Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders

Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear

Observability and nonlinear filtering

This paper develops a connection between the asymptotic stability of nonlinear filters and a notion of observability. We consider a general class of hidden Markov models in continuous time with compact signal state space, and call such a model observable if no two initial measures of the signal process give rise to the same law of the observation process. We demonstrate that observability implies stability of the filter, i.e., the filtered estimates become insensitive to the initial measure at large times. For the special case where the signal is a finite-state Markov process and the observations are of the white noise type, a complete (necessary and sufficient) characterization of filter stability is obtained in terms of a slightly weaker detectability condition. In addition to observability, the role of controllability in filter stability is explored. Finally, the results are partially extended to non-compact signal state spaces

Non-adaptive Heisenberg-limited metrology with multi-channel homodyne measurements

We show a protocol achieving the ultimate Heisenberg-scaling sensitivity in the estimation of a parameter encoded in a generic linear network, without employing any auxiliary networks, and without the need of any prior information on the parameter nor on the network structure. As a result, this protocol does not require a prior coarse estimation of the parameter, nor an adaptation of the network. The scheme we analyse consists of a single-mode squeezed state and homodyne detectors in each of the M output channels of the network encoding the parameter, making it feasible for experimental applications

Multi-parameter estimation of the state of two interfering photonic qubits

It is demonstrated a two-photon interfering technique based on polarization-resolved measurements for the simultaneous estimation with the maximum sensitivity achievable in nature of multiple parameters associated with the polarization state of two interfering photonic qubits. This estimation is done by exploiting a novel interferometry technique based on polarization-resolved two-photon interference. We show the experimental feasibility and accuracy of this technique even when a limited number of sampling measurements is employed. This work is relevant for the development of quantum technologies with photonic qubits and sheds light on the physics at the interface between multiphoton interference, boson sampling, multi-parameter quantum sensing and quantum information processing

Subclinical thyroid dysfunction and the risk of heart failure events: an individual participant data analysis from 6 prospective cohorts.

BACKGROUND: American College of Cardiology/American Heart Association guidelines for the diagnosis and management of heart failure recommend investigating exacerbating conditions such as thyroid dysfunction, but without specifying the impact of different thyroid-stimulation hormone (TSH) levels. Limited prospective data exist on the association between subclinical thyroid dysfunction and heart failure events. METHODS AND RESULTS: We performed a pooled analysis of individual participant data using all available prospective cohorts with thyroid function tests and subsequent follow-up of heart failure events. Individual data on 25 390 participants with 216 248 person-years of follow-up were supplied from 6 prospective cohorts in the United States and Europe. Euthyroidism was defined as TSH of 0.45 to 4.49 mIU/L, subclinical hypothyroidism as TSH of 4.5 to 19.9 mIU/L, and subclinical hyperthyroidism as TSH <0.45 mIU/L, the last two with normal free thyroxine levels. Among 25 390 participants, 2068 (8.1%) had subclinical hypothyroidism and 648 (2.6%) had subclinical hyperthyroidism. In age- and sex-adjusted analyses, risks of heart failure events were increased with both higher and lower TSH levels (P for quadratic pattern <0.01); the hazard ratio was 1.01 (95% confidence interval, 0.81-1.26) for TSH of 4.5 to 6.9 mIU/L, 1.65 (95% confidence interval, 0.84-3.23) for TSH of 7.0 to 9.9 mIU/L, 1.86 (95% confidence interval, 1.27-2.72) for TSH of 10.0 to 19.9 mIU/L (P for trend <0.01) and 1.31 (95% confidence interval, 0.88-1.95) for TSH of 0.10 to 0.44 mIU/L and 1.94 (95% confidence interval, 1.01-3.72) for TSH <0.10 mIU/L (P for trend=0.047). Risks remained similar after adjustment for cardiovascular risk factors. CONCLUSION: Risks of heart failure events were increased with both higher and lower TSH levels, particularly for TSH ≥10 and <0.10 mIU/L

Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

Heisenberg scaling precision in multi-mode distributed quantum metrology

We consider the estimation of an arbitrary parameter φ, such as the temperature or a magnetic field, affecting in a distributed manner the components of an arbitrary linear optical passive network, such as an integrated chip. We demonstrate that Heisenberg scaling precision (i.e. of the order of 1/N, where N is the number of probe photons) can be achieved without any iterative adaptation of the interferometer hardware and by using only a simple, single, squeezed light source and well-established homodyne measurements techniques. Furthermore, no constraint on the possible values of the parameter is needed but only a preliminary shot-noise estimation (i.e. with a precision of) easily achievable without any quantum resources. Indeed, such a classical knowledge of the parameter is enough to prepare a single, suitable optical stage either at the input or the output of the network to monitor with Heisenberg-limited precision any variation of the parameter to the order of without the need to iteratively modify such a stage