Deformable Model for 3D Intramodal Nonrigid Breast Image Registration with Fiducial Skin Markers

We implemented a new approach to intramodal non-rigid 3D breast image registration. Our method uses fiducial skin markers (FSM) placed on the breast surface. After determining the displacements of FSM, finite element method (FEM) is used to distribute the markers’ displacements linearly over the entire breast volume using the analogy between the orthogonal components of the displacement field and a steady state heat transfer (SSHT). It is valid because the displacement field in x, y and z direction and a SSHT problem can both be modeled using LaPlace’s equation and the displacements are analogous to temperature differences in SSHT. It can be solved via standard heat conduction FEM software with arbitrary conductivity of surface elements significantly higher than that of volume elements. After determining the displacements of the mesh nodes over the entire breast volume, moving breast volume is registered to target breast volume using an image warping algorithm. Very good quality of the registration was obtained. Following similarity measurements were estimated: Normalized Mutual Information (NMI), Normalized Correlation Coefficient (NCC) and Sum of Absolute Valued Differences (SAVD). We also compared our method with rigid registration technique

Longitudinal Study on Oral Health in Subjects with Alzheimer's Disease

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111087/1/j.1532-5415.1994.tb06074.x.pd

A characterization of major salivary gland flow rates in the presence of medications and systemic diseases

The purpose of this study was to characterize the effects of medications and systemic diseases on major salivary gland flow rates. Unstimulated and 2% citrate-stimulated parotid and submandibular salivas were collected from 293 subjects of the oral physiology component of the Baltimore Longitudinal Study of Aging. The influence of the number of medications and diseases on salivary flow rates was determined by separate one-way ANOVA tests. There was an overall decrease in both parotid and submandibular flow rates with increasing numbers of medications and systemic diseases. However, this was significant (p < 0.05) only for unstimulated submandibular flow rates (with increasing numbers of systemic diseases) and stimulated submandibular flow rates (with increasing numbers of systemic diseases and medications). Unstimulated flow rates rapidly approached zero with increasing numbers of medications and diseases. These results suggest that the submandibular gland may be more sensitive to physiologic permutations than the parotid gland. In addition, individuals being treated for multiple systemic diseases and taking numerous medications may be more susceptible to salivary hypofunction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30580/1/0000217.pd

Fitting and Interpreting Continuous-Time Latent Markov Models for Panel Data

Multistate models are used to characterize disease processes within an individual. Clinical studies often observe the disease status of individuals at discrete time points, making exact times of transitions between disease states unknown. Such panel data pose considerable modeling challenges. Assuming the disease process progresses according a standard continuous-time Markov chain (CTMC) yields tractable likelihoods, but the assumption of exponential sojourn time distributions is typically unrealistic. More flexible semi-Markov models permit generic sojourn distributions yet yield intractable likelihoods for panel data in the presence of reversible transitions. One attractive alternative is to assume that the disease process is characterized by an underlying latent CTMC, with multiple latent states mapping to each disease state. These models retain analytic tractability due to the CTMC framework but allow for flexible, duration-dependent disease state sojourn distributions. We have developed a robust and efficient expectation-maximization (EM) algorithm in this context. Our complete data state space consists of the observed data and the underlying latent trajectory, yielding computationally efficient expectation and maximization steps. Our algorithm outperforms alternative methods measured in terms of time to convergence and robustness. We also examine the frequentist performance of latent CTMC point and interval estimates of disease process functionals based on simulated data. The performance of estimates depends on time, functional, and data-generating scenario. Finally, we illustrate the interpretive power of latent CTMC models for describing disease processes on a data-set of lung transplant patients. We hope our work will encourage wider use of these models in the biomedical setting

Is baseline aerobic fitness associated with illness and attrition rate in military training?

Background Respiratory illnesses are a leading cause of morbidity and medical discharge in the military. This study aimed to investigate the effects of baseline aerobic fitness on haematological, salivary and mood variables, and simultaneously, in a novel approach, to identify factors precipitating illness and attrition rate in recruits during military training. Methods Thirty-five healthy male recruits from an Army Training Regiment undertaking 12 weeks of training were prospectively investigated. Their 2.4 km run time (RT) was used as a surrogate of baseline aerobic fitness. Saliva and venous blood samples were analysed for secretory IgA, full blood counts and cell cytokine production (interleukin (IL) 6 and IL-8), respectively. Each recruit completed questionnaires on mood profile, and gastrointestinal and upper respiratory tract symptoms (URTS). Results Significant salivary and haematological perturbations were observed and coincided with increased duration of URTS/week and mood disturbance over this military training period. From Start to End: leucocyte count decreased by 28% ( p<0.001); neutrophil percentage (%) decreased by 13% (p<0.01); lymphocyte % increased by 17% (p<0.05); the neutrophil:lymphocyte ratio decreased by 22% (p<0.01); eosinophil% increased by 71% (p<0.01). From Start to Mid to End: monocyte% increased by 68% at Mid (p<0.01) but only by 30% at End (p<0.01); IL-6 increased by 39% at Mid (p<0.01) and a further 61% by End. The 2.4 km RT was significantly associated with URTS duration (p<0.01). In addition, a 1-min increase in 2.4 km RT increased a recruit’s risk 9.8-fold of developing URTS lasting, on average, 3.36 days/week. In recruits ranked with high-URTS duration their RT was 48 s slower (p<0.01) than those with low-URTS, and their attrition rate reached 45%. Conclusions The least fit recruits may have found training more physically demanding as reflected in the higher URTS duration, which may have led to a high attrition rate from the Army. It is worth considering that baseline aerobic fitness might be an important factor in illness development and attrition rate in recruits during this type of military training

Chelation in Metal Intoxication

Chelation therapy is the preferred medical treatment for reducing the toxic effects of metals. Chelating agents are capable of binding to toxic metal ions to form complex structures which are easily excreted from the body removing them from intracellular or extracellular spaces. 2,3-Dimercaprol has long been the mainstay of chelation therapy for lead or arsenic poisoning, however its serious side effects have led researchers to develop less toxic analogues. Hydrophilic chelators like meso-2,3-dimercaptosuccinic acid effectively promote renal metal excretion, but their ability to access intracellular metals is weak. Newer strategies to address these drawbacks like combination therapy (use of structurally different chelating agents) or co-administration of antioxidants have been reported recently. In this review we provide an update of the existing chelating agents and the various strategies available for the treatment of heavy metals and metalloid intoxications

Salivary Markers for Oral Cancer Detection

Oral cancer refers to all malignancies that arise in the oral cavity, lips and pharynx, with 90% of all oral cancers being oral squamous cell carcinoma. Despite the recent treatment advances, oral cancer is reported as having one of the highest mortality ratios amongst other malignancies and this can much be attributed to the late diagnosis of the disease. Saliva has long been tested as a valuable tool for drug monitoring and the diagnosis systemic diseases among which oral cancer. The new emerging technologies in molecular biology have enabled the discovery of new molecular markers (DNA, RNA and protein markers) for oral cancer diagnosis and surveillance which are discussed in the current review

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta