Clausena anisata, Haemanthus albiflos, and Artemisia afra were the most cited. The leaves were the most common part used in the medicinal preparations. Our findings are discussed in relation to the importance of the documentation of medicinal plants.The current rate of deforestation in Africa constitutes a serious danger to the future of medicinal plants on this continent. Conservation of these medicinal plants in the field and the scientific documentation of our knowledge about them are therefore crucial. An ethnobotanical survey of plants used for the treatment of tuberculosis (TB) was carried out in selected areas of the Eastern Cape, South Africa. These areas were Hala, Ncera, Sheshegu, and Gquamashe, all within the Nkonkobe Municipality. One hundred informants were interviewed. The survey included the identification of scientific and vernacular names of the plants used for treatment of TB as well as the methods of preparation and administration, the part used, dosage, and duration of treatment. The survey revealed 30 plants belonging to 21 families which are commonly used by traditional healers for the treatment of TB and associated diseases. Of these plants  Mycobacterium tuberculosis. TB infects nine million people every year most of them being children, and it leads to approximately two million deaths annually [Tuberculosis (TB) is a fearful disease in developing nations, especially in the Asian and African continents, probably due to their inadequate means for the management and treatment of the disease. It is caused by a bacterium calledannually , 2. Thesannually –5.TB is a very common disease in South Africa. According to reports, it is the fifth largest cause of death in this country , 7. For Africa is endowed with an enormous wealth of plant resources . Herbal The Eastern Cape Province of South Africa is known for its richness in plant species . The inhThe aim of this study was to document the plant species used exclusively for the treatment of TB by the traditional healers in selected areas of Nkonkobe Municipality, Eastern Cape Province of South Africa .The study area falls within Amathole district area latitudes from 30°00 to 34°15′S and longitudes from 22°C 45′ to 30°15′E. This area consists of many villages which are generally described as rural and poor with high prevalence of TB. Sangomas in xhosa speaking communities. Knowledgeable village elders who use medicinal plants were also consulted to provide information on the medicinal plants and their importance in the treatment of tuberculosis. This method proved to be a very viable and an effective option of data collection. The choice to employ this particular method was heavily influenced by the literacy levels, remote locations visited, and willingness of the respondents that supplied the information needed for the study. The questionnaire was designed to elicit information on the demographic structures of the respondents, names of plants commonly used in the treatment of tuberculosis, plant parts used, the methods of preparation, and therapeutic application including details on administration and dosages. Interviews were conducted in the local language of the respondents and, with the help of an interpreter, it was translated to English. Samples of the plant material used for the management of tuberculosis were collected from the wild. Scientific identification of samples collected was done in the Department of Botany, University of Fort  Hare, Giffen Herbarium, where herbarium specimens are kept; and thereby reference to standard botanical classification and nomenclature [An ethnobotanical survey on medicinal plants was carried out in order to obtain phytotherapeutic information on plants useful for the treatment of tuberculosis in Eastern Cape Province, South Africa. This survey was conducted in the following villages within the Nkonkobe Municipality: Hala, Ncera, Sheshegu, and Gquamashe, using a well-structured questionnaire. One hundred informants were interviewed using semistructured questionnaire in order to obtain information from the rural dwellers including traditional healers known asnclature , 16. IdeFor quantitative analysis, an ethnobotanical index was used to evaluate the local importance of those species in the study area using the relative frequency of citations (RFC).The ethnobotanical data on plant species collected for this study were elaborated and analysed. The different plant species were grouped into their respective families, with information on most cited species, plant parts used method of preparation, therapeutic application, dosage, mode of use and mode of treatment was also provided. Quantitative analysis of the data was done to know the diversity of species of plants in the study area, to verify the potential of local knowledge (importance) of the communities studied. Therefore, from the citations, the number of species, the number of respondents who gave some information, and information on the plant species were supplied. The ethnobotanical indices are found on the basic structure of the ethnobotanical information. Data analyses were followed by ethnobotanical indexes using relative frequency of citation. N is the number of respondents.Relative frequency of citation (RFC) is used to find out probability between number of people who give citation to each species and number of all respondents. The result described local importance of each species. RFC was calculated thusThe traditional healers who participated and also shared their wealth of knowledge on the information of plant usage during the ethnobotanical survey were adequately informed that this research shall not be for commercial purposes but will serve as a way of conserving indigenous knowledge as regards the traditional management of tuberculosis in Nkonkobe Municipality, Eastern Cape, South Africa. Ethical approval for the study was granted by the University of Fort Hare's Ethics Committee (UREC).In this study, 80% of the respondents were males and 20% were females . General Clausena anisata Hook, Haemanthus albiflos L, Artemisia afra Jacq. ex Willd, Carpobrotus edulis (L.) Bolus, Ptaeroxylon obliquum Thunb, and Tulbaghia violaceae Harv.   followed Clausena anisata was the most useful plant species (RFC = 0.1) with 10 citations (10% of the informants). It was followed by Haemanthus albiflos (RFC = 0.07) with 7 citations, and also Artemisia afra (RFC = 0.006) Clausena anisata was the most cited plant in this study. The recipes for the treatment of tuberculosis within the study area were made up of plant parts such as leaves, bark, fruit, and root only. These recipes were prepared as concoctions, macerations, and infusions while the mode of administration is oral  is one of unique experiences applied to traditional knowledge that is transferred to younger generation and is still developed by rural indigenous communities in specific geographical areas. The characteristics of IK come into view and are developed in specific society; they are unique and exclusive .The observation that a greater proportion of the informants were males could be attributed to the fact that male respondents were bold and courageous to talk and have rapport with the interviewer unlike their female counterparts who prefer to shy away.Generally, older people were mostly engaged in the practice of using herbs for healing. This information on the age of the respondents implies that youths in the study areas are not fully engaged in the traditional medicine practice and this suggests a breakdown in dissemination of knowledge between the old and younger generation. This simply implies that with time this knowledge may be lost  unless efforts are made to reverse the situation. Artemisia afra is used by the traditional healers in Amathole District to treat Flu and TB, and it is also used by the Zulu people [ Haemanthus albiflos was reported to have shown significant difference against DNA viruses and all RNA viruses [ Carpobrotus edulis was reported to have showed significant difference for the treatment of TB and as immune booster for HIV patients in Nkonkobe Municipality [A great proportion of the plant species documented have been validated through phytochemical and pharmaceutical research; some, although, not evaluated for their efficacy are used to treat TB and opportunistic diseases associated with tuberculosis in South Africa and other parts of the world. For instance,u people –20. The  viruses  likewisecipality , 20. Furcipality  reportedCannabis sativa was also reported, through infusion and inhalation, to be used for the treatment of TB among the Zulu people, Hutchings et al. [ Eucalyptus camaldulensis inhibited the growth of Bacillus cereus, Escherichia coli, Klebsiella pneumonia, and Staphylococcus aureus [ Asparagus africanus and Ficus sur which showed positive result against Mycobacterium tuberculosis; similarly, Ghosal et al. 1985 [ Haemanthus genus produce several alkaloids which have therapeutic effect against coughs and dropsy asthma and as topical antiseptics. Also extracts from several species of Amaryllidaceae plants have been found to possess pronounced antibacterial and antifungal activities [s et al. . Leaf exs aureus . Madikizs aureus  documental. 