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As demonstrated by neuroimaging data, the human brain contains systems that control responses to threat. The revised Reinforcement Sensitivity Theory of personality predicts that individual differences in the reactivity of these brain systems produce anxiety and fear-related personality traits. Here we discuss some of the challenges in testing this theory and, as an example, present a pilot study that aimed to dissociate brain activity during pursuit by threat and goal conflict. We did this by translating the Mouse Defense Test Battery for human fMRI use. In this version, dubbed the Joystick Operated Runway Task (JORT), we repeatedly exposed 24 participants to pursuit and goal conflict, with and without threat of electric shock. The runway design of JORT allowed the effect of threat distance on brain activation to be evaluated independently of context. Goal conflict plus threat of electric shock caused deactivation in a network of brain areas that included the fusiform and middle temporal gyri, as well as the default mode network core, including medial frontal regions, precuneus and posterior cingulate gyrus, and laterally the inferior parietal and angular gyri. Consistent with earlier research, we also found that imminent threat activated the midbrain and that this effect was significantly stronger during the simple pursuit condition than during goal conflict. Also consistent with earlier research, we found significantly greater hippocampal activation during goal conflict than pursuit by imminent threat. In conclusion, our results contribute knowledge to theories linking anxiety disorders to altered functioning in defensive brain systems and also highlight challenges in this research domain.
Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.
Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.
Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).
Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.
Decreases in Fe status have been reported in military women during initial training periods of 8–10 weeks. The present study aimed to characterise Fe status and associations with physical performance in female New Zealand Army recruits during a 16-week basic combat training (BCT) course. Fe status indicators – Hb, serum ferritin (sFer), soluble transferrin receptor (sTfR), transferrin saturation (TS) and erythrocyte distribution width (RDW) – were assessed at the beginning (baseline) and end of BCT in seventy-six volunteers without Fe-deficiency non-anaemia (sFer <12 µg/l; Hb ≥120 g/l) or Fe-deficiency anaemia (sFer <12 µg/l; Hb <120 g/l) at baseline or a C-reactive protein >10 mg/l at baseline or end. A timed 2·4 km run followed by maximum press-ups were performed at baseline and midpoint (week 8) to assess physical performance. Changes in Fe status were investigated using paired t tests and associations between Fe status and physical performance evaluated using Pearson correlation coefficients. sFer (56·6 (sd 33·7) v. 38·4 (sd 23·8) µg/l) and TS (38·8 (sd 13·9) v. 34·4 (sd 11·5) %) decreased (P<0·001 and P=0·014, respectively), while sTfR (1·21 (sd 0·27) v. 1·39 (sd 0·35) mg/l) and RDW (12·8 (sd 0·6) v. 13·2 (sd 0·7) %) increased (P<0·001) from baseline to end. Hb (140·6 (sd 7·5) v. 142·9 (sd 7·9) g/l) increased (P=0·009) during BCT. At end, sTfR was positively (r 0·29, P=0·012) and TS inversely associated (r –0·32, P=0·005) with midpoint run time. There were no significant correlations between Fe status and press-ups. Storage and functional Fe parameters indicated a decline in Fe status in female recruits during BCT. Correlations between tissue-Fe indicators and run times suggest impaired aerobic fitness. Optimal Fe status appears paramount for enabling success in female recruits during military training.
Rare copy number variants (CNVs) are associated with risk of neurodevelopmental disorders characterised by varying degrees of cognitive impairment, including schizophrenia, autism spectrum disorder and intellectual disability. However, the effects of many individual CNVs in carriers without neurodevelopmental disorders are not yet fully understood, and little is known about the effects of reciprocal copy number changes of known pathogenic loci.
We aimed to analyse the effect of CNV carrier status on cognitive performance and measures of occupational and social outcomes in unaffected individuals from the UK Biobank.
We called CNVs in the full UK Biobank sample and analysed data from 420 247 individuals who passed CNV quality control, reported White British or Irish ancestry and were not diagnosed with neurodevelopmental disorders. We analysed 33 pathogenic CNVs, including their reciprocal deletions/duplications, for association with seven cognitive tests and four general measures of functioning: academic qualifications, occupation, household income and Townsend Deprivation Index.
