Effectiveness of population-based recovery actions for threatened southern mountain caribou.

Habitat loss is affecting many species, including the southern mountain caribou (Rangifer tarandus caribou) population in western North America. Over the last half century, this threatened caribou population's range and abundance have dramatically contracted. An integrated population model was used to analyze 51 years (1973-2023) of demographic data from 40 southern mountain caribou subpopulations to assess the effectiveness of population-based recovery actions at increasing population growth. Reducing potential limiting factors on threatened caribou populations offered a rare opportunity to identify the causes of decline and assess methods of recovery. Southern mountain caribou abundance declined by 51% between 1991 and 2023, and 37% of subpopulations were functionally extirpated. Wolf reduction was the only recovery action that consistently increased population growth when applied in isolation, and combinations of wolf reductions with maternal penning or supplemental feeding provided rapid growth but were applied to only four subpopulations. As of 2023, recovery actions have increased the abundance of southern mountain caribou by 52%, compared to a simulation with no interventions. When predation pressure was reduced, rapid population growth was observed, even under contemporary climate change and high levels of habitat loss. Unless predation is reduced, caribou subpopulations will continue to be extirpated well before habitat conservation and restoration can become effective.

Dentists' knowledge of non-surgical root canal treatment, a systematic review.

OBJECTIVES: Dental practice is based upon dentists' cognitions, knowledge being foundational. Knowledge is attained through education and perception. Although knowledge is modulated by beliefs, attitudes, preferences, and behaviors, it is essential to evidence-based practice. Cross-sectional studies uniformly demonstrate that community NSRCT is of sub-optimal quality worldwide, is lack of knowledge a problem? Our purpose was to measure dentists' knowledge of root canal treatment (NSRCT). DATA: Quantitative and qualitative data were extracted: purpose, topics assessed, authors cited knowledge sources, number of dentists studied, number of questions, authors descriptors of knowledge level,% correct answers by question, authors recommendations. SOURCES: OVID Medline, EMBASE, Web of Science, and hand-searching. STUDY SELECTION: Studies which had measured dentists' knowledge of non-surgical root canal treatment that was valuable, reliable, and had practical implications which could be implemented. A total of 51 papers from 19 countries measured the knowledge of 15,580 dentists using 445 questions on 29 root canal treatment topics. CONCLUSIONS: 'Gold standards' were from literature, external bodies, or expert consensus in 47, 31, and 2 papers respectively. Levels of knowledge by percentage correct answers among studies were poor to moderate and varied considerably. The mean, for the 50 studies where overall study percentages could be calculated, was 57 %, standard deviation 17 %, and a range of 16 % to 82 %. Authors' adjectives describing knowledge levels were generally negative. Additional education was advised in 49 papers, but without evidence that education was inadequate; 6 papers recommended increased use of protocols; only 5 papers advocated research on the cause of lack of knowledge. CLINICAL SIGNIFICANCE: Dentists' root canal treatment knowledge was found to be poor to moderate, as well variable. This may constrain quality of care. However, provision of information without attention to dentists' cognitions and motivations may not be successful. Educational strategies and goals should be re-evaluated. Evidence-based practice faces many barriers.

Color- and strength-graded zirconia: Strength, light transmission, and composition.

