Analysis of organosilicone surfactants and their degradation products

In this work the analysis of the organosilicone surfactant Silwet L-77 and components thereof is described. The commercial product Silwet L-77 was demonstrated to comprise of ∼70% M₂D-C₃-O-(EO)ₙ-CH₃ (1),* ∼5% M₂D-C₃-O- (EO)ₙ-H (2) and ∼25% polar constituents. M₂D-C₃-O-(EO)ₙ-CH₃ oligomers were obtained by reversed-phase chromatography of Silwet L-77, and by synthetic procedures. Pure oligomers (n = 3, 6 and 9) were synthesised by reaction of the corresponding allyl-capped oligoethoxylate monomethyl ether M₂Dᴴ over a Pt catalyst. The allyl-capped ethoxylate monomethyl ethers were synthesised by reaction of allyl chloride with the corresponding ethoxylate monomethyl ethers (n = 3, 6 and 9). The longer chained oligoethylene glycols (n = 6 and 9) were prepared by etherification of smaller oligomers. Preparation of the organosilicone compounds M₂D-C₃-O-EO-COCH₃ and M₂D-C₃-OH were also investigated. Atmospheric pressure ionisation mass spectrometry (API/MS) is demonstrated to be a valid and informative method for the characterisation and quantitation of the organosilicone surfactants. Consistently reproducible quantitative results were achieved using an online HPLC separation system. Atmospheric pressure chemical ionisation (APcI) was used to enable high sample throughput, and the resulting HPLC/APcI/MS data obtained were improved both in reproducibility and sensitivity over conventional HPLC methods. The uptake mechanisms of agrochemical formulations and the role that surfactants play in this process are not well understood. The quantitative API/MS method developed and the use of synthesised Silwet L-77 components (1) enabled investigation of Silwet L-77 uptake into plant foliage (Chenopodium album). The influence of Silwet L-77 and constituents thereof on herbicide uptake was addressed, and dosage, spread, surfactant structure, solvation and solubility were implicated as important for uptake enhancement. Aspects of Silwet L-77 degradation were also addressed, for which API/MS methods were shown to be valid and informative. The well-established instability of Silwet L-77 to acid and alkaline conditions was characterised in more detail, with products, mechanisms and relative rates presented. Certain limitations of the API/MS method (i.e. product overlap, analyte suppression) required the use of additional methods to supplement the results obtained (LC/MS, GC/MS and NMR). The range of products formed in the degradation of Silwet L-77 were numerous as a result of the ability of the siloxane moiety to rearrange into a variety of lengths and structures, and compounded by the large number of components comprising the Silwet L-77 formulation. Unequivocal assignment of degradation product structure was thus complicated. Mass recovery following degradation was reduced in all experiments indicating the loss of volatile siloxane compounds. This was confirmed by headspace analysis. An increase in overall water-solubility for the degradation products over the parent surfactant was also observed. Rates and products appeared to be dependent on the conditions used, and were especially influenced by the solution pH. The use of fourier transform ion cyclotron resonance mass spectrometry (FTICR/MS) enabled the tentative assignment of four major products in the water-soluble fraction of degraded Silwet L-77. These were CH₃O(EO)ₙH (20), [1-SiCH₃+H] (21), cyclic tetramer [28; R¹, R², R³, R⁴ = C₃-O-(EO)ₙ-CH₃] and linear dimer [24; R¹, R² = TMS; R³, R⁴ = (EO)ₙ-CH₃]. Analysis of the degradation of purified M₂D-C₃-O-(EO)ₙ-Me (ave. n ∼7.5) samples by electrospray mass spectrometry (ESI/MS), FTICR/MS