The use of inorganic nanoparticles as probes to label and track cells in vivo is already a reality. While superparamagnetic nanoparticles have been the subject of clinical studies involving magnetic resonance imaging, quantum dots and gold nanoparticles are starting to be explored for similar goals in pre-clinical studies involving fluorescence and photoacoustic imaging. Although exciting results have been obtained from in vivo investigations, there appears to be a general lack of understanding on the effects of physicochemical properties on the labelling efficiency and toxicity of those nanoparticles, as well as on their stability in the intracellular microenvironment; essential requirements for using them as probes for cellular tracking. In this tutorial review, we look at what the current literature can teach us in respect to cell interactions with these nanoparticles, with the perspective of using them as probes for cell labelling. We also examine the findings obtained in pre-clinical studies that expose potential misinterpretation that can occur when using inorganic nanoparticles for in vivo imaging.

Conditions with limb pterygia and congenital contractures were reviewed as part of a study of over 350 infants with arthrogryposis. Emphasis was placed on inheritance and variability of distinct pterygium conditions. Eleven patients with limb pterygia were recognized in our study and are described here. Seven of the 350 patients with congenital contractures had the autosomal recessively inherited multiple pterygium syndrome (Patients 1-7). Three of the seven are sibs, a fourth was born to consanguineous parents, and three were chance isolated cases. These seven had multiple joint webs, unusual finger contractures, syndactyly, rocker bottom feet, ptosis, antimongoloid slant of palpebral fissures, epicanthal folds, highly arched palate, scoliosis, and short stature. There is intrafamilial variability. Three patients from one family had a lethal multiple pterygium syndrome. Two were monozygotic twins. They had webbing and contractures of the elbows, knees, neck, and fingers, calcaneovalgus deformity of the feet, and an unusual facial appearance: hypertelorism, flat nose, antimongoloid slant of palpebral fissures, apparently low-set ears. One had a cleft palate. Internal malformations included: bilateral pulmonary hypoplasia, small heart, absence of the appendix, and attenuation of the ascending and transverse colon. One sporadic case of lethal popliteal pterygium with facial clefts was studied. Multiple anomalies included: ankyloblepharon filiforme adnatum, upslanting palpebral fissures, hypoplasia of nasal cartilages, frenula, clefts into the oropharynx lateral to the mouth, apparently low-set ears with slit-like canals, large popliteal pterygia, syndactyly with fusion of all digits in hands and feet, and hypoplastic labia.

We developed a coating method to produce functionalized small quantum dots (sQDs), ~ 9 nm in diameter, that were stable for over a month. We made sQDs in four emission wavelengths, from 527 nm to 655 nm and with different functional groups. AMPA receptors on live neurons were labeled with sQDs and post-synaptic density proteins were visualized with super-resolution microscopy. Their diffusion behavior indicates that sQDs access the synaptic clefts significantly more often than commercial QDs.

Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

Accurate estimates of the under-five mortality rate in a developing world context are a key barometer of the health of a nation. This paper describes a new model to analyze survey data on mortality in this context. We are interested in both spatial and temporal description, that is wishing to estimate under-five mortality rate across regions and years and to investigate the association between the under-five mortality rate and spatially varying covariate surfaces. We illustrate the methodology by producing yearly estimates for subnational areas in Kenya over the period 1980-2014 using data from the Demographic and Health Surveys, which use stratified cluster sampling. We use a binomial likelihood with fixed effects for the urban/rural strata and random effects for the clustering to account for the complex survey design. Smoothing is carried out using Bayesian hierarchical models with continuous spatial and temporally discrete components. A key component of the model is an offset to adjust for bias due to the effects of HIV epidemics. Substantively, there has been a sharp decline in Kenya in the under-five mortality rate in the period 1980-2014, but large variability in estimated subnational rates remains. A priority for future research is understanding this variability. In exploratory work, we examine whether a variety of spatial covariate surfaces can explain the variability in under-five mortality rate. Temperature, precipitation, a measure of malaria infection prevalence, and a measure of nearness to cities were candidates for inclusion in the covariate model, but the interplay between space, time, and covariates is complex.

Adherence to oral daily bisphosphonate regimens in postmenopausal osteoporosis is currently suboptimal. Less frequent dosing regimens are likely to improve patient adherence and thus, potentially, patient outcomes. A multicenter, randomized, double-blind, noninferiority study was conducted in 235 women (53-80 yr old; time since menopause >/==" BORDER="0"> 3 yr) with postmenopausal osteoporosis [lumbar spine (L1-L4) bone mineral density (BMD) T-score

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The analysis of area-level aggregated summary data is common in many disciplines including epidemiology and the social sciences. Typically, Markov random field spatial models have been employed to acknowledge spatial dependence and allow data-driven smoothing. In the context of an irregular set of areas, these models always have an ad hoc element with respect to the definition of a neighborhood scheme. In this article, we exploit recent theoretical and computational advances to carry out modeling at the continuous spatial level, which induces a spatial model for the discrete areas. This approach also allows reconstruction of the continuous underlying surface, but the interpretation of such surfaces is delicate since it depends on the quality, extent and configuration of the observed data. We focus on models based on stochastic partial differential equations. We also consider the interesting case in which the aggregate data are supplemented with point data. We carry out Bayesian inference and, in the language of generalized linear mixed models, if the link is linear, an efficient implementation of the model is available via integrated nested Laplace approximations. For nonlinear links, we present two approaches: a fully Bayesian implementation using a Hamiltonian Monte Carlo algorithm and an empirical Bayes implementation, that is much faster and is based on Laplace approximations. We examine the properties of the approach using simulation, and then apply the model to the classic Scottish lip cancer data.