•Realised ES are a product of the potential service and specified beneficiaries.•Natural capital (NC) and human-derived capital (HDC) are both essential for ES.•HDC plays a role even at the stage of ...potential ecosystem services.•It is possible but not always easy to separate the contribution of NC and HDC to ES.•Sustainable management should identify critical NC and HDC for each service.
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There is growing interest in the role that natural capital plays in underpinning ecosystem services. Yet, there remain differences and inconsistencies in the conceptualisation of capital and ecosystem services and the role that humans play in their delivery. Using worked examples in a stocks and flows systems approach, we show that both natural capital (NC) and human-derived (produced, human, social, cultural, financial) capital (HDC) are necessary to create ecosystem services at many levels. HDC plays a role at three stages of ecosystem service delivery. Firstly, as essential elements of a combined social-ecological system to create a potential ecosystem service. Secondly, through the beneficiaries in shaping the demand for that service. Thirdly, in the form of additional capital required to realise the ecosystem service flow. We show that it is possible, although not always easy, to separately identify how these forms of capital contribute to ecosystem service flow. We discuss how applying a systems approach can help identify critical natural capital and critical human-derived capital to guide sustainable management of the stocks and flows of all forms of capital which underpin provision of multiple ecosystem services. The amount of realised ecosystem service can be managed in several ways: via the NC & HDC which govern the potential service, and via factors which govern both the demand from the beneficiaries, and the efficiency of use of the potential service by those beneficiaries.
Summary
Lapatinib is a tyrosine kinase inhibitor used for the treatment of breast cancer. Paracetamol is an analgesic commonly applied to patients with mild or moderate pain and fever. Cancer ...patients are polymedicated, which involves high risk of drug interactions during therapy. The aim of the study was to assess the interaction between lapatinib and paracetamol in rats. The rats were divided into three groups of eight animals in each. One group received lapatinib + paracetamol (I
L + PA
), another group received lapatinib (II
L
), whereas the last group received paracetamol (III
PA
). A single dose of lapatinib (100 mg/kg b.w.) and paracetamol (100 mg/kg b.w.) was administered orally. Plasma concentrations of lapatinib, paracetamol and its metabolites – glucuronide and sulphate, were measured with the validated HPLC-MS/MS method and HPLC-UV method, respectively. The pharmacokinetic parameters of both drugs were calculated using non-compartmental methods. The co-administration of lapatinib and paracetamol increased the area under the plasma concentration-time curve (AUC) and the maximum concentration (C
max
) of lapatinib by 239.6% (
p
= 0.0030) and 184% (
p
= 0.0011), respectively. Lapatinib decreased the paracetamol AUC
0-∞
by 48.8% and C
max
by 55.7%. In the I
L + PA
group the C
max
of paracetamol glucuronide was reduced, whereas the C
max
of paracetamol sulphate was higher than in the III
PA
group. Paracetamol significantly affected the enhanced plasma exposure of lapatinib. Additionally, lapatinib reduced the concentrations of paracetamol. The co-administration of lapatinib decreased the paracetamol glucuronidation but increased the sulphation. The findings of this study may be of clinical relevance to patients requiring analgesic therapy.
structure: see text. A practical, chromotography-free asymmetric synthesis was developed for the large scale preparation of an endothelin receptor antagonist 2. This synthesis includes a new ...efficient process for the preparation of 6-bromo-2,3-dihydrobenzofuran, a stereoselective conjugate addition of an aryllithium followed by stereospecific addition of the Grignard reagent of the top aryl bromide, and an aminophosphate-mediated sterospecific intramolecular enolate alkylation, which led to the formation of the five-membered ring bearing three contiguous asymmetric centers.
Tramadol/paracetamol is a fixed-dose combination prescribed for the relief of moderate to severe pain. The combination acts synergistically and guarantees the rapid onset of paracetamol and the ...prolonged analgesic effect of tramadol with good tolerability. These drugs are often used in various formulations in the treatment of patients with postoperative pain, e.g. after stomach resection. Gastrectomy leads to pathophysiological changes within the alimentary tract, which may affect the process of drug absorption. The aim of the research was an analysis of the pharmacokinetics of tramadol/paracetamol from effervescent and conventional tablets in patients after total gastrectomy.
