the COVID-19 pandemic demonstrate a remarkable achievement and are currently being used in high income countries with much success. However, new SARS-CoV-2 variants are threatening this success via mutations that lessen the efficacy of antigen-specific antibodies. One simple approach to assisting with this issue is focusing on strategies that build on the non-specific protection afforded by the innate immune response. The BCG vaccine has been shown to provide broad protection beyond tuberculosis disease, including against respiratory viruses, and ongoing studies are investigating its efficacy as a tool against SARS-CoV-2. Gamma delta (γδ) T cells, particularly the Vδ2 subtype, undergo rapid expansion after BCG vaccination due to MHC-independent mechanisms. Consequently, γδ T cells can produce diverse defenses against virally infected cells, including direct cytotoxicity, death receptor ligands, and pro-inflammatory cytokines. They can also assist in stimulating the adaptive immune system. BCG is affordable, commonplace and non-specific, and therefore could be a useful tool to initiate innate protection against new SARS-CoV-2 variants. However, considerations must also be made to BCG vaccine supply and the prioritization of countries where it is most needed to combat tuberculosis first and foremost.

Methods for estimating the cost of treat-and-release emergency department visits.

OBJECTIVE: To evaluate and compare approaches to estimating the service delivery cost of emergency department (ED) visits from total charge data only. DATA SOURCES: The 2013-2017 Healthcare Cost and Utilization Project's (HCUP) State Emergency Department Databases (SEDD) and the Centers for Medicare and Medicaid Services Healthcare Cost Report Information System (HCRIS) public use files. STUDY DESIGN: Compare a baseline approach (requiring cost-center-level charge detail) and four alternative methods (relying on total charges only) for estimating ED visit costs. Estimation errors are calculated after applying each method to a sample of ED visits, treating estimates from the baseline approach as the "true" cost. Performance metrics are calculated at the visit and hospital levels. DATA COLLECTION/EXTRACTION METHODS: The charges, revenue center codes, and patient/hospital characteristics were extracted from the SEDD. Detailed costs and charges were extracted from HCRIS public use files. PRINCIPAL FINDINGS: Baseline ("true") ED visit costs increased from $383 to $420 per visit between 2013 and 2017. Three methods performed comparatively well estimating mean cost per visit. The method using an overall cost-to-charge ratio (CCR) for all ancillary cost centers without regression adjustment (ANC-CCR) performed the worst, overestimating "true" costs by $63-$113 per visit. The other three methods, which used CCRs computed from selected cost centers, exhibited much smaller bias, with two of the methods yielding estimates within $2 of the "true" cost in 2017. Compared with ANC-CCR, the other three methods had more compact estimation error distributions. The estimated mean visit costs from all four methods have relatively small statistical variance, with 95% confidence intervals for mean cost in a hospital with 25,000 ED visits ranging between $4 and $7. CONCLUSIONS: When cost-center-level charge detail for ED visits is unavailable, alternative methods relying on total ED charges can estimate ED service costs for patient and hospital segments.

The long shadow of socioeconomic deprivation over the modern management of acute myeloid leukemia: time to unravel the challenges.

Biological and non-biological variables unrelated to acute myeloid leukemia (AML) preclude standard therapy in many settings, with "real world" patients under-represented in clinical trials and prognostic models. Here, using a case-based format, we illustrate the impact that socioeconomic and anthropogeographical constraints can have on optimally managing AML in 4 different healthcare systems. The granular details provided, emphasize the need for the development and targeting of socioeconomic interventions that are commensurate with the changing landscape of AML therapeutics, in order to avoid worsening the disparity in outcomes between patients with biologically similar disease.

Metabolic Scar Assessment with18F-FDG PET: Correlation to Ischemic Ventricular Tachycardia Substrate and Successful Ablation Sites.

