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The Murchison Widefield Array (MWA) is an open access telescope dedicated to studying the low-frequency (80–300 MHz) southern sky. Since beginning operations in mid-2013, the MWA has opened a new observational window in the southern hemisphere enabling many science areas. The driving science objectives of the original design were to observe 21 cm radiation from the Epoch of Reionisation (EoR), explore the radio time domain, perform Galactic and extragalactic surveys, and monitor solar, heliospheric, and ionospheric phenomena. All together
programs recorded 20 000 h producing 146 papers to date. In 2016, the telescope underwent a major upgrade resulting in alternating compact and extended configurations. Other upgrades, including digital back-ends and a rapid-response triggering system, have been developed since the original array was commissioned. In this paper, we review the major results from the prior operation of the MWA and then discuss the new science paths enabled by the improved capabilities. We group these science opportunities by the four original science themes but also include ideas for directions outside these categories.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Laboratory identification of carbapenem-resistant Enterobacteriaceae (CRE) is a key step in controlling its spread. Our survey showed that most Veterans Affairs laboratories follow VA guidelines for initial CRE identification, whereas 55.0% use PCR to confirm carbapenemase production. Most respondents were knowledgeable about CRE guidelines. Barriers included staffing, training, and financial resources.
The parent-child relationship undergoes substantial reorganization over the transition to adolescence. Navigating this change is a challenge for parents because teens desire more behavioral autonomy as well as input in decision-making processes. Although it has been demonstrated that changes in parental socialization approaches facilitates adolescent adjustment, very little work has been devoted to understanding the underlying mechanisms supporting parents’ abilities to adjust caregiving during this period. Guided by self-regulation models of parenting, the present study examined how parental physiological and cognitive regulatory capacities were associated with hostile and insensitive parent conflict behavior over time. From a process-oriented perspective, we tested the explanatory role of parents’ dysfunctional child-oriented attributions in this association. A sample of 193 fathers, mothers, and their early adolescent (ages 12–14) participated in laboratory-based research assessments spaced approximately 1 year apart. Parental physiological regulation was measured using square root of the mean of successive differences during a conflict task; cognitive regulation was indicated by set-shifting capacity. Results showed that parental difficulties in vagal regulation during parent-adolescent conflict were associated with increased hostile conflict behavior over time; however, greater set-shifting capacity moderated this association for fathers only. In turn, father's dysfunctional attributions regarding adolescent behavior mediated the moderating effect. The results highlight how models of self-regulation and social cognition may explain the determinants of hostile parenting with differential implications for fathers during adolescence.
Shunt-related adverse events are frequent in infants after modified Blalock–Taussig despite use of acetylsalicylic acid prophylaxis. A higher incidence of acetylsalicylic acid-resistance and sub-therapeutic acetylsalicylic acid levels has been reported in infants. We evaluated whether using high-dose acetylsalicylic acid can decrease shunt-related adverse events in infants after modified Blalock–Taussig.
In this single-centre retrospective cohort study, we included infants ⩽1-year-old who underwent modified Blalock–Taussig placement and received acetylsalicylic acid in the ICU. We defined acetylsalicylic acid treatment groups as standard dose (⩽7 mg/kg/day) and high dose (⩾8 mg/kg/day) based on the initiating dose.
There were 34 infants in each group. Both groups were similar in age, gender, cardiac defect type, ICU length of stay, and time interval to second stage or definitive repair. Shunt interventions (18 versus 32%, p=0.16), shunt thrombosis (14 versus 17%, p=0.74), and mortality (9 versus 12%, p=0.65) were not significantly different between groups. On multiple logistic regression analysis, single-ventricle morphology (odds ratio 5.2, 95% confidence interval of 1.2–23, p=0.03) and post-operative red blood cells transfusion ⩾24 hours [odds ratio 15, confidence interval of (3–71), p<0.01] were associated with shunt-related adverse events. High-dose acetylsalicylic acid treatment [odds ratio 2.6, confidence interval of (0.7–10), p=0.16] was not associated with decrease in these events.