1985  reportedtivities . Clausena anisata, Haemanthus albiflos, Asparagus africanus, Araujia sericifera, Scabiosa albanensis, and Silene undulate were recorded for the first time for the management of TB in Nkonkobe Municipality, Eastern Cape Province. This investigation plays a significant role in the medicinal plant research in the context of management of  TB and its opportunistic diseases in Eastern Cape Province. Hence, the above listed plants are widely used for treating different ailment; for instance C. anisata was reported to treat measles and bronchial problem in Nigeria [ Clausena anisata against oral candidiasis and fungal infections of the skin [To the best of our knowledge Nigeria . In Tanzthe skin . C. anisata leaf have been used for the treatment of respiratory ailments. This finding is in line with the present study which justifies the widespread use of C. anisata for the treatment of TB in Nkonkobe Municipality. York et al. [ Cryptococcus neoformans, Klebsiella pneumonia, Moraxella catarrhalis, Mycobacterium smegmatis, and Staphylococcus aureus in KwaZulu-Natal. The aqueous and methanol leaf extract of C. anisata was also reported in Ethiopia to have exhibited anti-antimycobacterium properties against Mycobacterium tuberculosis and Mycobacterium bovis.Hutching et al.  reportedk et al.  reportedThe current study was undertaken to investigate local communities in Nkonkobe Municipality, Eastern Cape Province, as regard the treatment and management of TB. The documented medicinal plants used by the Xhosa herbalist reflect a rich ethnomedicinal knowledge in the municipality. These results strengthen the firm belief that traditional medicines are readily accessible and still play an important role in meeting the basic health care of many people in African communities. Clausena anisata, Haemanthus albiflos, Artemisia afra, Carpobrotus edulis, Ptaeroxylon obliquum, and Tulbaghia violacea. The most frequently mentioned species was Clausena anisata known locally as Iperepes. Many studies have revealed some bioactive chemical compositions in these plants which probably justify their pharmacological properties. The following five species were recorded for the first time for the management of TB in Eastern Cape Province, South Africa: Clausena anisata, Haemanthus albiflos, Araujia sericifera, Scabiosa albanensis, and Silene undulate. This study has contributed to the scientific documentation of medicinal plants used for the treatment of TB. This is necessary in the rural communities to avert the erosion of traditional medicine knowledge. The larger percentage of the traditional healers is old people; therefore, this legacy needs to be conserved. Further studies are in progress on the antituberculosis assay to validate ethnopharmacology relevance of the most mentioned plants in the study area.Phytomedicinal information on the treatment of TB in this region is well established. Thirty plants belonging to 21 families were mentioned to be used for the treatment of TB and associated diseases. Other diseases treated using these plants were respiratory infections. The commonly mentioned species are


A common radiometric platform for the development of application-specific metrics to quantify the performance of sensors and systems is described. Using this platform, sensor and system performance may be quantified in terms of the accuracy of measurements of standardized sets of source distributions. The prototype platform consists of spectrally programmable light sources that can generate complex spectral distributions in the ultraviolet, visible and short-wave infrared regions for radiometric, photometric and colorimetric applications. In essence, the programmable spectral source is a radiometric platform for advanced instrument characterization and calibration that can also serve as a basis for algorithm testing and instrument comparison. Current radiometric source standards disseminated by national metrology institutes (NMIs) such as the National Institute of Standards and Technology (NIST) in the United States utilize traditional technologies, e.g., tungsten filament lamps and blackbodies; reflectance plaques and integrating spheres. These standards are spatially uniform and have spectral properties that vary smoothly with wavelength. These are important characteristics with respect to the practical, economic, and consistent dissemination of standards with values that are traceable to the International System of Units (SI) with the lowest possible uncertainties. These sources are ideal for cases where customers’ applications utilize sources with similar spectral and spatial properties. However, there are many applications of critical significance where the sources have unique properties. Many types of measurement bias exist in radiometry, and these effects are exacerbated when the calibration and the target source differ in their fundamental influencing parameters such as spectral or spatial distribution, brightness, or temporal behavior. As a consequence, while the existing sources provided by NMIs are important for general calibration applications, they tend to have limited utility for advanced characterization and calibration measurements. The absence of relevant, application-specific, radiometric artifacts to evaluate the performance of instruments, or to provide an application-specific calibration source standard, limits the ability of end users to verify the measurement results, sometimes with adverse consequences. Therefore, the need exists for advanced calibration artifacts to improve measurement accuracies in a wide variety of applications, ranging from basic colorimetric characterization to remote sensing radiometry.In general, advanced calibration artifacts include spatially as well as spectrally complex distributions. Accordingly, there are two independent components to a full calibration platform capable of generating spatially and spectral complex scenes: a spectral component and a spatial component. Thus, a fully integrated radiometric characterization and calibration facility would have the capability of generating standardized sets of spatially complex scenes with high spectral fidelity . SpectraIt is time-consuming, expensive, and often impractical to develop and maintain different sets of calibration artifacts for each type of calibration, or for each anticipated application of an instrument. This has motivated the concept of a unified, generalized, radiometric calibration platform, preferably using common technologies and base elements, that can operate over a wide spectral range, from the ultraviolet to the thermal infrared, with at most modest changes to the basic structure. This platform will be used to generate a wide variety of standard calibration artifacts, i.e., source spectral and spatial distributions, needed for advanced radiometric characterization and calibration of sensors. The radiometric values of the platform can be made traceable to the values of reference standards using detector-based protocols. In addition to the reduction of uncertainties that arise from measurement bias, more efficient utilization of resources can be achieved by combining individual test, characterization, and calibration procedures that are required for a thorough understanding of a sensor’s performance into procedures that utilize advanced radiometric platforms. Savings can also be achieved by utilizing these platforms as artifacts for sensor intercomparisons for applications where multiples of “identical” units are used by a wide number of customers or participants.In this work, we describe the development of the first component of a complete radiometric platform, an Advanced Radiometric Source (ARS), capable of generating complex spectral distributions. Several example radiometric characterization and calibration applications of the technology are described.A variety of different approaches to the development of spectrally tunable sources have recently been described, including the use of spatial light modulators , 4, 7, 8While a variety of SLMs can be used, the two ARSs described in this work use a Digital Micromirror Device (DMD)The fundamental radiometric distribution of the source depends on the spectral output of the primary source and the imaging properties of the spectroradiometer. An arbitrarily shaped spectrum, representing a target spectral radiance, is generated by turning on different numbers of elements of a micro-mirror column corresponding to a specific wavelength. Consequently, the source intensity can be modulated by changing the number of mirror elements “on” while maintaining a constant spectral distribution. The system can be operated in either dc or ac mode (at rates up to 5 kHz), creating either constant or time-varying spectral distributions.Two prototype ARSs have been built, one that operates in the visible (Vis) spectral region, from approximately 400 nm to 700 nm, and one that operates in the short-wave infrared (SWIR) region, from approximately 1000 nm to 2500 nm. Common software has been developed for both platforms; the software generates a binary spectral image on the DMD that creates an arbitrary target spectrum. The target spectrum is read in from a file, peak normalized, and re-sampled to place it on the wavelength grid of the 1024 DMD image columns. Wavelength and intensity calibrations, specific to each ARS, are then applied. For the intensity calibrations, it was simply assumed that the relative intensity at a given wavelength, corresponding to a given DMD column, is proportional to the number of mirrors (from 0 to 768) turned “on” in that column. The binary images sent to the DMD are symmetric about a horizontal line drawn through its center to take advantage of the symmetry of the illumination source, which is generally aligned to be centered on the DMD.The Vis ARS operates in the typical spectroradiometer configuration, while the SWIR ARS is configured to operate in the reverse fashion from this configuration. In the typical configuration, light goes through a slit and is dispersed before hitting the DMD. In the reverse configuration, the opposite is true. Broadband light is incident on the DMD. Reflected light from the DMD is dispersed and is then incident on a slit. Both sources are detector-based; the Vis ARS uses a spectroradiometer while the SWIR ARS has been tested with a Fourier Transform Infrared (FTIR) spectrometer. Taking advantage of the wavelength stability of spectroradiometers, both ARSs can be based on single element detectors, which is a simpler, cost-effective approach. A single-element silicon detector is suitable for the Vis ARS while either an extended Indium Gallium Arsenide (extended InGaAs) or Indium Antimonide (InSb) detector is appropriate for the SWIR ARS.The Vis ARS has the standard spectroradiometer configuration, shown in The incident light is collimated using a cylindrical lens, diffracted by a visible grating, then imaged onto the DMD using a second cylindrical lens. The light reflected from the DMD when the mirrors are “on” is collected by a collection lens and coupled into a liquid light guide. The light guide is introduced into a small integrating sphere, where the output is measured with a spectroradiometer. Note that the quality of any spectral match with a target light distribution is directly related to the quality of the spectroradiometer-measured spectral distribution. Any systematic errors in the spectroradiometer measurements will be incorporated into the source spectral distribution. Scattered light within a spectroradiometer is a common source of significant measurement error with these instruments. For the lowest uncertainty measurements, the spectroradiometer was first characterized and corrected for its stray light response .A bit map image sent to the DMD consisting of a vertical strip of all elements in one or several columns 'on' corresponds to a virtual exit slit in the spectroradiometer. As different columns are turned on, the virtual exit slit moves across the dispersed image, and different spectral distributions are reflected onto the imaging mirror. Complex spectral distributions are generated by turning on series of mirrors across the DMD array. For