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Excessive mobilization of body reserves during the transition from pregnancy to lactation imposes a risk for metabolic diseases on dairy cows. We aimed to establish an experimental model for high v. normal mobilization and herein characterized performance, metabolic and endocrine changes from 7 weeks antepartum (a.p.) to 12 weeks postpartum (p.p.). Fifteen weeks a.p., 38 pregnant multiparous Holstein cows were allocated to two groups that were fed differently to reach either high or normal body condition scores (HBCS: 7.2 NEL MJ/kg dry matter (DM); NBCS: 6.8 NEL MJ/kg DM) at dry-off. Allocation was also based on differences in body condition score (BCS) in the previous and the ongoing lactation that was further promoted by feeding to reach the targeted BCS and back fat thickness (BFT) at dry-off (HBCS: >3.75 and >1.4 cm; NBCS: <3.5 and <1.2 cm). Thereafter, both groups were fed identical diets. Blood samples were drawn weekly from 7 weeks a.p. to 12 weeks p.p. to assess the serum concentrations of metabolites and hormones. The HBCS cows had greater BCS, BFT and BW than the NBCS cows throughout the study and lost more than twice as much BFT during the first 7 weeks p.p. compared with NCBS. Milk yield and composition were not different between groups, except that lactose concentrations were greater in NBSC than in HBCS. Feed intake was also greater in NBCS, and NBCS also reached a positive energy balance earlier than HBCS. The greater reduction in body mass in HBCS was accompanied by greater concentrations of non-esterified fatty acids, and β-hydroxybutyrate in serum after calving than in NBCS, indicating increased lipomobilization and ketogenesis. The mean concentrations of insulin across all time-points were greater in HBCS than in NBCS. In both groups, insulin and IGF-1 concentrations were lower p.p than in a.p. Greater free thyroxine (fT4) concentrations and a lower free 3-3′-5-triiodothyronine (fT3)/fT4 ratio were observed in HBCS than in NBCS a.p., whereas p.p. fT3/fT4 ratio followed a reverse pattern. The variables indicative for oxidative status had characteristic time courses; group differences were limited to greater plasma ferric reducing ability values in NBSC. The results demonstrate that the combination of pre-selection according to BCS and differential feeding before dry-off to promote the difference was successful in obtaining cows that differ in the intensity of mobilizing body reserves. The HBCS cows were metabolically challenged due to intense mobilization of body fat, associated with reduced early lactation dry matter intake and compromised antioxidative capacity.
Malaria elimination is on global agendas following successful transmission reductions. Nevertheless moving from low to zero transmission is challenging. South Africa has an elimination target of 2018, which may or may not be realised in its hypoendemic areas.
The Agincourt Health and Demographic Surveillance System has monitored population health in north-eastern South Africa since 1992. Malaria deaths were analysed against individual factors, socioeconomic status, labour migration and weather over a 21-year period, eliciting trends over time and associations with covariates.
Of 13 251 registered deaths over 1.58 million person-years, 1.2% were attributed to malaria. Malaria mortality rates increased from 1992 to 2013, while mean daily maximum temperature rose by 1.5 °C. Travel to endemic Mozambique became easier, and malaria mortality increased in higher socioeconomic groups. Overall, malaria mortality was significantly associated with age, socioeconomic status, labour migration and employment, yearly rainfall and higher rainfall/temperature shortly before death.
Malaria persists as a small but important cause of death in this semi-rural South African population. Detailed longitudinal population data were crucial for these analyses. The findings highlight practical political, socioeconomic and environmental difficulties that may also be encountered elsewhere in moving from low-transmission scenarios to malaria elimination.
Visualization experiments are performed to investigate the development of instability waves within the boundary layer on a slender cone under high Mach number conditions. The experimental facility is a reflected-shock wind tunnel, allowing both low (Mach-8 flight equivalent) and high-enthalpy conditions to be simulated. Second-mode instability waves are visualized using a high-speed schlieren set-up, with pulse bursting of the light source allowing the propagation speed of the wavepackets to be unambiguously resolved. This, in combination with wavelength information derived from the images, enables the calculation of the disturbance frequencies. At the lower-enthalpy conditions, we concentrate on the late laminar and transitional regions of the flow. General characteristics are revealed through time-resolved and ensemble-averaged spectra on both smooth and porous ceramic surfaces of the cone. Analysis of the development of individual wavepackets is then performed. It is found that the wavepacket structures evolve from a ‘rope-like’ appearance to become more interwoven as the disturbance nears breakdown. The wall-normal disturbance distributions of both the fundamental and first harmonic, which initially have local maxima at the wall and near
–0.75, exhibit an increase in signal energy close to the boundary-layer edge during this evolution. The structure angle of the disturbances also undergoes subtle changes as the wavepacket develops prior to breakdown. Experiments are also performed at high-enthalpy (
) conditions in the laminar regime, and the visualization technique is shown to be capable of resolving wavepacket propagation speeds and frequencies at such conditions. The visualizations reveal a somewhat different wall-normal distribution to the low-enthalpy case, with the disturbance energy concentrated much more towards the wall. This is attributed to the highly cooled nature of the wall at high enthalpy.
