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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.
Selective pressure exerted by the widespread use of antibacterial drugs is accelerating the development of resistant bacterial populations. The purpose of this scoping review was to summarise the range of studies that use dynamic models to analyse the problem of bacterial resistance in relation to antibacterial use in human and animal populations. A comprehensive search of the peer-reviewed literature was performed and non-duplicate articles (n = 1486) were screened in several stages. Charting questions were used to extract information from the articles included in the final subset (n = 81). Most studies (86%) represent the system of interest with an aggregate model; individual-based models are constructed in only seven articles. There are few examples of inter-host models outside of human healthcare (41%) and community settings (38%). Resistance is modelled for a non-specific bacterial organism and/or antibiotic in 40% and 74% of the included articles, respectively. Interventions with implications for antibacterial use were investigated in 67 articles and included changes to total antibiotic consumption, strategies for drug management and shifts in category/class use. The quality of documentation related to model assumptions and uncertainty varies considerably across this subset of articles. There is substantial room to improve the transparency of reporting in the antibacterial resistance modelling literature as is recommended by best practice guidelines.
The 9th meeting of the African Society of Human Genetics, in partnership with the Senegalese Cancer Research and Study Group and the Human Heredity and Health in Africa (H3Africa) Consortium, was held in Dakar, Senegal. The theme was Strengthening Human Genetics Research in Africa. The 210 delegates came from 21 African countries and from France, Switzerland, UK, UAE, Canada and the USA. The goal was to highlight genetic and genomic science across the African continent with the ultimate goal of improving the health of Africans and those across the globe, and to promote the careers of young African scientists in the field. A session on the sustainability of genomic research in Africa brought to light innovative and practical approaches to supporting research in resource-limited settings and the importance of promoting genetics in academic, research funding, governmental and private sectors. This meeting led to the formation of the Senegalese Society for Human Genetics.
Cerebral blood volume and metabolism of oxygen decline as part of human ageing, and this has been previously shown to be related to cognitive decline. There is some evidence to suggest that polyphenol-rich foods can play an important role in delaying the onset or halting the progression of age-related health disorders such as CVD and Alzheimer’s disease and to improve cognitive function. In the present study, an acute, placebo-controlled, double-blinded, cross-over, randomised Latin-square design study with a washout period of at least 14 d was conducted on twenty-seven, middle-aged (defined as 45–60 years) volunteers. Participants received either a 60 ml dose of Montmorency tart cherry concentrate (MC), which contained 68·0 (sd 0·26) mg cyanidin-3-glucoside/l, 160·75 (sd 0·55) mean gallic acid equivalent/l and 0·59 (sd 0·02) mean Trolox equivalent/l, respectively, or a placebo. Cerebrovascular responses, cognitive performance and blood pressure were assessed at baseline and 1, 2, 3 and 5 h following consumption. There were significant differences in concentrations of total Hb and oxygenated Hb during the task period 1 h after MC consumption (P≤0·05). Furthermore, MC consumption significantly lowered systolic blood pressure (P≤0·05) over a period of 3 h, with peak reductions of 6±2 mmHg at 1 h after MC consumption relative to the placebo. Cognitive function and mood were not affected. These results show that a single dose of MC concentrate can modulate certain variables of vascular function; however, this does not translate to improvements in cognition or mood.
Older people with dementia are at increased risk of physical decline and falls. Balance and mood are significant predictors of falls in this population. The aim of this study was to determine the effect of a tailored home-based exercise program in community-dwelling older people with dementia.
Forty-two participants with mild to moderate dementia were recruited from routine health services. All participants were offered a six-month home-based, carer-enhanced, progressive, and individually tailored exercise program. Physical activity, quality of life, physical, and psychological assessments were administered at the beginning and end of the trial.
Of 33 participants (78.6%) who completed the six-month reassessment ten (30%) reported falls and six (18%) multiple falls during the follow-up period. At reassessment, participants had better balance (sway on floor and foam), reduced concern about falls, increased planned physical activity, but worse knee extension strength and no change in depression scores. The average adherence to the prescribed exercise sessions was 45% and 22 participants (52%) were still exercising at trial completion. Those who adhered to ≥70% of prescribed sessions had significantly better balance at reassessment compared with those who adhered to <70% of sessions.
