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Cognitive deficits in depressed adults may reflect impaired decision-making. To investigate this possibility, we analyzed data from unmedicated adults with Major Depressive Disorder (MDD) and healthy controls as they performed a probabilistic reward task. The Hierarchical Drift Diffusion Model (HDDM) was used to quantify decision-making mechanisms recruited by the task, to determine if any such mechanism was disrupted by depression.
Data came from two samples (Study 1: 258 MDD, 36 controls; Study 2: 23 MDD, 25 controls). On each trial, participants indicated which of two similar stimuli was presented; correct identifications were rewarded. Quantile-probability plots and the HDDM quantified the impact of MDD on response times (RT), speed of evidence accumulation (drift rate), and the width of decision thresholds, among other parameters.
RTs were more positively skewed in depressed v. healthy adults, and the HDDM revealed that drift rates were reduced—and decision thresholds were wider—in the MDD groups. This pattern suggests that depressed adults accumulated the evidence needed to make decisions more slowly than controls did.
Depressed adults responded slower than controls in both studies, and poorer performance led the MDD group to receive fewer rewards than controls in Study 1. These results did not reflect a sensorimotor deficit but were instead due to sluggish evidence accumulation. Thus, slowed decision-making—not slowed perception or response execution—caused the performance deficit in MDD. If these results generalize to other tasks, they may help explain the broad cognitive deficits seen in depression.
Fatigue syndromes (FSs) affect large numbers of individuals, yet evidence from epidemiological studies on adverse outcomes, such as premature death, is limited.
Cohort study involving 385 general practices in England that contributed to the Clinical Practice Research Datalink (CPRD) with linked inpatient Hospital Episode Statistics (HES) and Office for National Statistics (ONS) cause of death information. A total of 10 477 patients aged 15 years and above, diagnosed with a FS during 2000–2014, were individually matched with up to 20 comparator patients without a history of having a FS. Prevalence ratios (PRs) were estimated to compare the FS and comparison cohorts on clinical characteristics. Adjusted hazard ratios (HRs) for subsequent adverse outcomes were estimated from stratified Cox regression models.
Among patients diagnosed with FSs, we found elevated baseline prevalence of: any psychiatric illness (PR 1.77; 95% CI 1.72–1.82), anxiety disorders (PR 1.92; 1.85–1.99), depression (PR 1.89; 1.83–1.96), psychotropic prescriptions (PR 1.68; 1.64–1.72) and comorbid physical illness (PR 1.28; 1.23–1.32). We found no significant differences in risks for: all-cause mortality (HR 0.99; 0.91–1.09), natural death (HR 0.99; 0.90–1.09), unnatural death (HR 1.00; 0.59–1.72) or suicide (HR 1.68; 0.78–3.63). We did, however, observe a significantly elevated non-fatal self-harm risk: HR 1.83; 1.56–2.15.
The absence of elevated premature mortality risk is reassuring. The raised prevalence of mental illness and increased non-fatal self-harm risk indicate a need for enhanced assessment and management of psychopathology associated with fatigue syndromes.
To compare the effects of empiric carbapenems versus cycling cefepime and piperacillin/tazobactam on the rates of vancomycin-resistant Enterococcus (VRE) colonization, bloodstream infections, and outcomes of patients admitted with acute leukemia.
Retrospective clinical study with VRE molecular strain typing and gastrointestinal microbiome comparison.
A regional referral center for acute leukemia.
342 consecutive patients admitted with newly diagnosed acute leukemia.
In September 2015, we changed our empiric antibiotic of choice for neutropenic fever from a carbapenem to the cycling regimen. We studied 214 consecutive patients during the carbapenem period and 128 during the cycling period. Surveillance for VRE stool colonization was conducted weekly. Representative stool samples were analyzed for VRE MLST types and changes in the composition and diversity of the fecal microbiota.
The change in empiric antibiotics was associated with a significant decrease in VRE colonization (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.27–0.66), a switch in the dominant VRE MLST types on the unit, and some modifications in the gastrointestinal microbiome. There were no differences in total gram-positive or gram-negative BSIs. During the carbapenem period, we observed higher absolute numbers of Candida spp and fewer ESBL BSIs, but these did not reach statistical significance. Patients during the carbapenem period had longer lengths of stay and durations of severe neutropenia and 10% higher hospital cost.