and HPLC/ESI/MS indicated CH₃O(EO)ₙH (20), [1-SiCH₃+H] (21) and [1- 2SiCH₃+2H] (22) as common degradation products. The linear dimer 24, [R¹ = H, R² = TMS; R³, R⁴ = (EO)ₙ-CH₃] was also indicated. The results also demonstrated that the HO(EO)ₙH, M₂D-C₃-O-(EO)n-H (2) and (Mᴿ)₂D-O-(EO)ₙ-CH₂CH= CH₂ (9, 10, 11; R = H or CH₃) compounds observed in the Silwet L-77 degradation mixture were synthetic by-products rather than degradation products. The degradation of single M₂D-C₃-O-(EO)ₙ-R oligomers confirmed the CH₃O(EO)ₙH (20), [1-SiCH₃+H] (21) and [1-2SiCH₃+2H] (22) as degradation products, and also indicated a range of linear and cyclic products both with and without the EO chains and terminal TMS groups intact. In general, the more silylated analogues of a structural series partitioned preferentially into the heptane-soluble fraction, and higher EO content derivatives were more commonly observed in the water-soluble fraction. Typically the products formed followed that for expected silanol stabilities, with longer EO chain products more stable as low condensation polymers and silanols, and short EO chains more commonly observed in cyclic products. The GC/MS analysis of the heptane-soluble fraction of acid-degraded Silwet L-77 enabled the tentative assignment of the cyclic trimer, 27 [R¹, R², R³ = -C₃- OH] product. ¹H and ¹³C NMR data also indicated this structure. ¹H NMR of the water-soluble fraction showed proton integration values indicative of the [1- 2SiCH₃+2H] (22) structure. After 2 years, the terminal Mᴿ groups were no longer detectable and extensive condensation had occurred, as determined by ²⁹Si NMR. The results demonstrated the rapid degradation of Silwet L-77 and derivatives thereof under extremes of pH and the highly complex nature of the products which are formed. API/MS was a valid and informative method for the study of the products formed, especially the high resolution FTICR/MS technique. Investigation into the stability of Silwet L-77 solutions on typical soil substrates indicated that there is little chance of surfactant persistence in aqueous soil environments. Reduced recovery was considered to be a result of degradation and/or strong sorption processes. Losses were most significant on substrates exhibiting extreme supernatant pH values (montmorillonite, halloysite). Reduced recoveries were also higher with higher clay content. Studies on clays indicated that supernatant pH, potential for intercalation and surface charges are important factors in the recovery process. In the case of the montmorillonite and illite clays, recoveries may be more significantly affected by sorption, as strong surfactant substrate interactions were observed immediately following application. The results obtained support previous observations that Silwet L-77 is relatively benign in the natural environment. Primary degradation is rapid and ultimate degradation to naturally occurring compounds i.e. CO₂, H₂O and Si(OH)₄, can be predicted according to the structures of the observed intermediates. However covalent bonding of degradation products to substrates was observed which may result in some environmental accumulation. In land applications this could cause aggregation of silicate minerals and/or affect the sorption capacity of the soil. An increase in sorption capacity could have positive or detrimental effects. The concentrations required for biotoxicity for Silwet L-77 and degradation products thereof are in large excess of any likely input by agricultural practices. Phytotoxicity was also low and this appeared to be a result of the dilution effects caused by high spreading. *M₂D- [Si(CH₃)₃-O]₂-Si(CH₃)- ; C₃ = (CH₂)₃; EO = CG₂CH₂

