Addition of basal insulin to oral antidiabetic agents: a goal-directed approach to type 2 diabetes therapy

The objective of this article is to review current findings in the published literature on the efficacy of insulin therapy in combination with oral antidiabetic agents, with a focus on practical information that might help to provide an evidence-based template for selecting how best to combine oral agents and basal insulin in patients with type 2 diabetes. Here we review the current oral agents used to treat type 2 diabetes, their mechanisms of action, and how they can be combined with insulin therapy to help patients achieve guideline-recommended glycemic goals. While practical advice exists for initiating a therapeutic regimen comprised of basal insulin and oral agent(s), direction as to appropriate therapy for individual patients with differing physiologic requirements is needed. Oral antidiabetic therapy in combination with insulin provides an effective therapeutic option for patients who are unable to achieve or maintain glycemic goals on oral therapy alone.     

A teaching exercise for the identification of bacteria using an interactive computer program

An interactive computer program written in Fortran is described which provides an exercise in the identification of bacteria. The program, IDEN, provides a novel way of enhancing a student's approach to systematic bacteriology and numerical identification procedures. An unknown bacterium is assigned to a student who is provided with a list of possible species and a list of tests which may be carried out. The student's objective is the correct identification of the unknown in the most economical manner. An indication is given concerning the way in which this program can be used to enhance theoretical instruction and practical investigation.     

Nutrigenomics-based personalised nutritional advice: in search of a business model?

Nutritional advice has mainly focused on population-level recommendations. Recent developments in nutrition, communication, and marketing sciences have enabled potential deviations from this dominant business model in the direction of personalisation of nutrition advice. Such personalisation efforts can take on many forms, but these have in common that they can only be effective if they are supported by a viable business model. The present paper takes an inventory of approaches to personalised nutrition currently available in the market place as its starting point to arrive at an identification of their underlying business models. This analysis is presented as a unifying framework against which the potential of nutrigenomics-based personalised advice can be assessed. It has uncovered nine archetypical approaches to personalised nutrition advice in terms of their dominant underlying business models. Differentiating features among such business models are the type of information that is used as a basis for personalisation, the definition of the target group, the communication channels that are being adopted, and the partnerships that are built as a part of the business model. Future research should explore the consumer responses to the diversity of “archetypical” business models for personalised nutrition advice as a source of market information on which the delivery of nutrigenomics-based personalised nutrition advice may further build.     

A smoking cessation intervention program for family physicians.

Family physicians are able to approach many patients who smoke but are often hesitant to help them quit. Lack of knowledge about effective interventions is a major reason for this hesitancy. The important components that have been tested in physician-initiated smoking cessation interventions are advice to quit, information about the risks of smoking and techniques for quitting, nicotine gum, setting a date for quitting and offers of supportive follow-up visits. We describe a cessation program developed for family physicians that incorporates these factors into three types of visits over a 2-month period: the challenge visit, which occurs during a regular office visit and focuses on advice and setting a date to quit; the quit-date visit, which involves instructing patients on the proper use of nicotine gum, if applicable, and confirming their desire to quit; and four supportive follow-up visits, which provide continuing encouragement for 2 months and allow physicians to monitor withdrawal symptoms, relapses and other problems. Such a program can be effectively incorporated into a general practice.     

So you think you want to save the world

There is increasing interest among both medical and other professional communities in becoming involved in global health, development, and other charitable work. There has also been a proliferation of opportunities in the field. Nonetheless, it is still difficult to find practical information on the daily realities of development work or advice on the difficulties inherent to this type of work. This article is intended for individuals who are interested in becoming involved in global health and development work. Through a discussion that touches on development economics, the history, psychology, and current state of development aid, the common conflicts, as well as the rewards of development work, this article aims to prepare the interested individual for the experience of global health and development work. The article also provides practical suggestions and references for those searching for an opportunity in the field, with an emphasis on global health opportunities.     

