The amplitude and origin of sea-level variability during the Pliocene epoch.

Earth is heading towards a climate that last existed more than three million years ago (Ma) during the 'mid-Pliocene warm period'1, when atmospheric carbon dioxide concentrations were about 400 parts per million, global sea level oscillated in response to orbital forcing2,3 and peak global-mean sea level (GMSL) may have reached about 20 metres above the present-day value4,5. For sea-level rise of this magnitude, extensive retreat or collapse of the Greenland, West Antarctic and marine-based sectors of the East Antarctic ice sheets is required. Yet the relative amplitude of sea-level variations within glacial-interglacial cycles remains poorly constrained. To address this, we calibrate a theoretical relationship between modern sediment transport by waves and water depth, and then apply the technique to grain size in a continuous 800-metre-thick Pliocene sequence of shallow-marine sediments from Whanganui Basin, New Zealand. Water-depth variations obtained in this way, after corrections for tectonic subsidence, yield cyclic relative sea-level (RSL) variations. Here we show that sea level varied on average by 13 ± 5 metres over glacial-interglacial cycles during the middle-to-late Pliocene (about 3.3-2.5 Ma). The resulting record is independent of the global ice volume proxy3 (as derived from the deep-ocean oxygen isotope record) and sea-level cycles are in phase with 20-thousand-year (kyr) periodic changes in insolation over Antarctica, paced by eccentricity-modulated orbital precession6 between 3.3 and 2.7 Ma. Thereafter, sea-level fluctuations are paced by the 41-kyr period of cycles in Earth's axial tilt as ice sheets stabilize on Antarctica and intensify in the Northern Hemisphere3,6. Strictly, we provide the amplitude of RSL change, rather than absolute GMSL change. However, simulations of RSL change based on glacio-isostatic adjustment show that our record approximates eustatic sea level, defined here as GMSL unregistered to the centre of the Earth. Nonetheless, under conservative assumptions, our estimates limit maximum Pliocene sea-level rise to less than 25 metres and provide new constraints on polar ice-volume variability under the climate conditions predicted for this century.

Tinnitus update: what can be done for the ringing?

Physicians will frequently encounter patients who report tinnitus. Tinnitus is a symptom whereby there is the perception of sound or sounds in the ear or head in the absence of an external source of sound. Most individuals experiencing tinnitus will have a neutral reaction to the percept, but in a small proportion of patients, tinnitus can be a debilitating symptom. When it causes burden, patients can be affected in multiple different facets of life, including impairment in sleep, hearing cognition and psychological and psychiatric well-being, often resulting in high healthcare utilisation and societal costs. Hence, chronic, disabling tinnitus is a complex condition with multifactorial causes and multiple perpetuating biopsychosocial factors. Despite efforts to increase knowledge about its pathophysiology and research into treatments, little impact on real-world clinical practice has been seen. There are no proven effective pharmacological treatments or complementary medicines specifically for chronic, disabling tinnitus. Despite this, there is a role for treating this condition through a multidisciplinary approach specifically targeting comorbid active psychiatric conditions, using hearing aids in appropriate clinical settings such as in those with a coassociated confirmed hearing loss, and specialised cognitive behavioural therapy for patients reporting bothersome tinnitus. Cognitive behavioural therapy remains the most valuable evidence-based intervention in this regard. This narrative review attempts to summarise the current understanding in terms of pathophysiology, assessment and treatment of tinnitus for the internal physician who may encounter patients with disabling, chronic tinnitus.

Comparative Analysis of Recurrence-Free Survival and Mortality in Postmastectomy Patients: Insights From Multidecade, Multiinstitutional Propensity Score Matching.

INTRODUCTION: Disparities in postmastectomy reconstructive care are widely acknowledged. However, there is limited understanding regarding the impact of reconstructive services on cancer recurrence and breast cancer-related mortality. Therefore, this study aims to examine how patient-specific factors and breast reconstruction status influence recurrence-free survival and mortality rates in breast cancer patients. METHODS: Retrospective chart review was performed to collect data on patients who underwent mastectomy at 2 institutions within the New York-Presbyterian system from 1979 to 2019. Sociodemographic information, medical history, and the treatment approach were recorded. Propensity score matching, logistic regression, unpaired t test, and chi-square test were used for statistical analysis. RESULTS: Overall, cancer recurrence occurred in 6.62% (317) of patients, with 16.8% (803) overall mortality rate. For patients who had relapsed disease, completion of the reconstruction sequence was correlated with an earlier detection of cancer recurrence and improved survival odds (P < 0.05). Stratified analysis of the reconstruction group alone showed mortality benefit among patients who underwent free flap procedures (P < 0.05). CONCLUSION: Patients undergoing breast reconstruction after mastectomy are likely to have better access to follow-up care and improved interfacing with the healthcare system. This may increase the speed at which cancer recurrence is detected. This study highlights the need for consistent plastic surgery referral and continued monitoring by all members of the breast cancer care team for cancer recurrence among patients.