STATEMENT OF PROBLEM: Natural teeth are graded in terms of translucency and strength. Graded zirconia materials are now available with a higher yttria content on the top or in the enamel zone to increase surface translucency and a lower yttria content on the bottom or in the dentin zone to increase strength. Such materials could provide multiple advantages over uniform materials and reduce the need for porcelain veneering in anterior artificial crowns; however, studies on the properties of these materials are lacking. PURPOSE: The purpose of this in vitro study was to measure and compare the biaxial flexural strength, percentage light transmission, elemental content, and phase content of zones within and among color graded zirconia blocks and color- and strength-graded zirconia blocks. MATERIAL AND METHODS: Disks of a color graded material (Katana STML) and a strength- and color-graded material (IPS e.max ZirCAD Prime) were fabricated (Zircom Furnace). Biaxial flexural strength was measured using a piston-on-3-ball test in a universal testing machine (n=10). Absolute light transmission was measured with a spectrophotometer. Elemental compositions were quantified for 3 zones in each of the 2 zirconia materials using X-ray fluorescence analysis. Zirconia phase fractions were quantified for 3 zones using X-ray diffraction analysis (XRD). Where appropriate, 2-way ANOVA, 1-way ANOVA, and Tukey multiple pairwise comparison testing were used to determine which of the 6 zones differed from one another (α=.05). RESULTS: The color-graded zirconia exhibited gradients in light transmission and differences in phase content in the 3 zones measured. The color- and strength-graded zirconia exhibited gradients in light transmission, biaxial flexural strength, elemental composition, and phase content in the 3 zones measured. The bottom, dentin, or intaglio layer of a strength graded zirconia material was substantially stronger than all other zones of either material (P<.05). The top, enamel, zones of both materials possessed high light transmissibility (P<.05). The 2 materials differed with respect to biaxial strength (P<.001), light transmission (P<.02), elemental composition, and phase composition overall, as well as in most zone-by zone comparisons (P<.05). The performance and composition of the color graded material was consistent with it being a 5Y material throughout. The performance and composition of the color and strength graded material was consistent with it having a 3Y bottom zone and a 5Y top zone. CONCLUSIONS: A strength-graded and color-graded zirconia material offers potential advantages in both strength and translucency.

Cardiometabolic Effects of Denosumab in Premenopausal Women with Breast Cancer Receiving Estradiol Suppression: RCT.

CONTEXT: Menopause is associated with changes in musculoskeletal, body composition, and metabolic parameters that may be amplified in premenopausal women receiving estradiol suppression for breast cancer. Denosumab offsets deleterious skeletal effects of estradiol suppression and has been reported to have effects on body composition and metabolic parameters in pre-clinical and observational studies, though evidence from double-blind randomized controlled trials is limited. OBJECTIVE: To assess the effect of denosumab on body composition and metabolic parameters. METHODS: In a pre-specified secondary analysis of a 12-month randomized, double-blind, placebo-controlled trial, 68 premenopausal women with breast cancer initiating ovarian function suppression and aromatase inhibition were randomized to denosumab 60-mg or placebo administered at baseline and 6 months. Outcome measures were total and regional fat and lean mass (DXA), body mass index (BMI), waist and hip circumference, fasting glucose, HOMA-IR, and lipid profile. Using a mixed model, between-group mean adjusted differences, MAD, [95% confidence interval], over time are reported. RESULTS: Over 12 months, relative to placebo, android and gynoid fat mass decreased in the denosumab group (-266 g [95%CI -453 to -79], P = 0.02, and -452 g [95%CI -783 to -122], P = 0.03, respectively). Total fat mass and waist circumference were lower in the denosumab group but not significantly so (-1792g [95% CI -3346 to -240], P = 0.08 and (- 3.77 cm [95% CI -6.76 to -0.79], P = 0.06, respectively). No significant treatment effects were detected in lean mass, BMI, hip circumference, fasting glucose, HOMA-IR, or lipid profile. CONCLUSIONS: In premenopausal women receiving estradiol suppression, denosumab decreases some measures of fat mass with no detectable effects on other measures of body composition or metabolic parameters.

First-Line Ipatasertib, Atezolizumab, and Taxane Triplet for Metastatic Triple-Negative Breast Cancer: Clinical and Biomarker Results.

