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C-reactive protein (CRP) is a candidate biomarker for major depressive disorder (MDD), but it is unclear how peripheral CRP levels relate to the heterogeneous clinical phenotypes of the disorder.
To explore CRP in MDD and its phenotypic associations.
We recruited 102 treatment-resistant patients with MDD currently experiencing depression, 48 treatment-responsive patients with MDD not currently experiencing depression, 48 patients with depression who were not receiving medication and 54 healthy volunteers. High-sensitivity CRP in peripheral venous blood, body mass index (BMI) and questionnaire assessments of depression, anxiety and childhood trauma were measured. Group differences in CRP were estimated, and partial least squares (PLS) analysis explored the relationships between CRP and specific clinical phenotypes.
Compared with healthy volunteers, BMI-corrected CRP was significantly elevated in the treatment-resistant group (P = 0.007; Cohen's d = 0.47); but not significantly so in the treatment-responsive (d = 0.29) and untreated (d = 0.18) groups. PLS yielded an optimal two-factor solution that accounted for 34.7% of variation in clinical measures and for 36.0% of variation in CRP. Clinical phenotypes most strongly associated with CRP and heavily weighted on the first PLS component were vegetative depressive symptoms, BMI, state anxiety and feeling unloved as a child or wishing for a different childhood.
CRP was elevated in patients with MDD, and more so in treatment-resistant patients. Other phenotypes associated with elevated CRP included childhood adversity and specific depressive and anxious symptoms. We suggest that patients with MDD stratified for proinflammatory biomarkers, like CRP, have a distinctive clinical profile that might be responsive to second-line treatment with anti-inflammatory drugs.
Declaration of interest
S.R.C. consults for Cambridge Cognition and Shire; and his input in this project was funded by a Wellcome Trust Clinical Fellowship (110049/Z/15/Z). E.T.B. is employed half time by the University of Cambridge and half time by GlaxoSmithKline; he holds stock in GlaxoSmithKline. In the past 3 years, P.J.C. has served on an advisory board for Lundbeck. N.A.H. consults for GlaxoSmithKline. P.d.B., D.N.C.J. and W.C.D. are employees of Janssen Research & Development, LLC., of Johnson & Johnson, and hold stock in Johnson & Johnson. The other authors report no financial disclosures or potential conflicts of interest.
We have been pursuing a program of hot star UV spectroscopy in local group galaxies over several years with HST. We have also obtained WFPC2 images in parallel and pointed exposures with several broad band filters.
• The imaging data have been used to generate colour-magnitude plots of central fields, clusters and halo fields in M31, M33 and NGC 6822. We have compared these with high-mass model isochrones from recent models, to examine the stellar populations that are indicated. M33 contains a substantial young cluster population whose mass and age appear to be related. The western outer wisps of NGC 6822 contain a relatively young population of stars.
• Most of the spectra have been reported and modelled in published papers: we note here the first comparison of stars in NGC 6822 with others from local group galaxies.
• We have also discussed the interstellar extinction in M31 and find it is similar to the Galaxy after allowance for comparable amounts of halo extinction that resembles that of the Magellanic Clouds.
The present paper provides an approach for the design and analysis of variety trials that are used to obtain quality trait data. These trials are multi-phase in nature, comprising a field phase followed by one or more laboratory phases. Typically the laboratory phases are costly relative to the field phase and this imposes a limit on the number of samples that can be tested. Historically, this has been achieved by sacrificing field replication, either by testing a single replicate plot for each variety or a single composite sample, obtained by combining material from several field replicates. An efficient statistical analysis cannot be applied to such data so that valid inference and accurate prediction of genetic effects may be precluded. A solution that has appeared recently in the literature is the use of partial replication, in which some varieties are tested using multiple field replicates and the remainder as single replicates only. In the present paper, an approach is proposed in which some varieties are tested using individual field replicate samples and others as composite samples. Replication in the laboratory is achieved by splitting a relatively small number of field samples into sub-samples for separate processing. It is shown that, if necessary, some of the composite samples may be split for this purpose. It is also shown that, given a choice of field compositing and laboratory replication strategy, an efficient design for a laboratory phase may be obtained using model-based techniques. The methods are illustrated using two examples. It is demonstrated that the approach provides more accurate variety predictions compared with the partial replication approach and that the gains can be substantial if the field variation is large relative to the laboratory variation.