An Evolving Landscape: Return of Breast Sensation After Mastectomy Varies by Anatomic Region and Reconstructive Method.

PURPOSE: Loss of breast sensation after mastectomy has been well documented. Postoperative reinnervation of the breast is influenced by factors including reconstructive technique, patient comorbidities, and adjuvant treatment. However, little attention has been paid to the differences in sensation across regions of the breast and the impact of reconstructive method on these regional differences over time. METHODS: Patients undergoing nipple-sparing mastectomy with immediate autologous or alloplastic reconstruction were prospectively followed. Neurosensory testing was performed in 9 breast regions using a pressure-specified sensory device. Patients were stratified by reconstructive technique, and regional sensation was compared at different preoperative and postoperative time points using Student t tests. RESULTS: One hundred ninety-two patients were included; 106 underwent autologous reconstruction via neurotized deep inferior epigastric artery perforator flap, and 86 underwent 2-stage alloplastic reconstruction. Preoperative sensation thresholds did not differ between reconstructive cohorts in any region and averaged 18.1 g/mm2. In the first year after mastectomy, decreased sensation was most pronounced in the inner breast regions and at the nipple areolar complex (NAC) in both reconstructive cohorts. At 4 years postoperatively, sensation increased the most at the NAC in the alloplastic cohort (34.0 g/mm2 decrease) and at the outer lateral region in the autologous cohort (30.4 g/mm2 threshold decrease). The autologous cohort experienced improved sensation compared with the alloplastic cohort in 5 of 9 regions at 1 year postoperatively, and in 7 of 9 regions at 4 years postoperatively; notably, only sensation at the outer superior and outer medial regions did not differ significantly between cohorts at 4 years postoperatively. CONCLUSIONS: Although patients undergoing breast reconstruction experience increased breast sensation over time, the return of sensation is influenced by type of reconstruction and anatomic region. Regions closer to and at the NAC experience the greatest loss of sensation after mastectomy, although the NAC itself undergoes the most sensation recovery of any breast region in those with alloplastic reconstruction.Autologous reconstruction via a neurotized deep inferior epigastric artery perforator flap results in increased return of sensation compared with alloplastic reconstruction, particularly in the inferior and lateral quadrants of the breast.

Impact of Comorbidities on Sensory Return After Breast Reconstruction.

PURPOSE: Breast anesthesia after mastectomy and reconstruction has been an ongoing concern with few improvements made in recent years. At present, there is a lack of studies evaluating the impact of comorbidities on sensation restoration. Identifying risk factors (RF) will be helpful with preoperative counseling. METHODS: This was a prospective study on patients who underwent mastectomy and immediate implant-based or neurotized deep inferior epigastric perforator (DIEP) flap-based reconstruction. Neurosensory testing was performed at predefined time points using a pressure specified device. Patients were stratified based on reconstruction type and comorbidities, including obesity (≥30 kg/m2), age (>55 years), hypertension, alcohol use, and smoking status. Sensory comparisons among the comorbidity groups were conducted using unpaired 2-sample t tests. RESULTS: A total of 239 patients were included in this study with 109 patients in the implant cohort and 131 patients in the DIEP cohort. One patient underwent bilateral reconstruction using both reconstructive modalities. Preoperatively, age older than 55 years was identified as an RF for reduced breast sensation in the implant cohort (difference in threshold, 10.7 g/mm2), whereas obesity was identified as an RF in the DIEP cohort (difference in threshold, 8 g/mm2). During the first 2 years postreconstruction, age older than 55 years and tobacco use history were found to be negatively correlated with breast sensation for both cohorts. With DIEP reconstruction specifically, obesity was identified as an additional RF during the early postoperative period. Of note, none of the comorbidities were found to be long-term RFs for reduced breast sensitivity. All breast sensation levels returned to comparable levels across all comorbidities by 4 years postreconstruction. CONCLUSIONS: Currently, various comorbidities have been recognized as RFs for several postoperative complications including extended postoperative stay, necrosis, infection, and reoperation. However, our findings suggest that, although age, smoking history, and obesity showed transient associations with reduced breast sensation during the initial years postreconstruction, they play no role in the long-term potential of sensory nerve regeneration.

Proliferation Patterns of MCF-7 Breast Cancer Cells in Lipoaspirate Conditioned Media.

