Synthetic Studies on Tetracyclic Diquinane Lycopodium Alkaloids Magellanine, Magellaninone and Paniculatine.

(-)-Magellanine, (+)-magellaninone, and (+)-paniculatine are three natural products isolated from the Lycopodium family that share a unique 6-5-5-6-fused tetracyclic diquinane core skeleton. Several members of this family have potent s anti-inflammatory and acetylcholinesterase-inhibitory properties and are under development for the treatment of Alzheimer's and other neurodegenerative diseases. Several research groups have undertaken the formal and total syntheses of this class of natural products. This review highlights over 20 reported total syntheses of these three alkaloids and the development of synthetic methods for the assembly of their core skeletons.

Application of native plants in constructed floating wetlands as a passive remediation approach for PFAS-impacted surface water.

Strategies for remediation of per- and polyfluoroalkyl substances (PFAS) generally prioritise highly contaminated source areas. However, the mobility of PFAS in the environment often results in extensive low-level contamination of surface waters across broad areas. Constructed Floating Wetlands (CFWs) promote the growth of plants in buoyant structures where pollutants are assimilated into plant biomass. This study examined the hydroponic growth of Juncus krausii, Baumea articulata and Phragmites australis over a 28-day period for remediation of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) contaminated (0.2 µg/L to 30 µg/L) urban stormwater. With increasing PFOA and PFOS concentrations, accumulation in plant species increased although root and shoot distribution varied depending on PFAS functional group. Less PFOA than PFOS accumulated in plant roots (0.006-0.16 versus 0.008-0.68 µg/g), while more PFOA accumulated in the plant shoots (0.02-0.55 versus 0.01-0.16 µg/g) indicating translocation to upper plant portions. Phragmites australis accumulated the highest overall plant tissue concentrations of PFOA and PFOS. The NanoSIMS data demonstrated that PFAS associated with roots and shoots was absorbed and not just surface bound. These results illustrate that CFWs have the potential to be used to reduce PFAS contaminants in surface waters.

Primary Eccrine Adenocarcinoma: A Rare but Dangerous Lesion of the Eyelid.

Sweat gland carcinomas can be of eccrine or apocrine origin, with the former being more common in the eyelid. They can also be of three different types, the most common of which is mucin-producing sweat gland carcinoma, which is most often a low-grade malignancy. Here, we report a case of a primary estrogen receptor-positive eccrine adenocarcinoma of the eyelid that clinically presented like a cyst of Moll. Importantly, in our experience with this lesion, this rare malignancy was repeatedly misdiagnosed as less sinister lesions, surgical resection margins of the lesion could be easily underestimated, and close liaison with our general surgical colleagues was vital to exclude more common breast carcinoma. This case highlights the dangers of referral recommendation policies (e.g., procedures of limited clinical value as used by primary care) and the importance of incisional biopsy in the management of periocular lesions.

Outcomes of ocular evisceration and enucleation in the British Armed Forces from Iraq and Afghanistan.

BACKGROUND/OBJECTIVES: To evaluate outcomes from all British military patients who underwent eye removal during the Iraq and Afghanistan wars. SUBJECTS/METHODS: Retrospective case note review of all patients (n = 19) who had undergone either evisceration or enucleation, on a database of all military patients repatriated to the Royal Centre for Defence Medicine, Birmingham. RESULTS: Twenty eye removals were performed on 19 patients, of which 14 (70%) were eviscerations and 6 (30%) were enucleations. Orbital wall fractures were seen in 12 (61%) patients, with orbital floor fractures being the most common. The eye removal was a primary procedure in five of fourteen eviscerations, and five of six enucleations. Complications were seen after four (28.6%) eviscerations patients and two (33.3%) enucleations. Postoperative pain was problematic after three (21.4%) eviscerations but no enucleations. Orbital implants were placed during three of the five primary enucleations, with good outcomes in two. One patient however required implant retrieval and wound washout due to a high risk of infection and communication with the intra-cranial space. CONCLUSIONS: Evisceration and enucleation are both viable options in the management of severe ocular trauma in military patients. Evisceration and enucleation have similar complication rates and outcomes, and both have low rates of sympathetic ophthalmia. Primary orbital implants can be at high risk in cases with orbital roof fracture, but can provide good outcomes in select patients.

