Cost effectiveness analysis of different approaches of screening for familial hypercholesterolaemia

Objectives To assess the cost effectiveness of strategies to screen for and treat familial hypercholesterolaemia. Design Cost effectiveness analysis. A care pathway for each patient was delineated and the associated probabilities, benefits, and costs were calculated. Participants Simulated population aged 16­54 years in England and Wales. Interventions Identification and treatment of patients with familial hypercholesterolaemia by universal screening, opportunistic screening in primary care, screening of people admitted to hospital with premature myocardial infarction, or tracing family members of affected patients. Main outcome measure Cost effectiveness calculated as cost per life year gained (extension of life expectancy resulting from intervention) including estimated costs of screening and treatment. Results Tracing of family members was the most cost effective strategy (£3097 (&5066, $4479) per life year gained) as 2.6 individuals need to be screened to identify one case at a cost of £133 per case detected. If the genetic mutation was known within the family then the cost per life year gained (£4914) was only slightly increased by genetic confirmation of the diagnosis. Universal population screening was least cost effective (£13 029 per life year gained) as 1365 individuals need to be screened at a cost of £9754 per case detected. For each strategy it was more cost effective to screen younger people and women. Targeted strategies were more expensive per person screened, but the cost per case detected was lower. Population screening of 16 year olds only was as cost effective as family tracing (£2777 with a clinical confirmation). Conclusions Screening family members of people with familial hypercholesterolaemia is the most cost effective option for detecting cases across the whole population

Cascaded acceleration of proton beams in ultrashort laser-irradiated microtubes

A cascaded ion acceleration scheme is proposed by use of ultrashort laser-irradiated microtubes. When the electrons of a microtube are blown away by intense laser pulses, strong charge-separation electric fields are formed in the microtube both along the axial and along the radial directions. By controlling the time delay between the laser pulses and a pre-accelerated proton beam injected along the microtube axis, we demonstrate that this proton beam can be further accelerated by the transient axial electric field in the laser-irradiated microtube. Moreover, the collimation of the injected proton beam can be enhanced by the inward radial electric field. Numerical simulations show that this cascaded ion acceleration scheme works efficiently even at non-relativistic laser intensities, and it can be applied to injected proton beams in the energy range from 1 to 100 MeV. Therefore, it is particularly suitable for cascading acceleration of protons to higher energy.Comment: 13 pages, 4 figure

Cyclonic entrainment of preconditioned shelf waters into a frontal eddy

The volume transport of nutrient-rich continental shelf water into a cyclonic frontal eddy (entrainment) was examined from satellite observations, a Slocum glider and numerical simulation outputs. Within the frontal eddy, parcels of water with temperature/salinity signatures of the continental shelf (18-19 degrees C and >35.5, respectively) were recorded. The distribution of patches of shelf water observed within the eddy was consistent with the spiral pattern shown within the numerical simulations. A numerical dye tracer experiment showed that the surface waters (= 95%) shelf waters. Particle tracking experiments showed that water was drawn into the eddy from over 4 degrees of latitude (30-34.5 degrees S). Consistent with the glider observations, the modeled particles entrained into the eddy sunk relative to their initial position. Particles released south of 33 degrees S, where the waters are cooler and denser, sunk 34 m deeper than their release position. Distance to the shelf was a critical factor in determining the volume of shelf water entrained into the eddy. Entrainment reduced to 0.23 Sv when the eddy was furthest from the shelf, compared to 0.61 Sv when the eddy was within 10 km of the shelf. From a biological perspective, quantifying the entrainment of shelf water into frontal eddies is important, as it is thought to play a significant role in providing an offshore nursery habitat for coastally spawned larval fish

Local Passive Acoustic Monitoring of Narwhal Presence in the Canadian Arctic: A Pilot Project

Long-term community-based monitoring of narwhals (Monodon monoceros) is needed because narwhals are important to local Inuit and are facing changes in their environment. We examined the suitability of passive acoustic recording for monitoring narwhals, using data gathered in the Canadian Arctic from an autonomous acoustic recorder (Repulse Bay, 2006) and a hand-held digital recorder (Koluktoo Bay, 2006 – 08). We found a relationship between the number of narwhals observed passing a fixed point and the number of calls heard. In addition, we found that an automated call detector could isolate segments of recording containing narwhal vocalizations over long recording periods containing non-target sound, thus decreasing the time spent on the analysis. Collectively, these results suggest that combining passive acoustic sampling with an automated call detector offers a useful approach for local monitoring of the presence and relative abundance of narwhals.La nécessité d’avoir un programme communautaire de surveillance à long terme des narvals (Monodon monoceros) s’avère évidente étant donné que les narvals revêtent de l’importance aux yeux des Inuits de la région et que leur environ­nement est en pleine évolution. Nous explorons la pertinence d’un programme de surveillance par acoustique passive pour les populations de narvals à partir de données récoltées dans l’Arctique canadien à l’aide d’une enregistreuse autonome (Repulse Bay, 2006) et d’une enregistreuse portable (Koluktoo Bay, 2006 – 2008). Grâce à des enregistrements accompagnés d’obser­vations sur le terrain, nous avons trouvé une corrélation entre le nombre de vocalisations entendues et le nombre de narvals observés. L’utilisation d’un détecteur automatique de vocalisations de narvals a permis d’isoler des segments d’enregis­trements contenant des vocalisations de narvals sur de longues périodes d’enregistrement contenant des sons non-ciblés, et ainsi diminuer le temps d’analyse. Ces résultats suggèrent que la combinaison de surveillance acoustique passive avec l’utili­sation d’un détecteur automatique offre une approche utile pour la surveillance locale de la présence et de l’abondance relative des narvals

Multisite Evaluation of Cepheid Xpert Carba-R Assay for Detection of Carbapenemase-Producing Organisms in Rectal Swabs.