Most CNVs (24 out of 33) were associated with reduced performance on at least one cognitive test or measure of functioning. The changes on the cognitive tests were modest (average reduction of 0.13 s.d.) but varied markedly between CNVs. All 12 schizophrenia-associated CNVs were associated with significant impairments on measures of functioning.
CNVs implicated in neurodevelopmental disorders, including schizophrenia, are associated with cognitive deficits, even among unaffected individuals. These deficits may be subtle but CNV carriers have significant disadvantages in educational attainment and ability to earn income in adult life.
The crystal structure of tlapallite has been determined using single-crystal X-ray diffraction and supported by electron probe micro-analysis, powder diffraction and Raman spectroscopy. Tlapallite is trigonal, space group P321, with a = 9.1219(17) Å, c = 11.9320(9) Å and V = 859.8(3) Å3, and was refined to R1 = 0.0296 for 786 reflections with I > 2σ(I). This study resulted from the discovery of well-crystallised tlapallite at the Wildcat prospect, Utah, USA. The chemical formula of tlapallite has been revised to (Ca,Pb)3CaCu6[Te4+3Te6+O12]2(Te4+O3)2(SO4)2·3H2O, or more simply (Ca,Pb)3CaCu6Te4+8Te6+2O30(SO4)2·3H2O, from H6(Ca,Pb)2(Cu,Zn)3(TeO3)4(TeO6)(SO4). The tlapallite structure consists of layers containing distorted Cu2+O6 octahedra, Te6+O6 octahedra and Te4+O4 disphenoids (which together form the new mixed-valence phyllotellurate anion [Te4+3Te6+O12]12−), Te4+O3 trigonal pyramids and CaO8 polyhedra. SO4 tetrahedra, Ca(H2O)3O6 polyhedra and H2O groups fill the space between the layers. Tlapallite is only the second naturally occurring compound containing tellurium in both the 4+ and 6+ oxidation states with a known crystal structure, the other being carlfriesite, CaTe4+2Te6+O8. Carlfriesite is the predominant secondary tellurium mineral at the Wildcat prospect. We also present an updated structure for carlfriesite, which has been refined to R1 = 0.0230 for 874 reflections with I > 2σ(I). This updated structural refinement improves upon the one reported previously by refining all atoms anisotropically and presenting models of bond valence and Te4+ secondary bonding.
Despite children’s unique vulnerability, clinical guidance and resources are lacking around the use of radiation medical countermeasures (MCMs) available commercially and in the Strategic National Stockpile to support immediate dispensing to pediatric populations. To better understand the current capabilities and shortfalls, a literature review and gap analysis were performed.
A comprehensive review of the medical literature, Food and Drug Administration (FDA)-approved labeling, FDA summary reviews, medical references, and educational resources related to pediatric radiation MCMs was performed from May 2016 to February 2017.
Fifteen gaps related to the use of radiation MCMs in children were identified. The need to address these gaps was prioritized based upon the potential to decrease morbidity and mortality, improve clinical management, strengthen caregiver education, and increase the relevant evidence base.
Key gaps exist in information to support the safe and successful use of MCMs in children during radiation emergencies; failure to address these gaps could have negative consequences for families and communities. There is a clear need for pediatric-specific guidance to ensure clinicians can appropriately identify, triage, and treat children who have been exposed to radiation, and for resources to ensure accurate communication about the safety and utility of radiation MCMs for children. (Disaster Med Public Health Preparedness. 2019;13:639-646)
Building on the recent advances in next-generation sequencing, the integration of genomics, proteomics, metabolomics, and other approaches hold tremendous promise for precision medicine. The approval and adoption of these rapidly advancing technologies and methods presents several regulatory science considerations that need to be addressed. To better understand and address these regulatory science issues, a Clinical and Translational Science Award Working Group convened the Regulatory Science to Advance Precision Medicine Forum. The Forum identified an initial set of regulatory science gaps. The final set of key findings and recommendations provided here address issues related to the lack of standardization of complex tests, preclinical issues, establishing clinical validity and utility, pharmacogenomics considerations, and knowledge gaps.
