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To evaluate quality of life and patient preference for schizophrenia treatment in a community based study comparing the use of aripiprazole to the standard of care (SOC).
This open-label, 26-week, multi-centre, randomised study compared aripiprazole with SOC (olanzapine, quetiapine or risperidone) in patients with schizophrenia (DSM-IV-TR criteria). The primary effectiveness variable was the mean total score of the Investigator Assessment Questionnaire (IAQ) at Week 26. The outcome research variables included the Preference of Medicine (POM) questionnaire, the Quality of Life Scale (QLS), and the EuroQoL-5D (EQ-5D). The results from these outcome research variables are the focus of this paper addressing quality of life and patient preference.
A total of 555 patients were randomised to receive aripiprazole (n = 284) or SOC (n = 271). The OC data at Week 26, reported that more respondents rated the study medication as ‘much better’ compared with their previous medication in the aripiprazole group versus SOC for patients (59% vs 35%, P < 0.001) and caregivers (58% vs 30%, P = 0.014). The improvement in QLS total score was also significantly greater in the aripiprazole group compared with SOC – mean change from baseline in QLS total score of 16.21 vs 10.01 (P < 0.001) at Week 26 (OC data set). A greater proportion of patients (93% vs 85%; P = 0.005) in the aripiprazole group had a satisfactory response on the EQ-5D Self Care Scale; all other EQ-5D scores were similar.
The study findings suggest that quality of life and patient medication preference measures were better for aripiprazole than for SOC.
Koch’s postulates originally proposed a one microorganism–one disease approach to disease; however, it is now clear that many diseases of plants and animals are associated with changes in the taxonomic composition and function of the microbiome, and that health and disease are mediated by a dynamic interplay between host factors, environmental factors, the host microbiota and pathogenic microorganisms. Commensal microbes can become pathogenic under certain conditions, and disease can arise from complex polymicrobial infections. Although causation and correlation can be difficult to untangle, it is clear that the host microbiome plays a key role in resisting colonisation by pathogens across all host taxa, from plants to animals to humans. This offers exciting possibilities for manipulating microbiomes in order to reduce pathogenic infection in a range of contexts, including agriculture, wildlife and human health, through the use of probiotics, prebiotics and microbiome transplants, among other approaches.
A classic example of microbiome function is its role in nutrient assimilation in both plants and animals, but other less obvious roles are becoming more apparent, particularly in terms of driving infectious and non-infectious disease outcomes and influencing host behaviour. However, numerous biotic and abiotic factors influence the composition of these communities, and host microbiomes can be susceptible to environmental change. How microbial communities will be altered by, and mitigate, the rapid environmental change we can expect in the next few decades remain to be seen. That said, given the enormous range of functional diversity conferred by microbes, there is currently something of a revolution in microbial bioengineering and biotechnology in order to address real-world problems including human and wildlife disease and crop and biofuel production. All of these concepts are explored in further detail throughout the book.
Buruli ulcer (BU) belongs to the group of neglected tropical diseases and constitutes a public health problem in many rural communities in Côte d’Ivoire. The transmission patterns of this skin infection are poorly defined, hence the current study aimed to contribute to the understanding, perceptions and interpretations of its mode of transmission using a socio-environmental approach. Social and environmental risk factors that may expose people to infection, and the dynamics of local transfer of knowledge and practices related to BU, were assessed in two endemic locations in southern Côte d’Ivoire, i.e. Taabo and Daloa. Data were generated by the administration of a household questionnaire (N=500) between February and June 2012 to assess how the population perceived transmission of BU, focus group discussions with local communities (N=8) to analyse ideologies regarding transmission patterns and semi-structured interviews with patients or their parents, former BU patients and traditional healers (N=30). The interviewees’ empirical knowledge of the disease was found to be close to its biomedical description. Their aetiological perception of the disease was linked to natural (e.g. dirty water, insects) and supernatural (e.g. witchcraft, fate) causes. Some informants attributed the spread of the disease to recently immigrated neighbouring communities whose arrival coincided with an increase in reported BU cases. However, the general consensus seemed to be that the main mode of transmission was contact with infested soil or ulcerated wounds. The participants were aware that BU was a socio-environmental problem in these endemic areas, offering a good starting point for educational campaigns for at-risk communities. Buruli ulcer control programmes should therefore include educational campaigns and Water, Sanitation and Hygiene (WASH) interventions for those at risk in affected communities.