Removal of emerging drugs of addiction by wastewater treatment and water recycling processes and impacts on effluent-associated environmental risk.

Drugs of addiction, have been recognized as potential contaminants of concern to the environment. Effluent wastewater discharge is a major source of contamination to aquatic receiving environments. A year-long monitoring program was undertaken in Australia to characterise the fate of four emerging drugs of addiction: methamphetamine; MDMA; pharmaceutical opioids: codeine and morphine and a metabolite: benzoylecgonine in four wastewater treatment plants operating with different secondary treatment technologies: conventional activated sludge (CAS), membrane bioreactors (MBR), integrated fixed-film AS (IFAS) and sequencing batch reactor (SBR). The effect of subsequent tertiary treatment (coagulation/flocculation) on the removal efficiency was also assessed. Drugs were detected in influent and effluent samples (mean concentration ranged from 43-4777 and 17-1721 ng/L, respectively). Treated effluents had noticeably lower levels compared to raw influents. Removal efficiency of compounds depended on the secondary treatment employed, with IFAS and MBR performing the best with significant removal of compounds (≈90%) followed by CAS (54-96%) and lastly SBR (42-83%). Despite the low levels of drugs measured after the secondary treatment, near complete removal after tertiary treatment (≈99%) was recorded, which demonstrated the effectiveness of using the coagulation/flocculation process as an effective step for enhancing the removal efficiency. The levels of drugs were at a low level in the effluents released into the environment and used for recycling and all posed a low environmental risk in urban water courses based on the risk assessment. The information given here provides new and useful information to the water industry and regulators on the efficiency of drug removal in a range of wastewater treatment configurations.

Monitoring of airborne particulates near industrial silica sand mining and processing facilities.

To quantify risk of ambient exposure to airborne particulates around industrial silica sand operations, this study used EPA-certified federal reference method monitors to measure the levels of PM10 and PM2.5 particulate matter. The monitoring sites were chosen based upon EPA siting criteria, dichotomous samplers were calibrated before and after sampling, and pre- and post-weight filter weights were recorded. PM2.5 levels were significantly higher (paired t-tests) at both sites - averages of 7.70 ± 6.15 and 22.7 ± 31.714;µg/m3 - than concurrent background levels of 5.11 and 6.57µg/m3 respectively; and 98th percentile values were 24.9 and 111 µg/m3, respectively. Average PM10 levels were 24.2 and 49.0 µg/m3, and second-highest annual levels were 45.5 and 69.1 µg/m3 (two years) and 62.9 ug/m3 (2015) and 61.5 ug/m3 (2016), respectively for the two sites. Neither precipitation nor wind speed or direction appeared to affect PM2.5 or PM10 concentrations.

Study of the impacts of process changes of a pulp and paper mill on aerated stabilization basin (ASB) performance.

A laboratory scale (LS) and a field-based pilot plant (PP), designed to simulate aerobic stabilization basin (ASB) operation, were utilized to assess the potential impacts of changes in pulp and paper (P&P) mill operations on full-scale (FS) ASB performance. Two stages of investigation were conducted. The first was undertaken to determine the potential of pre-alum treatment of pulp mill wastewaters on ASB performance. The second investigation was conducted to assess ASB performance where wastewaters transitioned from being coagulated pulp and paper mill wastewaters to paper mill wastewaters only. Simulation ASB performance was assessed based on removals of BOD5, colour, UV@254 nm and nutrients [total phosphorus (TP) and nitrogen compounds (TN)]. Pre-alum treatment of pulp mill wastewaters with subsequent ASB treatment following mixing with paper mill wastewaters showed high percentage removals of BOD5. Despite low TP concentrations (≤0.05 mg/L) and low nutrient to BOD5 ratios of wastewaters in the LS-ASB trial, the high % BOD5 removal indicated recycling of nutrients from sludge [sourced from the FS-ASB]. Despite coagulation of pulp mill wastewater being performed using a very high alum dose (∼2000 mg/L) to remove colour and its precursors, colour formation remained high throughout the simulated ASB trials. Simulation of discontinuation of pulping indicated that colour would reduce rapidly to low levels in ASB wastewaters, but that TP and TN concentrations would persist for longer periods of time and decline slowly. Survey data of water qualities of the FS-ASB system obtained before, during and 2 years after discontinuation of pulping are presented.

