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An inflammation-induced imbalance in the kynurenine pathway (KP) has been reported in major depressive disorder but the utility of these metabolites as predictive or therapeutic biomarkers of behavioral activation (BA) therapy is unknown.
Serum samples were provided by 56 depressed individuals before BA therapy and 29 of these individuals also provided samples after 10 weeks of therapy to measure cytokines and KP metabolites. The PROMIS Depression Scale (PROMIS-D) and the Sheehan Disability Scale were administered weekly and the Beck depression inventory was administered pre- and post-therapy. Data were analyzed with linear mixed-effect, general linear, and logistic regression models. The primary outcome for the biomarker analyses was the ratio of kynurenic acid to quinolinic acid (KynA/QA).
BA decreased depression and disability scores (p's < 0.001, Cohen's d's > 0.5). KynA/QA significantly increased at post-therapy relative to baseline (p < 0.001, d = 2.2), an effect driven by a decrease in QA post-therapy (p < 0.001, uncorrected, d = 3.39). A trend towards a decrease in the ratio of kynurenine to tryptophan (KYN/TRP) was also observed (p = 0.054, uncorrected, d = 0.78). The change in KynA/QA was nominally associated with the magnitude of change in PROMIS-D scores (p = 0.074, Cohen's f2 = 0.054). Baseline KynA/QA did not predict response to BA therapy.
The current findings together with previous research show that electronconvulsive therapy, escitalopram, and ketamine decrease concentrations of the neurotoxin, QA, raise the possibility that a common therapeutic mechanism underlies diverse forms of anti-depressant treatment but future controlled studies are needed to test this hypothesis.
Tear staining (TS) in the pig has been related to different stressors and may be a useful tool for assessing animal welfare on farm. The aim of the current study was to investigate TS across the finisher period and its possible relation to age, growth, sex and experimentally induced stressors. The study included 80 finisher pens divided between three batches. Within each batch, the pens either included pigs with docked or undocked tails, had straw provided (150 g/pig/day) or not and had a low (1.21 m2/pig, 11 pigs) or high stocking density (0.73 m2/pig, 18 pigs). Tear staining (scores 1 to 4; from smaller to larger tear stain area, respectively) and tail damage were scored on each individual pig three times per week over the 9-week study period, and the individual maximum TS score within each week was chosen for further analysis. Data were analysed using logistic regression separately for each of the four possible TS score levels. The TS scores 1 and 2 decreased with weeks into the study period and were negatively related to the average daily gain (ADG) of the pigs, whereas the TS score 4 increased with weeks into the study period and was positively related to ADG. None of the TS scores differed between females and castrated males, and neither straw provision nor lowering the stocking density affected the TS scores. However, the TS score 1 decreased the last week before an event of tail damage (at least one pig in the pen with a bleeding tail wound), whereas the TS score 4 increased. The results of the current study advocates for a relation between TS and the factors such as age, growth and stress in the pig, while no relation was found between TS and the environmental factors straw provision and lowered stocking density. The relations to age and growth are important to take into consideration if using TS as a welfare assessment measure in the pig in the future.
Loose farrowing pens have been considered as alternatives to crates to enhance sow welfare. A major concern with pen systems is often higher piglet pre-weaning mortality, especially due to crushing by the sow. An optimal management of light and mat surface temperature may promote greater piglet use of the creep, which has been associated with reduced piglet crushing. A total of 108 sows and their piglets were studied in sow welfare and piglet protection pens on a commercial piggery, across two replicates. Sows were randomly assigned to pens arranged within two creep treatments (bright creep: 300 lx v. dark creep: 4 lx), considering mat temperature as a covariate. Twelve sows and their litters in each treatment (24 in total) had their behaviour continuously recorded for 72-h postpartum (pp), and four focal piglets per litter were weighed on the first and third days pp. In situ behaviour observations were performed daily (from 0800 to 1700 h) on all sows and their litters, every 15 min over 72-h pp to record piglet time spent in the creep, latency to enter the creep for the first time, latency for the litter to remain in the creep for at least 10 min, and piglet and sow use of pen areas immediately in front of (A2) and farthest from the creep (A3). Piglets with access to bright creeps spent on average 7.2% more time (P<0.01) in the creeps than piglets in pens with Dark creeps. In addition, for each degree increase in mat temperature, piglets spent on average 2.1% more time (P<0.01) in the creep. Piglets in pens with bright creeps spent less time in A2 (P=0.04) and the least time in A3 (P=0.01). Light or mat temperature did not affect sow use of pen areas or piglet weight gain. Piglets with bright creeps tended (P=0.06) to take longer to enter the creep for the first time after birth, but the latency for 30.0% of the litter to remain clustered for 10 min tended (P=0.08) to be shorter in bright compared to dark creeps. Overall, piglet use of the creep increased with warm mat temperatures and brightness, which should be further investigated as potential strategies to promote piglet safety and reduce crushing in pen farrowing systems.
