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N-Methyl-D-Aspartate Receptor (NMDAR) hypofunction is hypothesised to underlie psychosis but this has not been tested early in illness.
Our aim was to determine if NMDAR availability was lower in patients with first episode psychosis compared to healthy controls.
To address this, we studied 40 volunteers (21 patients with first episode psychosis and 19 matched healthy controls) using PET imaging with an NMDAR selective ligand, [18F]GE179, that binds to the ketamine binding site to index its distribution volume ratio (DVR) and volume of distribution (VT). Striatal glutamatergic indices (glutamate and Glx) were measured simultaneously using magnetic resonance spectroscopy imaging (1H-MRS).
Hippocampal DVR, but not VT, was significantly lower in patients relative to controls (p=0.02, Cohen’s d=0.81; p=0.15, Cohen’s d=0.49), and negatively associated with total (rho=-0.47, p= 0.04), depressive (rho=-0.67, p=0.002), and general symptom severity (rho=-0.74, p<0.001). Exploratory analyses found no significant differences in other brain regions (anterior cingulate cortex, thalamus, striatum and temporal cortex). We found an inverse relationship between hippocampal NMDAR availability and striatal glutamate levels in people with first-episode psychosis (rho = -0.74, p <0.001) but not in healthy controls (rho = -0.22, p = 0.44).
These findings are consistent with the NMDAR hypofunction hypothesis and identify the hippocampus as a key locus for relative NMDAR hypofunction, although further studies should test specificity and causality.
Area-level residential instability (ARI), an index of social fragmentation, has been shown to explain the association between urbanicity and psychosis. Urban upbringing has been shown to be associated with decreased gray matter volumes (GMV)s of brain regions corresponding to the right caudal middle frontal gyrus (CMFG) and rostral anterior cingulate cortex (rACC).
We hypothesize that greater ARI will be associated with reduced right posterior CMFG and rACC GMVs.
Data were collected at baseline as part of the North American Prodrome Longitudinal Study. Counties where participants resided during childhood were geographically coded using the US Censuses to area-level factors. ARI was defined as the percentage of residents living in a different house five years ago. Generalized linear mixed models tested associations between ARI and GMVs.
This study included 29 HC and 64 CHR-P individuals who were aged 12 to 24 years, had remained in their baseline residential area, and had magnetic resonance imaging scans. ARI was associated with reduced right CMFG (adjusted β = -0.258; 95% CI = -0.502 – -0.015) and right rACC volumes (adjusted β = -0.318; 95% CI = -0.612 – -0.023). The interaction terms (ARI X diagnostic group) in the prediction of both brain regions were not significant, indicating that the relationships between ARI and regional brain volumes held for both CHR-P and HCs.
Like urban upbringing, ARI may be an important social environmental characteristic that adversely impacts brain regions related to schizophrenia.
Early adolescents (ages 10–14) living in low- and middle-income countries have heightened vulnerability to psychosocial risks, but available evidence from these settings is limited. This study used data from the Global Early Adolescent Study to characterize prototypical patterns of emotional and behavioral problems among 10,437 early adolescents (51% female) living in the Democratic Republic of Congo (DRC), Malawi, Indonesia, and China, and explore the extent to which these patterns varied by country and sex. LCA was used to identify and classify patterns of emotional and behavioral problems separately by country. Within each country, measurement invariance by sex was evaluated. LCA supported a four-class solution in DRC, Malawi, and Indonesia, and a three-class solution in China. Across countries, early adolescents fell into the following subgroups: Well-Adjusted (40–62%), Emotional Problems (14–29%), Behavioral Problems (15–22%; not present in China), and Maladjusted (4–15%). Despite the consistency of these patterns, there were notable contextual differences. Further, tests of measurement invariance indicated that the prevalence and nature of these classes differed by sex. Findings can be used to support the tailoring of interventions targeting psychosocial adjustment, and suggest that such programs may have utility across diverse cross-national settings.
We present a numerical study of the dynamics of an elastic fibre in a shear flow at low Reynolds number, and seek to understand several aspects of the fibre's motion using the equations for slender-body theory coupled to the elastica. The numerical simulations are performed in the bead-spring framework including hydrodynamic interactions in two theoretical schemes: the generalized Rotne–Prager–Yamakawa model and a multipole expansion corrected for lubrication forces. In general, the two schemes yield similar results, including for the dominant scaling features of the shape that we identify. In particular, we focus on the evolution of an initially straight fibre oriented in the flow direction and show that the time scales of fibre bending, curling and rotation, which depend on its length and stiffness, determine the overall motion and evolution of the shapes. We document several characteristic time scales and curvatures representative of the shape that vary as power laws of the bending stiffness and fibre length. The numerical results are further supported by an interpretation using an elastica model.
Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.
The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.
We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.
We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.
Acute change in mental status (ACMS), defined by the Confusion Assessment Method, is used to identify infections in nursing home residents. A medical record review revealed that none of 15,276 residents had an ACMS documented. Using the revised McGeer criteria with a possible ACMS definition, we identified 296 residents and 21 additional infections. The use of a possible ACMS definition should be considered for retrospective nursing home infection surveillance.
Basic Self disturbances (BSD), including changes of the 'pre-reflexive' sense of self and the loss first-person perspective, are characteristic of the schizophrenic spectrum disorders and highly prevalent in subjects at 'ultra high risk' for psychosis (UHR). The current literature indicates that cortical midline structures (CMS) may be implicated in the neurobiological substrates of the 'basic self' in healthy controls.
Neuroanatomical investigation of BSD in a UHR sample
To test the hypotheses :(i) UHR subjects have higher 'Examination of Anomalous Self Experience, EASE' scores as compared to controls, (ii) UHR subjects have neuroanatomical alterations as compared to controls in CMS, (iii) within UHR subjects, EASE scores are directly related to structural CMS alterations.
32 HR subjects (27 antipsychotics-naïve) and 17 healthy controls (HC) were assessed with the 57-items semi-structured EASE interview. Voxel-Based Morphometry (VBM) was conducted in the same subjects, with a-priori Region of Interests (ROIs) defined in the CMS (anterior/posterior cingulate and medial-prefrontal cortex).
Despite high variability in the HR group, the overall EASE score was higher (t-test >0.01, Cohen's d =2.91) in HR (mean=30.15, SD=16.46) as compared to HC group (mean=1.79, SD=2.83). UHR subjects had gray matter reduction in CMS as compared to HC (p>0.05 FWE-corrected). Across the whole sample, lower gray matter volume in the anterior cingulate was correlated with higher EASE scores (p>0.05).
This study provides preliminary evidence that gray matter reductions in the CMS are correlated with BSD in UHR people.
Evidence suggests that early trauma may have a negative effect on cognitive functioning in individuals with psychosis, yet the relationship between childhood trauma and cognition among those at clinical high risk (CHR) for psychosis remains unexplored. Our sample consisted of 626 CHR children and 279 healthy controls who were recruited as part of the North American Prodrome Longitudinal Study 2. Childhood trauma up to the age of 16 (psychological, physical, and sexual abuse, emotional neglect, and bullying) was assessed by using the Childhood Trauma and Abuse Scale. Multiple domains of cognition were measured at baseline and at the time of psychosis conversion, using standardized assessments. In the CHR group, there was a trend for better performance in individuals who reported a history of multiple types of childhood trauma compared with those with no/one type of trauma (Cohen d = 0.16). A history of multiple trauma types was not associated with greater cognitive change in CHR converters over time. Our findings tentatively suggest there may be different mechanisms that lead to CHR states. Individuals who are at clinical high risk who have experienced multiple types of childhood trauma may have more typically developing premorbid cognitive functioning than those who reported minimal trauma do. Further research is needed to unravel the complexity of factors underlying the development of at-risk states.
Externalizing disorders are known to be partly heritable, but the biological pathways linking genetic risk to the manifestation of these costly behaviors remain under investigation. This study sought to identify neural phenotypes associated with genomic vulnerability for externalizing disorders.
One-hundred fifty-five White, non-Hispanic veterans were genotyped using a genome-wide array and underwent resting-state functional magnetic resonance imaging. Genetic susceptibility was assessed using an independently developed polygenic score (PS) for externalizing, and functional neural networks were identified using graph theory based network analysis. Tasks of inhibitory control and psychiatric diagnosis (alcohol/substance use disorders) were used to measure externalizing phenotypes.
