Pondering the future.

Despite growing tensions as the Canadian health care system evolves, the system will survive over the next decade and strengthen its societal objectives, sometimes dragging physicians along. With the shift of the intellectual centre away from the universities, research and researchers will find funding security but career insecurity in the private sector. The independent investigator will become rare as "big science" becomes the norm, and basic science departments will have a decade of confusion as they struggle for a new place in the renewed medical schools. The move toward problem-based, community-oriented medical education will be completed, clinical faculty will become salaried and the smaller numbers of graduates will be more controlled in their practices. Medicine as a profession will adopt a renewed philosophical framework and will broaden in its scope to the benefit of Canadians.     

The information system design for the Flora North America Program

The Flora North America Program will create a computer data bank of taxonomic information about the vascular plants of North America north of Mexico. The system, which will serve a broad range of users, will provide for the acquisition, editing, and storage of data and the preparation of a variety of products. It will grow and evolve over a long period of time, continually incorporating changes to data and new categories of information as they become available. The system will utilize an existing computer program package, the IBM Generalized Information System (GIS), for creating, maintaining, querying, and generating reports from its files of data. In addition to a file of taxonomic, ecological, and geographic data about each taxon, the system will build and maintain a series of authority or dictionary files to control system content. The first major system product will be a published flora, generated by computer. Many other catalogs and indexes will be prepared and specific questions may be asked of the data bank to meet individual user needs for information.     

Reducing salt intake for prevention of cardiovascular diseases in high-risk patients by advanced health education intervention (RESIP-CVD study), Northern Thailand: study protocol for a cluster randomized trial

ABSTRACT: BACKGROUND: Decreasing salt consumption can prevent cardiovascular diseases (CVD). Practically, it is difficult to promote people's awareness of daily salt intake and to change their eating habits in terms of reducing salt intake for better cardiovascular health. Health education programs visualizing daily dietary salt content and intake may promote lifestyle changes in patients at high risk of cardiovascular disease. METHODS: This is a cluster randomized trial. A total of 800 high-CVD-risk patients attending diabetes and hypertension clinics at health centers in Muang District, Chiang Rai province, Thailand, will be studied with informed consent. A health center recruiting 100 participants is a cluster, the unit of randomization. Eight clusters will be randomized into intervention and control arms and followed up for 1 year. Within the intervention clusters the following will be undertaken: (1) salt content in the daily diet will be measured and shown to study participants; (2) 24-hour salt intake will be estimated in overnight-collected urine and the results shown to the participants; (3) a dietician will assist small group health education classes in cooking meals with less salt. The primary outcome is blood pressure change at the 1-year follow-up. Secondary outcomes at the 1-year follow-up are estimated 24-hoursalt intake, incidence of CVD events and CVD death. The intention-to-treat analysis will be followed.Blood pressure and estimated 24-hour salt intake will be compared between intervention and control groups at the cluster and individual level at the 1-year follow-up. Clinical CVD events and deaths will be analyzed by time-event analysis. Retinal blood vessel calibers of CVD-risk patients will be assessed cross-sectionally. Behavioral change to reduce salt intake and the influencing factors will be determined by structured equation model (SEM). Multilevel regression analyses will be applied. Finally, the cost effectiveness of the intervention will be analyzed. DISCUSSION: This study is unique as it will recruit the individuals most vulnerable to CVD morbidity and mortality by applying the general Framingham CVD risk scoring system. Dietary salt reduction will be applied as a prioritized, community level intervention for the prevention of CVD in a developing country.Trial registrationISRCTN39416277.     

For the law, neuroscience changes nothing and everything

The rapidly growing field of cognitive neuroscience holds the promise of explaining the operations of the mind in terms of the physical operations of the brain. Some suggest that our emerging understanding of the physical causes of human (mis)behaviour will have a transformative effect on the law. Others argue that new neuroscience will provide only new details and that existing legal doctrine can accommodate whatever new information neuroscience will provide. We argue that neuroscience will probably have a transformative effect on the law, despite the fact that existing legal doctrine can, in principle, accommodate whatever neuroscience will tell us. New neuroscience will change the law, not by undermining its current assumptions, but by transforming people's moral intuitions about free will and responsibility. This change in moral outlook will result not from the discovery of crucial new facts or clever new arguments, but from a new appreciation of old arguments, bolstered by vivid new illustrations provided by cognitive neuroscience. We foresee, and recommend, a shift away from punishment aimed at retribution in favour of a more progressive, consequentialist approach to the criminal law.     