Pigs selected for high performance may be more at risk of developing diseases. This study aimed to assess the health and performance of two pig lines divergently selected for residual feed intake (RFI) (low RFI (LRFI) v. high RFI (HRFI)) and housed in two contrasted hygiene conditions (poor v. good) using a 2×2 factorial design (n=40/group). The challenge period (Period 1), started on week zero (W0) when 12-week-old pigs were transferred to good or poor housing conditions. At week 6 (W6), half of the pigs in each group were slaughtered. During a recovery period (Period 2) from W6 to W13 to W14, the remaining pigs (n=20/group) were transferred in good hygiene conditions before being slaughtered. Blood was collected every three (Period 1) or 2 weeks (Period 2) to assess blood indicators of immune and inflammatory responses. Pulmonary lesions at slaughter and performance traits were evaluated. At W6, pneumonia prevalence was greater for pigs housed in poor than in good conditions (51% v. 8%, respectively, P<0.001). Irrespective of hygiene conditions, lung lesion scores were lower for LRFI pigs than for HRFI pigs (P=0.03). At W3, LRFI in poor conditions had the highest number of blood granulocytes (hygiene×line, P=0.03) and at W6, HRFI pigs in poor conditions had the greatest plasma haptoglobin concentrations (hygiene×line, P=0.02). During Period 1, growth rate and growth-to-feed ratio were less affected by poor hygiene in LRFI pigs than in HRFI pigs (hygiene×line, P=0.001 and P=0.02, respectively). Low residual feed intake pigs in poor conditions ate more than the other groups (hygiene×line, P=0.002). Irrespective of the line, fasting plasma glucose concentrations were higher in poor conditions, whereas fasting free fatty acids concentrations were lower than in good conditions. At the end of Period 2, pneumonia prevalence was similar for both housing conditions (39% v. 38%, respectively). During Period 2, plasma protein concentrations were greater for pigs previously housed in poor than in good conditions during Period 1. Immune traits, gain-to-feed ratio, BW gain and feed consumption did not differ during Period 2. Nevertheless, at W12, BW of HRFI previously housed in poor conditions was 13.4 kg lower than BW of HRFI pigs (P<0.001) previously housed in good conditions. In conclusion, health of the most feed efficient LRFI pigs was less impaired by poor hygiene conditions. This line was able to preserve its health, growth performance and its feed ingestion to a greater extent than the less efficient HRFI line.
The primary goal was to investigate the effects of l-carnitine on fuel efficiency, as an antioxidant, and for muscle recovery in Labrador retrievers. Dogs were split into two groups, with one group being supplemented with 250 mg/d of Carniking™ l-carnitine powder. Two experiments (Expt 1 and Expt 2) were performed over a 2-year period which included running programmes, activity monitoring, body composition scans and evaluation of recovery using biomarkers. Each experiment differed slightly in dog number and design: fifty-six v. forty dogs; one endurance and two sprint runs per week v. two endurance runs; and differing blood collection time points. All dogs were fed a low-carnitine diet in which a fixed amount was offered based on maintaining the minimum starting weight. Results from Expt 1 found that the carnitine dogs produced approximately 4000 more activity points per km compared with the control group during sprint (P = 0·052) and endurance runs (P = 0·0001). Male carnitine dogs produced half the creatine phosphokinase (CPK) following exercise compared with male control dogs (P = 0·05). Carnitine dogs had lower myoglobin at 6·69 ng/ml following intensive exercise compared with controls at 24·02 ng/ml (P = 0·0295). Total antioxidant capacity (TAC) and thiobarbituric acid reactive substance (TBARS) results were not considered significant. In Expt 2, body composition scans indicated that the carnitine group gained more total tissue mass while controls lost tissue mass (P = 0·0006) and also gained lean mass while the control group lost lean mass (P < 0·0001). Carnitine dogs had lower CPK secretion at 23·06 v. control at 28·37 mU/ml 24 h after post-run (P = 0·003). Myoglobin levels were lower in carnitine v. control dogs both 1 h post-run (P = 0·0157; 23·83 v. 37·91 ng/ml) and 24 h post-run (P = 0·0189; 6·25 v.13·5 ng/ml). TAC indicated more antioxidant activity in carnitine dogs at 0·16 mmv. control at 0·13 mm (P = 0·0496). TBARS were also significantly lower in carnitine dogs both pre-run (P = 0·0013; 15·36 v. 23·42 µm) and 1 h post-run (P = 0·056; 16·45 v. 20·65 µm). Supplementing l-carnitine in the form of Carniking™ had positive benefits in Labrador retrievers for activity intensity, body composition, muscle recovery and oxidative capacity.
