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To evaluate the association between novel pre- and post-operative biomarker levels and 30-day unplanned readmission or mortality after paediatric congenital heart surgery.
Children aged 18 years or younger undergoing congenital heart surgery (n = 162) at Johns Hopkins Hospital from 2010 to 2014 were enrolled in the prospective cohort. Collected novel pre- and post-operative biomarkers include soluble suppression of tumorgenicity 2, galectin-3, N-terminal prohormone of brain natriuretic peptide, and glial fibrillary acidic protein. A model based on clinical variables from the Society of Thoracic Surgery database was developed and evaluated against two augmented models.
Unplanned readmission or mortality within 30 days of cardiac surgery occurred among 21 (13%) children. The clinical model augmented with pre-operative biomarkers demonstrated a statistically significant improvement over the clinical model alone with a receiver-operating characteristics curve of 0.754 (95% confidence interval: 0.65–0.86) compared to 0.617 (95% confidence interval: 0.47–0.76; p-value: 0.012). The clinical model augmented with pre- and post-operative biomarkers demonstrated a significant improvement over the clinical model alone, with a receiver-operating characteristics curve of 0.802 (95% confidence interval: 0.72–0.89; p-value: 0.003).
Novel biomarkers add significant predictive value when assessing the likelihood of unplanned readmission or mortality after paediatric congenital heart surgery. Further exploration of the utility of these novel biomarkers during the pre- or post-operative period to identify early risk of mortality or readmission will aid in determining the clinical utility and application of these biomarkers into routine risk assessment.
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.
Children of parents with major mood and psychotic disorders are at increased risk of psychopathology, including psychotic symptoms. It has been suggested that the risk of psychosis may be more often transmitted from parent to opposite-sex offspring (e.g., from father to daughter) than to same-sex offspring (e.g., from father to son). To test whether sex-specific transmission extends to early manifestations of psychosis, we examined sex-specific contributions to psychotic symptoms among offspring of mothers and fathers with depression, bipolar disorder and schizophrenia. We assessed psychotic symptoms in 309 offspring (160 daughters and 149 sons) aged 8–24 years (mean=13.1, s.d.=4.3), of whom 113 had a mother with schizophrenia, bipolar disorder or major depression and 43 had a father with schizophrenia, bipolar disorder or major depression. In semi-structured interviews, 130 (42%) offspring had definite psychotic symptoms established and confirmed by psychiatrists on one or more assessments. We tested the effects of mental illness in parents on same-sex and opposite-sex offspring psychotic symptoms in mixed-effect logistic regression models. Psychotic symptoms were more prevalent among daughters of affected fathers and sons of affected mothers than among offspring of the same sex as their affected parent. Mental illness in the opposite-sex parent increased the odds of psychotic symptoms (odds ratio (OR)=2.65, 95% confidence interval (CI) 1.43–4.91, P=0.002), but mental illness in the same-sex parent did not have a significant effect on psychotic symptoms in offspring (OR=1.13, 95% CI 0.61–2.07, P=0.697). The opposite-sex-specific parent-of-origin effects may suggest X chromosome-linked genetic transmission or inherited chromosomal modifications in the etiology of psychotic symptoms.
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.
Artificial rearing is a common practice for rearing calves from the dairy herd destined for beef production. In commercial practice calves are typically weaned from 5 to 9 weeks old. There are four criteria that can be used to determine weaning time: - age, compound feed intake, liveweight, and, milk price and quota policy. Late weaning systems are based on the theory of giving the calf the best possible start in life, but are costly with high milk intakes (Davis and Drackley, 1998). Hence emphasis is usually placed on early weaning of the calf and encouraging concentrate intake. The objective of this study was to determine the effect of weaning at either 6 or 8 weeks old on the performance dairy-bred beef calves.
It is reported that supplementing pregnant ewes with supra-optimal levels of vitamin E improves neonatal lamb vigour and growth rate (Merrell, 1998). The biochemical mechanism behind these observations has yet to be elucidated as several studies report negligible placental vitamin E transfer in ruminants (Van Saun et al., 1989); consequently, lambs may be clinically deficient in this nutrient at birth and achieve a satisfactory vitamin E status via colostrum ingestion. Lamb vitamin E status may be further diminished by the addition of polyunsaturated fatty acids (PUFAs) to the maternal diet. However, PUFA supplementation demonstrably enhances foetal and neonatal development in human studies (Morley, 1998) although these effects have not been investigated in ruminants to any depth. The objective of this experiment was to investigate the effects of dietary vitamin E in combination with long-chain PUFA supplementation of ewes on ewe and lamb performance.
