Fala: Through the Lens of Zarefsky’s Fourth Distinction

Attention to public image is an ongoing responsibility for a President in a free society, by virtue of the fact that public opinion and favorability influence voting inclinations. Power influences, legislatively and symbolically, and the way it is wielded defines each President. Fala served as a figurative sponge that absorbed criticism against Roosevelt and wiped it away. Although public opinion regarding Roosevelt’s politics was often very divided, Fala provided a positive distraction that shifted the public’s focus away from Roosevelt’s disability and served as a humanizing figure for adults and children alike to adore

Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review

For individuals affected by Type 1 diabetes (T1D), a chronic disease in which the pancreas does not produce any insulin, maintaining the blood glucose (BG) concentration as much as possible within the safety range (70-180\ua0mg/dl) allows avoiding short- and long-term complications. The tuning of exogenous insulin infusion can be difficult, especially because of the inter- and intra-day variability of physiological and behavioral factors. Continuous glucose monitoring (CGM) sensors, which monitor glucose concentration in the subcutaneous tissue almost continuously, allowed improving the detection of critical hypo- and hyper-glycemic episodes. Moreover, their integration with insulin pumps for continuous subcutaneous insulin infusion allowed developing algorithms that automatically tune insulin dosing based on CGM measurements in order to mitigate the incidence of critical episodes. In this work, we aim at reviewing the literature on methods for CGM-based automatic attenuation or suspension of basal insulin with a focus on algorithms, their implementation in commercial devices and clinical evidence of their effectiveness and safety

Type 1 diabetes patient decision-making modeling for the in silico assessment of insulin treatment scenarios

In type 1 diabetes (T1D) exogenous insulin is administered to compensate for the absence of endogenous insulin production by pancreas beta-cells. T1D subjects must finely tune insulin doses to maintain blood glucose (BG) concentration within the normal range (70-180 mg/dl). For such a purpose, every day, T1D subjects need to frequently monitor their BG concentration and make several treatment decisions, e.g. the calculation of insulin and carbohydrate (CHO) doses to counterbalance, respectively, high and low BG values. The safety and effectiveness of T1D insulin therapies are normally assessed by clinical trials, which unfortunately are usually time-demanding, expensive and often present constraints of low numerosity and short duration, with consequently low probability of observing rare but risky situations, like severe hypoglycemia. These limitations can be overcome by the use of in silico clinical trials, based on computer simulations, that allow to test medical device-based treatments in a large number of subjects, over a long period, under reproducible conditions, at limited costs, and without implicating any risk for real subjects. A popular powerful tool to perform in silico clinical trials in T1D is the UVA/Padova T1D simulator, i.e. a model of glucose, insulin and glucagon dynamics in T1D subjects. However, to test insulin therapies in a real-life scenario, the UVA/Padova T1D simulator alone is not sufficient because a mathematical description of other fundamental components, like the device used for glucose monitoring and the patient's behavior in making treatment decisions, is required. The aim of this thesis is to design a mathematical model of T1D patients making treatment decisions fully usable for the comprehensive in silico assessment of insulin treatment scenarios. In particular, in the first part of the thesis we develop three submodels that the UVA/Padova T1D simulator requires (as complement) to pursue this scope. Specifically, we design a model of self-monitoring of blood glucose (SMBG) device, a model of minimally-invasive sensor for continuous glucose monitoring (CGM), and a model of the patient’s behavior in tuning CHO intakes and insulin doses according to SMBG and/or CGM measurements. The parameters of these models are either fitted on real data or derived from literature studies. The overall model, in the following called T1D decision-making (T1D-DM) model, can be used for several in silico experiments. To demonstrate its usefulness, in the second part of this thesis we apply the T1D-DM model to assess safety and effectiveness of nonadjunctive CGM use, i.e. the use of CGM measurements to make treatment decisions without requiring confirmatory SMBG measurements collected by fingerstick. This specific application is currently of great scientific and industrial interest for the diabetes technology research community because, until clinical evidence of its safety is provided, nonadjunctive CGM use cannot be approved by U.S. regulatory agencies, like the Food and Drug Administration. The thesis is organized in six chapters. In Chapter 1, after introducing T1D therapy, the importance of in silico clinical trials is discussed, both in general and specifically for the assessment of nonadjunctive CGM use. Then, some state-of-art simulation techniques are briefly introduced discussing their open problems. The aim of the thesis is illustrated at the end of the chapter. In Chapter 2, we analyse more in depth the limitations of the approaches currently available in the literature for the assessment of insulin treatments. In particular, we demonstrate that a recently proposed simulation method to "replay" in silico real-life treatment scenarios has domain of validity limited to small adjustments of basal insulin, calling for the development of more sophisticated techniques like that proposed in this thesis. In Chapter 3, our simulation method based on the T1D-DM model is presented. This model allows to simulate, in a real-life scenario, the glucose profiles of T1D subjects using SMBG and/or CGM to make treatment decisions. The T1D-DM model is composed of four components: A) the UVA/Padova T1D simulator, B) a model of glucose monitoring devices, C) a model of patient's behavior and treatment decisions and D) a model of the insulin pump. In particular, as far as B) is concerned, two different SMBG error models are derived by data collected with two popular SMBG devices (One Touch Ultra 2 and Bayer Contour Next USB). Using a recently published methodology which takes into account the main sensor error components, a CGM model is derived from data collected by a state-of-art CGM sensor (Dexcom G5 Mobile). Regarding C), a model of the patient's behavior in making treatment decisions based on SMBG and/or CGM, such as administration of insulin boluses and hypotreatments, is designed to simulate treatments based on i) SMBG, ii) adjunctive CGM, or iii) nonadjunctive CGM. In order to reproduce a real-life scenario, the model includes components describing the mistakes real subjects commonly make, such as miscalculation of meal CHO content and early/delayed insulin administrations. In Chapter 4 and Chapter 5, two in silico trials based on the T1D-DM model are designed to assess nonadjunctive CGM use. In the first trial, nonadjunctive CGM is compared to SMBG and adjunctive CGM over a two-week period in 100 virtual subjects. Results show that the use of CGM (both adjunctive and nonadjunctive) significantly improves glycemic control compared to SMBG, while no significant change is observed between adjunctive CGM and nonadjunctive CGM. This suggests that CGM is ready to substitute SMBG for T1D treatment. In the second trial, the impact of thresholds used for CGM hypo/hyperglycemic alerts on the performance of nonadjunctive CGM use is assessed. Results show that time in hypoglycemia is reduced by nonadjunctive CGM use with any alert setting, while time in hyperglycemia is significantly worsen by nonadjunctive CGM use, compared to SMBG, when the high alert threshold is set to 350 mg/dl or higher. Finally, the major findings of the work carried out in this thesis, its possible applications and margin of improvements are summarized in Chapter 6