the SWIR ARS, a single-grating commercial spectroradiometer was used in reverse mode  are readily commercially available, and use of these instruments in the ARS would enable a closer match of the ARS spectral distribution to the fine structure target distribution. Incorporation of an ocean-color ARS into measurement activities that are designed to produce consistent and accurate calibration and validation datasets for satellite sensors, such as the Sensor Intercomparison and Merger for Biological and Interdisciplinary Oceanic Studies (SIMBIOS) Project [ Project , would gColorimetric quantities of a light source can be measured with a colorimeter that has three or four channels consisting of detectors with spectral filters; the channels are designed to have relative spectral responsivities (RSRs) that mimic the color matching functions defined by the International Committee on Illumination (CIE) . No colox, y) and 10 % in luminance (Y) while the manufacturers’ specifications (specified for Illuminant A) are 0.002 in x, y and 2 % in Y [Colorimeters and spectroradiometers are normally calibrated against an incandescent standard lamp operated at a correlated color temperature of ≈2856 K, approximating the CIE Standard Illuminant A . When th2 % in Y . Higher 2 % in Y , 20.Using the ARS, a variety of spectral distributions can be readily generated to provide a more useful or accurate metric for the evaluation of the performance of colorimeters for both general and specific applications. In one specific application, a spectrally tunable source, capable of matching the spectral distribution of primary red, green, blue and white colors of displays, would enable accurate and rapid calibration of a colorimeter or spectroradiometer used to measure the colorimetric properties of the display .a. An additional set of six color samples are often included representing a strong red, yellow, green, and blue; and representing complexion and foliage colors.In a more general application, the source can be used to generate spectral distributions according to established protocols that evaluate the performance of colorimeters. For example, protocols can be developed to generate a colorimeter Color Measuring Index (CMI), which can be thought of as the detector analog to a source Color Rendering Index (CRI) . The CRITo generate a colorimeter CMI, a set of spectral distributions can be generated by the ARS, and their colors measured by the colorimeter and a reference spectroradiometer. Then, the differences between the colors measured by the colorimeter and the reference spectroradiometer can be calculated, and a numerical value assigned for each spectral distribution based on the measured difference. A general CMI would be the average of the numerical values for the measured spectral distributions. The set of spectral distributions generated by the ARS will be determined by a standards organization, but could in principle be the same or similar to the distributions used to generate a CRI for sources. In this application, the RSRs of the colorimeter channels do not need to be known, and the CMI is based on measured, not calculated, values. The availability of the ARS enables source distributions to be realized that are no longer to be based on material samples  and Planckian excitation source spectral distributions. This gives standards organizations a great deal of flexibility in the defined spectral distributions to be measured not previously available, and should result in a useful, practical metric describing the general performance of the colorimeter.With the trend toward performance-based metrology requirements, NMI’s well-defined role in establishing and defining metrics to verify the performance of radiometric systems is becoming more critical. Current calibration artifacts lack the spectral and spatial complexity often required for advanced radiometric calibration protocols necessary to achieve the requisite instrument performance for a defined application. Cost effective artifacts and efficient means of scale dissemination must be achieved. The development of spectrally tunable sources enables NMI measurement and calibration services to respond to new radiometric requirements by providing necessary, relevant technology that tests the end performance of radiometric systems used in critical applications. The next step involves incorporating the advanced radiometric sources in high fidelity spatial scene generators to produce complex spatial scenes for the characterization of imaging systems . Togethe


The Brazilian Biotechnology Network aims at the academic sector. The academic sector is represented by 48 Graduate Courses registered at CAPES  /Ministry of Education, specifically in the area of Biotechnology. There are an even larger number of Graduate Courses related to Biotechnology but registered at CAPES in other areas such Biochemistry, Genetics. Pharmacology among others. So the Biotechnology academic sector is not irrelevant. However less than 1% of the scientific output in Biotechnology in Brazil reaches the market. The main goal of the Brazilian Biotechnology Network is to increase the visibility of the science that is produced in the Biotechnology sector in Brazil and related areas of application to catalyse the transfer of innovative scientific results to the industry. The academic and the private biotechnology sector do not interact. For this reason the number of scientists in Brazil hired by the private sector is small although Brazil graduates more than 1000 PhDs /year This reality differs considerably from the context in the United States that for this reason and others control 70% of the Biotechnology business in the world. In 2011 [http://blogs.nature.com/tradesecrets/author/lbarreto. In my last contribution published in September 26 I state that the efforts to develop biotechnology in Brazil now exceeds three decades. This analysis that deals with Opportunities and Limitations for Biotechnology Innovation in Brazil is part of an eBook published by Bentham Books [During the last three years I have contributed to the Bioentrepreneur blog of Nature Biotechnology: Since the seventies Brazil started training young scientists in plant genetic engineering and molecular biology, hoping to incorporate this nascent technology into EMBRAPA's  plant breeding efforts. This work I started in the 80s took place at The National Center for Genetic Resources and Biotechnology (CENARGEN) and added to the efforts of a dozen excellent geneticists. The soybean revolution in Brazil was brought about by Romeu Kihl; aluminum-resistant corn developed for the acidic "cerrado" soil was created by Ricardo Magnavacca; and the foundations of maize breeding had been previously done by the late Ernesto Paterniani. Eleuzio Curvello did cotton, and Alcides Carvalho, coffee, for 52 years of his life. Dalmo Giacometti and Silvio Moreira, citrus. Marcilio Dias and Hiroshi Ikuta are the fathers of the vegetable genetics; Raul Moreira tackled banana; Ady Raul da Silva, wheat. Finally Frederico Menezes Veiga, sugarcane in the North of Rio de Janeiro. Through all this, plant breeding has continuously built cultivars to feed our seed industry. High-tech seeds and low-cost farming practices were the result of seed laws and plant breeder's law in Brazil. The end result is that Brazil can competitively produce nearly 200 million tons of grain because it is cheap for the farmer. Brazil tried to follow the growth of commercial biology. In the '90s, Brazil introduced protections for intellectual property around genetics and plant breeding rights as aid before, but that efforts were not sufficient, because Brazil suffered through rampant inflation for decades even as it invested in Biotechnology.The e-Book describes adjustments that must be made to assure the success of our investments, particularly to the laws and regulatory framework. The book investigates the immense possibilities of agricultural biotech in Brazil, partly because the mechanisms of public private interactions are well designed and in operation. The public perception in Brazil and many other countries has turned against genetic engineering for political and ideological reasons: when the first engineered soybean resistant to glyphosate was released commercially a campaign against transgenic plants prevented the application of this technology in agriculture for almost a decade in Brazil. However, the world adopted recombinant DNA technology in the pharmaceutical area and most products utilized internationally by the public in this industry (including Brazil) are genetically engineered. There is a twisted public perception problem in the Ag Biotech that has to be faced globally, particularly in Europe. The only solution is to focus biotech on the issues surrounding poverty (discussed in one of the e-book's chapters).http://portal.anvisa.gov.br/wps/portal/anvisa-ingles). Brazil has never produced a block buster or registered a pharmaceutical product at the FDA. Large corporations in general do not invest in Brazil, claiming Brazil's patent laws are not adequate. And finally, Brazil has no risk capital funds (Burrill & Co is a solitary actor).In the pharmaceutical industry in Brazil the context is quite different. Brazil lags behind many developed and emerging countries, and does not have an equivalent to EMBRAPA in the public pharmaceutical area. The area is growing, however , because the market is a demanding one. We import active principles from other countries and commercialize foreign products for our market here. So we are growing without innovation. There are initiatives that pull large, nationally funded companies together as consortia, and which propose "biosimilars" for monoclonal antibodies with expiring patents, but there is no innovation as an initiative. Brazil has no contract manufacturing organization, and not one CMO or cGMP-facility. Because of this, Brazil cannot scale up its pharmaceutical products, nor can it properly conduct the clinical studies needed for registration at ANVISA (There is a movement in the right direction, however. The government is supplying loans for biotech projects, allowing repayment in 10 to 15 years, with subsidized interest and the absence of capital payment for 3 to 5 years. Also, the federal government and private sector are funding scholarships to train 100,000 students in the next five years at all levels from high school to PhD. This is great news, but there are many more problems that need to be resolved in the coming decade. In 2005 Brazil sanctioned an Innovation Law. We estimated that in ten years 10 billion US$ would flow to the Biotechnology sector. The decade is almost over and funds never came by.


