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The aim of this study was to estimate the effectiveness of first-line biologic disease modifying drugs(boDMARDs), and their approved biosimilars (bsDMARDs), compared with conventional (csDMARD) treatment, in terms of ACR (American College of Rheumatology) and EULAR (European League against Rheumatism) responses.
Systematic literature search, on eight databases to January 2017, sought ACR and EULAR data from randomized controlled trials (RCTs) of boDMARDs / bsDMARDs (in combination with csDMARDs, or monotherapy). Two adult populations: methotrexate (MTX)-naïve patients with severe active RA; and csDMARD-experienced patients with moderate-to-severe active RA. Network meta-analyses (NMA) were conducted using a Bayesian Markov chain Monte Carlo simulation using a random effects model with a probit link function for ordered categorical.
Forty-six RCTs met the eligibility criteria. In the MTX-naïve severe active RA population, no biosimilar trials meeting the inclusion criteria were identified. MTX plus methylprednisolone (MP) was most likely to achieve the best ACR response. There was insufficient evidence that combination boDMARDs was superior to intensive (two or more) csDMARDs. In the csDMARD-experienced, moderate-to-severe RA population, the greatest effects for ACR responses were associated with tocilizumab (TCZ) monotherapy, and combination therapy (plus MTX) with bsDMARD etanercept (ETN) SB4, boDMARD ETN and TCZ. These treatments also had the greatest effects on EULAR responses. No clear differences were found between the boDMARDs and their bsDMARDs.
In MTX-naïve patients, there was insufficient evidence that combination boDMARDs was superior to two or more csDMARDs. In csDMARD-experienced patients, boDMARDs and bsDMARDs were comparable and all combination boDMARDs / bsDMARDs were superior to single csDMARD.
To test the feasibility of using telehealth to support antimicrobial stewardship at Veterans Affairs medical centers (VAMCs) that have limited access to infectious disease-trained specialists.
A prospective quasi-experimental pilot study.
Two rural VAMCs with acute-care and long-term care units.
At each intervention site, medical providers, pharmacists, infection preventionists, staff nurses, and off-site infectious disease physicians formed a videoconference antimicrobial stewardship team (VAST) that met weekly to discuss cases and antimicrobial stewardship-related education.
Descriptive measures included fidelity of implementation, number of cases discussed, infectious syndromes, types of recommendations, and acceptance rate of recommendations made by the VAST. Qualitative results stemmed from semi-structured interviews with VAST participants at the intervention sites.
Each site adapted the VAST to suit their local needs. On average, sites A and B discussed 3.5 and 3.1 cases per session, respectively. At site A, 98 of 140 cases (70%) were from the acute-care units; at site B, 59 of 119 cases (50%) were from the acute-care units. The most common clinical syndrome discussed was pneumonia or respiratory syndrome (41% and 35% for sites A and B, respectively). Providers implemented most VAST recommendations, with an acceptance rate of 73% (186 of 256 recommendations) and 65% (99 of 153 recommendations) at sites A and B, respectively. Qualitative results based on 24 interviews revealed that participants valued the multidisciplinary aspects of the VAST sessions and felt that it improved their antimicrobial stewardship efforts and patient care.
This pilot study has successfully demonstrated the feasibility of using telehealth to support antimicrobial stewardship at rural VAMCs with limited access to local infectious disease expertise.
In September 2016, an imported case of measles in Edinburgh in a university student resulted in a further 17 confirmed cases during October and November 2016. All cases were genotype D8 and were associated with a virus strain most commonly seen in South East Asia. Twelve of the 18 cases were staff or students at a university in Edinburgh and 17 cases had incomplete or unknown measles mumps rubella (MMR) vaccination status. The public health response included mass follow-up of all identified contacts, widespread communications throughout universities in Edinburgh and prompt vaccination clinics at affected campuses. Imported cases of measles pose a significant risk to university student cohorts who may be undervaccinated, include a large number of international students and have a highly mobile population. Public health departments should work closely with universities to promote MMR uptake and put in place mass vaccination plans to prevent rapidly spreading measles outbreaks in higher educational settings in future.
Paratuberculosis (Johne’s disease) is a chronic invariably fatal enteritis of cattle caused by the bacterium Mycobacterium avium subspecies paratuberculosis and has recently been isolated from wild rabbits. One potential route of transmission of M.a.paratuberculosis from rabbits to cattle is the ingestion of rabbit excreta contaminating pasture. Here we (1) determine the prevalence and level of infection in rabbits and their excreta (2) quantify the level of rabbit faeces contaminating cattle pastures and (3) determine the impact of rabbit faeces on cattle grazing behaviour.