The research was carried out on patients after gastrectomy with Roux-en-Y reconstruction. The patients received two tramadol/paracetamol fixed-dose combination tablets in a single orally administered dose of 75/650 mg (2 × 37.5/325 mg). The patients were subjected to one of the two study drug group with: I. effervescent tablet (ET) (n = 14; mean SD age, 63.4 10.1 years; weight, 75.5 15.3kg; and BMI, 26.0 4.6kg/m(2)) and II. conventional tablet (CT) (n = 12; mean SD age, 66.8 7.7 years; weight, 79.8 17.8kg; and BMI, 27.4 5.3kg/m(2)). Blood samples were collected within 10 h after the drug administration. The plasma concentrations of tramadol and paracetamol were measured with validated HPLC (high-performance liquid chromatography) method with UV detection.
The comparison of the paracetamol and tramadol C(max) ratio for the ET group with that of the CT group gave ratios of 1.16 90% confidence interval (CI) 1.06, 1.27 and 0.86 (90% CI 0.72, 1.02), respectively. The comparison of the paracetamol and tramadol AUC(0-t) ratio for the ET group with that of the CT group showed ratios of 0.99 (90% CI 0.88, 1.10) and 1.00 (90% CI 0.82, 1.22), respectively. The comparison of the difference for the effervescent and conventional formulation gave an estimated decrease in t(max) of 0.5 h for paracetamol and 0.13 h for tramadol.
In view of the changes in the pharmacokinetics of paracetamol and tramadol in the patients after gastric resection for both formulations compared the conventional tablet seems to be more appropriate due to the comparable rate of absorption of both substances, higher concentrations of tramadol and comparable exposure to paracetamol.
Droplet growth in warm turbulent clouds Devenish, B. J.; Bartello, P.; Brenguier, J.-L. ...
Quarterly journal of the Royal Meteorological Society,
July 2012 Part B, Volume:
138, Issue:
667
Journal Article
A catalyst system of Rh
2(oct)
4/DIPEA or TMU allows for the rapid construction of α-alkoxyketones from the corresponding α-diazo ketone and alcohol. This methodology was applied to the synthesis of ...immunoregulant
1.
Marine harbours are the focus of a diverse range of activities and subject to multiple anthropogenically induced pressures. Support for environmental management options aimed at improving degraded ...harbours depends on understanding the factors which influence people's perceptions of harbour environments. We used an online survey, across 12 harbours, to assess sources of variation people's perceptions of harbour health and ecological engineering. We tested the hypotheses: 1) people living near impacted harbours would consider their environment to be more unhealthy and degraded, be more concerned about the environment and supportive of and willing to pay for ecological engineering relative to those living by less impacted harbours, and 2) people with greater connectedness to the harbour would be more concerned about and have greater perceived knowledge of the environment, and be more supportive of, knowledgeable about and willing to pay for ecological engineering, than those with less connectedness. Across twelve locations, the levels of degradation and modification by artificial structures were lower and the concern and knowledge about the environment and ecological engineering were greater in the six Australasian and American than the six European and Asian harbours surveyed. We found that people's perception of harbours as healthy or degraded, but not their concern for the environment, reflected the degree to which harbours were impacted. There was a positive relationship between the percentage of shoreline modified and the extent of support for and people's willingness to pay indirect costs for ecological engineering. At the individual level, measures of connectedness to the harbour environment were good predictors of concern for and perceived knowledge about the environment but not support for and perceived knowledge about ecological engineering. To make informed decisions, it is important that people are empowered with sufficient knowledge of the environmental issues facing their harbour and ecological engineering options.
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•Most residents have a good understanding of harbour condition.•Concern for the environment is, however, low in degraded harbours.•Most residents support ecological engineering but have poor knowledge of initiatives.•To improve harbour health, greater stakeholder engagement is needed.
Sex differences in glioblastoma (GBM) incidence and outcome are well recognized, and emerging evidence suggests that these extend to genetic/epigenetic and cellular differences, including immune ...responses. However, the mechanisms driving immunologic sex differences are not fully understood. Here, we demonstrate that T cells play a critical role in driving GBM sex differences. Male mice exhibited accelerated tumor growth, with decreased frequency and increased exhaustion of CD8+ T cells in the tumor. Furthermore, a higher frequency of progenitor exhausted T cells was found in males, with improved responsiveness to anti-PD-1 treatment. Moreover, increased T-cell exhaustion was observed in male GBM patients. Bone marrow chimera and adoptive transfer models indicated that T cell-mediated tumor control was predominantly regulated in a cell-intrinsic manner, partially mediated by the X chromosome inactivation escape gene Kdm6a. These findings demonstrate that sex-biased predetermined behavior of T cells is critical for inducing sex differences in GBM progression and immunotherapy response.
