Statistics for Spatial Data.

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Modern Applied Statistics With S

Molecular imaging is the visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. Molecular imaging agents are probes used to visualize, characterize and measure biological processes in living systems. These two definitions were put forth by the Sociey of Nuclear Medicine (SNM) in 2007 as a way to capture the interdisciplinary nature of this relatively new field. The emergence of molecular imaging as a scientific discipline is a result of advances in chemistry, biology, physics and engineering, and the application of imaging probes and technologies has reshaped the philosophy of drug discovery in the pharmaceutical sciences by providing more cost effective ways to evaluate the efficacy of a drug candidate and allowing pharmaceutical companies to reduce the time it takes to introduce new therapeutics to the marketplace. Finally the impact of molecular imaging on clinical medicine has been extensive since it allows a physician to diagnose a patient’s illness, prescribe treatment and monitor the efficacy of that treatment non-invasively.

Single Photon Emission Computed Tomography (SPECT) and Positron Emission Tomography (PET) were the first molecular imaging modalities used clinically. SPECT requires the use of a contrast agent labeled with a gamma emitting radionuclide, which should have an ideal gamma energy of 100-250 keV. These gamma rays are recorded by the detectors of a dedicated gamma camera or SPECT instrument and after signal processing can be converted into an image indentifying the localization of the radiotracer. PET requires the injected radiopharmaceutical to be labeled with a positron emitting radionuclide. As the radionuclide decays it ejects a positron from its nucleus which travels a short distance before being annihilated with an electron to release two 511 keV gamma rays 180° apart that are detected by the PET scanner (Figure 1). After sufficient acquisition time the data are reconstructed using computer based algorithms to yield images of the radiotracer’s location within the organism. When compared to SPECT, PET has greater advantages with respect to sensitivity and resolution and has been gaining in clinical popularity, with the number of PET-based studies expected to reach 3.2 million by 2010.1 While SPECT and PET technology has been around for decades, its use remained limited because of the limited availability of relevant isotopes which had to be produced in nuclear reactors or particle accelerators. However, the introduction of the small biomedical cyclotron, the self-contained radionuclide generator and the dedicated small animal or clinical SPECT and PET scanners to hospitals and research facilities has increased the demand for SPECT and PET isotopes.



Figure 1

Cartoon depicting the fundamental principle of Positron Emission Tomography (PET). As the targeting group interacts with the cell surface receptor, the positron emitting radio-metal decays by ejecting β+ particles from its nucleus. After traveling ...



Traditional PET isotopes such as 18F, 15O, 13N and 11C have been developed for incorporation into small molecules, but due to their often lengthy radio-syntheses, short half-lives and rapid clearance, only early time points were available for imaging, leaving the investigation of biological processes, which occur over the duration of hours or days, difficult to explore. With the continuing development of biological targeting agents such as proteins, peptides, antibodies and nanoparticles, which demonstrate a range of biological half-lives, a need arose to produce new radionuclides with half-lives complementary with their biological properties. As a result, the production and radiochemistry of radiometals such as Zr, Y, In, Ga and Cu have been investigated as radionuclide labels for biomolecules since they have the potential to combine their favorable decay characteristics with the biological characteristics of the targeting molecule to become a useful radiopharmaceutical (Tables ​(Tables11 and ​and22).2



Table 1

Gamma- and Beta-Emitting Radiometals





Table 2

Positron-Emitting Radiometals



The number of papers published describing the production or use of these radiometals continues to expand rapidly, and in recognition of this fact, the authors have attempted to present a comprehensive review of this literature as it relates to the production, ligand development and radiopharmaceutical applications of radiometals (excluding 99mTc) since 1999. While numerous reviews have appeared describing certain aspects of the production, coordination chemistry or application of these radiometals,2-18 very few exhaustive reviews have been published.10,12 Additionally, this review has been written to be used as an individual resource or as a companion resource to the review written by Anderson and Welch in 1999.12 Together, they provide a literature survey spanning 50 years of scientific discovery. To accomplish this goal, this review has been organized into three sections: the first section discusses the coordination chemistry of the metal ions Zr, Y, In, Ga and Cu and their chelators in the context of radiopharmaceutical development; the second section describes the methods used to produce Zr, Y, In, Ga and Cu radioisotopes; and the final section describes the application of these radiometals in diagnostic imaging and radiotherapy.

