Assessment of carotid plaque vulnerability using structural and geometrical determinants

BACKGROUND: Because many acute cerebral ischemic events are caused by rupture of vulnerable carotid atheroma and subsequent thrombosis, the present study used both idealized and patient-specific carotid atheromatous plaque models to evaluate the effect of structural determinants on stress distributions within plaque. METHODS AND RESULTS: Using a finite element method, structural analysis was performed using models derived from in vivo high-resolution magnetic resonance imaging (MRI) of carotid atheroma in 40 non-consecutive patients (20 symptomatic, 20 asymptomatic). Plaque components were modeled as hyper-elastic materials. The effects of varying fibrous cap thickness, lipid core size and lumen curvature on plaque stress distributions were examined. Lumen curvature and fibrous cap thickness were found to be major determinants of plaque stress. The size of the lipid core did not alter plaque stress significantly when the fibrous cap was relatively thick. The correlation between plaque stress and lumen curvature was significant for both symptomatic (p=0.01; correlation coefficient: 0.689) and asymptomatic patients (p=0.01; correlation coefficient: 0.862). Lumen curvature in plaques of symptomatic patients was significantly larger than those of asymptomatic patients (1.50+/-1.0 mm(-1) vs 1.25+/-0.75 mm(-1); p=0.01). CONCLUSION: Specific plaque morphology (large lumen curvature and thin fibrous cap) is closely related to plaque vulnerability. Structural analysis using high-resolution MRI of carotid atheroma may help in detecting vulnerable atheromatous plaque and aid the risk stratification of patients with carotid disease.     

Cost-effectiveness analysis of different embryo transfer strategies in England

Objective  The objective of this study was to assess the cost-effectiveness of different embryo transfer strategies for a single cycle when two embryos are available, and taking the NHS cost perspective.
Design  Cost-effectiveness model.
Setting  Five in vitro fertilisation (IVF) centres in England between 2003/04 and 2004/05.
Population  Women with two embryos available for transfer in three age groups (<30, 30–35 and 36–39 years).
Methods  A decision analytic model was constructed using observational data collected from a sample of fertility centres in England. Costs and adverse outcomes are estimated up to 5 years after the birth. Incremental cost per live birth was calculated for different embryo transfer strategies and for three separate age groups: less than 30, 30–35 and 36–39 years.
Main outcome measures  Premature birth, neonatal intensive care unit admissions and days, cerebral palsy and incremental cost-effectiveness ratios.
Results  Single fresh embryo transfer (SET) plus frozen single embryo transfer (fzSET) is the more costly in terms of IVF costs, but the lower rates of multiple births mean that in terms of total costs, it is less costly than double embryo transfer (DET). Adverse events increase when moving from SET to SET+fzSET to DET. The probability of SET+fzSET being cost-effective decreases with age. When SET is included in the analysis, SET+fzSET no longer becomes a cost-effective option at any threshold value for all age groups studied.
Conclusions  The analyses show that the choice of embryo transfer strategy is a function of four factors: the age of the mother, the relevance of the SET option, the value placed on a live birth and the relative importance placed on adverse outcomes. For each patient group, the choice of strategy is a trade-off between the value placed on a live birth and cost.     

Spontaneous pregnancy after successful ICSI treatment: evaluation of risk factors in 899 families in Germany

There are only scarce data on the incidence of spontaneous pregnancy in infertility patients. Contraception after infertility treatment is another topic that has been neglected so far. Therefore, a questionnaire was sent to 1614 couples with a child conceived by intracytoplasmic sperm injection (ICSI) aged 4-6 years. A total of 899 couples responded (response rate 55.7%). A total of 10.9% of couples had used contraception. Of the couples that had actively tried to conceive, 20.0% had conceived spontaneously, resulting in a live-birth rate of 16.4%. 74.5% of these pregnancies were conceived within 2 years after delivery. A further 26.6% of couples conceived again by ICSI, with a live-birth rate of 20.9%. Maternal age was the only prognostic factor for spontaneous conception. Parents of multiples after ICSI did not have a higher chance of spontaneous conception than parents of singletons. Couples can be counselled that one out of five couples conceive spontaneously after successful ICSI. Even when assuming that none of the families that were lost to follow-up had conceived spontaneously, one out of eight couples would have conceived spontaneously. Therefore, it is important to counsel patients about the possibility of natural conception and necessity to use contraception despite their history of subfertility.     

