SummarySmall 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.

In recent years, Italy has been registering peaks in death rates, particularly among the elderly during the winter season. Influenza epidemics have been indicated as one of the potential determinants of such an excess. The objective of our study was to estimate the influenza-attributable contribution to excess mortality during the influenza seasons from 2013/14 to 2016/17 in Italy. Methods: We used the EuroMomo and the FluMomo methods to estimate the annual trend of influenzaattributable excess death rate by age group. Population data were provided by the National Institute of Statistics, data on influenza like illness and confirmed influenza cases were provided by the National Institutes of Health. As an indicator of weekly influenza activity (IA) we adopted the Goldstein index, which is the product of the percentage of patients seen with influenza-like illness (ILI) and percentage of influenza-positive specimens, in a given week. Results: We estimated excess deaths of 7,027, 20,259, 15,801 and 24,981 attributable to influenza epidemics in the 2013/14, 2014/15, 2015/16 and 2016/17, respectively, using the Goldstein index. The average annual mortality excess rate per 100,000 ranged from 11.6 to 41.2 with most of the influenzaassociated deaths per year registered among the elderly. However children less than 5 years old also reported a relevant influenza attributable excess death rate in the 2014/15 and 2016/17 seasons (1.05/ 100,000 and 1.54/100,000 respectively). Conclusions: Over 68,000 deaths were attributable to influenza epidemics in the study period. The observed excess of deaths is not completely unexpected, given the high number of fragile very old subjects living in Italy. In conclusion, the unpredictability of the influenza virus continues to present a major challenge to health professionals and policy makers. Nonetheless, vaccination remains the most effective means for reducing the burden of influenza, and efforts to increase vaccine coverage and the introduction of new vaccine strategies (such as vaccinating healthy children) should be considered to reduce the influenza attributable excess mortality experienced in Italy and in Europe in the last seasons.

2'-C-Methyl analogues of selective adenosine receptor agonists such as (R)-PIA, CPA, CCPA, NECA, and IB-MECA were synthesized in order to further investigate the subdomain that binds the ribose moiety. Binding affinities of these new compounds at A1 and A2A receptors in bovine brain membranes and at A3 in rat testis membranes were determined and compared. It was found that the 2'-C-methyl modification resulted in a decrease of the affinity, particularly at A2A and A3 receptors. When such modification was combined with N6-substitutions with groups which induce high potency and selectivity at A1 receptors, the high affinity was retained and the selectivity was increased. Thus, 2-chloro-2'-C-methyl-N6-cyclopentyladenosine (2'-Me-CCPA), which displayed a Ki value of 1.8 nM at A1 receptors, was selective for A1 vs A2A and A3 receptors by 2166- and 2777-fold, respectively, resulting in one of the most potent and A1-selective agonists so far known. In functional assay, this compound inhibited forskolin-stimulated adenylyl cyclase activity with an IC50 value of 13.1 nM, acting as a full agonist.

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.

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.

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A bone healing assessment is crucial for the successful treatment of fractures, particularly in terms of the timing of support devices. However, in clinical practice, this assessment is only made qualitatively through bone manipulation and X-rays, and hence cannot be repeated as often as might be required. The present study reconsiders the quantitative method of frequency response analysis for healing assessments, and specifically for fractures treated with an external fixator. The novelty consists in the fact that bone excitation and response are achieved through fixator pins, thus overcoming the problem of transmission through soft-tissues and their damping effect. The main objective was to develop and validate a test procedure in order to characterize the treated bone. More than 80 tests were performed on a tibia phantom alone, a phantom with pins, and a phantom with a complete fixator. Different excitation techniques and input-output combinations were compared. The results demonstrated the effectiveness of a procedure based on impact tests using a micro-hammer. Pins and fixator were demonstrated to influence the frequency response of the phantom by increasing the number of resonant frequencies. This procedure will be applied in future studies to monitor healing both in in vitro and in vivo conditions.