Microlocal analysis of the X-ray transform in non-smooth geometry

We prove that the geodesic X-ray transform is injective on $L^2$ when the Riemannian metric is simple but the metric tensor is only finitely differentiable. The number of derivatives needed depends explicitly on dimension, and in dimension $2$ we assume $g\in C^{10}$. Our proof is based on microlocal analysis of the normal operator: we establish ellipticity and a smoothing property in a suitable sense and then use a recent injectivity result on Lipschitz functions. When the metric tensor is $C^k$, the Schwartz kernel is not smooth but $C^{k-2}$ off the diagonal, which makes standard smooth microlocal analysis inapplicable.Comment: 17 page

Drawing-Based Automatic Dementia Screening Using Gaussian Process Markov Chains

Screening tests play an important role for early detection of dementia. Among those widely used screening tests, drawing tests have gained much attention in clinical psychology. Traditional evaluation of drawing tests totally relies on the appearance of drawn picture, but does not consider any time-dependent behaviour. We demonstrated that the processing speed and direction can reflect the decline of cognitive function, and thus may be useful for disease screening. We proposed a model of Gaussian process Markov chains (GPMC) to study the complex associations within the drawing data. Specifically, we modeled the process of drawing in a state-space form, where a drawing state is composed of drawing direction and velocity with consideration of the processing time. For temporal modeling, our scope focused more on discrete-time Markov chains on continuous state space. Because of the short processing time of picture drawing, we applied higher-order of Markov chains to model long-term temporal correlation across drawing states. Gaussian process regression was used for universal function approximation to flexibly infer the state transition function. With Gaussian process prior to the distribution of function space, we could encode high-level function properties such as noisiness, smoothness and periodicity. We also derived an efficient training mechanism for complex Gaussian process regression on bivariate Markov chains. With GPMC, we present an optimal decision rule based on Bayesian decision theory. We applied our proposed method to a drawing test for dementia screening, i.e. interlocking pentagon-drawing test. We tested our models with 256 subjects who are aged from 65 to 95. Finally, comparing to the traditional methods, our models showed remarkable improvement in drawing test for dementia screening

Age composition and survival of public housing stock in Hong Kong

Emerging notably in more developed regions, building stock ageing which is characterised by shrinking new completions and falling “mortality” has been posing challenges to various stakeholders in built environment. To find way out of this transition, we need to know how long buildings will last these days and the factors leading to their “mortality”. By using data from 1950s till to date, a comprehensive investigation is conducted to analyse the age composition and life expectancy of public housing stock in Hong Kong. What comes after are survival analysis and empirical analysis of those demolished to identify the key factors leading to demolition. Presented in this paper are the preliminary findings as well as the research agenda on the theme to model age composition and survival of both private and public building stocks in Hong Kong and other similar cities in Asia Pacific Rim such as Adelaide and Singapore, together with research activities to formulate policies for sustainable urban management

Zebrafish Behavioral Profiling Links Drugs to Biological Targets and Rest/Wake Regulation

A major obstacle for the discovery of psychoactive drugs is the inability to predict how small molecules will alter complex behaviors. We report the development and application of a high-throughput, quantitative screen for drugs that alter the behavior of larval zebrafish. We found that the multidimensional nature of observed phenotypes enabled the hierarchical clustering of molecules according to shared behaviors. Behavioral profiling revealed conserved functions of psychotropic molecules and predicted the mechanisms of action of poorly characterized compounds. In addition, behavioral profiling implicated new factors such as ether-a-go-go–related gene (ERG) potassium channels and immunomodulators in the control of rest and locomotor activity. These results demonstrate the power of high-throughput behavioral profiling in zebrafish to discover and characterize psychotropic drugs and to dissect the pharmacology of complex behaviors

Glucocorticoid Compounds Modify Smoothened Localization and Hedgehog Pathway Activity

The Hedgehog signaling pathway is linked to a variety of diseases, notably a range of cancers. The first generation of drug screens identified Smoothened (Smo), a membrane protein essential for signaling, as an attractive drug target. Smo localizes to the primary cilium upon pathway activation, and this transition is critical for the response to Hedgehog ligands. In a high content screen directly monitoring Smo distribution in Hedgehog-responsive cells, we identified different glucocorticoids as specific modulators of Smo ciliary accumulation. One class promoted Smo accumulation, conferring cellular hypersensitivity to Hedgehog stimulation. In contrast, a second class inhibited Smo ciliary localization and signaling activity by both wild-type Smo, and mutant forms of Smo, SmoM2, and SmoD473H, that are refractory to previously identified Smo antagonists. These findings point to the potential for developing glucocorticoid-based pharmacological modulation of Smo signaling to treat mutated drug-resistant forms of Smo, an emerging problem in long-term cancer therapy. They also raise a concern about potential crosstalk of glucocorticoid drugs in the Hedgehog pathway, if therapeutic administration exceeds levels associated with on-target transcriptional mechanisms of glucocorticoid action.Chemistry and Chemical BiologyMolecular and Cellular BiologyStem Cell and Regenerative Biolog

Temporal trends and patterns of infective endocarditis in a Chinese population:A territory-wide study in Hong Kong (2002-2019)

BACKGROUND: The characteristics of infective endocarditis (IE) in Asians are poorly understood. Therefore, we aim to describe the epidemiological trends and clinical features of IE in Hong Kong. METHODS: All patients with incident IE from 2002–2019 in a territory-wide clinical database in Hong Kong were identified. We studied the age- and sex-adjusted and one-year mortality of IE between 2002 and 2019 and identified significant contributors to 1-year all-cause death using the attributable fraction. We used propensity score and inverse propensity of treatment weighting to study the association of surgery with mortality. FINDINGS: A total of 5139 patients (60.4 ± 18.2years, 37% women) were included. The overall incidence of IE was 4.9 per 100,000 person-year, which did not change over time (P = 0.17). Patients in 2019 were older and more comorbid than those in 2002. The one-year crude mortality rate was 30% in 2002, which did not change significantly over time (P = 0.10). Between 2002 and 2019, the rate of surgery increased and was associated with a 51% risk reduction in 1-year all-cause mortality (Hazard Ratio 0.49 [0.28–0.87], P = 0.015). Advanced age (attributable fraction 19%) and comorbidities (attributable fraction 15%) were significant contributors to death. INTERPRETATION: The incidence of IE in Hong Kong did not change between 2002 and 2019. Patients with IE in 2019 were older and had more comorbidities than those in 2002. Mortality of IE remains persistently high in Hong Kong. Together, these data can guide public health strategies to improve the outcomes of patients with IE. FUNDING: This work was supported by Sanming Project of Medicine in Shenzhen, China [No. SZSM201911020] and HKU-SZH Fund for Shenzhen Key Medical Discipline [No. SZXK2020081]

A bayesian meta-analysis of multiple treatment comparisons of systemic regimens for advanced pancreatic cancer

© 2014 Chan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Background: For advanced pancreatic cancer, many regimens have been compared with gemcitabine (G) as the standard arm in randomized controlled trials. Few regimens have been directly compared with each other in randomized controlled trials and the relative efficacy and safety among them remains unclear