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Mean cerebral blood flow velocity (mean-CBFV) obtained from Transcranial Doppler (TCD) poorly predicts cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (aSAH). Variability descriptors of mean-CBFV obtained during extended TCD recordings may improve this prediction. We assessed the feasibility of generating reliable linear and non-linear descriptors of mean-CBFV variability using extended recordings in aSAH patients and in healthy controls. We also explored which of those metrics might have the ability to discriminate between aSAH patients and healthy controls, and among patients who would go on to develop vasospasm and those who would not.
Bilateral mean-CBFV, blood pressure, and heart rate were continuously recorded for 40 minutes in aSAH patients (n = 8) within the first 5 days after ictus, in age-matched healthy controls (n = 8) and in additional young controls (n = 8). We obtained linear [standard deviation, coefficient of variations, and the very-low (0.003–0.040 Hz), low (0.040–0.150 Hz), and high-frequency (0.15–0.4 Hz) power spectra] and non-linear (Fractality, deterministic Chaos analyses) variability metrics.
We successfully obtained TCD recordings from patients and healthy controls and calculated the desired metrics of mean-CBFV variability. Differences were appreciable between aSAH patients and healthy controls, as well as between aSAH patients who later developed vasospasm and those who did not.
A 40-minute TCD recording provides reliable variability metrics in aSAH patients and healthy controls. Future studies are required to determine if mean-CBFV variability metrics remain stable over time, and whether they may serve to identify patients who are at greatest risk of developing cerebral vasospasm after aSAH.
We report on our project to study the activity in both the Sun and low mass stars. Utilising high cadence, Hα observations of a filament eruption made using the CRISP spectropolarimeter mounted on the Swedish Solar Telescope has allowed us to determine 3D velocity maps of the event. To gain insight into the physical mechanism which drives the event we have qualitatively compared our observation to a 3D MHD reconnection model. Solar-type and low mass stars can be highly active producing flares with energies exceeding erg. Using K2 and TESS data we find no correlation between the number of flares and the rotation phase which is surprising. Our solar flare model can be used to aid our understanding of the origin of flares in other stars. By scaling up our solar model to replicate observed stellar flare energies, we investigate the conditions needed for such high energy flares.
Increased plasma α-1 acid glycoprotein (AGP) is correlated with reduced growth rates in neonatal swine. The specific physiological mechanisms contributing to this relationship are unknown. This study was performed to determine if AGP can modify muscle metabolism by examining glucose oxidation and protein synthesis in the C2C12 muscle cell line. Cells were used for experiments 4 days post-fusion as myotubes. Myotubes were exposed to AGP for 24 h, with the last 4 h used to monitor 14C-glucose oxidation or to measure protein synthesis by incorporation of 3H-tyrosine. Treatment of C2C12 myotubes with mouse AGP (100 µg/ml) reduced glucose oxidation (P<0.01, n=3 trials), whereas bovine insulin (1 µM) stimulated glucose oxidation (P<0.05, n=3 trials). Treatment with AGP in combination with insulin reduced 14C-glucose oxidation (P<0.05, n=3 trials), similar to the effect of AGP alone. Glucose transport, as measured by 3H-deoxyglucose uptake, was increased by 38% with 1 µM insulin (P<0.05, n=3 trials), whereas AGP alone increased glucose uptake by 36% (P<0.05, n=3 trials). The combination of insulin and AGP in the medium resulted in an 88% increase in glucose uptake (P<0.01, n=3 trials). Protein synthesis was measured by 3H-tyrosine incorporation into C2C12 myotubes. Insulin stimulated a 18% increase in 3H-tyrosine incorporation (P<0.05, n=6 trials). The incorporation of 3H-tyrosine into myotubes was reduced by 20% with AGP incubation (P<0.01, n=6 trials), like the 20% decrease in 3H-tyrosine incorporation in response to the combination of AGP and insulin (P<0.01, n=6 trials). Protein breakdown, as measured by the release of 3H-tyrosine from C2C12 myotubes, was reduced 27% by insulin (P<0.01, n=6 trials). Treatment with AGP had no effect on protein breakdown (P>0.05, n=6 trials), whereas incubation with both AGP and insulin reduced 3H-tyrosine release by 15% (P<0.01, n=6 trials). First, these data indicate that the acute phase protein AGP can interact with the skeletal muscle to reduce glucose oxidation, but this is not the result of an effect on glucose transport. Second, AGP can specifically reduce protein synthesis. Lastly, AGP can inhibit insulin-stimulated glucose oxidation, protein synthesis and breakdown.