Violence is a major public health issue, globally and on the African continent. This paper looks at Uganda and begins the process of identifying the factors that predict violence in that country. The purpose is to interpret the implications of the study results for violence prevention programs.The study includes the responses of 2 399 Ugandans collected in 2011 by the Fifth Round of the Afrobarometer surveys. The study concentrates on 259 respondents who reported either they or someone else in their family had been the victim of violence, defined as being physically attacked, in the last year.Logistical regression analysis identified six factors that predict physical violence in Uganda. In order, these included being the victim of a property crime, age, gender, fear of crime in the home, poverty, and residential crowding. The surprising findings relate to what may be called target hardening, especially for those likely to be re-victimized. Respondents did tend to be re-victimized, with about 61 percent of violence victims also property crime victims. Fear of crime in home was another predictor of violence victimization, and many of these respondents had been crime victims.These findings imply that target hardening should be the basis to begin to implement violence prevention programs in Uganda. The suggestion is crime prevention personnel/ law enforcement need to respond to reported incidents of property and/or violence victimization and attempt to prepare victims to protect both their premises and their persons in the future. The maj country  domestic country  as well  country .There has been an increasing volume of calls to develop violence prevention programs at the country, continental and international levels, as well as the concomitant need to begin to develop violence prevention programs . One appThe International Crime Victim Survey (ICVS)  was firsThis study's Data Source is Afrobarometer, a collaborative research effort produced by social scientists from 35 African countries. The Project′s objectives are as follows; 1) to produce scientifically reliable data on public opinion in sub-Saharan Africa; 2) to strengthen institutional capacity for survey research in Africa; and 3) to broadly disseminate and apply survey results. Begun in 1999, five rounds of the survey have been completed; Uganda was included in all five waves, as well as two other country specific surveys. The most recent survey was conducted in 2011, and became available in 2013.The Survey consisted of face-to face Interviews completed by 2 399, 18 years of age or older. These interviews were conducted in fifteen different languages. The sampling frame included all nine Ugandan provinces, and the final sample supports estimates to the national population of all adults in Uganda that is accurate to within a margin of error of plus or minus 2 percentage points at a confidence level of 95 percent. The sampling procedures used in all of the Afrobarometer surveys are explained in detail in Bratton, Mattes and Gyimah-Boadi (2005) .The dependent variable: violence victimization: survey respondents were asked about criminal victimization. One question asked “over the past year, how often, if ever, have you or anyone in your family been physically attacked?” Fixed responses were provided as follows: never; just once or twice; several times; many times; and always. The study's dependent variable was created by treating never as one category (0) and all other affirmative responses were coded as one (1). This dichotomous variable is the study's dependent variable and provides the basis for the logistic regression presented below.The independent variables: a poverty scale used in the Afrobarometer studies was adopted from Mattes et al. (2003) [. (2003) , factor The sample social and demographic characteristics are displayed in In The independent variables listed in The surprising finding in Before the implications of these findings for crime prevention in Uganda are addressed, there are several issues that need to be mentioned. One of these is what Shepard  defined The logistical regression analysis showed that there were five highly significant factors that predicted violence in Uganda. In order of their magnitude, these included being a victim of property crime, poverty, age, gender, and fear of crime in the home; residential crowding also reached significance in the logistical regression analysis, at a lesser significance level. These findings present possible ways to approach crime prevention programs in Uganda. They suggest that target hardening should be the basis to begin to develop and implement violence prevention programs. This approach would mean that crime prevention/ law enforcement personnel should respond and follow-up incidents of reported property and/ or violence victimization in their jurisdictions. The purpose would be to attempt to prepare and assist victims to better protect both their premises and their persons. Target hardening refers to issues like improving locks, installing proper night lighting and clearing bushes from in front of their windows that might impede visibility of their property and neighborhoods. Personal experience with target hardening programs suggests that residents become open to target hardening approaches, and personnel, once they have been victimized. Also, once victimized, residents are more encouraged to develop local neighborhood groups that provide security for themselves and those in their own communities.


Although a rare disease, uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 persons per year in Europe. Only a few consistent risk factors have been identified for this disease. We present the study design of an ongoing incident case-control study on uveal melanoma (acronym: RIFA study) that focuses on radiofrequency radiation as transmitted by radio sets and wireless telephones, occupational risk factors, phenotypical characteristics, and UV radiation.We conduct a case-control study to identify the role of different exposures in the development of uveal melanoma. The cases of uveal melanoma were identified at the Division of Ophthalmology, University of Essen, a referral centre for tumours of the eye. We recruit three control groups: population controls, controls sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, and sibling controls. For each case the controls are matched on sex and age (five year groups), except for sibling controls. The data are collected from the study participants by short self-administered questionnaire and by telephone interview. During and at the end of the field phase, the data are quality-checked.To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding. Although a rare disease, uveal melanoma of the eye is the most common primary intraocular malignancy in adults, with an incidence rate of up to 1.0 per 100,000 person years  in Europe ,3. AnothSome uveal melanoma are associated with neurofibromatosis. However, the vast majority of familial cases reported are non-syndromic . Some reOccupation may be also relevant, and may include chemical work ,12, arc The population-wide introduction of analog and digital mobile phone techniques in the recent years, which has been coined as the mobile revolution , has resUntil now, the majority of epidemiological cancer studies focussed on brain cancer because the brain may be exposed to RFR -20. WithThe RIFA study is planned to answer several etiologic questions with a special focus on electromagnetic radiation especially radio-frequency radiation as emitted by mobile phones and radio sets. First, is the finding of an increased risk of uveal melanoma among subjects with frequent use of RFR devices reproducible? Second, if there is an association, is this association site-specific in terms of laterality of the uveal melanoma and major site of mobile phone use? Third, if there is an association, is there a dose-response relationship between RFR and uveal melanoma risk? Another set of etiologic question relates to pigmentation characteristics including iris colour, hair colour, tendency of the skin to burn and to tan, freckling, number of cutaneous nevi. A further study questions relates to exposure to work and leisure time related ambient ultraviolet radiation and uveal melanoma risk. In addition, our study focuses on several occupational exposures or jobs that are suspected to be associated with an increased risk of uveal melanoma ,15 incluth, 2002 to September 24th, 2004 are eligible, if they are referred to the Division of Ophthalmology, University of Duisburg-Essen during the recruitment period, are aged 20–74 years at diagnosis, are living in Germany, and are capable to complete the interview in German. The majority (about 70–80%) of uveal melanoma treated at the University Hospital Essen receive episcleral plaque therapy without histological verification. For this reason we did not include a reference pathologist who reviews the diagnostic certainty of the cases. Experiences from our previous case-control studies showed that there is a nearly perfect agreement between the local eye doctors in the reference centre and the international reference pathologist  [The case recruitment is hospital-based and takes place in the Division of Ophthalmology, University of Essen which is a the referral centre for eye cancer in Germany, currently treating about 400–500 eye cancer patients per year. Eligible uveal melanoma cases have to fulfil several criteria. Patients with newly diagnosed first uveal melanoma located in the choroid, iris, and/or ciliary body  during t London) .We considered a diagnosis of uveal melanoma as definite if the results of the clinical examination of the eye  and ultrasound  were unambiguous. The inclusion and exclusion criteria of the cases are listed in table th, 2002 through March 31th, 2004. Assuming comparable incidences of uveal melanoma in the federal states of Germany, the crude rate (referred cases divided by population at risk aged 20–74 years) may be considered as an indicator of the referral effect.Interim analyses showed that the majority of cases comes from the territory of former West Germany. Figure Obviously, the referral effect varies by federal states. However, it is difficult to judge whether the case referral to the Division of Ophthalmology, University of Duisburg-Essen is a random sample of all newly diagnosed uveal melanoma cases in Germany. We therefore decided to recruit three different control groups. First, if we assume that cases treated in Essen are a random sample of all cases in Germany, a population-based control group would be the most appropriate control group. For this approach, we randomly select controls from mandatory lists of residence that cover the total population of the city or local district. These lists are regarded as the most complete sampling frame for population-based studies in Germany.Second, if the referred cases are not a random sample of all newly diagnosed cases of uveal melanoma in Germany, a control group sampled from those ophthalmologists who referred cases to the Division of Ophthalmology, University of Duisburg-Essen, would be most appropriate ,26. To iIn addition, we recruit sibling controls of cases (matching ratio 1:1) in order to assess whether genetic factors may confound the effect of exposure. The sibling controls are matched in genetic background. The inclusion criteria of the three control groups are presented in table Based on our former uveal melanoma case-control studies ,22 we esPopulation-based prevalence estimates of mobile phone use in the general population are scant. A recent telephone survey from 2001 showed that 82% of male and 74% of female participants aged 14–44 years use mobile phones; within the age group 45–59 years, 63% of male and 58% of female participants use mobile phones. The oldest age group (> = 60 years) shows considerable lower prevalences of mobile phone use  . To deteTable The questionnaire on mobile phone use is the same instrument which has been used by the international case-control study on brain cancer and mobile phone use sponsored by the International Agency for Research on Cancer, called Interphone study . In contCompared to other studies on the aetiology of uveal melanoma, the RIFA study uses a detailed assessment of pigmentary characteristics. The self-administered questionnaire contains a eye and hair colour card that allows the participants to choose the most appropriate colour of their eyes and hairs at age 20 years. During the telephone interview, the skin reaction to sun exposure  is asked according the concept of Fitzpatrick . FitzpatFor the assessment of nevi of the upper arms and the dorsum of the feet with a diameter of at least 3 mm, participants receive a template with a 3 mm hole that enables them to count all nevi of this minimum size. In addition, the CATÍ (computer assisted telephone interview) includes a detailed history of sunburns in the recent 15 years before interview and tendency to freckle as a child. The CATI contains a question on eye colour with the typical categorical answers as has been used by several others , we use 16 job-specific supplementary questionnaires to obtain details of the job tasks and materials used.The quality control program includes several procedures. The study is designed to fulfill the recommendations of the German Good Epidemiologic Practises .Eight month before the main study started, a manual of standard operating procedures (MOP) was written and a pilot study of four weeks was conducted to test the field work and exposure questionnaires. After some minor revisions of the MOP, report forms, and questionnaire instruments, the principal investigator and participating epidemiologists had to sign that they fully agree with the final version of the MOP.Interviewers of the study were introduced into the field work and were blinded against our study hypotheses. After an initial