PURPOSE: To evaluate a triplet regimen combining immune checkpoint blockade, AKT pathway inhibition, and (nab-) paclitaxel as first-line therapy for locally advanced/metastatic triple-negative breast cancer (mTNBC). PATIENTS AND METHODS: The single-arm CO40151 phase Ib study (NCT03800836), the single-arm signal-seeking cohort of IPATunity130 (NCT03337724), and the randomized phase III IPATunity170 trial (NCT04177108) enrolled patients with previously untreated mTNBC. Triplet therapy comprised intravenous atezolizumab 840 mg (days 1 and 15), oral ipatasertib 400 mg/day (days 1-21), and intravenous paclitaxel 80 mg/m2 (or nab-paclitaxel 100 mg/m2; days 1, 8, and 15) every 28 days. Exploratory translational research aimed to elucidate mechanisms and molecular markers of sensitivity and resistance. RESULTS: Among 317 patients treated with the triplet, efficacy ranged across studies as follows: median progression-free survival (PFS) 5.4 to 7.4 months, objective response rate 44% to 63%, median duration of response 5.6 to 11.1 months, and median overall survival 15.7 to 28.3 months. The safety profile was consistent with the known toxicities of each agent. Grade ≥3 adverse events were more frequent with the triplet than with doublets or single-agent paclitaxel. Patients with PFS >10 months were characterized by NF1, CCND3, and PIK3CA alterations and increased immune pathway activity. PFS <5 months was associated with CDKN2A/CDKN2B/MTAP alterations and lower predicted phosphorylated AKT-S473 levels. CONCLUSIONS: In patients with mTNBC receiving an ipatasertib/atezolizumab/taxane triplet regimen, molecular characteristics may identify those with particularly favorable or unfavorable outcomes, potentially guiding future research efforts.

Effects of aromatase inhibitor therapy on adiposity and cardiometabolic health in postmenopausal women: a controlled cohort extension study.

Purpose: We previously demonstrated that 12 months of aromatase inhibitor (AI) treatment was not associated with a difference in body composition or other markers of cardiometabolic health when compared to controls. Here we report on the pre-planned extension of the study. The pre-specified primary hypothesis was that AI therapy for 24 months would lead to increased visceral adipose tissue (VAT) area when compared to controls. Methods: We completed a 12-month extension to our prospective 12-month cohort study of 52 women commencing AI treatment (median age 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (63.5 years). Our primary outcome of interest was VAT area. Secondary and exploratory outcomes included other measures of body composition, hepatic steatosis, measures of atherosclerosis and vascular reactivity. Using mixed models and the addition of a fourth time point, we increased the number of study observations by 79 and were able to rigorously determine the treatment effect. Results: Among study completers (AI = 39, controls = 40), VAT area was comparable between groups over 24 months, the mean-adjusted difference was -1.54 cm2 (95% CI: -14.9; 11.9, P = 0.79). Both groups demonstrated parallel and continuous increases in VAT area over the observation period that did not diverge or change between groups. No statistically significant difference in our secondary and exploratory outcomes was observed between groups. Conclusions: While these findings provide reassurance that short-to-medium-term exposure to AI therapy is not associated with metabolically adverse changes when compared to controls, risk evolution should be less focussed on the AI-associated effect and more on the general development of cardiovascular risk over time.

Land use change increases contaminant sequestration in blue carbon sediments.

Coastal blue carbon habitats perform many important environmental functions, including long-term carbon and anthropogenic contaminant storage. Here, we analysed twenty-five 210Pb-dated mangrove, saltmarsh, and seagrass sediment cores from six estuaries across a land-use gradient to determine metal, metalloid, and phosphorous sedimentary fluxes. Cadmium, arsenic, iron, and manganese had linear to exponential positive correlations between concentrations, sediment flux, geoaccumulation index, and catchment development. Increases in anthropogenic development (agricultural or urban land uses) from >30 % of the total catchment area enhanced mean concentrations of arsenic, copper, iron, manganese, and zinc between 1.5 and 4.3-fold. A ~ 30 % anthropogenic land-use was the threshold in which blue carbon sediment quality begins to be detrimentally impacted on an entire estuary scale. Fluxes of phosphorous, cadmium, lead, and aluminium responded similarly, increasing 1.2 to 2.5-fold when anthropogenic land-use increased by at least 5 %. Exponential increases in phosphorus flux to estuary sediments seem to precede eutrophication as observed in more developed estuaries. Overall, multiple lines of evidence revealed how catchment development drives blue carbon sediment quality across a regional scale.

Influence of yttria content and surface treatment on the strength of translucent zirconia materials.

