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Tuberous sclerosis complex is a rare genetic disorder leading to the growth of hamartomas in multiple organs, including cardiac rhabdomyomas. Children with symptomatic cardiac rhabdomyoma require frequent admissions to intensive care units, have major complications, namely, arrhythmias, cardiac outflow tract obstruction and heart failure, affecting the quality of life and taking on high healthcare cost. Currently, there is no standard pharmacological treatment for this condition, and the management includes a conservative approach and supportive care. Everolimus has shown positive effects on subependymal giant cell astrocytomas, renal angiomyolipoma and refractory seizures associated with tuberous sclerosis complex. However, evidence supporting efficacy in symptomatic cardiac rhabdomyoma is limited to case reports. The ORACLE trial is the first randomised clinical trial assessing the efficacy of everolimus as a specific therapy for symptomatic cardiac rhabdomyoma.
ORACLE is a phase II, prospective, randomised, placebo-controlled, double-blind, multicentre protocol trial. A total of 40 children with symptomatic cardiac rhabdomyoma secondary to tuberous sclerosis complex will be randomised to receive oral everolimus or placebo for 3 months. The primary outcome is 50% or more reduction in the tumour size related to baseline. As secondary outcomes we include the presence of arrhythmias, pericardial effusion, intracardiac obstruction, adverse events, progression of tumour reduction and effect on heart failure.
ORACLE protocol addresses a relevant unmet need in children with tuberous sclerosis complex and cardiac rhabdomyoma. The results of the trial will potentially support the first evidence-based therapy for this condition.
Over 400,000 people live in care home settings in the UK. One way of understanding and improving the quality of care provided is by measuring and understanding the quality of life (QoL) of those living in care homes. This review aimed to identify and examine the psychometric properties including feasibility of use of dementia-specific QoL measures developed or validated for use in care settings.
Instruments were identified using four electronic databases (PubMed, PsycINFO, Web of Science, and CINAHL) and lateral search techniques. Searches were conducted in January 2017. Studies which reported on the development and/or validation of dementia specific QoL instruments for use in care settings written in English were eligible for inclusion. The methodological quality of the studies was assessed using the COSMIN checklist. Feasibility was assessed using a checklist developed specifically for the review.
Six hundred and sixteen articles were identified in the initial search. After de-duplication, screening and further lateral searches were performed, 25 studies reporting on 9 dementia-specific QoL instruments for use in care home settings were included in the review. Limited evidence was available on the psychometric properties of many instruments identified. Higher-quality instruments were not easily accessible or had low feasibility of use.
Few high-quality instruments of QoL validated for use in care home settings are readily or freely available. This review highlights the need to develop a well-validated measure of QoL for use within care homes that is also feasible and accessible.
The study objective was to determine the prevalence of Staphylococcus aureus colonisation in the nares and oropharynx of healthy persons and identify any risk factors associated with such S. aureus colonisation. In total 263 participants (177 adults and 86 minors) comprising 95 families were enrolled in a year-long prospective cohort study from one urban and one rural county in eastern Iowa, USA, through local newspaper advertisements and email lists and through the Keokuk Rural Health Study. Potential risk factors including demographic factors, medical history, farming and healthcare exposure were assessed. Among the participants, 25.4% of adults and 36.1% minors carried S. aureus in their nares and 37.9% of adults carried it in their oropharynx. The overall prevalence was 44.1% among adults and 36.1% for minors. Having at least one positive environmental site for S. aureus in the family home was associated with colonisation (prevalence ratio: 1.34, 95% CI: 1.07–1.66). The sensitivity of the oropharyngeal cultures was greater than that of the nares cultures (86.1% compared with 58.2%, respectively). In conclusion, the nares and oropharynx are both important colonisation sites for healthy community members and the presence of S. aureus in the home environment is associated with an increased probability of colonisation.
In the MEETINGDEM project, the Meeting Centers Support Program (MCSP) was adaptively implemented and evaluated in three European countries: Italy, Poland, and the United Kingdom. The aim of this study was to investigate overall and country-specific facilitators and barriers to the implementation of MCSP in these European countries.
A qualitative multiple case study design was used. Based on the theoretical model of adaptive implementation, a checklist was composed of potential facilitators and barriers to the implementation of MCSP. This checklist was administered among stakeholders involved in the implementation of MCSP to trace the experienced facilitators and barriers. Twenty-eight checklists were completed.