Selective pressure exerted by the widespread use of antibacterial drugs is accelerating the development of resistant bacterial populations. The purpose of this scoping review was to summarise the range of studies that use dynamic models to analyse the problem of bacterial resistance in relation to antibacterial use in human and animal populations. A comprehensive search of the peer-reviewed literature was performed and non-duplicate articles (n = 1486) were screened in several stages. Charting questions were used to extract information from the articles included in the final subset (n = 81). Most studies (86%) represent the system of interest with an aggregate model; individual-based models are constructed in only seven articles. There are few examples of inter-host models outside of human healthcare (41%) and community settings (38%). Resistance is modelled for a non-specific bacterial organism and/or antibiotic in 40% and 74% of the included articles, respectively. Interventions with implications for antibacterial use were investigated in 67 articles and included changes to total antibiotic consumption, strategies for drug management and shifts in category/class use. The quality of documentation related to model assumptions and uncertainty varies considerably across this subset of articles. There is substantial room to improve the transparency of reporting in the antibacterial resistance modelling literature as is recommended by best practice guidelines.
Fetuin A (also known as α2-Heremans–Schmid glycoprotein) is a protein primarily expressed by the liver and secreted into the blood. Previous studies have suggested that plasma concentrations of fetuin A are elevated with impaired growth rate in swine. The present study was designed to examine the relationship of porcine fetuin A with growth rate in the pig and to also elucidate the regulation of fetuin A expression by examining the hormonal and cytokine regulation of fetuin A mRNA abundance in hepatocytes prepared from suckling piglets. Quantitative real-time PCR assay was used to quantify the number of fetuin A mRNA molecules/molecule cyclophilin mRNA. Total RNA was isolated from liver of three different groups of pigs to assess changes in mRNA abundance of fetuin A: normal piglets at day 1, day 7 day 21 or 6 months of age (n=6 for each age); runt and control piglets at day 1 of age (n=4); slow growing and normal growing piglets at 21 days of age (n=8). Following birth, fetuin A gene expression increased from day 1 and 7 of age (P<0.05), and then declined at 21 days of age (P<0.05), with a much greater decline to 6 months of age (P<0.01). Fetuin A mRNA abundance was higher in runt pigs v. their normal birth weight littermates (P<0.05). Similarly, fetuin A gene expression was higher in livers of pigs that were born at a normal weight but that grew much slower than littermates with the same birth weight (P<0.05). Hepatocytes were isolated from preweaned piglets and maintained in serum-free monolayer culture for up to 72 h to permit examination of the influences of hormones, cytokines and redox modifiers on fetuin A mRNA abundance. Fetuin A gene expression was enhanced by glucagon, T3 and resveratrol (P<0.05). Growth hormone, cytokines (interleukin6, tumor necrosis factor-α) and antioxidants (N-acetylcysteine, quercertin) reduced fetuin A mRNA abundance (P<0.05). A role for fetuin A in postnatal development is suggested by the differences in fetuin A mRNA abundance between runt piglets or slow growing piglets and their normal growing sized littermates. The hepatocyte experiments suggest multiple hormones and cytokines may contribute to the regulation of fetuin A during early growth of the pig.
The current study aimed to evaluate breeding effect on nitrogen use efficiency (NUE), its components and some agronomic traits and disease resistance in barley by using extensive germplasm covering 72 landraces and 123 cultivars released since 1910. Trials were established in southern Finland with a modified strip-plot experimental design. Prior to sowing, blocks were placement fertilized with compound nitrogen : phosphorus : potassium (NPK) fertilizer (N-P-K: 20–3–8) at the rate of 35 and 70 kg N/ha and unfertilized plots were placed at the other end of the fertilization block. The germplasm collection was genotyped with 1536 single nucleotide polymorphism (SNP) markers and phenotyped during a 2-year field experiment in 2011/12. Independent of row type, a positive breeding effect was evident in NUE and for other plant N traits, except that grain N slightly decreased. Breeding has improved NUE by 0·08 kg/year (26% over the century). Nitrogen utilization and N uptake efficiencies were also improved by breeding as were straw length, lodging tolerance, grain yield and yield components, without any sign of levelling-off. Bred cultivars were more resistant to leaf-damaging diseases, especially to net blotch. The SNP data indicated no reduction in overall genetic diversity. However, genetic diversity differed along the barley chromosomes showing either reduced or increased diversity in certain regions when landraces were compared with modern varieties.
