Temperature-controlled power modulation compensates for heterogeneous nanoparticle distributions: a computational optimization analysis for magnetic hyperthermia

Purpose: To study, with computational models, the utility of power modulation to reduce tissue temperature heterogeneity for variable nanoparticle distributions in magnetic nanoparticle hyperthermia.

Methods: Tumour and surrounding tissue were modeled by elliptical two- and three-dimensional computational phantoms having six different nanoparticle distributions. Nanoparticles were modeled as point heat sources having amplitude-dependent loss power. The total number of nanoparticles was fixed, and their spatial distribution and heat output were varied. Heat transfer was computed by solving the Pennes’ bioheat equation using finite element methods (FEM) with temperature-dependent blood perfusion. Local temperature was regulated using a proportional-integral-derivative (PID) controller. Tissue temperature, thermal dose and tissue damage were calculated. The required minimum thermal dose delivered to the tumor was kept constant, and heating power was adjusted for comparison of both the heating methods.

Results: Modulated power heating produced lower and more homogeneous temperature distributions than did constant power heating for all studied nanoparticle distributions. For a concentrated nanoparticle distribution, located off-center within the tumor, the maximum temperatures inside the tumor were 16% lower for modulated power heating when compared to constant power heating. This resulted in less damage to surrounding normal tissue. Modulated power heating reached target thermal doses up to nine-fold more rapidly when compared to constant power heating.

Conclusions: Controlling the temperature at the tumor-healthy tissue boundary by modulating the heating power of magnetic nanoparticles demonstrably compensates for a variable nanoparticle distribution to deliver effective treatment.     

Latent variable modelling of risk factors associated with childhood diseases: Case study for Nigeria

ObjectiveTo investigate the impact of various bio-demographic and socio-economic variables on joint childhood diseases in Nigeria with flexible geoadditive probit models.MethodsGeoadditive latent variable model (LVM) was applied where the three observable disease (diarrhea, cough, fever) variables were modelled as indicators for the latent individual variable “health status” or “frailty” of a child. This modelling approach allowed us to investigate the common influence of risk factors on individual frailties of children, thereby automatically accounting for association between diseases as indicators for health status. The LVM extended to analyze the impact of risk factors and the spatial effects on the unobservable variable “health status” of a child less than 5 years of age using the 2003 Demographic and Health Surveys (DHS) data for Nigeria.ResultsThe results suggest some strong underlying spatial patterns of the three ailments with a clear southeastern divide of childhood morbidities and this might be the results in the overlapping of the various risk factors.ConclusionsComorbidity with conditions such as cough, diarrhoea and fever is common in Nigeria. However, little is known about common risk factors and geographical overlaps in these illnesses. The search for overlapping common risk factors and their spatial effects may improve our understanding of the etiology of diseases for efficient and cost-effective control and planning of the three ailments.     

Gender Differences in the Cross-Sectional Relationships Between Sleep Duration and Markers of Inflammation: Whitehall II Study

Objective:

To examine the relationships between sleep and inflammatory markers because these may be important in the development of cardiovascular disease.

Methods and Results:

The relationship between self-reported sleep duration and interleukin-6 (IL-6) (n = 4642) and high-sensitivity C-reactive protein (hs-CRP) (n = 4677) was examined in individuals from the Whitehall II study. Following multiple adjustments, there were no overall linear or nonlinear trends between sleep duration and IL-6. However, in women but not men (interaction P < 0.05), levels of IL-6 tended to be lower in individuals who slept 8 hours (11% [95% confidence interval 4 to 17]) as compared to 7 hours. With hs-CRP, in the adjusted model, there was no association between hs-CRP and sleep duration in men. However, there was a significant nonlinear association in women, the level of hs-CRP being significantly higher in women short sleepers (5 hours or less) after multiple adjustments (P = 0.04) (interaction P < 0.05).

Conclusions:

No significant variation in inflammatory markers with sleep duration was observed in men. By contrast, both IL-6 and hs-CRP levels varied with sleep duration in women. The observed pattern of variation was different according to the inflammatory marker observed. Further longitudinal studies are required to fully investigate possible temporal relationships between short sleep and markers of inflammation.

Citation:

Miller MA; Kandala NB; Kivimaki M; Kumari M; Brunner EJ; Lowe GDO; Marmot MG; Cappuccio FP. Gender differences in the cross-sectional relationships between sleep duration and markers of inflammation: Whitehall II study. SLEEP 2009;32(7):857-864.     

Spatial analysis of risk factors for childhood morbidity in Nigeria

Recent Demographic and Health Surveys (DHS) from Sub-Saharan Africa (SSA) indicate a decline in childhood vaccination coverage but a high prevalence of childhood diarrhea, cough, and fever. We used Nigerian DHS data to investigate the impact of geographical factors and other important risk factors on diarrhea, cough, and fever using geoadditive Bayesian semiparametric models. A higher prevalence of childhood diarrhea, cough, and fever is observed in the northern and eastern states, while lower disease prevalence is observed in the western and southern states. In addition, children from mothers with higher levels of education and those from poor households had a significantly lower association with diarrhea; children delivered in hospitals, living in urban areas, or from mothers having received prenatal visits had a significantly lower association with fever. Our maps are a novel and relevant tool to help local governments to improve health-care interventions and achieve Millennium Development Goals (MDG4).     

