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Surveillance for acute flaccid paralysis (AFP) cases are essential for polio eradication. However, as most poliovirus infections are asymptomatic and some regions of the world are inaccessible, additional surveillance tools require development. Within England and Wales, we demonstrate how inclusion of environmental sampling (ENV) improves the sensitivity of detecting both wild and vaccine-derived polioviruses (VDPVs) when compared to current surveillance. Statistical modelling was used to estimate the spatial risk of wild and VDPV importation and circulation in England and Wales. We estimate the sensitivity of each surveillance mode to detect poliovirus and the probability of being free from poliovirus, defined as being below a pre-specified prevalence of infection. Poliovirus risk was higher within local authorities in Manchester, Birmingham, Bradford and London. The sensitivity of detecting wild poliovirus within a given month using AFP and enterovirus surveillance was estimated to be 0.096 (95% CI 0.055–0.134). Inclusion of ENV in the three highest risk local authorities and a site in London increased surveillance sensitivity to 0.192 (95% CI 0.191–0.193). The sensitivity of ENV strategies can be compared using the framework by varying sites and the frequency of sampling. The probability of being free from poliovirus slowly increased from the date of the last case in 1993. ENV within areas thought to have the highest risk improves detection of poliovirus, and has the potential to improve confidence in the polio-free status of England and Wales and detect VDPVs.
With one in ten young people being affected by ill mental health and stigma regularly cited as a factor affecting access to early intervention services, focussing resources on school based stigma reduction strategies seems prudent. ‘Headucate’, a student society, designed a 50 minute workshop which aims to increase mental health literacy and decrease stigma.
Repeated, cross sectional surveys were carried out at three time points; 1) immediately before (n=77), 2) Immediately after (n=81) and 3) three months post workshop (n=73). The surveys were paper based versions of the Reported Intended Behaviours Score (RIBS) and Mental Health Knowledge Scale (MAKS) utilising a social distance scale.
Four year 10 classed (pupils aged 14-15) were recruited. Post hoc t-tests were carried out when one-way ANOVAS were significant.
Disorder knowledge (from MAKS) and intended contact (from RIBS) significantly increased between time points one and two (p<0.01 and <0.004 respectively) but then decreased.
Analysis of the question pertaining to knowing where to access help showed a statistically significant increase (p<0.001) between time points one and two and then a decrease at time three, albeit to a higher value than at time point one (3.45 compared to 3.13, P=0.088).
Headucate workshops offer a low resource option which is well accepted by students. Like other school based stigma reduction strategies, a dramatic increase was seen between immediately before and after indicating that the workshop resonates with the pupils, but there was little sustained change in attitudes.
CACNA1I (hCaV3.3) encodes the α1 pore-forming subunit of human voltage-gated T-type calcium channels. CaV3.3 is expressed in a limited subset of neurons including GABAergic neurons of the thalamic reticular nucleus (TRN) where they support oscillatory activity essential for sleep spindle generation. CACNA1I is implicated in schizophrenia risk by emerging genetics including genome-wide association studies (PGC, 2014), and exome sequencing of trio samples (Gulsuner et al., 2013). In order to understand the impact of disease-associated sequence variation on the function of CaV3.3, we set out to analyze a complete set of rare mis-sense coding variations in CACNA1I in a Swedish cohort, including 15 variations identified in patients, 20 identified in control subjects, and 23 in both. We established a heterologous expression system of isogenic cell lines, each carrying single-copy inducible cDNA variants of hCaV3.3, and evaluated their functional impact on channel function by electrophysiology, calcium imaging, and biochemistry. We found at least five coding variations impaired overall channel protein abundance, as well as whole cell current density. In addition, we identified hCaV3.3 variants with altered voltage-dependence of channel activation and inactivation. Overall, we found that reduced calcium influx through hCaV3.3 is associated with the group of variants identified in patients, compared to those in both patients and controls. Our findings suggest that patient-specific rare variations of CACNA1I may influence channel-dependent functions, including rebound bursting in TRN neurons, with potential implications for schizophrenia pathophysiology.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Surgical site infections (SSIs) are among the most common healthcare-associated infections in low- and middle-income countries. To encourage establishment of actionable and standardized SSI surveillance in these countries, we propose simplified surveillance case definitions. Here, we use NHSN reports to explore concordance of these simplified definitions to NHSN as ‘reference standard.’