Long-chain polyunsaturated fatty acids (PUFAs) are essential components of cellular membranes and are associated with prostaglandin synthesis. Supplementing ewes with long-chain PUFAs during gestation has been demonstrated to increase gestation length and improve lamb vigour (Capper et al., 2002). Furthermore, increasing the dietary vitamin E supplied to pregnant ewes is reported to increase lamb growth rate (Gentry et al., 1992). However, fish oil supplementation during lactation may reduce milk component yield and lamb growth rate (Capper et al., 2002). The objective of this experiment was to investigate the effects of dietary long-chain PUFA and vitamin E supplementation of pregnant ewes on lamb performance.
The long-chain polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA) and arachidonic acid (AA) are the most abundant fatty acids in the brain and are vital for its correct development and for that of the nervous system (Huang and Craig-Schmidt, 1996). Ruminant diets are low in DHA and its precursor alpha-linolenic acid. In addition, dietary PUFAs are substantially hydrogenated in the rumen. Consequently, it may be argued that the diets of pregnant and lactating ewes may be deficient in DHA and that a response to supplementation may be observed. Studies involving the supplementation of pregnant ewes with supraoptimal levels of vitamin E have shown that lambs born to supplemented dams are more vigorous immediately after birth and have higher liveweight gains (Merrell, 1998). The objective of this experiment was to investigate the effects of dietary long-chain PUFA in combination with vitamin E supplementation of ewes on ewe and lamb performance.
Psychotic symptoms are common in children and adolescents and may be early manifestations of liability to severe mental illness (SMI), including schizophrenia. SMI and psychotic symptoms are associated with impairment in executive functions. However, previous studies have not differentiated between ‘cold’ and ‘hot’ executive functions. We hypothesized that the propensity for psychotic symptoms is specifically associated with impairment in ‘hot’ executive functions, such as decision-making in the context of uncertain rewards and losses.
In a cohort of 156 youth (mean age 12.5, range 7–24 years) enriched for familial risk of SMI, we measured cold and hot executive functions with the spatial working memory (SWM) task (total errors) and the Cambridge Gambling Task (decision-making), respectively. We assessed psychotic symptoms using the semi-structured Kiddie Schedule for Affective Disorders and Schizophrenia interview, Structured Interview for Prodromal Syndromes, Funny Feelings, and Schizophrenia Proneness Instrument – Child and Youth version.
In total 69 (44.23%) youth reported psychotic symptoms on one or more assessments. Cold executive functioning, indexed with SWM errors, was not significantly related to psychotic symptoms [odds ratio (OR) 1.36, 95% confidence interval (CI) 0.85–2.17, p = 0.204). Poor hot executive functioning, indexed as decision-making score, was associated with psychotic symptoms after adjustment for age, sex and familial clustering (OR 2.37, 95% CI 1.25–4.50, p = 0.008). The association between worse hot executive functions and psychotic symptoms remained significant in sensitivity analyses controlling for general cognitive ability and cold executive functions.
Impaired hot executive functions may be an indicator of risk and a target for pre-emptive early interventions in youth.
Bentonite is one of the more safety-critical components of the engineered barrier system in the disposal concepts developed for many types of radioactive waste. It is used due to its favourable properties (including plasticity, swelling capacity, colloid filtration, low hydraulic conductivity, high retardation of key radionuclides) and its stability in relevant geological environments. However, bentonite is unstable under alkaline conditions and this has driven interest in low-alkali cements (leachate pH of 10–11). To build a robust safety case, it is important to have supporting natural analogue data to confirm understanding of the likely long-term performance of bentonite. In Cyprus, the presence of natural bentonite in close proximity to natural alkaline groundwaters permits the zones of potential bentonite/alkaline water reaction to be studied as an analogy of the potential reaction zones in the repository. Here, the results indicate minimal volumetric reaction of bentonite, with production of a palygorskite secondary phase.
To determine the frequency of multiple pathology [Alzheimer Disease (AD) plus Vascular Dementia and/or Dementia with Lewy Bodies] in patients enrolled in clinical trials of AD therapy, and to compare the cognitive and functional assessments between patients with pure AD and AD with multiple pathology.
We conducted a retrospective analysis of patients with a clinical diagnosis of AD who were enrolled in AD therapy clinical trials and subsequently received an autopsy for confirmation of their diagnosis from 2000 to 2009. Performance on cognitive screening tests, namely Modified Mini Mental state (3MS) exam, Mini Mental state Exam (MMSE) and Functional Rating Scale (FRS) were compared between patients with pure AD and multiple pathology.
Autopsy reports were available for 16/47 (34%) of deceased patients. Of these 16 patients, 5 (31%) had pure AD pathology, 10 (63%) had AD with other pathology, and 1 (6%) had non-AD pathology. Compared to patients with pure AD, patients with AD mixed with other pathology had poorer baseline FRS in problem-solving (p<0.01) and community affairs (p<0.02).
While the strict enrollment criteria for clinical trials identified the presence of AD pathology in the majority of cases (15/16), multiple pathology was more common than pure AD in our series of autopsied patients. Premortem biomarkers that can distinguish between pure AD and AD with multiple pathology will be beneficial in future clinical trials and dementia patient management.
