Disease

This paper examines what it is for a condition to be a disease. It falls into two sections. In the first I examine the best existing account of disease (as proposed by Christopher Boorse) and argue that it must be rejected. In the second I outline a more acceptable account of disease. According to this account, by disease we mean a condition that it is a bad thing to have, that is such that we consider the afflicted person to have been unlucky, and that can potentially be medically treated. All three criteria must be fulfilled for a condition to be a disease. The criterion that for a condition to be a disease it must be a bad thing is required to distinguish the biologically different from the diseased. The claim that the sufferer must be unlucky is needed to distinguish diseases from conditions that are unpleasant but normal, for example teething. Finally, the claim that for a condition to be a disease it must be potentially medically treatable is needed to distinguish diseases from other types of misfortune, for example economic problems and legal problems.     

Ventilation or dignified death for patients with high tetraplegia.

The case histories of the 37 patients of the Mersey Regional Spinal Injuries Centre who were artificially ventilated between 1968 and 1984 were reviewed. The patients and caring relatives were interviewed separately to determine their views. Of 21 patients who were still alive, 18 said that they would wish to be temporarily ventilated again if the need arose, two were undecided, and one said that she would wish to be allowed to die. Sixteen caring relatives said that they were glad that the decision to ventilate had been taken. Those who were not glad were all young mothers. The outcome from any combination of factors that existed before injury could not be predicted except that most patients over age 59 fared badly. Patients with spinal cord damage should be artificially ventilated if required, provided that this can be carried out well and that total emotional, educational, and physical support can be provided and maintained. Whether or not scarce resources should be deployed in this manner requires discussion.     

Alternative hypotheses for the effects of drugs in small-scale clinical studies

New drugs that will be investigated in the future are expected to deal with chronic diseases, where the number of patients available for controlled clinical trials will be small and where the long-term sequelae that it is hoped will be ameliorated take a long time to occur. Thus, it would be useful to construct powerful tests of hypotheses that can be used to compare subtle intermediate measures of change in condition. This paper examines the probabilistic characteristics of these measures and the changes in them that might be expected from drug therapy.     

Workshop on algal polysaccharides

Summary This workshop was an impromptu event, but the fact that a number of interesting problems were identified by the participants from the floor may indicate that it is worth repeating. If it is to be repeated, however, it is important that notice be given, and that the scope of the workshop be defined in advance, so that participants can be better informed and bring supporting data. The best approach would be to identify a convenor and define the scope of the workshop prior to the first circular for the next Seaweed Symposium; invitations could then be issued by the convenor for specific topics and data, and a very brief program could be issued with the third circular. Such a procedure may very well allow the identification of new areas for research.     

THE INTERNAL ORGANIZATION OF MITOCHONDRIA

Sections of mitochondria in Paramecium and Euplotes present a consistent pattern. The mitochondrion in these cells can be conceived of as a twisted mass of closely compacted tubules. Two general kinds of substances can be recognized: the electron-dense that borders the lumen of the tubule, and the less dense that forms the continuum. In sections of mitochondria in rat kidney and snail oviduct, tubular internal organization can be recognized. In the same organs, mitochondria with lamellar internal structure can be demonstrated. The thesis is developed that the mitochondrion is a structure capable of differentiation and change, and that developmental continuity among the different kinds may exist. Mitochondria that appear to be different may be quite similar basically; mitochondria that appear to be similar in structure may be different in other ways. The tubule is proposed as the most basic of the presently recognized mitochondrial structures.     

Simulation as experiment: a philosophical reassessment for biological modeling

Some scientific modelers suggest that complex simulation models that mimic biological processes should have a limited place in ecological and evolutionary studies. However, complex simulation models can have a role that is different from that of simpler models that are designed to be fit to data. Simulation can be viewed as another kind of experimental system and should be analyzed as such. Here, I argue that current discussions in the philosophy of science and in the physical sciences fields about the use of simulation as an experimental system have important implications for biology, especially complex sciences such as evolution and ecology. Simulation models can be used to mimic complex systems, but unlike nature, can be manipulated in ways that would be impossible, too costly or unethical to do in natural systems. Simulation can add to theory development and testing, can offer hypotheses about the way the world works and can give guidance as to which data are most important to gather experimentally.     