Out-of-home foods (takeaway, take-out and fast foods) have become increasingly popular in recent decades and are thought to be a key driver in increasing levels of overweight and obesity due to their unfavourable nutritional content. Individual food choices and eating behaviours are influenced by many interrelated factors which affect the results of nutrition-related public health interventions. While the majority of research based on out-of-home foods comes from Australia, the UK and USA, the same issues (poor dietary habits and increased prevalence of non-communicable disease) are of equal concern for urban centres in developing economies undergoing ‘nutrition transition’ at a global scale. The present narrative review documents key facets, which may influence out-of-home food consumption, drawn from biological, societal, environmental, demographic and psychological spheres. Literature searches were performed and references from relevant papers were used to find supplementary studies. Findings suggest that the strongest determinants of out-of-home food availability are density of food outlets and deprivation within the built environment; however, the association between socio-economic status and out-of-home food consumption has been challenged. In addition, the biological and psychological drives combined with a culture where overweight and obesity are becoming the norm makes it ‘fashionable’ to consume out-of-home food. Other factors, including age group, ethnicity and gender demonstrate contrasting effects and a lack of consensus. It is concluded that further consideration of the determinants of out-of-home food consumption within specific populations is crucial to inform the development of targeted interventions to reduce the impact of out-of-home foods on public health.
As chemical management options for weeds become increasingly limited due to selection for herbicide resistance, investigation of additional nonchemical tools becomes necessary. Harvest weed seed control (HWSC) is a methodology of weed management that targets and destroys weed seeds that are otherwise dispersed by harvesters following threshing. It is not known whether problem weeds in western Canada retain their seeds in sufficient quantities until harvest at a height suitable for collection. A study was conducted at three sites over 2 yr to determine whether retention and height criteria were met by wild oat, false cleavers, and volunteer canola. Wild oat consistently shed seeds early, but seed retention was variable, averaging 56% at the time of wheat swathing, with continued losses until direct harvest of wheat and fababean. The majority of retained seeds were >45 cm above ground level, suitable for collection. Cleavers seed retention was highly variable by site-year, but generally greater than wild oat. The majority of seed was retained >15 cm above ground level and would be considered collectable. Canola seed typically had >95% retention, with the majority of seed retained >15 cm above ground level. The suitability ranking of the species for management with HWSC was canola>cleavers>wild oat. Efficacy of HWSC systems in western Canada will depend on the target species and site- and year-specific environmental conditions.
Limitations of access have long restricted exploration and investigation of the cavities beneath ice shelves to a small number of drillholes. Studies of sea-ice underwater morphology are limited largely to scientific utilization of submarines. Remotely operated vehicles, tethered to a mother ship by umbilical cable, have been deployed to investigate tidewater-glacier and ice-shelf margins, but their range is often restricted. The development of free-flying autonomous underwater vehicles (AUVs) with ranges of tens to hundreds of kilometres enables extensive missions to take place beneath sea ice and floating ice shelves. Autosub2 is a 3600 kg, 6.7 m long AUV, with a 1600 m operating depth and range of 400 km, based on the earlier Autosub1 which had a 500 m depth limit. A single direct-drive d.c. motor and five-bladed propeller produce speeds of 1–2 m s−1. Rear-mounted rudder and stern-plane control yaw, pitch and depth. The vehicle has three sections. The front and rear sections are free-flooding, built around aluminium extrusion space-frames covered with glass-fibre reinforced plastic panels. The central section has a set of carbon-fibre reinforced plastic pressure vessels. Four tubes contain batteries powering the vehicle. The other three house vehicle-control systems and sensors. The rear section houses subsystems for navigation, control actuation and propulsion and scientific sensors (e.g. digital camera, upward-looking 300 kHz acoustic Doppler current profiler, 200 kHz multibeam receiver). The front section contains forward-looking collision sensor, emergency abort, the homing systems, Argos satellite data and location transmitters and flashing lights for relocation as well as science sensors (e.g. twin conductivity–temperature–depth instruments, multibeam transmitter, sub-bottom profiler, AquaLab water sampler). Payload restrictions mean that a subset of scientific instruments is actually in place on any given dive. The scientific instruments carried on Autosub are described and examples of observational data collected from each sensor in Arctic or Antarctic waters are given (e.g. of roughness at the underside of floating ice shelves and sea ice).