G-Band Position Effects on Meiotic Synapsis and Crossing over

An examination of synaptic data from a series of X-autosome translocations and crossover data from an extensive series of autosome-autosome translocations and autosomal inversions in mice has lead to the development of a hypothesis which predicts synaptic and recombinational behavior of chromosomal aberrations during meiosis. This hypothesis predicts that in heterozygotes for chromosomal rearrangements that meiotically align G-light chromatin with G-light chromatin lack of homology will be recognized. If homologous synapsis cannot proceed, synaptonemal complex formation will cease and there will be no physical suppression of crossing over in such rearrangements. However, if a chromosomal rearrangement aligns G-light chromatin with G-dark chromatin at the time of synapsis, lack of homology will not be recognized and synaptonemal complex formation will proceed nonhomologously through the G-dark chromatin. Crossing over will be physically suppressed in this region and this suppression of crossing over will be confined to the chromosome in which the G-light chromatin is nonhomologously synapsed with G-dark chromatin. When G-light chromatin is once again aligned with G-light chromatin, lack of homology again will be recognized and either homologous synapsis will be reinitiated (as in an inversion loop), or will cease altogether (as in some translocations). Unlike the previously described "synaptic adjustment", this nonhomologous synapsis of G-light with G-dark chromatin appears to compete with homologous synapsis during early pachynema.     

Experience of the use of probiotics for Salmonellae control in poultry

The Editors of Letters in Applied Microbiology will, at their discretion, publish invited and submitted 'Opinions' on subjects in the general area of Applied Microbiology. They will not be subjected to the normal refereeing procedures and reprints will not be provided. The 'Opinions' will not necessarily represent the views of the Society of Applied Bacteriology or of the Editors. The Editors may invite or readers may submit 'Responses' to published 'Opinions' , provided that they are not merely polemics, and these will also be published at the discretion of the Editors. 'Responses' will be treated precisely like 'Opinions' . They should clearly indicate, in their first sentence, the 'Opinion' to which they are a response.     

Revolutionizing medicine in the 21(st) century through systems approaches

Personalized medicine is a term for a revolution in medicine that envisions the individual patient as the central focus of healthcare in the future. The term "personalized medicine", however, fails to reflect the enormous dimensionality of this new medicine that will be predictive, preventive, personalized, and participatory-a vision of medicine we have termed P4 medicine. This reflects a paradigm change in how medicine will be practiced that is revolutionary rather than evolutionary. P4 medicine arises from the confluence of a systems approach to medicine and from the digitalization of medicine that creates the large data sets necessary to deal with the complexities of disease. We predict that systems approaches will empower the transition from conventional reactive medical practice to a more proactive P4 medicine focused on wellness, and will reverse the escalating costs of drug development an will have enormous social and economic benefits. Our vision for P4 medicine in 10 years is that each patient will be associated with a virtual data cloud of billions of data points and that we will have the information technology for healthcare to reduce this enormous data dimensionality to simple hypotheses about health and/or disease for each individual. These data will be multi-scale across all levels of biological organization and extremely heterogeneous in type - this enormous amount of data represents a striking signal-to-noise (S/N) challenge. The key to dealing with this S/N challenge is to take a "holistic systems approach" to disease as we will discuss in this article.     

The Physician of the Future

The good physician of the future will need to master not only the basic and traditional medical skills but many new concepts and techniques as well. He will need to be, as always, a compassionate and intelligent man. If he is to retain his status as a healer in the eyes of his patients, he will have to be fully aware of what is happening in the social and technological environment, or he will run the risk of being relegated to the position of a high-grade technician.He will have new physical tools and new thinking tools to help him. To understand and use these, and also to understand the technical world of the future, he will need a sound knowledge of the physical sciences and some fluency in the language of modern mathematics.     

Monitoring of neuromuscular function in the clinical setting.

This paper will review the basics of neurostimulation in the perioperative period. Following a brief overview of neuromuscular physiology, the mechanism of action of depolarizing and non-depolarizing relaxants will be discussed. The principles of neurostimulation will then be applied clinically when different patterns of stimulation (single twitch, train-of-four, post-tetanic twitch count, double burst) are described. Clinical assessment of neuromuscular function will then be compared with both subjective and objective means of assessment of adequacy of intraoperative relaxation and postoperative reversal. The principles reviewed in this paper will then be applied in the clinical setting, and risks and benefits associated with perioperative use of muscle relaxants will be discussed.     

