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Children of parents with mood and psychotic disorders are at elevated risk for a range of behavioral and emotional problems. However, as the usual reporter of psychopathology in children is the parent, reports of early problems in children of parents with mood and psychotic disorders may be biased by the parents' own experience of mental illness and their mental state.
Independent observers rated psychopathology using the Test Observation Form in 378 children and youth between the ages of 4 and 24 (mean = 11.01, s.d. = 4.40) who had a parent with major depressive disorder, bipolar disorder, schizophrenia, or no history of mood and psychotic disorders.
Observed attentional problems were elevated in offspring of parents with major depressive disorder, bipolar disorder and schizophrenia (effect sizes ranging between 0.31 and 0.56). Oppositional behavior and language/thought problems showed variable degrees of elevation (effect sizes 0.17 to 0.57) across the three high-risk groups, with the greatest difficulties observed in offspring of parents with bipolar disorder. Observed anxiety was increased in offspring of parents with major depressive disorder and bipolar disorder (effect sizes 0.19 and 0.25 respectively) but not in offspring of parents with schizophrenia.
Our results suggest that externalizing problems and cognitive and language difficulties may represent a general manifestation of familial risk for mood and psychotic disorders, while anxiety may be a specific marker of liability for mood disorders. Observer assessment may improve early identification of risk and selection of youth who may benefit from targeted prevention.
Introduction: Aeromedical helicopters and fixed wing aircraft are used across Canada to transfer patients to definitive care. Given height limitation in aeromedical transport, CPR performance can be affected. An adapted manual compression technique has been proposed by H. Koch (pron. Cook) that uses the elbow to compress the sternum rather than the conventional hand. This preliminary study evaluated the quality of Koch compressions versus conventional bimanual compressions. Methods: Paramedics (5), registered nurses (3) and a physician (1) were recruited. Each participant performed a 2 minute cycle of each technique, were randomized to determine which technique was performed first, and rested 5 minutes between compression cycles. A Resusci Anne SkillReporter manikin atop a stretcher in a BK117 helicopter was used. The compressors performed without feedback or prompting. Outcomes include compression rate, depth, recoil, and fatigue. Results: The mean conventional compression rate was (bpm) 118 +/− 13 versus 111 +/− 10 in the Koch scenario (p=0.02) (target 100 to 120). Mean conventional compression depth (mm) was 44 +/− 9 versus 49 +/− 7 in the Koch scenario (p=0.01) (target 50 to 60). The mean percentage of compressions with complete release in the conventional scenario was 86 +/− 20 versus 84 +/− 22 in the Koch scenario (p=0.9) (target 100%). Using a Modified Borg Scale of 1 to 10, mean provider fatigue after conventional CPR was 7 (+/− 1.6) versus 3 (+/− 1.2) using Koch technique (p<0.001). On average, Koch technique improved the percentage of compressions at target rate by 26%, the percentage at correct depth by 9%, overall compression quality score by 13% and were more less fatiguing. Conclusion: Using an elbow in a height-restricted environment improved compression depth and reduced provider fatigue. From our limited data, Koch compressions appear to improve compression quality. Further study and external validation are required.
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) represent a disease continuum with common genetic causes and molecular pathology. We recently identified mutations in the T-cell restricted intracellular antigen-1 (TIA1) protein as a cause of ALS +/− FTD. TIA1 is an RNA-binding protein containing a low complexity domain (LCD) that promotes the assembly of membrane-less organelles, such as stress granules (SG). Whole exome sequencing of two family members with fALS/FTD revealed a novel missense mutation in the TIA1 LCD (P362L). Subsequent screening identified five more TIA1 mutations in six additional ALS patients, but none in controls. All mutation carriers presented with weakness, behavioral abnormalities or language impairments and had a final diagnosis of ALS +/− FTD. Autopsy on five TIA1 mutation carriers showed widespread neurodegeneration with TDP-43 pathology. Round eosinophilic inclusions in lower motor neurons were a consistent feature. Cellular assays revealed abnormal SG dynamics in the presence of TIA1 mutations. In summary, missense mutations in the LCD of TIA1 are a newly recognized cause of ALS/FTD with TDP-43 pathology and strengthen the role of RNA metabolism in the pathogenesis in this disease.
