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Lymphatic filariasis (LF) threatens nearly 20% of the world's population and has handicapped one-third of the 120 million people currently infected. Current control and elimination programs for LF rely on mass drug administration of albendazole plus diethylcarbamazine (DEC) or ivermectin. Only the mechanism of action of albendazole is well understood. To gain a better insight into antifilarial drug action in vivo, we treated gerbils harbouring patent Brugia malayi infections with 6 mg kg−1 DEC, 0.15 mg kg−1 ivermectin or 1 mg kg−1 albendazole. Treatments had no effect on the numbers of worms present in the peritoneal cavity of treated animals, so effects on gene expression were a direct result of the drug and not complicated by dying parasites. Adults and microfilariae were collected 1 and 7 days post-treatment and RNA isolated for transcriptomic analysis. The experiment was repeated three times. Ivermectin treatment produced the most differentially expressed genes (DEGs), 113. DEC treatment yielded 61 DEGs. Albendazole treatment resulted in little change in gene expression, with only 6 genes affected. In total, nearly 200 DEGs were identified with little overlap between treatment groups, suggesting that these drugs may interfere in different ways with processes important for parasite survival, development, and reproduction.
The purpose of this work was to develop accurate calibration standards which were fully characterized in terms of uniformity and concentration using fundamental measuring methods. Three similar sets of vacuum deposits were commercially made, each set containing the single deposits CuS, KCl, CaF2, Cr, Fe, Cu, RbNO3, SrF2, MoO3 , BaF2, and Pb. Thickness variations in each deposit were measured with PIXEA (proton induced x-ray excitation analysis) measurements taken at 6 to 8 positions along the deposit diameters. Relative elemental concentrations on corresponding deposits from each set were measured using multiple XRF intercomparisons. One set of deposits was destructively analyzed at the National Bureau of Standards with isotope dilution thermal ionization mass spectrometry (IDMS) in order to calibrate the remaining sets of vacuum deposits. The calibrated deposits were compared with standards from two commercial sources. For seven elements heavier than chlorine there was an average deviation of 13.5% between the calibrated deposits and the commercial standards. Disagreements as large as 15% were observed between standards from the two commercial suppliers.
Most studies underline the contribution of heritable factors for psychiatric disorders. However, heritability estimates depend on the population under study, diagnostic instruments, and study designs that each has its inherent assumptions, strengths, and biases. We aim to test the homogeneity in heritability estimates between two powerful, and state of the art study designs for eight psychiatric disorders.
We assessed heritability based on data of Swedish siblings (N = 4 408 646 full and maternal half-siblings), and based on summary data of eight samples with measured genotypes (N = 125 533 cases and 208 215 controls). All data were based on standard diagnostic criteria. Eight psychiatric disorders were studied: (1) alcohol dependence (AD), (2) anorexia nervosa, (3) attention deficit/hyperactivity disorder (ADHD), (4) autism spectrum disorder, (5) bipolar disorder, (6) major depressive disorder, (7) obsessive-compulsive disorder (OCD), and (8) schizophrenia.
Heritability estimates from sibling data varied from 0.30 for Major Depression to 0.80 for ADHD. The estimates based on the measured genotypes were lower, ranging from 0.10 for AD to 0.28 for OCD, but were significant, and correlated positively (0.19) with national sibling-based estimates. When removing OCD from the data the correlation increased to 0.50.
Given the unique character of each study design, the convergent findings for these eight psychiatric conditions suggest that heritability estimates are robust across different methods. The findings also highlight large differences in genetic and environmental influences between psychiatric disorders, providing future directions for etiological psychiatric research.
22q11.2 deletion syndrome (22q11.2DS) is associated with a high risk of childhood as well as adult psychiatric disorders, in particular schizophrenia. Childhood cognitive deterioration in 22q11.2DS has previously been reported, but only in studies lacking a control sample.
To compare cognitive trajectories in children with 22q11.2DS and unaffected control siblings.
A longitudinal study of neurocognitive functioning (IQ, executive function, processing speed and attention) was conducted in children with 22q11.2DS (n = 75, mean age time 1 (T1) 9.9, time 2 (T2) 12.5) and control siblings (n = 33, mean age T1 10.6, T2 134).
Children with 22q11.2DS exhibited deficits in all cognitive domains. However, mean scores did not indicate deterioration. When individual trajectories were examined, some participants showed significant decline over time, but the prevalence was similar for 22q11.2DS and control siblings. Findings are more likely to reflect normal developmental fluctuation than a 22q11.2DS-specific abnormality.
Childhood cognitive deterioration is not associated with 22q11.2DS. Contrary to previous suggestions, we believe it is premature to recommend repeated monitoring of cognitive function to identifying individual children with 22q11.2DS at high risk of developing schizophrenia.
Simultaneous observations of 8 Seyfert 1 type AGN (Fairall-9, Mrk 590, NGC 4051, 3C 273, NGC 5548, Mrk 841, Q 1821+643 and 3C 390.3) obtained with ROSAT and IUE (RIASS program), and for 5 sources (Fairall-9, NGC 4051, 3C 273, Mrk 841 and Q 1821+643) with Ginga, have been analysed with the aim of describing the UV to soft X-ray spectral component in these sources.
A number of copy number variants (CNVs) have been suggested as
susceptibility factors for schizophrenia. For some of these the data
remain equivocal, and the frequency in individuals with schizophrenia is
To determine the contribution of CNVs at 15 schizophrenia-associated loci
(a) using a large new data-set of patients with schizophrenia
(n = 6882) and controls (n = 6316),
and (b) combining our results with those from previous studies.