Yukon Territory (YT) is a remote region in northern Canada with ongoing spread of tuberculosis (TB). To explore the utility of whole genome sequencing (WGS) for TB surveillance and monitoring in a setting with detailed contact tracing and interview data, we used a mixed-methods approach. Our analysis included all culture-confirmed cases in YT (2005–2014) and incorporated data from 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) genotyping, WGS and contact tracing. We compared field-based (contact investigation (CI) data + MIRU-VNTR) and genomic-based (WGS + MIRU-VNTR + basic case data) investigations to identify the most likely source of each person's TB and assessed the knowledge, attitudes and practices of programme personnel around genotyping and genomics using online, multiple-choice surveys (n = 4) and an in-person group interview (n = 5). Field- and genomics-based approaches agreed for 26 of 32 (81%) cases on likely location of TB acquisition. There was less agreement in the identification of specific source cases (13/22 or 59% of cases). Single-locus MIRU-VNTR variants and limited genetic diversity complicated the analysis. Qualitative data indicated that participants viewed genomic epidemiology as a useful tool to streamline investigations, particularly in differentiating latent TB reactivation from the recent transmission. Based on this, genomic data could be used to enhance CIs, focus resources, target interventions and aid in TB programme evaluation.
Non-invasive prenatal testing (NIPT) for the detection of foetal aneuploidy through analysis of cell-free DNA (cfDNA) in maternal blood is offered routinely by many healthcare providers across the developed world. This testing has recently been recommended for evaluative implementation in the UK National Health Service (NHS) foetal anomaly screening pathway as a contingent screen following an increased risk of trisomy 21, 18 or 13. In preparation for delivering a national service, we have implemented cfDNA-based NIPT in our Regional Genetics Laboratory. Here, we describe our validation and verification processes and initial experiences of the technology prior to rollout of a national screening service.
Data are presented from more than 1000 patients (215 retrospective and 840 prospective) from ‘high- and low-risk pregnancies’ with outcome data following birth or confirmatory invasive prenatal sampling. NIPT was by the Illumina Verifi® test.
Our data confirm a high-fidelity service with a failure rate of ~0.24% and a high sensitivity and specificity for the detection of foetal trisomy 13, 18 and 21. Secondly, the data show that a significant proportion of patients continue their pregnancies without prenatal invasive testing or intervention after receiving a high-risk cfDNA-based result. A total of 46.5% of patients referred to date were referred for reasons other than high screen risk. Ten percent (76/840 clinical service referrals) of patients were referred with ultrasonographic finding of a foetal structural anomaly, and data analysis indicates high- and low-risk scan indications for NIPT.
NIPT can be successfully implemented into NHS regional genetics laboratories to provide high-quality services. NHS provision of NIPT in patients with high-risk screen results will allow for a reduction of invasive testing and partially improve equality of access to cfDNA-based NIPT in the pregnant population. Patients at low risk for a classic trisomy or with other clinical indications are likely to continue to access cfDNA-based NIPT as a private test.
Consanguineous marriages potentially play an important role in the transmission of β-thalassaemia in many communities. This study aimed to determine the rate and socio-demographic associations of consanguineous marriages and to assess the influence on the prevalence of β-thalassaemia in Sri Lanka. Three marriage registrars from each district of Sri Lanka were randomly selected to prospectively collect data on all couples who registered their marriage during a 6-month period starting 1st July 2009. Separately, the parents of patients with β-thalassaemia were interviewed to identify consanguinity. A total of 5255 marriages were recorded from 22 districts. The average age at marriage was 27.3 (±6.1) years for males and 24.1 (±5.7) years for females. A majority (71%) of marriages were ‘love’ marriages, except in the Moor community where 84% were ‘arranged’ marriages. Overall, the national consanguinity rate was 7.4%. It was significantly higher among ethnic Tamils (22.4%) compared with Sinhalese (3.8%) and Moors (3.2%) (p < 0.001). Consanguinity rates were also higher in ‘arranged’ as opposed to ‘love’ marriages (11.7% vs 5.6%, p < 0.001). In patients with β-thalassaemia, the overall consanguinity rate was 14.5%; it was highest among Tamils (44%) and lowest among Sinhalese (12%). Parental consanguinity among patients with β-thalassaemia was double the national average. Although consanguinity is not the major factor in the transmission of the disease in the country, emphasis should be given to this significant practice when conducting β-thalassaemia prevention and awareness campaigns, especially in high-prevalence communities.
