Increasing use of metal and metal oxide nanoparticles Me(O)NPs in products means many will inevitably find their way into marine systems. Their likely fate here is sedimentation following ...hetero-aggregation with natural organic matter and/or free anions, putting benthic, sediment-dwelling and filter feeding organisms most at risk. In marine systems, Me(O)NPs can absorb to micro-organisms with potential for trophic transfer following consumption. Filter feeders, especially bivalves, accumulate Me(O)NPs through trapping them in mucus prior to ingestion. Benthic in-fauna may directly ingest sedimented Me(O)NPs. In fish, uptake is principally via the gut following drinking, whilst Me(O)NPs caught in gill mucus may affect respiratory processes and ion transport. Currently, environmentally-realistic Me(O)NP concentrations are unlikely to cause significant adverse acute health problems, however sub-lethal effects e.g. oxidative stresses have been noted in many organisms, often deriving from dissolution of Ag, Cu or Zn ions, and this could result in chronic health impacts.
•Nanoparticle (NP) use increasing, and NPs ultimately discharged to marine systems.•Metal ion dissolution from NPs causes oxidative stress at relevant concentrations.•Bioaccumulation & trophic transfer of NPs likely at all levels of marine food webs.•Biofilms & filter feeders are major NP accumulators, but many Classes lack study.•Current release levels unlikely to cause chronic damage, but may be a future issue.
Exposure to metal (oxide) nanoparticles causes sub-lethal effects in marine organisms, the extent of which is related principally to the organisms' feeding regime, habitat and lifestyle.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The year 1956 marked a point when British drama and theater fell into the hands of a group of young playwrights who revolutionized the stage. During that time, playwrights such as Samuel Beckett and ...Harold Pinter made the British theater as rich, varied, and vital as any national theater in history. This reference chronicles the history of British theater from 1956 to 1995 by providing detailed information about the playwrights of that period.Included are entries for some three dozen British playwrights active between 1956 and 1995. Entries are arranged alphabetically to facilitate use. Each entry supplies biographical information, the production history for particular plays, a survey of the playwright's critical reception, an assessment of the dramatist's work, and primary and secondary bibliographies. A selected, general bibliography at the end of the volume directs the reader to important sources of additional information about this period in theater history.
Prolonged exposure to microbial products such as lipopolysaccharide can induce a form of innate immune memory that blunts subsequent responses to unrelated pathogens, known as lipopolysaccharide ...tolerance. Sepsis is a dysregulated systemic immune response to disseminated infection that has a high mortality rate. In some patients, sepsis results in a period of immunosuppression (known as 'immunoparalysis')
characterized by reduced inflammatory cytokine output
, increased secondary infection
and an increased risk of organ failure and mortality
. Lipopolysaccharide tolerance recapitulates several key features of sepsis-associated immunosuppression
. Although various epigenetic changes have previously been observed in tolerized macrophages
, the molecular basis of tolerance, immunoparalysis and other forms of innate immune memory has remained unclear. Here we perform a screen for tolerance-associated microRNAs and identify miR-221 and miR-222 as regulators of the functional reprogramming of macrophages during lipopolysaccharide tolerization. Prolonged stimulation with lipopolysaccharide in mice leads to increased expression of miR-221 and mir-222, both of which regulate brahma-related gene 1 (Brg1, also known as Smarca4). This increased expression causes the transcriptional silencing of a subset of inflammatory genes that depend on chromatin remodelling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT (signal transducer and activator of transcription), which in turn promotes tolerance. In patients with sepsis, increased expression of miR-221 and miR-222 correlates with immunoparalysis and increased organ damage. Our results show that specific microRNAs can regulate macrophage tolerization and may serve as biomarkers of immunoparalysis and poor prognosis in patients with sepsis.
G protein-coupled receptors play a major role in transmembrane signalling in higher organisms and many are important drug targets. We report the 2.7 Å resolution crystal structure of a β
1
...-adrenergic receptor in complex with the high-affinity antagonist cyanopindolol. The modified turkey receptor had been selected to be in its antagonist conformation and its thermostability improved by earlier limited mutagenesis. The ligand-binding pocket comprises 15 side chains from amino acid residues in 4 transmembrane α-helices and extracellular loop 2. This loop defines the entrance of the ligand-binding pocket and is stabilised by two disulphide bonds and a sodium ion. Cyanopindolol binding to the β
1
-adrenergic receptor and carazolol binding to the β
2
-adrenergic receptor involve similar interactions. A short well-defined helix in cytoplasmic loop 2, not observed in either rhodopsin or the β
2
-adrenergic receptor, directly interacts via a tyrosine with the highly conserved DRY motif at the end of helix 3 that is essential for receptor activation.