Older people with dementia are at increased risk of physical decline and falls. Balance and mood are significant predictors of falls in this population. The aim of this study was to determine the effect of a tailored home-based exercise program in community-dwelling older people with dementia.
Forty-two participants with mild to moderate dementia were recruited from routine health services. All participants were offered a six-month home-based, carer-enhanced, progressive, and individually tailored exercise program. Physical activity, quality of life, physical, and psychological assessments were administered at the beginning and end of the trial.
Of 33 participants (78.6%) who completed the six-month reassessment ten (30%) reported falls and six (18%) multiple falls during the follow-up period. At reassessment, participants had better balance (sway on floor and foam), reduced concern about falls, increased planned physical activity, but worse knee extension strength and no change in depression scores. The average adherence to the prescribed exercise sessions was 45% and 22 participants (52%) were still exercising at trial completion. Those who adhered to ≥70% of prescribed sessions had significantly better balance at reassessment compared with those who adhered to <70% of sessions.
This trial of a tailored home-based exercise intervention presents preliminary evidence that this intervention can improve balance, concern about falls, and planned physical activity in community-dwelling older people with dementia. Future research should determine whether exercise interventions are effective in reducing falls and elucidate strategies for enhancing uptake and adherence in this population.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
Serum α1-acid glycoprotein (AGP) is elevated during late gestation and at birth in the pig and rapidly declines postnatally. In contrast, the pig is born with minimal lipid stores in the adipose tissue, but rapidly accumulates lipid during the first week. The present study examined if AGP can affect adipose tissue metabolism in the neonatal pig. Isolated cell cultures or tissue explants were prepared from dorsal subcutaneous adipose tissue of preweaning piglets. Porcine AGP was used at concentrations of 0, 100, 1000 and 5000 ng/ml medium in 24 h incubations. AGP reduced the messenger RNA (mRNA) abundance of the lipogenic enzymes, malic enzyme (ME), fatty acid synthase and acetyl coA carboxylase by at least 40% (P<0.001). The activity of ME and citrate lyase were also reduced by AGP (P<0.05). Glucose oxidation was reduced by treatment with 5000 ng AGP/ml medium (P<0.05). The 14C-glucose incorporation into fatty acids was reduced by ~25% by AGP treatment for 24 h with 1000 ng AGP/ml medium (P<0.05). The decrease in glucose metabolism by AGP appears to function through an inhibition in insulin-mediated glucose oxidation and incorporation into fatty acids. This was supported by the analysis of the mRNA abundance for sterol regulatory element-binding protein (SREBP), carbohydrate regulatory element-binding protein (ChREBP) and insulin receptor substrate 1 (IRS1), which all demonstrated reductions of at least 23% in response to AGP treatment (P<0.05). These data demonstrate an overall suppression of lipogenesis due to AGP inhibition of lipogenic gene expression in vitro, which the metabolic data and SREBP, ChREBP and IRS1 gene expression analysis suggest is through an inhibition in insulin-mediated events. Second, these data suggest that AGP may contribute to limiting lipogenesis within adipose tissue during the perinatal period, as AGP levels are highest for any serum protein at birth.
Single doses of resveratrol have previously been shown to increase cerebral blood flow (CBF) with no clear effect on cognitive function or mood in healthy adults. Chronic resveratrol consumption may increase the poor bioavailability of resveratrol or otherwise potentiate its psychological effects. In this randomised, double-blind, placebo-controlled, parallel-groups study, a total of sixty adults aged between 18 and 30 years received either placebo or resveratrol for 28 d. On the 1st and 28th day of treatment, the performance of cognitively demanding tasks (serial subtractions, rapid visual information processing and 3-Back) (n 41 complete data sets) was assessed, alongside blood pressure (n 26) and acute (near-IR spectroscopy (NIRS)) and chronic (transcranial Doppler) measures of CBF (n 46). Subjective mood, sleep quality and health questionnaires were completed at weekly intervals (n 53/54). The results showed that the cognitive effects of resveratrol on day 1 were restricted to more accurate but slower serial subtraction task performance. The only cognitive finding on day 28 was a beneficial effect of resveratrol on the accuracy of the 3-Back task before treatment consumption. Subjective ratings of ‘fatigue’ were significantly lower across the entire 28 d in the resveratrol condition. Resveratrol also resulted in modulation of CBF parameters on day 1, as assessed by NIRS, and significantly increased diastolic blood pressure on day 28. Levels of resveratrol metabolites were significantly higher both before and after the day’s treatment on day 28, in comparison with day 1. These results confirm the acute CBF effects of resveratrol and the lack of interpretable cognitive effects.