(OC-6-35)-(2,2′-Bipyridine-κ2 N,N′)dimeth­yl(3-sulfido­propionato-κ2 S,O)platinum(IV)

The title complex, [Pt(CH3)2(SCH2CH2CO2)(C10H8N2)], is formed by the unusual oxidative addition of the disulfide, R 2S2 (R = CH2CH2CO2H), to (2,2′-bipyridine)­dimethyl­platin­um(II) with elimination of RSH. The product contains an unusual six-membered thiol­ate–carboxyl­ate chelate ring. This slightly distorted octa­hedral complex exhibits cis angles ranging from 77.55 (11) to 97.30 (8)° due to the presence of the thiol­ate–carboxyl­ate chelate ring and the constrained bipyridine group. The crystal packing appears to be controlled by a combination of π-stacking [centroid–centroid distance = 3.611 (2) Å] and C—H⋯O inter­actions

Surface embedding, topology and dualization for spin networks

Spin networks are graphs derived from 3nj symbols of angular momentum. The surface embedding, the topology and dualization of these networks are considered. Embeddings into compact surfaces include the orientable sphere S^2 and the torus T, and the not orientable projective space P^2 and Klein's bottle K. Two families of 3nj graphs admit embeddings of minimal genus into S^2 and P^2. Their dual 2-skeletons are shown to be triangulations of these surfaces.Comment: LaTeX 17 pages, 6 eps figures (late submission to arxiv.org

Vanishing wildlife corridors and options for restoration: a case study from Tanzania

Conserving wildlife corridors is increasingly important for maintaining ecological and genetic connectivity in times of unprecedented habitat fragmentation. Documenting connectivity loss, assessing root causes, and exploring restoration options are therefore priority conservation goals. A 2009 nationwide assessment in Tanzania documented 31 major remaining corridors, the majority of which were described as threatened. The corridor between the Udzungwa Mountains and the Selous Game Reserve in south-central Tanzania, a major link between western and southern wildlife communities, especially for the African elephant Loxodonta africana, provides an illuminating case study. A preliminary assessment in 2005 found that connectivity was barely persisting via two remaining routes. Here we present assessments of these two corridors conducted from 2007-2010, using a combination of dung surveys, habitat mapping and questionnaires. We found that both corridor routes have become closed over the last five years. Increased farming and livestock keeping, associated with both local immigration and population growth, were the main reasons for corridor blockage. However, continued attempts by elephants to cross by both routes suggest that connectivity can be restored. This entails a process of harmonizing differing land owners and uses towards a common goal. We provide recommendations for restoring lost connectivity and discuss the prospects for preventing further loss of corridors across the country

Multiple forms of discrimination and internalized stigma compromise retention in HIV care among adolescents: findings from a South African cohort

Introduction Efficacious antiretroviral treatment (ART) enables people to live long and healthy lives with HIV but young people are dying from AIDS‐related causes more than ever before. Qualitative evidence suggest that various forms of HIV‐related discrimination and resulting shame act as profound barriers to young people’s engagement with HIV services. However, the impact of these risks on adolescent retention in HIV care has not been quantified. This study has two aims: (1) to examine whether and how different types of discrimination compromise retention in care among adolescents living with HIV in South Africa; and (2) to test whether internalized stigma mediates these relationships. Methods Between 2014 and 2017, adolescents living with HIV (aged 10 to 19) from 53 health facilities in the Eastern Cape, South Africa, were interviewed at baseline (n = 1059) and 18‐month follow‐up (n = 979, 92.4%), with responses linked to medical records. Data were analysed through multiple regression and mediation models. Results About 37.9% of adolescents reported full retention in care over the 2‐year period, which was associated with reduced odds of viral failure (OR: 0.371; 95% CI: .224, .614). At baseline, 6.9% of adolescents reported discrimination due to their HIV status; 14.9% reported discrimination due to HIV in their families and 19.1% reported discrimination in healthcare settings. Healthcare discrimination was associated with reduced retention in care both directly (effect: −0.120; CI: −0.190, −0.049) and indirectly through heightened internalized stigma (effect: 0.329; 95% CI: 0.129, 0.531). Discrimination due to family HIV was associated with reduced retention in care both directly (effect: −0.074, CI: −0.146, −0.002) and indirectly through heightened internalized stigma (effect: 0.816, CI: 0.494, 1.140). Discrimination due to adolescent HIV was associated with reduced retention in care only indirectly, through increased internalized stigma (effect: 0.408; CI: 0.102, 0.715). Conclusions Less than half of adolescents reported 2‐year retention in HIV care. Multiple forms of discrimination and the resultant internalized stigma contributed to this problem. More intervention research is urgently needed to design and test adolescent‐centred interventions so that young people living with HIV can live long and healthy lives in the era of efficacious anti‐retroviral treatment

Establishing nurse-led active surveillance for men with localised prostate cancer: development and formative evaluation of a model of care in the ProtecT trial.