INTRODUCTION: Autologous fat grafting (AFG) is a common technique used to enhance aesthetic outcomes in postmastectomy breast reconstruction patients. Adipokines are hormones secreted by adipose tissue that play a critical role in regulating metabolic processes and the immune system. However, dysregulated adipokine secretion and signaling can contribute to the development and progression of cancer by promoting angiogenesis, altering the immune response, and inducing the epithelial mesenchymal transition. We aimed to assess how breast cancer cells behave in conditioned media derived from fat grafting lipoaspirates and gain a better understanding of the potential interactions that may occur within the tumor microenvironment. METHODS: Patients who were undergoing AFG as a part of breast reconstruction at NY-Presbyterian/Weill Cornell Medical Center between March 2021 and July 2023 were consented and enrolled in the study. This study was approved by the Weill Cornell Medicine Institutional Review Board (#20-10022850-14). Conditioned media is created using 20% of patient lipoaspirate secretome and 80% starving media. The growth of MCF-7, a human ER/PR+ breast cancer cell line, in conditioned media is assessed using CyQUANT. RESULTS: The breast cancer cells incubated in conditioned media displayed similar growth trends as those in complete media, which is enriched for cell growth (P > 0.05). MCF-7 cell behavior in conditioned media differed significantly from their proliferation patterns when serum starved in 100% starving media (P < 0.05). DISCUSSION: Our results suggest that there may be inherent factors within the lipoaspirate that may promote MCF-7 proliferation. One potential implication is that AFG used for breast reconstruction should be delayed until local-regional disease control has been established. In addition, based on the in vitro proliferation patterns of breast cancer cells in conditioned media, the safety profile of AFG may be enhanced if the procedure is performed after attaining negative margins and the completion breast cancer treatment.

Infection After Lower-Limb Osseointegration: A Single-Center Retrospective Evaluation of Pathogens, Management, and Outcomes.

PURPOSE: Osseointegration (OI) is a novel alternative to traditional socket-suspended prostheses for lower-limb amputees, eliminating the socket-skin interface and allowing for weight bearing directly on the skeletal system. However, the stoma through which the implant attaches to the external prosthesis creates an ingress route for bacteria, and infection rates as high as 66% have been reported. The aims of this study are to classify infection management and long-term outcomes in this patient population to maximize implant salvage. METHODS: An institutional review board-approved retrospective analysis was performed on all patients who underwent lower-limb OI at our institution between 2017 and 2022. Demographic, operative, and outcome data were collected for all patients. Patients were stratified by the presence and severity of infection. Chi-square and t tests were performed on categorical and continuous data, respectively, using an alpha of 0.05. RESULTS: One hundred two patients met our study criteria; 62 had transfemoral OI and 40 had transtibial OI. Patients were followed for 23.8 months on average (range, 3.5-63.7). Osteomyelitis was more likely than soft tissue infection to be polymicrobial in nature (71% vs 23%, P < 0.05). Infections at the stoma were mostly (96%) managed with oral antibiotics alone, whereas deeper soft tissue infections also required intravenous antibiotics (75%) or operative washout (19%). Osteomyelitis was managed with intravenous antibiotics and required operative attention; 5 (71%) underwent washout and 2 (29%) underwent explantation. Both implants were replaced an average of 3.5 months after explantation. There was no correlation between history of soft tissue infection and development of osteomyelitis (P > 0.05). The overall implant salvage rate after infection was 96%. CONCLUSIONS: This study describes our institution's experience managing infection after OI and soft tissue reconstruction. Although infections do occur, they are easily treatable and rarely require operative intervention. Explantation due to infection is rare and can be followed up with reimplantation, reaffirming that OI is a safe and effective treatment modality.

Assessing Long-Term Volume Retention in Breast Fat Grafting: A Comparative Study of Lipoaspirate Processing Techniques.

INTRODUCTION: Autologous fat grafting is a method of improving aesthetic outcomes after both breast reconstruction and aesthetic surgery through volume enhancement and tissue contouring. Long-lasting effects are linked to greater patient satisfaction and more optimal augmentation results. Harvesting, processing, and injection techniques may all affect the longevity of deformity filling. Our objective is to evaluate the effect of lipoaspirate processing modality on longitudinal volume retention after surgery. METHODS: A prospective, single-institution, randomized control trial placed consented postmastectomy fat grafting patients into 1 of 3 treatment arms (active filtration, low-pressure decantation, and standard decantation) in a 1:1:1 ratio. A preoperative 3-dimensional scan of the upper torso was taken as baseline. At the 3-month postoperative visit, another 3D scan was taken. Audodesk Meshmixer was used to evaluate the volume change. RESULTS: The volume of fat injected during the initial procedure did not differ significantly between the treatment arms (P > 0.05). Both active filtration and low-pressure decantation resulted in higher percentage volume retention than traditional decantation (P < 0.05). Active filtration and low-pressure decantation exhibited comparable degrees of fat maintenance at 3 months (P > 0.05). DISCUSSION: Compared with using traditional decantation as the lipoaspirate purification technique, active filtration and low-pressure decantation may have led to higher levels of cell viability by way of reduced cellular debris and other inflammatory components that may contribute to tissue resorption and necrosis. Further immunohistochemistry studies are needed to examine whether active filtration and low-pressure decantation lead to lipoaspirates with more concentrated viable adipocytes, progenitor cells, and factors for angiogenesis.

Timeline and Incidence of Postoperative Complications in Prepectoral, Dual-Plane, and Total Submuscular Alloplastic Reconstruction With and Without Biosynthetic Scaffold Usage.