Cross-cultural comparison of correlates of quality of life and health status: the Whitehall II Study (UK) and the Western New York Health Study (US)

Measures of quality of life (QoL) have been found to be predictors of mortality and morbidity; however, there is still limited understanding of the multifaceted nature of these measures and of potential correlates. Using two large populations from the UK and US, we aimed to evaluate and compare measured levels of QoL and the key factors correlated with these levels. Participants were 6,472 white subjects (1,829 women) from the Whitehall II Study (mean age 55.8 years) and 3,684 white subjects (1,903 women) from the Western New York Health Study (mean age 58.7 years). QoL was assessed in both using the physical and mental health component summaries of the short form-36 questionnaire (SF-36). Analysis of covariance was used to compare gender-specific mean scores for the two populations across several potential correlates (including socio-demographic, lifestyle and co-morbidity factors). Levels of reported physical QoL tended to be higher in the UK population (51.2 vs. 48.6) while mental QoL was higher in the US group (53.1 vs. 51.1). Age, sleep duration and depressive symptoms were the main factors correlated with both physical and mental QoL in both samples. Increasing age was associated with poorer physical health but higher mental health scores in both populations (P<0.001). Sleep duration below 6 or above 8 h was associated with lower levels of QoL. Depressive symptoms were strongly associated with poorer mental health scores (P<0.001) while higher BMI, lower physical activity levels and presence of cardiovascular disease were associated with poorer physical health in both samples and gender (P<0.05). There were consistent findings for correlates of QoL in this cross-cultural comparison of two populations from the UK and US. Strongest associations were between lifestyle and co-morbidity factors and the physical health component of the SF-36 rather than the mental health component. This is a novel finding which warrants further consideration.     

The application of near-infrared oximetry to cerebral monitoring during aneurysm embolization: a comparison with intraprocedural angiography

Near-infrared spectroscopy (NIRS) has been used to monitor regional cerebral oxygen saturation (rSO2) in patients at risk of cerebral desaturation during surgical and neurointerventional procedures. However, the quantitative capabilities of the method have been questioned, as has its validation compared with jugular bulb oximetry. Here, we compare NIRS data acquired during coil embolization procedures with incidence of vasospasm as detected from angiography. Thirty-two subarachnoid hemorrhage patients underwent embolization. Bilateral SomaSensor strips (Invos 4100, Somanetics) were affixed to the forehead at constant anatomic positions, avoiding frontal sinuses and scalp hair. Mean arterial pressure, SaO2, end-tidal pCO2, temperature and Hb were held within a narrow range during the procedure. Ipsilateral angiography was performed every 10 to 15 minutes. An independent neuroradiologist classified any vasospasm in the parent vessel as mild (25% baseline), moderate (50%), severe (75%), or total (100%). Of all, 15/32 (46.9%) patients developed spasm; in 2 it was severe or total. There was no significant association between World Federation of Neurological Surgeons grade and baseline rSO2 signal (either ipsilateral or contralateral to the side of the aneurysm) (P=0.598). There was no significant association between side of aneurysm and baseline rSO2 signal (P=0.243). However, episodes of angiographic spasm were strongly associated with reduction in trend ipsilateral NIRS signal (P<0.001); furthermore, the degree of spasm (especially more than 75% vessel diameter reduction) was associated with a greater reduction in same-side NIRS signal (P<0.001) (2-level random effects regression model, Stata 8.2, Stata Corp, TX). NIRS may have a useful role to play in the detection of cerebral desaturation secondary to vasospasm during neuroendovascular procedures.     

Meta-analysis of short sleep duration and obesity in children and adults

BACKGROUND: Recent epidemiological studies suggest that short sleep duration may be associated with the development of obesity from childhood to adulthood. OBJECTIVES: To assess whether the evidence supports the presence of a relationship between short sleep duration and obesity at different ages, and to obtain an estimate of the risk. METHODS: We performed a systematic search of publications using MEDLINE (1996-2007 wk 40), EMBASE (from 1988), AMED (from 1985), CINHAL (from 1982) and PsycINFO (from 1985) and manual searches without language restrictions. When necessary, authors were contacted. Criteria for inclusion were: report of duration of sleep as exposure, BMI as continuous outcome and prevalence of obesity as categorical outcome, number of participants, age, and gender. Results were pooled using a random effect model. Sensitivity analysis was performed, heterogeneity and publication bias were also checked. Results are expressed as pooled odds ratios (OR [95% confidence intervals, CIs]) and as pooled regression coefficients (beta; 95% CIs). RESULTS: Of 696 studies identified, 45 met the inclusion criteria (19 in children and 26 in adults) and 30 (12 and 18, respectively) were pooled in the meta-analysis for a total of 36 population samples. They included 634,511 participants (30,002 children and 604,509 adults) from around the world. Age ranged from 2 to 102 years and included boys, girls, men and women. In children the pooled OR for short duration of sleep and obesity was 1.89 (1.46 to 2.43; P < 0.0001). In adults the pooled OR was 1.55 (1.43 to 1.68; P < 0.0001). There was no evidence of publication bias. In adults, the pooled beta for short sleep duration was -0.35 (-0.57 to -0.12) unit change in BMI per hour of sleep change. CONCLUSIONS: Cross-sectional studies from around the world show a consistent increased risk of obesity amongst short sleepers in children and adults. Causal inference is difficult due to lack of control for important confounders and inconsistent evidence of temporal sequence in prospective studies.