Accumulation of pharmaceuticals, perfluorinated compounds, plasticisers and illicit drug metabolite in aquatic sediment and plants in three rivers of Greater London and SE England

Accumulation of persistent organic pollutants (POPs) in sediment (n=23) and aquatic plants (n=15) was assessed by ultrasonicationassisted extraction (UAE) followed by an in-house validated method for solid phase extraction (SPE) and liquid chromatography tandem mass spectrometry (LC-MS/MS). Eleven POPs were selected: inter alia pharmaceuticals acetaminophen, diclofenac and ethinylestradiol, illicit drug metabolite benzoylecgonine, perfluorinated compounds perfluorooctanoic acid (PFOA), perfluorononanoic acid, perfluorooctanesulfonic acid (PFOS) and perfluorobutane sulfonic acid (PFBS), and plasticisers bisphenol-A (BPA), 4’-hydroxyacetophenone (HAP) and bisphenol-S (BPS). Sediment samples were air dried, homogenised, sieved to 500 um then subjected to UAE for 20 m at 45°C in an extraction solution of 50:50 acetonitrile (ACN):Methanol (MeOH) with 1% acetic acid (v/v) followed by SPE and LC-MS/MS analysis. Bioaccumulation in aquatic plants was assessed using two species: Water Starwart (Callitriche sp., n=8) and Pondweed (Potamogeton sp., n=7). All plant samples were air dried, powdered, homogenised then subjected to UAE for 20 m at 40°C in an extraction solution of 25:75 ACN:MeOH with 1% acetic acid (v/v) followed by SPE and LCMS/MS analysis. Mean recoveries were 76% for sediment and 82% for plants. Ten of eleven POPs were detected in sediments with frequencies ranging from 22-83% (benzoylecgonine and BPA respectively) and mean quantifiable concentrations ranging from 0.84-11.1 ng/g (BPS and BPA respectively). Organic matter content in sediment samples was estimated using standard methods for loss on ignition and ranged from 1.2-6.4%. Seven of eleven POPs were detected in Callitriche sp. with frequencies ranging from 13% (acetaminophen) to 100% (HAP, BPS, PFBS and PFOA) and mean quantifiable concentrations ranging from 0.42-113 ng/g (diclofenac and PFOS respectively). Lastly, eight of eleven POPs were detected in Potamogeton sp. with frequencies ranging from 14-100% (acetaminophen and HAP respectively) and mean quantifiable concentrations from 0.38-71.0 ng/g (acetaminophen and HAP respectively). Overall, levels of target POPs were lowest in sediment and highest in Callitriche sp. with mean levels as much as 18.3 and 11.5 times higher (PFOS) than in sediment and Potamogeton sp. respectively. The extent to which POP bioaccumulation may affect higher trophic levels is unclear and warrants further investigation

Astrocyte Unfolded Protein Response Induces a Specific Reactivity State that Causes Non-Cell-Autonomous Neuronal Degeneration.

Recent interest in astrocyte activation states has raised the fundamental question of how these cells, normally essential for synapse and neuronal maintenance, become pathogenic. Here, we show that activation of the unfolded protein response (UPR), specifically phosphorylated protein kinase R-like endoplasmic reticulum (ER) kinase (PERK-P) signaling-a pathway that is widely dysregulated in neurodegenerative diseases-generates a distinct reactivity state in astrocytes that alters the astrocytic secretome, leading to loss of synaptogenic function in vitro. Further, we establish that the same PERK-P-dependent astrocyte reactivity state is harmful to neurons in vivo in mice with prion neurodegeneration. Critically, targeting this signaling exclusively in astrocytes during prion disease is alone sufficient to prevent neuronal loss and significantly prolongs survival. Thus, the astrocyte reactivity state resulting from UPR over-activation is a distinct pathogenic mechanism that can by itself be effectively targeted for neuroprotection

A mixed-methods study to investigate feasibility and acceptability of an early warning score for preterm infants in neonatal units in Kenya: results of the NEWS-K study

