To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Little is known about the prevalence of mental health outcomes in UK personnel at the end of the British involvement in the Iraq and Afghanistan conflicts.
We examined the prevalence of mental disorders and alcohol misuse, whether this differed between serving and ex-serving regular personnel and by deployment status.
This is the third phase of a military cohort study (2014–2016; n = 8093). The sample was based on participants from previous phases (2004–2006 and 2007–2009) and a new randomly selected sample of those who had joined the UK armed forces since 2009.
The prevalence was 6.2% for probable post-traumatic stress disorder, 21.9% for common mental disorders and 10.0% for alcohol misuse. Deployment to Iraq or Afghanistan and a combat role during deployment were associated with significantly worse mental health outcomes and alcohol misuse in ex-serving regular personnel but not in currently serving regular personnel.
The findings highlight an increasing prevalence of post-traumatic stress disorder and a lowering prevalence of alcohol misuse compared with our previous findings and stresses the importance of continued surveillance during service and beyond.
Declaration of interest:
All authors are based at King's College London which, for the purpose of this study and other military-related studies, receives funding from the UK Ministry of Defence (MoD). S.A.M.S., M.J., L.H., D.P., S.M. and R.J.R. salaries were totally or partially paid by the UK MoD. The UK MoD provides support to the Academic Department of Military Mental Health, and the salaries of N.J., N.G. and N.T.F. are covered totally or partly by this contribution. D.Mu. is employed by Combat Stress, a national UK charity that provides clinical mental health services to veterans. D.MacM. is the lead consultant for an NHS Veteran Mental Health Service. N.G. is the Royal College of Psychiatrists’ Lead for Military and Veterans’ Health, a trustee of Walking with the Wounded, and an independent director at the Forces in Mind Trust; however, he was not directed by these organisations in any way in relation to his contribution to this paper. N.J. is a full-time member of the armed forces seconded to King's College London. N.T.F. reports grants from the US Department of Defense and the UK MoD, is a trustee (unpaid) of The Warrior Programme and an independent advisor to the Independent Group Advising on the Release of Data (IGARD). S.W. is a trustee (unpaid) of Combat Stress and Honorary Civilian Consultant Advisor in Psychiatry for the British Army (unpaid). S.W. is affiliated to the National Institute for Health Research Health Protection Research Unit (NIHR HPRU) in Emergency Preparedness and Response at King's College London in partnership with Public Health England, in collaboration with the University of East Anglia and Newcastle University. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, the Department of Health, Public Health England or the UK MoD.
A cluster of Salmonella Paratyphi B variant L(+) tartrate(+) infections with indistinguishable pulsed-field gel electrophoresis patterns was detected in October 2015. Interviews initially identified nut butters, kale, kombucha, chia seeds and nutrition bars as common exposures. Epidemiologic, environmental and traceback investigations were conducted. Thirteen ill people infected with the outbreak strain were identified in 10 states with illness onset during 18 July–22 November 2015. Eight of 10 (80%) ill people reported eating Brand A raw sprouted nut butters. Brand A conducted a voluntary recall. Raw sprouted nut butters are a novel outbreak vehicle, though contaminated raw nuts, nut butters and sprouted seeds have all caused outbreaks previously. Firms producing raw sprouted products, including nut butters, should consider a kill step to reduce the risk of contamination. People at greater risk for foodborne illness may wish to consider avoiding raw products containing raw sprouted ingredients.
SNP in the vitamin D receptor (VDR) gene is associated with risk of lower respiratory infections. The influence of genetic variation in the vitamin D pathway resulting in susceptibility to upper respiratory infections (URI) has not been investigated. We evaluated the influence of thirty-three SNP in eleven vitamin D pathway genes (DBP, DHCR7, RXRA, CYP2R1, CYP27B1, CYP24A1, CYP3A4, CYP27A1, LRP2, CUBN and VDR) resulting in URI risk in 725 adults in London, UK, using an additive model with adjustment for potential confounders and correction for multiple comparisons. Significant associations in this cohort were investigated in a validation cohort of 737 children in Manchester, UK. In all, three SNP in VDR (rs4334089, rs11568820 and rs7970314) and one SNP in CYP3A4 (rs2740574) were associated with risk of URI in the discovery cohort after adjusting for potential confounders and correcting for multiple comparisons (adjusted incidence rate ratio per additional minor allele ≥1·15, Pfor trend ≤0·030). This association was replicated for rs4334089 in the validation cohort (Pfor trend=0·048) but not for rs11568820, rs7970314 or rs2740574. Carriage of the minor allele of the rs4334089 SNP in VDR was associated with increased susceptibility to URI in children and adult cohorts in the United Kingdom.
Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88) presented a critique of our recently published paper in Cell Reports entitled ‘Large-Scale Cognitive GWAS Meta-Analysis Reveals Tissue-Specific Neural Expression and Potential Nootropic Drug Targets’ (Lam et al., Cell Reports, Vol. 21, 2017, 2597–2613). Specifically, Hill offered several interrelated comments suggesting potential problems with our use of a new analytic method called Multi-Trait Analysis of GWAS (MTAG) (Turley et al., Nature Genetics, Vol. 50, 2018, 229–237). In this brief article, we respond to each of these concerns. Using empirical data, we conclude that our MTAG results do not suffer from ‘inflation in the FDR [false discovery rate]’, as suggested by Hill (Twin Research and Human Genetics, Vol. 21, 2018, 84–88), and are not ‘more relevant to the genetic contributions to education than they are to the genetic contributions to intelligence’.
Foodborne non-typhoidal salmonellosis causes approximately 1 million illnesses annually in the USA. In April 2015, we investigated a multistate outbreak of 65 Salmonella Paratyphi B variant L(+) tartrate(+) infections associated with frozen raw tuna imported from Indonesia, which was consumed raw in sushi. Forty-six (92%) of 50 case-patients interviewed ate sushi during the week before illness onset, and 44 (98%) of 45 who specified ate sushi containing raw tuna. Two outbreak strains were isolated from the samples of frozen raw tuna. Traceback identified a single importer as a common source of tuna consumed by case-patients; this importer issued three voluntary recalls of tuna sourced from one Indonesian processor. Four Salmonella Weltevreden infections were also linked to this outbreak. Whole-genome sequencing was useful in establishing a link between Salmonella isolated from ill people and tuna. This outbreak highlights the continuing foodborne illness risk associated with raw seafood consumption, the importance of processing seafood in a manner that minimises contamination with pathogenic microorganisms and the continuing need to ensure imported foods are safe to eat. People at higher risk for foodborne illness should not consume undercooked animal products, such as raw seafood.
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.
Zirconolite glass-ceramics are being developed as potential wasteforms for the disposition of Pu wastes in the UK. Previous studies utilised a variety of surrogates whilst this work uses both cold-press and sinter and hot isostatic press methods to validate the wasteform with PuO2. A cold press and sinter sample was fabricated as part of a validation study for plutonium incorporation in hot isostatically pressed (HIPed) wasteforms. The results confirmed the cold-press and sinter, achieved successful waste incorporation and a microstructure and phase assemblage that was in agreement with those expected of a HIPed equivalent. A HIP sample was fabricated of the same composition and characterised by SEM and XRD. Results were in agreement with the sintered sample and achieved complete waste incorporation into the glass-ceramic wasteform. These samples have demonstrated successful incorporation of PuO2 into glass-ceramic HIPed wasteforms proposed for processing Pu-based waste-streams in the UK.
We agree with Lake and colleagues on their list of “key ingredients” for building human-like intelligence, including the idea that model-based reasoning is essential. However, we favor an approach that centers on one additional ingredient: autonomy. In particular, we aim toward agents that can both build and exploit their own internal models, with minimal human hand engineering. We believe an approach centered on autonomous learning has the greatest chance of success as we scale toward real-world complexity, tackling domains for which ready-made formal models are not available. Here, we survey several important examples of the progress that has been made toward building autonomous agents with human-like abilities, and highlight some outstanding challenges.
Observations from basal water-pressure sensors along the length of Bench Glacier, Alaska, USA, show that diurnal fluctuations of water pressure are seasonal and restricted to summer. Most notable about these fluctuations is their disappearance in the late summer and early autumn, long before the seasonal end of diurnal meltwater input. Here we present data documenting the end of diurnal water-pressure fluctuations during the 2002 and 2003 melt seasons. The end of diurnal fluctuations occurred abruptly in multiple boreholes spaced meters to kilometers apart. There was no obvious spatial progression of termination events, and a clear correlation with meteorological forcing or discharge in the outlet stream was not apparent. After diurnal pressure fluctuations ended, basal water pressure returned to a high, generally steady, value either in an irregular pattern or by a distinct increase. This high water pressure was interrupted by episodic, acyclic events throughout the autumn before becoming stable and high in winter.
Observations from along the length of Bench Glacier, Alaska, USA, show that the subglacial water-pressure field undergoes a multiphase transition from a winter mode to a summer mode. Data were collected at the glacier surface, the outlet stream, and in a network of 47 boreholes spanning the length of the 7 km long glacier. The winter pressure field was near overburden, with low-magnitude (centimeter to meter scale) and long-period (days to weeks) variations. During a spring speed-up event, boreholes showed synchronous variations and a slight pressure drop from prior winter values. Diurnal pressure variations followed the speed-up, with their onset associated with a glacier-wide pressure drop and flood at the terminus stream. Diurnal variations with swings of up to 80% of overburden pressure were typical of mid-summer. Several characteristics of our observations contradict common conceptions about the seasonal development of the subglacial drainage system and the linkages between subglacial hydrology and basal sliding: (1) increased water pressure did not accompany high sliding rates; (2) the drainage system showed activity characteristic of the spring season long before abundant water was available on the glacier surface; (3) the onset of both spring activity and diurnal variations of the drainage system did not show a spatial progression along the length of the glacier.