Field based pilot-scale drinking water distribution system: Simulation of long hydraulic retention times and microbiological mediated monochloramine decay.

Drinking water distribution systems with long hydraulic retention times (HRTs) commonly encounter rapid microbiological-mediated monochloramine decay that results in microbial regrowth and nitrification with reduction in alkalinity. In this paper, we report the design and operation of a field-based pilot-scale distribution system (PDS) operated at flows that simulate long HRTs (∼10 days) to promote rapid microbiological monochloramine decay over long periods. The PDS is designed to enable the testing of chemical treatment for the control of nitrification and monochloramine decay. The PDS has two identical cylindrical polyethylene tanks (DS1 & DS2), each of 1 m diameter and 1.8 m height (∼1 kL) holding 900 m of polyethylene (PE) tubing with sampling points every 300 m intervals. Microbial mediated decay (determined by the Fm test) of monochloramine occurred as treated (alum coagulated and flocculated) and chloraminated water passed through the DSs. In this manuscript we report: •An inexpensive, flexible and compact system that can be readily set-up at a full-scale water treatment plant, requiring minimal supervision for operation.•A 'draw & fill' system for achieving control on HRT's through the pipes.

Admission Hyperoxia Is a Risk Factor for Mortality in Pediatric Intensive Care.

OBJECTIVES: To determine whether the association between hyperoxia and increased risk-adjusted mortality in adult intensive care patients is also observed in a pediatric intensive care population. DESIGN: Single-center retrospective analysis of admissions to ICU over a 5-year period commencing January 1, 2012, examining the relationship between PaO2 measured within the first hour of admission and risk-adjusted mortality. Standardized mortality rates were calculated using the Pediatric Index of Mortality-3, and patients were grouped into 50 mm Hg (6.67 kPa) PaO2 bands to assess the relationship between initial PaO2 and risk-adjusted mortality. SETTING: Tertiary PICU with 17 beds and 1,100 annual admissions located in metropolitan Sydney, Australia. PATIENTS: A total of 1,447 patients 0-18 years old with PaO2 recorded at admission to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 5,176 patients admitted to the ICU during the study period and 1,447 (28%) with PaO2 recorded at admission. A U-shaped relationship between raw mortality and admission PaO2 was observed, with lowest mortality (2.3% and 2.6%, respectively) observed in the 101-150 (13.5-20.0 kPa) and 151-200 mm Hg (20.1-26.7 kPa) bands and the highest mortality observed in patients with PaO2 less than 50 mm Hg (6.67 kPa) with mortality of 5.3%, or greater than 350 mm Hg (46.7 kPa) with mortality of 18.2%. Hyperoxia at admission was associated with an increase in risk-adjusted mortality, with polynomial regression indicating a strong correlation between PaO2 band and risk-adjusted outcome (r = 0.845). When included in a multivariate model that included the Pediatric Index of Mortality-3 variables, the odds ratio for hyperoxia (defined as PaO2 > 250 mm Hg [33.3 kPa]) predicting death was 2.66 (p = 0.047). CONCLUSIONS: In this single-center study, hyperoxia at admission to the PICU was highly correlated with increased risk-adjusted mortality. Further investigation of these observations in a large multicenter cohort is warranted.

Modelling of THM formation potential and DOM removal based on drinking water catchment characteristics.