Preterm birth (< 37 weeks gestation) complications are the leading cause of neonatal mortality. Early-warning scores (EWS) are charts where vital signs (e.g., temperature, heart rate, respiratory rate) are recorded, triggering action. To evaluate whether a neonatal EWS improves clinical outcomes in low-middle income countries, a randomised trial is needed. Determining whether the use of a neonatal EWS is feasible and acceptable in newborn units, is a prerequisite to conducting a trial. We implemented a neonatal EWS in three newborn units in Kenya. Staff were asked to record infants’ vital signs on the EWS during the study, triggering additional interventions as per existing local guidelines. No other aspects of care were altered. Feasibility criteria were pre-specified. We also interviewed health professionals (n = 28) and parents/family members (n = 42) to hear their opinions of the EWS. Data were collected on 465 preterm and/or low birthweight (< 2.5 kg) infants. In addition to qualitative study participants, 45 health professionals in participating hospitals also completed an online survey to share their views on the EWS. 94% of infants had the EWS completed at least once during their newborn unit admission. EWS completion was highest on the day of admission (93%). Completion rates were similar across shifts. 15% of vital signs triggered escalation to a more senior member of staff. Health professionals reported liking the EWS, though recognised the biggest barrier to implementation was poor staffing. Newborn unit infant to staff ratios varied between 10 and 53 staff per 1 infant, depending upon time of shift and staff type. A randomised trial of neonatal EWS in Kenya is possible and acceptable, though adaptations are required to the form before implementation

Emollients for preventing atopic eczema: Cost‐effectiveness analysis of the BEEP trial

BackgroundRecent discoveries have led to the suggestion that enhancing skin barrier from birth might prevent eczema and food allergy. ObjectiveTo determine the cost‐effectiveness of daily all‐over‐body application of emollient during the first year of life for preventing atopic eczema in high‐risk children at 2 years from a health service perspective. We also considered a 5‐year time horizon as a sensitivity analysis. MethodsA within‐trial economic evaluation using data on health resource use and quality of life captured as part of the BEEP trial alongside the trial data. Parents/carers of 1394 infants born to families at high risk of atopic disease were randomised 1:1 to the emollient group, which were advised to apply emollient (Doublebase Gel or Diprobase Cream) to their child at least once daily to the whole body during the first year of life or usual care. Both groups received advice on general skin care. The main economic outcomes were incremental cost‐effectiveness ratio (ICER), defined as incremental cost per percentage decrease in risk of eczema in the primary cost‐effectiveness analysis. Secondary analysis, undertaken as a cost‐utility analysis, reports incremental cost per Quality‐Adjusted Life Year (QALY) where child utility was elicited using the proxy CHU‐9D at 2 years. ResultsAt 2 years, the adjusted incremental cost was £87.45 (95% CI −54.31, 229.27) per participant, whilst the adjusted proportion without eczema was 0.0164 (95% CI −0.0329, 0.0656). The ICER was £5337 per percentage decrease in risk of eczema. Adjusted incremental QALYs were very slightly improved in the emollient group, 0.0010 (95% CI −0.0069, 0.0089). At 5 years, adjusted incremental costs were lower for the emollient group, −£106.89 (95% CI −354.66, 140.88) and the proportion without eczema was −0.0329 (95% CI −0.0659, 0.0002). The 5‐year ICER was £3201 per percentage decrease in risk of eczema. However, when inpatient costs due to wheezing were excluded, incremental costs were lower and incremental effects greater in the usual care group. ConclusionsIn line with effectiveness endpoints, advice given in the BEEP trial to apply daily emollient during infancy for eczema prevention in high‐risk children does not appear cost‐effective

Emollient application from birth to prevent eczema in high-risk children: the BEEP RCT.