Modelling of biofilms

A mixed-culture biofilm (MCB) model is available which describes the progression of biofilm thickness and the spatial distribution and development in time of dissolved and paniculate components in the biofilm. The MCB model is able to predict the physico-chemical conditions at the interface between the biofilm and the solid surface, on which the biofilm grows, as a function of the conditions in the bulk fluid, the microbial composition of the biofilm, and the transport and transformation processes which take place in the biofilm. The mass balance equations of the MCB model are generally valid and can be applied to almost any microbial system if its kinetics and stoichiometry can be provided. AQUASIM is a new computer program for the identification and simulation of aquatic systems. The program solves the equations of the MCB model. It has a window-type user interface and includes routines for simulation, sensitivity analysis, automatic parameter estimation and data fitting. The MCB model has been developed and is primarily used in the field of waste water treatment. However, under certain conditions and with some additional simplifications this model can also be used for the investigation of biofouling and biocorrosion problems. The possibilities and limitations of the application of the MCB model and of AQUASIM to this type of problem are briefly discussed.     

Doctor on a mountaineering expedition.

Doctors are welcome members on mountaineering expeditions to remote areas, but practical advice on how to prepare and what kit to take can be difficult to find. This article is a ragbag of useful advice on diverse topics. It explains the necessary preparation, provides tips for a healthy expedition, and summarises the common disorders encountered at high altitude. The comprehensive drug and equipment lists and first aid kit for climbers were used for the 1992 Everest in winter expedition. They are there to be sacrificed to personal preference and the experience and size of individual expeditions.     

Prediction of common folding structures of homologous RNAs.

We have developed an algorithm and a computer program for simultaneously folding homologous RNA sequences. Given an alignment of M homologous sequences of length N, the program performs phylogenetic comparative analysis and predicts a common secondary structure conserved in the sequences. When the structure is not uniquely determined, it infers multiple structures which appear most plausible. This method is superior to energy minimization methods in the sense that it is not sensitive to point mutation of a sequence. It is also superior to usual phylogenetic comparative methods in that it does not require manual scrutiny for covariation or secondary structures. The most plausible 1-5 structures are produced in O(MN2 + N3) time and O(N2) space, which are the same requirements as those of widely used dynamic programs based on energy minimization for folding a single sequence. This is the first algorithm probably practical both in terms of time and space for finding secondary structures of homologous RNA sequences. The algorithm has been implemented in C on a Sun SparcStation, and has been verified by testing on tRNAs, 5S rRNAs, 16S rRNAs, TAR RNAs of human immunodeficiency virus type 1 (HIV-1), and RRE RNAs of HIV-1. We have also applied the program to cis-acting packaging sequences of HIV-1, for which no generally accepted structures yet exist, and propose potentially stable structures. Simulation of the program with random sequences with the same base composition and the same degree of similarity as the above sequences shows that structures common to homologous sequences are very unlikely to occur by chance in random sequences.     

The digital language of amino acids

Summary. The subject of this paper is a digital approach to the investigation of the biochemical basis of genetic processes. The digital mechanism of nucleic acid and protein bio-syntheses, the evolution of biomacromolecules and, especially, the biochemical evolution of genetic language have been analyzed by the application of cybernetic methods, information theory and system theory, respectively. This paper reports the discovery of new methods for developing the new technologies in genetics. It is about the most advanced digital technology which is based on program, cybernetics and informational systems and laws. The results in the practical application of the new technology could be useful in bioinformatics, genetics, biochemistry, medicine and other natural sciences.     

F型肉毒梭菌培养液可滤性实验的初步研究

目的通过探索F型肉毒梭菌培养液可滤性实验,为现有生产工艺提供科学的优化方案。方法分别采用不同型号的过滤器,通过不同的过滤组合对F型肉毒梭菌培养液进行澄清过滤。结果采用K700P过滤器(过滤精度6.0～15.0μm)对F型肉毒梭菌培养液进行一级澄清过滤,采用50P过滤器(过滤精度0.5～0.85μm)对料液进行二级澄清过滤,对F型肉毒梭菌培养液具有良好的澄清效果。结论可滤性实验的探索对于F型肉毒梭菌培养液批生产量的扩大具有切实可行的指导意义。     

Proposed guidelines to evaluate scientific validity and evidence for genotype-based dietary advice