Carbapenem-sparing empiric antibiotic regimens may have advantages related to VRE ecology, gastrointestinal dysbiosis, duration of neutropenia, cost and length of stay.
Autism spectrum disorder (ASD) is associated with pervasive social deficits as well as marked emotion dysregulation across the life span. Decreased social motivation accounts in part for social difficulties, but factors moderating its influence are not fully understood. In this paper, we (a) characterize social and emotional functioning among children and adolescents with ASD, (b) explore contributions of social motivation and emotion dysregulation to social skill, and (c) consider biological sex and intellectual functioning as moderators of these associations. In a sample of 2,079 children and adolescents with ASD from the Simons Simplex Collection, we document direct effects of social motivation, internalizing symptoms, aggression, attention problems, irritability, and self-injurious behavior on children's social skills. Furthermore, dysregulation in several domains moderated the association between social motivation and social skill, suggesting a blunting effect on social motivation in the context of emotional difficulties. Moreover, when considering only individuals with intellectual skills in the average range or higher, biological sex further moderated these associations. Findings add to our understanding of social–emotional processes in ASD, suggest emotion dysregulation as a target of intervention in the service of social skill improvements, and build on efforts to understand sources of individual difference that contribute to heterogeneity among individuals with ASD.
The Roman period sees the introduction of many new plants and animals into Britain, with a profound impact on people's experience of their environment. Sweet chestnut is considered to be one such introduction, for which records of sweet chestnut wood and charcoal from archaeological excavations of Romano-British period contexts have been used as evidence. This paper reviews the records for sweet chestnut in Britain pre-a.d. 650, by critically evaluating original excavation reports and examining archived specimens. This review re-assesses the original identifications of sweet chestnut and/or their dating and concludes that most of the evidence that justified sweet chestnut's status as a Roman archaeophyte is untenable. The review emphasises the importance of securely identifying and directly dating plant material and of long-term curation by museums and archives. The Supplementary Material online (https://doi.org/10.1017/S0068113X19000011) contains details of all published records of finds of sweet chesnut.
Optical parametric chirped-pulse amplification (OPCPA) [Dubietis et al., Opt. Commun. 88, 437 (1992)] implemented by multikilojoule Nd:glass pump lasers is a promising approach to produce ultraintense pulses (
). Technologies are being developed to upgrade the OMEGA EP Laser System with the goal to pump an optical parametric amplifier line (EP OPAL) with two of the OMEGA EP beamlines. The resulting ultraintense pulses (1.5 kJ, 20 fs,
) would be used jointly with picosecond and nanosecond pulses produced by the other two beamlines. A midscale OPAL pumped by the Multi-Terawatt (MTW) laser is being constructed to produce 7.5-J, 15-fs pulses and demonstrate scalable technologies suitable for the upgrade. MTW OPAL will share a target area with the MTW laser (50 J, 1 to 100 ps), enabling several joint-shot configurations. We report on the status of the MTW OPAL system, and the technology development required for this class of all-OPCPA laser system for ultraintense pulses.
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.
Australian mosquito species significantly impact human health through nuisance biting and the transmission of endemic and exotic pathogens. Surveillance programmes designed to provide an early warning of mosquito-borne disease risk require reliable identification of mosquitoes. This study aimed to investigate the viability of Matrix-Assisted Laser Desorption/Ionization–Time-of-Flight Mass Spectrometry (MALDI-TOF MS) as a rapid and inexpensive approach to the identification of Australian mosquitoes and was validated using a three-step taxonomic approach. A total of 300 mosquitoes representing 21 species were collected from south-eastern New South Wales and morphologically identified. The legs from the mosquitoes were removed and subjected to MALDI-TOF MS analysis. Fifty-eight mosquitoes were sequenced at the cytochrome c oxidase subunit I (cox1) gene region and genetic relationships were analysed. We create the first MALDI-TOF MS spectra database of Australian mosquito species including 19 species. We clearly demonstrate the accuracy of MALDI-TOF MS for identification of Australian mosquitoes. It is especially useful for assessing gaps in the effectiveness of DNA barcoding by differentiating closely related taxa. Indeed, cox1 DNA barcoding was not able to differentiate members of the Culex pipiens group, Cx. quinquefasciatus and Cx. pipiens molestus, but these specimens were correctly identified using MALDI-TOF MS.
