Different somatic alterations of the HRPT2 gene in a patient with recurrent sporadic primary hyperparathyroidism carrying an HRPT2 germline mutation

Early onset of primary hyperparathyroidism (PHPT) and multiglandular involvement suggest a familial form in which germline mutation of a PHPT-related gene(s) and a somatic event at the same locus can be often demonstrated. We investigated the involvement of multiple endocrine neoplasia type 1 (MEN1) and HRPT2 genes in a 39-year-old man with recurrent PHPT. PHPT was firstly diagnosed at the age of 21 and the patient had two recurrences separated by extended periods of normocalcemia. This unusual history prompted us to investigate other family members and study the MEN1 and HRPT2 genes. An HRPT2 germline missense mutation in exon 3 (R91P) was found in the index case, which was associated with different HRPT2 somatic alterations in each of the three examined parathyroid tumors. These findings are consistent with Knudson's 'two hit' concept of biallelic inactivation of classical tumor suppressor genes. Screening of 15 asymptomatic relatives was negative for the R91P germline mutation. All the three abnormal parathyroid specimens showed cystic features at histology and were negative for parafibromin immunostaining. In one specimen, diffuse parafibromin staining was evident in a rim of normal parathyroid tissue surrounding the adenomatous lesion. Our study shows that different somatic genetic events at the HRPT2 locus are responsible for the asynchronous occurrence of multiple adenomas in a patient carrying an HRPT2 germline mutation. The finding of diffuse parafibromin staining in a rim of normal parathyroid tissue, but not in the contiguous adenomatous lesion, reinforces the concept that loss of parafibromin expression is responsible for the development of parathyroid tumors in this setting

Small Area Estimation of Latent Economic Well-being

© The Author(s) 2019. Small area estimation (SAE) plays a crucial role in the social sciences due to the growing need for reliable and accurate estimates for small domains. In the study of well-being, for example, policy makers need detailed information about the geographical distribution of a range of social indicators. We investigate data dimensionality reduction using factor analysis models and implement SAE on the factor scores under the empirical best linear unbiased prediction approach. We contrast this approach with the standard approach of providing a dashboard of indicators or a weighted average of indicators at the local level. We demonstrate the approach in a simulation study and a real data application based on the European Union Statistics for Income and Living Conditions for the municipalities of Tuscany

Charge transport and trapping in Cs-doped poly(dialkoxy-p-phenylene vinylene) light-emitting diodes

Al/Cs/MDMO-PPV/ITO (where MDMO-PPV stands for poly[2-methoxy-5-(3'-7'-dimethyloctyloxy)-1,4phenylene vinylene] and ITO is indium tin oxide) light-emitting diode (LED) structures, made by physical vapor deposition of Cs on the emissive polymer layer, have been characterized by electroluminescence, current-voltage, and admittance spectroscopy. Deposition of Cs is found to improve the balance between electron and hole currents, enhancing the external electroluminescence efficiency from 0.01 cd A-1 for the bare Al cathode to a maximum of 1.3 cd A-1 for a Cs coverage of only 1.5×1014 atoms/cm2. By combining I-V and admittance spectra with model calculations, in which Cs diffusion profiles are explicitly taken into account, this effect could be attributed to a potential drop at the cathode interface due to a Cs-induced electron donor level 0.61 eV below the lowest unoccupied molecular orbital. In addition, the admittance spectra in the hole-dominated regime are shown to result from space-charge-limited conduction combined with charge relaxation in trap levels. This description allows us to directly determine the carrier mobility, even in the presence of traps. In contrast to recent literature, we demonstrate that there is no need to include dispersive transport in the description of the carrier mobility to explain the excess capacitance that is typically observed in admittance spectra of p-conjugated materials

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

Gerarchie urbane deboli o strutture reticolari? Il caso dell'Alta Val di Serchio

Alla luce delle nuove tendenze, anche il sistema insediativo dell'alta Val di Serchio in provincia di Lucca, da sempre caratterizzato da una fitta rete di centri di piccole dimensioni con funzioni di organizzazione territoriale a livello subprovinciale, ha subito profonde trasformazioni: cambiano i rapporti, si instaurano nuovi equilibri e viene da chiedersi che tipo di centralità possa realizzarsi in una situazione tanto complessa, dove la crescente affermazione delle reti telematiche e i continui processi d'innovazione tecnologica rivestono un ruolo fondamentale. O forse se non sia il caso di parlare, piuttosto, di rapporti a rete fra i singoli centri; nuove realtà che, in virtù di legami di interdipendenza e di fenomeni di complementarità funzionale, si vanno autoconcentrando, con l'evidente risultato di una forma insediativa più diffusa. Ci chiediamo, pertanto se le trame attuali non siano altro che effetto di un costante indebolimento di una gerarchia urbana già incompleta e storicamente frammentata. Attraverso l'analisi di indicatori demografici e macro-economicima, soprattutto, attraverso la lettura dei risultati raggiunti mediante l'applicazione alla ricerca di un ipotetico "reticolo" con cui dimostrare, da un lato, il consolidarsi di processi di forte interrelazione all'interno del sistema insediativo della Valle e, dall'altro, l'avvenuta apertura verso contesti esterni di un'area -prevalentemente montuosa e collinare- che, almeno parzialmente, si è sempre dimostrata chiusa rispetto alla rete delle relazioni territoriali a scala più ampia

The national settlement system of Italy at the beginning of the 1990s

The paper presents recent changes in the Italian settlement system and variation in urban hierarchical relations. Functional classification of towns and their new position compared with the situation at the beginning of 1980s, is newly proposed in terms of three categories of cities, medium-sized towns and small towns. The analysis and verification attempted in this study have revealed a marked reduction in the number of small towns as well as shifts in functional characteristics within urban areas in Italy

Lucca: evoluzione e struttura di una città media

Il lavoro, dopo un'introduzione storica sulla città di Lucca, tratta l'assetto distributivo della popolazione, con particolare riferimento alla disposizione della residenza di vari gruppi sociali, con l'intento di verificare se esiste una corrispondenza con uno dei modelli classici dell'utilizzazione del suolo urbano

B. Cardinale, Barriere geografiche e mobilità in Italia, F. Angeli, 2000, pp.173, bibl. ("Scienze geografiche", 9)

L'analisi di Bernardo Cardinale, con riferimento ai capoluoghi italiani, cerca di tracciare un quadro complessivo sull'ineguale efficienza delle reti viarie del nostro paese e di ipotizzare, altresì, percorsi di riequilibrio territoriale nel tentativo di sanare squilibri economici di natura sia ambientale sia politica. Barriere geografiche "perimetrali", "orografiche", "sociali", indagate attraverso un'impostazione di matrice funzionalista che permette all'autore di avanzare proposte concrete per superare i vincoli dello spazio geografico