This article reviews recent advances utilizing field-ion microscopy (FIM) to extract atomic-scale three-dimensional images of materials. This capability is not new, as the first atomic-scale reconstructions of features utilizing FIM were demonstrated decades ago. The rise of atom probe tomography, and the application of this latter technique in place of FIM has unfortunately severely limited further FIM development. Currently, the ubiquitous availability of extensive computing power makes it possible to treat and reconstruct FIM data digitally and this development allows the image sequences obtained utilizing FIM to be extremely valuable for many material science and engineering applications. This article demonstrates different applications of these capabilities, focusing on its use in physical metallurgy and semiconductor science and technology.
This review summarizes the results from the INRA (Institut National de la Recherche Agronomique) divergent selection experiment on residual feed intake (RFI) in growing Large White pigs during nine generations of selection. It discusses the remaining challenges and perspectives for the improvement of feed efficiency in growing pigs. The impacts on growing pigs raised under standard conditions and in alternative situations such as heat stress, inflammatory challenges or lactation have been studied. After nine generations of selection, the divergent selection for RFI led to highly significant (P<0.001) line differences for RFI (−165 g/day in the low RFI (LRFI) line compared with high RFI line) and daily feed intake (−270 g/day). Low responses were observed on growth rate (−12.8 g/day, P<0.05) and body composition (+0.9 mm backfat thickness, P=0.57; −2.64% lean meat content, P<0.001) with a marked response on feed conversion ratio (−0.32 kg feed/kg gain, P<0.001). Reduced ultimate pH and increased lightness of the meat (P<0.001) were observed in LRFI pigs with minor impact on the sensory quality of the meat. These changes in meat quality were associated with changes of the muscular energy metabolism. Reduced maintenance energy requirements (−10% after five generations of selection) and activity (−21% of time standing after six generations of selection) of LRFI pigs greatly contributed to the gain in energy efficiency. However, the impact of selection for RFI on the protein metabolism of the pig remains unclear. Digestibility of energy and nutrients was not affected by selection, neither for pigs fed conventional diets nor for pigs fed high-fibre diets. A significant improvement of digestive efficiency could likely be achieved by selecting pigs on fibre diets. No convincing genetic or blood biomarker has been identified for explaining the differences in RFI, suggesting that pigs have various ways to achieve an efficient use of feed. No deleterious impact of the selection on the sow reproduction performance was observed. The resource allocation theory states that low RFI may reduce the ability to cope with stressors, via the reduction of a buffer compartment dedicated to responses to stress. None of the experiments focussed on the response of pigs to stress or challenges could confirm this theory. Understanding the relationships between RFI and responses to stress and energy demanding processes, as such immunity and lactation, remains a major challenge for a better understanding of the underlying biological mechanisms of the trait and to reconcile the experimental results with the resource allocation theory.
Cytomegalovirus (CMV) is the leading cause of congenital infection and non-genetic sensorineural hearing loss in children. There are no recent data on the incidence of CMV infection during pregnancy in Canada. This present study was undertaken to determine the seroprevalence of CMV IgG antibodies and the rate of seroconversion in a cohort of pregnant women in the province of Québec, Canada. We used serum samples and questionnaire data collected as part of the 3D Pregnancy and Birth Cohort Study (2010–2013) conducted in Québec, Canada. CMV IgG antibodies were determined in serum samples collected at the first and third trimesters. Associations between independent variables and seroprevalence were assessed using logistic regression, and associations with seroconversions, by Poisson regression. Of 1938 pregnant women tested, 40·4% were seropositive for CMV at baseline. Previous CMV infection was associated with: working as a daycare educator, lower education, lower income, having had children, first language other than French or English, and being born outside Canada or the United States. Of the 1122 initially seronegative women, 24 (2·1%) seroconverted between their first and third trimesters. The seroconversion rate was 1·4 [95% confidence interval (CI) 0·9–2·1]/10 000 person-days at risk or 3·9 (95% CI 2·5–5·9)/100 pregnancies (assuming a 280-day gestation). The high proportion of pregnant women susceptible to CMV infection (nearly 60%) and the subsequent rate of seroconversion are of concern.