Actions of recombinant human γ-interferon and tumor necrosis factor α on the proliferation and osteoblastic characteristics of human trabecular bone cells in vitro

Using cultured human osteoblast-like cells, we studied the effects of tumor necrosis factor (TNF) and recombinant human γ-interferon (γ-IFN) on osteoblast growth and function, and demonstrated that TNF stimulated bone cell proliferation and prostaglandin production while inhibiting 1,25-(OH)₂D₃—stimulated alkaline phosphatase activity and osteocalcin release. In contrast, γ-IFN inhibited proliferation and stimulated alkaline phosphatase activity of the cells, while inhibiting 1,25-(OH)₂D₃—stimulated osteocalcin production and having variable effects on the release of prostaglandins, depending on the presence of other factors. Our results suggest that TNF and γ-IFN can act directly on bone-forming cells to affect both their proliferation and their differentiated function, and that changes in the ability of cells to produce these factors in disease states may contribute to alterations in the integrity of connective tissue matrices.     

Novel method for combined linkage and genome-wide association analysis finds evidence of distinct genetic architecture for two subtypes of autism

The Autism Genome Project has assembled two large datasets originally designed for linkage analysis and genome-wide association analysis, respectively: 1,069 multiplex families genotyped on the Affymetrix 10 K platform, and 1,129 autism trios genotyped on the Illumina 1 M platform. We set out to exploit this unique pair of resources by analyzing the combined data with a novel statistical method, based on the PPL statistical framework, simultaneously searching for linkage and association to loci involved in autism spectrum disorders (ASD). Our analysis also allowed for potential differences in genetic architecture for ASD in the presence or absence of lower IQ, an important clinical indicator of ASD subtypes. We found strong evidence of multiple linked loci; however, association evidence implicating specific genes was low even under the linkage peaks. Distinct loci were found in the lower IQ families, and these families showed stronger and more numerous linkage peaks, while the normal IQ group yielded the strongest association evidence. It appears that presence/absence of lower IQ (LIQ) demarcates more genetically homogeneous subgroups of ASD patients, with not just different sets of loci acting in the two groups, but possibly distinct genetic architecture between them, such that the LIQ group involves more major gene effects (amenable to linkage mapping), while the normal IQ group potentially involves more common alleles with lower penetrances. The possibility of distinct genetic architecture across subtypes of ASD has implications for further research and perhaps for research approaches to other complex disorders as well.     

Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers

Comparative effectiveness research has become an integral part of health care planning in most developed countries. In a simulated cohort of women, aged 30–65, who tested positive for BRCA1 or BRCA2 mutations, we compared outcomes of mammography with and without MRI, prophylactic oophorectomy with and without mastectomy, mastectomy alone, and chemoprevention. Methods: Using Treeage 9.02 software, we developed Markov models with 25,000 Monte Carlo simulations and conducted probabilistic sensitivity analysis. We based mutation penetrance rates, breast and ovarian cancer incidence, and mortality rates, and costs in terms of 2009 dollars, on published studies and data from the Surveillance, Epidemiology, and End Results (SEER) Program and the Centers for Medicare and Medicaid Services. We used preference ratings obtained from mutation carriers and controls to adjust survival for quality of life (QALYs). Results: For BRCA1 mutation carriers, prophylactic oophorectomy at 1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For < i > BRCA2 < /i > carriers, prophylactic oophorectomy, at1,741 per QALY, was more cost effective than both surgeries and dominated all other interventions. For BRCA2 carriers, prophylactic oophorectomy, at 4,587 per QALY, was more cost effective than both surgeries. Without quality adjustment, both mastectomy and BSO surgeries dominated all other interventions. In all simulations, preventive surgeries or chemoprevention dominated or were more cost effective than screening because screening modalities were costly. Conclusion: Our analysis suggested that among BRCA1/2 mutation carriers, prophylactic surgery would dominate or be cost effective compared to chemoprevention and screening. Annual screening with MRI and mammography was the most effective strategy because it was associated with the longest quality-adjusted survival, but it was also very expensive.     