This trial of a tailored home-based exercise intervention presents preliminary evidence that this intervention can improve balance, concern about falls, and planned physical activity in community-dwelling older people with dementia. Future research should determine whether exercise interventions are effective in reducing falls and elucidate strategies for enhancing uptake and adherence in this population.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
Multiple sulfatase deficiency (MSD) is a rare autosomal recessive inborn error of lysosomal metabolism. The clinical phenotypic spectrum encompasses overlapping features of variable severity and is suggestive of individual single sulfatase deficiencies (i.e., metachromatic leukodystrophy, mucopolysaccharidosis, and X-linked ichthyosis).
We describe a 3-year-old male with severe hypotonia, developmental regression and progressive neurodegeneration, coarse facial features, nystagmus (from ocular albinism), and dysmyelinating motor sensory neuropathy. Ethics approval was obtained from the Western University Ontario.
Extensive investigative work-up identified deficiencies of multiple sulfatases: heparan sulfate sulfamidase: 6.5 nmoles/mg/protein/17 hour (reference 25.0-75.0), iduronate-2-sulfate sulfatase: 9 nmol/mg/protein/4 hour (reference 31-110), and arylsulfatase A: 3.8 nmoles/hr/mg protein (reference 22-50). The identification of compound heterozygous pathogenic mutations in the SUMF1 gene c.836 C>T (p.A279V) and c.1045C>T (p.R349W) confirmed the diagnosis of MSD.
The complex clinical manifestations of MSD and the unrelated coexistence of ocular albinism as in our case can delay diagnosis. Genetic counselling should be provided to all affected families.
the maternally inherited MTTL1 A3243G mutation in the mitochondrial genome causes MelaS (Mitochondrial encephalopathy lactic acidosis with Stroke-like episodes), a condition that is multisystemic but affects primarily the nervous system. Significant intra-familial variation in phenotype and severity of disease is well recognized.
retrospective and ongoing study of an extended family carrying the MTTL1 A3243G mutation with multiple symptomatic individuals. tissue heteroplasmy is reviewed based on the clinical presentations, imaging studies, laboratory findings in affected individuals and pathological material obtained at autopsy in two of the family members.
there were seven affected individuals out of thirteen members in this three generation family who each carried the MTTL1 A3243G mutation. the clinical presentations were varied with symptoms ranging from hearing loss, migraines, dementia, seizures, diabetes, visual manifestations, and stroke like episodes. three of the family members are deceased from MelaS or to complications related to MelaS.
the results of the clinical, pathological and radiological findings in this family provide strong support to the current concepts of maternal inheritance, tissue heteroplasmy and molecular pathogenesis in MelaS. neurologists (both adult and paediatric) are the most likely to encounter patients with MelaS in their practice. genetic counselling is complex in view of maternal inheritance and heteroplasmy. newer therapeutic options such as arginine are being used for acute and preventative management of stroke like episodes.
We present the characteristics of a high temperature CMOS integrated circuit process based on 4H silicon carbide designed to operate at temperatures beyond 300°C. N-channel and P-channel transistor characteristics at room and elevated temperatures are presented. Both channel types show the expected low values of field effect mobility well known in SiC MOSFETS. However the performance achieved is easily capable of exploitation in CMOS digital logic circuits and certain analogue circuits, over a wide temperature range.
Data is also presented for the performance of digital logic demonstrator circuits, in particular a 4 to 1 analogue multiplexer and a configurable timer operating over a wide temperature range. Devices are packaged in high temperature ceramic dual in line (DIL) packages, which are capable of greater than 300°C operation. A high temperature “micro-oven” system has been designed and built to enable testing and stressing of units assembled in these package types. This system heats a group of devices together to temperatures of up to 300°C while keeping the electrical connections at much lower temperatures. In addition, long term reliability data for some structures such as contact chains to n-type and p-type SiC and simple logic circuits is summarized.