Catchment properties influence the character and concentration of dissolved organic matter (DOM). Surface and subsurface runoff from discrete catchments were collected and DOM was measured and assessed in terms of its treatability by Enhanced Coagulation and potential for disinfection by-product (trihalomethane, THMFP) formation potential. Models were developed of [1] DOM character [i.e. SUVA and SpCoL] and concentration (measured as dissolved organic carbon), [2] treatability of DOM by coagulation/flocculation processes and [3] specific THMFP based on the catchment features including: (a) surface and sub-surface soil texture (% clay: 5-25%), (b) topography (% slope: 5-15%) and (c) vegetation cover [i.e. high photosynthetic vegetation, low photosynthetic vegetation and bare soil] extracted from RapidEye satellite imagery using spectral mixture analysis. From these models, a catchment management decision support tool was designed for application by catchment managers to support decision-making of land-use and expected water quality related to water resources for drinking water supply. SOFTWARE AND DATA AVAILABILITY: Data sets used for models developing presented in this paper have been published in Research Data Australia (RDA) under the title of "Impacts of catchment properties on DOM and nutrients in waters from drinking water catchments".1 These data sets are available in open access and published in June 2017. A catchment management decision support model (CMDSM) tool was developed. Macros created using Visual Basic for Applications in Excel 2010. Excel 2010 or higher is required to open the CMDSM tool. The tool is provided by the University of South Australia (UniSA) and is not currently available on-line so please contact the corresponding author for access or further information.

Seasonal variation in the nature of DOM in a river and drinking water reservoir of a closed catchment.

Dissolved organic matter (DOM) in surface waters used for drinking purposes can vary markedly in character depending on its source within catchments and the timing and intensity of rainfall events. Here we report the findings of a study on the character and concentration of DOM in waters collected during different seasons from Myponga River and Reservoir, South Australia. The character of DOM was assessed in terms of its treatability by enhanced coagulation and potential for disinfection by-product i.e. trihalomethane (THM) formation. During the wet seasons (winter and spring), water samples from the river had higher DOC concentrations (X¯: 21 mg/L) and DOM of higher average molecular weight (AMW: 1526 Da) than waters collected during the dry seasons (summer and autumn: DOC: 13 mg/L; AMW: 1385 Da). Even though these features led to an increase in the percentage removal of organics by coagulation with alum (64% for wet compared with 53% for dry season samples) and a lower alum dose rate (10 versus 15 mg alum/mg DOC removal), there was a higher THM formation potential (THMFP) from wet season waters (treated waters: 217 µg/L vs 172 µg/L). For reservoir waters, samples collected during the wet seasons had an average DOC concentration (X¯: 15 mg/L), percentage removal of organics by alum (54%), alum dose rates (13 mg/mg DOC) and THMFP (treated waters: 207 µg/L) that were similar to samples collected during the dry seasons (mean DOC: 15 mg/L; removal of organics: 52%; alum dose rate: 13 mg/mg DOC; THMFP: 212 µg/L for treated waters). These results show that DOM present in river waters and treatability by alum are highly impacted by seasonal environmental variations. However these in reservoir waters exhibit less seasonal variability. Storage of large volumes of water in the reservoir enables mixing of influent waters and stabilization of water quality.

Characterization of dissolved organic matter for prediction of trihalomethane formation potential in surface and sub-surface waters.

Dissolved organic matter (DOM) in surface waters used for drinking purposes can vary markedly in character dependent on their sources within catchments. The character of DOM further influences the formation of disinfection by products when precursor DOM present in drinking water reacts with chlorine during disinfection. Here we report the development of models that describe the formation potential of trihalomethanes (THMFP) dependent on the character of DOM in waters from discrete catchments with specific land-use and soil textures. DOM was characterized based on UV absorbance at 254 nm, apparent molecular weight and relative abundances of protein-like and humic-like compounds. DOM character and Br concentration (up to 0.5 mg/L) were used as variables in models (R(2)>0.93) of THMFP, which ranged from 19 to 649 µg/L. Chloroform concentration (12-594 µg/L) and relative abundance (27-99%) were first modeled (R(2)>0.85) and from these, the abundances of bromodichloromethane and chlorodibromomethane estimated using power and exponential functions, respectively (R(2)>0.98). From these, the abundance of bromoform is calculated. The proposed model may be used in risk assessment of catchment factors on formation of trihalomethanes in drinking water, in context of treatment efficiency for removal of organic matter.