Industry is increasingly aware that sustainability combines environmental, societal, and economic considerations in product development and that this linkage, while driving improved performance, can pose both a business opportunity and a challenge. On one hand, innovations make good business sense by bringing new products to supply a growing market demand for sustainable goods. On the other hand, new regulatory standards demand cleaner, less-toxic products, which can be difficult to develop economically, and require an agreed-upon infrastructure to demonstrate compliance, which can also be difficult and expensive. In this article, we discuss how measurements, standards, and data, being developed and deployed worldwide by national metrology institutes (NMIs) and standards-developing organizations (SDOs), are helping industry enable the sustainable use of materials. Examples include bio-based polymers, lightweight automobiles, fly-ash-based concrete, and lead-free solders. Measurements, standards, and data also support energy efficiency and renewable energy and ease industry compliance with new and emerging regulations, including those that demand less-toxic components.
Inelastic neutron scattering methods were used in conjunction with Raman spectroscopy to probe the vibrational density of states of the hydrofluorocarbons (HFCs) 134 (HF2C-CF2H) and 134a (F3C-CFH2) adsorbed in the cages of dehydrated Na-X zeolite. A comparison of the vibrational spectra of the encaged HFC species with those of their gas-phase analogs indicates that the HFCs adsorb nondissociatively at room temperature and are most likely associated with Na cations in the supercages at the SIII sites. Guest-host interactions are manifested by adsorption-induced perturbations of the gas-phase torsional and C-H stretching vibrations and the presence of additional features presumably due to low-energy whole-molecule vibrations and adsorbate-coupled zeolite framework vibrations. Moreover, although the 134 trans conformer is favored by 5 kJ/mole in the gas phase at 300 K, the gauche conformer seems to be more prevalent in the zeolite at this temperature and below. This suggests that a sizeable fraction of the Na-X adsorption sites provides a stabilizing configuration for the otherwise higher-energy gauche conformation, perhaps due to hydrogen-bonding interactions with the zeolite framework.
Atomic layer deposition (ALD) was performed on quantities of multiwalled carbon nanotubes (MWCNTs) in a rotary reactor. Because of nucleation difficulties, Al2O3 ALD grew as nanospheres on the MWCNTs. After a NO2 nucleation treatment, Al2O3 ALD films grew conformally and noncovalently functionalized the surface of the MWCNT. This Al2O3 ALD film served as a platform for the growth of W ALD metal. The uncoated and ALD-coated MWCNTs were characterized with transmission electron microscopy and x-ray photoelectron spectroscopy. This study demonstrates that ALD can be performed on quantities of very high surface area MWCNT substrates.
Patients whose symptoms are ‘unexplained by disease’ often have a poor symptomatic outcome after specialist consultation, but we know little about which patient factors predict this. We therefore aimed to determine predictors of poor subjective outcome for new neurology out-patients with symptoms unexplained by disease 1 year after the initial consultation.
The Scottish Neurological Symptom Study was a 1-year prospective cohort study of patients referred to secondary care National Health Service neurology clinics in Scotland (UK). Patients were included if the neurologist rated their symptoms as ‘not at all’ or only ‘somewhat explained’ by organic disease. Patient-rated change in health was rated on a five-point Clinical Global Improvement (CGI) scale (‘much better’ to ‘much worse’) 1 year later.
The 12-month outcome data were available on 716 of 1144 patients (63%). Poor outcome on the CGI (‘unchanged’, ‘worse’ or ‘much worse’) was reported by 482 (67%) out of 716 patients. The only strong independent baseline predictors were patients' beliefs [expectation of non-recovery (odds ratio [OR] 2.04, 95% confidence interval [CI] 1.40–2.96), non-attribution of symptoms to psychological factors (OR 2.22, 95% CI 1.51–3.26)] and the receipt of illness-related financial benefits (OR 2.30, 95% CI 1.37–3.86). Together, these factors predicted 13% of the variance in outcome.
Of the patients, two-thirds had a poor outcome at 1 year. Illness beliefs and financial benefits are more useful in predicting poor outcome than the number of symptoms, disability and distress.
Clinical guidelines recommend the routine use of a single antipsychotic
drug in a standard dose, but prescriptions for high-dose and combined
antipsychotics are common in clinical practice.
To evaluate the effectiveness of a quality improvement programme in
reducing the prevalence of high-dose and combined antipsychotic
prescribing in acute adult in-patient wards in the UK.
Baseline audit was followed by feedback of benchmarked data and delivery
of a range of bespoke change interventions, and then by a further audit 1
Thirty-two services participated, submitting data for 3942 patients at
baseline and 3271 patients at the 1-year audit. There was little change
in the prevalence of high-dose (baseline 36%; re-audit 34%) or combined
antipsychotic prescribing (baseline 43%; re-audit 39%). As required
(‘p.r.n.’) prescriptions were the principal cause of both high-dose and
combined antipsychotic prescribing on both occasions.