Our ability to reliably use radiocarbon (14C) dates of mollusk shells to estimate calendar ages may depend on the feeding preference and habitat of a particular species and the geology of the region. Gastropods that feed by scraping are prone to incorporation of carbon from the substrate into their shells as evidenced by studies comparing the radiocarbon dates of shells and flesh from different species on different substrates (Dye 1994; Hogg et al. 1998). Limpet shells (Patella sp.) are commonly found in prehistoric midden deposits in the British Isles and elsewhere, however these shells have largely been avoided for radiocarbon dating in regions of limestone outcrops. Results from limpets (Patella vulgata) collected alive on limestone and volcanic substrates on the coasts of Ireland indicate that the shells were formed in equilibrium with the seawater, with no significant 14C offsets. Limpets collected from the east coast of Northern Ireland have elevated 14C due to the output of Sellafield nuclear fuel reprocessing plant. In all locations, the flesh was depleted in 14C compared to the shells. The results will have an important consequence for radiocarbon dating of midden deposits as well as the bone of humans and animals who fed on the limpets.
Additional crystallographic data are given for the recently reported mineral middlebackite, which has been described for discoveries at Iron Knob in South Australia and Passo di San Lugano near Trento, Italy. The material examined in the present study was from a third finding of the mineral, viz. from a quartz outcrop at Mooloo Downs Station in Western Australia within which it was co-located with the chemically- and structurally-related mineral moolooite, CuIIC2O4·nH2O, reported by Clarke and Williams (1986). In this study, the crystal structure was elucidated independently of the other studies using a combination of the a priori charge flipping and simulated annealing methods with synchrotron radiation diffraction (SRD) powder data. The principal crystal data for the Mooloo Downs material are: space group P21/c with lattice parameters a = 7.2659(18) Å, b = 5.7460(11) Å, c = 5.6806(11) Å, β = 104.588(3)°; Vc = 229.46(18) Å3; empirical formula CuII2C2O4(OH)2 with 2 formula units per unit cell; and calculated density = 3.605 g cm−3. The lattice parameters agree approximately with values given for the other studies, but not within the reported error estimates. The atom coordinates, interatomic distances, and angles for the Mooloo Downs material are compared with those from the other studies using single crystal data, with the values from all three studies agreeing approximately, but again not within the reported uncertainties. The crystal chemistry found for middlebackite received strong confirmation through the synthesis for the first time of di-copper oxalate di-hydroxide. Laboratory X-ray diffraction powder data for the synthetic form of the mineral from this study agree closely with the SRD data for the natural mineral.
To define optimal thromboprophylaxis strategy after stent implantation in superior or total cavopulmonary connections.
Stent thrombosis is a rare complication of intravascular stenting, with a perceived higher risk in single-ventricle patients.
All patients who underwent stent implantation within superior or total cavopulmonary connections (caval vein, innominate vein, Fontan, or branch pulmonary arteries) were included. Cohort was divided into aspirin therapy alone versus advanced anticoagulation, including warfarin, enoxaparin, heparin, or clopidogrel. Primary endpoint was in-stent or downstream thrombus, and secondary endpoints included bleeding complications.
A total of 58 patients with single-ventricle circulation underwent 72 stent implantations. Of them 14 stents (19%) were implanted post-superior cavopulmonary connection and 58 (81%) post-total cavopulmonary connection. Indications for stenting included vessel/conduit stenosis (67%), external compression (18%), and thrombotic occlusion (15%). Advanced anticoagulation was prescribed for 32 (44%) patients and aspirin for 40 (56%) patients. Median follow up was 1.1 (25th–75th percentile, 0.5–2.6) years. Echocardiograms were available in 71 patients (99%), and advanced imaging in 44 patients (61%). Thrombosis was present in two patients on advanced anticoagulation (6.3%) and none noted in patients on aspirin (p = 0.187). Both patients with in-stent thrombus underwent initial stenting due to occlusive left pulmonary artery thrombus acutely post-superior cavopulmonary connection. There were seven (22%) significant bleeding complications for advanced anticoagulation and none for aspirin (p < 0.001).
Antithrombotic strategy does not appear to affect rates of in-stent thrombus in single-ventricle circulations. Aspirin alone may be sufficient for most patients undergoing stent implantation, while pre-existing thrombus may warrant advanced anticoagulation.
Few studies have used genomic epidemiology to understand tuberculosis (TB) transmission in rural and remote settings – regions often unique in history, geography and demographics. To improve our understanding of TB transmission dynamics in Yukon Territory (YT), a circumpolar Canadian territory, we conducted a retrospective analysis in which we combined epidemiological data collected through routine contact investigations with clinical and laboratory results. Mycobacterium tuberculosis isolates from all culture-confirmed TB cases in YT (2005–2014) were genotyped using 24-locus Mycobacterial Interspersed Repetitive Units-Variable Number of Tandem Repeats (MIRU-VNTR) and compared to each other and to those from the neighbouring province of British Columbia (BC). Whole genome sequencing (WGS) of genotypically clustered isolates revealed three sustained transmission networks within YT, two of which also involved BC isolates. While each network had distinct characteristics, all had at least one individual acting as the probable source of three or more culture-positive cases. Overall, WGS revealed that TB transmission dynamics in YT are distinct from patterns of spread in other, more remote Northern Canadian regions, and that the combination of WGS and epidemiological data can provide actionable information to local public health teams.