Herbicide resistance is ‘wicked’ in nature; therefore, results of the many educational efforts to encourage diversification of weed control practices in the United States have been mixed. It is clear that we do not sufficiently understand the totality of the grassroots obstacles, concerns, challenges, and specific solutions needed for varied crop production systems. Weed management issues and solutions vary with such variables as management styles, regions, cropping systems, and available or affordable technologies. Therefore, to help the weed science community better understand the needs and ideas of those directly dealing with herbicide resistance, seven half-day regional listening sessions were held across the United States between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide resistance management. The major goals of the sessions were to gain an understanding of stakeholders and their goals and concerns related to herbicide resistance management, to become familiar with regional differences, and to identify decision maker needs to address herbicide resistance. The messages shared by listening-session participants could be summarized by six themes: we need new herbicides; there is no need for more regulation; there is a need for more education, especially for others who were not present; diversity is hard; the agricultural economy makes it difficult to make changes; and we are aware of herbicide resistance but are managing it. The authors concluded that more work is needed to bring a community-wide, interdisciplinary approach to understanding the complexity of managing weeds within the context of the whole farm operation and for communicating the need to address herbicide resistance.
Seven half-day regional listening sessions were held between December 2016 and April 2017 with groups of diverse stakeholders on the issues and potential solutions for herbicide-resistance management. The objective of the listening sessions was to connect with stakeholders and hear their challenges and recommendations for addressing herbicide resistance. The coordinating team hired Strategic Conservation Solutions, LLC, to facilitate all the sessions. They and the coordinating team used in-person meetings, teleconferences, and email to communicate and coordinate the activities leading up to each regional listening session. The agenda was the same across all sessions and included small-group discussions followed by reporting to the full group for discussion. The planning process was the same across all the sessions, although the selection of venue, time of day, and stakeholder participants differed to accommodate the differences among regions. The listening-session format required a great deal of work and flexibility on the part of the coordinating team and regional coordinators. Overall, the participant evaluations from the sessions were positive, with participants expressing appreciation that they were asked for their thoughts on the subject of herbicide resistance. This paper details the methods and processes used to conduct these regional listening sessions and provides an assessment of the strengths and limitations of those processes.
A significant portion of ruminant production in the tropics relies on the grazing of native grasses growing in acid, low-fertility soils. Under these conditions, animal production is generally limited by the low quality and availability of forage supply. The introduction of forage legumes into grazing systems is commonly accepted as a way to alleviate this problem. However, many of the tropical forage legumes adapted to acid soils and selected on the basis of good agronomic performance have limited feeding value. This could be associated with increased production of secondary metabolites such as condensed tannins (CT), which have the ability to bind and precipitate proteins, carbohydrates and other molecules (Mueller-Harvey and McAllan, 1992). High intake of CT by ruminants has been associated with depressed intake and reduced digestibilities of protein and cell wall of temperate (Barry and Duncan, 1984; Pritchard et al, 1988) and tropical (Carulla, 1994) forage legumes. However, more recent work showed that intake and digestibility of tropical legumes was not only influenced by CT concentration but also by cell wall content (Barahona et al, 1997). In the ongoing process of identifying legume germplasm for acid soils, the use of in vitro techniques has been of great benefit. Gas production methods have considerable appeal in this respect due to their ability to evaluate digestion kinetics and their potential to simulate digestion processes in the rumen. Pendong et al. (1996) using temperate forages, showed that the pressure transducer gas technique of Theodorou et al. (1994) could be used to assess digestible organic matter disappearance as well as fermentation kinetics. A similar assessment was undertaken in the current study in which the tannin contents and cell-wall characteristics of tanniniferous legumes from Colombia were determined and related using measurements made in laboratories in Colombia and the United Kingdom.
In addition to assessing rate and extent of gas production from fermenting forages in vitro with rumen micro-organisms, gas production methods (e.g. Theodorou et at, 1994) may be used also to study the degradation kinetics of forage dry matter and its fractions. As the substrate dry matter can be lost only through fermentation or solution, this removes the error inherent in the polyester bag method caused by fine particle losses from bags being deemed part of the ‘soluble’ fraction.
The pressure transducer technique (PTT) of Theodorou et al. (1994) was used to measure gas production from nine tropical forage samples (Table 1). Nine bottles were prepared from each of the forage samples. Two bottles of each forage were harvested after 8, 24 and 48 h of incubation and a further three bottles at 72 h, to determine dry matter (DM) and organic matter (OM) losses. The same nine forages were assessed using the polyester bag method (Mehrez and Ørskov, 1977) to obtain DM and OM disappearance after rumen incubations of 4, 8, 24, 48 and 72 h. The soluble fraction was determined by hand washing. The reproducibility of measured losses, at given times, was examined using concordance (rc) correlation (Lin, 1989) and mean square prediction error (MSPE, Bibby and Toutenberg, 1977). Also the simple exponential model was used to estimate the fractional rate of DM degradation (kd) and asymptote A (%) for each forage and the values obtained using PTT (kd,ptt) and in situ (kd,bag) compared using rc and MSPE.
Sugar cane bagasse is produced in large quantities in Brazil. The cultivated area of sugar cane in recent years has been around 4.2 X 106 ha/year, with a production of about 270 X 106 t/year of cane. As each tonne of cane produces around 300 kg of bagasse by-product, a large quantity of bagasse is generated.
Bagasse is of low dry matter (DM) digestibility (about 250 g/kg), because of lignification. Efforts have been made to improve the digestibility of bagasse using treatment with chemicals (sodium hydroxide, ammonia) or steam (Abdalla et al., 1990). Although steam and pressure treatments have improved in situ degradability, intake and digestibility in cattle were disappointing (Mello et al, 1989). Recently treatment of bagasse with irradiation and ammonia have been investigated.
At maintenance at least, the whole tract digestibility of several foods in sheep and cattle is similar, consequently much of the information on the nutritive value of dairy cow foods in food composition tables is derived from studies conducted in sheep. However, Adesogan (1996) reported that in whole-crop wheat (WCW), starch digestibility is higher in sheep than in dairy cows. This study examined the validity of using sheep to model the ruminal degradation of WCW in cows by comparing the degradability of dry matter (DM) and nitrogen (N) of urea-treated WCW in both species.
Winter wheat (cv. Hussar) was harvested at 540 g DM per kg and conserved following urea application at target rates of 20 or 40g/kg DM (WCW2 and WCW4 respectively). The degradability of the forages was examined in dairy cows given 6 kg dairy concentrate and grass silage ad libitum and in wethers given 2.4 kg/day of grass silage supplemented with 0.36kg/day of rolled, mineralized barley.
The longstanding association between the major histocompatibility complex (MHC) locus and schizophrenia (SZ) risk has recently been accounted for, partially, by structural variation at the complement component 4 (C4) gene. This structural variation generates varying levels of C4 RNA expression, and genetic information from the MHC region can now be used to predict C4 RNA expression in the brain. Increased predicted C4A RNA expression is associated with the risk of SZ, and C4 is reported to influence synaptic pruning in animal models.
Based on our previous studies associating MHC SZ risk variants with poorer memory performance, we tested whether increased predicted C4A RNA expression was associated with reduced memory function in a large (n = 1238) dataset of psychosis cases and healthy participants, and with altered task-dependent cortical activation in a subset of these samples.
We observed that increased predicted C4A RNA expression predicted poorer performance on measures of memory recall (p = 0.016, corrected). Furthermore, in healthy participants, we found that increased predicted C4A RNA expression was associated with a pattern of reduced cortical activity in middle temporal cortex during a measure of visual processing (p < 0.05, corrected).
These data suggest that the effects of C4 on cognition were observable at both a cortical and behavioural level, and may represent one mechanism by which illness risk is mediated. As such, deficits in learning and memory may represent a therapeutic target for new molecular developments aimed at altering C4’s developmental role.
22q11.2 deletion syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however, the links between developmental coordination disorder (DCD), intellectual function and psychiatric disorder remain unexplored.