Previous evidence has suggested an association between cryptosporidiosis and consumption of unfiltered drinking water from Loch Katrine in Scotland. Before September 2007, the water was only micro-strained and chlorinated; however, since that time, coagulation and rapid gravity filtration have been installed. In order to determine risk factors associated with cryptosporidiosis, including drinking water, we analysed data on microbiologically confirmed cases of cryptosporidiosis from 2004 to 2010. We identified an association between the incidence of cryptosporidiosis and unfiltered Loch Katrine drinking water supplied to the home (odds ratio 1·86, 95% confidence interval 1·11–3·11, P = 0·019). However, while filtration appears to be associated with initially reduced rates of cryptosporidiosis, evidence suggests it may paradoxically make those consumers more susceptible to other transmission routes in the long-term. These findings support implementation of similar treatment for other unfiltered drinking-water supplies, as a means of reducing cryptosporidiosis associated with drinking water.
The aim of this study was to estimate the amount of childhood hepatitis B virus transmission in children born in the UK, a very low-prevalence country, that is preventable only by universal hepatitis B immunization of infants. Oral fluid specimens were collected from schoolchildren aged 7–11 years in four inner city multi-ethnic areas and tested for the presence of antibody to hepatitis B core antigen (anti-HBc). Those found positive or indeterminate were followed up with testing on serum to confirm their hepatitis B status. The overall prevalence of anti-HBc in children was low [0·26%, 95% confidence interval (CI) 0·14–0·44]. The estimated average annual incidence of hepatitis B was estimated to be 29·26/100 000 children (95% CI 16·00–49·08). The total incidence that is preventable only by a universal infant immunization programme in the UK was estimated to be between 5·00 and 12·49/100 000. The study demonstrates that the extent of horizontal childhood hepatitis B virus transmission is low in children born in the UK and suggests that schools in the UK are an uncommon setting for the transmission of the virus. Targeted hepatitis B testing and immunization of migrants from intermediate- and high-prevalence countries is likely to be a more effective measure to reduce childhood transmission than a universal infant immunization programme.
During 2006–2007, the KwaZulu-Natal coast of South Africa was exposed to several large swell events (Ho > 3 m), near the peak of the lunar nodal cycle, causing shoreline recession. The largest swell (Hs = 8.5 m) struck the coast on the March equinox (18th–20th) and generated a strong storm-return flow. Observations made before, during and after record dramatic coastal erosion (shoreline recession of up to 40 m and substantial property damage). This swell event removed the semi-continuous nearshore bar system and ‘conditioned’ the coast such that lesser subsequent swell events accomplished much greater amounts of coastal erosion than expected (up to 100 m at certain erosion hotspots) because waves reached the coast without significant energy dissipation. Subsequent bar generation rebuilt the inshore bars within six months. The styles of erosion during the March ’07 event and other 2007 swells were markedly different. Lesser swells are focused by headlands and result in megarip development and activation of erosion hotspots. The March ’07 event still-water level was raised (equinoctial spring high tide and a storm surge of 0.33–0.45 m) to a level that rendered most headlands (and erosion hotspots) ineffective and resulted in laterally extensive erosion of soft shorelines. Results record cumulative effects of successive swell events on coastal behaviour that proved to be critical in enabling erosion to proceed at rapid rates after the coast had been initially destabilized. Unlike hurricanes and tsunamis, surges associated with swell events are relatively minor and therefore extensive erosion is linked with high lunar tides. There is circumstantial evidence that swell-induced erosion follows the broad 18.6 yr lunar nodal tidal cycle when the chances of large swells coinciding with high water levels are increased.
Healthcare-associated hepatitis B virus (HBV) outbreaks have been reported in the USA and from several countries in Europe. Patient-to-patient transmission of HBV in these settings has been linked to several different types of exposure but one of the most common exposures implicated is the use of ‘finger-stick’ lancet devices for blood glucose testing. This article is an account of the investigations into a series of HBV outbreaks linked to the use of lancing devices in community healthcare settings in the UK. Between February 2004 and December 2006, nine individuals with acute HBV infection were reported to five local units of the Health Protection Agency. Investigations identified a further 12 individuals with HBV infection in residents in these settings. The epidemiological and environmental evidence suggests that HBV transmission occurred mostly from a significant breakdown in infection control measures in blood glucose testing. The occurrence of these outbreaks has highlighted the confusion that exists and the need for clear recommendations regarding the use of such devices in the UK.