interviewer training course, interviewers are regularly monitored and receive regular training courses.The recruitment progress, given as number of registered cases and controls, distribution of inclusion and exclusion criteria, response proportions, is monitored monthly. The analysis of nonresponse reasons is supplemented by an short questionnaire for subjects not willing to participate. This questionnaire includes few demographic and exposure items that help us to assess potential selection effects due to nonresponse.A plausibility control of the interview data is done quarterly and is the basis for the regular training courses of the interviewers.The completeness of case registration is checked by regular comparison of the list of registered cases with lists of admissions to the referral centre. In addition we compare our list of cases with data of the hospital information system that includes information on diagnoses.The self-administered short questionnaires are visually edited by the study personnel before the telephone interview starts. The visual editing includes a completeness check and coding of the life-long job history. For each job period, the occupation and branch of industry is coded according to ISCO-68  and NACEThe CATI contains internal quality checks that prevent data entry errors. For example, interviewers are not able to fill in the detailed questions on mobile phones, if the entry question on ever having used mobile phone has been answered with no.At the end of the field phase, the data are quality-checked. To estimate the effect of exposures on uveal melanoma risk, we will use conditional logistic regression that accounts for the matching factors and allows to control for potential confounding. We will classify people exposed to an occupational category if they ever worked within this category for at least six months. The quantification of mobile phone use will be based on average number of phone calls and average duration of phone calls per time unit. The association between pigmentary characteristics and uveal melanoma risk will be assessed by detailed matrix containing information on hair colour at age 20 years, eye colour, freckling tendency, and skin colour. Final results of these analyses are scheduled to be published in summer 2005.None declared.The pre-publication history for this paper can be accessed here:


The insect exoskeleton or cuticle is a bi-partite composite of proteins and chitin that provides protective, skeletal and structural functions. Little information is available about the molecular structure of this important complex that exhibits a helicoidal architecture. Scores of sequences of cuticular proteins have been obtained from direct protein sequencing, from cDNAs, and from genomic analyses.Most of these cuticular protein sequences contain motifs found only in arthropod proteins.Drosophila melanogaster and the Anopheles gambiae genomes, that have been predicted to be cuticular proteins, based on a Pfam motif (PF00379) responsible for chitin binding in Arthropod cuticle. The total number of the database entries is 445: 370 derive from insects, 60 from Crustacea and 15 from Chelicerata. The database can be accessed from our web server at .cuticleDB is a relational database containing all structural proteins of Arthropod cuticle identified to date. Many come from direct sequencing of proteins isolated from cuticle and from sequences from cDNAs that share common features with these authentic cuticular proteins. It also includes proteins from the CuticleDB was primarily designed to contain correct and full annotation of cuticular protein data. The database will be of help to future genome annotators. Users will be able to test hypotheses for the existence of known and also of yet unknown motifs in cuticular proteins. An analysis of motifs may contribute to understanding how proteins contribute to the physical properties of cuticle as well as to the precise nature of their interaction with chitin. One particular family of cuticular proteins constitutes one of the largest multigene families known in insects . UnrelatThe database nomenclature is based either on the names given by those who deposited the sequences or on codes assigned by genome projects. Thus, we have retained the existing names/codes for the convenience of the users.cuticle, exoskeletal, carapace) to the Protein databases of Entrez and Uniprot (release 1.8) [Anopheles gambiae and Drosophila melanogaster, from Ensembl [The data collection has been basically done in two ways. First, by submitting appropriate keywords ase 1.8)  we colle Ensembl  and EBI, Ensembl . This mo Ensembl  and most  we coll Ensembl . A short Ensembl , and, as Ensembl , was wid Ensembl ,3and refIn order to ensure that our data collection is complete, we scanned all protein sequences of Uniprot (release 1.9) for PF00379. Again manual filtration was required. In addition to PF00379, other motifs have been described in cuticular proteins, some are found along with PF00379 while others define other families of cuticular proteins ,3. All rThe data for our database was obtained by parsing the fields Definition, Accession, GI from Version, Organism and Origin from the Entrez entries. From the Uniprot entries we used Primary accession number, Protein name, Origin of the protein, Cross-references and Sequence information. This retrieval was done with Perl scripts. Additional information, concerning temporal and local expression of the proteins or corresponding mRNAs, was drawn from literature.The data have been organised based on a relational model and is stored in a PostgreSQL database system. The user has supervisory access through our Apache web-server. The database is managed by an interferential software, written in Java, which tends to settle any web-server's query. Also, it implements a homemade computational tool that performs motif search as described below.The main page of cuticleDB includes the following interfaces: Introduction, Data Retrieval, User manual and Contact. On clicking the Data Retrieval icon, users are presented with the search interface of the database. The query can be done in two ways: either by searching in fields or by gathering a set of proteins Figure .The separate fields in which the user may search are Protein name, Taxonomy, references in other databases  and the protein sequence. The protein sequence can be searched against any pattern according to the user's imagination and, therefore, hypotheses for novel motifs can be tested. This is performed by a separate, homemade tool that has been integrated in cuticleDB and which gives the user the opportunity to detect new motifs in cuticular proteins. The integration of this tool is of importance especially in a database such as this, given the significance of motifs not only in cuticular proteins, but in structural proteins in general.Users can gather all protein entries from a single species (35 species are included in cuticleDB) or all protein entries whose protein sequence contains one of a series of motifs. However, this series of motifs has been pre-selected by the constructors of the database and cannot be modified by the user. The selection criterion was the frequency of appearance of these motifs in the literature. The most commonly found motifs were searched against all protein sequences of the database and have properly been assigned to each entry.A typical cuticleDB entry contains the following fields: Protein Name, References to other databases , Taxonomy, Expression Details, Protein Sequence and its Length, Database-Source of the sequence and the method by which the sequence was obtained Figure . The fieD. melanogaster, A. gambiae). The only verified cuticular proteins are those where the complete protein sequence or a unique N-terminal region was determined from a protein extracted from a cleaned cuticle or where a specific antibody reacted with proteins in cuticle or extracted from it. Finding mRNA in the epidermis is presumptive evidence that a protein is cuticular. The majority of cuticular proteins in this database were designated as cuticular proteins based on their sequence similarity to authentic cuticular proteins. Such proteins where sequence is the sole criterion for assignment are marked as "putative" in the database. Furthermore, at present, the annotation of the proteins of A. gambiae is preliminary. Many proteins are missing signal peptides, other clearly have been incorrectly assembled. Such sequences are marked as preliminary as well as putative. This database will be continuously updated at regular intervals to accommodate annotation.Taxonomic data are taken from Entrez. The total number of entries in cuticleDB is 445. These proteins are distributed in the three large taxa: Insecta (370 entries), Crustacea (60 entries) and Chelicerata (15 entries). The database includes entries from 6 orders of the class Insecta: Diptera (258 entries), Lepidoptera (39 entries), Orthoptera (37 entries), Hemiptera (6 entries), Coleoptera (22 entries), Dictyoptera (8 entries). The large number of proteins in Diptera is due to the inclusion of cuticular proteins from the two genomes . Both oSubsequently, we used these Profile Hidden Markov Models as a prediction tool for classifying the cuticular proteins into two groups RR1, RR2. The prediction was in agreement with the literature as far as the known RR1 and RR2 proteins are concerned. The total number of RR1 and RR2 proteins in cuticleDB are 132 and 148, respectively. The start and end positions of the two motif-types are shown in the corresponding entry of each protein. A smaller class, RR-3, with 75 conserved residues was also identified by Andersen [We have also studied the appearance of another motif: AAP(A/V). This small, hydrophobic tetrapeptide has been found to occur mainly in proteins of hard cuticles ,3, whereThe most severe problem of genome projects to date is that of correct annotation. So, accurate and specialized databases as cuticleDB with its description of highly conserved motifs will be of help to genome annotators. Therefore, cuticleDB can be used as a basis for annotating new cuticular proteins by similarity in future Arthropod genome projects.cuticleDB can also be utilized in molecular research as well, due to its focus on motif appearance. Cuticular proteins, as is the case with all structural proteins are marked by the presence of characteristic motifs. Some motifs are repeated within a protein sequence, whereas others appear only once. cuticleDB has been designed in such a way that the user can have a complete view of motif occurrence in the sequence of each protein entry. First, each entry shows the exact position of the most common cuticle motifs in the protein sequence. Secondly, the user is given the opportunity to search the sequence for novel motifs and therefore, test hypotheses for the existence of new patterns. Subsequently, hypotheses for possible interactions between cuticle macromolecules (either proteins with chitin or proteins with proteins) can be tested. Moreover, our results of the RR1 and RR2 predictions can be used as a guide for identifying a certain protein as coming from either soft or from hard regions of the cuticle. Most importantly, the information about the RR1 and RR2 distinction can be used for studies of cuticle's mechanical properties. As RR1 and RR2 proteins appear in soft and hard cuticles respectively, which means that the former interact with chitin more loosely than the latter, one can gain an insight in cuticle's molecular construction combining our data on the sequences of RR1 and RR2 proteins with some experimental work. Moreover, one could use the Expression Details, namely where and when each protein is expressed, when studying the differential construction of the cuticle among different developmental stages or among different regions of a single cuticle.The goal of cuticleDB constructors was the collection of all cuticular protein sequences that have appeared to date and their detailed and correct annotation. The better the organisation of the data, the easier the work will be for researchers dealing with cuticle and structural proteins in general. cuticleDB will help them to answer questions like : 'What kind of proteins appear in hard cuticles?' 'Why do RR2 proteins interact with chitin more tightly than RR1 proteins?' 'Which motifs contribute to protein-protein interaction in the cuticle?' 'From which stage can a certain protein be extracted?' Furthermore, it is hoped that, detection of common properties of these proteins, as well as recognition of important differences that are responsible for cuticle's complexity and important functions will be facilitated by its existence.Last but not least, it is hoped that this database will be of help to genome annotators in the near future as more arthropod genomes become available.. An e.mail biodb@biol.uoa.gr may also be used for comments, corrections and further data (sequence) submission.cuticleDB was created and is maintained in the Department of Cell Biology and Biophysics, Faculty of Biology of the National and Kapodistrian University of Athens. It is freely available at the URL: RR1: The extended Rebers and Riddiford Consensus, type IRR2: The extended Rebers and Riddiford Consensus, type IIHMM: Hidden Markov ModelCKM performed the data collection, and test procedures, and also participated in the design and the implementation of the databaseICS carried out the design of the algorithms and the database,. implemented all the algorithms, and also created the web interfaceVAI supervised the data collection and the testsJHW compiled the first draft of known cuticular proteins, provided a critique of the data base during its constructionSJH coordinated and supervised the whole project, suggesting the general directions and innovative features of the databaseAll authors have read and accepted the final manuscript.