High-dose acetylsalicylic acid may not be sufficient in reducing shunt-related adverse events in infants after modified Blalock–Taussig. Post-operative red blood cells transfusion may be a modifiable risk factor for these events. A randomised trial is needed to determine appropriate acetylsalicylic acid dosing in infants with modified Blalock–Taussig.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
Studies involving clinically recruited samples show that genetic liability to schizophrenia overlaps with that for several psychiatric disorders including bipolar disorder, major depression and, in a population study, anxiety disorder and negative symptoms in adolescence.
We examined whether, at a population level, association between schizophrenia liability and anxiety disorders continues into adulthood, for specific anxiety disorders and as a group. We explored in an epidemiologically based cohort the nature of adult psychopathology sharing liability to schizophrenia.
Schizophrenia polygenic risk scores (PRSs) were calculated for 590 European-descent individuals from the Christchurch Health and Development Study. Logistic regression was used to examine associations between schizophrenia PRS and four anxiety disorders (social phobia, specific phobia, panic disorder and generalised anxiety disorder), schizophrenia/schizophreniform disorder, manic/hypomanic episode, alcohol dependence, major depression, and – using linear regression – total number of anxiety disorders. A novel population-level association with hypomania was tested in a UK birth cohort (Avon Longitudinal Study of Parents and Children).
Schizophrenia PRS was associated with total number of anxiety disorders and with generalised anxiety disorder and panic disorder. We show a novel population-level association between schizophrenia PRS and manic/hypomanic episode.
The relationship between schizophrenia liability and anxiety disorders is not restricted to psychopathology in adolescence but is present in adulthood and specifically linked to generalised anxiety disorder and panic disorder. We suggest that the association between schizophrenia liability and hypomanic/manic episodes found in clinical samples may not be due to bias.
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.
Globally, the prevalence of tuberculosis (TB) disease is higher in males. This study examined the effect of sex and age on Mycobacterium tuberculosis (Mtb) infection. Demographic and exposure data were collected on household contacts of sputum smear-positive pulmonary TB patients in Brazil. Contacts with tuberculin skin test induration ⩾10 mm at baseline or 12 weeks were considered Mtb infected. The study enrolled 917 household contacts from 160 households; 508 (55.4%) were female, median age was 21.0 years (range 0.30–87.0) and 609 (66.4%) had Mtb infection. The proportion infected increased with age from 63.3% in girls <5 years to 75.4% in women ⩾40 years and from 44.9% in boys <5 years to 73.6% in men ⩾40 years. Multivariable modelling showed the odds of infection increased between age 5 and 14 years among female contacts (OR 1.5 per 5-year age increase; 95% CI 1.1–2.2; P = 0.02) and between ages 0–4 and 15–39 years among male contacts (OR 2.7, 95% CI 0.83–8.9 and 1.1, 95% CI 0.99–1.3 per 5-year age increase; P = 0.10, 0.07, respectively). The study suggests that the age at which Mtb infection increases most is different in females compared with males. Studies are needed to explore whether these findings are due to differences in host susceptibility, exposure outside the household or other factors.