Doping porous oxides with organic functionalities has become increasingly useful for the detection of many types of compounds and molecules. So far the detection of microorganisms by this process has not been firmly established. There is, however, a need to develop easy to use, sensitive devices for the detection of microorganisms in potable water supplies. For example, the need for a sensor that can detect a pathogenic parasite called Cryptosporidium parvum has emerged in the United States. In this report, we describe the production of such a device via the sol-gel method. The sol-gel sensor can detect trace amounts of Cryptosporidium parvum. The advantages of the porous oxide matrix lead to high sensitivity. The sensor is easy to use and inexpensive. The presence of Cryptosporidium parvum is indicated by a color change in an otherwise colorless gel. Absorbance intensities for the enzyme-linked antibody used in the study correlated appropriately to oocyst concentration in the solution.
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.
Methods of perceptual voice evaluation have yet to achieve satisfactory consistency; complete acceptance of a recognised clinical protocol is still some way off.
Materials and methods:
Three speech and language therapists rated the voices of 43 patients attending the problem asthma clinic of a teaching hospital, according to the grade-roughness-breathiness-asthenicity-strain (GRBAS) scale and other perceptual categories.
Results and analysis:
Use of the GRBAS scale achieved only a 64.7 per cent inter-rater reliability and a 69.6 per cent intra-rater reliability for the grade component. One rater achieved a higher degree of consistency. Improved concordance on the GRBAS scale was observed for subjects with laryngeal abnormalities. Raters failed to reach any useful level of agreement in the other categories employed, except for perceived gender.
These results should sound a note of caution regarding routine adoption of the GRBAS scale for characterising voice quality for clinical purposes. The importance of training and the use of perceptual anchors for reliable perceptual rating need to be further investigated.
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.
The present study investigated the effect of maternal vitamin E and fatty acid supplementation on lamb antioxidant status. Forty-eight ewes were fed one of four concentrate diets supplemented with a basal (50 mg/kg) or supranutritional (500 mg/kg) level of vitamin E plus a source of either saturated fat (Megalac®; Volac Ltd, Royston, Hertfordshire, UK) or long-chain PUFA (fish oil) from 6 weeks prepartum until 4 weeks postpartum. Blood samples were taken from ewes and lambs at intervals throughout the experiment and, at parturition, muscle, brain and blood samples were obtained from twelve lambs (three per treatment). Colostrum and milk samples were obtained at 12 h and 21 d after parturition, respectively. Supranutritional vitamin E supplementation of the ewe significantly increased concentrations of vitamin E in neonatal lamb tissues although plasma concentrations were undetectable. A significant increase in lamb birth weight resulted from increasing the dietary vitamin E supply to the ewe. Furthermore, maternal plasma, colostrum and milk vitamin E concentrations were increased by vitamin E supplementation, as were lamb plasma concentrations at 14 d of age. Neonatal vitamin E status was not significantly affected by fat source although plasma vitamin E concentrations in both ewes and suckling lambs were reduced by fish oil supplementation of the ewe. Fish oil supplementation reduced vitamin E concentrations in colostrum and milk and the activity of glutathione peroxidase in suckling lambs. The data suggest that the vitamin E status of the neonatal and suckling lamb may be manipulated by vitamin E supplementation of the ewe during pregnancy and lactation.
Comparison of glycolysis in Brugia pahangi and Onchocerca volvulus by C nuclear magnetic resonance (NMR) spectroscopy showed that the former organism is predominantly a lactate fermenter and the latter resembles more closely the metabolism of a mixed acid fermenter producing lactate, succinate, acetate, ethanol, formate and carbon dioxide. Both organisms synthesize glycogen as a storage carbohydrate. Glutaminolysis in both organisms proceeds by the δ-aminobutyrate shunt to produce succinate which is then further metabolized to acetate and carbon dioxide as end-products.
The depression and lability of mood which have been previously reported on the fifth day after childbirth are largely restricted to women with high neuroticism scores. The pattern of day-to-day mood changes is the same after Caesarian section as after vaginal delivery, but there is no ‘day five’ phenomenon after hysterectomy. Post-partum mood disturbance is less prominent in women who return home 48 hours after delivery.
Native bee pollinators were collected and observed on cultivated blueberry, raspberry, and cranberry and on natural non-cultivated plants such as blackberry, buttercup, fireweed, thistle, and hairy cat's ear. Higher abundance and diversity of native bees were found on natural vegetation than on berry crops. Native bee populations on berry crops increased from 1981 to 1982, although diversity was similar. Native bees were not abundant enough to ensure adequate pollination of berry crops, and therefore, the use of managed honey bees is advisable. Pesticide impact, competition with managed honey bees, and habitat destruction have probably decreased native bee populations in agricultural areas of the Fraser Valley.
The use of a standard measure of native pollinator abundance, bees observed/min/m2, is recommended for future studies of this kind.