Nutrigenetic research examines the effects of inter-individual differences in genotype on responses to nutrients and other food components, in the context of health and of nutrient requirements. A practical application of nutrigenetics is the use of personal genetic information to guide recommendations for dietary choices that are more efficacious at the individual or genetic subgroup level relative to generic dietary advice. Nutrigenetics is unregulated, with no defined standards, beyond some commercially adopted codes of practice. Only a few official nutrition-related professional bodies have embraced the subject, and, consequently, there is a lack of educational resources or guidance for implementation of the outcomes of nutrigenetic research. To avoid misuse and to protect the public, personalised nutrigenetic advice and information should be based on clear evidence of validity grounded in a careful and defensible interpretation of outcomes from nutrigenetic research studies. Evidence requirements are clearly stated and assessed within the context of state-of-the-art ‘evidence-based nutrition’. We have developed and present here a draft framework that can be used to assess the strength of the evidence for scientific validity of nutrigenetic knowledge and whether ‘actionable’. In addition, we propose that this framework be used as the basis for developing transparent and scientifically sound advice to the public based on nutrigenetic tests. We feel that although this area is still in its infancy, minimal guidelines are required. Though these guidelines are based on semi-quantitative data, they should stimulate debate on their utility. This framework will be revised biennially, as knowledge on the subject increases.     

How Teens Become Engaged in Youth Development Programs: The Process of Motivational Change in a Civic Activism Organization

The question of how youth become engaged or motivated is vital to youth development programs, because engagement influences not only program retention but the likelihood of youth gaining the benefits that programs offer. This article reports on an in-depth study aimed at generating grounded theory about the change process through which youth who are initially disengaged become motivated by program activities. Youth in a civic activism program were interviewed over a 4-month period and qualitative analyses were used to derive a model of this change process. This process was found to proceed from the youth forming a personal connection to the program's mission to becoming intrinsically motivated by work on program activities. The analyses suggested that peers and the adult leader played important roles in supporting motivational change at each stage. The model developed from the investigation draws on existing theories of motivation.     

A conversational program for analytical modelling of action potentials in nerve and muscle.

A conversational program is described which is being used for exploratory modelling of digestive tract electrical activity. The structure of the mathematical model is based on the Hodgkin-Huxley equations for nerve axons and the Noble equations for Purkinje fibres of the heart. The parameters of the models are changed conversationally to investigate the effects of frequency, amplitude and waveshape. In this way it is intended to extend the models to include nervous control. The program is also being used to correlate the behaviour of H-H type equations with the simpler dynamics of Van der Pol's equation which is the basis of an oscillator-array model for the stomach and small intestines.     

Introduction to advantages and problems of shaken cultures

Shaking bioreactors are the most frequently used reaction vessels in biotechnology and have been so for many decades. In spite of their large practical importance, very little is known about the characteristic properties of shaken cultures from an engineering point of view. The few publications available contain to some extent contradicting statements and conflicting advice concerning the correct operating conditions of shaking bioreactors. Depending on the investigated microbial system, the engineering parameters may more or less significantly influence the experimental results in a quantitative as well as in a qualitative manner. Unfortunately, these kind of interactions are often overlooked or ignored by scientists. Precise knowledge about the controlling hydrodynamic phenomena in shaking bioreactors and quantitative information about the physical parameters influencing the cultures are needed to assure reproducible and meaningful operating conditions. In this introduction, the state of the art of culturing microorganisms in shaking bioreactors is reviewed and some issues of their practical application in screening and process development projects are addressed.     

Integrating guideline development and implementation: Analysis of guideline development manual instructions for generating implementation advice

ABSTRACT: BACKGROUND: Guidelines are important tools that inform health care delivery based on best available research evidence. Guideline use is in part based on quality of the guidelines, which varies. Others hypothesized this is due to limited instructions in guideline development manuals. The purpose of this study was to examine manual instructions for implementation advice. METHODS: We used a directed and summative content analysis approach based on an established framework of guideline implementability. Six manuals identified by another research group were examined to enumerate implementability domains and elements. RESULTS: Manuals were similar in content but lacked sufficient detail in particular domains. Most frequently this was Accomodation, which includes information that would help guideline users anticipate and/or overcome organizational and system level barriers. In more than one manual information was also lacking for Communicability, information that would educate patients or facilitate their involvement in shared decision making, and Applicability, or clinical parameters to help clinicians tailor recommendations for individual patients. DISCUSSION: Most manuals that direct guideline development lack complete information about incorporating implementation advice. These findings can be used by those who developed the manuals to consider expanding their content in these domains. It can also be used by guideline developers as they plan the content and implementation of their guidelines so that the two are integrated. New approaches for guideline development and implementation may need to be developed. Use of guidelines might be improved if they included implementation advice, but this must be evaluated through ongoing research.     