Major depressive disorder (MDD) is a highly heterogeneous condition in terms of symptom presentation and, likely, underlying pathophysiology. Accordingly, it is possible that only certain individuals with MDD are well-suited to antidepressants. A potentially fruitful approach to parsing this heterogeneity is to focus on promising endophenotypes of depression, such as neuroticism, anhedonia, and cognitive control deficits.
Within an 8-week multisite trial of sertraline v. placebo for depressed adults (n = 216), we examined whether the combination of machine learning with a Personalized Advantage Index (PAI) can generate individualized treatment recommendations on the basis of endophenotype profiles coupled with clinical and demographic characteristics.
Five pre-treatment variables moderated treatment response. Higher depression severity and neuroticism, older age, less impairment in cognitive control, and being employed were each associated with better outcomes to sertraline than placebo. Across 1000 iterations of a 10-fold cross-validation, the PAI model predicted that 31% of the sample would exhibit a clinically meaningful advantage [post-treatment Hamilton Rating Scale for Depression (HRSD) difference ⩾3] with sertraline relative to placebo. Although there were no overall outcome differences between treatment groups (d = 0.15), those identified as optimally suited to sertraline at pre-treatment had better week 8 HRSD scores if randomized to sertraline (10.7) than placebo (14.7) (d = 0.58).
A subset of MDD patients optimally suited to sertraline can be identified on the basis of pre-treatment characteristics. This model must be tested prospectively before it can be used to inform treatment selection. However, findings demonstrate the potential to improve individual outcomes through algorithm-guided treatment recommendations.
Research demonstrates the importance of nutrition for early brain development. Few studies have examined the effectiveness of multiple micronutrient powders (MNP) on child development. This study examined the impacts of home fortification with MNP on motor and mental development, executive function and memory of children living in Bihar. This two-arm cluster-randomised effectiveness trial selected seventy health sub-centres to receive either MNP and nutrition counselling (intervention) or nutrition counselling alone (control) for 12 months. Front-line health workers delivered the intervention to all households in study communities with a child aged 6–18 months. Data were collected using cross-sectional surveys at baseline and endline by selecting households from intervention (baseline, n 2184; endline, n 2170) and control (baseline, n 2176; endline, n 2122) communities using a two-stage cluster-randomised sampling strategy. Children in the intervention group had a significantly larger improvement from baseline to endline compared with those in the control group on scores for motor and mental development (Cohen’s d, motor=0·12; 95 % CI 0·03, 0·22; mental=0·15; 95 % CI 0·06, 0·25). Greater impacts of MNP on motor and mental development were observed in children from households with higher stimulation scores at baseline compared with those with lower stimulation (Cohen’s d, motor=0·20 v. 0·09; mental=0·22 v. 0·14; Pinteraction<0·05). No significant treatment differences were seen for executive function or memory. Home fortification with MNP through the existing health infrastructure in Bihar was effective in improving motor and mental development and should be considered in combination with other child development interventions such as stimulation.
Factors associated with relapse among children who are discharged after reaching a threshold denoted ‘recovered’ from moderate acute malnutrition (MAM) are not well understood. The aim of this study was to identify factors associated with sustained recovery, defined as maintaining a mid-upper-arm circumference≥12·5 cm for 1 year after release from treatment. On the basis of an observational study design, we analysed data from an in-depth household (HH) survey on a sub-sample of participants within a larger cluster randomised controlled trial (cRCT) that followed up children for 1 year after recovery from MAM. Out of 1497 children participating in the cRCT, a subset of 315 children participated in this sub-study. Accounting for other factors, HH with fitted lids on water storage containers (P=0·004) was a significant predictor of sustained recovery. In addition, sustained recovery was better among children whose caregivers were observed to have clean hands (P=0·053) and in HH using an improved sanitation facility (P=0·083). By contrast, socio-economic status and infant and young child feeding practices at the time of discharge and HH food security throughout the follow-up period were not significant. Given these results, we hypothesise that improved water, sanitation and hygiene conditions in tandem with management of MAM through supplemental feeding programmes have the possibility to decrease relapse following recovery from MAM. Furthermore, the absence of associations between relapse and nearly all HH-level factors indicates that the causal factors of relapse may be related mostly to the child’s individual, underlying health and nutrition status.