Brain tumor behavior is driven by aberrations in the genome and epigenome. Many of these changes, such as IDH mutations in diffuse low-grade glioma (DLGG), are common amongst the same class of tumour and can be incorporated into the diagnostic criteria. However, any given tumor may have other, less common genomic aberrations that are essential for its biological behavior and may inform on underlying aberrant cellular pathways, and potential therapeutic agents. Precision oncology is a genomics-based approach which profiles these alterations to better manage cancer patients and has established itself within the practice of oncology and is slowly making its way into neuro-oncology. The BC Cancer’s Personalized OncoGenomics (POG) program has profiled 16 adult tumours originating from the central nervous system using whole genome and transcriptome analysis (WGTA), for the first time, within a meaningful clinical timeframe/setting. As expected, primary genomic drivers were consistent with their respective diagnoses, though secondary drivers were found to be unique to each tumour. Although these analyses did not result in altered clinical management for these patients, primarily due to availability of drug or clinical trials, they highlight the heterogeneity of secondary drivers in cancers and provide clinicians with meaningful biological information. Lastly, the data generated by POG has highlighted the frequency and complexity of novel driver fusions which are predicted to behave similarly to canonical driver events in their respective tumours. The information available to clinicians through POG has provided paramount knowledge into the biology of each unique tumour.
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.
To understand increasing rates of hepatitis C virus (HCV) infection in Tennessee, we conducted testing, risk factor analysis and a nested case–control study among persons who use drugs. During June–October 2016, HCV testing with risk factor assessment was conducted in sexually transmitted disease clinics, family planning clinics and an addiction treatment facility in eastern Tennessee; data were analysed by using multivariable logistic regression. A nested case–control study was conducted to assess drug-using risks and behaviours among persons who reported intranasal or injection drug use (IDU). Of 4753 persons tested, 397 (8.4%) were HCV-antibody positive. HCV infection was significantly associated with a history of both intranasal and IDU (adjusted odds ratio (aOR) 35.4, 95% confidence interval (CI) 24.1–51.9), IDU alone (aOR 52.7, CI 25.3–109.9), intranasal drug use alone (aOR 2.6, CI 1.8–3.9) and incarceration (aOR 2.7, CI 2.0–3.8). By 4 October 2016, 574 persons with a reported history of drug use; 63 (11%) were interviewed further. Of 31 persons who used both intranasal and injection drugs, 26 (84%) reported previous intranasal drug use, occurring 1–18 years (median 5.5 years) before their first IDU. Our findings provide evidence that reported IDU, intranasal drug use and incarceration are independent indicators of risk for past or present HCV infection in the study population.
The SPICA mid- and far-infrared telescope will address fundamental issues in our understanding of star formation and ISM physics in galaxies. A particular hallmark of SPICA is the outstanding sensitivity enabled by the cold telescope, optimised detectors, and wide instantaneous bandwidth throughout the mid- and far-infrared. The spectroscopic, imaging, and polarimetric observations that SPICA will be able to collect will help in clarifying the complex physical mechanisms which underlie the baryon cycle of galaxies. In particular, (i) the access to a large suite of atomic and ionic fine-structure lines for large samples of galaxies will shed light on the origin of the observed spread in star-formation rates within and between galaxies, (ii) observations of HD rotational lines (out to ~10 Mpc) and fine structure lines such as [C ii] 158 μm (out to ~100 Mpc) will clarify the main reservoirs of interstellar matter in galaxies, including phases where CO does not emit, (iii) far-infrared spectroscopy of dust and ice features will address uncertainties in the mass and composition of dust in galaxies, and the contributions of supernovae to the interstellar dust budget will be quantified by photometry and monitoring of supernova remnants in nearby galaxies, (iv) observations of far-infrared cooling lines such as [O i] 63 μm from star-forming molecular clouds in our Galaxy will evaluate the importance of shocks to dissipate turbulent energy. The paper concludes with requirements for the telescope and instruments, and recommendations for the observing strategy.