Antibiograms have effectively improved antibiotic prescribing in acute-care settings; however, their effectiveness in skilled nursing facilities (SNFs) is currently unknown.
To develop SNF-specific antibiograms and identify opportunities to improve antibiotic prescribing.
Design and Setting.
Cross-sectional and pretest-posttest study among residents of 3 Maryland SNFs.
Antibiograms were created using clinical culture data from a 6-month period in each SNF. We also used admission clinical culture data from the acute care facility primarily associated with each SNF for transferred residents. We manually collected all data from medical charts, and antibiograms were created using WHONET software. We then used a pretest-posttest study to evaluate the effectiveness of an antibiogram on changing antibiotic prescribing practices in a single SNF. Appropriate empirical antibiotic therapy was defined as an empirical antibiotic choice that sufficiently covered the infecting organism, considering antibiotic susceptibilities.
We reviewed 839 patient charts from SNF and acute care facilities. During the initial assessment period, 85% of initial antibiotic use in the SNFs was empirical, and thus only 15% of initial antibiotics were based on culture results. Fluoroquinolones were the most frequently used empirical antibiotics, accounting for 54.5% of initial prescribing instances. Among patients with available culture data, only 35% of empirical antibiotic prescribing was determined to be appropriate. In the single SNF in which we evaluated antibiogram effectiveness, prevalence of appropriate antibiotic prescribing increased from 32% to 45% after antibiogram implementation; however, this was not statistically significant (P = .32).
Implementation of antibiograms may be effective in improving empirical antibiotic prescribing in SNFs.
Many marine fisheries in South American Atlantic coasts (SAAC) are threatened by overfishing and under serious risk of collapsing. The SAAC comprises a diversity of environments, possesses a complex oceanography and harbours a vast biodiversity that provide an enormous potential for using parasites as biological tags for fish stock delineation, a prerequisite for the implementation of control and management plans. Here, their use in the SAAC is reviewed. Main evidence is derived from northern Argentine waters, where fish parasite assemblages are dominated by larval helminth species that share a low specificity, long persistence and trophic transmission, parasitizing almost indiscriminately all available fish species. The advantages and constraints of such a combination of characteristics are analysed and recommendations are given for future research. Shifting the focus from fish/parasite populations to communities allows expanding the concept of biological tags from local to regional scales, providing essential information to delineate ecosystem boundaries for host communities. This new concept arose as a powerful tool to help the implementation of ecosystem-based approaches to fisheries management, the new paradigm for fisheries science. Holistic approaches, including parasites as biological tags for stock delineation will render valuable information to help insure fisheries and marine ecosystems against further depletion and collapse.
Patient registries represent an important method of organizing “real world” patient information for clinical and research purposes. Registries can facilitate clinical trial planning and recruitment and are particularly useful in this regard for uncommon and rare diseases. Neuromuscular diseases (NMDs) are individually rare but in aggregate have a significant prevalence. In Canada, information on NMDs is lacking. Barriers to performing Canadian multicentre NMD research exist which can be overcome by a comprehensive and collaborative NMD registry.
We describe the objectives, design, feasibility and initial recruitment results for the Canadian Neuromuscular Disease Registry (CNDR).
The CNDR is a clinic-based registry which launched nationally in June 2011, incorporates paediatric and adult neuromuscular clinics in British Columbia, Alberta, Ontario, Quebec, New Brunswick and Nova Scotia and, as of December 2012, has recruited 1161 patients from 12 provinces and territories. Complete medical datasets have been captured on 460 “index disease” patients. Another 618 “non-index” patients have been recruited with capture of physician-confirmed diagnosis and contact information. We have demonstrated the feasibility of blended clinic and central office-based recruitment. “Index disease” patients recruited at the time of writing include 253 with Duchenne and Becker muscular dystrophy, 161 with myotonic dystrophy, and 71 with ALS.
The CNDR is a new nationwide registry of patients with NMDs that represents an important advance in Canadian neuromuscular disease research capacity. It provides an innovative platform for organizing patient information to facilitate clinical research and to expedite translation of recent laboratory findings into human studies.