/pdf/coordinating-radiometals-of-copper-gallium-indium-yttrium-3clup681fj.pdf

Coordinating Radiometals of Copper, Gallium, Indium, Yttrium and Zirconium for PET and SPECT Imaging of Disease

Renal osteodystrophy

The availability of massive digital traces of human whereabouts has offered a series of novel insights on the quantitative patterns characterizing human mobility. In particular, numerous recent studies have lead to an unexpected consensus: the considerable variability in the characteristic travelled distance of individuals coexists with a high degree of predictability of their future locations. Here we shed light on this surprising coexistence by systematically investigating the impact of recurrent mobility on the characteristic distance travelled by individuals. Using both mobile phone and GPS data, we discover the existence of two distinct classes of individuals: returners and explorers. As existing models of human mobility cannot explain the existence of these two classes, we develop more realistic models able to capture the empirical findings. Finally, we show that returners and explorers play a distinct quantifiable role in spreading phenomena and that a correlation exists between their mobility patterns and social interactions.

/pdf/returners-and-explorers-dichotomy-in-human-mobility-4zci3xx49m.pdf

Returners and explorers dichotomy in human mobility

The aim of the study was to assess the safety and efficacy of CT-guided percutaneous radiofrequency (RF) ablation of osteoid osteoma (OO). From 1997 to 2001, RF ablation was performed on 38 patients with OO, diagnosed clinically and by radiography, scintigraphy, contrast-enhanced MRI, and CT. Treatment was performed via percutaneous (n=29) or surgical (n=9) access, under CT guidance in all cases, with an 18-gauge straight electrode. Patients were discharged within 24 h and followed up clinically (at 1 week and every 6–12 months) and with MRI (at 6 months) and scintigraphy (after 1 year). The technical success rate was 100%. Complications occurred in two patients, consisting in local skin burns. The follow-up range was 12–66 months (mean ± SD, 35.5±7.5 months). Prompt pain relief and return to normal activities were observed in 30 of 38 patients. Persistent pain occurred in eight patients; two patients refused further RF ablation and were treated surgically; RF ablation was repeated in six cases achieving successful results in five. One patient reported residual pain and is being evaluated for surgical excision. Primary and secondary clinical success rates were 78.9 (30/38 patients) and 97% (35/36 patients), respectively. CT-guided RF ablation of OO is safe and effective. Persistent lesions can be effectively re-treated. Several imaging modalities are needed for the diagnosis of OO and for the follow-up after treatment, particularly in patients with persistent symptoms.

CT-guided radiofrequency ablation of osteoid osteoma: long-term results.

BACKGROUND Achieving adequate fixation strength in osteoporotic bone is a challenge. In this study, we examined the use of hydroxyapatite-coated tapered external-fixation pins for the fixation of wrist fractures in patients with osteoporosis. METHODS Twenty female patients with osteoporosis and a fracture of the wrist were divided into two paired groups and randomized to receive either standard tapered pins or hydroxyapatite-coated tapered pins. Two pins were inserted in the distal part of the radius, two pins were inserted in the second metacarpal, and an external fixation device was mounted. All fixation devices were removed six weeks after surgery. RESULTS The mean pin-insertion torque (and standard deviation) was 461 +/- 254 Nmm in the group managed with standard pins and 332 +/- 176 Nmm in the group managed with hydroxyapatite-coated pins (p = 0.01). The mean pin-extraction torque was 191 +/- 155 Nmm in the group managed with standard pins and 600 +/- 214 Nmm in the group managed with hydroxyapatite-coated pins (p < 0.0001, power 95%). The mean extraction torque was lower than the corresponding insertion torque at each pin position in the group managed with standard pins (p < 0.05), whereas the mean extraction torque was higher than the corresponding insertion torque at each pin position in the group managed with hydroxyapatite-coated pins (p = 0.001). Two patients managed with standard pins and no patient managed with hydroxyapatite-coated pins had a pin-track infection. Pain during pin removal did not differ between the two groups. CONCLUSIONS The present study showed that hydroxyapatite-coated tapered external-fixation pins provided improved fixation in the treatment of wrist fractures in patients with osteoporosis.