The morphology of englacial drainage networks and their temporal evolution are poorly characterised, particularly within cold ice masses. At present, direct observations of englacial channels are restricted in both spatial and temporal resolution. Through novel use of a terrestrial laser scanning (TLS) system, the interior geometry of an englacial channel in Austre Brøggerbreen, Svalbard, was reconstructed and mapped. Twenty-eight laser scan surveys were conducted in March 2016, capturing the glacier surface around a moulin entrance and the uppermost 122 m reach of the adjoining conduit. The resulting point clouds provide detailed 3-D visualisation of the channel with point accuracy of 6.54 mm, despite low (<60%) overall laser returns as a result of the physical and optical properties of the clean ice, snow, hoar frost and sediment surfaces forming the conduit interior. These point clouds are used to map the conduit morphology, enabling extraction of millimetre-to-centimetre scale geometric measurements. The conduit meanders at a depth of 48 m, with a sinuosity of 2.7, exhibiting teardrop shaped cross-section morphology. This improvement upon traditional surveying techniques demonstrates the potential of TLS as an investigative tool to elucidate the nature of glacier hydrological networks, through reconstruction of channel geometry and wall composition.
Infections caused by multidrug-resistant gram-negative organisms (MDRGNOs) have been increasing every year. The objective of this study was to describe the prevalence of MDRGNOs and factors associated with MDRGNOs in patients with spinal cord injury or disorder (SCI/D).
Retrospective cohort study.
Department of Veterans Affairs (VA) electronic health record data from 142 VA facilities were evaluated for 19,642 patients with SCI/D. Multivariable cluster-adjusted models were fit to identify factors associated with MDRGNO.
Gram-negative (GN) cultures occurred in 44% of patients with SCI/D receiving care at VA facilities, and 11,527 (41.3%) GN cultures had an MDRGNO. The most frequent GN organisms (GNOs) were Escherichia coli (28.5%), Klebsiella pneumoniae (17.0%), and Pseudomonas aeruginosa (16.0%). Two-thirds of GN cultures were from the outpatient setting, where MDRGNO prevalence was 37.6%. Significant geographic variation in the prevalence of MDRGNOs was identified (South, 44.7%; Northeast, 44.3%; West, 36.8%; Midwest, 34.4%). Other factors associated with an MDRGNO were older age, injury characteristics, comorbidities, specimen type, healthcare setting, and healthcare exposure. Black (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.39–1.78) and Hispanic race (OR, 1.58; 95% CI, 1.28–1.95), polymicrobial culture (OR, 2.67; 95% CI, 2.46–2.90), and antibiotic use in the previous 90 days (OR, 1.62; 95% CI, 1.50–1.76) were also associated with having an MDRGNO.
MDRGNOs were common in community and healthcare settings among veterans with SCI/D, with significant geographic variation. Health care and antibiotic exposures were significant factors associated with MDRGNOs. Priority should be given to controlling the spread of MDRGNOs in this special population, including a focus on judicious use of antibiotics.
A range of endophenotypes characterise psychosis, however there has been limited work understanding if and how they are inter-related.
This multi-centre study includes 8754 participants: 2212 people with a psychotic disorder, 1487 unaffected relatives of probands, and 5055 healthy controls. We investigated cognition [digit span (N = 3127), block design (N = 5491), and the Rey Auditory Verbal Learning Test (N = 3543)], electrophysiology [P300 amplitude and latency (N = 1102)], and neuroanatomy [lateral ventricular volume (N = 1721)]. We used linear regression to assess the interrelationships between endophenotypes.
The P300 amplitude and latency were not associated (regression coef. −0.06, 95% CI −0.12 to 0.01, p = 0.060), and P300 amplitude was positively associated with block design (coef. 0.19, 95% CI 0.10–0.28, p < 0.001). There was no evidence of associations between lateral ventricular volume and the other measures (all p > 0.38). All the cognitive endophenotypes were associated with each other in the expected directions (all p < 0.001). Lastly, the relationships between pairs of endophenotypes were consistent in all three participant groups, differing for some of the cognitive pairings only in the strengths of the relationships.
The P300 amplitude and latency are independent endophenotypes; the former indexing spatial visualisation and working memory, and the latter is hypothesised to index basic processing speed. Individuals with psychotic illnesses, their unaffected relatives, and healthy controls all show similar patterns of associations between endophenotypes, endorsing the theory of a continuum of psychosis liability across the population.