From 1989 to 2004, the breeding success of African penguins
Spheniscus demersus at Robben Island, South Africa was significantly related to estimates of the abundance of both their main prey species, ...anchovy
Engraulis encrasicolus and sardine
Sardinops sagax, and to the combined biomass of these species. When the combined spawner biomass of fish prey was less than 2
million
ton, pairs fledged an average of 0.46 chicks annually. When it was above 2
million
ton, annual breeding success had a mean value of 0.73 chicks per pair. Given previously estimated values of survival and age at first breeding, these levels of breeding success are inadequate to sustain the African penguin population. With the higher level of breeding success, an equilibrium situation might be attained if adult survival could be increased by 6–7% per annum. Attempts to reduce mortality of penguins have included the collection, cleaning and return to the wild of oiled birds, culling of Cape fur seals
Arctocephalus pusillus pusillus seen preying on penguins around breeding localities and control of the spread of disease. Management of the purse-seine fishery should ensure adequate escapement of fish to maintain the combined biomass of anchovy and sardine above 2
million
ton. The maintenance of suitable breeding habitat and removal of feral predators from breeding localities will also be important in improving breeding success.
The interface between the intervertebral disc and the vertebral body is important to the discs' biomechanics and physiology, and is widely implicated in its pathology. This study aimed to explore ...biochemically and structurally the bony endplate, cartilage endplate and intervertebral disc, below the nucleus and below the annulus in healthy bovine tails. Multiphoton imaging and spontaneous Raman spectroscopy were employed. Raman spectroscopy provided relative quantification of mineral and matrix components across the vertebral endplate and its adjacent areas with microscopic spatial resolution. Microscopy utilising second-harmonic generation (SHG) and two-photon fluorescence (TPF) allowed for the structural identification of distinct endplate regions. The cartilage endplate was revealed as structurally distinct from both the bone and disc, supporting its biomechanical function as a transition zone between the soft and hard tissue components. The collagen fibres were continuous across the tidemark which defines the interface between the mineralised and non-mineralised regions of the endplate. Raman spectroscopy revealed gradients in phosphate and carbonate content through the depth of the endplate and also differences beneath the nucleus and annulus consistent with a higher rate of remodelling under the annulus.
Multiphoton imaging and Raman spectroscopy reveal chemistry and micro-structure of the bovine vertebral endplate.
Chondrocytes dedifferentiate during ex vivo expansion on 2-dimensional surfaces. Aggregation of the expanded cells into 3-dimensional pellets, in the presence of induction factors, facilitates their ...redifferentiation and restoration of the chondrogenic phenotype. Typically 1×10(5)-5×10(5) chondrocytes are aggregated, resulting in "macro" pellets having diameters ranging from 1-2 mm. These macropellets are commonly used to study redifferentiation, and recently macropellets of autologous chondrocytes have been implanted directly into articular cartilage defects to facilitate their repair. However, diffusion of metabolites over the 1-2 mm pellet length-scales is inefficient, resulting in radial tissue heterogeneity. Herein we demonstrate that the aggregation of 2×10(5) human chondrocytes into micropellets of 166 cells each, rather than into larger single macropellets, enhances chondrogenic redifferentiation. In this study, we describe the development of a cost effective fabrication strategy to manufacture a microwell surface for the large-scale production of micropellets. The thousands of micropellets were manufactured using the microwell platform, which is an array of 360×360 µm microwells cast into polydimethylsiloxane (PDMS), that has been surface modified with an electrostatic multilayer of hyaluronic acid and chitosan to enhance micropellet formation. Such surface modification was essential to prevent chondrocyte spreading on the PDMS. Sulfated glycosaminoglycan (sGAG) production and collagen II gene expression in chondrocyte micropellets increased significantly relative to macropellet controls, and redifferentiation was enhanced in both macro and micropellets with the provision of a hypoxic atmosphere (2% O2). Once micropellet formation had been optimized, we demonstrated that micropellets could be assembled into larger cartilage tissues. Our results indicate that micropellet amalgamation efficiency is inversely related to the time cultured as discreet microtissues. In summary, we describe a micropellet production platform that represents an efficient tool for studying chondrocyte redifferentiation and demonstrate that the micropellets could be assembled into larger tissues, potentially useful in cartilage defect repair.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Vast stretches of agricultural land in southern and
central Africa are burnt between June and September each year, which
releases large quantities of aerosol into the atmosphere. The resulting
smoke ...plumes are carried west over the Atlantic Ocean at altitudes between 2
and 4 km. As only limited observational data in West Africa have existed
until now, whether this pollution has an impact at lower altitudes has
remained unclear. The Dynamics-aerosol-chemistry-cloud interactions in West
Africa (DACCIWA) aircraft campaign took place in southern West Africa during
June and July 2016, with the aim of observing gas and aerosol properties in
the region in order to assess anthropogenic and other influences on the
atmosphere. Results presented here show that a significant mass of aged accumulation
mode aerosol was present in the southern West African monsoon layer, over