Socio-economic gradients in diet quality are well established. However, the influence of material socio-economic conditions particularly in childhood, and the use of multiple disaggregated socio-economic measures on diet quality have been little studied in the elderly. In the present study, we examined childhood and adult socio-economic measures, and social relationships, as determinants of diet quality cross-sectionally in 4252 older British men (aged 60–79 years). A FFQ provided data on daily fruit and vegetable consumption and the Elderly Dietary Index (EDI), with higher scores indicating better diet quality. Adult and childhood socio-economic measures included occupation/father's occupation, education and household amenities, which combined to create composite scores. Social relationships included social contact, living arrangements and marital status. Both childhood and adult socio-economic factors were independently associated with diet quality. Compared with non-manual social class, men of childhood manual social class were less likely to consume fruit and vegetables daily (OR 0·80, 95 % CI 0·66, 0·97), as were men of adult manual social class (OR 0·65, 95 % CI 0·54, 0·79), and less likely to be in the top EDI quartile (OR 0·73, 95 % CI 0·61, 0·88), similar to men of adult manual social class (OR 0·66, 95 % CI 0·55, 0·79). Diet quality decreased with increasing adverse adult socio-economic scores; however, the association with adverse childhood socio-economic scores diminished with adult social class adjustment. A combined adverse childhood and adulthood socio-economic score was associated with poor diet quality. Diet quality was most favourable in married men and those not living alone, but was not associated with social contact. Diet quality in older men is influenced by childhood and adulthood socio-economic factors, marital status and living arrangements.
This study was designed to determine whether methyl-β-cyclodextrin (MCD) can substitute for albumin in incubation medium for neonatal swine adipose tissue explants, or whether MCD affects metabolism and cytokine expression. Subcutaneous adipose tissue explants (100 ± 10 mg) were prepared from 21-day-old pigs. Explants were incubated in medium 199 supplemented with 25 mM HEPES, 1.0 nM insulin at 37°C. The medium also contained bovine serum albumin (BSA) or MCD at 0%, 0.05%, 0.1%, 0.2% or 0.3%. Tissue explants were treated with these media for 1 h and then switched to the same basal incubation medium containing 0.05% BSA. Explants were removed from basal medium at 2 or 8 h of incubation, and real-time PCR was performed to assess expression of tumor necrosis α (TNF) and interleukin 6 (IL6), acetyl CoA carboxylase (ACAC) and fatty acid synthase (FASN). Alternatively, rates of 14C-glucose oxidation and lipogenesis were monitored ± insulin (100 nM), following MCD treatment. Incubation with BSA had minimal effects on gene expression or adipose tissue metabolism, only producing a doubling in TNF mRNA abundance (P < 0.01). Treatment with MCD increased TNF mRNA abundance by eightfold (P < 0.009), whereas IL6 gene expression increased a 100-fold (P < 0.001) with a suppression in ACAC and FASN expression (P < 0.01). This was paralleled by MCD inhibition of insulin-stimulated glucose oxidation and lipogenesis (P < 0.001). Addition of a TNF antibody to the incubation medium alleviated this inhibition of insulin-stimulated glucose metabolism by ∼30% (P < 0.05).
The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7–11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0·26%, 95% confidence interval (CI) 0·14–0·44]. The estimated average annual incidence of hepatitis B was estimated to be 29·26/100 000 children (95% CI 16·00–49·08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5·00 and 12·49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.
Surveillance of acute hepatitis B in England is necessary to estimate incidence, determine routes of transmission and inform public health actions. Here we describe an automated process to extract information on testing for markers of hepatitis B infection in English sentinel laboratories between 2002 and 2008. The resulting data were used to identify individuals with acute infections, describe their characteristics and estimate the incidence of infection. Two-thirds of acute infections were in males. Heterosexual exposure and injecting drug use were the main risks reported. Annual incidence was estimated at 1·3/100 000 person-years overall (1·7 and 0·6 for males and females, respectively) and declined each year. Automated extraction of hepatitis B markers, including quantitative results where available, can help to classify HBV status more accurately for surveillance. HBV incidence in England is at its lowest level in recent years.