Improvement of the bone-pin interface strength in osteoporotic bone with use of hydroxyapatite-coated tapered external-fixation pins. A prospective, randomized clinical study of wrist fractures.

Small-area estimation techniques have typically relied on plug-in estimation based on models containing random area effects. More recently, regression M-quantiles have been suggested for this purpose, thus avoiding conventional Gaussian assumptions, as well as problems associated with the specification of random effects. However, the plug-in M-quantile estimator for the small-area mean can be shown to be the expected value of this mean with respect to a generally biased estimator of the small-area cumulative distribution function of the characteristic of interest. To correct this problem, we propose a general framework for robust small-area estimation, based on representing a small-area estimator as a functional of a predictor of this small-area cumulative distribution function. Key advantages of this framework are that it naturally leads to integrated estimation of small-area means and quantiles and is not restricted to M-quantile models. We also discuss mean squared error estimation for the resulting estimators, and demonstrate the advantages of our approach through model-based and design-based simulations, with the latter using economic data collected in an Australian farm survey.

/pdf/robust-estimation-of-small-area-means-and-quantiles-3hfw72d6cs.pdf

Robust estimation of small-area means and quantiles

The timely, accurate monitoring of social indicators, such as poverty or inequality, on a finegrained spatial and temporal scale is a crucial tool for understanding social phenomena and policymaking, but poses a great challenge to official statistics. This article argues that an interdisciplinary approach, combining the body of statistical research in small area estimation with the body of research in social data mining based on Big Data, can provide novel means to tackle this problem successfully. Big Data derived from the digital crumbs that humans leave behind in their daily activities are in fact providing ever more accurate proxies of social life. Social data mining from these data, coupled with advanced model-based techniques for fine-grained estimates, have the potential to provide a novel microscope through which to view and understand social complexity. This article suggests three ways to use Big Data together with small area estimation techniques, and shows how Big Data has the potential to mirror aspects of well-being and other socioeconomic phenomena.

/pdf/small-area-model-based-estimators-using-big-data-sources-32kw7v6nz4.pdf

Small Area Model-Based Estimators Using Big Data Sources

Abstract The timely, accurate monitoring of social indicators, such as poverty or inequality, on a finegrained spatial and temporal scale is a crucial tool for understanding social phenomena and policymaking, but poses a great challenge to official statistics. This article argues that an interdisciplinary approach, combining the body of statistical research in small area estimation with the body of research in social data mining based on Big Data, can provide novel means to tackle this problem successfully. Big Data derived from the digital crumbs that humans leave behind in their daily activities are in fact providing ever more accurate proxies of social life. Social data mining from these data, coupled with advanced model-based techniques for fine-grained estimates, have the potential to provide a novel microscope through which to view and understand social complexity. This article suggests three ways to use Big Data together with small area estimation techniques, and shows how Big Data has the potential to mirror aspects of well-being and other socioeconomic phenomena.

Stefano Marchetti

Papers

CT-guided radiofrequency ablation of osteoid osteoma: long-term results.

Improvement of the bone-pin interface strength in osteoporotic bone with use of hydroxyapatite-coated tapered external-fixation pins. A prospective, randomized clinical study of wrist fractures.

Robust estimation of small-area means and quantiles

Small Area Model-Based Estimators Using Big Data Sources

Small area model-based estimators using big data sources