INTRODUCTION: Acellular dermal matrices and synthetic meshes are commonly used to improve inframammary-fold definition, minimize muscle excision, and allow for greater control over the surgical technique in implant-based breast reconstruction. The aims of this study are to compare various combinations of placement planes and biosynthetic scaffolds and to further examine the respective incidences of postoperative complications and the timeline of capsular contracture development. METHODS: A data set consisting of 220 patients (393 samples) who underwent 2-stage reconstruction between 2012 and 2021 was used in the study. χ 2 , Fisher exact test, and 1-way analysis of variance were used to identify significant differences between the 4 subgroups. Cox proportional-hazards model and Kaplan-Meier estimator were used for survival analysis. RESULTS: On univariate logistic regression (odds ratio, 0.21; P = 0.005), survival analysis ( P = 0.0082), and Cox-proportional hazard model (hazard ratio, 1.6; P = 0.01), poly-4-hydroxybutyrate mesh usage was linked to an increased risk of capsular contracture development. Prepectoral placement with no mesh and dual-plane placement with acellular dermal matrix showed similar timelines of capsular contracture development. The lowest incidences of capsular contracture occurred in the prepectoral placement and no mesh (49/161, 30.4%) and total submuscular subgroups (3/14, 21.4%). Infection, necrosis, and revision surgery rates did not differ significantly between the 4 groups. CONCLUSIONS: The use of poly-4-hydroxybutyrate mesh in 2-stage breast reconstruction is correlated with a statistically significant increase in capsular contracture. Prepectoral placement with no biosynthetic scaffold had one of the lowest rates of contracture and may provide the most optimal balance between economic and clinical considerations in implant-based reconstruction.

Osseointegration for Lower Limb Amputation: Understanding the Risk Factors and Time Courses of Soft Tissue Complications.

PURPOSE: Lower-limb osseointegrated prostheses are a novel alternative to traditional socket-suspended prostheses, which are often associated with poor fit, soft tissue damage, and pain. Osseointegration eliminates the socket-skin interface and allows for weight-bearing directly on the skeletal system. However, these prostheses can also be complicated by postoperative issues that can negatively impact mobility and quality of life. Little is known about the incidence of or risk factors for these complications as few centers currently perform the procedure. METHODS: A retrospective analysis was performed on all patients who underwent single-stage lower limb osseointegration at our institution between 2017 and 2021. Patient demographics, medical history, operative data, and outcomes were collected. Fisher exact test and unpaired t tests were performed to identify risk factors for each adverse outcome, and time-to-event survival curves were generated. RESULTS: Sixty patients met our study criteria: 42 males and 18 females with 35 transfemoral and 25 transtibial amputations. The cohort had an average age of 48 years (range, 25-70 years) and follow-up period of 22 months (range, 6-47 months). Indications for amputation were trauma (50), prior surgical complication (5), cancer (4), and infection (1). Postoperatively, 25 patients developed soft tissue infections, 5 developed osteomyelitis, 6 had symptomatic neuromas, and 7 required soft tissue revisions. Soft tissue infections were positively correlated with obesity and female sex. Neuroma development was associated with increased age at osseointegration. Neuromas and osteomyelitis were both associated with decreased center experience. Subgroup analysis by amputation etiology and anatomic location did not show significant differences in outcomes. Notably, hypertension (15), tobacco use (27), and prior site infection (23) did not correlate with worse outcomes. Forty-seven percent of soft tissue infections occurred in the 1 month after implantation, and 76% occurred in the first 4 months. CONCLUSIONS: These data provide preliminary insights into risk factors for postoperative complications arising from lower limb osseointegration. These factors are both modifiable (body mass index, center experience), and unmodifiable (sex, age). As this procedure continues to expand in popularity, such results are necessary to inform best practice guidelines and optimize outcomes. Further prospective studies are needed to confirm the above trends.

An Evaluation of Native Breast Dimension and Tissue Expander Inflation Rate on the Risk of Capsular Contracture Development in Postmastectomy Reconstruction.

INTRODUCTION: Capsular contracture is a common complication after 2-stage breast reconstruction. The relationships between native breast size, the rate of tissue expander expansion, and capsule formation have not been elucidated. This study aims to evaluate how these factors contribute to capsular contracture and establish cutoff values for increased risk. METHODS: A data set consisting of 229 patients who underwent 2-stage breast reconstruction between 2012 and 2021 was included in the study. The rate of expansion is estimated as the final expanded volume subtracted by the initial filling volume of the tissue expander over time elapsed. The native breast size was estimated using various preoperative breast measurements and the weight of mastectomy specimen (grams). Further stratified analysis evaluated patients separately based on postoperative radiation status. RESULTS: Greater nipple-inframammary fold distance and faster tissue expander enlargement rate conferred decreased odds of developing capsular contracture ( P < 0.05). On stratified analysis, faster tissue expansion rate was not significant in the nonradiated cohort but remained a significant negative predictor in the radiation group (odds ratio, 0.996; P < 0.05). Cut-point analysis showed an expansion rate of <240 mL/mo and a nipple-inframammary fold value of <10.5 cm as conferring a greater risk of capsular contracture. CONCLUSION: Smaller inframammary fold distance may be associated with a higher risk of capsular contracture. Slower expansion rates correlate with increased odds of contracture in patients undergoing adjuvant radiation. Breast geometry should be considered when risk stratifying various reconstruction approaches (implant vs autologous). In addition, longer delays between implant exchange and initial tissue expansion should be avoided if clinically feasible.