We used Illumina microarrays to analyse our data. Analyses were
restricted to 520 766 probes common to all arrays used in the different
We found higher rates in participants with schizophrenia than in controls
for 13 of the 15 previously implicated CNVs. Six were nominally
significantly associated (P<0.05) in this new
data-set: deletions at 1q21.1, NRXN1, 15q11.2 and
22q11.2 and duplications at 16p11.2 and the Angelman/Prader–Willi
Syndrome (AS/PWS) region. All eight AS/PWS duplications in patients were
of maternal origin. When combined with published data, 11 of the 15 loci
showed highly significant evidence for association with schizophrenia
We strengthen the support for the majority of the previously implicated
CNVs in schizophrenia. About 2.5% of patients with schizophrenia and 0.9%
of controls carry a large, detectable CNV at one of these loci. Routine
CNV screening may be clinically appropriate given the high rate of known
deleterious mutations in the disorder and the comorbidity associated with
these heritable mutations.
When challenged with information about the future, healthy participants show an optimistically biased updating pattern, taking desirable information more into account than undesirable information. However, it is unknown how patients suffering from major depressive disorder (MDD), who express pervasive pessimistic beliefs, update their beliefs when receiving information about their future. Here we tested whether an optimistically biased information processing pattern found in healthy individuals is absent in MDD patients.
MDD patients (n = 18; 13 medicated; eight with co-morbid anxiety disorder) and healthy controls (n = 19) estimated their personal probability of experiencing 70 adverse life events. After each estimate participants were presented with the average probability of the event occurring to a person living in the same sociocultural environment. This information could be desirable (i.e. average probability better than expected) or undesirable (i.e. average probability worse than expected). To assess how desirable versus undesirable information influenced beliefs, participants estimated their personal probability of experiencing the 70 events a second time.
Healthy controls showed an optimistic bias in updating, that is they changed their beliefs more toward desirable versus undesirable information. Overall, this optimistic bias was absent in MDD patients. Symptom severity correlated with biased updating: more severely depressed individuals showed a more pessimistic updating pattern. Furthermore, MDD patients estimated the probability of experiencing adverse life events as higher than healthy controls.
Our findings raise the intriguing possibility that optimistically biased updating of expectations about one's personal future is associated with mental health.
Wildlife reservoir hosts of bovine tuberculosis (bTB) include Eurasian badgers (Meles meles) and brushtail possum (Trichosurus vulpecula) in the UK and New Zealand, respectively. Similar species warrant further investigation in the northern lower peninsula of Michigan, USA due to the continued presence of bTB on cattle farms. Most research in Michigan, USA has focused on interactions between white-tailed deer (Odocoileus virginianus) and cattle (Bos taurus) for the transmission of the infectious agent of bTB, Mycobacterium bovis, due to high deer densities and feeding practices. However, limited data are available on medium-sized mammals such as Virginia opossum (Didelphis virginiana; hereafter referred to as opossum) and their movements and home range in Michigan near cattle farms. We conducted surveillance of medium-sized mammals on previously depopulated cattle farms for presence of M. bovis infections and equipped opossum with Global Positioning System (GPS) technology to assess potential differences in home range between farms inside and outside the bTB core area that has had cattle test positive for M. bovis. On farms inside the bTB core area, prevalence in opossum was comparable [6%, 95% confidence interval (CI) 2·0–11·0] to prevalence in raccoon (Procyon lotor; 4%, 95% CI 1·0–9·0, P = 0·439) whereas only a single opossum tested positive for M. bovis on farms outside the bTB core area. The prevalence in opossum occupying farms that had cattle test positive for M. bovis was higher (6·4%) than for opossum occupying farms that never had cattle test positive for M. bovis (0·9%, P = 0·01). Mean size of home range for 50% and 95% estimates were similar by sex (P = 0·791) both inside or outside the bTB core area (P = 0·218). Although surveillance efforts and home range were not assessed on the same farms, opossum use of farms near structures was apparent as was selection for farms over surrounding forested habitats. The use of farms, stored feed, and structures by opossum, their ability to serve as vectors of M. bovis, and their propensity to ingest contaminated sources of M. bovis requires additional research in Michigan, USA.
A compact spectrometer-on-a-chip featuring a plasmonic molecular interaction region has been conceived, designed, modeled, and partially fabricated. The silicon-on-insulator (SOI) system is the chosen platform for the integration. The low loss of both silicon and SiO2 between 3 and 4 μm wavelengths enables silicon waveguides on SiO2 as the basis for molecular sensors at these wavelengths. Important characteristic molecular vibrations occur in this range, namely the bond stretching modes C-H (Alkynes), O-H (monomeric alcohols, phenols) and N-H (Amines), as well as CO double bonds, NH2, and CN. The device consists of a broad-band infrared LED, photonic waveguides, photon-to-plasmon transformers, a molecular interaction region, dispersive structures, and detectors. Photonic waveguide modes are adiabatically converted into SPPs on a neighboring metal surface by a tapered waveguide. The plasmonic interaction region enhances optical intensity, which allows a reduction of the overall device size without a reduction of the interaction length, in comparison to ordinary optical methods. After the SPPs propagate through the interaction region, they are converted back into photonic waveguide modes by a second taper. The dispersing region consists of a series of micro-ring resonators with photodetectors coupled to each resonator. Design parameters were optimized via electro-dynamic simulations. Fabrication was performed using a combination of photo- and electron-beam-lithography together with standard silicon processing techniques.
Electronic structure calculations using the Heyd-Scuseria-Ernzerhof (HSE) hybrid functional are presented for NO-pair complexes with and without hydrogen to test the hypothesis that such defect complexes could lead to shallower levels than for isolated NO and hence p-type doping. The H is found to bind strongly to one of the N in the pair and removes thecorresponding defect level from the gap but the second N’s polaronic defect level in the gap remains deep.