Confronto di varie metodologie per l'analisi e la progettazione di edifici irregolari in muratura secondo le Norme Tecniche per le Costruzioni

La presente tesi si pone l'obiettivo di confrontare delle metodologie di progettazione ed analisi degli edifici in muratura mediante l'utilizzo delle NTC-08. Si vanno a confrontare alcuni tipi di analisi sismiche, in particolare analisi statiche lineari e non lineari, alcuni approcci di modellazione a macroelementi e si cercherà di capire in che modo varia la risposta strutturale di edifici irregolari in muratura al variare di caratteristiche geometriche e meccanicheope

Wearable continuous glucose monitoring sensors: A revolution in diabetes treatment

Worldwide, the number of people affected by diabetes is rapidly increasing due to aging populations and sedentary lifestyles, with the prospect of exceeding 500 million cases in 2030, resulting in one of the most challenging socio-health emergencies of the third millennium. Daily management of diabetes by patients relies on the capability of correctly measuring glucose concentration levels in the blood by using suitable sensors. In recent years, glucose monitoring has been revolutionized by the development of Continuous Glucose Monitoring (CGM) sensors, wearable non/minimally-invasive devices that measure glucose concentration by exploiting different physical principles, e.g., glucose-oxidase, fluorescence, or skin dielectric properties, and provide real-time measurements every 1–5 min. CGM opened new challenges in different disciplines, e.g., medicine, physics, electronics, chemistry, ergonomics, data/signal processing, and software development to mention but a few. This paper first makes an overview of wearable CGM sensor technologies, covering both commercial devices and research prototypes. Then, the role of CGM in the actual evolution of decision support systems for diabetes therapy is discussed. Finally, the paper presents new possible horizons for wearable CGM sensor applications and perspectives in terms of big data analytics for personalized and proactive medicine

FO028FRIED'S FRAILTY SCALE IDENTIFIES THOSE ELDERLY PATIENTS WITH ADVANCED CHRONIC KIDNEY DISEASE THAT MAY BENEFIT FROM A THOROUGH GERIATRIC EVALUATION

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Native Hypovitaminosis D in CKD Patients : From Experimental Evidence to Clinical Practice

Native hypovitaminosis D (n-hVITD) is frequently found from the early stages of chronic kidney disease (CKD) and its prevalence increases with CKD progression. Even if the implications of n-hVITD in chronic kidney disease-mineral bone disorder (CKD-MBD) have been extensively characterized in the literature, there is a lot of debate nowadays about the so called "unconventional effects" of native vitamin D (25(OH)VitD) supplementation in CKD patients. In this review, highlights of the dimension of the problem of n-hVITD in CKD stages 2-5 ND patients will be presented. In addition, it will focus on the "unconventional effects" of 25(OH)VitD supplementation, the clinical impact of n-hVITD and the most significant interventional studies regarding 25(OH)VitD supplementation in CKD stages 2-5 ND

Trattamento dell’iperuricemia nel paziente nefropatico: è giunto il momento di agire?

