Bayesian spatial analysis of demographic survey data: an application to contraceptive use at first sexual intercourse.

In this paper we analyze the spatial patterns of the risk of unprotected sexual intercourse for Italian women during their initial experience with sexual intercourse. We rely on geo-referenced survey data from the Italian Fertility and Family Survey, and we use a Bayesian approach relying on weakly informative prior distributions. Our analyses are based on a logistic regression model with a multilevel structure. The spatial pattern uses an intrinsic Gaussian conditional autoregressive (CAR) error component. The complexity of such a model is best handled within a Bayesian framework, and statistical inference is carried out using Markov Chain Monte Carlo simulation. In contrast with previous analyses based on multilevel model, our approach avoids the restrictive assumption of independence between area effects. This model allows us to borrow strength from neighbors in order to obtain estimates for areas that may, on their own, have inadequate sample sizes. We show that substantial geographical variation exists within Italy (Southern Italy has higher risks of unprotected first-time sexual intercourse), and that the spatial pattern is stable across birth cohorts. The findings are robust with respect to the specification of the prior distribution. We argue that spatial analysis can give useful insights on unmet reproductive health needs. (KEYWORDS: spatial statistical demography, contraceptive use, hierarchical Bayesian modeling, Monte Carlo Markov Chain, multilevel statistical models, Italy, FFS

KRIGING PREDICTION FROM A CIRCULAR GRID: APPLICATION TO WAFER DIFFUSION

In the production process of silicon wafers, which are crystalline slices used as substrate of electronic micro-circuits, the thickness of the SiO2 deposition on their top is a main characteristic to be controlled during the process. The experimental design that is commonly used to monitor the thickness to the target value consists of a regular array of points lying on concentric circles, the silicon wafer itself being a disk. To speed up the control process, the engineers aim to use just only a limited subset of such points. To reconstruct the values on untried locations of the silicon wafer, the Kriging interpolation has been proposed because of its recog- nized ability in providing fairly good predictions. In this paper, we consider two methodological issues related to universal Kriging models. First, we discuss the modeling of the covariance structure among the measured points; in fact, spatial data usually show a strong correlation when they come from spatially near observed points. Second, we put forward an algebraic method to assess the identifiability of trend models, based both on the full experimental design and on special fractions of it. Our findings are illustrated by a data set from an industrial applicatio

Time-Resolved Profiling Reveals ATF3 as a Novel Mediator of Endocrine Resistance in Breast Cancer

Breast cancer is one of the leading causes of death for women worldwide. Patients whose tumors express Estrogen Receptor α account for around 70% of cases and are mostly treated with targeted endocrine therapy. However, depending on the degree of severity of the disease at diagnosis, 10 to 40% of these tumors eventually relapse due to resistance development. Even though recent novel approaches as the combination with CDK4/6 inhibitors increased the overall survival of relapsing patients, this remains relatively short and there is a urgent need to find alternative targetable pathways. In this study we profiled the early phases of the resistance development process to uncover drivers of this phenomenon. Time-resolved analysis revealed that ATF3, a member of the ATF/CREB family of transcription factors, acts as a novel regulator of the response to therapy via rewiring of central signaling processes towards the adaptation to endocrine treatment. ATF3 was found to be essential in controlling crucial processes such as proliferation, cell cycle, and apoptosis during the early response to treatment through the regulation of MAPK/AKT signaling pathways. Its essential role was confirmed in vivo in a mouse model, and elevated expression of ATF3 was verified in patient datasets, adding clinical relevance to our findings. This study proposes ATF3 as a novel mediator of endocrine resistance development in breast cancer and elucidates its role in the regulation of downstream pathways activities

Abrogating GPT2 in triple negative breast cancer inhibits tumor growth and promotes autophagy

Uncontrolled proliferation and altered metabolic reprogramming are hallmarks of cancer. Active glycolysis and glutaminolysis are characteristic features of these hallmarks and required for tumorigenesis. A fine balance between cancer metabolism and autophagy is a prerequisite of homeostasis within cancer cells. Here we show that glutamate pyruvate transaminase 2 (GPT2), which serves as a pivot between glycolysis and glutaminolysis, is highly upregulated in aggressive breast cancers, particularly the triple negative breast cancer (TNBC) subtype. Abrogation of this enzyme results in decreased TCA cycle intermediates, which promotes the rewiring of glucose carbon atoms and alterations in nutrient levels. Concordantly, loss of GPT2 results in an impairment of mechanistic target of rapamycin complex 1 (mTORC1) activity as well as the induction of autophagy. Furthermore, in vivo xenografts studies have shown that autophagy induction correlates with decreased tumor growth and that markers of induced autophagy correlate with low GPT2 levels in patient samples. Taken together, these findings indicate that cancer cells have a close network between metabolic and nutrient sensing pathways necessary to sustain tumorigenesis, and that aminotransferase reactions play an important role in maintaining this balance

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

Fragmentation and logical omniscience

It would be good to have a Bayesian decision theory that assesses our decisions and thinking according to everyday standards of rationality — standards that do not require logical omniscience (Garber 1983, Hacking 1967). To that end we develop a “fragmented” decision theory in which a single state of mind is represented by a family of credence functions, each associated with a distinct choice condition (Lewis 1982, Stalnaker 1984). The theory imposes a local coherence assumption guaranteeing that as an agent's attention shifts, successive batches of "obvious" logical information become available to her. A rule of expected utility maximization can then be applied to the decision of what to attend to next during a train of thought. On the resulting theory, rationality requires ordinary agents to be logically competent and to often engage in trains of thought that increase the unification of their states of mind. But rationality does not require ordinary agents to be logically omniscient