Personalized medicine: revolutionizing drug discovery and patient care.

Advances in human genome research are opening the door to a new paradigm for practising medicine that promises to transform healthcare. Personalized medicine, the use of marker-assisted diagnosis and targeted therapies derived from an individual's molecular profile, will impact the way drugs are developed and medicine is practiced. Knowledge of the molecular basis of disease will lead to novel target identification, toxicogenomic markers to screen compounds and improved selection of clinical trial patients, which will fundamentally change the pharmaceutical industry. The traditional linear process of drug discovery and development will be replaced by an integrated and heuristic approach. In addition, patient care will be revolutionized through the use of novel molecular predisposition, screening, diagnostic, prognostic, pharmacogenomic and monitoring markers. Although numerous challenges will need to be met to make personalized medicine a reality, with time, this approach will replace the traditional trial-and-error practice of medicine.     

Use of antibodies to the lipopolysaccharide core region in the treatment of gram-negative sepsis and shock

In this paper we review evidence in favor of a protective role for antibodies directed at the lipopolysaccharide (LPS) core region of Gram-negative bacilli. It will be shown that, given the right animal model, polyclonal antisera raised against O-antigen lacking, rough mutant strains, can be shown to protect animals against lethal sepsis due to a variety a bacterial species. Evidence for a protective role obtained from clinical studies will also be discussed. It will be stressed how difficult it is to prove that the antibodies directed against the LPS-core, and not other proteins present in the polyclonal anti-rough strain antisera, were responsible for the observed protective effects. The solution to some of these problems is the production of monoclonal antibodies (Mabs). We will discuss the findings that purified anti-core Mabs may give false-positive outcomes of protection studies, due to the induction of tolerance by small amounts of contaminating endotoxin, present in the antibody preparation. The need to administer the Mab therapeutically instead of prophylactically to the test animals, will be stressed. It will be shown how we succeeded in determining the epitope-specificities of several anti-core antibodies. It will be shown also that use of Elisa alone for characterization of anti-core Mabs may lead to false conclusions concerning epitope specificities. We will prove that synthetic KDO-(=ketodeoxycctanate) and lipid A-containing antigens are indispensable tools for thorough characterization of Mabs. Using this methodology we were able to discriminate between specific antigen-antibody interactions, and the ability of some Mabs to bind “non-specifically” to hydrophobic surfaces. The relationship between epitope specificity and protective effects of anti-core Mabs will be described. Finally, we will demonstrate that a KDO-specific Mabs is capable of protecting mice against lethal sepsis; in other words, it will be shown conclusively that Mabs to defined epitopes in LPS core region are cross-protective.     

Protein translocation across and integration into membranes

This review concentrates mainly on the translocation of proteins across the endoplasmic reticulum membrane and cytoplasmic membrane in bacteria. It will start with a short historical review and will pinpoint the crucial questions in the field. Special emphasis will be given to the present knowledge on the molecular details of the first steps, i.e., on the function of the signal recognition particle and its receptor. The knowledge on the signal peptidase and the ribosome receptor(s) will also be summarized. The various models for the translocation of proteins across and the integration of proteins into membranes will be critically discussed. In particular, the function of signal, stop-transfer, and insertion sequences will be dealt with and molecular differences discussed. The cotranslational mode of membrane transfer will be compared with the post-translational transport found for mitochondria and chloroplasts. This review will conclude with open questions and an outlook.     

碳税和硫税治理下中国未来的碳排放趋势

基于气候治理背景,计算模拟了征收碳税和硫税后的经济影响和减排效果。结果发现,基准情景下,中国经济将保持不断增长的趋势,到2100年,GDP总量将达到69.95万亿美元,碳排放呈现环境库兹涅茨曲线特征,高峰值出现在2034年,碳排放高峰为3832Mt C。在收税治理策略下,无论单独征收硫税还是单独征收碳税,我国的GDP均会受到影响,碳排放都会减少。同时征收碳税和硫税,碳排放显著降低,碳排放高峰出现在2031年,峰值估计为3111Mt C,较基准情景下碳排放高峰降低了721Mt C,高峰值出现的年份也提前了3a,完全满足2030年左右实现碳高峰的承诺。     

A mathematical model of cancer treatment by immunotherapy

In this paper, a detailed mathematical study of cancer immunotherapy will be presented. General principles of cancer immunotherapy and the model equations and hypotheses will be discussed. Mathematical analyses of the model equations with regard to dissipativity, boundedness of solutions, invariance of non-negativity, nature of equilibria, persistence, extinction and global stability will be analyzed. It will also be shown that bifurcations can occur, and criteria for total cure will also be derived.     