The functional and molecular imaging characteristics of ischemic ventricular tachycardia (VT) substrate are incompletely understood. Our objective was to compare regional 18F-FDG PET tracer uptake with detailed electroanatomic maps (EAMs) in a more extensive series of postinfarction VT patients to define the metabolic properties of VT substrate and successful ablation sites. Methods: Three-dimensional (3D) metabolic left ventricular reconstructions were created from perfusion-normalized 18F-FDG PET images in consecutive patients undergoing VT ablation. PET defects were classified as severe (defined as <50% uptake) or moderate (defined as 50%-70% uptake), as referenced to the maximal 17-segment uptake. Color-coded PET scar reconstructions were coregistered with corresponding high-resolution 3D EAMs, which were classified as indicating dense scarring (defined as voltage < 0.5 mV), normal myocardium (defined as voltage > 1.5 mV), or border zones (defined as voltage of 0.5-1.5 mV). Results: All 56 patients had ischemic cardiomyopathy (ejection fraction, 29% ± 12%). Severe PET defects were larger than dense scarring, at 63.0 ± 48.4 cm2 versus 13.8 ± 33.1 cm2 (P < 0.001). Similarly, moderate/severe PET defects (≤70%) were larger than areas with abnormal voltage (≤1.5 mV) measuring 105.1 ± 67.2 cm2 versus 56.2 ± 62.6 cm2 (P < 0.001). Analysis of bipolar voltage (23,389 mapping points) showed decreased voltage among severe PET defects (n = 10,364; 0.5 ± 0.3 mV) and moderate PET defects (n = 5,243; 1.5 ± 0.9 mV, P < 0.01), with normal voltage among normal PET areas (>70% uptake) (n = 7,782, 3.2 ± 1.3 mV, P < 0.001). Eighty-eight percent of VT channel or exit sites (n = 44) were metabolically abnormal (severe PET defect, 78%; moderate PET defect, 10%), whereas 12% (n = 6) were in PET-normal areas. Metabolic channels (n = 26) existed in 45% (n = 25) of patients, with an average length and width of 17.6 ± 12.5 mm and 10.3 ± 4.2 mm, respectively. Metabolic channels were oriented predominantly in the apex or base (86%), harboring VT channel or exit sites in 31%. Metabolic rapid-transition areas (>50% change in 18F-FDG tracer uptake/15 mm) were detected in 59% of cases (n = 33), colocalizing to VT channels or exit sites (15%) or near these sites (85%, 12.8 ± 8.5 mm). Metabolism-voltage mismatches in which there was a severe PET defect but voltage indicating normal myocardium were seen in 21% of patients (n = 12), 41% of whom were harboring VT channel or exit sites. Conclusion: Abnormal 18F-FDG uptake categories could be detected using incremental 3D step-up reconstructions. They predicted decreasing bipolar voltages and VT channel or exit sites in about 90% of cases. Additionally, functional imaging allowed detection of novel molecular tissue characteristics within the ischemic VT substrate such as metabolic channels, rapid-transition areas, and metabolism-voltage mismatches demonstrating intrasubstrate heterogeneity and providing possible targets for imaging-guided ablation.

Curative Intent Surgery of Oral Malignant Melanoma and Regional Lymph Node Biopsy Assessment in 25 Dogs: 2006-2017.

Medical records were searched for dogs that had received curative intent surgery for oral malignant melanoma and ipsilateral excisional regional lymph node biopsy. Twenty-seven dogs were operated on and 25 dogs of these dogs met the inclusion criteria of signalment, post-excision margin status, presence of metastasis for each biopsied lymphocentrum, survival time post-excision, presence of recurrence or metastasis at follow-up or at death/euthanasia, location of the primary tumor, and any postoperative adjuvant treatment. These 25 dogs had complete tumor excision with tumor-free margins and 19 (76%) had postoperative adjuvant therapy. Median survival time after excision for the dogs in this study was 335.5 days. Results of this study support previous work that documents prolonged survival time following complete excision of oral malignant melanoma with tumor-free surgical margins in dogs. Additionally, 4 dogs (16%) had histologically confirmed regional lymph node metastasis at the time of definitive surgery.

Investigation of an alternative approach for real-time cleaning verification in the pharmaceutical industry.

Within the pharmaceutical industry, it is a regulatory requirement to ensure that pharmaceutical drug manufacturing equipment is clean prior to use. Cleaning processes of manufacturing equipment are performed using a "validated" process and subsequently verified since inadequate cleaning can result in a contaminated or adulterated product. Historically, cleanliness of equipment within Drug Substance/Product/Active Pharmaceutical Ingredient (API) manufacturing is validated and verified using direct swabbing of the equipment and subsequent analytical testing of the swab extract. In this study, a novel approach has been evaluated using a number of innovative technologies and techniques to develop and validate a methodology based on an in situ hand-held Process Analytical Technology (PAT) to verify manufacturing equipment cleanliness and eliminate swabbing and associated off-line laboratory testing. Specular reflectance Mid Infrared (Mid-IR) spectroscopy was used to detect and quantify surface residue. It is expected that this analytical technique will allow the elimination or reduction of the number of swabs and subsequent off-line analytical testing required during cleaning verification of manufacturing equipment in the pharmaceutical and biopharmaceutical industry. This study was focused on the development and validation of a Mid-IR based calibration model. The results indicate that surface a residue of 0.19 µg cm-2 for a specific molecule is detectable using a specular reflectance Mid-IR technique.

Plastic Surgery Chairs and Program Directors: Are the Qualifications Different for Men and Women?

BACKGROUND: The gender disparity between the number of female and male chairs and program directors has been previously established. The aim of this study was to determine whether any differences in objective credentials existed between male and female plastic surgery department chairs/division chiefs and program directors. METHODS: Information about each plastic surgery program director and chair/chief was extracted from the websites of all institutions affiliated with a plastic surgery residency program. For each individual, information about the length of their career, number of fellowships completed, and number of publications was recorded. The two-tailed t test was used to compare differences between male and female chairs and program directors. RESULTS: A total of 99 chairs were recorded, of which nine (9.1 percent) were female. Of the 99 program directors, 13 (13.1 percent) were female. There was no difference in the number of years in practice or number of fellowships between men and women for either position. On average, male chairs had significantly fewer publications than female chairs (71.9 versus 128; p < 0.05). There was no significant difference in the number of publications between male and female program directors. Compared to program directors, chairs had significantly more years in practice and numbers of publications, which held true for both men and women. CONCLUSIONS: Women are not only underrepresented in the department chair and program director positions, but also possess higher qualifications that may reflect differences in standards for promotion and appointment. Additional research is needed to elucidate the reasons behind the observed differences in qualifications.