A polygenic externalizing disorder score (PS) predicted connectivity in a brain circuit (10 nodes, nine links) centered on left amygdala that included several cortical [bilateral inferior frontal gyrus (IFG) pars triangularis, left rostral anterior cingulate cortex (rACC)] and subcortical (bilateral amygdala, hippocampus, and striatum) regions. Directional analyses revealed that bilateral amygdala influenced left prefrontal cortex (IFG) in participants scoring higher on the externalizing PS, whereas the opposite direction of influence was observed for those scoring lower on the PS. Polygenic variation was also associated with higher Participation Coefficient for bilateral amygdala and left rACC, suggesting that genes related to externalizing modulated the extent to which these nodes functioned as communication hubs.
Findings suggest that externalizing polygenic risk is associated with disrupted connectivity in a neural network implicated in emotion regulation, impulse control, and reinforcement learning. Results provide evidence that this network represents a genetically associated neurobiological vulnerability for externalizing disorders.
Five vermiculite samples collected from Béni Bousera, Morocco and four from Palabora, South Africa were investigated by X-ray diffraction, chemical analysis, 57Fe Mössbauer spectroscopy, and 27Al magic angle spinning nuclear magnetic resonance. The X-ray diffraction studies indicate that all vermiculites have very similar crystallographic parameters. The chemical analyses and the NMR spectra indicate that the Béni Bousera vermiculites contain Al3+ cations in both octahedral and tetrahedral sheets and the Palabora vermiculites contain Al3+ in the tetrahedral sheet. The Mössbauer spectra indicate that the Béni Bousera vermiculites contain more Fe2+ cations than the Palabora vermiculites and do not contain tetrahedral Fe3+ cations. The different cation compositions and distribution in the two sets of vermiculites may result from different parent minerals, i.e. chlorite in the case of Béni Bousera and phlogopite in the case of Palabora, and different genetic processes, i.e. weathering in Béni Bousera and hydrothermal alteration in Palabora.
Trioctahedral micas in the Karlovy Vary pluton range in composition from Fe-biotites in the granites of the Older Intrusive Complex (OIC) through siderophyllite and lithian siderophyllite to zinnwaldite in the granites of the Younger Intrusive Complex (YIC). Li + AlVI + Si would appear to substitute for Fe2+ + AlIV in biotite with a formula similar to that given in Henderson et al. (1989), but Li + Si appears to substitute for Fe2+ + AlIV in the Li-micas. In mica vs. host rock plots, Rb and F show positive linear covariation except for the Li-mica granites, but femic constituents and tFeO/(tFeO + MgO) have separate trends for OIC and YIC granites and micas. Further differences between OIC and YIC granite micas are seen in their Ti and Mg contents and in plots like V vs. SiO2, AlIVvs. Fe/(Fe+Mg) and Li vs. total iron as Fe2+ and in the results of discriminant analysis. These reveal a geochemical hiatus between OIC and YIC granite micas that coincides with a major temporal hiatus.
Biotite compositions in the YIC granites are similar to those in the granites of the Cornubian batholith and reveal a similar magmatic evolution and genesis in which later biotites evolve to lithian siderophyllites with some enrichment in trace alkalis and F. It is suggested that the biotite granites in the YIC were derived from the products of partial fusion of the OIC granites. A less well-marked geochemical hiatus exists between YIC biotites and zinnwaldites. In some plots (e.g. Si vs. Li, Li vs. tFe) apparent continuity between biotite and the Li-micas suggests continuous evolution, but in others (e.g. Rb vs. TiO2, Rb(biotite) vs. Rb(rock)), Li-mica data points stand apart from the biotites suggesting, like the whole rock data, a separate evolution. Comparison with the more abundant data for Li-micas of the Cornubian batholith suggests derivation of the Li-mica granites by partial fusion of the OIC/YIC granite residues.
To test the hypothesis that long-term care facility (LTCF) residents with Clostridium difficile infection (CDI) or asymptomatic carriage of toxigenic strains are an important source of transmission in the LTCF and in the hospital during acute-care admissions.
A 6-month cohort study with identification of transmission events was conducted based on tracking of patient movement combined with restriction endonuclease analysis (REA) and whole-genome sequencing (WGS).
Veterans Affairs hospital and affiliated LTCF.
The study included 29 LTCF residents identified as asymptomatic carriers of toxigenic C. difficile based on every other week perirectal screening and 37 healthcare facility-associated CDI cases (ie, diagnosis >3 days after admission or within 4 weeks of discharge to the community), including 26 hospital-associated and 11 LTCF-associated cases.