Objectives To develop a nurse-led, urologist-supported model of care for men managed by active surveillance or active monitoring (AS/AM) for localised prostate cancer and provide a formative evaluation of its acceptability to patients, clinicians and nurses. Nurse-led care, comprising an explicit nurse-led protocol with support from urologists, was developed as part of the AM arm of the Prostate testing for cancer and Treatment (ProtecT) trial. Design Interviews and questionnaire surveys of clinicians, nurses and patients assessed acceptability. Setting Nurse-led clinics were established in 9 centres in the ProtecT trial and compared with 3 non-ProtecT urology centres elsewhere in UK. Participants Within ProtecT, 22 men receiving AM nurse-led care were interviewed about experiences of care; 11 urologists and 23 research nurses delivering ProtecT trial care completed a questionnaire about its acceptability; 20 men managed in urology clinics elsewhere in the UK were interviewed about models of AS/AM care; 12 urologists and three specialist nurses working in these clinics were also interviewed about management of AS/AM. Results Nurse-led care was commended by ProtecT trial participants, who valued the flexibility, accessibility and continuity of the service and felt confident about the quality of care. ProtecT consultant urologists and nurses also rated it highly, identifying continuity of care and resource savings as key attributes. Clinicians and patients outside the ProtecT trial believed that nurse-led care could relieve pressure on urology clinics without compromising patient care. Conclusions The ProtecT AM nurse-led model of care was acceptable to men with localised prostate cancer and clinical specialists in urology. The protocol is available for implementation; we aim to evaluate its impact on routine clinical practice

British Society of Gastroenterology/Association of Coloproctology of Great Britain and Ireland/Public Health England post-polypectomy and post-colorectal cancer resection surveillance guidelines

These consensus guidelines were jointly commissioned by the British Society of Gastroenterology (BSG), the Association of Coloproctology of Great Britain and Ireland (ACPGBI) and Public Health England (PHE). They provide an evidence-based framework for the use of surveillance colonoscopy and non-colonoscopic colorectal imaging in people aged 18 years and over. They are the first guidelines that take into account the introduction of national bowel cancer screening. For the first time, they also incorporate surveillance of patients following resection of either adenomatous or serrated polyps and also post-colorectal cancer resection. They are primarily aimed at healthcare professionals, and aim to address: Which patients should commence surveillance post-polypectomy and post-cancer resection? What is the appropriate surveillance interval? When can surveillance be stopped? two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The Appraisal of Guidelines for Research and Evaluation (AGREE II) instrument provided a methodological framework for the guidelines. The BSG's guideline development process was used, which is National Institute for Health and Care Excellence (NICE) compliant. two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps The key recommendations are that the high-risk criteria for future colorectal cancer (CRC) following polypectomy comprise either: Two or more premalignant polyps including at least one advanced colorectal polyp (defined as a serrated polyp of at least 10 mm in size or containing any grade of dysplasia, or an adenoma of at least 10 mm in size or containing high-grade dysplasia); or five or more premalignant polyps This cohort should undergo a one-off surveillance colonoscopy at 3 years. Post-CRC resection patients should undergo a 1 year clearance colonoscopy, then a surveillance colonoscopy after 3 more years

A bird’s eye view: using circuit theory to study urban landscape connectivity for birds

Context Connectivity is fundamental to understanding how landscape form influences ecological function. However, uncertainties persist due to the difficulty and expense of gathering empirical data to drive or to validate connectivity models, especially in urban areas, where relationships are multifaceted and the habitat matrix cannot be considered to be binary. Objectives This research used circuit theory to model urban bird flows (i.e. ‘current’), and compared results to observed abundance. The aims were to explore the ability of this approach to predict wildlife flows and to test relationships between modelled connectivity and variation in abundance. Methods Circuitscape was used to model functional connectivity in Bedford, Luton/Dunstable, and Milton Keynes, UK, for great tits (Parus major) and blue tits (Cyanistes caeruleus), drawing parameters from published studies of woodland bird flows in urban environments. Model performance was then tested against observed abundance data. Results Modelled current showed a weak yet positive agreement with combined abundance for P. major and C. caeruleus. Weaker correlations were found for other woodland species, suggesting the approach may be expandable if re-parameterised. Conclusions Trees provide suitable habitat for urban woodland bird species, but their location in large, contiguous patches and corridors along barriers also facilitates connectivity networks throughout the urban matrix. Urban connectivity studies are well-served by the advantages of circuit theory approaches, and benefit from the empirical study of wildlife flows in these landscapes to parameterise this type of modelling more explicitly. Such results can prove informative and beneficial in designing urban green space and new developments

