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White matter development during adolescents is crucial for a mature integration of neural networks in the brain. Autism spectrum condition (ASC), characterized by social and communication difficulties and rigid behaviour may interact with white matter development observed during adolescence. Changes in white matter development may link autistic symptoms to its genetic underpinnings and explain a 10-fold increase in susceptibility to ASC among siblings of individuals with ASC.
We used diffusion tensor imaging to study an association between age and white matter integrity measures, fractional anisotropy (FA) and mean diffusivity (MD), in adolescents with ASC, their siblings and age-matched healthy controls. Diffusion-weighted data were acquired with 64-direction protocol with 3mm slices and TR of 6600ms and tract-based spatial statistics analysis was performed.
The control subjects showed robust signs of increase in white matter integrity correlated with age. In contrast, individuals with ASC showed significantly lower negative correlation between MD and age in a broad area centred in the right superior longitudinal fasciculus (rSLF). When the three eigenvalues constituting a tensor ellipsoid were considered separately, siblings of individuals with ASC showed a diminished negative correlation between the second eigenvalue and age also centred in the rSLF.
Adolescents with ASC and their siblings experience alterations in white matter development in comparison to age-matched healthy controls, which are similar in direction yet different in scale for the two affected groups. The alterations are observed in the area associated with flexibility of behaviour and may explain both symptoms of ASC and increased susceptibility to ASC.
Effective preventive strategies could reduce disability and the long term social and health complications associated with depression, but options are limited. Cognitive bias modification (CBM) is a novel, simple, and safe intervention that corrects the attentional and interpretive biases associated with depression.
To determine if CBM decreases the one-year onset of major depression in adults at risk.
This randomised controlled trial will recruit adults with subsyndromal depression living in Australia (parallel design, 1:1 allocation ratio). The intervention will be delivered via the internet over 52 weeks. The primary outcome of interest is the onset of a major depression according to DSM-IV-TR criteria. Secondary outcomes of interest include change in the severity of depressive (Patient Health Questionnaire, PHQ-9) and changes in attention and interpretive biases. Outcomes will be collected 3, 6, 9 and 12 months after randomisation.
Preliminary data on a subsample of 20 participants showed that the mean±SE PHQ-9 score of controls was 7.5±0.9 at study entry and 7.1±1.5 at week 6 (paired t-test=0.29, p=0.779), whereas the mean±SE score of active CBM participants was 7.4±1.0 and 4.4±1.1, respectively (paired t=6.00, p<0.001). The mean PHQ-9 difference between control and active CBM participants over 6 weeks was 2.6±1.5 points (t=1.79, p=0.090). One of 11 controls (9.1%) and 0/9 active CBM participants showed evidence of clinically significant depressive symptoms at week 6 (i.e., PHQ-9≥15).
By March 2015, 6-months preliminary data will be available on 165 participants.
At archaeological sites located on islands or near the coast, the potential exists for lipid extracts of potsherds to contain fatty acids (FA) from both aquatic and terrestrial organisms, meaning that consideration must be given to marine reservoir effects (MRE) in radiocarbon (14C) analyses. Here we studied the site of Bornais (Outer Hebrides, UK) where a local MRE, ΔR of –65 ± 45 yr was determined through the paired 14C determinations of terrestrial and marine faunal bones. Lipid analysis of 49 potsherds, revealed aquatic biomarkers in 45% of the vessels, and δ13C values of C16:0 and C18:0 FAs revealed ruminant and marine product mixing for 71% of the vessels. Compound-specific 14C analysis (CSRA) of FAs yielded intermediate 14C ages between those of terrestrial and marine bones from the same contexts, confirming an MRE existed. A database containing δ13C values for FAs from reference terrestrial and marine organisms provided endmembers for calculating the percentage marine-derived C (%marine) in FAs. We show that lipid 14C dates can be corrected using determined %marine and ΔR values, such that pottery vessels from coastal locations can be 14C dated by CSRA of FAs.
Schizophrenia is associated with robust hippocampal volume deficits but subregion volume deficits, their associations with cognition, and contributing genes remain to be determined.
Hippocampal formation (HF) subregion volumes were obtained using FreeSurfer 6.0 from individuals with schizophrenia (n = 176, mean age ± s.d. = 39.0 ± 11.5, 132 males) and healthy volunteers (n = 173, mean age ± s.d. = 37.6 ± 11.3, 123 males) with similar mean age, gender, handedness, and race distributions. Relationships between the HF subregion volume with the largest between group difference, neuropsychological performance, and single-nucleotide polymorphisms were assessed.
This study found a significant group by region interaction on hippocampal subregion volumes. Compared to healthy volunteers, individuals with schizophrenia had significantly smaller dentate gyrus (DG) (Cohen's d = −0.57), Cornu Ammonis (CA) 4, molecular layer of the hippocampus, hippocampal tail, and CA 1 volumes, when statistically controlling for intracranial volume; DG (d = −0.43) and CA 4 volumes remained significantly smaller when statistically controlling for mean hippocampal volume. DG volume showed the largest between group difference and significant positive associations with visual memory and speed of processing in the overall sample. Genome-wide association analysis with DG volume as the quantitative phenotype identified rs56055643 (β = 10.8, p < 5 × 10−8, 95% CI 7.0–14.5) on chromosome 3 in high linkage disequilibrium with MOBP. Gene-based analyses identified associations between SLC25A38 and RPSA and DG volume.
