Combined reflectance and fluorescence spectroscopy for in vivo detection of cervical pre-cancer

Optical technologies, such as reflectance and fluorescence spectroscopy, have shown the potential to provide improved point-of-care detection methods for cervical neoplasia that are sensitive, specific, and cost-effective. Our specific goals are to analyze the diagnostic potential of reflectance and fluorescence spectra, alone and in combination, to discriminate normal and precancerous cervical tissue in vivo and to identify which classification features contain significant diagnostic information. Reflectance spectra are measured at four source-detector separations and fluorescence emission spectra are measured at 16 excitation wavelengths, from 324 sites in 161 patients. These 20 spectral features are permuted in all possible combinations of one, two, and three; and classification algorithms are developed to evaluate the diagnostic performance of each combination. Algorithms based on fluorescence spectra alone yield better diagnostic performance than those based on reflectance spectra alone. The combination of fluorescence and reflectance do not significantly improve diagnostic performance compared to fluorescence alone, except in the case of discriminating high-grade precancers from columnar normal tissue. In general, fluorescence emission spectra at 330- to 360-nm and 460- to 470-nm excitation provide the best diagnostic performance for separating all pairs of tissue categories.     

Comparative Disease Assessment: a multi-causal approach for estimating the burden of mortality

Journal of Public Health - The Comparative Risk Assessment (CRA) framework comprehensively evaluates the impact of exposure to risk factors on health populations using the counterfactual causal...     

A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: Report of a pilot clinical trial

Background: There is evidence of a relationship between epidermal growth factor (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor (EGF-R) in different human tumors, which makes this system an interesting target for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies against the EGF-R has been assayed in clinics. Our approach consists of active immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled to a carrier protein.Patients and methods: Ten patients with histologically-proven malignant carcinomas (colon, lung, stomach and prostate) in advanced clinical stages were enrolled. Patients were immunized twice (on days 0 and 15) with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64k Neisseria Meningitidis recombinant protein (P64k, five patients), intradermically, using aluminium hydroxyde as adjuvant.Results: In both groups 60% of patients developed anti-EGF antibody titers without evidence of toxicity. Secondary reactions were very mild, limited to erythema and itching at the site of injection, which disappeared without medication.Conclusions: We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.     

In Silico identification of M. TB proteins with diagnostic potential

The development of a new tuberculosis (TB) vaccine has become one of the main objectives of the scientific community. Protein antigens have been widely explored as subunit TB vaccines, however lipid antigens could be equally important to be used or included in such a vaccine. The aim of this study was to demonstrate the potential of a liposome formulation composed of an extract of lipids from Mycobacterium smegmatis (Ms) as a TB vaccine candidate. We evaluated the immunogenicity of this formulation as well as the cross reactive response against antigens from Mycobacterium tuberculosis (MTb) in BALB/c mice. We determined the anti-liposome IgG response in sera from TB patients and from healthy subjects who displayed a positive (PPD+) or negative (PPD-) tuberculin skin test. A significant increase in anti-liposome IgG (p<0.05) was detected in animals immunized with Bacille Calmette-Guérin (BCG) compared with all groups, and in the group immunized with liposomes from Ms (LMs) compared to animals immunized with either LMs adjuvanted with aluminium (LMs-A) or the negative control group (phosphate buffered saline, PBS) respectively. With respect to the cross reactive response against a cocktail of cell wall antigens (CWA) from MTb, significantly higher IgG levels were observed in animals immunized with BCG and LMs compared to negative controls and either, aluminium-adjuvanted liposomes (LMs-A) or montanide (LMs-M) (p<0.05). Furthermore, the anti-liposome IgG response was significantly superior in sera from pulmonary TB patients compared to PPD+ and PPD- healthy subjects (p<0.001) suggesting the expression of these antigens in vivo during active MTb infection. The results obtained provide some evidence for the potential use of liposomes containing total lipid extracts of Ms as a TB vaccine candidate.

     

Engaging Undergraduates to Solve Global Health Challenges: A New Approach Based on Bioengineering Design

Recent reports have highlighted the need for educational programs to prepare students for careers developing and disseminating new interventions that improve global public health. Because of its multi-disciplinary, design-centered nature, the field of Biomedical Engineering can play an important role in meeting this challenge. This article describes a new program at Rice University to give undergraduate students from all disciplines a broad background in bioengineering and global health and provides an initial assessment of program impact. Working in partnership with health care providers in developing countries, students in the Beyond Traditional Borders (BTB) initiative learn about health challenges of the poor and put this knowledge to work immediately, using the engineering design process as a framework to formulate solutions to complex global health challenges. Beginning with a freshman design project and continuing through a capstone senior design course, the BTB curriculum uses challenges provided by partners in the developing world to teach students to integrate perspectives from multiple disciplines, and to develop leadership, communication, and teamwork skills. Exceptional students implement their designs under the guidance of clinicians through summer international internships. Since 2006, 333 students have designed more than 40 technologies and educational programs; 28 have been implemented in sub-Saharan Africa, Latin America, the Caribbean, southeast Asia, and the United States. More than 18,000 people have benefited from these designs. 95% of alumni who completed an international internship reported that participation in the program changed or strengthened their career plans to include a focus on global health medicine, research, and/or policy. Empowering students to use bioengineering design to address real problems is an effective way to teach the new generation of leaders needed to solve global health challenges.     

Austronesian genetic signature in East African Madagascar and Polynesia

The dispersal of the Austronesian language family from Southeast Asia represents the last major diaspora leading to the peopling of Oceania to the East and the Indian Ocean to the West. Several theories have been proposed to explain the current locations, and the linguistic and cultural diversity of Austronesian populations. However, the existing data do not support unequivocally any given migrational scenario. In the current study, the genetic profile of 15 autosomal STR loci is reported for the first time for two populations from opposite poles of the Austronesian range, Madagascar at the West and Tonga to the East. These collections are also compared to geographically targeted reference populations of Austronesian descent in order to investigate their current relationships and potential source population(s) within Southeast Asia. Our results indicate that while Madagascar derives 66.3% of its genetic makeup from Africa, a clear connection between the East African island and Southeast Asia can be discerned. The data suggest that although geographic location has influenced the phylogenetic relationships between Austronesian populations, a genetic connection that binds them beyond geographical divides is apparent.     

The automatic implantable cardioverter-defibrillator: efficacy, complications and survival in patients with malignant ventricular arrhythmias

Ninety-four patients underwent surgery for automatic implantable cardioverter-defibrillator implantation. Ninety patients were discharged from the hospital with the device and were followed up for a mean period of 17 +/- 10 months. Forty-six patients experienced at least one discharge of the device under circumstances consistent with a malignant ventricular arrhythmia. One sudden death occurred. Complications included perioperative death (3 patients), post-operative ventricular tachycardia (12 patients) and atrial fibrillation (8 patients), perioperative myocardial infarction (1 patient) and device discharges for sinus tachycardia and supraventricular arrhythmias (17 patients). Six and 12 month survival rates by life table analysis were 98.7 and 95.4%, respectively. Thus, the automatic implantable cardioverter-defibrillator is a highly effective and relatively low risk treatment modality for patients with refractory life-threatening ventricular arrhythmias.