Of the 37 CDI cases, 7 (18·9%) were linked to LTCF residents with LTCF-associated CDI or asymptomatic carriage, including 3 of 26 hospital-associated CDI cases (11·5%) and 4 of 11 LTCF-associated cases (36·4%). Of the 7 transmissions linked to LTCF residents, 5 (71·4%) were linked to asymptomatic carriers versus 2 (28·6%) to CDI cases, and all involved transmission of epidemic BI/NAP1/027 strains. No incident hospital-associated CDI cases were linked to other hospital-associated CDI cases.
Our findings suggest that LTCF residents with asymptomatic carriage of C. difficile or CDI contribute to transmission both in the LTCF and in the affiliated hospital during acute-care admissions. Greater emphasis on infection control measures and antimicrobial stewardship in LTCFs is needed, and these efforts should focus on LTCF residents during hospital admissions.
Research on the cities of the Classical Greek world has traditionally focused on mapping the organisation of urban space and studying major civic or religious buildings. More recently, newer techniques such as field survey and geophysical survey have facilitated exploration of the extent and character of larger areas within urban settlements, raising questions about economic processes. At the same time, detailed analysis of residential buildings has also supported a change of emphasis towards understanding some of the functional and social aspects of the built environment as well as purely formal ones. This article argues for the advantages of analysing Greek cities using a multidisciplinary, multi-scalar framework which encompasses all of these various approaches and adds to them other analytical techniques (particularly micro-archaeology). We suggest that this strategy can lead towards a more holistic view of a city, not only as a physical place, but also as a dynamic community, revealing its origins, development and patterns of social and economic activity. Our argument is made with reference to the research design, methodology and results of the first three seasons of fieldwork at the city of Olynthos, carried out by the Olynthos Project.
Greenhouse experiments in central Texas assessed the relative importance of above- and belowground interactions of semidwarf Mit wheat and Marshall ryegrass during vegetative growth. One experiment used partitions to compare the effect of no (controls), aboveground only, belowground only, and full interaction for 75 d after planting (DAP) one wheat and nine ryegrass plants in soil volumes of 90, 950, and 3,800 ml. The results with the different soil volumes were similar. Wheat growth in the aboveground interaction only did not differ from controls. However, the full or belowground only interaction of wheat with ryegrass reduced wheat height, leaf number, tillering, leaf area, percent total nonstructural carbohydrates in shoot, and dry weights of leaves, stems, and roots 45 and 75 DAP compared to controls. Wheat in full and belowground interaction only did not differ from one another in growth. A replacement series experiment of 56 d also showed that the competitive advantage of ryegrass was relatively greater in root than in shoot growth. No allelopathic response of wheat to ryegrass occurred. While the tallness of the semidwarf wheat minimized aboveground interference by ryegrass, the root growth of the thinner and more fibrous roots of ryegrass greatly enhanced its belowground competitiveness.
A greenhouse experiment compared the vegetative growth in pure cultures and mixtures of winter Triticum aestivum cultivar ‘Mit’ and Lolium multiflorum cultivar ‘Marshall’ in continuously watered controls and drought treatments. Control L. multiflorum in pure culture 14 wk after planting produced more leaf area, tillers, and dry weights of stem and root than control T. aestivum in pure culture. The greater seed size, larger initial leaf area, and height allowed T. aestivum to produce greater final leaf area and dry stem weight in control mixtures than L. multiflorum. Watering following drought shifted the relative performance of the two species in pure cultures and mixtures compared to controls. The ability of T. aestivum to maintain a greater leaf expansion rate during drought and a greater leaf area afterward than L, multiflorum allowed T. aestivum to attain greater growth than L. multiflorum in pure cultures exposed to temporary drought followed by watering. Conversely, drought and its relief enhanced the relative competitiveness of L. multiflorum compared to controls in mixtures with T. aestivum. During 4 wk of watering following the drought, L. multiflorum in mixtures grew vigorously and was similar to T. aestivum in all measures except in height and dry stem weight. Thus, L. multiflorum was similar in root growth with T. aestivum in control and drought mixtures and had its aboveground competitiveness amplified by the cycle of drought and watering in this study. There was no evidence of an allelopathic interaction between the two species.