Treatability of organic matter derived from surface and subsurface waters of drinking water catchments.

The treatability of NOM present in runoff and subsurface waters from discrete zero-order catchments (ZOCs) with three land management practices (Australian native vegetation, pine plantation, grasslands) on varying soil textures of a closed drinking water reservoir-catchment was investigated. Subsurface water samples were collected by lysimeters and shallow piezometers and surface waters by installation of barriers that diverted waters to collection devices. For small sample volumes collected, a 'micro' jar testing procedure was developed to assess the treatability of organics by enhanced coagulation using alum, under standardised conditions. DOM present in water samples was quantified by measurement of DOC and UV absorbance (at 254 nm) and characterized using these and F-EEM. The mean alum dose rate (mg alum per mg DOC removed or Al/DOC) was found to be lower for DOM from sandy soil ZOCs (21.1 ± 11.0 Al/DOC) than from clayey soil ZOCs (38.6 ± 27.7 Al/DOC). ZOCs with Pinus radiata had prominent litter layers (6.3 ± 2.6 cm), and despite differences in soil textures showed similarity in DOM character in subsurface waters, and in alum dose rates (22.2 ± 5.5 Al/DOC). For sandy soil ZOCs, the lowest alum dose rates (16.5 ± 10.6 Al/DOC) were for waters from native vegetation catchment while, for clayey soil ZOCs, waters from pine vegetation had the lowest alum dose rates (23.0 ± 5.0 Al/DOC). Where ZOCs have a prominent O horizon, soil minerals had no apparent influence on the treatability of DOM.

The effect of vegetation and soil texture on the nature of organics in runoff from a catchment supplying water for domestic consumption.

The influence of vegetation and soil texture on the concentration and character of dissolved organic matter (DOM) present in runoff from the surface and sub-surface of zero order catchments of the Myponga Reservoir-catchment (South Australia) was investigated to determine the impacts of catchment characteristics and land management practices on the quality of waters used for domestic supply. Catchments selected have distinct vegetative cover (grass, native vegetation or pine) and contrasting texture of the surface soil horizon (sand or clay loam/clay). Water samples were collected from three slope positions (upper, middle, and lower) at soil depths of ~30 cm and ~60 cm in addition to overland flows. Filtered (0.45 µm) water samples were analyzed for dissolved organic carbon (DOC) and UV-visible absorbance and by F-EEM and HPSEC with UV and fluorescence detection to characterize the DOM. Surface and sub-surface runoff from catchments with clay soils and native vegetation or grass had lower DOC concentrations and lower relative abundances of aromatic, humic-like and high molecular weight organics than runoff from sandy soils with these vegetative types. Sub-surface flows from two catchments with Pinus radiata had similar DOC concentrations and DOM character, regardless of marked variation in surface soil texture. Runoff from catchments under native vegetation and grass on clay soils resulted in lower DOC concentrations and hence would be expected to have lower coagulant demand in conventional treatment for potable water supply than runoff from corresponding sandy soil catchments. However, organics in runoff from clay catchments would be more difficult to remove by coagulation. Surface waters from the native vegetation and grass catchments were generally found to have higher relative abundance of organic compounds amenable to removal by coagulation compared with sub-surface waters. Biophysical and land management practices combine to have a marked influence on the quality of source water used for domestic supply.

The value of fused SPECT/CT in the evaluation of solitary skull lesion.