Selection of animals for improved feed efficiency can affect sustainability of animal production because the most efficient animals may face difficulties coping with challenges. The objective of this study was to determine the effects of an inflammatory challenge (using an intravenous injection of complete Freund’s adjuvant – CFA) in piglets from two lines of pigs divergently selected during the fattening period for a low (RFI−) or a high (RFI+) residual feed intake (RFI; difference between actual feed intake and theoretical feed requirements). Nitrogen and energy balances (including heat production – HP – and its components: activity-related HP – AHP, thermic effect of feeding, and resting HP) were measured individually in thirteen 20-kg BW castrated male piglets (six and seven from RFI+ and RFI− line, respectively) fed at the same level (1.72 MJ ME/kg BW0.60 per day) from 3 days before to 3 days after CFA injection. Dynamics of dietary U-13C-glucose oxidation were estimated from measurements of 13CO2 production on the day before and 3 days after the CFA injection. Oxidation of dietary nutrients and lipogenesis were calculated based on HP and O2 consumption and CO2 production. The data were analyzed as repeated measurements within piglets in a mixed model. Before CFA injection, RFI− piglets had a lower resting energy expenditure than RFI+ piglets, which tended to increase energy retention because of a higher energy retention as fat. The CFA injection did not affect feed intake from the day following CFA injection onwards but it increased energy retention (P=0.04). Time to recover 50% of 13C from dietary glucose as expired 13CO2 was higher in RFI+ piglets before inducing inflammation but decreased after to the level of RFI− piglets (P<0.01). Oxidation of U-13C-glucose tended to slightly increased in RFI− piglets and to decreased in RFI+ piglets (P=0.10) because of CFA. Additionally, RFI− piglets had a lower respiratory quotient during the 1st day following the CFA injection whereas RFI+ piglets tended to have a higher respiratory quotient. In conclusion, selection for RFI during the fattening period also affected the energy metabolism of pigs during earlier stages of growth. The effects of CFA injection were moderated in both lines but the most efficient animals (RFI−) exhibited a marked re-orientation of nutrients only during the 1st day after CFA, and seemed to recover thereafter, whereas the less efficient piglets expressed a more prolonged alteration of their metabolism.
The quiet Sun observed in polarized light exhibits a rich and complex magnetic structuring which is still not fully resolved nor understood. The present work is intended to contribute to the debate about the origin of the quiet sun magnetic fields, in relation or not to the global solar dynamo. We present analysis of center-to-limb polarization measurements obtained with the SOT/SP spectropolarimeter onboard the Hinode satellite outside active regions, in 2007 and 2013, i.e. at a minimum and a maximum of the solar cycle, respectively. We compare the spatial fluctuation Fourier spectra of unsigned circular and linear polarization images after corrections for polarization bias and focus variations between the two data sets. The decay of active regions is clearly a source of magnetic fields in the quiet Sun. It leads to a global increase of the polarization fluctuation power spectrum in 2013 in the network. In the internetwork, we observe no variation of the polarization fluctuation power at mesogranular and granular scales, whereas it increases at sub-granular scales. We interpret these results in the following way. At the mesogranular and granular scales very efficient mechanisms of magnetic field removal are operating in the internetwork, that leads to a dissipation or a concentration of magnetic fields on smaller scales. So the cycle-invariant magnetic signal that we detect at mesogranular and granular scales must be continuously created by a dynamo mechanism which is independent of the solar cycle.