Streamlining the Fat: A Systematic Review of Active Closed Wash and Filtration in Autologous Fat Grafting After Breast Reconstruction.

Although fat grafting in breast reconstruction continues to grow in popularity, the optimal technique remains elusive and outcomes are varied. This systematic review of available controlled studies utilizing active closed wash and filtration (ACWF) systems sought to examine differences in fat processing efficiency, aesthetic outcomes, and revision rates. A literature search was performed from inception to February 2022 following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) in Ovid MEDLINE (Wolters Kluwer, Alphen aan den Rijn, the Netherlands), Ovid Embase (Wolters Kluwer), and Cochrane Library (Wiley, Hoboken, NJ). Two independent reviewers screened the studies for eligibility with Covidence software. Bibliographies and citing references from selected articles were screened from Scopus (Elsevier, Amsterdam, the Netherlands). The search identified 3476 citations, with 6 studies included. Three studies demonstrated a significantly higher volume of graftable fat harvested in a significantly lower mean grafting time with ACWF than with their respective controls. With respect to adverse events, 3 studies reported significantly lower incidences of nodule or cyst formation with ACWF with respect to control. Two studies reported a significantly lower incidence of fat necrosis with ACWF vs control, with this trend upheld in 2 additional studies. Three studies reported significantly lower revision rates with ACWF with respect to control. No study reported inferiority with ACWF for any outcome of interest. These data suggest that ACWF systems yield higher fat volumes in less time than other common techniques, with decreased rates of suboptimal outcomes and revisions, thereby supporting active filtration as a safe and efficacious means of fat processing that may reduce operative times. Further large-scale, randomized trials are needed to definitively demonstrate the above trends.

Emergency department care of patients with Duchenne muscular dystrophy.

Patients with Duchenne muscular dystrophy are living longer and are increasingly seen in Emergency Departments. Though the most common cause of death remains progressive respiratory failure, increased life expectancies have unmasked the significance of progressive myocardial dysfunction, now associated with nearly 40% of mortalities in the DMD population. Cardiac complications such as arrhythmias and cardiomyopathy are becoming ever more widely recognized. Emergency physicians may encounter DMD patients with untreated, undiagnosed or worsening of known heart disease. This review will initially familiarize the emergency physician with the pathophysiology and lifetime trajectory of care for these patients before describing specific emergency department evaluation and treatment.

A Cost-Benefit Analysis of Osseointegrated Prostheses for Lower Limb Amputees in the US Health Care System.

BACKGROUND: Patients with transfemoral and transtibial amputations generally rely on socket-suspended (SS) prostheses for ambulation. The use of these aids can be complicated by poor fit, leading to tissue damage, pain at the socket-limb interface, and inability to ambulate. Osseointegrated implants (OIs) directly anchor a prosthesis to the patient's residual limb, eliminating these issues. However, they require customized components and additional surgeries. The purpose of this study was to conduct the first cost-benefit analysis of OI prostheses compared to SS prostheses for lower limb amputees in the United States. METHODS: A retrospective chart review was performed on all patients who received unilateral lower limb OI prostheses at our institution. Costs were calculated in a bottom-up approach using Current Procedural Terminology codes. Utilities and SS prosthesis costs were derived from previous studies. A Monte Carlo model was used to project costs and lifetime quality-adjusted life years for OI and SS prostheses, and the incremental cost-effectiveness ratio (ICER) of OI compared SS prostheses was determined. RESULTS: Twenty-five patients (12 female) were included in the study. The mean follow-up was 17 months postimplantation. The average cost of OI surgery was $54,463. Twenty percent of patients required preimplantation soft tissue revision surgery ($49,191). Complication rates per year and average costs were as follows: soft tissue infection (29%, $435), bone/implant infection (11%, $11,721), neuroma development (14%, $14,659), and mechanical failure (17%, $46,513). The ICER was $44,660. A cost-effectiveness acceptability curve demonstrated that OI was favored over SS in 78% of cases at a willingness-to-pay of $100,000 per quality-adjusted life year. In a 1-way sensitivity analysis, the ICER was most sensitive to the mechanical failure rate, mechanical failure cost, and prior SS prosthesis costs. CONCLUSIONS: The model shows that OI prostheses provide a higher quality of life at affordable costs when compared to poorly tolerated SS prostheses in patients with lower limb amputations in the United States. The cost-effectiveness is largely determined by the patient's previous SS prosthesis costs and is limited by the frequency and costs of OI mechanical failure. More research must be done to understand the long-term benefits and risks of OI prostheses.

