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In 2011 the Incidence Assay Critical Path Working Group reviewed the current state of HIV incidence assays and helped to determine a critical path to the introduction of an HIV incidence assay. At that time the Consortium for Evaluation and Performance of HIV Incidence Assays (CEPHIA) was formed to spur progress and raise standards among assay developers, scientists and laboratories involved in HIV incidence measurement and to structure and conduct a direct independent comparative evaluation of the performance of 10 existing HIV incidence assays, to be considered singly and in combinations as recent infection test algorithms. In this paper we report on a new framework for HIV incidence assay evaluation that has emerged from this effort over the past 5 years, which includes a preliminary target product profile for an incidence assay, a consensus around key performance metrics along with analytical tools and deployment of a standardized approach for incidence assay evaluation. The specimen panels for this evaluation have been collected in large volumes, characterized using a novel approach for infection dating rules and assembled into panels designed to assess the impact of important sources of measurement error with incidence assays such as viral subtype, elite host control of viraemia and antiretroviral treatment. We present the specific rationale for several of these innovations, and discuss important resources for assay developers and researchers that have recently become available. Finally, we summarize the key remaining steps on the path to development and implementation of reliable assays for monitoring HIV incidence at a population level.
There are no existing longitudinal studies of inflammatory markers and atopic disorders in childhood and risk of hypomanic symptoms in adulthood. This study examined if childhood: (1) serum interleukin-6 (IL-6) and C-reactive protein (CRP); and (2) asthma and/or eczema are associated with features of hypomania in young adulthood.
Participants in the Avon Longitudinal Study of Parents and Children, a prospective general population UK birth cohort, had non-fasting blood samples for IL-6 and CRP measurement at the age of 9 years (n = 4645), and parents answered a question about doctor-diagnosed atopic illness before the age of 10 years (n = 7809). These participants completed the Hypomania Checklist at age 22 years (n = 3361).
After adjusting for age, sex, ethnicity, socio-economic status, past psychological and behavioural problems, body mass index and maternal postnatal depression, participants in the top third of IL-6 values at 9 years, compared with the bottom third, had an increased risk of hypomanic symptoms by age 22 years [adjusted odds ratio 1.77, 95% confidence interval (CI) 1.10–2.85, p < 0.001]. Higher IL-6 levels in childhood were associated with adult hypomania features in a dose–response fashion. After further adjustment for depression at the age of 18 years this association remained (adjusted odds ratio 1.70, 95% CI 1.03–2.81, p = 0.038). There was no evidence of an association of hypomanic symptoms with CRP levels, asthma or eczema in childhood.
Higher levels of systemic inflammatory marker IL-6 in childhood were associated with hypomanic symptoms in young adulthood, suggesting that inflammation may play a role in the pathophysiology of mania. Inflammatory pathways may be suitable targets for the prevention and intervention for bipolar disorder.
A post-authorisation safety study was carried out as part of the EU Risk Management Plan to examine the long-term (up to 12 months) use of quetiapine XL as prescribed in general practice in England.
To present a description of the drug utilisation characteristics of quetiapine XL.
An observational, population-based cohort design using the technique of Modified Prescription-Event Monitoring (M-PEM). Patients were identified from dispensed prescriptions issued by general practitioners (GPs) for quetiapine XL between September 2008 and February 2013. Questionnaires were sent to GPs 12 months following the 1st prescription for each individual patient, requesting drug utilisation information. Cohort accrual was extended to recruit additional elderly patients (special population of interest). Summary descriptive statistics were calculated.
The final M-PEM cohort consisted of 13,276 patients; median age 43 years (IQR: 33, 55) and 59.0% females. Indications for prescribing included bipolar disorder (n = 3820), MDD (n = 2844), schizophrenia (n = 2373) and other (non-licensed) indications (n = 3750). Where specified, 59.3% (7869/13,276) were reported to have used quetiapine IR (immediate release formulation) previously at any time. The median start dose was highest for patients with schizophrenia (300 mg/day [IQR 150, 450]). The final elderly cohort consisted of 3127 patients and 28.5% had indications associated with dementia. The median start dose for elderly patients was highest for patients with schizophrenia or BD (both 100 mg/day [IQR 50, 300]).
The prevalence of off-label prescribing in terms of indication and high doses was common, as was use in special populations such as the very elderly. Whilst off-label use may be unavoidable in certain situations, GPs may need to re-evaluate prescribing in circumstances where there may be safety concerns. This study demonstrates the ongoing importance of observational studies such as M-PEM to gather real-world clinical data to support the post-marketing benefit:risk management of new medications, or existing medications for which license extensions have been approved.