STATEMENT OF PROBLEM: Newly developed translucent zirconia materials have been used for anterior monolithic complete coverage restorations. Surface treatments can improve adhesion, as well as decrease or increase the strength of ceramics. However, information on the influence of surface treatments on the strength of translucent zirconias is sparse. PURPOSE: The purpose of this in vitro study was to measure and characterize the effects of different surface treatments, including airborne-particle abrasion, on the strength of different translucent 4 mol% and 5 mol% yttria-stabilized zirconia materials. MATERIALS AND METHODS: Disks (N=160) made from 4 types of translucent yttria-stabilized zirconia materials were surface-treated in 4 ways: Control groups were hand-polished with 2000-grit silicon carbide abrasive paper; as-machined; glass bead airborne-particle abraded; and alumina airborne-particle abraded. The biaxial flexural strength was measured by using a piston-on-3-ball test in a universal testing machine. The simple main effects of material type and surface treatment and their interaction on biaxial flexural strength were evaluated with 2-way ANOVA (α=.05). A priori, 1-way ANOVA and the Tukey multiple comparisons tests were used within material and treatment types (α=.05). Surface morphology was assessed by using scanning electron microscopy. Translucency, absolute transmittance, was measured by using a spectrophotometer. RESULTS: Two-way ANOVA revealed that the effects of zirconia type, surface treatment, and their interaction all significantly affected biaxial flexural strength (P<.001). One-way ANOVA revealed that the 4Y material was stronger than all 5Y materials, regardless of surface treatment; all 5Y materials were ranked from strongest to weakest as polished; as-machined, or glass bead abraded; and alumina abraded. The 4Y material was stronger when alumina abraded than when glass bead abraded. Scanning electron microscopy showed that as-polished surfaces were smoother than all others; as-machined and glass bead abraded surfaces displayed little difference; alumina abraded was the roughest; and differences among materials were not discerned. The 1-way ANOVA and multiple comparisons testing showed that the 4Y material had less absolute transmittance, approximately 5% less, than all the 5Y materials. CONCLUSIONS: Zirconia material type and surface treatment influenced the strength of translucent zirconia materials; a 4 mol% zirconia material was stronger than 5 mol% zirconia materials for all surface treatments tested; airborne-particle abrasion using alumina had a slight strengthening effect on a 4 mol% zirconia but had a weakening effect on 5 mol% materials; airborne-particle abrasion by using alumina produced the roughest surfaces on all materials; and the 4 mol% material was slightly less translucent than the 5 mol% materials.

Effects of aromatase inhibitor therapy on visceral adipose tissue area and cardiometabolic health in postmenopausal women with early and locally advanced breast cancer.

OBJECTIVE: Aromatase inhibitor (AI) therapy provides oncological benefits in postmenopausal women with oestrogen receptor-positive breast cancer. However, AI treatment has been associated with increased cardiovascular risk. In nonbreast cancer populations, experimentally induced low oestrogen states and natural transition to menopause have been associated with increases in visceral adipose tissue (VAT), a known surrogate marker for cardiometabolic risk. Given that AI treatment blocks oestradiol production, we hypothesized that AI treatment would increase VAT. METHODS: We conducted a prospective 12-month cohort study of 52 postmenopausal women newly initiating AI treatment (median age: 64.5 years) and 52 women with breast pathology not requiring endocrine therapy (median age: 63.5 years). VAT area and other body composition parameters were measured at baseline, 6 months and 12 months using dual X-ray absorptiometry. Other risk markers of cardiometabolic health were also assessed. RESULTS: In women initiating AI treatment, there was no statistically significant difference in VAT area after 12 months when compared to controls, with a mean adjusted difference of -5.00 cm2 (-16.9, 6.91), p = .55. Moreover, changes in total fat mass, lean mass, subcutaneous adipose tissue area, hepatic steatosis and measures in endothelial function were also not statistically different between groups after 12 months. Findings were similar after adjustments for activity levels and coronavirus disease 2019 lockdown duration. CONCLUSIONS: These data provide reassurance that over the initial 12 months of AI therapy, AI treatment is not associated with metabolically adverse changes in body composition, hepatic steatosis or vascular reactivity. The impact of extended AI therapy on cardiometabolic health requires further study.