Exploring PCDD/Fs and potentially toxic elements in sewage sludge during smouldering treatment.

Potentially toxic elements (PTEs), persistent organic pollutants, and emerging contaminants make sewage sludge management challenging. There is significant interest in thermal treatment technologies that can destroy these compounds. The most common thermal treatment, incineration, poses risks due to formation and/or release of hazardous substances in process emissions such as polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) and PTEs. Smouldering has been introduced recently as a potential treatment for managing sewage sludge. Smouldering systems present several advantages over traditional incinerators; however, there are still uncertainties regarding process by-products. This key question was investigated in three laboratory-scale tests (0.08 m radius) and five oil drum-scale tests (0.3 m radius) that were evaluated for PCDD/Fs and PTEs in the mixture before and after treatment as well as in process emissions. Volatile organic compounds (VOCs) were also measured. These experiments represent a broad spectrum of conditions to evaluate process emissions, from robust self-sustaining to extinction of smouldering. Robust smouldering had negligible PCDD/Fs in process emissions. Weak smouldering had low levels of PCDD/Fs (emissions factor: 3.3 ± 0.3 µg TEQ/Mg dried sludge destroyed), levels less than uncontrolled emissions from commercial incinerators. Overall, smouldering acted as a sink for PCDD/Fs, as only 0-3% of the PCDD/Fs originally present in the sludge were released in the emissions, and >99% of the remainder were destroyed with <1% remaining in post-treatment ash. No evidence was found to support de novo synthesis or precursor reactions forming new PCDD/Fs. In addition, 94-100% of all the PTEs analyzed were retained in the post-smouldered material. These results indicate that only minimal emissions treatment for PTEs, PCDD/Fs, and VOCs may be necessary for future sewage sludge smouldering systems. These low emissions risks combined with its unique ability to handle high moisture content waste, indicate that smouldering has significant potential as a valuable waste management technique.

Self-rated executive dysfunction in adults with epilepsy and effects of a cognitive-behavioral intervention (HOBSCOTCH).

RATIONALE: Cognitive problems are common in adults with epilepsy and significantly affect their quality of life. HOBSCOTCH (HOme Based Self-management and COgnitive Training CHanges lives) was developed to teach problem-solving and compensatory memory strategies to these individuals. This study examined whether HOBSCOTCH is associated with improvement in specific aspects of subjective executive functions. METHODS: Fifty-one adults, age 18-65, with epilepsy and subjective cognitive concerns were randomized to receive HOBSCOTCH (n = 31) or a care-as-usual control sample (n = 20). Participants completed the Behavior Rating Inventory of Executive Function-Adult version (BRIEF-A), as well as the Patient Health Questionnaire-9 (PHQ-9) to assess depression. Rates of elevated (i.e., T ≥ 65, impaired) BRIEF-A scores at baseline, as well as pre-post score changes for the BRIEF-A clinical scales were evaluated. Significance was set at α = 0.05, one-tailed, given our directional hypothesis. RESULTS: At baseline, a considerable percentage of patients in the overall sample endorsed executive dysfunction on BRIEF-A scales: Inhibit = 28%, Shift = 51%, Emotional Control = 45%, Self-Monitor = 33%, Initiate = 35%, Working Memory = 88%, Plan/Organize = 45%, Task Monitor = 47%, Organization of Materials = 28%. Significant improvement was seen in mean T-scores for Inhibit, Shift, Initiate, and Working Memory in the treatment group, but only Working Memory improved in the control group. The control group endorsed worse task monitoring and organization of materials at baseline and follow-up. Change in depression was not observed for either group, and there was no association between changes in depression and BRIEF-A scores. CONCLUSIONS: A sizeable subset of adults with epilepsy reported experiencing executive dysfunction in their everyday lives, especially for working memory. HOBSCOTCH resulted in amelioration of subjective executive functioning independent of changes in mood.

A performance comparison of the most commonly used minimally invasive monitors of cardiac output.