Cardiovascular risk prediction tools are important for cardiovascular disease (CVD) prevention, however, which algorithms are appropriate for people with severe mental illness (SMI) is unclear.
To determine the cost-effectiveness using the net monetary benefit (NMB) approach of two bespoke SMI-specific risk algorithms compared to standard risk algorithms for primary CVD prevention in those with SMI, from an NHS perspective.
A microsimulation model was populated with 1000 individuals with SMI from The Health Improvement Network Database, aged 30–74 years without CVD. Four cardiovascular risk algorithms were assessed; (1) general population lipid, (2) general population BMI, (3) SMI-specific lipid and (4) SMI-specific BMI, compared against no algorithm. At baseline, each cardiovascular risk algorithm was applied and those high-risk (> 10%) were assumed to be prescribed statin therapy, others received usual care. Individuals entered the model in a ‘healthy’ free of CVD health state and with each year could retain their current health state, have cardiovascular events (non-fatal/fatal) or die from other causes according to transition probabilities.
The SMI-specific BMI and general population lipid algorithms had the highest NMB of the four algorithms resulting in 12 additional QALYs and a cost saving of approximately £37,000 (US$ 58,000) per 1000 patients with SMI over 10 years.
The general population lipid and SMI-specific BMI algorithms performed equally well. The ease and acceptability of use of a SMI-specific BMI algorithm (blood tests not required) makes it an attractive algorithm to implement in clinical settings.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The holotype partial skull of Agorophius pygmaeus (the monotypic form for both the genus Agorophius and the Family Agorophiidae) has been missing for approximately 140 years. Since the discovery of Agorophius pygmaeus, many additional taxa and specimens have been placed in the Family Agorophiidae, only to be reclassified and removed later. This has created confusion as to what is and what is not an agorophiid and a lack of clarity as to what characteristics delimit the Agorophiidae. A newly discovered skull of an agorophiid recently collected from an underwater cliff face of the Ashley River, South Carolina, USA, is assigned to Agorophius pygmaeus. It derives from the base of the Ashley Formation (early Oligocene). The new specimen consists of most of the skull and periotics, which are well preserved and described for the first time in an agorophiid. The new specimen provides an opportunity to diagnose the Agorophiidae and place the genus and species within the phylogenetic context of the early odontocete radiation in the Oligocene, along with other taxa such as the Ashleycetidae, Mirocetidae, Patriocetidae, Simocetidae, Waipatiidae, and Xenorophidae. Based on this new understanding, Agorophiidae are known with certainty only from the early Oligocene of South Carolina, with other undescribed, potential agorophiid specimens from the Oligocene of the North Pacific region (Japan, Mexico, and Washington State).
Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracommunity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are important. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems.
In traditional transit timing variations (TTVs) analysis of multi-planetary systems, the individual TTVs are first derived from transit fitting and later modelled using n-body dynamic simulations to constrain planetary masses. We show that fitting simultaneously the transit light curves with the system dynamics (photo-dynamical model) increases the precision of the TTV measurements and helps constrain the system architecture. We exemplify the advantages of applying this photo-dynamical model to a multi-planetary system found in K2 data very close to 3:2 mean motion resonance, K2-19. In this case the period of the larger TTV variations (libration period) is much longer (>1.5 years) than the duration of the K2 observations (80 days). However, our method allows to detect the short period TTVs produced by the orbital conjunctions between the planets that in turn permits to uniquely characterise the system. Therefore, our method can be used to constrain the masses of near-resonant systems even when the full libration curve is not observed.
Little is known about the relative extent of crime against people with
severe mental illness (SMI).
To assess the prevalence and impact of crime among people with SMI
compared with the general population.
A total of 361 psychiatric patients were interviewed using the national
crime survey questionnaire, and findings compared with those from 3138
general population controls participating in the contemporaneous national
Past-year crime was experienced by 40% of patients v.
14% of controls (adjusted odds ratio (OR) = 2.8, 95% CI 2.0–3.8); and
violent assaults by 19% of patients v. 3% of controls
(adjusted OR = 5.3, 95% CI 3.1–8.8). Women with SMI had four-, ten- and
four-fold increases in the odds of experiencing domestic, community and
sexual violence, respectively. Victims with SMI were more likely to
report psychosocial morbidity following violence than victims from the
People with SMI are at greatly increased risk of crime and associated
morbidity. Violence prevention policies should be particularly focused on
people with SMI.