Landraces (including heritage varieties) are an important agrobiodiversity resource offering considerable value as a buffer against crop failures, as a crop for niche markets, and as a source of diversity for crop genetic improvement activities underpinning future food security. Home gardens are reservoirs of landrace diversity, but some of the accessions held in them are vulnerable or threatened with extinction. Those associated with seed saving networks have added security, for example, ca. 800 varieties are stored in the Heritage Seed Library (HSL) of Garden Organic, UK. In this study, Amplified Fragment Length Polymorphisms-based genetic analysis of accessions held in the HSL was used to (a) demonstrate the range of diversity in the collection, (b) characterize accessions to aid collection management and (c) promote broader use of the collection. In total, 171 accessions were included from six crops: Vicia faba L., Pisum sativum L., Daucus carota L., Cucumis sativus L., Lactuca sativa L. and Brassica oleracea L. var. acephala (DC.) Metzq. Average expected heterozygosity ranged from 0.18 to 0.28 in D. carota; 0.02–0.18 in P. sativum; 0.05–0.18 in L. sativa; 0.15–0.26 in B. oleracea var. acephala; 0.15–0.37 in C. sativus and 0.07–0.36 in V. faba. Genetic diversity and Fst values generally reflected the breeding system and cultivation history of the different crops. Comparisons of the diversity found in heritage varieties with that found in commercial varieties did not show a consistent pattern. Principal coordinates analysis and Unweighted Pair Group Method with Arithmetic Mean cluster analysis were used to identify four potential duplicate accession pairs.
Group housing of gestating sows benefits their welfare by allowing them freedom of movement and the opportunity for social interaction. However, social life could also bring disadvantages for individuals who receive direct aggression or are displaced from the feeder. The aim of this study was to investigate associations between social behaviour, body condition and live weight. Gestating sows (n=298) were investigated on a commercial farm. Sows were housed in mixed parity groups where two single space, ad libitum trough feeders served 12 animals. Sows were weighed, body condition scored and had their back fat layer measured at mixing, 4 weeks after insemination and again before farrowing. Social status was estimated based on the numbers of won and lost agonistic interactions at mixing and at the end of gestation. In addition, tear staining was scored before the farrowing and reproductive performance data were collected. With the aid of video recordings, 100 to 150 interactions per group were observed. Winning percentage at mixing and at the end of gestation were associated (P<0.05) and appeared relatively stable within individuals. Tear staining scores and litter sizes were not associated with winning percentage at the end of gestation. However, live weight, relative weight, body condition and back fat thickness were associated with winning percentage (P<0.05), giving heavier animals an advantage. Low winning percentage related to lower live weight gain, probably due to poorer success in competition for feed. Live weight within a mixed parity group could be used as a proxy measure for social status. Sows with low body condition score and submissive sows might need special attention with regard to group dynamics and housing to alleviate the effects of competition in group housing.
Depression can impair the immunogenicity of vaccine administration in adults. Whereas many vaccinations are administered in childhood, it is not known whether adolescent or adult onset depression is associated with impairments in the maintenance of protection of childhood vaccines. This study tested the hypothesis that individuals with adolescent or adult onset mood disorders would display compromised immunity to measles, a target of childhood vaccination.
IgG antibodies to measles were quantified using a solid phase immunoassay in volunteers with bipolar disorder (BD, n = 64, mean age of onset = 16.6 ± 5.6), currently depressed individuals with major depressive disorder (cMDD, n = 85, mean age of onset = 17.9 ± 7.0), remitted individuals with a history of MDD (rMDD, n = 82, mean age of onset = 19.2 ± 8.6), and non-depressed comparison controls (HC, n = 202), all born after the introduction of the measles vaccine in the USA in 1963.