Patient-reported outcomes in the ProtecT randomized trial of clinically localized prostate cancer treatments: Study design, and baseline urinary, bowel and sexual function and quality of life

Objectives: To present the baseline patient-reported outcome measures (PROMs) in the Prostate Testing for Cancer and Treatment (ProtecT) randomized trial comparing active monitoring, radical prostatectomy and external-beam conformal radiotherapy for localized prostate cancer and to compare results with other populations. Materials and Methods: A total of 1643 randomized men, aged 50-69 years and diagnosed with clinically localized disease identified by prostate-specific antigen (PSA) testing, in nine UK cities in the period 1999-2009 were included. Validated PROMs for disease-specific (urinary, bowel and sexual function) and condition-specific impact on quality of life (Expanded Prostate Index Composite [EPIC], 2005 onwards; International Consultation on Incontinence Questionnaire-Urinary Incontinence [ICIQ-UI], 2001 onwards; the International Continence Society short-form male survey [ICSmaleSF]; anxiety and depression (Hospital Anxiety and Depression Scale [HADS]), generic mental and physical health (12-item short-form health survey [SF-12]; EuroQol quality-of-life survey, the EQ-5D-3L) were assessed at prostate biopsy clinics before randomization. Descriptive statistics are presented by treatment allocation and by men's age at biopsy and PSA testing time points for selected measures. Results: A total of 1438 participants completed biopsy questionnaires (88%) and 77-88% of these were analysed for individual PROMs. Fewer than 1% of participants were using pads daily (5/754). Storage lower urinary tract symptoms were frequent (e.g. nocturia 22%, 312/1423). Bowel symptoms were rare, except for loose stools (16%, 118/754). One third of participants reported erectile dysfunction (241/735) and for 16% (118/731) this was a moderate or large problem. Depression was infrequent (80/1399, 6%) but 20% of participants (278/1403) reported anxiety. Sexual function and bother were markedly worse in older men (65-70 years), whilst urinary bother and physical health were somewhat worse than in younger men (49-54 years, all P < 0.001). Bowel health, urinary function and depression were unaltered by age, whilst mental health and anxiety were better in older men (P < 0.001). Only minor differences existed in mental or physical health, anxiety and depression between PSA testing and biopsy assessments. Conclusion: The ProtecT trial baseline PROMs response rates were high. Symptom frequencies and generic quality of life were similar to those observed in populations screened for prostate cancer and control subjects without cancer

Type III Nrg1 Back Signaling Enhances Functional TRPV1 along Sensory Axons Contributing to Basal and Inflammatory Thermal Pain Sensation

Type III Nrg1, a member of the Nrg1 family of signaling proteins, is expressed in sensory neurons, where it can signal in a bi-directional manner via interactions with the ErbB family of receptor tyrosine kinases (ErbB RTKs) [1]. Type III Nrg1 signaling as a receptor (Type III Nrg1 back signaling) can acutely activate phosphatidylinositol-3-kinase (PtdIns3K) signaling, as well as regulate levels of α7* nicotinic acetylcholine receptors, along sensory axons [2]. Transient receptor potential vanilloid 1 (TRPV1) is a cation-permeable ion channel found in primary sensory neurons that is necessary for the detection of thermal pain and for the development of thermal hypersensitivity to pain under inflammatory conditions [3]. Cell surface expression of TRPV1 can be enhanced by activation of PtdIns3K [4], [5], [6], making it a potential target for regulation by Type III Nrg1. We now show that Type III Nrg1 signaling in sensory neurons affects functional axonal TRPV1 in a PtdIns3K-dependent manner. Furthermore, mice heterozygous for Type III Nrg1 have specific deficits in their ability to respond to noxious thermal stimuli and to develop capsaicin-induced thermal hypersensitivity to pain. Cumulatively, these results implicate Type III Nrg1 as a novel regulator of TRPV1 and a molecular mediator of nociceptive function