The quality improvement programme did not have a demonstrable impact on
prescribing practice in the majority of services. Future efforts to align
practice with clinical guidelines need to specifically target the culture
and practice of p.r.n. prescribing.
The study of genetic diversity in malaria populations is expected to provide new insights for the deployment of control measures. Plasmodium falciparum diversity in Africa and Asia is thought to reflect endemicity. In comprehensive epidemiological surveys reported here the genetic and antigenic structure of P. falciparum in the Venezuelan Amazon were studied over a 2-year period. DNA polymorphisms in glutamate-rich protein (GLURP), merozoite-surface protein 1 (MSP1) and MSP2 genes, in a multicopy element (PfRRM), all showed low diversity, 1 predominant genotype, and virtually no multi-clonal infections. Moreover, linkage disequilibrium was seen between GLURP, MSP1 and MSP2. Specific antibody responses against MSP1 and MSP2 recombinant antigens reflected the low genetic diversity observed in the parasite population. This is unexpected in a mesoendemic area, and suggests that the low diversity here may not only relate to endemicity but to other influences such as a bottleneck effect. Linkage disequilibrium and a predominant genotype may imply that P. falciparum frequently propagates with an epidemic or clonal population structure in the Venezuelan Amazon.
Neurocognitive impairments in euthymic patients with bipolar disorder may represent trait rather than state variables.
To test the hypothesis that euthymic patients with bipolar disorder would exhibit impairment in verbal learning and memory and executive function compared with healthy controls matched for age, gender and premorbid IQ.
Twenty euthymic patients with bipolar disorder were matched, on a case-by-case basis, to twenty healthy community controls. Cases and controls were tested with a battery of neuropsychological tests.
Impairments were found in cases compared with controls in tests of verbal learning and memory. Verbal learning and memory correlated negatively with the number of manic episodes.
Impaired verbal learning and memory may be a trait variable in bipolar disease. There are implications for adherence to medication and relapse and for the role of early treatment interventions. Prospective designs and targeting first-episode groups may help to differentiate trait v. disease process effects.
Based on interviews with 122 men who had used violence against their partner, and employing Goffman's (1971) concept of ‘remedial work’, this paper interrogates violent men's perceptions, constructions and understandings of domestic violence and their responses to its use. Accounts of women partners are also examined. ‘Remedial work’ involves the perpetrator of an act of untoward behaviour in various forms of ‘damage limitation’ intended to change the meaning of the offensive act into one that is deemed acceptable. Goffman's three related devices of remedial work – ‘accounts, apologies, and requests’ – are used to explore men's narratives of violent events, their definitions of the event, rationales and perceptions of consequences. Revealed are the exculpatory and expiatory discourses which dominate men's narratives and which expose the purposeful yet paradoxical nature of their responses to violence, directed at mitigating and obfuscating culpability while at the same time seeking forgiveness and absolution. We suggest that through these devices men seek to impose their own definitions upon their woman partner and thereby neutralise or eradicate her experience of abuse and control the ways in which she interprets and responds to it. These findings strongly support Goffman's theoretical conception. In addition, they highlight the need for further investigation of how men's and women's accounts, definitions and responses to violence are interactionally connected through men's attempts to define the violence in exculpatory and expiatory terms and in women's resistance to such definitions and their implications.
Cowpox is an orthopoxvirus infection endemic in European wild rodents, but with a wide host
range including human beings. In this longitudinal study we examined cowpox in two wild
rodent species, bank voles Clethrionomys glareolus and wood mice Apodemus sylvaticus, to
investigate the dynamics of a virus in its wild reservoir host. Trapping was carried out at
4-weekly intervals over 3 years and each animal caught was uniquely identified, blood sampled
and tested for antibodies to cowpox. Antibody prevalence was higher in bank voles than in
wood mice and seroconversion varied seasonally, with peaks in autumn. Infection was most
common in males of both species but no clear association with age was demonstrated. This
study provides a model for studying other zoonotic infections that derive from wild mammals
since other approaches, such as one-off samples, will fail to detect the variation in infection
and thus, risk to human health, demonstrated here.
Background. Chronic fatigue syndrome (CFS) and major depressive disorder (MDD) share many
symptoms and aetiological factors but may have different neurobiological underpinnings. We
wished to determine the profile of the biological variables disturbed in CFS and MDD, and identify
any critical factors that differentiate the disorders.