Relative to HC, both the cMDD group (p = 0.021, adjusted odds ratios (OR) = 0.47, confidence interval (CI) = 0.24–0.90), and the rMDD group (p = 0.038, adjusted OR = 0.50, CI = 0.26–0.97) were less likely to test seropositive for measles. Compared with unmedicated MDD participants, currently medicated MDD participants had a longer lifetime duration of illness and were less likely to test seropositive for measles.
Individuals with adolescent or adult onset MDD are less likely to test seropositive for measles. Because lower IgG titers are associated with increased risk of measles infection, MDD may increase the risk and severity of infection possibly because of impaired maintenance of vaccine-related protection from measles.
Phased Array Feed (PAF) technology is the next major advancement in radio astronomy in terms of combining high sensitivity and large field of view. The Focal L-band Array for the Green Bank Telescope (FLAG) is one of the most sensitive PAFs developed so far. It consists of 19 dual-polarization elements mounted on a prime focus dewar resulting in seven beams on the sky. Its unprecedented system temperature of ~17 K will lead to a 3 fold increase in pulsar survey speeds as compared to contemporary single pixel feeds. Early science observations were conducted in a recently concluded commissioning phase of the FLAG where we clearly demonstrated its science capabilities. We observed a selection of normal and millisecond pulsars and detected giant pulses from PSR B1937+21.
Although repeatedly associated with white matter microstructural alterations, bipolar disorder (BD) has been relatively unexplored using complex network analysis. This method combines structural and diffusion magnetic resonance imaging (MRI) to model the brain as a network and evaluate its topological properties. A group of highly interconnected high-density structures, termed the ‘rich-club’, represents an important network for integration of brain functioning. This study aimed to assess structural and rich-club connectivity properties in BD through graph theory analyses.
We obtained structural and diffusion MRI scans from 42 euthymic patients with BD type I and 43 age- and gender-matched healthy volunteers. Weighted fractional anisotropy connections mapped between cortical and subcortical structures defined the neuroanatomical networks. Next, we examined between-group differences in features of graph properties and sub-networks.
Patients exhibited significantly reduced clustering coefficient and global efficiency, compared with controls globally and regionally in frontal and occipital regions. Additionally, patients displayed weaker sub-network connectivity in distributed regions. Rich-club analysis revealed subtly reduced density in patients, which did not withstand multiple comparison correction. However, hub identification in most participants indicated differentially affected rich-club membership in the BD group, with two hubs absent when compared with controls, namely the superior frontal gyrus and thalamus.
This graph theory analysis presents a thorough investigation of topological features of connectivity in euthymic BD. Abnormalities of global and local measures and network components provide further neuroanatomically specific evidence for distributed dysconnectivity as a trait feature of BD.
With the increasing use of complex quantitative models in applications throughout the financial world, model risk has become a major concern. Such risk is generated by the potential inaccuracy and inappropriate use of models in business applications, which can lead to substantial financial losses and reputational damage. In this paper, we deal with the management and measurement of model risk. First, a model risk framework is developed, adapting concepts such as risk appetite, monitoring, and mitigation to the particular case of model risk. The usefulness of such a framework for preventing losses associated with model risk is demonstrated through case studies. Second, we investigate the ways in which different ways of using and perceiving models within an organisation both lead to different model risks. We identify four distinct model cultures and argue that in conditions of deep model uncertainty, each of those cultures makes a valuable contribution to model risk governance. Thus, the space of legitimate challenges to models is expanded, such that, in addition to a technical critique, operational and commercial concerns are also addressed. Third, we discuss through the examples of proxy modelling, longevity risk, and investment advice, common methods and challenges for quantifying model risk. Difficulties arise in mapping model errors to actual financial impact. In the case of irreducible model uncertainty, it is necessary to employ a variety of measurement approaches, based on statistical inference, fitting multiple models, and stress and scenario analysis.