This article traces the career of Celso-Ramon Garcia (1922–2004), noted physician, educator, and internationally renowned pioneer in the field of reproductive endocrinology. His work helped to formulate oral contraceptives used by millions of women throughout the world. Garcia's research collaborators included Gregory Pincus and John Rock, who together finalized the landmark clinical data needed to secure initial FDA approval for "the pill" in 1960. In addition to Garcia's monumental work in contraceptive endocrinology, his scholarly interests encompassed physiology of the menopause, minimally invasive reproductive surgery, as well as psychological aspects of infertility. Closely identified with the University of Pennsylvania, Garcia was instrumental in establishing the first formal clinical program in reproductive biology and influenced countless young scientists whose training he supervised and mentored. His distinguished career was emblematic of the best of the medical profession, characterized by compassion, intellect, and a sincere desire to help others. Our manuscript outlines Garcia's wide range of interests, acknowledges his superior fund of knowledge, and honors his humanitarian spirit – all of which contributed to an impressive legacy of medical discoveries. The impact of Prof. Garcia's work will continue to be felt for many years. Celso-Ramon Garcia Figure , who depGarcia was raised speaking Spanish, but his English diction and elocution were so honed by his teachers in grammar and high school that hardly a trace of accent was left to be detected by the Boston Brahmans he would later encounter. Along the way his interests took seemingly improbable turns, yet there was a clear rationale that was beyond the imagination of the average physician. Indeed, his work presaged several important developments in the field of reproductive medicine. Garcia began his career with an interest in obstetrics, but ended up conducting clinical research on contraception that on more than one occasion was nominated for the Nobel Prize in Medicine or Physiology. He was revered as a meticulous abdominal infertility surgeon, yet he embraced the fledgling field of endoscopy and endoscopic surgery. While being celebrated for his surgical technique, he promoted research into the psychological aspects of infertility. Towards the end of his career he became interested in sexuality in the menopause, bringing his career through the full cycle from obstetrics, to family planning, to infertility to reproductive aging. His accomplishments in each of these spheres were well recognized by his peers who chose him President of the American Association of Planned Parenthood Physicians, Chairman of the Board of Directors of Planned Parenthood of America, Founding President of the Society of Reproductive Surgeons, and President of the American Society of Reproductive Medicine and bestowed upon him the Scientific Leadership Award from the Global Alliance for Women's Health, a non-governmental organization of the United Nations.Garcia's course to greatness was based on a diverse set of skills that he used creatively throughout his career. He majored in chemistry at Queens College where he revealed a remarkable aptitude for analysis of organic compounds. During his undergraduate studies, Garcia served as a teaching fellow in chemistry at New York University and authored two papers on qualitative and quantitative analysis. These are the earliest public manifestations of his passion for rigor and precision, which subsequently guided his clinical practice and his scholarship. After receiving his baccalaureate degree he entered medical school at the Long Island College of Medicine (now SUNY-Downstate) and graduated in 1945. He completed a rotating internship at the Norwegian Hospital in Brooklyn and then served two years in the U.S. Army Medical Corps in Fairbanks Alaska and then the Phoenixville General Army Hospital outside of Philadelphia. Garcia started a residency in pathology at Cumberland Hospital in Brooklyn where he was introduced to Sam Lubin, who became his friend and mentor. Lubin's work focused on uterine pathology and contractility and this sparked Garcia's interest in obstetrics and gynecology. With Lubin, Garcia would later publish papers on the effects of meperidine on labor.After a year of pathology residency and a year as a research fellow, Garcia transferred to the obstetrics and gynecology program at Cumberland Hospital. With a pathologist's keen eye and an appreciation of tissue biology/healing, Garcia was well-equipped to excel in the art of reproductive surgery. In the operating rooms at Cumberland Hospital Garcia met Shirley Stoddard, the newly appointed Director of Surgical Nursing; she was to become his wife and lifelong companion. After completing residency, Garcia explored openings in academia but few opportunities were available. One exception was an advertisement for assistant professor of obstetrics and gynecology at the newly established medical school at University of Puerto Rico, for which Garcia applied and was accepted in 1953.Garcia's research during residency, mentored by Lubin, had focused on obstetrical issues – something that he could have easily developed as a junior faculty member at the University of Puerto Rico. However, Garcia was about to embark on the first of several sharp turns that would lead him into seemingly improbable arenas. His arrival in Puerto Rico fortuitously coincided with the time for the first large scale clinical trials of the oral contraceptive pill. Within a year of Garcia's arrival, Gregory Pincus  was in Puerto Rico looking for sites to conduct these trials. It was there that Pincus was first introduced to Garcia. Pincus had an uncanny ability to sense talent; he always surrounded himself with the brightest people. Pincus, undoubtedly impressed by Garcia's fund of knowledge in organic chemistry, training in pathology, and of course, the fact that he was bilingual in addition to his training in obstetrics and gynecology, promptly recruited Garcia to oversee his important research program in Puerto Rico.Pincus would subsequently introduce Garcia to John Rock, who arranged for Garcia to be named Sydney Graves Fellow in infertility and gynecology at the Free Hospital for Women in Brookline, Massachusetts. There, Garcia continued to work on oral contraceptives but also pursued clinical work in infertility. Although the Graves fellowship no longer exists, contemporary reproductive medicine was developed by its incumbents. Rock had an interesting manner of selecting these fellows. He usually interviewed candidates over breakfast in his hotel room at the annual meeting of the American College of Obstetricians and Gynecologists. He could identify the smart ones within a minute, and had little patience for individuals who were not well-spoken. The diction and elocution drilling Garcia had endured and his insistence on precision brought him through with flying colors.Garcia quickly became indispensable to Rock. Garcia moved to Boston, where he held assistant and instructor faculty posts at Harvard Medical School. During this time, Garcia also commuted to Puerto Rico to manage the oral contraceptive trials. Rock had a thriving infertility practice and Garcia did much of the surgery. Garcia's contributions to Rock's clinical practice were, however, underappreciated and when it came time for Garcia to be proposed for a full-time position at the Free Hospital for Women, the job did not materialize. This scenario is not unfamiliar to practitioners in our field, and it elicited the obvious reaction: Rock and Garcia pulled up stakes and took their hugely lucrative practice to the Faulkner Hospital in Boston. But after a short interval, the Rock/Garcia partnership was persuaded to return to the Free Hospital where an appropriate appointment was arranged for Garcia. Mrs. Stanley McCormick, a benefactor of remarkable vision who had provided initial funds to Pincus and colleagues at the Worcester Foundation to begin studies on oral contraceptive steroids, helped establish the Rock Reproduction Study Center at the Free Hospital campus, greatly facilitating research and training.By 1960, Pincus had recruited Garcia to the Worcester Foundation as a senior scientist and director of the training program in Physiology of Reproduction. Sponsored by grants from the Ford Foundation and National Institutes of Health, this was the first training program of its kind. The discipline of reproductive biology as we know it today had its roots in the Worcester program. Although Garcia was appointed chief of the infertility clinic at Massachusetts General Hospital in 1962, he continued to visit Puerto Rico to perform follow-up examinations on women who had participated in the oral contraceptive trials in gratitude for their role and with genuine concern for potential untoward long-term effects. That was a personal mission, not a mandated component of the study protocol. This post-trial surveillance helped identify rare side effects that ultimately led to product reformulation and lowering of the steroid content of oral contraceptives. Garcia subsequently carried out groundbreaking studies on patient acceptance of oral contraceptives, recognizing that future developments in family planning must address the social and demographic aspects, including cultural differences in preferences for methods.th century. This is in good part Garcia's legacy [The technologies that gave men and women the ability to control their own reproduction through contraception and infertility treatments are arguably among the most important medical advances of the 20s legacy -3. WhileImportant medical advances like "the pill" or IVF do not come without controversy, societal baggage, and rhetoric. The pill's creators fully understood these implications, and knew such peripheral distractions would take away from the significance of their work. Consequently, there was no phone call from Sweden despite several nominations to the Nobel committee. But it is best to look back on the history of the development of the oral contraceptive with awe and wonder. Indeed, the commercial availability of oral contraceptives was also important because it established a formal approval and regulatory framework for pharmacologic agents of an entirely new class: drugs designed to be used by healthy people for long periods of time. It provided a clear understanding of how post-marketing surveillance can lead to product reformulations that reduce side effects without reducing efficacy. It yielded an understanding of how sociology and demography must be incorporated into the development of pharmaceuticals and the practice of medicine.Garcia maintained his connections with Rock and Rock's family of protégés, one of whom (L.M.) later lured him and other Rock/Pincus trainees, Edward Wallach and John V. Kelly, to the Department of Obstetrics and Gynecology at the University of Pennsylvania. Garcia spent the rest of his career at Penn developing the specialty of reproductive surgery, particularly microsurgical approaches. Here again came the totally un-expected. Garcia was at his best when confronted with the most challenging open abdominal procedures, which always ended