Oxidation of serum proteins can lead to carbonyl formation that alters their function and is often associated with stress-related diseases. As it is recommended that all pigs reared in modern production facilities be given supplemental iron at birth to prevent anemia, and metals can catalyze the carbonylation of proteins, the primary objective of this study was to determine whether standard iron dextran treatment was associated with enhanced serum protein oxidation in newborn piglets. Piglets were treated with 100 mg of iron dextran intramuscularly either on the day of birth, or on the third day after birth. Blood samples were collected from piglets 48 or 96 h after treatment and serum was harvested. For quantification, serum protein carbonyls were converted to hydrazones with dinitrophenyl hydrazine and analyzed spectrophotometrically. To identify and determine relative distribution of carbonylated proteins, serum protein carbonyls were derivatized with biotin hydrazide, separated by two-dimensional polyacrylamide gel electrophoresis, stained with avidin-fluorescein and identified by mass spectrometry. The standard iron dextran treatment was associated with no increase in total oxidized proteins if given either on the first or third day of life. In addition, with a few noted exceptions, the overall distribution and identification of oxidized proteins were similar between control and iron dextran-treated pigs. These results indicate that while iron dextran treatment is associated with a marked increase in circulating iron, it does not appear to specifically induce the oxidation of serum proteins.
Between March and June 2008, 12 cases of hepatitis A were notified in Winchester. Cases were from a primary school and a nursery school with no direct linkage. Hepatitis A virus (HAV) RNA sequenced from nine cases confirmed the strain in both schools to be identical. The outbreak could have affected three other schools and a maternity unit and was controlled by immunization and screening of neonates in the maternity unit by dried blood spots. No neonates were infected and no further cases were reported until 5 months later when the index case's mother became infected with same strain of virus associated with the outbreak despite vaccination. Neither the source of the outbreak or the subsequent infection of the index case's mother was identified; however, with the timing of the cases continued transmission in the community by children with asymptomatic infection or a recurrent source cannot be ruled out.
During 2006–2007, the KwaZulu-Natal coast of South Africa was exposed to several large swell events (Ho > 3 m), near the peak of the lunar nodal cycle, causing shoreline recession. The largest swell (Hs = 8.5 m) struck the coast on the March equinox (18th–20th) and generated a strong storm-return flow. Observations made before, during and after record dramatic coastal erosion (shoreline recession of up to 40 m and substantial property damage). This swell event removed the semi-continuous nearshore bar system and ‘conditioned’ the coast such that lesser subsequent swell events accomplished much greater amounts of coastal erosion than expected (up to 100 m at certain erosion hotspots) because waves reached the coast without significant energy dissipation. Subsequent bar generation rebuilt the inshore bars within six months. The styles of erosion during the March ’07 event and other 2007 swells were markedly different. Lesser swells are focused by headlands and result in megarip development and activation of erosion hotspots. The March ’07 event still-water level was raised (equinoctial spring high tide and a storm surge of 0.33–0.45 m) to a level that rendered most headlands (and erosion hotspots) ineffective and resulted in laterally extensive erosion of soft shorelines. Results record cumulative effects of successive swell events on coastal behaviour that proved to be critical in enabling erosion to proceed at rapid rates after the coast had been initially destabilized. Unlike hurricanes and tsunamis, surges associated with swell events are relatively minor and therefore extensive erosion is linked with high lunar tides. There is circumstantial evidence that swell-induced erosion follows the broad 18.6 yr lunar nodal tidal cycle when the chances of large swells coinciding with high water levels are increased.
Healthcare-associated hepatitis B virus (HBV) outbreaks have been reported in the USA and from several countries in Europe. Patient-to-patient transmission of HBV in these settings has been linked to several different types of exposure but one of the most common exposures implicated is the use of ‘finger-stick’ lancet devices for blood glucose testing. This article is an account of the investigations into a series of HBV outbreaks linked to the use of lancing devices in community healthcare settings in the UK. Between February 2004 and December 2006, nine individuals with acute HBV infection were reported to five local units of the Health Protection Agency. Investigations identified a further 12 individuals with HBV infection in residents in these settings. The epidemiological and environmental evidence suggests that HBV transmission occurred mostly from a significant breakdown in infection control measures in blood glucose testing. The occurrence of these outbreaks has highlighted the confusion that exists and the need for clear recommendations regarding the use of such devices in the UK.