Major depressive disorder (MDD) and generalized anxiety disorder (GAD) have the highest co-morbidity rates within the internalizing disorders cluster, yet no Internet-based cognitive behavioural therapy (iCBT) programme exists for their combined treatment.
We designed a six-lesson therapist-assisted iCBT programme for mixed anxiety and depression. Study 1 was a randomized controlled trial (RCT) comparing the iCBT programme (n = 46) versus wait-list control (WLC; n = 53) for patients diagnosed by structured clinical interview with MDD, GAD or co-morbid GAD/MDD. Primary outcome measures were the Patient Health Questionnaire nine-item scale (depression), Generalized Anxiety Disorder seven-item scale (generalized anxiety), Kessler 10-item Psychological Distress scale (distress) and 12-item World Health Organization Disability Assessment Schedule II (disability). The iCBT group was followed up at 3 months post-treatment. In study 2, we investigated the adherence to, and efficacy of the same programme in a primary care setting, where patients (n = 136) completed the programme under the supervision of primary care clinicians.
The RCT showed that the iCBT programme was more effective than WLC, with large within- and between-groups effect sizes found (>0.8). Adherence was also high (89%), and gains were maintained at 3-month follow-up. In study 2 in primary care, adherence to the iCBT programme was low (41%), yet effect sizes were large (>0.8). Of the non-completers, 30% experienced benefit.
Together, the results show that iCBT is effective and adherence is high in research settings, but there is a problem of adherence when translated into the ‘real world’. Future efforts need to be placed on developing improved adherence to iCBT in primary care settings.
Insulin plays an important role in regulating the partitioning of nutrients to the mammary gland, particularly in lactating ruminants fed concentrate-based diets. There is evidence that the nutritional status of the animals might also affect their response to insulin. This is largely untested in early lactating ruminants fed fresh forage. To investigate nutritional effects on insulin response, 12 lactating sheep, housed indoors, were allocated to one of two treatment groups (hyperinsulinaemic euglycaemic clamp (HEC) or control) in a randomised block design and fed perennial ryegrass (Lolium perenne)/white clover (Trifolium repens) pasture. Mammary amino acid (AA) net uptake from plasma and utilisation for milk protein synthesis was measured during the 4th day of the HEC using arterio–venous concentration differences, and 1-13C-leucine was used to estimate whole body and mammary gland leucine kinetics. There was no change in feed intake, milk protein output and mammary blood flow during the HEC (P > 0.1). The HEC decreased (P < 0.1) the arterial concentrations of all essential AA (EAA) except histidine. The mammary net uptake of some EAA (isoleucine, leucine, methionine and phenylalanine) was reduced by the HEC (P < 0.1). Leucine oxidation in the mammary gland was not altered during the HEC (P > 0.1) but mammary protein synthesis was reduced by the HEC (P < 0.05). These results show that sheep mammary gland can adapt to changing AA precursor supply to maintain milk protein production during early lactation, when fed fresh forage. How this occurs remains unclear, and this area deserves further study.
Non-diabetic individuals who are non-secretors of blood group antigens are prone to superficial infections by Candida albicans. In this study, 216 patients with diabetes mellitus who were denture wearers were examined for the presence or absence of denture stomatitis. There was an overall trend for non-secretors to be prone to denture stomatitis compared with secretors. Stepwise linear discriminant analysis was used to dissect the contribution of secretor status and other variables to the development of the disease. Secretor status was found to be a contributory factor among patients with non-insulin dependent diabetes but not among those with insulin-dependent diabetes. The possible reasons for this are discussed.