with the pelvis in a pristine state, not a drop of blood, all surfaces meticulously re-peritonealized, no risk of inflammation or adhesion. Garcia's novel regimen of intraperitoneal corticoids and antihistamines (an early anti-adhesion therapy) was merely icing on the cake. The two-stage tuboplasty procedure was celebrated both locally and internationally. Yet this master of the open abdomen quickly recognized the potential of minimally invasive surgery, establishing one of the first endoscopic surgery programs in USA after a brief sabbatical with his colleague, Professor Kurt Semm in Kiel, Germany.During his career, Garcia authored numerous textbook chapters on surgery of the ovaries, tubes and uterus that guided a generation of gynecologists in reconstructive surgery. He was also an early advocate of laser and electrosurgical methods, as well as microsurgical techniques designed to minimize tissue trauma. When Garcia's residents and fellows under-performed, he could not mask his displeasure, yet when they excelled he could not hide his joy. His concern for the outcomes of a rapidly evolving medical specialty led him to develop one of the first electronic infertility data registries .In 1968, Garcia made yet another change in tack, developing an interest in psychological aspects of infertility. While this may have puzzled colleagues who knew Garcia only by reputation as a surgeon, those of us who worked with him knew well his holistic commitment to medicine and his devotion – unprecedented even in the current era – to his patients and their families. He had a profound understanding of the human frailties that emerge during the rigors of infertility treatment. One of us (J.F.S.) assisted Garcia in the care of an attorney's wife who underwent a two-stage tuboplasty. The husband demanded to be present during all medical examinations of his wife, he tape recorded all sessions, and refused to pay for Garcia's services, despite the fact that she conceived within three months after the hoods were removed from her reconstructed tubes. Garcia did not press the attorney for payment – he knew that the treatment course was exceptionally arduous with considerable post-surgery discomfort. When this same lawyer called eight months later asking if Garcia would serve as an expert witness in a plaintiff's medical malpractice case, Garcia thanked him for his call and politely said his schedule would not permit it, never mentioning the unpaid bill. He forgave, but he did not forget.Later in his career, Garcia and his colleagues undertook studies on the menopause that presaged the current interest in female sexual dysfunction. In retrospect, this was a logical extension of his long-standing interest in the social and psychological aspects first of contraception and family planning, and later of infertility. Garcia published on perimenopausal sexuality, and reported the first studies the relationship between sex steroid levels and sexual behavior. Garcia also recognized the need for multidisciplinary collaboration in the care of women, particularly in the post-reproductive years, and co-authored an early self-help manual for menopausal women . The WomGarcia gracefully retired from practice to devote time to his wife and family. This life transition, seamlessly executed, surprised many who were familiar with Garcia's intensity. But there should have been no surprise. Garcia demanded the highest technical standards from residents and fellows in the operating room, the same standards that he held for himself. He would not carry on if he could not perform to those standards, and he would not neglect his wife who needed increasing medical attention.Throughout his professional life, Celso-Ramon Garcia was a major force driving innovation in clinical care, and ultimately the evolution of the field of reproductive medicine. Let all who follow in the arena of reproductive endocrinology honor his contributions, appreciate the unique attributes that made him a great physician and educator, and gain insight from a truly remarkable career.The author(s) declare that they have no competing interests.JLS and LM contributed equally to this work and its revisions.


Bony defects arising from tumor resection or debridement after infection, non-union or trauma present a challenging problem to orthopedic surgeons, as well as patients due to compliance issues. Current treatment options are time intensive, require more than one operation and are associated with high rate of complications. For this reason, we developed a new surgical procedure to bridge a massive long bone defect.in situ periosteal sleeve is elevated circumferentially off of healthy diaphyseal bone adjacent to the bone defect. Then, the adjacent bone is osteotomized and the transport segment is moved along an intramedullary nail, out of the periosteal sleeve and into the original diaphyseal defect, where it is docked. Vascularity is maintained through retention of the soft tissue attachments to the in situ periosteal sleeve. In addition, periosteal osteogenesis can be augmented through utilization of cancellous bone graft or in situ cortical bone adherent to the periosteal sleeve.To bridge the gap, an The proposed procedure is novel in that it exploits the osteogenic potential of the periosteum by replacing the defect arising from resection of tissue out of a pathological area with a defect in a healthy area of tissue, through transport of the adjacent bone segment. Furthermore, the proposed procedure has several advantages over the current standard of care including ease of implementation, rapid patient mobilization, and no need for specialized implants  or costly orthobiologics.e.g. the Ilizarov procedure) as well as areas of the world where surgeons have little access to expensive, complex devices and orthobiologics.The proposed procedure offers a viable and potentially preferable alternative to the current standard treatment modalities, particularly in areas of the world where few surgeons are trained for procedures such as distraction osteogenesis ( Surgical treatment modalities involving auto/allografting and bone regeneration via distraction osteogenesis are complex, time intensive procedures of inherently high risk due to vagaries of organ donation, in the case of allografts, and the complexity of soft and hard tissue salvage during the process of distraction osteogenesis. In addition, orthobiologics are costly and their dosage regimes as well as efficacy are currently the subject of much research [Replacement of bone where there is none is one of the most challenging problems facing orthopedic surgeons today. In the case of tumor resection or trauma, massive bone defects must be filled with regenerate bone as quickly as possible in order to restore function. Current standards for bridging of massive bone defects in long bones generally follow a theme of research -3.Both bone grafting and bone transport procedures are complex for the surgeon as well as for the patient. Furthermore, they are susceptible to complications such as delayed union, extensive treatment time periods, infections, and insufficient mechanical function outcomes that can result in fractures. The high complication rates of these procedures exacerbate the previously mentioned difficulties associated with these treatment modalities, from the perspective of the surgeon as well as that of the patient. In short, the inherent risk of complications increases the need for patient compliance and clinical follow-up. Despite the effort associated with these procedures, their results are often less than satisfactory. Hence, the complexity and shortcomings of current state-of-the-art surgical procedures have provided impetus to develop a new treatment modality that provides a relatively straightforward, single step procedure with a high probability of success for the bridging of massive bone defects in long bones. The procedure is straightforward and can be implemented in operating rooms across the world without the need for high-tech equipment or expensive orthobiologics. The purpose of this manuscript is to describe the novel procedure.The proposed procedure is applicable for clinical scenarios including tumor resection as well as debridement after an infection or non-union. In the case of reconstruction after tumor resection Fig. , a transThe proposed procedure depends to a large degree on bone's inherent healing strategies. Bone is a remarkably resilient tissue capable of adaptation to the most extreme biological and mechanical environments; this capacity for self-regeneration without scarring is based on bone's endogenous healing strategies. First, bone remodels itself through osteoclastic resorption and osteoblastic matrix apposition; by constantly reweaving itself, the structure is dynamic and optimal for prevailing mechanical function. Furthermore, the natural healing cascade of bone after trauma recapitulates embryonic endochondral ossification. Hence, modeling, growth and remodeling confer a means to regenerate functional tissue at any time in the life cycle of a bone. The "raw materials" necessary to replace bone are located in the environment or produced by the cells that do the work of regeneration, i.e. osteoclasts and osteoblasts. In the case of regeneration of bone in defects, further potentially key constituents to the formation of a functional regenerate in situ include a patent blood supply, chemical gradients of morphogens and/or cytokines, a template onto which the cells can anchor themselves during the rebuilding process (e.g. graft or a scaffold), and biophysical stimuli such as fluid flow and/or cell level strains. The proposed procedure essentially replaces the defect site in a pathological zone with a defect site in a healthy bed of tissue and provides for progenitor cells through the surrounding, healthy periosteum as well as many of the other key constituents for successful tissue regeneration, as defined above.proof of feasibility for the proposed procedure. An 11-year old male presented with a low grade surface osteosarcoma of the tibia. After resection of the tumor, the fibula was resected for transfer and the surrounding periosteum was left behind to serve as an osteo-inductive and -conductive sleeve  as well as where surgeons have less access to expensive, complex devices and orthobiologics.The proposed procedure is novel in that it introduces for the first time the possibility to bridge a massive defect in a long bone using a single stage procedure. Furthermore, the proposed procedure has several advantages over the current standard of care including ease of implementation, lack of requirement for specialized implants  or costly orthobiologics, and rapid patient mobilization. This makes the proposed procedure a viable and potentially preferable alternative to the current standard treatment modalities, particularly areas of the world where few surgeons are trained for procedures such as distraction osteogenesis  declare that they have no competing interests.UK conceived of the technical innovation, organized its design and coordination, and drafted the manuscript. DSS was the senior surgeon in the clinical case showing feasibility. Both authors read and approved the final manuscript.