BACKGROUND: Atopic eczema is a common childhood skin problem linked with asthma, food allergy and allergic rhinitis that impairs quality of life. OBJECTIVES: To determine whether advising parents to apply daily emollients in the first year can prevent eczema and/or other atopic diseases in high-risk children. DESIGN: A United Kingdom, multicentre, pragmatic, two-arm, parallel-group randomised controlled prevention trial with follow-up to 5 years. SETTING: Twelve secondary and four primary care centres. PARTICIPANTS: Healthy infants (at least 37 weeks' gestation) at high risk of developing eczema, screened and consented during the third trimester or post delivery. INTERVENTIONS: Infants were randomised (1 : 1) within 21 days of birth to apply emollient (Doublebase Gel®; Dermal Laboratories Ltd, Hitchin, UK or Diprobase Cream®) daily to the whole body (excluding scalp) for the first year, plus standard skin-care advice (emollient group) or standard skin-care advice only (control group). Families were not blinded to allocation. MAIN OUTCOME MEASURES: Primary outcome was eczema diagnosis in the last year at age 2 years, as defined by the UK Working Party refinement of the Hanifin and Rajka diagnostic criteria, assessed by research nurses blinded to allocation. Secondary outcomes up to age 2 years included other eczema definitions, time to onset and severity of eczema, allergic rhinitis, wheezing, allergic sensitisation, food allergy, safety (skin infections and slippages) and cost-effectiveness. RESULTS: One thousand three hundred and ninety-four newborns were randomised between November 2014 and November 2016; 693 emollient and 701 control. Adherence in the emollient group was 88% (466/532), 82% (427/519) and 74% (375/506) at 3, 6 and 12 months. At 2 years, eczema was present in 139/598 (23%) in the emollient group and 150/612 (25%) in controls (adjusted relative risk 0.95, 95% confidence interval 0.78 to 1.16; p = 0.61 and adjusted risk difference -1.2%, 95% confidence interval -5.9% to 3.6%). Other eczema definitions supported the primary analysis. Food allergy (milk, egg, peanut) was present in 41/547 (7.5%) in the emollient group versus 29/568 (5.1%) in controls (adjusted relative risk 1.47, 95% confidence interval 0.93 to 2.33). Mean number of skin infections per child in the first year was 0.23 (standard deviation 0.68) in the emollient group versus 0.15 (standard deviation 0.46) in controls; adjusted incidence rate ratio 1.55, 95% confidence interval 1.15 to 2.09. The adjusted incremental cost per percentage decrease in risk of eczema at 2 years was £5337 (£7281 unadjusted). No difference between the groups in eczema or other atopic diseases was observed during follow-up to age 5 years via parental questionnaires. LIMITATIONS: Two emollient types were used which could have had different effects. The median time for starting emollients was 11 days after birth. Some contamination occurred in the control group (< 20%). Participating families were unblinded and reported on some outcomes. CONCLUSIONS: We found no evidence that daily emollient during the first year of life prevents eczema in high-risk children. Emollient use was associated with a higher risk of skin infections and a possible increase in food allergy. Emollient use is unlikely to be considered cost-effective in this context. FUTURE RESEARCH: To pool similar studies in an individual patient data meta-analysis. TRIAL REGISTRATION: This trial is registered as ISRCTN21528841. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 12/67/12) and is published in full in Health Technology Assessment; Vol. 28, No. 29. See the NIHR Funding and Awards website for further award information

Emollients for prevention of atopic dermatitis; 5‐year findings from the BEEP randomised trial

Background The effectiveness of emollients for preventing atopic dermatitis/eczema is controversial. The Barrier Enhancement for Eczema Prevention trial evaluated the effects of daily emollients during the first year of life on atopic dermatitis and atopic conditions to age 5 years. Methods 1394 term infants with a family history of atopic disease were randomized (1:1) to daily emollient plus standard skin-care advice (693 emollient group) or standard skin-care advice alone (701 controls). Long-term follow-up at ages 3, 4 and 5 years was via parental questionnaires. Main outcomes were parental report of a clinical diagnosis of atopic dermatitis and food allergy. Results Parents reported more frequent moisturizer application in the emollient group through to 5 years. A clinical diagnosis of atopic dermatitis between 12 and 60 months was reported for 188/608 (31%) in the emollient group and 178/631 (28%) in the control group (adjusted relative risk 1.10, 95% confidence interval 0.93 to 1.30). Although more parents in the emollient group reported food reactions in the previous year at 3 and 4 years, cumulative incidence of doctor-diagnosed food allergy by 5 years was similar between groups (92/609 [15%] emollients and 87/632 [14%] controls, adjusted relative risk 1.11, 95% confidence interval 0.84 to 1.45). Findings were similar for cumulative incidence of asthma and hay fever. Conclusions Daily emollient application during the first year of life does not prevent atopic dermatitis, food allergy, asthma or hay fever

Petrogenesis and geochemical halos of the amphibolite facies, Lower Proterozoic, Kerry Road volcanogenic massive sulfide deposit, Loch Maree Group, Gairloch, NW Scotland