Will genetics really revolutionize the drug discovery process?

Genetics has played only a modest role in drug discovery, but new technologies will radically change this. Whole genome sequencing will identify new drug discovery targets, and emerging methods for the determination of gene function will increase the ability to select robust targets. Detection of single nucleotide polymorphisms and common polymorphisms will enhance the investigation of polygenic diseases and the use of genetics in drug development. Oligonucleotide arraying technologies will allow analysis of gene expression patterns in novel ways.     

Trophic matches and mismatches: can polar bears reduce the abundance of nesting snow geese in western Hudson Bay?

Climate change driven advances in the date of sea ice breakup will increasingly lead to a loss of spring polar bear foraging opportunities on ringed seal pups creating a phenological trophic ‘mismatch’. However, the same shift will lead to a new ‘match’ between polar bears and ground nesting birds. This new match will be especially prevalent along the Cape Churchill Peninsula of western Hudson Bay where both polar bears and nesting snow geese are abundant. Easily foraged goose eggs will provide at least some of the earlier arriving polar bears with compensation for the energy deficit accrued through lost seal hunting opportunities. We examine the potential impact of changes in the extent and pattern of polar bear egg predation on snow goose abundance using projection models that account not only for increases in the temporal overlap of the two species but also for autocorrelation and stochasticity in the processes underlying polar bear onshore arrival and snow goose incubation. Egg predation will reduce reproductive output of the nesting lesser snow geese and, under all but trivial rates, will lead to a reduction in the size of their nesting population on the Cape Churchill Peninsula. Stochasticity associated with the asymmetrical advances in polar bear onshore arrival and the snow goose incubation period will lead to periodic mismatches in their overlap. These, in turn, will allow snow goose abundance to increase periodically. Climate driven changes in trophic matches and mismatches may reduce snow goose numbers but will not eliminate this over‐abundant species that poses a threat to Arctic landscapes.     

Studies of emergy flow in a compound agro-ecosystem in the Taihu Lake area, Jiangsu Province, China

Emergy flow in a compound agro-ecosystem in the Taihu Lake area of Jiangsu province, China, is studied with a set of numeric models. Model parameters are based on 11 years of records. Results show that total emergy production of two producing subsystems will decline although emergy input into the two subsystems and emergy production of the fish subsystem are growing. Emergy efficiency of the producing subsystems, both gross and net, will decrease, while emergy efficiency of the compound ecosystem will grow up first and then gradually decline. Net emergy production of the producing subsystems will gradually decline, but that of the compound ecosystem will firstly increase and then decrease. Net emergy allocation per human capita in the compound ecosystem will slowly inecrease, but it will decrease if the animal subsystem is removed from the ecosystem; this shows that the animal subsystem is a necessary part of the compound ecosystem. Relative to buffering capacity, emergy efficiency of the compound ecosystem, and recent living quality of local people, sustainable development of the ecosystem is discussed.     

Antifertility drugs. Introductory remarks

The introductory remarks on the subject of antifertility drugs made by V.A. Drill at the 1970 Pharmacology Society Symposium are presented. The development of oral contraceptives is described. It is noted that oral contraceptives were develoepd coincident with the increasing public awareness of the "population explosion". At a certain point in the population growth, the public interest will become manifest, and each nation will establish a population policy. Among the papers presented at the symposium will be 2 by Dr. Saunders and Dr. Goldzieher, which review certain of the basic and clinical studies performed with oral contraceptives. Dr. Rudel will discuss the low-dose progestins. Drs. Duncan and Pharris will describe new approaches which are currently being explored. Ultimately, in order to control world population effectively, an immunological treatment may be required whereby 1 injection will control fertility for 2.5, or even 10 years. Dr. Garcia will summarize papers on this area of study.