AIM: The aim of this study was to evaluate the role of single photon emission computed tomography and/or computed tomography (SPECT/CT) in differentiating metastatic from benign solitary skull lesions. MATERIALS AND METHODS: Consecutive patients who had a SPECT/CT of the head subsequent to a whole-body bone scan (WBS) for the evaluation of a single skull lesion were selected. A single skull lesion on the WBS was further evaluated with SPECT/CT to characterize the lesion. The results of the SPECT/CT were correlated with other radiologic examinations performed within 2 weeks. An average follow-up interval after the SPECT/CT was 8.9 months to correlate with additional radiologic imaging studies and clinical information. RESULTS: A total of 19 lesions in 19 patients were seen on the WBS and 2 additional lesions on the SPECT/CT. All lesions demonstrated focal increased tracer uptake. The SPECT/CT correctly identified 3 out of 3 metastatic lesions and 12 out of 17 benign lesions, that is 71% of lesions were correctly classifised as metastatic or benign lesions. Only 1 patient was classified incorrectly as metastatic lesion with SPECT/CT when it was proven benign by other imaging modalities and follow-up. The sensitivity, specificity, positive and negative predictive values of SPECT/CT images in identifying metastatic lesions were 100%, 92%, 75%, and 100%, respectively. Five lesions remained indeterminate even after the SPECT/CT interpretation and were confirmed benign by other imaging modalities. CONCLUSION: SPECT/CT can help identify benign versus metastatic solitary skull lesions in most of the patients with high sensitivity and specificity.

Extremes of weight centile are associated with increased risk of mortality in pediatric intensive care.

INTRODUCTION: Although numerous studies have linked extremes of weight with poor outcome in adult intensive care patients, the effect of weight on intensive care outcome has not previously been reported in the pediatric population. The aim of this study was to investigate the relationship between admission weight centile and risk-adjusted mortality in pediatric intensive care patients. METHODS: Data were collected on 6337 consecutively admitted patients over an 8.5 year period in a 15 bed pediatric intensive care unit (ICU) located in a university-affiliated tertiary referral children's hospital. A weight centile variable was entered into a multivariate logistic regression model that included all other pediatric index of mortality (PIM-2) variables, in order to determine whether weight centile was an independent risk factor for mortality. RESULTS: Weight centile was associated with mortality in both univariate and multivariate analysis, with the lowest mortality being associated with weights on the 75th centile and increasing symmetrically around this nadir. A transformed weight centile variable (absolute value of weight centile-75) was independently associated with mortality (odds ratio 1.02, P = 0.000) when entered into a multivariate logistic regression model that included the PIM-2 variables. CONCLUSIONS: In this single-center cohort, weight centile was an independent risk factor for mortality in the ICU, with mortality increasing for patients at either end of the weight spectrum. These observations suggest that the accuracy of mortality prediction algorithms may be improved by inclusion of weight centile in the models. A prospective multicenter study should be undertaken to confirm our findings.

After-hours admissions are not associated with increased risk-adjusted mortality in pediatric intensive care.

OBJECTIVE: To examine the influence of time of admission on risk-adjusted mortality and length of stay for nonelective patients admitted to a pediatric intensive care unit (ICU) without 24-h per day in-house intensivist coverage. DESIGN: Data analyzed came from a comprehensive, prospectively collected ICU database. SETTING: A 12-bed pediatric ICU located in a university-affiliated tertiary referral children's hospital. PATIENTS: Subjects consisted of 4,456 consecutive nonelective patients admitted over a 10-year period (1997-2006). INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Patients were categorized according to time of admission to the ICU as either in-hours (0800-1800 Monday-Friday and 0800-1200 on weekends), when an intensivist is present in the ICU, or after-hours (all other times), when intensivists attend only on an as-needed basis. Multivariate logistic regression was used to assess the effect of time of admission on outcome after adjustment for severity of illness using the Paediatric Index of Mortality (PIM). Patients admitted after hours had a lower risk-adjusted mortality than those admitted during normal working hours, with an odds ratio for death of 0.712 (95% confidence interval 0.518-0.980, p = 0.037). Length of stay was also significantly shorter for patients admitted after hours (44.05h vs. 50.0h, p = 0.001). CONCLUSIONS: A lack of in-house intensivist presence is not associated with any increase in mortality or length of stay for patients admitted to our pediatric ICU; on the contrary, after-hours admission in this cohort was associated with a decreased risk-adjusted mortality and a shorter length of stay.