The development of an economic capital model requires a decision to be made regarding how to aggregate capital requirements for the individual risk factors while taking into account the effects of diversification. Under the Individual Capital Adequacy Standards framework, UK life insurers have commonly adopted a correlation matrix approach due to its simplicity and ease in communication to the stakeholders involved, adjusting the result, where appropriate, to allow for non-linear interactions. The regulatory requirements of Solvency II have been one of the principal drivers leading to an increased use of more sophisticated aggregation techniques in economic capital models. This paper focusses on a simulation-based approach to the aggregation of capital requirements using copulas and proxy models. It describes the practical challenges in parameterising a copula including how allowance may be made for tail dependence. It also covers the challenges associated with fitting and validating a proxy model. In particular, the paper outlines how insurers could test, communicate and justify the choices made through the use of some examples.
Among extant crinoids, the feather stars are the most diverse and occupy the greatest bathymetric range, being especially common in reef environments. Feather stars possess a variety of morphological, behavioral and physiological traits that have been hypothesized to be critical to their success, especially in their ability to cope with predation. However, knowledge of their predators is exceptionally scant, consisting primarily of circumstantial evidence of attacks by fishes. In this study the question whether regular echinoids, recently shown to consume stalked crinoids, also consume feather stars is explored. Aquarium observations indicate that regular echinoids find feather stars palatable, including feather stars known to be distasteful to fish, and that regular echinoids can capture and eat live feather stars, including those known to swim. Gut-content analyses of the echinoid Araeosoma fenestratum (Thomson, 1872), which is commonly observed with large populations of the feather star Koehlermetra porrecta (Carpenter, 1888) in video transects from marine canyons off the coast of France, revealed elements of feather stars in the guts of 6 of 13 individuals. The high proportion of crinoid material (up to 90%), and the presence of articulated crinoid skeletal elements in the gut of A. fenestratum, suggest that these echinoids consumed at least some live crinoids, although they may have also ingested some postmortem remains found in the sediment. Additionally, photographic evidence from the northeast Atlantic suggests that another regular echinoid, Cidaris cidaris (Linnaeus, 1758), preys on feather stars. Thus in spite of the broad suite of antipredatory adaptations, feather stars are today subject to predation by regular echinoids and may have been since the Mesozoic, when this group of crinoids first appeared.
Untreated maternal depression during the postpartum period can have a profound impact on the short- and long-term psychological and physical well-being of children. There is, therefore, an imperative for increased understanding of the determinants of depression and depression-related healthcare access during this period.
Respondents were 11 089 mothers of 9-month-old infants recruited to the Growing Up in Ireland study. Of this sample, 10 827 had complete data on all relevant variables. Respondents provided sociodemographic, socioeconomic and household information, and completed the Center for Epidemiologic Studies Depression Scale (CESD).
11.1% of mothers scored above the CESD threshold for depression. 10.0% of depressed mothers and 25.4% of depressed fathers had depressed partners. Among depressed mothers, 73.1% had not attended a healthcare professional for a mental health problem since the birth of the cohort infant. In the adjusted model, the likelihood of depression was highest in mothers who: had lower educational levels (odds ratio (OR) 1.26; 95% confidence intervals (CIs) 1.08, 1.46); were unemployed (OR 1.27; 95% CIs 1.10, 1.47); reported previous mental health problems (OR 6.55; 95% CIs 5.68, 7.56); reported that the cohort child was the result of an unintended pregnancy (OR 1.43; 95% CIs 1.22, 1.68), was preterm (OR 1.35; 95% CIs 1.07, 1.70), or had health/developmental problems (OR 1.20; 95% CIs 1.04, 1.39); had no partner in the household (OR 1.33; 95% CIs 1.04, 1.70) or were living with a depressed partner (OR 2.66; 95% CIs 1.97, 3.60); reported no family living nearby (OR 1.33; 95% CIs 1.16, 1.54); were in the lowest income group (OR 1.60; 95% CIs 1.21, 2.12). The primary determinant of not seeking treatment for depression was being of non-white ethnicity (OR 2.21; 95% CIs 1.18, 4.13).
Results highlight the prevalence of maternal depression in the later postpartum period, particularly for lower socioeconomic groups, those with previous mental health problems, and those with limited social support. The large proportion of unmet need in depressed mothers, particularly among ethnic minority groups, emphasises the need for a greater awareness of postpartum mental health problems and increased efforts by healthcare professionals to ensure that mothers can access the required services.