both the ocean and the continent. A median dry aerosol concentration of 6.2 µg m−3 (standard temperature and pressure, STP) was observed over the Atlantic Ocean upwind of the major cities, with an interquartile
range from 5.3 to 8.0 µg m−3. This concentration increased to a
median of 11.1 µg m−3 (8.6 to 15.7 µg m−3) in the
immediate outflow from cities. In the continental air mass away from the
cities, the median aerosol loading was 7.5 µg m−3 (5.9 to 10.5 µg m−3). The accumulation mode aerosol population over land
displayed similar chemical properties to the upstream population, which
implies that upstream aerosol is a significant source of aerosol pollution
over the continent. The upstream aerosol is found to have most likely
originated from central and southern African biomass burning. This
demonstrates that biomass burning plumes are being advected northwards,
after being entrained into the monsoon layer over the eastern tropical
Atlantic Ocean. It is shown observationally for the first time that they
contribute up to 80 % to the regional aerosol loading in the monsoon layer
over southern West Africa. Results from the COSMO-ART (Consortium for Small-scale Modeling – Aerosol and Reactive Trace gases) and GEOS-Chem
models support this conclusion, showing that observed aerosol concentrations
over the northern Atlantic Ocean can only be reproduced when the
contribution of transported biomass burning aerosol is taken into account. As a result, the large and growing emissions from the coastal cities are
overlaid on an already substantial aerosol background. Simulations using
COSMO-ART show that cloud droplet number concentrations can increase by up
to 27 % as a result of transported biomass burning aerosol. On a regional scale this renders cloud properties and precipitation less sensitive to
future increases in anthropogenic emissions. In addition, such high
background loadings will lead to greater pollution exposure for the large
and growing population in southern West Africa. These results emphasise the
importance of including aerosol from across country borders in the
development of air pollution policies and interventions in regions such as
West Africa.
There are few effective interventions for dementia.
To determine the clinical effectiveness and cost-effectiveness of an intervention to promote self-management, independence and self-efficacy in ...people with early-stage dementia.
To undertake a randomised controlled trial of the Journeying through Dementia intervention compared with usual care, conduct an internal pilot testing feasibility, assess intervention delivery fidelity and undertake a qualitative exploration of participants' experiences.
A pragmatic two-arm individually randomised trial analysed by intention to treat.
A total of 480 people diagnosed with mild dementia, with capacity to make informed decisions, living in the community and not participating in other studies, and 350 supporters whom they identified, from 13 locations in England, took part.
Those randomised to the Journeying through Dementia intervention (
= 241) were invited to take part in 12 weekly facilitated groups and four one-to-one sessions delivered in the community by secondary care staff, in addition to their usual care. The control group (
= 239) received usual care. Usual care included drug treatment, needs assessment and referral to appropriate services. Usual care at each site was recorded.
The primary outcome was Dementia-Related Quality of Life score at 8 months post randomisation, with higher scores representing higher quality of life. Secondary outcomes included resource use, psychological well-being, self-management, instrumental activities of daily living and health-related quality of life.
Participants were randomised in a 1 : 1 ratio. Staff conducting outcome assessments were blinded.
Outcome measures were administered in participants' homes at baseline and at 8 and 12 months post randomisation. Interviews were conducted with participants, participating carers and interventionalists.
The mean Dementia-Related Quality of Life score at 8 months was 93.3 (standard deviation 13.0) in the intervention arm (
= 191) and 91.9 (standard deviation 14.6) in the control arm (
= 197), with a difference in means of 0.9 (95% confidence interval -1.2 to 3.0;
= 0.380) after adjustment for covariates. This effect size (0.9) was less than the 4 points defined as clinically meaningful. For other outcomes, a difference was found only for Diener's Flourishing Scale (adjusted mean difference 1.2, 95% confidence interval 0.1 to 2.3), in favour of the intervention (i.e. in a positive direction). The Journeying through Dementia intervention cost £608 more than usual care (95% confidence interval £105 to £1179) and had negligible difference in quality-adjusted life-years (-0.003, 95% confidence interval -0.044 to 0.038). Therefore, the Journeying through Dementia intervention had a mean incremental cost per quality-adjusted life-year of -£202,857 (95% confidence interval -£534,733 to £483,739); however, there is considerable uncertainty around this. Assessed fidelity was good. Interviewed participants described receiving some benefit and a minority benefited greatly. However, negative aspects were also raised by a minority. Seventeen per cent of participants in the intervention arm and 15% of participants in the control arm experienced at least one serious adverse event. None of the serious adverse events were classified as related to the intervention.
Study limitations include recruitment of an active population, delivery challenges and limitations of existing outcome measures.
The Journeying through Dementia programme is not clinically effective, is unlikely to be cost-effective and cannot be recommended in its existing format.
Research should focus on the creation of new outcome measures to assess well-being in dementia and on using elements of the intervention, such as enabling enactment in the community.
This trial is registered as ISRCTN17993825.
This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 26, No. 24. See the NIHR Journals Library website for further project information.