Methods. Thirty patients with CFS, 20 with MDD and 15 healthy controls – matched group-wise
for age and sex – were recruited. Subjects were given a detailed battery of motor and cognitive tests,
including measures of psychomotor speed, memory and maximal voluntary muscle contraction in
both the morning and evening that were balanced to avoid order effects.
Results. CFS patients generally performed worse on cognitive tests than healthy controls, but better
than patients with MDD. Both patient groups had markedly impaired motor function compared
with healthy controls. MDD subjects showed a significantly greater diurnal improvement in
maximal voluntary contraction than healthy controls.
Conclusions. Patients with CFS and MDD show similarly substantial motor impairment, but
cognitive deficits are generally more marked in MDD. Diurnal changes in some functions in MDD
may differentiate the disorder from CFS.
In the last two decades there have been a number of social, medical and legal
initiatives in the UK and elsewhere to provide assistance to women who
suffer violence from their partner. The most recent innovations focus on
responding to the men who perpetrate this violence. In this article we
present the initial results of the first British study of programmes for
violent men. The three-year study used a longitudinal method to compare
the effects of two court mandated programmes with other, more orthodox,
forms of criminal justice intervention (fines, admonishment, traditional probation,
prison). Here we describe the men's programmes, locate the current
study in the context of existing evaluations of similar programmes operating
in North America, outline the methods employed, present the results of the
post-hoc matching used to assess the probable effects of selection bias and
using subsequent prosecutions and the accounts of women, compare the
impact of different criminal justice interventions. The results indicate that
twelve months after the criminal justice intervention a significant proportion
of the Programme men had not subsequently been violent to their partner.
This was in contrast to men sanctioned in other ways (the Other CJ
group) who were much less likely to have changed their violent behaviour.
Early manic relapse following lithium discontinuation offers an important opportunity to investigate the relationship between symptoms, effects of treatment and regional brain activation in bipolar affective disorder.
Fourteen stable bipolar patients on lithium were examined with neuropsychological measures, clinical ratings and single photon emission computed tomography (SPECT) before and after acute double-blind withdrawal of lithium. Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric analysis was used to examine the change in brain perfusion on lithium withdrawal, and the relationship between symptom severity and brain perfusion separately both between and within subjects.
Lithium withdrawal was associated with an important redistribution of brain perfusion, with increases in inferior posterior regions and decreases in limbic areas, particularly anterior cingulate cortex. Seven of the 14 patients developed manic symptoms during the placebo phase, correlating with relative increases in perfusion of superior anterior cingulate and possibly left orbito-frontal cortex.
The important effect of lithium withdrawal on brain perfusion implies that after withdrawal of lithium, the brain develops an abnormal state of activity in limbic cortex. The structures involved did not co-localise with those apparently modulated by manic symptoms.
The spontaneous diurnal variation of mood and other symptoms provides a substrate for the examination of the relationship between symptoms and regional brain activation in depression.
Twenty unipolar depressed patients with diurnal variation of mood were examined at 8 a.m. and 8 p.m. with neuropsychological measures, clinical ratings and single photon emission tomography (SPET). Brain perfusion maps were spatially transformed into standard stereotactic space and compared pixel-by-pixel. A parametric (correlational) analysis was used to examine the relationship between symptom severity and brain perfusion, both between and within subjects.
Global depression severity and an independent ‘vital’ depression factor were associated in subjects with increased perfusion in cingulate and other paralimbic areas. In addition there was a probable association between an increase in an anxious-depression factor and reduced frontal neocortical perfusion.
Depressive symptom changes are associated with metabolic changes in the cingulate gyrus and associated paralimbic structures.
Hollow-fibre, laminate-flake and microencapsulated formulations of the synthetic sex pheromone (a 1:1 mixture of (Z, Z)- and (Z, E)-7, 11-hexadecadienyl acetate) of Pectinophora gossypiella (Saunders) were compared in large-scale mating disruption trials in Egypt in 1982. Fifty-hectare blocks of cotton were treated at regular intervals throughout the season with the formulated pheromone as the sole means of controlling the pest. The pheromone treatments were compared with conventional insecticide spray treatments in other 50-ha blocks of cotton sited in the same localities. Comparisons of numbers of infested flowers and green boils, open boll counts, crop development, yield of seed cotton, lint quality and seed damage in pheromone-and insecticide-treated blocks, showed that adequate levels of control were achieved using the pheromone formulations, which were equal in effect to the insecticide sprays. Beneficial insects were found in greater numbers in the pheromone-treated areas than in areas treated with insecticides.