Pesticide occurrence in an agriculturally intensive and ecologically important coastal aquatic system in Australia.

Coastal agricultural practices are often located in catchments upstream of ecologically important aquatic systems. Here, we investigate the occurrence of pesticides in a coastal creek flowing into a habitat-protected area within the Solitary Islands Marine Park, Australia. Water samples were collected from six sites along a creek transect during three sampling periods. Samples were analysed for 171 pesticide analytes, including organochlorines, organophosphates, herbicides, and fungicides. Five insecticides, two herbicides, and two fungicides were detected. The neonicotinoid imidacloprid was detected at 5 out of 6 sites, with concentrations reaching 294 µg L-1, the highest yet detected in Australian waterways. The organophosphate insecticide dimethoate was detected at 4 sites, which occurred at the 2nd highest detected concentration in the study (12.8 µg L-1). The presence of these pesticides in the aquatic environment downstream of horticulture in this and other regions may have serious implications for stream biota and ecologically important marine ecosystems.

Including migrant oncology patients in research: A multisite pilot randomised controlled trial testing consultation audio-recordings and question prompt lists.

Background: Oncology patients who are migrants or refugees face worse outcomes due to language and communication barriers impacting care. Interventions such as consultation audio-recordings and question prompt lists may prove beneficial in mediating communication challenges. However, designing robust research inclusive of patients who do not speak English is challenging. This study therefore aimed to: a) pilot test and assess the appropriateness of the proposed research design and methods for engaging migrant populations, and b) determine whether a multi-site RCT efficacy assessment of the communication intervention utilising these methods is feasible. Methods: This study is a mixed-methods parallel-group, randomised controlled feasibility pilot trial. Feasibility outcomes comprised assessment of: i) screening and recruitment processes, ii) design and procedures, and iii) research time and costing. The communication intervention comprised audio-recordings of a key medical consultation with an interpreter, and question prompt lists and cancer information translated into Arabic, Greek, Traditional, and Simplified Chinese. Results: Assessment of feasibility parameters revealed that despite barriers, methods utilised in this study supported the inclusion of migrant oncology patients in research. A future multi-site RCT efficacy assessment of the INFORM communication intervention using these methods is feasible if recommendations to strengthen screening and recruitment are adopted. Importantly, hiring of bilingual research assistants, and engagement with community and consumer advocates is essential. Early involvement of clinical and interpreting staff as key stakeholders is likewise recommended. Conclusion: Results from this feasibility RCT help us better understand and overcome the challenges and misconceptions about including migrant patients in clinical research.

Analysis of socioeconomic factors in laryngology clinic utilization for treatment of dysphonia.

OBJECTIVE: To evaluate the association between patient socioeconomic and demographic factors and tertiary care utilization for dysphonia in a localized metropolitan area of the American Midwest. METHODS: Multivariate regression analysis was used to correlate patient demographics and population level data (e.g., age, gender, race, insurance, median income, education level) with tertiary laryngology utilization for dysphonia care at our institution between 2000 and 2019. Initial analyses characterized tertiary laryngology utilization rates for all regional ZIP codes and correlated these data with census information for household income and education. Dysphonia patient demographics were compared among populations cared for in our entire academic Otolaryngology department, our health system, and the regional population. RESULTS: Among 1,365,021 patients in our health system, there were 7066 tertiary laryngology visits with a diagnosis of dysphonia. Dysphonia patients as compared to the overall health system were older (62.0 vs. 50.8 years), more likely to be female (63.7 vs. 50.2%) and more likely to have insurance (98.4 vs. 87.5%, all p < .001). Patient and population-level factors including insurance status, education, and black race showed positive correlation with laryngology utilization while median income did not. CONCLUSIONS AND RELEVANCE: Insurance status, education level, and race correlated with utilization of tertiary laryngology services for the evaluation of dysphonia in our community, while median income did not. Black patients utilized tertiary laryngology care at higher rates compared to departmental and regional population utilization data. These results underscore important demographic and disease-specific factors that may affect utilization of subspecialty care in Otolaryngology. LEVEL OF EVIDENCE: IV.