Antarctic and Southern Ocean science is vital to understanding natural variability, the processes that govern global change and the role of humans in the Earth and climate system. The potential for new knowledge to be gained from future Antarctic science is substantial. Therefore, the international Antarctic community came together to ‘scan the horizon’ to identify the highest priority scientific questions that researchers should aspire to answer in the next two decades and beyond. Wide consultation was a fundamental principle for the development of a collective, international view of the most important future directions in Antarctic science. From the many possibilities, the horizon scan identified 80 key scientific questions through structured debate, discussion, revision and voting. Questions were clustered into seven topics: i) Antarctic atmosphere and global connections, ii) Southern Ocean and sea ice in a warming world, iii) ice sheet and sea level, iv) the dynamic Earth, v) life on the precipice, vi) near-Earth space and beyond, and vii) human presence in Antarctica. Answering the questions identified by the horizon scan will require innovative experimental designs, novel applications of technology, invention of next-generation field and laboratory approaches, and expanded observing systems and networks. Unbiased, non-contaminating procedures will be required to retrieve the requisite air, biota, sediment, rock, ice and water samples. Sustained year-round access to Antarctica and the Southern Ocean will be essential to increase winter-time measurements. Improved models are needed that represent Antarctica and the Southern Ocean in the Earth System, and provide predictions at spatial and temporal resolutions useful for decision making. A co-ordinated portfolio of cross-disciplinary science, based on new models of international collaboration, will be essential as no scientist, programme or nation can realize these aspirations alone.
Surface enhanced Raman scattering (SERS) is a sensitive and reproducible vibrational spectroscopic technique used to detect and characterize molecules near the surface of noble metals like Au, Ag, Pt, Cu, etc. SERS enhances Raman signals through light-induced plasmonic vibrations occurring on irregular metal surfaces and localized electromagnetic augmentation. To better define nano-scale regions of the Raman signal enhancement, we generated gold nanoparticles with a unique multi-branched configuration along with surface-adsorbed fluorescent reporter molecules. The reporter molecules included a set of near-infra red active fluorescent dyes IR820 (green cyanine, photo electronic dye), DTTC (3, 3'-diethylthiatricarbocyanine iodide) and DTDC (3, 3'- diethylthiadicarbocyanine iodide). We employed a one-pot synthesis method in order to generate a stellate configuration in gold nanoparticles through the reduction of HAuCl4 with Good’s buffer, HEPES, at pH 7.4 and room temperature. A cell viability assay was performed with normal esophageal cells exposed to the multi-branched gold nanoparticles and SERS molecules to assess their toxicity. Our results demonstrate the capacity of multibranched gold nanoparticles linked to Raman reporter molecules to generate distinct signature spectra and, with the exception of the gold nanoparticles functionalized with DTTC, remain non-toxic to normal esophageal cells.
This paper presents a novel, compact, single-sideband (SSB) subharmonically-pumped (SHP) direct upconverter developed in a uniplanar 0.18 μm GaAs technology. A total of 100 MHz in-phase and quadrature signals directly modulate the second harmonic of a 30 GHz carrier signal, producing a 60.1 GHz output. Two pairs of antiparallel diodes reduce feed-through of the 30 GHz local oscillator (LO) signal to the mixer's RF output. Novel structures patterned in the center conductor of a coplanar waveguide (CPW) provide matching and size-reduction simultaneously. The 2.1mm2 circuit also uses a miniaturized Wilkinson divider based on asymmetric coplanar stripline and a standard CPW 90° coupler. The SSB SHP direct upconverter exhibits a conversion loss of 10 dB, a lower-sideband rejection of 15 dB and 2fLO suppression of approximately 25 dB over a wide frequency range from 52–61 GHz.
Surveillance for new and re-emerging animal diseases in England and Wales is based on post-mortem and syndromic analysis of laboratory data collated in a central database by the Animal Health and Veterinary Laboratories Agency (AHVLA), with the aim of providing early warning of disease events prior to clinical diagnosis. Understanding the drivers for participation in such systems is critical to the success of attempts to improve surveillance sensitivity. The aim of this study was to investigate the decision-making process governing the submission of biological samples on which this surveillance system is based by use of questionnaires. Data extracted were used to structure and parameterize scenario trees modelling the probability of generating an entry in the surveillance database. The mean probability for database entry per case ranged from 0·085 for neurological disorders to 0·25 for enteric disease. These findings illustrate the importance of on-farm decision making to the generation of surveillance data.