A divergent selection experiment with mice, using plasma concentrations of insulin-like growth factor-1 (IGF-1) at 42 days of age as the selection criterion, was undertaken for 7 generations. Lines were not replicated. To obtain sufficient plasma for the IGF-1 assay, blood from four individuals was volumetrically bulked to obtain a litter mean IGF-1 concentration. This necessitated the use of between family selection. Although inbreeding accumulated in a linear fashion in each of the high, control and low lines, the rates were different for each line (3·6, 1·6 and 5·3% per generation for the high, control and low lines, respectively). As a consequence, the effects of selection and inbreeding are confounded in this experiment. Divergence between the high and low lines in plasma concentrations of IGF-1 continued steadily until generation 5. In generations 6 and 7, there was a reduced degree of divergence and this contributed towards the low realized heritability value of 0.15 ± 0.12. Six-week liveweight showed a steady positive correlated response to selection for or against plasma concentrations of IGF-1 until generation 4 (high-low difference = 1·7 g = 12%). In generation 5, a substantial drop in 6-week liveweight in the low line relative to both the high and control lines occurred (high-low difference, 3·9; g, 25%). This difference was maintained until generation 7.
This experiment suggests that genetic variation exists at 6 weeks of age in plasma concentrations of IGF-1 in mice. Furthermore, genetic covariation between plasma IGF-1 concentrations and liveweight at 6 weeks of age is likely to be positive. Further experiments have been initiated to examine these theories.
Stalking is often viewed as a precursor to violence, but determining which stalkers might attack is a difficult task. This study overcomes shortfalls in previous investigations by adopting a pseudo-prospective design and examining potential risk factors for different types of stalker.
Demographic, behavioural and diagnostic information was collected from stalkers referred to a community forensic mental health service (n=211). Potential risk factors for stalking violence were identified using odds ratios and χ2 tests, and entered into logistic regression models. Model utility was assessed using receiver operating characteristic curves.
Amongst Rejected ex-intimate stalkers, violence was best predicted by previous violence, making threats and being employed (area under the curve=0.75), while for stalkers with other motives and relationships to the victim, being aged less than 30 years, substance use at the time of stalking and prior violence best predicted stalking violence (area under the curve=0.80).
Stalkers at increased risk of violence can be accurately identified by examining motivational and relationship type in conjunction with specific relevant risk factors. Previous violence is a particularly important risk factor, as are threats amongst ex-intimate stalkers. Approach behaviours and psychosis were shown to be less useful in predicting violence.
The introduction of large single crystal and high performance CdZnTe (CZT) grown by the traveling heater method (THM) in 2006 has defied conventional myths about the capability of this crystal growth method with respect to the production of spectroscopic grade CZT and its commercialization prospect in medical imaging application. Since then, a lot of progresses have been made, both in the crystal growth and the devices sides. This paper focuses on the development of THM CZT in recent years. Crystalline defects which challenge the thickness scalability of large volume CZT detectors along with efforts and achievements in overcoming these challenges are discussed. Advances in THM CZT crystal growth include 100mm diameter ingot and state-of-the-art device fabrication will also be presented.
Metal/polymer system joints are widely encountered nowadays in microscopic structures such as displays and microchips. In several critical cases they undergo thermal and mechanical loading, with contact failure due to fracture as a possible consequence. Because of their variety in nature and composition metal/polymer joints have become major challenges for experimental, theoretical, and numerical studies. Here we report on results of molecular dynamics simulations carried out to study the mechanical response of a metal/polymer joint, in this case the Cu/polybutadiene model system. The behavior of Cu and the cross-linked polybutadiene are modeled, respectively, by the Embedded Atom Method (EAM) and the Universal Force Field (UFF). Loading is applied under compression. Different potentials are used to describe the interactions in the metal/polymer interface, which allows us to qualitatively analyze possible mechanisms of failure in these joints, below the metal melting point and above the polymer glass transition temperatures.
An assessment of the natural radiation dose to wildlife in England and Wales was made to determine the contribution it may make to the total radiation dose estimated during environmental impact assessments. Significant use was made of systematic datasets for environmental media (stream sediments, stream waters and soils), in particular those produced by the Geochemical Baseline Survey of the Environment (G-BASE) project. This provided extensive, although variable, coverage for different elements and sample types after normalisation of data to account for changes in sampling and analysis over time. Almost complete coverage for K in stream sediments was achieved by merging G-BASE and Wolfson Atlas data. This required normalisation of the Wolfson data to the G-BASE results. Coverage was improved greatly for U and Th in sediments, and K, U and Th in soils, by using the strong relationship between soils and sediments and geology (both solid and superficial) to extrapolate the data. The total U, Th and K data were used to derive activity concentrations of 238U and 232Th series radionuclides and 40K. External dose rates to wildlife were then estimated from derived media concentrations; internal dose rates were estimated from measured activities in biota or activities predicted using recommended concentration ratios.