Immunotherapies in patients with GBM have been unsuccessful due to a variety of factors, including the highly immunosuppressive tumor microenvironment in GBM. This study demonstrates that sex-biased T-cell behaviors are predominantly intrinsically regulated, further suggesting sex-specific approaches can be leveraged to potentially improve the therapeutic efficacy of immunotherapy in GBM. See related commentary by Alspach, p. 1966. This article is featured in Selected Articles from This Issue, p. 1949.
Available evidence supports ovary-sparing surgery for benign ovarian neoplasms; however, preoperative risk stratification of pediatric ovarian masses can be difficult. Our objective of this study was ...to characterize the surgical management of pediatric ovarian neoplasms across 10 children's hospitals and to identify factors that could potentially aid in the preoperative risk stratification of these lesions.
A retrospective review of girls and women aged 2 to 21 years who underwent surgery for an ovarian neoplasm between 2010 and 2016 at 10 children's hospitals was performed. Multivariable logistic regression was used to examine the relationships between the preoperative cohort characteristics, procedure performed, and risk of malignancy.
Among 819 girls and women undergoing surgery for an ovarian neoplasm, malignant lesions were identified in 11%. The overall oophorectomy rate for benign disease was 33% (range: 15%-49%) across institutions. Oophorectomy for benign lesions was independently associated with provider specialty (
= .002: adult gynecologist, 45%; pediatric surgeon, 32%; pediatric gynecologist, 18%), premenarchal status (
= .02), preoperative suspicion for malignancy (
< .0001), larger lesion size (
< .0001), and presence of solid components (
< .0001). Preoperative findings independently associated with malignancy included increasing size (
< .0001), solid components (
= .003), and age (
< .0001).
The rate of oophorectomy for benign ovarian disease remains high within the pediatric population. Identification of factors associated with the choice of procedure and the risk of malignancy may allow for improved preoperative risk stratification and fewer unnecessary oophorectomies. These results have been used to develop and validate a multidisciplinary preoperative risk stratification algorithm that is currently being studied prospectively across 10 institutions.
Based on comprehensive testing and educational history, children in grades 4-9 (on average 12 years) were diagnosed with dysgraphia (persisting handwriting impairment) or dyslexia (persisting word ...spelling/reading impairment) or as typical writers and readers (controls). The dysgraphia group (n = 14) and dyslexia group (n = 17) were each compared to the control group (n = 9) and to each other in separate analyses. Four brain region seed points (left occipital temporal gyrus, supramarginal gyrus, precuneus, and inferior frontal gyrus) were used in these analyses which were shown in a metaanalysis to be related to written word production on four indicators of white matter integrity and fMRI functional connectivity for four tasks (self-guided mind wandering during resting state, writing letter that follows a visually displayed letter in alphabet, writing missing letter to create a correctly spelled real word, and planning for composing after scanning on topic specified by researcher). For those DTI indicators on which the dysgraphic group or dyslexic group differed from the control group (fractional anisotropy, relative anisotropy, axial diffusivity but not radial diffusivity), correlations were computed between the DTI parameter and fMRI functional connectivity for the two writing tasks (alphabet and spelling) by seed points. Analyses, controlled for multiple comparisons, showed that (a) the control group exhibited more white matter integrity than either the dysgraphic or dyslexic group; (b) the dysgraphic and dyslexic groups showed more functional connectivity than the control group but differed in patterns of functional connectivity for task and seed point; and (c) the dysgraphic and dyslexic groups showed different patterns of significant DTI-fMRI connectivity correlations for specific seed points and written language tasks. Thus, dysgraphia and dyslexia differ in white matter integrity, fMRI functional connectivity, and white matter-gray matter correlations. Of clinical relevance, brain differences were observed in dysgraphia and dyslexia on written language tasks yoked to their defining behavioral impairments in handwriting and/or in word spelling and on the cognitive mind wandering rest condition and composition planning.
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