Audit of admission to medical school: III--applicants' perceptions and proposals for change.

Applicants to St Mary''s Hospital Medical School were asked to comment freely on the process of selection. They were particularly concerned about the role of interviews, excessive emphasis on academic achievement, the problem of rank-ordering choices on the UCCA form, and possible biases in selection. These concerns and the results of our survey suggest that candidates should not be asked to rank their choices in order of preference, that UCCA applications for medicine should be subject to an early closing date, that as many applicants as possible should be interviewed, that applicants should be encouraged to apply after taking A levels, that educational opportunity should be taken into account in assessing A level grades, and that mature students should be encouraged, not least by providing mandatory awards for a second degree in medicine.     

Probabilistic computation by neuromine networks

In this paper, we address the question, can biologically feasible neural nets compute more than can be computed by deterministic polynomial time algorithms? Since we want to maintain a claim of plausibility and reasonableness we restrict ourselves to algorithmically easy to construct nets and we rule out infinite precision in parameters and in any analog parts of the computation. Our approach is to consider the recent advances in randomized algorithms and see if such randomized computations can be described by neural nets. We start with a pair of neurons and show that by connecting them with reciprocal inhibition and some tonic input, then the steady-state will be one neuron ON and one neuron OFF, but which neuron will be ON and which neuron will be OFF will be chosen at random (perhaps, it would be better to say that microscopic noise in the analog computation will be turned into a megascale random bit). We then show that we can build a small network that uses this random bit process to generate repeatedly random bits. This random bit generator can then be connected with a neural net representing the deterministic part of randomized algorithm. We, therefore, demonstrate that these neural nets can carry out probabilistic computation and thus be less limited than classical neural nets.     

The determination of the best interests in relation to childhood immunisation

There are many different ethical arguments that might be advanced for and against childhood vaccinations. In this paper I explore one particular argument that focuses on the idea that such vaccinations are justifiable because they are held to be in the best interests of a particular child. Two issues arise from this idea. The first issue is how best interests are to be determined in this case. The second issue is what follows from this to justify potential interventions within the family in relation to such vaccinations. I argue that best interests must be characterised objectively in such situations and that this means that, in at least some cases, parental decision-making about vaccinating their children may be overridden.     

Drosophila Epsin mediates a select endocytic pathway that DSL ligands must enter to activate Notch

Recent findings suggest that Delta/Serrate/Lag2 (DSL) signals activate Notch by an unprecedented mechanism that requires the ligands to be endocytosed in signal-sending cells to activate the receptor in signal-receiving cells. Here, we show that cells devoid of Epsin, a conserved adaptor protein for Clathrin-mediated endocytosis, behave normally except that they cannot send DSL signals. Surprisingly, we find that Epsin is not required for bulk endocytosis of DSL proteins. Instead, Epsin appears to be essential for targeting DSL proteins to a special endocytic pathway that they must enter to acquire signaling activity. We present evidence that DSL proteins must be mono-ubiquitinated to be targeted by Epsin to this pathway. Furthermore, we show that the requirements for both Epsin and mono-ubiquitination can be bypassed by introducing the internalization signal that mediates endocytosis and recycling of the Low Density Lipoprotein (LDL) receptor. We propose that Epsin is essential for DSL signaling because it targets mono-ubiquitinated DSL proteins to an endocytic recycling compartment that they must enter to be converted into active ligands. Alternatively Epsin may be required to target mono-ubiquitinated DSL proteins to a particular subclass of coated pits that have special properties essential for Notch activation.     

Adaptive noise

In biology, noise implies error and disorder and is therefore something which organisms may seek to minimize and mitigate against. We argue that such noise can be adaptive. Recent studies have shown that gene expression can be noisy, noise can be genetically controlled, genes and gene networks vary in how noisy they are and noise generates phenotypic differences among genetically identical cells. Such phenotypic differences can have fitness benefits, suggesting that evolution can shape noise and that noise may be adaptive. For example, gene networks can generate bistable states resulting in phenotypic diversity and switching among individual cells of a genotype, which may be a bet hedging strategy. Here, we review the sources of noise in gene expression, the extent to which noise in biological systems may be adaptive and suggest that applying evolutionary rigour to the study of noise is necessary to fully understand organismal phenotypes.     