The Exploratorium in San Francisco offers museum visitors the opportunity to use and manipulate state-of-the-art microscopes to visualize an array of living specimens The Exploratorium, based in San Francisco, is a “hands on” science museum filled with interactive science and art exhibits, as well as a laboratory for the research and development of innovations in science education. In the summer of 2004, the Exploratorium launched the most ambitious microscope facility ever created for general public use. This initial phase of the project gives visitors the ability to image living specimens, as well as control the instruments themselves. Visitors can select among various specimens, move over them, change the magnification and focus, and, where appropriate, change the lighting to illuminate through the specimen, or use reflected light and fluorescence to dramatically change how it looks. They can image and explore tiny zebrafish embryos from the first stages of development to two-day-old fry with beating hearts and circulating blood cells, as well as a host of other organisms and cells from crawling amoebas to human blood cells.Below the surface, all living things share common features. The primary goals of this facility are to open a door on the wonder of the microscopic world to a diverse range of museum visitors and allow them to explore it, and to allow them to make connections to science and biomedical research. By empowering visitors with the instruments to explore this unfamiliar universe, the Exploratorium seeks to recreate some of the excitement and wonder that the earliest researchers found as they discovered another world all around them .The light microscope falls amongst the greatest inventions of human history. Images from it in the 17th century literally revolutionized our understanding of life, providing first-hand evidence of a previously unseen or unsuspected world of organisms and cells all around us. This knowledge profoundly shaped our view of life, and of our placement in the universe. Robert Hooke used a primitive early microscope to see the walls between cells in a piece of cork , and Anton van Leeuwenhoek's simple scope revealed a previously unknown world of microorganisms living inside his own mouth. Swimming sperm were observed in semen, changing our fundamental understanding of conception. Since that time our world has become populated by marvelously beautiful and intriguing images and movies created by scientists using precise lighting and optics. Most recently, computer-controlled image-capturing techniques and digital technologies capture events and processes too small, slow, or fast for our unaided eyes to see.Van Leeuwenhoek's first microscopes were probably about as powerful as a simple water-drop scope see ; he usedBringing a first-hand, high-quality microscope experience to a wide range of visitors and students has been a major challenge for many science museums and classrooms.In the expanded, frenetic classroom of the science museum exhibition floor, microscopes themselves are too delicate and precise for operation without assistance and supervision: the optics can be easily damaged, all but the most robust of specimens are easily destroyed, and the user interface with lighting, positioning, and focus compose a world unfamiliar to most novice users. Over the years, we had collected our share of failed and broken microscopes in various projects. For these reasons most microscopes in museums have been armored, stripped-down, single-magnification instruments.Problems related to the operation of the microscope hardware, however, represent only some of the challenges created by bringing uninitiated visitors to the microscopic world. The experience has to be repeatable. It has to be engaging. It has to be both simple and complex. It needs to work for individuals and groups. It needs to support investigation as well as provide essential information.An array of research scientists joined us as we began work to redefine and renew our existing presentation on biology, most notably Christian Sardet, a cell biologist with a passion for visualization imagery. During the summer and fall of 1999, we engaged in a series of conversations directed at defining and developing a publicly accessible microscope imaging station, and the more we explored, the more technically feasible the project became.At the same time, research-grade microscopes with high-quality optics underwent a revolution of their own. Many manufacturers planned to introduce fully automated, computer-controllable microscopes in their next models, and the prospects of having an off-the-shelf remotely controllable microscope seemed to solve a major hardware problem. It seemed as if software programs might be used to address many other user interface issues. In 2000, we applied for and received funding from the National Institutes of Health  and from the David and Lucile Packard Foundation to support the development of a microscope imaging facility.Seven months later we obtained the first microscope and its associated imaging equipment. But the software to control the microscopes proved dauntingly problematic. Programs that worked well in the laboratory proved difficult to adapt for our educational uses. Instead, we wrote our own programs to control stage movement (for specimen positioning), focus, specimen selection, magnification, and lighting. Each of these controls needed to be selectable and limited so that visitors might operate the microscope within a defined range.Caenorhabditis elegans attracted attention with its earthworm-like movements. Overall, these biomedically relevant specimens provided a treasure trove of potential educational activities for visitors.On a parallel track, with the generous help of numerous biomedical researchers and their laboratories across the United States, we explored specimens for their visitor attraction and interest. Not surprisingly, we found that familiar structures and organisms provided the best entry points. A zebrafish embryo with a beating heart, circulating blood, and twitching tail movements rated more popular than zebrafish or sea urchin embryos at earlier stages of development. The tiny transparent roundworm Given a range of wonderfully attractive specimens and potential activities, we then aimed to create an educational experience that combined the observable features in the specimens, supporting information, and further activities to be chosen as desired by the visitor. To achieve this, we adopted a multimedia approach . The incVisitors can pick and choose specimens of their choice, refine their selection, change magnification, and engage in suggested activities at their own pace with integrated appropriate information. Individuals and groups engage with the microscope imagery and companion information for relatively long periods of time, ranging from several minutes to upwards of 20 minutes, a long time for a museum exhibit. To expand the use of the microscope imagery beyond that of one or two visitors, we incorporated large plasma-screen presentations in to the Microscope Imaging Station facility.Escherichia coli) and a roundworm (C. elegans) and found that the genetically modified organisms emitted an eerie green glow under certain conditions. Other scientists built on this technique to create a powerful tool that makes hidden structures and processes easier to study. The coupling of vital staining with the green fluorescent protein gene allows scientists to observe events inside developing cells and detect the presence of diseased structures and environmental toxins with extreme sensitivity. This newly created sensitivity has sparked new insights and discoveries, re-revolutionizing the capabilities of the light microscope.In addition to using some of the latest devices in microscope technologies, the Imaging Station also provides a window on revolutionary research techniques. For example, in 1994, Columbia University's Martin Chalfie inserted a gene for a fluorescent jellyfish protein into a bacterium (http://www.exploratorium.edu/imaging_station).At the Imaging Station, visitors can take advantage of this technique to observe specific types of cells—such as the brain cells, sex cells, or muscle cells of roundworms. Visitors can also peer inside the developing embryo of a tropical zebrafish whose circulatory cells have been made visible by the protein made from the transplanted green fluorescent protein gene. In the immediate future, visitors will be able to closely examine living human blood cells and fruit flies that researchers use to study the genetics of a wide range of human disorders. Over the next year, we intend to add a major component on mouse stem cells and the process of differentiation. At the Imaging Station, visitors have access to seamless video footage of events that take place in a fraction of a second or occur slowly over weeks or months . Using tVideo S1Collected at the Microscope Imaging Station Many of the cells and organisms found in these movies are available via visitor-accessible microscopes on a daily basis. At the station, visitor-directed, microscope-based observations form the basis for informal education on basic and biomedically relevant research. Video microscopy and production by Kristina Yu.(5.4 KB MOV).Click here for additional data file.Materials. You'll need the clear plastic part of a CD case; if you can't find one, any thin sheet of rigid, clear plastic will work. Remove any paper or packaging so that you can see through the plastic. What to do. (1) Put the object you want to examine—a bug, a tiny leaf or plant, the small lettering on a coin or newspaper—on a flat surface. (2) Put one large drop of water on the center of the clear plastic. (An eyedropper makes this easy.) (3) Pick up the plastic and hold it horizontally so that the water drop is directly over the object. Move the plastic slowly back and forth to center the object, and up and down to focus. The water will form a curved shape that magnifies the object!