The Palaeoproterozoic Kerry Road deposit is one of the oldest examples of volcanogenic massive sulfide (VMS) mineralization. This small VMS deposit (~500,000 tons grading at 1.2% Cu, 3.5% Zn) is hosted in amphibolite facies mafic-siliciclastic units of the c. 2.0 Ga Loch Maree Group, Scotland. Sulfide mineralization consists of pyrite and pyrrhotite with subordinate chalcopyrite and sphalerite, occurring in disseminated, vein and semi-massive to massive textures. The deposit was highly deformed and metamorphosed during the c. 1.8–1.7 Ga Laxfordian Orogeny. Textural relationships of deformed sulfide minerals, related to early Laxfordian deformation (D1/D2), indicate initial high pressure-low temperature (100 MPa, 150 °C) conditions before reaching peak amphibolite facies metamorphism, as evident from pyrrhotite crossing the brittle/ductile transition prior to chalcopyrite. Late Laxfordian deformation (D3/D4) is marked by local retrograde greenschist facies at low pressure and temperature (&lt;1.2 MPa, &lt;200 °C), recorded by late red sphalerite remobilization. δ34S values from all sulfide minerals have a homogeneous mean of 0.8 ± 0.7‰ (n = 21), consistent with interaction of hydrothermal fluids in the host oceanic basalt-island arc setting envisaged for deposition of the Loch Maree Group. Microprobe analyses of amphiboles record evidence of the original alteration halo associated with the Kerry Road deposit, with a systematic Mg- and Si- enrichment from ferrotschermakite (~150 m) to Mg-hornblende (~90 m) to actinolite (0 m) on approach to the VMS deposit. Furthermore, whole rock geochemistry records a progressive enrichment in Si, Cu, Co, and S, and depletion in Al, Ti, V, Cr, Y and Zr with proximity to the VMS system. These elemental trends, together with amphibole geochemistry, are potentially useful exploration vectors to VMS mineralization in the Loch Maree Group, and in similar highly deformed and metamorphosed terranes elsewhere

A new high precision, U-Pb date from the oldest known rocks in southern Britain

A new high precision U–Pb zircon age of 710.8 ± 1.5 Ma for granophyric granitic rock from the Stanner Hanter Complex of the Welsh Borderland lies just within error of an older Rb–Sr isochron age. εNd values of −0.3 and −1.2 combined with TDM of 1394 Ma and 1468 Ma indicate that the magma incorporated an older crustal source component. The Nd data highlight differences with western Avalonia, the widely considered Late Neoproterozoic north American counterpart to southern Britain, and point toward a closer similarity with other Peri-Gondwanan terranes that incorporate older, cratonic source material

The Crescent Lake copper deposit, central Newfoundland: deep levels of a volcanogenic hydrothermal system?