BACKGROUND: Shock is common in critically ill and injured patients. Survival during shock is highly dependent on rapid restoration of tissue oxygenation with therapeutic goals based on cardiac output (CO) optimization. Despite the clinical availability of numerous minimally invasive monitors of CO, limited supporting performance data are available. METHODS: Following approval of the University of Saskatchewan Animal Research Ethics Board, we assessed the performance and trending ability of PiCCOplus™, FloTrac™, and CardioQ-ODM™ across a range of CO states in pigs. In addition, we assessed the ability of invasive mean arterial blood pressure (iMAP) to follow changes in CO using a periaortic transit-time flow probe as the reference method. Statistical analysis was performed with function-fail, bias and precision, percent error, and linear regression at all flow, low-flow (> 1 standard deviation [SD] below the mean), and high-flow (> 1 SD above the mean) CO conditions. RESULTS: We made a total of 116,957 paired CO measurements. The non-invasive CO monitors often failed to provide a CO value (CardioQ-ODM: 40.6% failed measurements; 99% confidence interval [CI], 38.5 to 42.6; FloTrac: 9.6% failed measurements; 99% CI, 8.7 to 10.5; PiCCOplus: 4.7% failed measurements; 99% CI, 4.5 to 4.9; all comparisons, P < 0.001). The invasive mean arterial pressure provided zero failures, failing less often than any of the tested CO monitors (all comparisons, P < 0.001). The PiCCOplus was most interchangeable with the flow probe at all flow states: PiCCOplus (20% error; 99% CI, 19 to 22), CardioQ-ODM (25% error; 99% CI, 23 to 27), FloTrac (34% error; 99% CI, 32 to 38) (all comparisons, P < 0.001). At low-flow states, CardioQ-ODM (43% error; 99% CI, 32 to 63) and Flotrac (45% error; 99% CI, 33 to 70) had similar interchangeability (P = 0.07), both superior to PiCCOplus (48% error; 99% CI, 42 to 60) (P < 0.001). Regarding CO trending, the CardioQ-ODM (correlation coefficient, 0.82; 99% CI, 0.81 to 0.83) was statistically superior to other monitors including iMAP, but at low flows iMAP (correlation coefficient, 0.58; 99% CI, 0.58 to 0.60) was superior to all minimally invasive CO monitors (all comparisons P < 0.001). CONCLUSIONS: None of the minimally invasive monitors of CO performed well at all tested flows. Invasive mean arterial blood pressure most closely tracked CO change at critical flow states.

RéSUMé: CONTEXTE: L'état de choc est fréquent chez les patients blessés et en urgence absolue. La survie pendant le choc dépend fortement de la restauration rapide de l'oxygénation tissulaire avec des objectifs thérapeutiques basés sur l'optimisation du débit cardiaque (DC). Malgré la disponibilité clinique de nombreux moniteurs minimalement invasifs du DC, il n'existe que des données limitées sur leur performance pour appuyer leur utilisation. MéTHODE: À la suite de l'approbation du comité d'éthique de la recherche animale de l'Université de la Saskatchewan, nous avons évalué la performance et la capacité de suivi des tendances des appareils PiCCOplus™, FloTrac™ et CardioQ-ODM™ sur une vaste gamme d'état de DC chez des cochons. Nous avons également évalué la capacité de la tension artérielle moyenne invasive (iMAP) à suivre les changements de DC en utilisant une sonde périaortique de débit basée sur le temps de transit comme méthode de référence. L'analyse statistique a été réalisée avec fonction-échec, biais et précision, pourcentage d'erreur et régression linéaire à des conditions de DC de tous les débits, de faible débit (> 1 écart-type [ET] au-dessous de la moyenne) et de débit élevé (> 1 ET au-dessus de la moyenne). RéSULTATS: Nous avons effectué un total de 116 957 mesures de DC appariées. Les moniteurs non invasifs de la DC n'ont souvent pas réussi à fournir une valeur de DC (CardioQ-ODM : 40,6% de mesures échouées; intervalle de confiance [IC] de 99 %, 38,5 à 42,6; FloTrac : 9,6 % de mesures échouées; IC 99 %, 8,7 à 10,5; PiCCOplus : 4,7 % de mesures échouées; IC 99 %, 4,5 à 4,9; toutes les comparaisons, P < 0,001). La tension artérielle moyenne invasive n'a fourni aucun échec plus souvent que n'importe lequel des moniteurs de DC testés (toutes les comparaisons, P < 0,001). Le PiCCOplus était le plus interchangeable avec la sonde de débit à tous les états de débit : PiCCOplus (erreur de 20 %; IC 99 %, 19 à 22), CardioQ-ODM (erreur de 25 %; IC 99 %, 23 à 27), FloTrac (erreur de 34 %; IC 99 %, 32 à 38) (toutes les comparaisons, P < 0,001). Aux états de débit faible, les moniteurs CardioQ-ODM (erreur de 43 %; IC 99 %, 32 à 63) et FloTrac (erreur de 45 %; IC 99 %, 33 à 70) présentaient une interchangeabilité similaire (P = 0,07), tous deux supérieurs au PiCCOplus (erreur de 48 %; IC 99 %, 42 à 60) (P < 0,001). En ce qui concerne le suivi des tendances de DC, le CardioQ-ODM (coefficient de corrélation, 0,82; IC 99 %, 0,81 à 0,83) était statistiquement supérieur aux autres moniteurs, y compris au iMAP, mais à faibles débits, l'iMAP (coefficient de corrélation, 0,58; IC 99 %, 0,58 à 0,60) était supérieure à tous les moniteurs de DC minimalement invasifs (toutes les comparaisons, P < 0,001). CONCLUSION: Aucun des moniteurs de DC minimalement invasif n'a donné de bons résultats à tous les débits testés. La tension artérielle moyenne invasive était le moniteur qui a suivi de plus près les changements de DC dans des états critiques de débit.

Can a virtual microbiology simulation be as effective as the traditional Wetlab for pharmacy student education?