Rapid identification of patients who are colonized with carbapenemase-producing organisms (CPO) is included in multiple national guidelines for containment of these organisms. In a multisite study, we evaluated the performance of the Cepheid Xpert Carba-R assay, a qualitative diagnostic test that was designed for the rapid detection and differentiation of the blaKPC, blaNDM, blaVIM, blaOXA-48, and blaIMP-1 genes from rectal swab specimens. A double rectal swab set was collected from 383 patients admitted at four institutions (2 in the United States, 1 in the United Kingdom, 1 in Spain). One swab was used for reference culture (MacConkey broth containing 1 mg/liter of meropenem and subcultured to a MacConkey agar plate with a 10-μg meropenem disk) and for sequencing of DNA obtained from carbapenem-nonsusceptible isolates for carbapenemase identification. The other swab was used for the Xpert Carba-R assay. In addition to the clinical rectal swabs, 250 contrived specimens (108 well-characterized CPO and 142 negative controls spiked onto negative rectal swabs) were tested. Overall, 149/633 (23.5%) samples were positive by the Xpert Carba-R assay. In 6 samples, multiple targets were detected (4 VIM/OXA-48, 1 IMP-1/NDM, and 1 NDM/KPC). The Xpert Carba-R assay detected 155 targets (26 IMP-1, 30 VIM, 27 NDM, 33 KPC, 39 OXA-48) within a time range of 32 to 48 min. The sensitivity, specificity, and positive and negative predictive values of the Xpert Carba-R assay compared to those of the reference culture and sequencing results were 96.6% (95% confidence interval [CI], 92.2% to 98.9%), 98.6% (95% CI, 97.1% to 99.4%), 95.3%, and 99.0%, respectively. The Cepheid Xpert Carba-R assay is an accurate and rapid test to identify rectal colonization with CPO, which can guide infection control programs to limit the spread of these organisms

Investigating the Effect of Withania somnifera, Selenium and Hydrocortisone on Blood Count and Bronchial Lavage of Experimental Asthmatic BALB/c Mice

The murine asthmatic Balb/c mouse model was used to investigate the effect of W. somnifera L., the  antioxidant selenium, W. somnifera and selenium in combination and hydrocortisone as positive control  on the number of white blood cells in blood smears and bronchial lavage smears as well as the platelet  distribution of asthmatic Balb/c mice. The mice were sensitised, nebulized and treated over a period of  43 days and blood smears were made of each individual animal and bronchial lavage was performed by  injecting 0.3ml of saline into the trachea of the mice, both on the day of termination. Light microscopy  analysis of the bronchial lavage revealed a significant decrease in the number of eosinophils counted in the  asthmatic and the different treatment groups. In the asthmatic group, numerous platelet clumps were found  distributed between white blood cells. Platelets were also found in the other treatment groups but are not  as prevalent as in the asthmatic group. Results from the blood smears showed the same trends, where cell  counts in control and hydrocortisone blood smears were decreased compared to that of the asthma group. It  is concluded that W. somnifera and W. somnifera combined with selenium significantly decreased the white  blood cells in both bronchial lavage as well as blood smears, suggesting that W. somnifera indeed has an  anti-inflammatory potential and it, in combination with an anti-oxidant like selenium, might successfully  be used in the treatment of asthma.

Application of in vivo micro-computed tomography in the temporal characterisation of subchondral bone architecture in a rat model of low-dose monosodium iodoacetate-induced osteoarthritis

The electronic version of this article is the complete one and can be found online at: http://arthritis-research.com/content/13/6/R210Introduction: Osteoarthritis (OA) is a complex, multifactorial joint disease affecting both the cartilage and the subchondral bone. Animal models of OA aid in the understanding of the pathogenesis of OA and testing suitable drugs for OA treatment. In this study we characterized the temporal changes in the tibial subchondral bone architecture in a rat model of low-dose monosodium iodoacetate (MIA)-induced OA using in vivo micro-computed tomography (CT). Methods: Male Wistar rats received a single intra-articular injection of low-dose MIA (0.2 mg) in the right knee joint and sterile saline in the left knee joint. The animals were scanned in vivo by micro-CT at two, six, and ten weeks post-injection, analogous to early, intermediate, and advanced stages of OA, to assess architectural changes in the tibial subchondral bone. The articular cartilage changes in the tibiae were assessed macroscopically and histologically at ten weeks post-injection. Results: Interestingly, tibiae of the MIA-injected knees showed significant bone loss at two weeks, followed by increased trabecular thickness and separation at six and ten weeks. The trabecular number was decreased at all time points compared to control tibiae. The tibial subchondral plate thickness of the MIA-injected knee was increased at two and six weeks and the plate porosity was increased at all time points compared to control. At ten weeks, histology revealed loss of proteoglycans, chondrocyte necrosis, chondrocyte clusters, cartilage fibrillation, and delamination in the MIA-injected tibiae, whereas the control tibiae showed no changes. Micro-CT images and histology showed the presence of subchondral bone sclerosis, cysts, and osteophytes. Conclusions: These findings demonstrate that the low-dose MIA rat model closely mimics the pathological features of progressive human OA. The low-dose MIA rat model is therefore suitable to study the effect of therapeutic drugs on cartilage and bone in a non-trauma model of OA. In vivo micro-CT is a non-destructive imaging technique that can track structural changes in the tibial subchondral bone in this animal model, and could also be used to track changes in bone in preclinical drug intervention studies for OA treatments.Geetha Mohan, Egon Perilli, Julia S Kuliwaba, Julia M Humphries, Ian H Parkinson and Nicola L Fazzalar

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study