Accurate and complete reporting of study methods, results and interpretation are essential components for any scientific process, allowing end-users to evaluate the internal and external validity of a study. When animals are used in research, excellence in reporting is expected as a matter of continued ethical acceptability of animal use in the sciences. Our primary objective was to assess completeness of reporting for a series of studies relevant to mitigation of pain in neonatal piglets undergoing routine management procedures. Our second objective was to illustrate how authors can report the items in the Reporting guidElines For randomized controLled trials for livEstoCk and food safety (REFLECT) statement using examples from the animal welfare science literature. A total of 52 studies from 40 articles were evaluated using a modified REFLECT statement. No single study reported all REFLECT checklist items. Seven studies reported specific objectives with testable hypotheses. Six studies identified primary or secondary outcomes. Randomization and blinding were considered to be partially reported in 21 and 18 studies, respectively. No studies reported the rationale for sample sizes. Several studies failed to report key design features such as units for measurement, means, standard deviations, standard errors for continuous outcomes or comparative characteristics for categorical outcomes expressed as either rates or proportions. In the discipline of animal welfare science, authors, reviewers and editors are encouraged to use available reporting guidelines to ensure that scientific methods and results are adequately described and free of misrepresentations and inaccuracies. Complete and accurate reporting increases the ability to apply the results of studies to the decision-making process and prevent wastage of financial and animal resources.
Estimates of the proportion of illness transmitted by food for different enteric pathogens are essential for foodborne burden-of-disease studies. Owing to insufficient scientific data, a formal synthesis of expert opinion, an expert elicitation, is commonly used to produce such estimates. Eleven experts participated in an elicitation to estimate the proportion of illnesses due to food in Australia for nine pathogens over three rounds: first, based on their own knowledge alone; second, after being provided with systematic reviews of the literature and Australian data; and finally, at a workshop where experts reflected on the evidence. Estimates changed significantly across the three rounds (P = 0·002) as measured by analysis of variance. Following the workshop in round 3, estimates showed smoother distributions with significantly less variation for several pathogens. When estimates were combined to provide combined distributions for each pathogen, the width of these combined distributions reflected experts’ perceptions of the availability of evidence, with narrower intervals for pathogens for which evidence was judged to be strongest. Our findings show that the choice of expert elicitation process can significantly influence final estimates. Our structured process – and the workshop in particular – produced robust estimates and distributions appropriate for inclusion in burden-of-disease studies.
An estimated 200 million children worldwide fail to meet their development potential due to poverty, poor health and unstimulating environments. Missing developmental milestones has lasting effects on adult human capital. Africa has a large burden of risk factors for poor child development. The objective of this paper is to identify scope for improvement at the country level in three domains – nutrition, environment, and mother–child interactions. We used nationally representative data from large-scale surveys, data repositories and country reports from 2000 to 2014. Overall, there was heterogeneity in performance across domains, suggesting that each country faces distinct challenges in addressing risk factors for poor child development. Data were lacking for many indicators, especially in the mother–child interaction domain. There is a clear need to improve routine collection of high-quality, country-level indicators relevant to child development to assess risk and track progress.
Tututepec was a regional capital that dominated much of southern Oaxaca, Mexico, during the Late Postclassic period (A.D. 1100-1522). This article synthesizes the results of compositional (neutron activation and petrography), stylistic, and iconographic analyses of pottery from commoner household excavations at Tututepec to address questions concerning ceramic production and distribution and also to shed light on aspects of political economy and domestic ritual at the capital. The study focuses primarily on Mixteca-Puebla polychromes, painted serving vessels bearing complex decorative motifs. Our compositional analyses, interpreted in light of the bedrock geology of the region, indicate that commoners obtained at least six to ten distinct varieties of pottery made from raw materials available locally within greater Tututepec. We argue that households probably acquired pottery through a central marketplace at the capital. In addition, our study demonstrates that commoners had regular access to polychromes from multiple producers, challenging the widespread notion that these vessels were restricted to elites who controlled their production. We argue that polychrome serving vessels played a prominent role in commonly occurring domestic rituals. Furthermore, commoners appear to have consciously selected vessels painted with imagery associated with warfare and sacrifice, suggesting that they actively supported the official imperial ideology of Tututepec.