BACKGROUND: Pharmacy practice education requires the development of proficiencies and an understanding of clinical microbiology. Learning in this area could be delivered using practical laboratory exercises, or potentially, simulation-based education. Simulation has previously successfully enhanced learning in health professional education. The current global climate due to COVID-19 has further highlighted the important role of technology-enhanced learning in delivering outcomes that meet the requisite learning objectives of a course. The aim of the present study was to compare the impact of a commercially available virtual microbiology simulation (VUMIE™) with a traditional wet laboratory (wetlab) on learner knowledge, skills and confidence in a second-year integrated pharmacotherapeutics course for Bachelor of Pharmacy students. METHODS: A randomised, crossover study was employed to determine whether the simulation intervention (VUMIE™) improves learning outcomes (knowledge, skills and confidence) of pharmacy students, when compared to a traditional wetlab intervention. Each student completed three 1-2 h length sessions, for both the wetlab and VUMIE™ interventions (6 sessions total). Data was collected using surveys deployed at baseline (pre-interventions), post-intervention 1 or 2 (VUMIE™ or wetlab) and endpoint (post-interventions 1 and 2). Statistical analysis was conducted using SPSS Statistics 25 and Instat™ software. RESULTS: Response rates were approximately 50% at initial survey and approximately 25% at endpoint survey. VUMIE™ produced higher post-intervention knowledge scores for the multiple-choice questions compared to the wetlab, however, the highest score was achieved at endpoint. Both interventions produced statistically significant differences for mean scores compared to baseline (pre-VUMIE™ and wetlab) across the domains of knowledge, skills and confidence. VUMIE™ produced higher post-intervention mean scores for knowledge, skills and confidence compared to post-intervention mean scores for the wetlab, however there was no statistical significance between the mean score for the two interventions, thus the VUMIE™ activity produced learning outcomes comparable to the wetlab activity. CONCLUSION: These findings suggest VUMIE™ provides similar effects on students' knowledge, skills, and confidence as a wetlab. The simulation's implementation was not cost-prohibitive, provided students with a physically and psychologically safe learning environment, and the benefit of being able to repeat activities, supporting deliberate practice.

Difluorocarbene Generation from TMSCF3: Kinetics and Mechanism of NaI-Mediated and Si-Induced Anionic Chain Reactions.

The mechanism of CF2 transfer from TMSCF3 (1), mediated by TBAT (2-12 mol %) or by NaI (5-20 mol %), has been investigated by in situ/stopped-flow 19F NMR spectroscopic analysis of the kinetics of alkene difluorocyclopropanation and competing TFE/c-C3F6/homologous perfluoroanion generation, 13C/2H KIEs, LFERs, CF2 transfer efficiency and selectivity, the effect of inhibitors, and density functional theory (DFT) calculations. The reactions evolve with profoundly different kinetics, undergoing autoinhibition (TBAT) or quasi-stochastic autoacceleration (NaI) and cogenerating perfluoroalkene side products. An overarching mechanism involving direct and indirect fluoride transfer from a CF3 anionoid to TMSCF3 (1) has been elucidated. It allows rationalization of why the NaI-mediated process is more effective for less-reactive alkenes and alkynes, why a large excess of TMSCF3 (1) is required in all cases, and why slow-addition protocols can be of benefit. Issues relating to exothermicity, toxicity, and scale-up are also noted.

Empirical orthogonal function regression: Linking population biology to spatial varying environmental conditions using climate projections.

Ecologists and oceanographers inform population and ecosystem management by identifying the physical drivers of ecological dynamics. However, different research communities use different analytical tools where, for example, physical oceanographers often apply rank-reduction techniques (a.k.a. empirical orthogonal functions [EOF]) to identify indicators that represent dominant modes of physical variability, whereas population ecologists use dynamical models that incorporate physical indicators as covariates. Simultaneously modeling physical and biological processes would have several benefits, including improved communication across sub-fields; more efficient use of limited data; and the ability to compare importance of physical and biological drivers for population dynamics. Here, we develop a new statistical technique, EOF regression, which jointly models population-scale dynamics and spatially distributed physical dynamics. EOF regression is fitted using maximum-likelihood techniques and applies a generalized EOF analysis to environmental measurements, estimates one or more time series representing modes of environmental variability, and simultaneously estimates the association of this time series with biological measurements. By doing so, it identifies a spatial map of environmental conditions that are best correlated with annual variability in the biological process. We demonstrate this method using a linear (Ricker) model for early-life survival ("recruitment") of three groundfish species in the eastern Bering Sea from 1982 to 2016, combined with measurements and end-of-century projections for bottom and sea surface temperature. Results suggest that (a) we can forecast biological dynamics while applying delta-correction and statistical downscaling to calibrate measurements and projected physical variables, (b) physical drivers are statistically significant for Pacific cod and walleye pollock recruitment, (c) separately analyzing physical and biological variables fails to identify the significant association for walleye pollock, and (d) cod and pollock will likely have reduced recruitment given forecasted temperatures over future decades.