A national survey was conducted of 3150 notified cases of whooping cough in order to determine age-specific pertussis vaccine efficacy by the ‘screening’ method. The cases were collected over two periods, one just prior to the start and one at the first peak of the whooping cough epidemic of 1989–90. Vaccination status was determined by a postal questionnaire to the reporting doctor and clinical data were also collected to provide efficacy estimates according to standardized case definitions. Overall, observed vaccine efficacy was high but differed between epidemic (87%) and non-epidemic (93%) periods (P = 0·03). Efficacy estimates were generally higher for typical or severe cases than for children with an atypical illness. Vaccine efficacy declined with age (P < 0·01) but estimates remained high up to the age of 8 years. This study will provide baseline data for comparison with efficacy observed from similar studies of children immunized at an accelerated schedule and from phase III studies of acellular pertussis vaccines performed elsewhere.
Surveillance reports and prevalence studies have indicated that injecting drug users (IDUs) contribute more to the hepatitis C epidemic in the United Kingdom than any other risk group. Information on both the prevalence and incidence of hepatitis C in IDUs is therefore essential to understanding the epidemiology of this infection. The prevalence of hepatitis C in specimens from the Unlinked Anonymous Prevalence Monitoring Programme collected in 1995, 1996, 1998, 1999, 2000, and 2001 was determined using residual syphilis serology specimens from IDUs attending 15 genitourinary medicine (GUM) clinics in and outside London. These specimens were tested for antibodies to hepatitis C virus (anti-HCV). Using this cross-sectional design, anti-HCV-negative specimens were tested for HCV RNA to identify incident infections during the ‘window’ period of infection, and thus to estimate HCV incidence. Results of the multivariable analysis showed that there was marked variation in prevalence by clinic (P<0·0001) and age (P<0·0001). Overall the majority of infections were in males and the overall prevalence in injectors declined over the study period from 36·9% to 28·7%. The annual incidence in these injectors was estimated as being 3·01% (95% CI 1·25–6·73). Over the study period HCV incidence decreased by 1·2% per year. Genotyping of the incident infections identified the most common genotype as type 1 with type 3 being more frequently seen after 1998. Of the prevalent infections, genotype 1 was the most common. The study has confirmed a higher prevalence of anti-HCV in IDUs in the London area compared to those outside London. How representative of the current injecting drug user population are IDUs attending GUM clinics is unclear. Even so, such studies allow prevalence and incidence to be estimated in individuals who have ever injected drugs and inform ongoing public health surveillance.
This study evaluated the first use of a combination of the lyophilized components of the conjugated group C vaccine Menjugate™ reconstituted with the liquid group B outer membrane vesicle (OMV) vaccine MeNZB™. At 6-week intervals, healthy residential students received three doses of MeNZB alone or concomitantly with one dose of Menjugate (MeNZB+MenC). Short-lasting injection-site reactions of mild or moderate intensity were frequent in both groups. There were no vaccine-related serious adverse events. After three doses, the percentage of subjects with serum bactericidal assay (SBA) titres ⩾1:8 against the serogroup B strain NZ98/254 was 82% for MeNZB+MenC and 78% for MeNZB. All subjects in the MeNZB+MenC group achieved SBA titres ⩾1:8 against serogroup strain C11 and 67% in the MeNZB group. All SBA and ELISA responses of the combined vaccine were at least as good as for MeNZB alone. After vaccination, the pharyngeal carriage rate of any meningococcus in the vaccinated group had declined from 40% to 21%.
This paper describes sentinel laboratory surveillance of hepatitis C antibody testing in England. Demographic and test result data were supplemented by follow-up questionnaires sent to the requesting clinician. Between October 2002 and September 2003 almost 75000 anti-HCV tests were performed in eight sentinel centres. More males were tested than females and over half of those tested were aged 25–44 years. Overall 5·7% (3333/58144, range 2·8–7·7%) individuals tested positive. Follow-up questionnaire data showed that 82% (1043/1277) of the positives had injecting drug use reported as the main risk exposure. The majority of negative individuals were undergoing routine screening as recommended for specific patient groups. Most individuals were asymptomatic. Antibody prevalence was estimated to be 34% in current injecting drug users and 42% in former injectors. Comparing positives to routine national surveillance suggests that only 53% (1782/3333) of diagnosed cases were reported. Sentinel laboratory data can provide valuable supplementary data to national surveillance.