The Crescent Lake Mine, near the village of Robert's Arm in central Newfoundland, produced small tonnages of high-grade copper ore from quartz veins in the late 1800's and the 1920's. Although a Crescent Lake-type deposit is not a viable exploration target in itself, its presence has been used to suggest a potential for either volcanogenic massive sulphides (VMS) such as the nearby Pilley's Island deposit, or for mesothermal or epithermal gold. Field relationships, petrography, geochemistry, mineral chemistry, and fluid inclusion and stable isotopic studies are used to constrain the genesis of the deposit Mineralization occurs in four sulphide stages and a late oxide stage, distinguished by ore microscopy. Sphalerite, galena, chalcopyrite, and newly recognized carrollite were deposited with quartz between two pyrite stages. Covellite and iron oxides indicate later oxidation. Fluid inclusions in vein quartz are aqueous fluid-vapour type with no daughter crystals, no CO2 or CH4, no boiling, and a narrow range of salinities (~ 3-7% NaCl equiv). The sulphides were likely deposited from homogeneous fluids at &#x3F;430 m depth. The wide range of homogenization temperatures (~112-250°C) can be interpreted as the result of either changing temperature or fluctuating fluid pressures during the episodic crack-seal vein formation. Ore-related chlorite has a distinctive blue birefringence and higher Fe/Fe+Mg values (- 0.51 vs. 0.42) than chlorite in barren host rock, similar to other VMS deposits. The average calculated crystallization temperature of hydrothermal chlorite (240 ± 2°C) is close to the maximum fluid inclusion homogenization temperatures and likely closer to the true fluid trapping temperature. Sulphur isotope determinations (&#x3B4;34Spy ≈ 5.4; &#x3B4;34Scp ≈ 2.8; &#x3B4;34Scp ≈ 2.2) are similar to the Gull Pond VMS deposit; they indicate isotopic disequilibrium between coeval sulphides but a homogeneous sulphur source during the ore-forming event. This study concludes that the Crescent Lake copper deposit is most likely part of a volcanogenic hydrothermal stockwork, possibly genetically related to the Pilley's Island deposit. R&#xC9;SUM&#xC9; La mine de Crescent Lake, situ&#xE9;e dans la r&#xE9;gion centrale de Terre-Neuve &#xE0; proximit&#xE9; du village de Robert's Arm, produisit de faibles tonnages de minerai &#xE0; forte teneur en cuivre, issu de veines de quartz, vers la fin des ann&#xE9;es 1800 et dans les ann&#xE9;es 1920. Bien qu'un gite de type Crescent Lake tout seul ne constitue pas une cible d'exploration viable, sa pr&#xE9;sence a &#xE9;t&#xE9; utilis&#xE9;e pour sugg&#xE9;rer l’&#xE9;ventualit&#xE9;' soit d'amas sulfur&#xE9;s volcanog&#xE8;nes (ASV), tel que le gite avoisinant de Pilley's Island, soit d'or m&#xE9;so-ou &#xE9;pithermal. La confrontation des donn&#xE9;es concemant les rapports sur le terrain, la p&#xE9;trographie, la g&#xE9;ochimie, la chimie des min&#xE9;raux, ainsi que l'&#xE9;tude des inclusions fluides et des isotopes stables, est employ&#xE9;e pour d&#xE9;finir la gen&#xE8;se du gite. La min&#xE9;ralisation se pr&#xE9;sente sous forme de quatre stades &#xE0; sulfures et d'un stade tardif &#xE0; oxydes, que Ton reconnait &#xE-; l'aide de la microscopie m&#xE9;talIographique. La sphal&#xE9;rite, la gal&#xE8;ne, la chalcopyrite ainsi qu'une carrollite d&#xE9;couverte r&#xE9;cemment, se sont accumul&#xE9;es avec du quartz entre deux stades &#xE0; pyrite. De la covellite et des oxydes de fer t&#xE9;moignent d'une oxydation ulterieure. Les inclusions fluides au sein du quartz filonien sont du type &#xE0; fluide aqueux et vapeur, sans crystaux rejetons, CO2, CH4 ni &#xE9;bullition, et montrent une garrune peu &#xE9;tendue de salinitis (-3-7% &#xE9;quiv. NaCl). Il semble que les sulfures aient pr&#xE9;cipit&#xE9; &#xE0; partir de fluides homog&#xE8;nes &#xE0; une profondeur d&#xE9;passant 430 m. Les valeurs Ires dispers&#xE9;es des temp&#xE9;ratures d'homog&#xE8;neisation (-112-250°C) pourraient resulter soit de changements de temp&#xE9;rature, soit de fluctuations dans la pr&#xE9;ssion du fluide, durant la formation &#xE9;pisodique de filons par colmatage de fractures en traction. La chlorite alli&#xE9;e au minerai possede une birefringence bleue caract&#xE9;ristique et des valeurs plus &#xE9;lev&#xE9;es du rapport Fe/Fe+Mg (- 0.51 vs. 0.42) que la chlorite pr&#xE9;sente dans laroche encaissante st&#xE9;rile, ce qui s'apparente aux autres gisements ASV. La moyenne calcui&#xE9;e des temp&#xE9;ratures de cristallisation de la chlorite hydrothermale (240 ± 2°C) se situe pr&#xE8;s des temp&#xE9;ratures maximales d'homog&#xE8;neisation des inclusions fluides et s'approche vraisemblablement plus des temp&#xE9;ratures r&#xE9;elles de capture des fluides. Le dosage des isotopes du soufire (&#x3B4;34Spy ≈ 5.4; &#x3B4;34Scp ≈ 2.8; &#x3B4;34Scp ≈ 2.2) ressemble &#xE0; celui du gisement ASV de Gull Pond; il ufmoigne d'un d&#xE9;s&#xE9;quilibre isotopique entre des sulfures synchrones mais aussi d'une source homog&#xE8;ne du soufire durant l’&#xE9;pisode m&#xE9;tallog&#xE8;ne. Une conclusion de cette &#xE9;tude est que le gite cuprif&#xE8;re de Crescent Lake fait le plus vraisemblablement partie d 'un stockwerk volcanog&#xE8;ne hydrothermal, possiblement reli&#xE9; par sa gen&#xE8;se au gite de Pilley's Island. [Traduit par le journal