Domestic and sexual violence are significant public health problems but little is known about the extent to which men and women with severe mental illness (SMI) are at risk compared with the general population. We aimed to compare the prevalence and impact of violence against SMI patients and the general population.
Three hundred and three randomly recruited psychiatric patients, in contact with community services for ⩾1 year, were interviewed using the British Crime Survey domestic/sexual violence questionnaire. Prevalence and correlates of violence in this sample were compared with those from 22 606 general population controls participating in the contemporaneous 2011/12 national crime survey.
Past-year domestic violence was reported by 27% v. 9% of SMI and control women, respectively [odds ratio (OR) adjusted for socio-demographics, aOR 2.7, 95% confidence interval (CI) 1.7–4.0], and by 13% v. 5% of SMI and control men, respectively (aOR 1.6, 95% CI 1.0–2.8). Past-year sexual violence was reported by 10% v. 2.0% of SMI and control women respectively (aOR 2.9, 95% CI 1.4–5.8). Family (non-partner) violence comprised a greater proportion of overall domestic violence among SMI than control victims (63% v. 35%, p < 0.01). Adulthood serious sexual assault led to attempted suicide more often among SMI than control female victims (53% v. 3.4%, p < 0.001).
Compared to the general population, patients with SMI are at substantially increased risk of domestic and sexual violence, with a relative excess of family violence and adverse health impact following victimization. Psychiatric services, and public health and criminal justice policies, need to address domestic and sexual violence in this at-risk group.
A 2009 oceanographic expedition of the Russian Academy of Sciences collected the anterior region of a single acorn worm (phylum Hemichordata, class Enteropneusta) by trawling at a depth of 5560 m in the Romanche Trench (equatorial Atlantic). The specimen was a ripe female with numerous, relatively small oocytes in each ovary. Phylogenetic analysis of rDNA sequences robustly placed the worm in the family Spengelidae. In addition, morphological features of the proboscis, collar, and anterior trunk region indicated that the worm was Glandiceps abyssicola, a species previously represented solely by the holotype, which had been dredged from the equatorial Atlantic in 1873 by the HMS ‘Challenger’ and subsequently sent to Germany for description by Spengel (1893). The holotype was presumably destroyed by World War II bombing; therefore, we here designate the Romanche Trench specimen as the neotype of G. abyssicola and supply an augmented species diagnosis.
Thirty pyrite samples from a wide range of localities were analysed using relative comparator and k0 neutron activation analysis (NAA) techniques at the University of Missouri Research Reactor, Columbia, Missouri, USA (MURR) and the Australian Nuclear Science and Technology Organisation, Lucas Heights, NSW, Australia (ANSTO), respectively. Statistical analyses of the trace-element data produced by the two methods showed a generally good correlation, with the majority of elemental concentrations of paired data reported by MURR and ANSTO being indistinguishable at a 0.05 significance level. Trace-element analyses of pyrite from Navajún in Spain by both techniques compare well with published data. There is evidence for contamination by Al, Na and Ti in one set of samples, this is likely to have been introduced by contact with a plastic used in sample preparation.
Standard acute psychiatric care in the UK is costly but problematic. Alternatives to standard in-patient wards exist, but little is known about their effectiveness, implementation and sustainability. This paper explores successful features and limitations of five residential alternative services in England and factors that facilitate or impede their initial and sustained implementation and success.
Semi-structured interviews about the functioning of six alternative services were conducted with 36 mental health professionals with good working knowledge of, and various connections with these services. A group interview with study researchers was also conducted. Data were analysed using thematic analysis.
One service did not show evidence of operating as an alternative and was excluded from further analysis. The remaining five alternatives are valued for providing a more holistic style of care than standard services that confers many perceived benefits. However, they are seen as less appropriate for compulsorily detained or highly disturbed patients, and as providing less comprehensive treatment packages than hospital settings. Factors identified as important to successful implementation and sustainability are: responding to known shortcomings in local acute care systems; balancing role clarity and adaptability; integration with other services; and awareness of the alternative among relevant local health-care providers.
Residential alternatives can play an important role in managing mental health crises. Their successful implementation and endurance depend on establishing and maintaining a valued position within local service systems. Findings contribute to bridging the gap between research evidence on the problems of standard acute care and delivering improved crisis management services.