Anthropogenic nitrate attenuation versus nitrous oxide release from a woodchip bioreactor.

Nitrogen loss via overland flow from agricultural land use is a global threat to waterways. On-farm denitrifying woodchip bioreactors can mitigate NO3- exports by increasing denitrification capacity. However, denitrification in sub-optimal conditions releases the greenhouse gas nitrous oxide (N2O), swapping the pollution from aquatic to atmospheric reservoirs. Here, we assess NO3--N removal and N2O emissions from a new edge-of-field surface-flow bioreactor during ten rain events on intensive farming land. Nitrate removal rates (NRR) varied between 5.4 and 76.2 g NO3--N m-3 wetted woodchip d-1 with a mean of 30.3 ± 7.3 g NO3--N m-3. The nitrate removal efficiency (NRE) was ∼73% in ideal hydrological conditions and ∼18% in non-ideal conditions. The fraction of NO3--N converted to N2O (rN2O) in the bioreactor was ∼3.3 fold lower than the expected 0.75% IPCC emission factor. We update the global bioreactor estimated Q10 (NRR increase every 10 °C) from a recent meta-analysis with previously unavailable data to >20 °C, yielding a new global Q10 factor of 3.1. Mean N2O CO2-eq emissions (431.9 ± 125.4 g CO2-eq emissions day-1) indicate that the bioreactor was not significantly swapping aquatic NO3- for N2O pollution. Our estimated NO3--N removal from the bioreactor (9.9 kg NO3--N ha-1 yr-1) costs US$13.14 per kg NO3--N removed and represents ∼30% NO3--N removal when incorporating all flow and overflow events. Overall, edge-of-field surface-flow bioreactors seem to be a cost-effective solution to reduce NO3--N runoff with minor pollution swapping to N2O.

Symptomology following mRNA vaccination against SARS-CoV-2.

Despite demonstrated efficacy of vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of coronavirus disease-2019 (COVID-19), widespread hesitancy to vaccination persists. Improved knowledge regarding frequency, severity, and duration of vaccine-associated symptoms may help reduce hesitancy. In this prospective observational study, we studied 1032 healthcare workers who received both doses of the Pfizer-BioNTech SARS-CoV-2 mRNA vaccine and completed post-vaccine symptom surveys both after dose 1 and after dose 2. We defined appreciable post-vaccine symptoms as those of at least moderate severity and lasting at least 2 days. We found that symptoms were more frequent following the second vaccine dose than the first (74% vs. 60%, P < 0.001), with >80% of all symptoms resolving within 2 days. The most common symptom was injection site pain, followed by fatigue and malaise. Overall, 20% of participants experienced appreciable symptoms after dose 1 and 30% after dose 2. In multivariable analyses, female sex was associated with greater odds of appreciable symptoms after both dose 1 (OR, 95% CI 1.73, 1.19-2.51) and dose 2 (1.76, 1.28-2.42). Prior COVID-19 was also associated with appreciable symptoms following dose 1, while younger age and history of hypertension were associated with appreciable symptoms after dose 2. We conclude that most post-vaccine symptoms are reportedly mild and last <2 days. Appreciable post-vaccine symptoms are associated with female sex, prior COVID-19, younger age, and hypertension. This information can aid clinicians in advising patients on the safety and expected symptomatology associated with vaccination.

Assessing pesticide, trace metal, and arsenic contamination in soils and dam sediments in a rapidly expanding horticultural area in Australia.