Previous studies have illustrated pediatric knowledge deficits among Emergency Medical Services (EMS) providers. The purpose of this study was to identify perspectives of a diverse group of EMS providers regarding pediatric prehospital care educational deficits and proposed methods of training improvements.
Purposive sampling was used to recruit EMS providers in diverse settings for study participation. Two separate focus groups of EMS providers (administrative and non-administrative personnel) were held in three locations (urban, suburban, and rural). A professional moderator facilitated focus group discussion using a guide developed by the study team. A grounded theory approach was used to analyze data.
Forty-two participants provided data. Four major themes were identified: (1) suboptimal previous pediatric training and training gaps in continuing pediatric education; (2) opportunities for improved interactions with emergency department (ED) staff, including case-based feedback on patient care; (3) barriers to optimal pediatric prehospital care; and (4) proposed pediatric training improvements.
Focus groups identified four themes surrounding preparation of EMS personnel for providing care to pediatric patients. These themes can guide future educational interventions for EMS to improve pediatric prehospital care.
BrownSA, HaydenTC, RandellKA, RappaportL, StevensonMD, KimIK. Improving Pediatric Education for Emergency Medical Services Providers: A Qualitative Study. Prehosp Disaster Med. 2017;32(1):20–26.
There is a paucity of information on the risk from potable water in non-passenger merchant vessels (NPMVs) particularly with regard to Legionella and other bacteria. This retrospective study examined water samples from 550 NPMVs docked in eight UK ports. A total of 1027 samples from 412 NPMVs were examined for total aerobic colony counts (ACC), coliforms, Escherichia coli and enterococci; 41% of samples yielded ACC above the action level (>1 × 103 c.f.u./ml) and 4·5% contained actionable levels (>1 c.f.u./100 ml) of faecal indicator bacteria. Eight hundred and three samples from 360 NPMVs were cultured specifically for Legionella and 58% of vessels proved positive for these organisms with 27% of samples showing levels greater than the UK upper action limit of 1 × 103 c.f.u./l. Cabin showers (49%) and hospital shower (45%) were frequently positive. A subset of 106 samples was analysed by quantitative polymerase chain reaction for Legionella and identified a further 11 Legionella-positive NPMVs, returning a negative predictive value of 100%. There was no correlation between NPMV age or size and any microbial parameters (P > 0·05). Legionella pneumophila serogroup 1 was isolated from 46% of NPMVs and sequence-based typing of 17 isolates revealed four sequence types (STs) previously associated with human disease. These data raise significant concerns regarding the management of microbial and Legionella risks on board NPMVs and suggest that better guidance and compliance are required to improve control.
This paper seeks to establish good practice in setting inputs for operational risk models for banks, insurers and other financial service firms. It reviews Basel, Solvency II and other regulatory requirements as well as publicly available literature on operational risk modelling. It recommends a combination of historic loss data and scenario analysis for modelling of individual risks, setting out issues with these data, and outlining good practice for loss data collection and scenario analysis. It recommends the use of expert judgement for setting correlations, and addresses information requirements for risk mitigation allowances and capital allocation, before briefly covering Bayesian network methods for modelling operational risks.
The Cycadales are a group of significant global conservation concern and have the highest extinction risk of all seed plants. Understanding the synchronisation of reproductive phenology of Cycadales may be useful for conservation by enabling the targeting of pollen and seed collection from wild populations and identifying the window of fertilisation to aid in the cultivation of Cycadales. Phenological data for 11 species of Zamia were gathered from herbarium specimens. Four phenological characters were coded with monthly character states. DNA was isolated and sequenced for 26S, CAB, NEEDLY, matK and rbcL, and a simultaneous phylogenetic analysis of phenology and DNA sequence data was carried out. Three major clades were recovered: a Caribbean clade, a Central American clade and a South American clade. Eight species showed statistically significant synchronisation in microsporangiate and ovulate phenological phases, indicating the time of fertilisation. Close reproductive synchronisation was consistently observed throughout the Caribbean clade (statistically significant in four of five species) but was less consistent in the Central American clade (statistically significant in one of two species) and South American clade (statistically significant in three of four species). Ultimately, phenology is shown to be a potential driver of speciation in some clades of Zamia and in others to be a potential barrier to hybridisation.