Altered microbial communities are thought to play an important role in eosinophilic oesophagitis, an allergic inflammatory condition of the oesophagus. Identification of the majority of organisms present in human-associated microbial communities is feasible with the advent of high throughput sequencing technology. However, these data consist of non-negative, highly skewed sequence counts with a large proportion of zeros. In addition, hierarchical study designs are often performed with repeated measurements or multiple samples collected from the same subject, thus requiring approaches to account for within-subject variation, yet only a small number of microbiota studies have applied hierarchical regression models. In this paper, we describe and illustrate the use of a hierarchical regression-based approach to evaluate multiple factors for a small number of organisms individually. More specifically, the zero-inflated negative binomial mixed model with random effects in both the count and zero-inflated parts is applied to evaluate associations with disease state while adjusting for potential confounders for two organisms of interest from a study of human microbiota sequence data in oesophagitis.
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.
The human immunodeficiency virus (HIV) epidemic in South Africa rapidly developed into a major pandemic. Here we analyse the development of the epidemic in a rural area of the country. The data used were collected between 1992 and 2013 in a longitudinal population survey, the Agincourt Health and Demographic Surveillance Study, in the northeast of the country. Throughout the period of study mortality rates were similar in all villages, suggesting that there were multiple index cases evenly spread geographically. These were likely to have been returning migrant workers. For those aged below 39 years the HIV mortality rate was higher for women, above this age it was higher for men. This indicates the protective effect of greater access to HIV testing and treatment among older women. The recent convergence of mortality rates for Mozambicans and South Africans indicates that the former refugee population are being assimilated into the host community. More than 60% of the deaths occurring in this community between 1992 and 2013 could be attributed directly or indirectly to HIV. Recently there has been an increasing level of non-HIV mortality which has important implications for local healthcare provision. This study demonstrates how evidence from longitudinal analyses can support healthcare planning.
Recent studies have provided strong evidence that variation in the gene neurocan (NCAN, rs1064395) is a common risk factor for bipolar disorder (BD) and schizophrenia. However, the possible relevance of NCAN variation to disease mechanisms in the human brain has not yet been explored. Thus, to identify a putative pathomechanism, we tested whether the risk allele has an influence on cortical thickness and folding in a well-characterized sample of patients with schizophrenia and healthy controls.
Sixty-three patients and 65 controls underwent T1-weighted magnetic resonance imaging (MRI) and were genotyped for the single nucleotide polymorphism (SNP) rs1064395. Folding and thickness were analysed on a node-by-node basis using a surface-based approach (FreeSurfer).
In patients, NCAN risk status (defined by AA and AG carriers) was found to be associated with higher folding in the right lateral occipital region and at a trend level for the left dorsolateral prefrontal cortex. Controls did not show any association (p > 0.05). For cortical thickness, there was no significant effect in either patients or controls.
This study is the first to describe an effect of the NCAN risk variant on brain structure. Our data show that the NCAN risk allele influences cortical folding in the occipital and prefrontal cortex, which may establish disease susceptibility during neurodevelopment. The findings suggest that NCAN is involved in visual processing and top-down cognitive functioning. Both major cognitive processes are known to be disturbed in schizophrenia. Moreover, our study reveals new evidence for a specific genetic influence on local cortical folding in schizophrenia.
Whether late-onset depression is a risk factor for or a prodrome of dementia remains unclear. We investigated the impact of depressive symptoms and early- v. late-onset depression on subsequent dementia in a cohort of elderly general-practitioner patients (n = 2663, mean age = 81.2 years).
Risk for subsequent dementia was estimated over three follow-ups (each 18 months apart) depending on history of depression, particularly age of depression onset, and current depressive symptoms using proportional hazard models. We also examined the additive prediction of incident dementia by depression beyond cognitive impairment.
An increase of dementia risk for higher age cut-offs of late-onset depression was found. In analyses controlling for age, sex, education, and apolipoprotein E4 genotype, we found that very late-onset depression (aged ⩾70 years) and current depressive symptoms separately predicted all-cause dementia. Combined very late-onset depression with current depressive symptoms was specifically predictive for later Alzheimer's disease (AD; adjusted hazard ratio 5.48, 95% confidence interval 2.41–12.46, p < 0.001). This association was still significant after controlling for cognitive measures, but further analyses suggested that it was mediated by subjective memory impairment with worries.
Depression might be a prodrome of AD but not of dementia of other aetiology as very late-onset depression in combination with current depressive symptoms, possibly emerging as a consequence of subjectively perceived worrisome cognitive deterioration, was most predictive. As depression parameters and subjective memory impairment predicted AD independently of objective cognition, clinicians should take this into account.
Young people with self-experienced cognitive thought and perception deficits (basic symptoms) may present with an early initial prodromal state (EIPS) of psychosis in which most of the disability and neurobiological deficits of schizophrenia have not yet occurred.
To investigate the effects of an integrated psychological intervention (IPI), combining individual cognitive–behavioural therapy, group skills training, cognitive remediation and multifamily psychoeducation, on the prevention of psychosis in the EIPS.