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DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Children with chronic invasive ventilator dependence living at home are a diverse group of children with special health care needs. Medical oversight, equipment management, and community resources ...vary widely. There are no clinical practice guidelines available to health care professionals for the safe hospital discharge and home management of these complex children.
To develop evidence-based clinical practice guidelines for the hospital discharge and home/community management of children requiring chronic invasive ventilation.
The Pediatric Assembly of the American Thoracic Society assembled an interdisciplinary workgroup with expertise in the care of children requiring chronic invasive ventilation. The experts developed four questions of clinical importance and used an evidence-based strategy to identify relevant medical evidence. Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology was used to formulate and grade recommendations.
Clinical practice recommendations for the management of children with chronic ventilator dependence at home are provided, and the evidence supporting each recommendation is discussed.
Collaborative generalist and subspecialist comanagement is the Medical Home model most likely to be successful for the care of children requiring chronic invasive ventilation. Standardized hospital discharge criteria are suggested. An awake, trained caregiver should be present at all times, and at least two family caregivers should be trained specifically for the child's care. Standardized equipment for monitoring, emergency preparedness, and airway clearance are outlined. The recommendations presented are based on the current evidence and expert opinion and will require an update as new evidence and/or technologies become available.
There is increasing evidence of a direct association between unaffordable housing and poor mental health, over and above the effects of general financial hardship. Type of housing tenure may be an ...important factor in determining how individuals experience and respond to housing affordability problems. This study investigated whether a relationship exists between unaffordable housing and mental health that differs for home purchasers and private renters among low-income households. Data from 2001 to 2010 of the longitudinal Household, Income and Labour Dynamics in Australia (HILDA) survey were analysed using fixed-effects linear regression to examine change in the SF-36 Mental Component Summary (MCS) score of individuals aged 25–64 years, associated with changes in housing affordability, testing for an interaction with housing tenure type. After adjusting for age, survey year and household income, among individuals living in households in the lower 40% of the national income distribution, private renters in unaffordable housing experienced somewhat poorer in mental health than when their housing was affordable (difference in MCS = −1.18 or about 20% of one S.D. of the MCS score; 95% CI: -1.95,-0.41; p = 0.003) while home purchasers experienced no difference on average. The statistical evidence for housing tenure modifying the association between unaffordable housing and mental health was moderate (p = 0.058). When alternatives to 40% were considered as income cut-offs for inclusion in the sample, evidence of a difference between renters and home purchasers was stronger amongst households in the lowest 50% of the income distribution (p = 0.020), and between the 30th and 50th percentile (p = 0.045), with renters consistently experiencing a decline in mental health while mean MCS scores of home purchasers did not change. In this study, private renters appeared to be more vulnerable than home purchasers to mental health effects of unaffordable housing. Such a modified effect suggests that tenure-differentiated policy responses to poor housing affordability may be appropriate.
•Housing costs impact on health and wellbeing, but do effects differ by tenure type?•We used data from a large, nationally representative Australian panel survey.•Only for renters did we observe poorer mental health when housing was unaffordable.•Unaffordable housing differentially affects mental health of renters and owners.•It may be appropriate to tailor policy responses according to housing tenure type.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Previous animal models have illustrated that reduced cortical activity in the developing brain has cascading activity-dependent effects on the microstructural organization of the spinal cord. A ...limited number of studies have attempted to translate these findings to humans with cerebral palsy (CP). Essentially, the aberrations in sensorimotor cortical activity in those with CP could have an adverse effect on the spinal cord microstructure. To investigate this knowledge gap, we utilized magnetoencephalographic (MEG) brain imaging to quantify motor-related oscillatory activity in fourteen adults with CP and sixteen neurotypical (NT) controls. A subset of these participants also underwent cervical-thoracic spinal cord MRI. Our results showed that the strength of the peri-movement beta desynchronization and the post-movement beta rebound were each weaker in the adults with CP relative to the controls, and these weakened responses were associated with poorer task performance. Additionally, our results showed that the strength of the peri-movement beta response was associated with the total cross-sectional area of the spinal cord and the white matter cross-sectional area. Altogether these results suggest that the altered sensorimotor cortical activity seen in CP may result in activity-dependent plastic changes within the spinal cord microstructure, which could ultimately contribute to the sensorimotor deficits seen in this population.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Fuzzy Logic is the key element in our research to try and understand the interrelationships in the universe. We have been using fuzzy logic in conjunction with matrixes and topographical / ...geometrical frameworks to map and examine the elements of knowledge, decision support, complexity, autonomous control, and the cause & effect of different phenomena in general. Our research is mainly about measuring the differences between either solid objects or mental concepts over space /time observations and then to model and project those differences. For us the secret of understanding our universe is not the objects in general, but more the specific action and reaction of objects in conjunction with each other. Fuzzy logic is the perfect tool for this type of approach as it allows us to model different movements and differences between objects, either solid or conceptual. The paper is made up of two parts, the first is more about the ideas, concepts and back ground of our projects, then the other part is broken down into projects or activities, where each is described in more detail. Each of the projects uses common elements of the other projects, so it is not so easy to explain on paper; of course we are always happy to reply to questions.