The deep interiors of cold, degenerate stars consist of a mixture of elements, either because of primordial inhomogeneities or because of incomplete nuclear burning. However, most existing calculations for the cooling of such bodies (subsequent to any nuclear burning) assume that the only source of luminosity is the heat content of the star. An additional (and potentially much larger) energy source is available if the elements have limited mutual solubility below some temperature. The resulting differentiation and gravitational settling can dramatically decrease the rate of cooling, enhance the number of (potentially) observable low luminosity bodies, and may deplete the atmosphere of heavy elements (if substantial mixing between the atmosphere and deep interior occurs). The observational evidence for these phenomena is equivocal at present.
Semiconvection is the name given to a situation that arises in the evolution of large-mass main-sequence stars and lower-mass horizontal-branch stars, in which a layer forms where almost all of the heat flux is transported by radiation, but where slow convection is required to redistribute a stably stratified solute (e.g. helium). For a general discussion on semiconvection, see Spiegel (1969). The main problem is to determine the correct relationship between the solute distribution and the temperature gradient in the inhomogeneous layer. Ledoux (1947) and Schwarzschild and Harm (1958) have proposed two very different prescriptions. Since theory and experiment indicate that the Schwarzschild-Harm (SH) prescription is correct for the onset of convection (in the form of overstability), Spiegel (1969) has proposed that SH are correct. However, neither observation (oceanographic or laboratory) nor theory precludes a substantial deviation from the SH prescription as applied to finite amplitude semiconvection. The observational evidence is only readily applicable to stars if Pr≳, 1, where Pr is the Prandtl number of the fluid. In fact, Pr≪ 1 in stars. It is shown below that if one could have stars in which Pr ≳ 1, then the SH prescription would probably be wrong, and the Ledoux criterion might then be nearer to being correct. In the real situation (Pr≪ 1), observations or experiments are lacking and theory alone does not provide an unequivocal answer to the problem. This paper does not attempt a complete discussion of the problem, and a more detailed report will be submitted elsewhere. Some aspects of the problem have already been discussed in the context of the giant planets (Stevenson and Salpeter 1977).
According to Oort (1965), the mass density in the solar neighbourhood (inferred from the gravity component normal to the galactic plane) is between 50% and 150% greater than the mass density inferred from non-dwarf stars. One possible explanation for the “missing mass” is an overabundance of faint M-dwarfs (Weistrop 1972), but present indications are that this overabundance is either small (Weistrop 1976; Sanduleak 1976) or non-existent (Faber et al. 1976; Eggen 1976). Nevertheless, Salpeter’s initial mass function (Salpeter 1955) suggests that the total mass may be dominated by low mass stars, including masses M≤0.08M⊙ which never undergo significant hydrogen burning.
A scalable approach for synthesis of ultra-thin (<10 nm) transition metal dichalcogenides (TMD) films on stretchable polymeric materials is presented. Specifically, magnetron sputtering from pure TMD targets, such as MoS2 and WS2, was used for growth of amorphous precursor films at room temperature on polydimethylsiloxane substrates. Stacks of different TMD films were grown upon each other and integrated with optically transparent insulating layers such as boron nitride. These precursor films were subsequently laser annealed to form high quality, few-layer crystalline TMDs. This combination of sputtering and laser annealing is commercially scalable and lends itself well to patterning. Analysis by Raman spectroscopy, scanning probe, optical, and transmission electron microscopy, and x-ray photoelectron spectroscopy confirm our assertions and illustrate annealing mechanisms. Electrical properties of simple devices built on flexible substrates are correlated to annealing processes. This new approach is a significant step toward commercial-scale stretchable 2D heterostructured nanoelectronic devices.
It was purely by chance, in 1989, that I saw in a newspaper an article announcing a competition sponsored by the Iraqi government to solve the riddle of how the Hanging Gardens of Babylon were irrigated. This proved to be the start of a project, which culminated in the submission of an entry for the competition in June 1990. As everyone is aware, the outbreak of hostilities in the Gulf followed soon after, ending any further communication on the matter.
Since that time, a considerable amount of further information has come into my possession, which has enabled me to expand on the initial written thesis. In this respect, I am particularly indebted to Dr. Irving Finkel's article in The Seven Wonders of the Ancient World (1988), which brought together all the ancient source material that is so difficult for an amateur like myself to obtain, and also to Joan Oates' Babylon (1979 and 1986) for much valuable background information.
I trust that my theories may prove to be of interest and perhaps also stimulate further discussion not only on the Hanging Gardens themselves but also on the much neglected subject of water raising devices of antiquity.