This study suggests that DG dysfunction is fundamentally involved in schizophrenia pathophysiology, that it may contribute to cognitive abnormalities in schizophrenia, and that underlying biological mechanisms may involve contributions from MOBP, SLC25A38, and RPSA.
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.
Current understanding of climate change impacts, adaptation and vulnerability among Inuit in the Arctic is relatively static, rooted in the community and time that case studies were conducted. This paper captures the dynamism of Inuit–climate relationships by applying a longitudinal approach to assessing vulnerability to climate change among Inuit in Ulukhaktok, Northwest Territories, Canada. Data were collected in 2005 and 2016 following a consistent methodology and analytical framework. Findings from the studies are analysed comparatively together with longitudinal datasets. The data reveal that many of the climatic changes recorded in 2005 that adversely affected hunting activities have been observed to be persisting or progressing, such as decreasing sea ice thickness and extent, and stronger and more consistent summer winds. Inuit are responding by altering travel routes and equipment, taking greater pre-trip precautions, and concentrating their efforts on more efficient and accessible hunts. Increasing living and subsistence costs and time-constraints, changes in the generation and transmission of environmental knowledge and land skills, and the concentration of country food sharing networks were identified as key constraints to adaptation. The findings indicate that the connections between subsistence activities and the wage economy are central to understanding how Inuit experience and respond to climate change.
We aimed to explore multiple perspectives regarding barriers to and facilitators of advance care planning (ACP) among African Americans to identify similarities or differences that might have clinical implications.
Qualitative study with health disparities experts (n = 5), community members (n = 9), and seriously ill African American patients and caregivers (n = 11). Using template analysis, interviews were coded to identify intrapersonal, interpersonal, and systems-level themes in accordance with a social ecological framework.
Participants identified seven primary factors that influence ACP for African Americans: religion and spirituality; trust and mistrust; family relationships and experiences; patient-clinician relationships; prognostic communication, care preferences, and preparation and control. These influences echo those described in the existing literature; however, our data highlight consistent differences by group in the degree to which these factors positively or negatively affect ACP. Expert participants reinforced common themes from the literature, for example, that African Americans were not interested in prognostic information because of mistrust and religion. Seriously ill patients were more likely to express trust in their clinicians and to desire prognostic communication; they and community members expressed a desire to prepare for and control the end of life. Religious belief did not appear to negate these desires.
Significance of results
The literature on ACP in African Americans may not accurately reflect the experience of seriously ill African Americans. What are commonly understood as barriers to ACP may in fact not be. We propose reframing stereotypical barriers to ACP, such as religion and spirituality, or family, as cultural assets that should be engaged to enhance ACP. Although further research can inform best practices for engaging African American patients in ACP, findings suggest that respectful, rapport-building communication may facilitate ACP. Clinicians are encouraged to engage in early ACP using respectful and rapport building communication practices, including open-ended questions.
Schizophrenia (SZ) is a severe neuropsychiatric disorder associated with disrupted connectivity within the thalamic-cortico-cerebellar network. Resting-state functional connectivity studies have reported thalamic hypoconnectivity with the cerebellum and prefrontal cortex as well as thalamic hyperconnectivity with sensory cortical regions in SZ patients compared with healthy comparison participants (HCs). However, fundamental questions remain regarding the clinical significance of these connectivity abnormalities.
Resting state seed-based functional connectivity was used to investigate thalamus to whole brain connectivity using multi-site data including 183 SZ patients and 178 matched HCs. Statistical significance was based on a voxel-level FWE-corrected height threshold of p < 0.001. The relationships between positive and negative symptoms of SZ and regions of the brain demonstrating group differences in thalamic connectivity were examined.
HC and SZ participants both demonstrated widespread positive connectivity between the thalamus and cortical regions. Compared with HCs, SZ patients had reduced thalamic connectivity with bilateral cerebellum and anterior cingulate cortex. In contrast, SZ patients had greater thalamic connectivity with multiple sensory-motor regions, including bilateral pre- and post-central gyrus, middle/inferior occipital gyrus, and middle/superior temporal gyrus. Thalamus to middle temporal gyrus connectivity was positively correlated with hallucinations and delusions, while thalamus to cerebellar connectivity was negatively correlated with delusions and bizarre behavior.
Thalamic hyperconnectivity with sensory regions and hypoconnectivity with cerebellar regions in combination with their relationship to clinical features of SZ suggest that thalamic dysconnectivity may be a core neurobiological feature of SZ that underpins positive symptoms.
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.
While a direct relation between hospital construction and concomitant infection rates has been clearly established, few data are available regarding the environmental decontamination effects of renovation in which surfaces are replaced and regarding subsequent infection incidence.