Historical coral skeleton (CS) δ18O and δ15N records were produced from samples recovered from sedimentary deposits, held in natural history museum collections, and cored into modern coral heads. ...These records were used to assess the influence of global warming and regional eutrophication, respectively, on the decline of coastal coral communities following the development of the Pearl River Delta (PRD) megacity, China. We find that, until 2007, ocean warming was not a major threat to coral communities in the Pearl River estuary; instead, nitrogen (N) inputs dominated impacts. The high but stable CS‐δ15N values (9‰–12‰ vs. air) observed from the mid‐Holocene until 1980 indicate that soil and stream denitrification reduced and modulated the hydrologic inputs of N, blunting the rise in coastal N sources during the early phase of the Pearl River estuary urbanization. However, an unprecedented CS‐δ15N peak was observed from 1987 to 1993 (>13‰ vs. air), concomitant to an increase of NH4+ concentration, consistent with the rapid Pearl River estuary urbanization as the main cause for this eutrophication event. We suggest that widespread discharge of domestic sewage entered directly into the estuary, preventing removal by natural denitrification hotspots. We argue that this event caused the dramatic decline of the Pearl River estuary coral communities reported from 1980 to 2000. Subsequently, the coral record shows that the implementation of improved wastewater management policies succeeded in bringing down both CS‐δ15N and NH4+ concentrations in the early 2000s. This study points to the potential importance of eutrophication over ocean warming in coral decline along urbanized coastlines and in particular in the vicinity of megacities.
What are the respective roles of eutrophication and ocean warming in the decline of coastal coral communities along expanding urban centers? Here, we use historical coral geochemical records from a heavily urbanized area, the Pearl River Delta (PRD), China, to formalize the link between urbanization‐driven eutrophication and coral reef ecosystems decline. Our study reveals that ocean warming had no measurable influence on the decline of the coral communities located in the estuary, whereas the development of the PRD megacity in the 1980s–1990s was linked to an unprecedented eutrophication event that triggered a major coral die‐off in the estuary.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Aim
To quantify the microstructural differences in the cervical‐thoracic spinal cord of adults with cerebral palsy (CP).
Method
Magnetic resonance imaging of the proximal spinal cord (C6–T3) was ...conducted on a cohort of adults with CP (n=13; mean age=31y 11mo, standard deviation SD 8y 7mo; range=20y 8mo–47y 6mo; eight females, five males) and population norm adult controls (n=16; mean age=31y 4mo, SD 9y 9mo; range=19y 4mo–49y 5mo; seven females, nine males). The cross‐sectional area (CSA) of the spinal cord, gray and white matter, magnetization transfer ratio (MTR), and fractional anisotropy of the cuneatus and corticospinal tracts were calculated.
Results
The total spinal cord CSA and proportion of the spinal cord gray matter CSA were significantly decreased in the adults with CP. The corticospinal tracts’ MTR was lower in the adults with CP. Individuals that had reduced gray matter also tended to have reduced MTR in their corticospinal tracts (r=0.42, p=0.029) and worse hand dexterity clinical scores (r=0.53, p=0.004).
Interpretation
These results show that there are changes in the spinal cord microstructure of adults with CP. Ultimately, these microstructural changes play a role in the extent of the hand sensorimotor deficits seen in adults with CP.
What this paper adds
Adults with cerebral palsy (CP) have a reduced spinal cord cross‐sectional area (CSA).
Spinal cord gray matter is reduced in adults with CP.
Spinal cord CSA is associated with hand dexterity.
Magnetization transfer ratio of corticospinal tracts was lower in adults with CP.
What this paper adds
Adults with cerebral palsy (CP) have a reduced spinal cord cross‐sectional area (CSA).
Spinal cord gray matter is reduced in adults with CP.
Spinal cord CSA is associated with hand dexterity.
Magnetization transfer ratio of corticospinal tracts was lower in adults with CP.
This article is commented on by Cohen‐Adad on page 896 of this issue.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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