To establish the prevalence of indicative DCD in children with 22q11.2DS and examine associations with IQ, neurocognition and psychopathology.
Neurocognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age 11.2, s.d. = 2.2) and 32 control siblings (mean age 11.5, s.d. = 2.1) were carried out in their homes. Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic.
Indicative DCD was found in 57 (81.4%) children with 22q11.2DS compared with 2 (6.3%) control siblings (odds ratio (OR) = 36.7, P < 0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (P < 0.001), attention-deficit hyperactivity disorder (ADHD) (P < 0.001) and autism-spectrum disorder (ASD) symptoms (P < 0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD (20 of 20), as did 90% of children with anxiety disorder (17 of 19) and 96% of children who screened positive for ASD (22 of 23). The Developmental Coordination Disorder Questionnaire score was related to sustained attention (P = 0.006), even after history of epileptic fits (P = 0.006) and heart problems (P = 0.009) was taken into account.
Clinicians should be aware of the high risk of coordination difficulties in children with 22q11.2DS and its association with risk of mental disorder and specific neurocognitive deficits.
Cauterisation techniques are commonly used and widely accepted for the management of epistaxis. This review assesses which methods of intranasal cautery should be endorsed as optimum treatment on the basis of benefits, risks, patient tolerance and economic assessment.
A systematic review of the literature was performed using a standardised methodology and search strategy.
Eight studies were identified: seven prospective controlled trials and one randomised controlled trial. Pooling of data was possible from 3 studies, yielding a total of 830 patients. Significantly lower re-bleed rates were identified (p < 0.01) using electrocautery (14.5 per cent) when compared to chemical cautery (35.1 per cent). No evidence suggested that electrocautery was associated with more adverse events or discomfort. Limited evidence supported the use of a vasoconstrictor agent and operating microscope during the procedure. The included studies had considerable heterogeneity in terms of design and outcome measures.
Consistent evidence suggests that electrocautery has higher success rates than chemical cautery, and is not associated with increased complications or patient discomfort. Lower quality evidence suggests that electrocautery reduces costs and duration of hospital stay.
Ruminant feeding standards in Brazil are generally based on systems developed for temperate regions and there is a serious lack of information on grazed tropical pasture which is the main feedstuff. Signal grass (Brachiaria decumbens) represents half of the total cultivated pastures in Brazil (Miles et al., 1996). This study investigated the intake and digestibility by sheep of signal grass hay cut after re-growths of 28 and 56 days to represent the range used in practice in the Brazilian savanna. Lucerne hay was included as a positive control. The hays were offered at two levels of intake to Santa Ines wether sheep.
In the Central Kenyan Highlands, dairy cattle ownership is a crucial element in poverty alleviation. For example, in Kiambu district just north of Nairobi, out of the population of 744010, 48% of 189709 households stall feed dairy cattle. Farm sizes average 1.1 to 2.0 ha per household. Producing sufficient forage for dairy cattle is difficult and low dry matter intake constrains dairy production and there is a positive correlation between stover intake and milk yield.. Napier grass comprised 40% of the total dry matter fed to cattle and maize forage 24% according to the project’s Rapid Rural Appraisal, maize thinnings and stover being routinely fed to livestock. In another survey, dry maize stover accounted for nearly 65% of dry matter intake of dairy cattle during October.
Speech disfluencies can guide the ways in which listeners interpret spoken language. Here, we examined whether three-year-olds, five-year-olds, and adults use filled pauses to anticipate that a speaker is likely to refer to a novel object. Across three experiments, participants were presented with pairs of novel and familiar objects and heard a speaker refer to one of the objects using a fluent (“Look at the ball/lep!”) or disfluent (“Look at thee uh ball/lep!”) expression. The salience of the speaker's unfamiliarity with the novel referents, and the way in which the speaker referred to the novel referents (i.e., a noun vs. a description) varied across experiments. Three- and five-year-olds successfully identified familiar and novel targets, but only adults’ looking patterns reflected increased looks to novel objects in the presence of a disfluency. Together, these findings demonstrate that adults, but not young children, use filled pauses to anticipate reference to novel objects.