Tear staining or chromodacryorrhea refers to a dark stain below the inner corner of the eye, caused by porphyrin-pigmented secretion from the Harderian gland. It has been shown to be a consistent indicator of stress in rats and to correlate with social stress and a barren environment in pigs. The current study was, to our knowledge, the first to test it on commercial pig farms as a potential welfare indicator. The study was carried out on three commercial farms in Finland, in connection to a larger study on the effects of different types of manipulable objects on tail and ear biting and other behavioural parameters. Farm A was a fattening farm, on which 768 growing-finishing pigs were studied in 73 pens. Farm B had a fattening unit, in which 656 growing-finishing pigs were studied in 44 pens, and a farrowing unit, in which 29 sows and their litters totalling 303 piglets were studied in 29 pens. Farm C was a piglet-producing farm, on which 167 breeder gilts were studied in 24 pens. Data collection included individual-level scoring of tear staining; scoring of tail and ear damage in the growing-finishing pigs and breeder gilts; a novel object test for the piglets; and a novel person test for the growing-finishing pigs on Farm B and the breeder gilts on Farm C. On Farm A, tear staining was found to correlate with tail damage scores (n=768, rs=0.14, P<0.001) and ear damage scores (n=768, rs=0.16, P<0.001). In the growing-finishing pigs on Farm B, tear staining of the left eye correlated with tail damage (n=656, rs=0.12, P<0.01) and that of the right eye correlated with ear damage (n=656, rs=0.10, P<0.01). On Farm A, tear-staining sores were lower in the treatment with three different types of manipulable objects as compared with controls (mean scores 3.3 and 3.9, respectively, n=31, F29=4.2, P<0.05). In the suckling piglets on Farm B, tear staining correlated with the latency to approach a novel object (n=29, rp=0.41, P<0.05). Although correlations with tail and ear damage were low, it was concluded that tear staining has promising potential as a new, additional welfare indicator for commercial pig farming. Further research is needed on the mechanisms of tear staining.
In June 2014 Public Health England confirmed a case of Legionnaires' disease (LD) in a neonate following birth at home in a hired birthing pool incorporating a heater and a recirculation pump which had been filled in advance of labour. The case triggered a public health investigation and a microbiological survey of an additional ten heated birthing pools hired or recently hired to the general public across England. The birthing pool used by the parent of the confirmed case was identified as the source of the neonate's infection following detection of Legionella pneumophila ST48 in both patient and environmental samples. Legionella species were detected by quantitative polymerase chain reaction but not culture in a further three pools together with other opportunistic pathogens identified by culture and matrix-assisted laser desorption ionization–time of flight (MALDI–ToF) mass spectrometry. A Patient Safety Alert from NHS England and Public Health England was issued stating that heated birthing pools filled in advance of labour should not be used for home births. This recommendation remains in place. This investigation in conjunction with other recent reports has highlighted a lack of awareness regarding the microbiological safety of heated birthing pools and their potential to be a source of LD and other opportunistic infections. Furthermore, the investigation raised important considerations with regards to microbiological sampling and testing in such incidents. Public health authorities and clinicians should consider LD in the differential diagnosis of severe respiratory infection in neonates within 14 days of a water birth.
Recent UV absorption line studies suggest that a large fraction of missing baryons are in the warm ionized and neutral phases, with about half of Milky Way-mass galaxies containing absorption systems with HI column densities of 1018 cm−2 or greater. This HI gas, which would have been difficult to detect with previous instruments, could be a significant contributor to the missing baryons. The Green Bank Telescope (GBT) presents a unique opportunity to detect this emission. We present results from GBT 21 cm observations of a sample of ten nearby optically luminous spirals, which reveal extended HI gas in half of our sample. The column densities of this extended HI are typically ~ 1 × 1019 cm−2, as measured at distances of 100 kpc from the center of the galaxies.
The ITRACK study explored the process and predictors of transition between Child and Adolescent Mental Health Services (CAMHS) and Adult Mental Health Services (AMHS) in the Republic of Ireland.
Following ethical approval, clinicians in each of Ireland’s four Health Service Executive (HSE) areas were contacted, informed about the study and were invited to participate. Clinicians identified all cases who had reached the transition boundary (i.e. upper age limit for that CAMHS team) between January and December 2010. Data were collected on clinical and socio-demographic details and factors that informed the decision to refer or not refer to the AMHS, and case notes were scrutinised to ascertain the extent of information exchanged between services during transition.