Industrial horticulture can release pesticides and trace metals/metalloids to terrestrial and aquatic environments. To assess long-term and more recent land contamination from an expanding horticultural region, we sampled soils from chemical mixing, crop production, and drainage areas, as well as retention reservoirs (dam) sediments, from 3 blueberry farms with varying land-use history in subtropical Australia. Soils were analysed for 97 different pesticides and trace metal/metalloid contents. The most recent farm had fungicides propiconazole and cyprodinil contents that may compromise soil invertebrate survival and/or nutrient recycling (5-125 mg kg-1). A site previously used to cultivate bananas had 6 dam sediment subsamples with arsenic contents over sediment quality guidelines (SQG); however, the soil content values were just below Australian health investigation levels (100 mg kg-1). Arsenic is suspected to originate from pesticide application during previous banana cultivation in the region. Dam sediment cores at all sites had mercury contents over the SQG likely due to fungicides or fertiliser impurities. Mean contents of mercury from dam sediments (141 ± 15.5 µg kg-1) were greater than terrestrial soils (78 ± 6.5 µg kg-1), and sediment profiles suggest mercury retention in anoxic sediments. Soils in chemical mixing areas at two sites were contaminated with copper and zinc which were above the national soil ecological investigation levels. Based on toxicity data, distribution, persistence, and mobility, we identified the fungicide cyprodinil, mercury, and phosphorus as contaminants of the greatest concern in this intensive horticulture area of Australia. Additional sampling (spatial, chemical speciation, biotic) is required to support mitigation efforts of the emerging contamination in the rapidly expanding blueberry farms of this region of Australia.

Cryptic night-time trace metal and metalloid contamination in an intensively cultivated coastal catchment.

Detailed, high resolution time-series observations were performed to investigate sources, diel cycling, natural attenuation, and loadings of dissolved trace metals/metalloids in a subtropical headwater stream draining intensive horticulture in Australia. A transect of ∼3 km away from the source (farms) showed >75% reduction in concentration and loads of most trace elements. Mercury and arsenic had elevated loads downstream relative to other elements. Hourly time-series sampling revealed elevated creek discharge at night, accompanied by elevated nickel, selenium, copper, and mercury loads. Inputs from groundwater or treated sewage used for irrigation within the catchment are likely sources. Groundwater bore and treated sewage samples were highly contaminated with either zinc, copper, or mercury. Comparisons of daily and hourly samples indicated common sampling strategies can underestimate horticultural contaminant loadings. Load estimates for mercury and copper derived from hourly samples were 1.6- to 7- fold greater than loads from daily sample data collected over 79 days with varying rainfall. These high contaminant concentrations and loads are of concern to food products receiving irrigation and protected waterbodies downstream.

Land use and episodic rainfall as drivers of nitrogen exports in subtropical rivers: Insights from δ15N-NO3-, δ18O-NO3- and 222Rn.

Ongoing land-use intensification in subtropical catchments is expected to release more inorganic nitrogen to downstream coastal waters similar to historical changes in temperate ecosystems. Here, we examined spatial and temporal drivers of stream nitrogen loads across a subtropical land-use gradient using the isotopic compositions of nitrate (NO3--N) and radon (222Rn), a natural groundwater tracer. We investigated eleven subtropical creeks/rivers over contrasting hydrological conditions in Australia. NOx-N (nitrite (NO2--N) + nitrate (NO3--N)) accounted for 13.1%, 34.0%, and 42.6% of total dissolved nitrogen (TDN-N) in forest, peri-urban and agricultural creeks, respectively. Following an 80 mm rain event, loads of dissolved inorganic nitrogen (DIN-N) from agriculture catchments reached 368 mg N m-2 catchment area day-1. Forest and peri-urban catchments had aquatic TDN-N loads 17.8% and 31.1% of loads from agricultural catchments. Radon observations suggest that nitrogen and phosphorus loads were driven primarily by surface runoff rather than groundwater discharge. The δ15N-NO3- and δ18O-NO3- values in the agriculture, forest and peri-urban catchments indicate fertilisers and soil nitrogen as the main sources of NO3--N. However, one of the catchments (Double Crossing Creek) received a mixture of recirculated greywater and chemical nitrogen fertilisers. Isotopic signatures imply significant NO3--N losses via denitrification during dry conditions. Groundwater discharge played a minor role because regional aquifers were not contaminated by nitrogen. Overall, intensive agricultural land use and episodic rainfall events were the major spatial and temporal drivers of nitrogen loads.

Durvalumab induced sarcoid-like pulmonary lymphadenopathy.