Main similarities between countries were related to the presence of suitable staff, management, and a project manager, and the fact that the MCSP is attuned to needs and wishes of people with dementia and informal caregivers. Main differences between countries were related to: communication with potential referrers, setting up an inter-organizational collaboration network, receiving support of national organizations, having clear discharge criteria for the MCSP and continuous PR in the region.
The results of this study provide insight into generic and country specific factors that can influence the implementation of MCSP in different European countries. This study informs further implementation and dissemination of MCSP in Europe and may also serve as an example for the dissemination and implementation of other effective psychosocial support interventions for people with dementia and their informal caregivers across and beyond Europe.
We present a nano-patterning process for semiconducting polymeric composites that could potentially be utilized for the development of polymer-based data storage devices. Nano-patterning (writing) operates on the basis of the mechanical interaction between the electrically unbiased tip of an atomic force microscope and the surface of polymeric composite films. Via friction forces, the tip/sample interaction produces a local increase of molecular disorder in the polymer matrix, inducing a localized lowering in the conductivity of the organic semiconductor. Herein we suggest a figure of merit for quantifying the efficiency of pattern formation and we address the dependence of the writing process on the thermal annealing temperature of the composite film. Control experiments on composite films deposited on substrates with different roughness suggest that the writing effect is invariant to the roughness of the substrate. The potential storage density of the writing process depends on the tip curvature.
We have observed 12 interacting galaxies using the Fabry-Perot interferometer GHαFaS (Galaxy Hα Fabry-Perot system) on the 4.2m William Herschel Telescope (La Palma). We have extracted the physical properties (sizes, Hα luminosity and velocity dispersion) of 236 HII regions for the full sample of interacting galaxies. We have derived the physical properties of 664 HII regions for a sample of 28 isolated galaxies observed with the same instrument in order to compare both populations of HII regions, finding that there are brighter and denser star forming regions in the interacting galaxies compared with the isolated galaxies sample.
High-redshift quasars are unique probes of the evolution of supermassive black holes and the intergalactic medium at the end of the epoch of reionization. We present the optical spectra of eight new z ~ 6 quasars selected from the Panoramic Survey Telescope & Rapid Response System 1 (Pan-STARRS1). Details of the selection strategy can be found in Bañados et al. (2014). With this work we increase the number of known quasars at z < 5.7 by more than 10%. The quasars discovered here span a large range of luminosities (19.6 ≤ zP1 ≤ 21.2) and are remarkably heterogeneous in their spectral features: half of them show bright emission lines whereas the other half show weak or no Lyα emission line. We find a larger fraction of weak–line emission quasars than in lower redshift studies, although still based on low number statistics, this may imply that the quasar population could be more diverse than previously thought.
Since their discovery, four species of human bocavirus (HBoV) have been described in patients with respiratory and gastrointestinal diseases. However, a clear causal association between HBoV-1 and gastroenteritis has not been demonstrated. In this study, we describe the detection and quantification of HBoV-1 in stools from children with acute non-bacterial gastroenteritis using quantitative polymerase chain reaction. HBoV-1 genome was detected in 10·6% of stools with frequent association with rotavirus and norovirus. The median of HBoV-1 viral load was 1·88 × 104 genome/ml, lower than previously shown in secretions of patients with respiratory infections, without any obvious association between high viral load and presence of HBoV as single agent. Thus, although HBoV-1 was frequently detected in these patients, there is no clear causal association of this agent with diarrhoea. Indeed, HBoV-1 DNA in stools of patients with gastroenteritis without respiratory symptoms may be a remnant of previous infections or associated with prolonged shedding of virus in the respiratory or digestive tracts.
We investigate the MgII 2800 and CIV 1540 absorption features of the gas in the halo of a foreground QSO through the absorption imprinting on the spectra of a background QSO that is closely aligned with the nearest quasar. We present the results for 13 QSO pairs (0.7 < z < 2.2) that allow us to probe the gas at distances between 60 kpc and 120 kpc from the QSO nucleus. We identify absorption features associated with the foreground QSO in 7 out of 10 systems for MgII, and one out of 3 for CIV (see example in Fig. 1). At variance with the case of inactive and less massive galaxies we find that relatively strong (EW ~ 1 Ang) absorption features are present out to a radius of 100 kpc. This suggests that a large extended halo is associated with massive galaxies.