The p21-activated kinases (PAKs) play important roles in cytoskeletal organization, cellular morphogenesis, and survival and have generated significant attention as potential therapeutic targets for ...cancer. Following a high-throughput screen, we identified an aminopyrazole scaffold-based series that was optimized to yield group I selective PAK inhibitors. A structure-based design effort aimed at targeting the ribose pocket for both potency and selectivity led to much-improved group I vs II selectivity. Early lead compounds contained a basic primary amine, which was found to be a major metabolic soft spot with in vivo clearance proceeding predominantly via N-acetylation. We succeeded in identifying replacements with improved metabolic stability, leading to compounds with lower in vivo rodent clearance and excellent group I PAK selectivity.
Warfarin pharmacogenomic algorithms reduce dosing error, but perform poorly in non-European-Americans. Electronic health record (EHR) systems linked to biobanks may allow for pharmacogenomic ...analysis, but they have not yet been used for this purpose.
We used BioVU, the Vanderbilt EHR-linked DNA repository, to identify European-Americans (n = 1022) and African-Americans (n = 145) on stable warfarin therapy and evaluated the effect of 15 pharmacogenetic variants on stable warfarin dose.
Associations between variants in VKORC1, CYP2C9 and CYP4F2 with weekly dose were observed in European-Americans as well as additional variants in CYP2C9 and CALU in African-Americans. Compared with traditional 5 mg/day dosing, implementing the US FDA recommendations or the International Warfarin Pharmacogenomics Consortium (IWPC) algorithm reduced error in weekly dose in European-Americans (13.5-12.4 and 9.5 mg/week, respectively) but less so in African-Americans (15.2-15.0 and 13.8 mg/week, respectively). By further incorporating associated variants specific for European-Americans and African-Americans in an expanded algorithm, dose-prediction error reduced to 9.1 mg/week (95% CI: 8.4-9.6) in European-Americans and 12.4 mg/week (95% CI: 10.0-13.2) in African-Americans. The expanded algorithm explained 41 and 53% of dose variation in African-Americans and European-Americans, respectively, compared with 29 and 50%, respectively, for the IWPC algorithm. Implementing these predictions via dispensable pill regimens similarly reduced dosing error.
These results validate EHR-linked DNA biorepositories as real-world resources for pharmacogenomic validation and discovery.
Objective
Febrile seizures may follow vaccination. Common variants in the sodium channel gene, SCN1A, are associated with febrile seizures, and rare pathogenic variants in SCN1A cause the severe ...developmental and epileptic encephalopathy Dravet syndrome. Following vaccination, febrile seizures may raise the specter of poor outcome and inappropriately implicate vaccination as the cause. We aimed to determine the prevalence of SCN1A variants in children having their first febrile seizure either proximal to vaccination or unrelated to vaccination compared to controls.
Methods
We performed SCN1A sequencing, blind to clinical category, in a prospective cohort of children presenting with their first febrile seizure as vaccine proximate (n = 69) or as non–vaccine proximate (n = 75), and children with no history of seizures (n = 90) recruited in Australian pediatric hospitals.
Results
We detected 2 pathogenic variants in vaccine‐proximate cases (p.R568X and p.W932R), both of whom developed Dravet syndrome, and 1 in a non–vaccine‐proximate case (p.V947L) who had febrile seizures plus from 9 months. All had generalized tonic–clonic seizures lasting >15 minutes. We also found enrichment of a reported risk allele, rs6432860‐T, in children with febrile seizures compared to controls (odds ratio = 1.91, 95% confidence interval = 1.31–2.81).
Interpretation
Pathogenic SCN1A variants may be identified in infants with vaccine‐proximate febrile seizures. As early diagnosis of Dravet syndrome is essential for optimal management and outcome, SCN1A sequencing in infants with prolonged febrile seizures, proximate to vaccination, should become routine. ANN NEUROL 2020;87:281–288
To describe the clinical activity patterns and nature of interventions of hospital-based liaison psychiatry services in England.
Multi-site, cross-sectional survey. 18 acute hospitals across England ...with a liaison psychiatry service. All liaison staff members, at each hospital site, recorded data on each patient they had face to face contact with, over a 7 day period. Data included location of referral, source of referral, main clinical problem, type of liaison intervention employed, staff professional group and grade, referral onto other services, and standard assessment measures.
A total of 1475 face to face contacts from 18 hospitals were included in the analysis, of which approximately half were follow-up reviews. There was considerable variation across sites, related to the volume of Emergency Department (ED) attendances, number of hospital admissions, and work hours of the team but not to the size of the hospital (number of beds). The most common clinical problems were co-morbid physical and psychiatric symptoms, self-harm and cognitive impairment. The main types of intervention delivered were diagnosis/formulation, risk management and advice. There were differences in the type of clinical problems seen by the services between EDs and wards, and also differences between the work conducted by doctors and nurses. Almost half of the contacts were for continuing care, rather than assessment. Eight per cent of all referrals were offered follow up with the LP team, and approximately 37% were referred to community or other services.
The activity of LP services is related to the flow of patients through an acute hospital. In addition to initial assessments, services provide a wide range of differing interventions, with nurses and doctors carrying out distinctly different roles within the team. The results show the volume and diversity of LP work. While much clinical contact is acute and confined to the inpatient episode, the LP service is not defined solely by an assessment and discharge function; cases are often complex and nearly half were referred for follow up including liaison team follow up.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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