Water levels were measured in boreholes spaced along the entire length of Bench Glacier, Alaska, USA, for a period in excess of 2 years. Instrumented boreholes were arranged as nine pairs along the center line of the glacier and an orthogonal grid of 16 boreholes in a 3600 m2 region at the center of the ablation area. Diurnal fluctuations of the water levels were found to be restricted to the late melt season. Pairs of boreholes spaced along the length of the ablation area often exhibited similar fluctuations and diurnal changes in water levels. Three distinct and independent types of diurnal fluctuations in water level were observed in clusters of boreholes within the grid of boreholes. Head gradients suggest water did not flow between clusters, and a single tunnel connecting the boreholes could not explain the observed pattern of diurnal water-level fluctuations. Inter-borehole and borehole-cluster connectivity suggests the cross-glacier width of influence of a segment of the drainage system connected to a borehole was limited to tens of meters. A drainage configuration whereby boreholes are connected to a somewhat distant tunnel by drainage pipes of differing lengths, often hundreds of meters, is shown with a numerical test to be a plausible explanation for the observed borehole behavior.
Observations of the motion and basal conditions of Worthington Glacier, Alaska, U.S.A., during late-winter and spring melt seasons revealed no evidence of a relationship between water pressure and sliding velocity. Measurements included borehole water levels (used as a proxy for basal water pressure), surface velocity, englacial deformation, sliding velocity, and time-lapse videography of subglacial water flow and bed characteristics. The boreholes were spaced 10–15 m apart; six were instrumented in 1997, and five in 1998. In late winter, the water-pressure field showed spatially synchronous fluctuations with a diurnal cycle. The glacier’s motion was relatively slow and non-cyclic. In spring, the motion was characterized by rapid, diurnally varying sliding. The basal water pressure displayed no diurnal signal, but showed high-magnitude fluctuations and often strong gradients between holes. This transition in character of the basal water-pressure field may represent a seasonal evolution of the drainage system from linked cavities to a network of isolated patches and conduits. These changes occurred as the glacier was undergoing a seasonal-velocity peak. The apparent lack of correlation between sliding velocity and water pressure suggests that local-scale water pressure does not directly control sliding during late winter or early in the melt season.
Academic health systems and their investigators are challenged to systematically assure clinical research regulatory compliance. This challenge is heightened in the emerging era of centralized single Institutional Review Boards for multicenter studies, which rely on monitoring programs at each participating site.
To describe the development, implementation, and outcome measurement of an institution-wide paired training curriculum and internal monitoring program for clinical research regulatory compliance.
Standard operating procedures (SOPs) were developed to facilitate investigator and research professional adherence to institutional policies, federal guidelines, and international standards. An SOP training curriculum was developed and implemented institution-wide. An internal monitoring program was launched, utilizing risk-based monitoring plans of pre-specified frequency and intensity, assessed upon Institutional Review Boards approval of each prospective study. Monitoring plans were executed according to an additional SOP on internal monitoring, with monitoring findings captured in a REDCap database.
We observed few major violations across 3 key domains of clinical research conduct and demonstrated a meaningful decrease in the rates of nonmajor violations in each, over the course of 2 years.
The paired training curriculum and monitoring program is a successful institution-wide clinical research regulatory compliance model that will continue to be refined.
Englacial and basal temperature data for the Greenland ice sheet (GrIS) are sparse and mostly limited to deep interior sites and ice streams, providing an incomplete representation of the thermal state of ice within the ablation zone. Here we present 11 temperature profiles at five sites along a 34 km east–west transect of West Greenland. These profiles depict ice temperatures along a flowline and local temperature variations between closely spaced boreholes. A temperate basal layer is present in all profiles, increasing in thickness in the flow direction, where it expands from ∼3% of ice height furthest inland to 100% at the margin. Temperate thickness growth is inconsistent with modeled heat contributions from strain heating, heat conduction, and vertical extension of the temperate layer. We suggest that basal crevassing, facilitated by water pressures at or near ice overburden pressure, is responsible for the large temperate ice thicknesses observed. High-temperature kinks at 51–85 m depth are likely remnants from the thermal influence of partially water-filled crevasses up ice sheet. Steep horizontal temperature gradients between closely grouped boreholes suggest the recent thermal influence of a moulin. These profiles demonstrate the ability of meltwater to rapidly alter ice temperatures at all depths within the ablation zone.