A framework for the implementation of new radiation therapy technologies and treatment techniques in low-income countries

We present a practical, generic, easy-to-use framework for the implementation of new radiation therapy technologies and treatment techniques in low-income countries. The framework is intended to standardize the implementation process, reduce the effort involved in generating an implementation strategy, and provide improved patient safety by reducing the likelihood that steps are missed during the implementation process. The 10 steps in the framework provide a practical approach to implementation. The steps are, 1) Site and resource assessment, 2) Evaluation of equipment and funding, 3) Establishing timelines, 4) Defining the treatment process, 5) Equipment commissioning, 6) Training and competency assessment, 7) Prospective risk analysis, 8) System testing, 9) External dosimetric audit and incident learning, and 10) Support and follow-up. For each step, practical advice for completing the step is provided, as well as links to helpful supplementary material. An associated checklist is provided that can be used to track progress through the steps in the framework. While the emphasis of this paper is on addressing the needs of low-income countries, the concepts also apply in high-income countries.     

Machine learning approach for the prediction of protein secondary structure

PROMIS (protein machine induction system), a program for machine learning, was used to generalize rules that characterize the relationship between primary and secondary structure in globular proteins. These rules can be used to predict an unknown secondary structure from a known primary structure. The symbolic induction method used by PROMIS was specifically designed to produce rules that are meaningful in terms of chemical properties of the residues. The rules found were compared with existing knowledge of protein structure: some features of the rules were already recognized (e.g. amphipathic nature of alpha-helices). Other features are not understood, and are under investigation. The rules produced a prediction accuracy for three states (alpha-helix, beta-strand and coil) of 60% for all proteins, 73% for proteins of known alpha domain type, 62% for proteins of known beta domain type and 59% for proteins of known alpha/beta domain type. We conclude that machine learning is a useful tool in the examination of the large databases generated in molecular biology.     

The role of physicians as medical review officers in workplace drug testing programs. In pursuit of the last nanogram.

In discussing the role of physicians in workplace drug testing programs, I focus on the recent Department of Transportation regulations that require drug testing in such regulated industries as interstate trucking, air transportation, mass transit, and the railroads. These regulations require that applicable drug testing programs employ physicians as medical review officers to evaluate positive tests that have been screened and confirmed by different techniques to determine if there is a legal medical explanation for the result. The drug testing program tests for the presence of amphetamine, cocaine, tetrahydrocannabinol, opiates, and phencyclidine. If an employee testing positive has an acceptable medical explanation, the result is to be reported as negative. Little practical advice exists for medical review officers, and they must be aware of key elements of the regulations and potential trouble spots.     

Emergency Health Planning

This paper outlines the development of emergency health planning as a function of government. Ten provinces have the basic responsibility for the organization, preparation and operation of medical, nursing, hospital and public health services in an emergency. The Department of National Health and Welfare is responsible for the provision of advice and assistance to the provincial and municipal governments in such matters. Eight provinces have now hired full-time planning staffs to co-ordinate the health planning of the Provincial Departments of Health and Provincial Emergency Measures Organization.Four major programs have been established. The first program provides for the continuity of leadership and guidance by health authorities at the federal, provincial and municipal level. Essential records have been developed and emergency legislation prepared. This program, however, will be of little use unless health services are organized at the municipal level. In this organizational program, advice and assistance have been provided to existing hospitals and departments of health in the conduct of disaster planning. The efforts of these agencies are co-ordinated by municipal health authorities into a community disaster plan. The third program deals with information and education of the general public and the health workers. This program is designed to make the family unit self-sufficient for up to seven days and the health worker prepared to undertake his emergency role. The first three programs are directed to the organization and training of manpower; the fourth program provides the necessary supplies. From the national medical stockpile of $18,000,000, some $12,000,000 has been received, packaged for long-term storage and distributed to regional depots across the country. To ensure their ready availability in time of emergency an agreement has been reached with seven provinces for the release of hospital disaster kits.