A total of 62 service users were identified as having crossed the transition boundary from nine CAMHS [HSE Dublin Mid-Leinster (n=40, 66%), HSE South (n=18, 30%), HSE West (n=2, 3%), HSE Dublin North (n=1, 2%)]. The most common diagnoses were attention deficit hyperactivity disorder (ADHD; n=19, 32%), mood disorders (n=16, 27%), psychosis (n=6, 10%) and eating disorders (n=5, 8%). Forty-seven (76%) of those identified were perceived by the CAMHS clinician to have an ‘on-going mental health service need’, and of these 15 (32%) were referred, 11 (23%) young people refused and 21 (45%) were not referred, with the majority (12, 57%) continuing with the CAMHS for more than a year beyond the transition boundary. Young people with psychosis were more likely to be referred [χ2 (2, 46)=8.96, p=0.02], and those with ADHD were less likely to be referred [χ2 (2, 45)=8.89, p=0.01]. Being prescribed medication was not associated with referral [χ2 (2, 45)=4.515, p=0.11]. In referred cases (n=15), there was documented evidence of consent in two cases (13.3%), inferred in another four (26.7%) and documented preparation for transition in eight (53.3%). Excellent written communication (100%) was not supported by face-to-face planning meetings (n=2, 13.3%), joint appointments (n=1, 6.7%) or telephone conversations (n=1, 6.7%) between corresponding clinicians.
Despite perceived on-going mental health (MH) service need, many young people are not being referred or are refusing referral to the AMHS, with those with ADHD being the most affected. CAMHS continue to offer on-going care past the transition boundary, which has resource implications. Further qualitative research is warranted to understand, in spite of perceived MH service need, the reason for non-referral by the CAMHS clinicians and refusal by the young person.
To examine beliefs about irritable bowel syndrome (IBS) management among primary care physicians.
There have been considerable advances in evidence synthesis concerning management of IBS in the last five years, with guidelines for its management in primary care published by the National Institute for Health and Care Excellence (NICE).
This was a cross-sectional web-based questionnaire survey of 275 primary care physicians. We emailed a link to a SurveyMonkey questionnaire, containing 18 items, to all eligible primary care physicians registered with three clinical commissioning groups in Leeds, UK. Participants were given one month to respond, with a reminder sent out after two weeks.
One-hundred and two (37.1%) primary care physicians responded. Among responders, 70% believed IBS was a diagnosis of exclusion, and >80% checked coeliac serology often or always in suspected IBS. Between >50% and >70% believed soluble fibre, antispasmodics, peppermint oil, and psychological therapies were potentially efficacious therapies. The respondents were less convinced that antidepressants or probiotics were effective. Despite perceived efficacy of psychological therapies, 80% stated these were not easily available. Levels of use of soluble fibre, antispasmodics, and peppermint oil were in the range of 40% to >50%. Most primary care physicians obtained up-to-date evidence about IBS management from NICE guidelines. Most primary care physicians still believe IBS is a diagnosis of exclusion, and many are reluctant to use antidepressants or probiotics to treat IBS. More research studies addressing diagnosis and treatment of IBS based in primary are required.
Piglets reared in swine production in the USA undergo painful procedures that include castration, tail docking, teeth clipping, and identification with ear notching or tagging. These procedures are usually performed without pain mitigation. The objective of this project was to develop recommendations for pain mitigation in 1- to 28-day-old piglets undergoing these procedures. The National Pork Board funded project to develop recommendations for pain mitigation in piglets. Recommendation development followed a defined multi-step process that included an evidence summary and estimates of the efficacies of interventions. The results of a systematic review of the interventions were reported in a companion paper. This manuscript describes the recommendation development process and the final recommendations. Recommendations were developed for three interventions (CO2/O2 general anesthesia, non-steroidal anti-inflammatory drugs (NSAIDs), and lidocaine) for use during castration. The ability to make strong recommendations was limited by low-quality evidence and strong certainty about variation in stakeholder values and preferences. The panel strongly recommended against the use of a CO2/O2 general anesthesia mixture, weakly recommended for the use of NSAIDs and weakly recommended against the use of lidocaine for pain mitigation during castration of 1- to 28-day-old piglets.