Numerosi studi epidemiologici condotti nella popolazione generale indicano che l\u2019iperuricemia si associa ad un incremento del rischio di sviluppare insufficienza renale. Inoltre, tra i soggetti che sono gi\ue0 affetti da una malattia renale cronica (MRC), l\u2019iperuricemia si associa sia ad una pi\uf9 rapida progressione di malattia sia ad un significativo incremento della mortalit\ue0 e degli eventi cardiovascolari. Tuttavia, ad oggi il ruolo causale dell\u2019iperuricemia nel determinare l\u2019insorgenza e la progressione del danno renale e cardiovascolare non \ue8 ancora completamente accertato, per cui le indicazioni al trattamento farmacologico dell\u2019iperuricemia asintomatica nei pazienti con MRC sono ancora affidate all\u2019orientamento personale del singolo medico. Al fine di stabilire se sia possibile esprimere un orientamento clinico basato sull\u2019evidenza abbiamo eseguito un\u2019analisi comparativa degli studi prospettici che hanno valutato l\u2019impatto della terapia ipouricemizzante con inibitori della xantino ossidasi (IXAO) rispetto all\u2019insorgenza e alla progressione del danno renale. Inoltre, dal momento che in passato nei soggetti con funzionalit\ue0 renale ridotta il trattamento con IXAO \ue8 stato associato ad un elevato rischio di tossicit\ue0, abbiamo analizzato la tossicit\ue0 di questi farmaci per vari gradi compromissione della funzione renale riassumendo indicazioni, controindicazioni e dosi consigliate nei pazienti affetti da MRC. In fine, a conclusione della nostra analisi abbiamo elaborato un algoritmo finalizzato ad orientare le decisioni cliniche in merito al trattamento dell\u2019iperuricemia nei soggetti affetti da MRC.Numerous epidemiological studies conducted in the general population indicate that hyperuricemia is associated with an increased risk of developing renal failure. Moreover, among those subjects who are already suffering from chronic kidney disease (CKD), hyperuricemia is associated with a more rapid progression of disease besides with an increased risk of mortality and cardiovascular events. However, to date, the causal role of hyperuricaemia in determining the onset and progression of cardiovascular and renal damage is not yet fully established. Therefore the indications for pharmacological treatment of hyperuricemia (and particulary of asymptomatic hyperuricemia) in patients with CKD are still assigned to the personal orientation of the physician. In order to produce an evidence-based clinical appraisal on this topic, we performed a comparative analysis that included all the prospective studies that have evaluated the impact of treatment with xanthine oxidase inhibithors (XOI) with respect to the onset and progression of CKD. Moreover, since in the past the treatment with XOI was associated with a high risk of toxicity in patients with impaired renal function, we analyzed the toxicity of these drugs for various degrees of renal function impairment summarizing indications, contraindications and recommended doses in patients affected by CKD. In the end, as conclusion of our analysis, we propose an algorithm aimed at guiding the clinical decisions about the treatment of hyperuricemia in patients with CKD

patients with hypertensive nephropathy and chronic kidney disease might not benefit from strict blood pressure control

Background/Aims: In patients with chronic kidney disease (CKD) strict blood pressure (BP) control is reno-protective. However, renal benefits from BP control might depend also on the etiology of CKD. We investigated if maintenance of BP at target is equally effective in subjects with hypertensive nephropathy (HN+) and in those with other nephropathies (HN-). Methods: We evaluated 148 patients with CKD (stages 3-5) in two visits at least 12 months apart. BP was measured both as office BP and 24h ambulatory blood pressure (ABP). Glomerular filtration rate (eGFR) was estimated with CKD-EPI formula. The slope of eGFR variation (ΔeGFR) was calculated as: (eGFR1-eGFR0)/months of follow up. Results: Cohort characteristics were: HN-(n=82) and HN+ (n=66), age (71±9 vs 74±9 years; p=0.09); prevalence of diabetes (57 vs 43%; p=0.19); average follow up (19±7 vs 21±9 months; p=0.3). HN- and HN+ did not differ regarding both baseline eGFR (34±18 vs 35±14 ml/min; p=0.97) and ΔeGFR (0.00±0.53 vs -0.06±0.35 ml/min/month, p=0.52). The proportion of patients with BP at target at both visits was similar in HN- and HN+ (office BP: HN- 18% and HN+ 27%; p=0.21; ABP: HN- 42% and HN+ 43; p=0.96). In patients with office BP at target at both visits HN- showed a significant improvement of ΔeGFR respect to HN+ (HN-: 0.240 ± 0.395 and HN+: -0.140±0.313 ml/min/ month; p=0.026). In patients with office BP not at target HN- and HN+ did not show any difference in ΔeGFR (HN- 0.00±0.47; HN+ -0.030±0.420 ml/min/month; p=0.66). ABP was not associated with differences in ΔeGFR either if it was at target (HN- 0.104±0.383 and HN+ 0.00±0.476 ml/min/month; p=0.42) or not (HN- -0.057±0.503 and HN+ -0.092±0.325 ml/ min/month; p=0.87). Conclusion: In patients with CKD and HN+ maintenance of BP targets recommended by current guidelines is less reno-protective than it is in HN-