A randomised controlled, multicentre, parallel group trial of 12 months of IPI v. supportive counselling (trial registration number: NCT00204087). Primary outcome was progression to psychosis at 12- and 24-month follow-up.
A total of 128 help-seeking out-patients in an EIPS were randomised. Integrated psychological intervention was superior to supportive counselling in preventing progression to psychosis at 12-month follow-up (3.2% v. 16.9%; P = 0.008) and at 24-month follow-up (6.3% v. 20.0%; P = 0.019).
Integrated psychological intervention appears effective in delaying the onset of psychosis over a 24-month time period in people in an EIPS.
The significance of the potential impacts of microbial activity on the transport properties of host rocks for geological repositories is an area of active research. Most recent work has focused on granitic environments. This paper describes pilot studies investigating changes in transport properties that are produced by microbial activity in sedimentary rock environments in northern Japan. For the first time, these short experiments (39 days maximum) have shown that the denitrifying bacteria, Pseudomonas denitrificans, can survive and thrive when injected into flow-through column experiments containing fractured diatomaceous mudstone and synthetic groundwater under pressurized conditions. Although there were few significant changes in the fluid chemistry, changes in the permeability of the biotic column, which can be explained by the observed biofilm formation, were quantitatively monitored. These same methodologies could also be adapted to obtain information from cores originating from a variety of geological environments including oil reservoirs, aquifers and toxic waste disposal sites to provide an understanding of the impact of microbial activity on the transport of a range of solutes, such as groundwater contaminants and gases (e.g. injected carbon dioxide).
The mixed-conducting perovskite oxide Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF), given its outstanding oxygen ionic and electronic transport properties, is considered a promising material composition for oxygen transport membranes (OTM) operated at high temperatures.
Its long-term stability under operating conditions is, however, still an important issue. Although the incompatibility of BSCF with CO2-containing atmospheres can be avoided by appropriate means (oxyfuel processes in the absence of carbon dioxide), the thermal as well as the chemical stability of BSCF itself are still under thorough investigation.
This work is focused on the stability of BSCF in the targeted temperature range for OTM applications (700…900 °C) and in atmospheres with low oxygen contents. Previous studies in literature suggest limited chemical stability below oxygen partial pressures pO2 of around 10-6 bar.
By using a coulometric titration method based on a zirconia “oxygen pump” setup, precise control of the oxygen partial pressure pO2 between 1 bar and 10-18 bar was facilitated. Combining electrical measurements on dense ceramic bulk samples performed as a function of pO2 with an XRD phase composition study of single phase BSCF powders subjected to various pO2 treatments, an assessment of the chemical stability of BSCF is facilitated as a function of oxygen partial pressure. It could thus be shown that the pO2 stability limit is considerably lower than previously assumed in literature.
Meat yield and quality are closely related to muscle development. The muscle characteristics mainly take place during embryonic and postnatal phases. Thus, genetic control of muscle development in early stages represents a significant stake to improve product quality and production efficiency. In bovine, several programmes have been developed to detect quantitative trait loci (QTL) affecting growth, carcass composition or meat quality traits. Such strategy is incontestably very powerful yet extremely cumbersome and costly when dealing with large animals such as ruminants. Furthermore, the fine mapping of the QTL remains a real challenge. Here, we proposed an alternative approach based on chemical mutagenesis in the mouse combined with comparative genomics to identify regions or genes controlling muscle development in cattle. At present, we isolated seven independent mouse lines of high interest. Two lines exhibit a hypermuscular phenotype, and the other five show various skeletomuscular phenotypes. Detailed characterisation of these mouse mutants will give crucial input for the identification and the mapping of genes that control muscular development. Our strategy will provide the opportunity to understand the function and control of genes involved in improvement of animal physiology.
With modern undulators generating light of an arbitrary polarization state, experiments exploiting this feature in the soft X-ray region are becoming increasingly widespread. Circularly polarized light in the soft X-ray region is of particular interest to investigate of magnetic metals such as Fe, Co and Ni, and the rare earths. A versatile multilayer polarimeter has been designed and developed to characterize the polarization state of the soft X-ray beam. A W/B4C multilayer transmission phase retarder and reflection analyser has been used for polarimetry measurements on the beamline (I06) at Diamond Light Source. The design details of the polarimeter and preliminary polarimetry results are presented.
Diphtheria is an uncommon disease in the UK due to an effective immunization programme; consequently when cases do arise, there can be delays in diagnosis and case-fatality rates remain high. We reviewed 102 patients with infections caused by toxigenic corynebacteria (an average of four per year) reported in the UK between 1986 and 2008: 42 Corynebacterium diphtheriae, 59 C. ulcerans and one C. pseudotuberculosis, as well as 23 asymptomatic carriers. Five fatalities were reported, all in unvaccinated patients. The major risk factor for C. diphtheriae infection continued to be travel to an endemic country. C. ulcerans infections became more common than C. diphtheriae infections in the UK; they were associated with contact with companion animals. The occurrence of indigenous severe C. ulcerans infections and imported C. diphtheriae cases highlights the need to maintain UK routine vaccination coverage at the 95% level in the UK, as recommended by the World Health Organization.