Retrospective clinical study with vancomycin-resistant Enterococcus (VRE) molecular strain typing and environmental cultures.
A regional referral center for acute leukemia and hematopoietic stem-cell transplantation.
Overall, 536 consecutive hospital admissions for newly diagnosed acute leukemia or a first autologous or allogeneic stem-cell transplantation were reviewed.
During 2009–2010, our unit underwent complete remodeling including replacement of all surfaces. We assessed the effects of this construction on the incidence of hospital-acquired VRE colonization before, during, and after the renovation.
We observed a sharp decrease in VRE colonization rates (hazard ratio, <0.23; 95% confidence interval, 0.18–0.44; P<.0001) during the first year after the renovation, with a return to near baseline rates thereafter. The known risk factors for VRE colonization appeared to be stable over the study interval. Environmental cultures outside of patient rooms revealed several contaminated areas that are commonly touched by unit personnel. Multilocus sequence typing of VRE isolates that were cryopreserved over the study interval showed that dominant strains prior to construction disappeared and were replaced by other strains after the renovation.
Unit reconstruction interrupted endemic transmission of VRE, which resumed with novel strains upon reopening. Contamination of environmental surfaces and shared equipment may play an important role in endemic transmission of VRE.
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.
The identification of the factors that influence the persistence of psychiatric disorder may assist practitioners to focus on young people who are particularly prone to poor outcomes, but population-based samples of sufficient size are rare.
This secondary analysis combined data from two large, population-based cross-sectional surveys in Great Britain (1999 and 2004) and their respective follow-ups (2002 and 2007), to study homotypic persistence among the 998 school-age children with psychiatric disorder at baseline. Psychiatric disorder was measured using the Development and Well-Being Assessment applying DSM-IV criteria. Factors relating to the child, family, and the severity and type of psychopathology at baseline were analysed using logistic regression.
Approximately 50% of children with at least one psychiatric disorder were assigned the same diagnostic grouping at 3-year follow-up. Persistent attention-deficit/hyperactivity disorder and anxiety were predicted by poor peer relationship scores. Persistent conduct disorder was predicted by intellectual disability, rented housing, large family size, poor family function and by severer baseline psychopathology scores.
Homotypic persistence was predicted by different factors for different groups of psychiatric disorders. Experimental research in clinical samples should explore whether these factors also influence response to interventions.
Introduction: The addition of computerized physician order entry (CPOE) to Emergency Departments in recent years has led to speculation over potential benefits and pitfalls. Recent studies have shown benefits to CPOE, though there lacks sufficient evidence on how it could change physician behaviour. Physician practices are known to be difficult to change, with getting evidence into daily practice being the main challenge of knowledge translation. Our study aims were to determine if well-designed electronic order sets for CPOE improved MD practices. Methods: The Calgary Zone Pain Management in the Emergency Department Working Group relied on a GRADE-based literature review for identifying best practices for analgesia and antiemetics, resulting in soft changes to the dedicated analgesia and antiemetic electronic order set noting working group preference, and emphasizing hydromorphone over morphine, as well as 4 mg ondansetron over 8 mg. The new electronic order set was started in the only Calgary Region order entry system on December 11th, 2014. Data was collected from July 2014 - May 2015. A Yates chi-squared analysis was completed on all orders in a category, as well as the subgroups of ED staff and residents, and orders placed using the new order set. Results: A total of 100460 orders were analyzed. The use of hydromorphone increased significantly across all 4 EDs. IV hydromorphone use increased (5.82% of all opioid orders up to 26.93%, P<0.0001) with a reciprocal decline in IV morphine (67.81% of all opioid orders down to 46.56%, P<0.0001). Similar effects were observed with ondansetron 4 mg IV orders increasing (1.37% of all ondansetron orders to 18.64%, P<0.0001) with a decrease in 8 mg dosing (15.75% of all ondansetron orders to 7.23%, P<0.0001). These results were replicated to a lesser degree in the non-ED staff and non-order set subgroups. Implementation of the new order set resulted in an increase of its use (37.64% of all opioid orders up to 49.29%, P<0.0001). Finally, a cost-savings analysis was completed showing a projected annual savings of $185,676.52 on medications alone. Conclusion: This data supports the manipulation of electronic order sets to help shape physician behaviour towards best practices. This provides another strong argument towards the benefits of CPOE, and can help maintain best practices in Emergency Medicine.
It is believed that the splitting of the SMC into two fragments and the production of the Inter-Cloud gas and the Magellanic Stream occurred in the one event 4 × 108 years ago. This event was a collision between the LMC and SMC. This time is too short for the Stream to be tidal, or be the result of stripping of the Inter-Cloud gas by a diffuse gaseous halo. It is proposed that the clouds in the Stream are the results of collisions between the Inter-Cloud gas and HVCs in the Galactic halo. A model of this process accounts for all of the observational features of the Stream. Observations of HVCs in the path of the Magellanic Clouds are used to predict the development of the Stream. The HVCs in our halo are thought to be a result of a collision of a galaxy with our Galaxy 6 × 109 years ago.