Accuracy and repeatability of fourier velocity encoded M‐mode and two‐dimensional cine phase contrast for pulse wave velocity measurement in the descending aorta

Purpose:

To assess the accuracy and repeatability of Fourier velocity encoded (FVE) M‐mode and two‐dimensional (2D) phase contrast with through‐plane velocity encoding (2D‐PC) for pulse wave velocity (PWV) evaluation in the descending aorta using five different analysis techniques.

Materials and Methods:

Accuracy experiments were conducted on a tubular human‐tissue‐mimicking phantom integrated into a flow simulator. The theoretical PWV value was derived from the Moens‐Korteweg equation after measurement of the tube elastic modulus by uniaxial tensile testing (PWV = 6.6 ± 0.7 m/s). Repeatability was assessed on 20 healthy volunteers undergoing three consecutive MR examinations.

Results:

FVE M‐mode PWV was more repeatable than 2D‐PC PWV independently of the analysis technique used. The early systolic fit (ESF) method, followed by the maximum of the first derivative (1st der.) method, was the most accurate (PWV = 6.8 ± 0.4 m/s and PWV = 7.0 ± 0.6 m/s, respectively) and repeatable (inter‐scan within‐subject variation δ = 0.096 and δ = 0.107, respectively) for FVE M‐mode. For 2D‐PC, the 1st der. method performed best in terms of accuracy (PWV = 6.8 ± 1.1 m/s), whereas the ESF algorithm was the most repeatable (δ = 0.386).

Conclusion:

FVE M‐mode allows rapid, accurate and repeatable central PWV evaluation when the ESF algorithm is used. 2D‐PC requires long scan times and can provide accurate although much less repeatable PWV measurements when the 1st der. method is used. J. Magn. Reson. Imaging 2010;31:1185–1194. © 2010 Wiley‐Liss, Inc.     

Strategies for success: a toolbox of coping strategies used by breastfeeding women

Aims. The purpose of this paper is to present the findings of two qualitative studies which identified strategies used by breastfeeding women to assist them to continue breastfeeding. Background. While breastfeeding initiation rates are high in Australia, the majority of women wean before the recommended time. The identification of interventions which may increase breastfeeding duration is therefore a research priority. Design. The Against All Odds study used a case‐controlled design to investigate the characteristics of women who continued to breastfeed in the face of extraordinary difficulties. Phase One of the I Think I Can study employed the Nominal Group Technique to investigate the views of subject matter experts regarding which psychological factors may influence the duration of breastfeeding. Method. Against All Odds study participants (n = 40) undertook a one‐ to two‐hour interview and the transcribed data were analysed using thematic analysis. Stratified purposeful sampling was employed in the I Think I Can study (n = 21), with participants assigned group membership according to their most recent breastfeeding experience. A fourth group was composed of experienced breastfeeding clinicians. The nominal group technique was used to generate group data and segments of the discussion were audiotaped and transcribed for thematic analysis. Results. Participants in both the studies raised strategies used to assist them in their efforts to cope with the challenges of breastfeeding and early motherhood. These strategies included increasing breastfeeding knowledge, staying relaxed and ‘looking after yourself’, the use of positive self‐talk, challenging unhelpful beliefs, problem solving, goal setting and the practice of mindfulness. Conclusions. Employment of these simple behavioural and cognitive strategies may assist women to cope with the pressures inherent in the experience of early mothering, thereby increasing the duration of breastfeeding. Relevance to clinical practice. These results may represent a ‘tool box’ of coping strategies which can be provided to women for use in the postnatal period.