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.
The development of laser wakefield accelerators (LWFA) over the past several years has led to an interest in very compact sources of X-ray radiation – such as “table-top” free electron lasers. However, the use of conventional undulators using permanent magnets also implies system sizes which are large. In this work, we assess the possibilities for the use of novel mini-undulators in conjunction with a LWFA so that the dimensions of the undulator become comparable with the acceleration distances for LWFA experiments (i.e., centimeters). The use of a prototype undulator using laser machining of permanent magnets for this application is described and the emission characteristics and limitations of such a system are determined. Preliminary electron propagation and X-ray emission measurements are taken with a LWFA electron beam at the University of Michigan.
The Meat Standards Australia (MSA) grading scheme has the ability to predict beef eating quality for each ‘cut×cooking method combination’ from animal and carcass traits such as sex, age, breed, marbling, hot carcass weight and fatness, ageing time, etc. Following MSA testing protocols, a total of 22 different muscles, cooked by four different cooking methods and to three different degrees of doneness, were tasted by over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia. Consumers scored the sensory characteristics (tenderness, flavor liking, juiciness and overall liking) and then allocated samples to one of four quality grades: unsatisfactory, good-every-day, better-than-every-day and premium. We observed that 26% of the beef was unsatisfactory. As previously reported, 68% of samples were allocated to the correct quality grades using the MSA grading scheme. Furthermore, only 7% of the beef unsatisfactory to consumers was misclassified as acceptable. Overall, we concluded that an MSA-like grading scheme could be used to predict beef eating quality and hence underpin commercial brands or labels in a number of European countries, and possibly the whole of Europe. In addition, such an eating quality guarantee system may allow the implementation of an MSA genetic index to improve eating quality through genetics as well as through management. Finally, such an eating quality guarantee system is likely to generate economic benefits to be shared along the beef supply chain from farmers to retailors, as consumers are willing to pay more for a better quality product.
Prior research has typically found a negative relationship between chronic pain and memory, and we examined whether cognitive control processes (e.g. reflection and rumination) moderated this relationship in individuals with Chiari malformation Type I (CM). CM is a neurological condition in which the cerebellar tonsils descend into the medullary and upper cervical spine regions potentially resulting in severe headaches and neck pain.
CM patients who had (n = 341) and had not (n = 297) undergone decompression surgery completed the McGill Pain Questionnaire-Short Form-Revised (SF-MPQ-2), the Rey Auditory Verbal Learning Test (RAVLT), and the Rumination-Reflection Questionnaire (RRQ). Immediate recall scores were compared to those of 102 healthy controls, and delayed recall performance was compared across other variables within the CM group.
CM patients performed more poorly on immediate recall than did controls. Within CM patients, we observed main effects for reflection and age, and a pain x reflection x surgical status (surgery v. no surgery) interaction in which non-decompressed individuals with low levels of pain and high levels of reflection showed superior delayed recall relative to non-decompressed individuals with higher pain and all decompressed individuals.
CM patients show an immediate recall deficit relative to controls, regardless of surgical status. High levels of reflection were associated with better delayed recall performance in non-decompressed CM patients with lower pain levels. High levels of chronic pain may overwhelm increased focused attention abilities, but higher levels of reflection partially overcome the distracting effects of pain and this may represent a type of resilience.
Accurately quantifying a consumer’s willingness to pay (WTP) for beef of different eating qualities is intrinsically linked to the development of eating-quality-based meat grading systems, and therefore the delivery of consistent, quality beef to the consumer. Following Australian MSA (Meat Standards Australia) testing protocols, over 19 000 consumers from Northern Ireland, Poland, Ireland, France and Australia were asked to detail their willingness to pay for beef from one of four categories that best described the sample; unsatisfactory, good-every-day, better-than-every-day or premium quality. These figures were subsequently converted to a proportion relative to the good-every-day category (P-WTP) to allow comparison between different currencies and time periods. Consumers also answered a short demographic questionnaire. Consumer P-WTP was found to be remarkably consistent between different demographic groups. After quality grade, by far the greatest influence on P-WTP was country of origin. This difference was unable to be explained by the other demographic factors examined in this study, such as occupation, gender, frequency of consumption and the importance of beef in the diet. Therefore, we can conclude that the P-WTP for beef is highly transferrable between different consumer groups, but not countries.