An effective method for enhancing milk production efficiency in dairy cows is to increase milk yield and significant progress has been achieved through intense selection, assisted by the application of new reproductive techniques. However this increased milk yield has been accompanied by a slow but steady decline in dairy cow fertility. The two main reasons for this reducing level of fertility appear to be selection for increased milk yield and large herd sizes, although the affect of the introduction of Holstein genes needs to be investigated. In addition, other negative consequences such as an increase in the incidence of metabolic diseases and lameness have been observed. This has given rise to public concern that the high-yielding dairy cow may be under a state of metabolic stress during peak lactation and therefore the welfare and performance of other body functions are compromised.
The reason for this decline in fertility is not well understood, although a nutritional influence on the initiation of oestrous cycles, follicular growth, oocyte quality and early embryonic development has been implicated. In early lactation dietary intake is unable to meet the demands of milk production and most cows enter a period of negative energy balance. Negative energy balance has a broadly similar effect to undernutrition leading to a mobilization of body reserves. Furthermore diets high in rumen degradable protein lead to an excess of rumen ammonia, which before it is converted to urea by the liver and excreted in the urine, may cause an alteration in the reproductive tract environment reducing embryo survival. Such major changes in the metabolic and endocrine systems can therefore influence fertility at a number of key points.
Possible reproductive sites where inadequate nutrition may have detrimental effects include: (i) the hypothalamic/pituitary gland where gonadotropin release may be impaired; (ii) a direct effect on the ovaries, where both follicular growth patterns and corpus luteum function may be directly influenced; (iii) the quality of the oocyte prior to ovulation may be reduced and coupled with an inadequate uterine environment will result in reduced embryo survival and (iv) there may be effects on subsequent embryo development. The initiation of normal oestrous cycles post partum is usually delayed in dairy cows with a higher genetic merit for milk production, confirming that intense selection towards high milk yield can compromise reproductive function. In addition, the effects of increased milk yield may include changes in circulating GH and insulin concentrations, which in turn alter both insulin-like growth factor (IGF) and IGF binding protein production. Nutrition has recently been shown to have a direct effect at the level of both the ovaries and the uterus to alter the expression of these growth factors.
In conclusion, further knowledge is required to determine how the metabolic changes associated with high milk output reduce fertility. Identification and understanding of the mechanisms involved and the key sites of action responsible for compromised reproductive function, will enable the identification of possible indices for future multiple-trait selection programmes.
Past improvement programmes in pigs have concentrated on lean growth, and have relied on direct comparisons of contemporaries in a common environment. The new mixed model technology now allows comparisons across environments and generations, and, by utilizing all possible genetic relationships, more accurate prediction of genetic merit for traits of low heritability. In addition, breeding programme design will benefit from more precise estimation of genetic parameters. Principal benefits of the new technology are greater flexibility of structure of breeding programmes, and faster improvement of litter size. The consequence will be larger populations under selection with lower costs per unit of genetic improvement. For national improvement schemes using a high proportion of AI matings, central testing stations could become unnecessary. Main research priorities are the optimum family structure to balance selection and inbreeding, more efficient computing strategies for large numbers of traits, and the incorporation of single genes into predictions of merit. The new technology will be important for the exploitation of biological advances in manipulation of both reproduction and the genome.
In nutritional terms productivity in dairy cows is best expressed in multiples of their energy requirements for maintenance, which is directly related to Metabolic Body Weight (MBW). Energy requirements can further be specified as those for free energy (fME), ketogenic energy (kME), glucogenic energy (gME) and aminogenic energy (aME). For maintenance, energy is required in an approximate ratio fME:gME:aME of 85:5:10.For a production level of 6x maintenance the required ratio of fME:kME:gME:aME is approximately 18:31:29:22, hence 70% of the required ME has to be delivered as specific nutrients.
During their productive life, dairy cattle alternate periods with high and periods with low risk of an inadequate nutrient supply. A period of high risk is between 10 days pre-partum and 90 days postpartum. High risk in this period means a high susceptibility for metabolic and reproductive disorders, many of which are interrelated. Negative Energy Balance (NEB) in early lactation is a metabolic status that is almost inevitable in high yielding dairy cows. In severe cases this is an important predisposing factor for metabolic disorders (paturient paresis, fatty liver, ketosis, displaced abomasum) and reproductive disorders (undetected heat, delayed ovarian cycle, reduced fertility, increased between calving interval).