Immune checkpoint inhibitors (ICIs) have become pivotal in the treatment of lung cancer. An increasing number of immune-related adverse events (irAEs) have been recognized with their use. To our knowledge, this is the first published case of sarcoid-like pulmonary lymphadenopathy associated with durvalumab, a monoclonal antibody against programmed death ligand-1 (PD-L1). A 76-year-old woman received adjuvant durvalumab for Stage IIA pT2aN1M0 (American Joint Committee on Cancer, Seventh edition) poorly differentiated lung adenocarcinoma. After three cycles, a sarcoid-like granulomatous reaction was identified in mediastinal and hilar lymph nodes. Although the lymphadenopathy remained stable in size with the ongoing treatment, progressive intracranial metastases were identified after a further three cycles of durvalumab. Sarcoid-like inflammation with the formation of non-caseating granulomas in the absence of systemic sarcoidosis is an irAE which may mimic disease progression. Although a subset of patients who experience this reaction may have a favourable response to checkpoint inhibition, progression of disease may occur contemporaneously.

A simple 3-point flexural method for measuring fracture toughness of the dental porcelain to zirconia bond and other brittle bimaterial interfaces.

PURPOSE: Porcelain fused to zirconia prostheses are widely used, but porcelain chipping, fracture, spalling and delamination are common clinical problems. Conventional bond strength testing is inherently unsuited for studying interfacial failure by cracking in brittle materials. Instead, fracture toughness is a more meaningful parameter because it can assess the robustness of the interface when subjected to loading, but fracture mechanics approaches have only rarely been used. Our purpose was to develop a novel, simple, 3-point flexural methodology and mathematical analysis to measure the fracture toughness of the porcelain to zirconia interface. METHODS: Equations were derived to estimate the fracture toughness of the bond by computing the interfacial energy release rate for a novel simple 3-point flexural test model. The test was validated using two different configurations of layered zirconia/porcelain beams (n = 10), approximating the dimensions of a fixed dental prosthesis, fabricated from a tetragonal polycrystalline zirconium dioxide partially stabilized with yttria and a feldspathic dental porcelain. RESULTS: Cracking along the bimaterial interface was produced and measured as a discrete event. Fracture toughness means (standard deviations) computed from the measured energy release rate, for the porcelain to zirconia interface in two different specimen configurations were 7.9 (1.3) and 5.3 (1.6) J/m2. CONCLUSIONS: Equations were derived to measure interfacial fracture toughness of brittle materials using a novel simple 3-point flexural test method. The test was then validated; estimates for the fracture toughness for the porcelain to zirconia bond, overlapped with previously published data derived from more complex 4-point notched tests.

The Role of Exparel Plus Meloxicam for Postoperative Pain Management.

PURPOSE OF REVIEW: Acute postoperative pain reduction is a major target against the opioid crisis. While opioids have traditionally been the mainstay for postoperative analgesia, current practice has focused on a multimodal approach to pain control, including ultrasound-guided blocks with longer acting local anesthetic agents. RECENT FINDINGS: Non-steroidal anti-inflammatory drugs (NSAIDs), such as meloxicam, are an important class of medications utilized to manage pain in the perioperative period. An additional treatment used in perioperative or postoperative pain relief is Exparel, a bupivacaine (sodium channel blocker) liposomal injectable suspension with a 3-4-day duration of action. The long-acting mechanism and formulation of Exparel consistently has demonstrated decreased opioid use and pain scores in patients undergoing many different surgical procedures. A concern is that pH negatively alters the efficacy of bupivacaine, as in cases of inflamed tissue and acidic fluid pH. For this reason, a combination medication with both meloxicam and bupivacaine has been developed, which normalizes pH and has anti-inflammatory and anti-pain conduction properties. Clinical studies demonstrate that this combination agent can be extremely beneficial in treating postoperative pain. This manuscript summarizes the newest developments with regard to liposomal bupivacaine and the non-steroidal meloxicam, their roles in effective treatment of postoperative pain, contraindications, special considerations of using these medications, and future considerations. HTX-011 pairs up a new extended-release formulation of the local anesthetic bupivacaine with meloxicam, a well-established non-steroidal anti-inflammatory drug (NSAID).