The comparison of these results with those for inactive (not hosting active black holes) galaxies (see e.g. Chen et al. 2010a) shows that the halo of QSOs is similar to that of inactive galaxies. In the observed sample we do not detect a significant enhancement of the absorption strengths, as it could be expected if the QSO nuclear activity were driven by intense gas accretion onto the black hole. Moreover along the line of sight of the QSO we do not detect any Mg II absorbers of the same strength of the transverse one. These results are in agreement with models that consider a non-isotropic emission of the QSO, which are hosted by massive gaseous halos.
A prospective cohort study with a 1-year telephone follow-up was performed to estimate the incidence of surgical-site infections (SSIs) in hip and knee prostheses. Twenty-five public hospitals equipped with orthopaedic units in two Italian regions were involved. An 8-month surveillance period was set to obtain significant data at a regional level and data were collected by the infection control nurses of each centre. One-year follow-up was completed in 75% of cases. SSIs were recorded in 45 cases (incidence rate 1·9/100 person-years, 95% CI 1·4–2·5). Thirty-six percent of SSIs were diagnosed during hospitalization and 95·3% within 90 days post-operation. This incidence is similar to that reported by European and USA surveillance systems. The proposed investigative method proved to be reliable and feasible. A prolonged surveillance for at least 3 months post-operation yields a good estimate of SSI in joint replacements.
Quantification of immunostaining is a widely used technique in pathology. Nonetheless, techniques that rely on human vision are prone to inter- and intraobserver variability, and they are tedious and time consuming. Digital image analysis (DIA), now available in a variety of platforms, improves quantification performance: however, the stability of these different DIA systems is largely unknown. Here, we describe a method to measure the reproducibility of DIA systems. In addition, we describe a new image-processing strategy for quantitative evaluation of immunostained tissue sections using DAB/hematoxylin-stained slides. This approach is based on image subtraction, using a blue low pass filter in the optical train, followed by digital contrast and brightness enhancement. Results showed that our DIA system yields stable counts, and that this method can be used to evaluate the performance of DIA systems. The new image-processing approach creates an image that aids both human visual observation and DIA systems in assessing immunostained slides, delivers a quantitative performance similar to that of bright field imaging, gives thresholds with smaller ranges, and allows the segmentation of strongly immunostained areas, all resulting in a higher probability of representing specific staining. We believe that our approach offers important advantages to immunostaining quantification in pathology.
We assessed total body water (TBW) and extracellular water (ECW) in thirty-four non-ascitic cirrhotics and twenty healthy controls by 2H2O and Br dilution. In the same subjects, bioelectric impedance (BI) was recorded at multiple frequencies. Body hydration was similar for controls (mean 55·6 (SD 6·7)), less-severe cirrhotics (Child-Pugh classification A; CPA; n 21, mean 56·2 (SD 6·2)) and moderately-severe cirrhotics (Child-Pugh classification B; CPB; n 13, mean 57·2 (SD 5·4)). However, intracellular water standardized per litre TBW was significantly higher in CPB subjects (mean 27·0 (SD 7·5); P<0·01) compared with CPA (mean 21·3 (SD 10·6)) and control subjects (mean 18·0 (SD 9·8)). Published formulas for predicting TBW and ECW from BI at multiple frequencies were applied to the cirrhotics. These formulas gave accurate predictions of TBW and ECW, although standard errors of estimates were higher for CPB subjects (TBW ≤ 2·5 and ECW ≤ 2·11) than those for CPA (TBW ≤ 2·0 and ECW ≤ 1·81) and control (TBW 1·4 and ECW 0·9 1) subjects
We present light curve analyses of contact binaries and comparisons with previously published cross-correlations radial velocity data. The critical parameter q (mass-ratio) obtained from a grid technique is confronted with the spectroscopic value. For total eclipsing systems, both values are always in a good or reasonable agreement, including some stars with shallow light curves. For partial eclipsing systems, convergent photometric and spectroscopic results are obtained for an important set of stars. Two exceptions are V523 Cas and XY Boo for which some arguments are suggested. We concluded that reliable parameter determinations can be obtained from pure photometric solutions, by means of grid techniques.