Adequate nutrient supply is required from 2 weeks pre-partum onwards. Critical issues are energy density, distribution between structural and non-structural carbohydrates and distribution between fME, kME, gME and aME. Practical solutions, which can help alleviate the metabolic and reproductive problems, could be a nutrient based feed evaluation system, a lower peak yield combined with an improved persistence and maybe a deliberately increased calving interval.
The relations between genetic change in domestic livestock and infectious disease (including both its epidemiology and the animal's reaction to it) are examined. The overall picture is confusing because there are different, and seemingly unrelated, ways of considering the issue. An attempt is made to put these together into a more general framework. Four processes of particular interest are distinguished and discussed in more detail: (i) the way a population's genetic potential for immunocompetence can be changed by breeding, (ii) the way an animal's immunocompetence is influenced by that animal's production potential, in combination with the environmental resources that are available to it at a given time, (iii) the way the disease status of an animal (and a population of animals) is influenced by its immunocompetence, and (iv) the way the production level of an animal is influenced by activation of its immune system. Ultimately, all four processes influence the realised level of production.
This comes down to four questions that need to be addressed: (i) can we use genetic variation in immunocompetence in animal breeding? (ii) does a higher production potential (today's direction of breeding) have a negative impact on immunocompetence? (iii) does improved immunocompetence result in improved health? and (iv) how large is the negative impact of disease on production?
For the past thirty years pig genetics has enjoyed a clear message from its end–users: reduce backfat and production costs. During that period, genetics, nutrition and health have together delivered improvements of some 60% in lean growth rate and feed efficiency. To compound the recent misfortunes of the UK industry, meat is now slipping further behind everything else on the supermarket shelf in quality, uniformity, and above all predictability. The notion of quality stretches far beyond the product into responsibility for animal welfare, human nutrition and food safety.
The industry's present dilemma arises from five factors:
1.uncertain market conditions with cyclical profitability
2.poor communication of what constitutes good quality
3.payment systems that no longer reflect what the market requires
4.independent management of the different steps in the pork value chain
5.possible effects of animal health on quality and uniformity.
Meanwhile the understanding of gene function and the ability to detect potentially useful genetic variation is gathering momentum. This paper examines the role that genetics can play in adding value, reducing risk and differentiating the product, from the perspective of a large vertically coordinated pork producer.
In commercial egg type chicken breeding three and four way crosses are used to produce commercial layers. The primary breeders are using closed nucleus breeding programmes, with birds kept under maximum biosecurity. All grand parents and parents are produced from a closed nucleus for the world wide demand of commercial layers. The breeding goals have been focused for several decades on increasing number of eggs per hen housed. Additional traits have become more important during the last decade, i.e. feed efficiency, internal and external egg quality and general adaptability. Prior to each selection, weights for individual traits within the selection index are adjusted to meet market demands. Breeding stock and commercial layers have to be bred to perform adequately in a variety of systems ranging from large intensive cage units to free range management under different environmental conditions world-wide.
Despite intensive selection for egg production the decrease in genetic variation observed in closed commercial lines is not yet critical. Peak production is approaching the biological limit of one egg a day. During this period genetic and phenotypic variation have been significantly reduced. But for early production (sexual maturity) and late production (persistency) genetic variation is still high. In a mating scheme avoiding full and half sib matings no serious inbreeding depression is observed. To achieve continued future genetic progress, selection pressure will shift to other traits like internal and external egg quality and perhaps behaviour traits which still respond to selection.
Primary breeders are responding to this challenge by testing pedigreed cross-line hens in a wide range of environments and housing systems while the pure-line elite stock is kept under conditions of maximum biosecurity. Marker assisted selection is already part of commercial breeding programmes. In the past, blood typing has been used to improve Marek's resistance, whereas today anonymous microsatellites which are linked to traits of economic interest are used for selection. In particular, selection between full sib males can give a major improvement.
The whole industry is getting more specialised. While the genetic potential of the birds is improved management and nutrition have also to be adapted to changing demands. The general goal for the future is to breed chickens with the ability to function well within a wider range of production conditions and do not respond to the slightest stress.