The mechanisms by which coatings develop on weathered grain surfaces, and their potential impact on rates of fluid-mineral interaction, have been investigated by examining feldspars from a 1.1 ky old soil in the Glen Feshie chronosequence, Scottish highlands. Using the focused ion beam technique, electron-transparent foils for characterization by transmission electron microscopy were cut from selected parts of grain surfaces. Some parts were bare whereas others had accumulations, a few micrometres thick, of weathering products, often mixed with mineral and microbial debris. Feldspar exposed at bare grain surfaces is crystalline throughout and so there is no evidence for the presence of the amorphous ‘leached layers’ that typically form in acid-dissolution experiments and have been described from some natural weathering contexts. The weathering products comprise sub-urn thick crystallites of an Fe-K aluminosilicate, probably smectite, that have grown within an amorphous and probably organic-rich matrix. There is also evidence for crystallization of clays having been mediated by fungal hyphae. Coatings formed within Glen Feshie soils after ∼1.1 ky are insufficiently continuous or impermeable to slow rates of fluid-feldspar reactions, but provide valuable insights into the complex weathering microenvironments on debris and microbe-covered mineral surfaces.
Salmonella infections in Antarctic wildlife were first reported in 1970 and in a search for evidence linking isolations with exposure to human activities, a comparison was made of serovars reported from marine fauna in the Antarctic region from 1982–2004 with those from marine mammals in the Northern hemisphere. This revealed that 10 (83%) Salmonella enterica serovars isolated from Antarctic penguins and seals were classifiable in high-frequency (HF) quotients for serovars prevalent in humans and domesticated animals. In Australia, 16 (90%) HF serovars were isolated from marine birds and mammals compared with 12 (86%) HF serovars reported from marine mammals in the Northern hemisphere. In Western Australia, HF serovars from marine species were also recorded in humans, livestock, mussels, effluents and island populations of wildlife in urban coastal areas. Low-frequency S. enterica serovars were rarely detected in humans and not detected in seagulls or marine species. The isolation of S. Enteritidis phage type 4 (PT4), PT8 and PT23 strains from Adélie penguins and a diversity of HF serovars reported from marine fauna in the Antarctic region and coastal areas of Australia, signal the possibility of transient serovars and endemic Salmonella strains recycling back to humans from southern latitudes in marine foodstuffs and feed ingredients.
A series of synthetic calcium silicates has been produced comprising nano-sized plates. The starting calcium silicate referred to as nano-structured calcium silicate, NCS, appears itself X-ray amorphous but contains impurities of calcite. These impurities decompose during the dry thermal conversion of the material into wollastonite. NCS can be enriched with calcium or silicon, respectively. The silicon enriched NCS can be hydrothermally transformed into a sheet material related to Ca7Si16O38(OH)2. The X-ray pattern of this material was sufficient to allow the calculation of its unit cell with a comparatively high figure of merit. The calcium enriched NCS can form two very distinctly different ceramic materials upon hydrothermal treatment, one a band material (formed below 200 °C) and the other a rose petal shaped material (formed above 210 °C). The X-ray diffraction patterns could not be resolved. The fit between the observed and calculated patterns was less than 50% as expressed in comparatively low figures of merit (unusually <20), which is attributed to calcium carbonate impurities in the samples disrupting the long range order. The patterns of these calcium enriched samples could be best compared to those of tobermorite or truscotite.
The pregnant uterus has a requirement for glucose that rises rapidly towards the end of pregnancy (Robinson et al., 1977). Despite this, the dry matter (DM) intake of the ewe is often depressed during this period causing excessive mobilisation of adipose tissue and an increased concentration of plasma ketones. Propylene glycol resists fermentation in the rumen and following absorption is converted to glucose and glycogen (Andrews, 1982). There is little data available on how in feed inclusion of propylene glycol affects the productivity and energy metabolism of late pregnant and lactating ewes.