Winter wheat is the predominant crop in Oklahoma, but winter annual grasses are becoming increasingly difficult to control. Summer crop rotations have not been generally adopted; it was decided, therefore, to use winter canola in a crop rotation. However, very little is known about how well herbicides used in canola production will control the winter annual grasses found in Oklahoma wheat fields. Thus, an experiment was conducted at three sites, and repeated the following year, to determine the efficacy of trifluralin, quizalofop, clethodim, and glyphosate in canola production. The weeds evaluated in the experiment were Italian ryegrass, feral cereal rye, and volunteer wheat, along with two varieties of canola: a glyphosate-resistant variety and a conventional variety. All herbicides effectively controlled volunteer wheat. Feral cereal rye and Italian ryegrass varied in response to the herbicide treatments. Trifluralin followed by (fb) quizalofop and glyphosate fb glyphosate were effective on all target species across locations. Effective control of grass weeds was obtained in both conventional and glyphosate-resistant winter canola. Most herbicide treatments improved canola yield over the nontreated check. This experiment demonstrates that Oklahoma wheat producers can effectively rotate to canola to use other herbicides for control of problematic grassy weeds.
A greenhouse experiment used a replacement series design to compare the vegetative growth 6 wk after emergence in pure cultures and mixtures of winter wheat and Italian ryegrass, with phosphorus (P) levels recommended by soil testing. The planting proportions of wheat and Italian ryegrass were 100 and 0%, 75 and 25%, 50 and 50%, 25 and 75%, and 0 and 100%, respectively. There was no alleopathic interaction between the species. Both species in all pure and mixed cultures had substantially less growth in the low-P than in the recommended P treatment. However, the relative performance of the two species differed between P treatments. In the recommended P treatment in pure culture, Italian ryegrass had more tillers and greater root weight and length than wheat. Pure culture wheat in the low-P treatment exceeded pure culture Italian ryegrass in leaf area, weights of leaves, stems, and roots, and root length. Thus, the growth of wheat was inhibited less by P deficiency than the growth of Italian ryegrass in pure culture. In the 50:50 mixture of the recommended P treatment, wheat had greater leaf, stem, and root weights than Italian ryegrass. In the 50:50 mixture of the low-P treatment, the two species were very similar in growth, except that Italian ryegrass had about three times more tillers than did wheat. Whereas P deficiency limited the growth of wheat less than Italian ryegrass in pure culture, P deficiency did not affect the relative competitiveness of Italian ryegrass as much as wheat in mixed cultures. The ability of Italian ryegrass to compete with wheat when P was limiting may result from a difference in root growth. Italian ryegrass had a greater fresh root length to fresh root weight ratio than did wheat in the low-P treatment in pure culture and in the 50:50 mixture. The greater surface area of Italian ryegrass roots likely enhanced the competitiveness of Italian ryegrass relative to wheat under P-deficit conditions. Thus, the use of the recommended P nutrition from soil testing may be a key component to diminish Italian ryegrass competition in wheat fields.
Sodium nitroprusside (SNP) has been reported to rapidly reduce psychotic symptoms in patients with schizophrenia. This has the potential to revolutionize treatment for schizophrenia. In this study, we tested the hypothesis that SNP leads to a reduction in psychotic symptoms and an improvement in spatial working memory (SWM) performance in patients with schizophrenia.
This was a single-centre, randomized, double-blind, placebo-controlled trial performed from 27 August 2014 to 10 February 2016 (clinicaltrials.gov identifier: NCT02176044). Twenty patients with schizophrenia aged 18–60 years with a diagnosis of schizophrenia or schizoaffective disorder were recruited from psychiatric outpatient clinics in the South London and Maudsley NHS Trust, London, UK. Baseline symptoms were measured using the Positive and Negative Syndrome Scale (PANSS) and the 18-item Brief Psychiatric Rating Scale (BPRS-18), and SWM was assessed using the CANTAB computerized test. Participants received either an infusion of SNP (0.5 μg/kg per min for 4 h) or placebo and were re-assessed for symptoms and SWM performance immediately after the infusion, and 4 weeks later.
SNP did not lead to any reduction in psychotic symptoms or improvement in SWM performance compared to placebo.
Although this study was negative, it is possible that the beneficial effects of SNP may occur in patients with a shorter history of illness, or with more acute exacerbation of symptoms.
We have recently used the atmospheric air-shower Cerenkov technique in an attempt to observe pulsed gamma radiation from two southern pulsars, PSR 0833—45 and MP 0959. Northern hemisphere observers do not agree whether the pulsars CP 0950, CP 1133 and CP 1919 are sources of gamma emission, either pulsed or uniform in time.