On the limitations of life cycle assessment and environmental systems analysis tools in general

The potential and limitations of life cycle assessment and environmental systems analysis tools in general are evaluated. More specifically this is done by exploring the limits of what can be shown by LCA and other tools. This is done from several perspectives. First, experiences from current LCAs and methodology discussions are used including a discussion on the type of impacts typically included, quality of inventory data, methodological choices in relation to time aspects, allocation, characterisation and weighting methods and uncertainties in describing the real world. Second, conclusions from the theory of science are practised. It is concluded that it can in general not be shown that one product is environmentally preferable to another one, even if this happens to be the case. This conclusion has important policy implications. If policy changes require that it must be shown that one product is more (or less) environmentally preferable before any action can be taken, then it is likely that no action is ever going to take place. If we want changes to be made, decisions must be taken on a less rigid basis. It is expected that in this decision making process, LCA can be a useful input. Since it is the only tool that can be used for product comparisons over the whole life cycle, it can not be replaced by any other tool and should be used. Increased harmonisation of LCA methodology may increase the acceptability of chosen methods and increase the usefulness of the tool.     

水团花药材鉴定方法的研究

目的:建立中药水团花的药材鉴定方法.方法:通过对主产地六批药材的研究,从薄层定性检查、水份测定、浸出物检查和灰分测定4个方面,建立了水团花的药材鉴定方法.结果:运用TLC法,定性鉴别了水团花中的2种化学成分;药材的含水量不得过9.6%;药材的水溶性浸出物不得少于31%;药材的醇溶性浸出物不得少于35%;药材的总灰分不得过5.0%.结论:该方法可用于控制水团花的质量.     

What is this stuff called fitness?

This paper considers a variety of attempts to define fitness in such a way as to defend the theory of evolution by natural selection from the criticism that it is a circular argument. Each of the definitions is shown to be inconsistent with the others. The paper argues that the environment in which an animal evolves can be defined only with respect to the properties of the phenotype of the animal and that it is therefore not illuminating to try to explain the phenotypic properties of the animal in terms of adaptation to an environment that is defined by those very properties. Furthermore, since there is no way that the environment can be defined independently of the presence of the animal there is no way that the quality of an animal can be assessed; and there can be no objective criteria by whichany form of selection can be carried out, therefore there can be no criteria by whichnatural selection can be carried out. It is proposed that fitness is nothing more than the production of offspring, that this is a phenotypic property like all the others, and if it is heritable then the offspring of the parents that produce the most offspring will themselves produce the most offspring, and that in principle it is impossible to account for this in terms of the other phenotypic properties of the fittest animals except by circular argument. Differential rates of reproduction are the causes of evolution and the phenotypic causes are strictly inexplicable.     

The evolutionary stability of automimicry

Internal defences such as toxins cannot be detected from a distance by a predator, and are likely to be costly to produce and maintain. Populations of well-defended prey may therefore be vulnerable to invasion from rare 'cheater' mutants that do not produce the toxin themselves but obtain some protection from their resemblance to their better defended conspecifics (automimicry). Although it is well established that well-defended and weakly defended morphs may coexist stably in protected dimorphisms, recent theoretical work suggests that such dimorphisms would not be resistant to invasion by novel mutants with defence levels intermediate to those present. Given that most defences (including toxins) are likely to be continuous traits, this implies that automimicry may tend to be a transitory phenomenon, and thus less likely to explain variation in defence levels in nature. In contrast to this, we show that automimicry can also be evolutionarily stable for continuous traits, and that it may evolve under a wide range of conditions. A recently developed geometric method allows us to determine directly from a trade-off curve whether an evolutionarily stable defence dimorphism is at all possible, and to make some qualitative inferences about the ecological conditions that may favour it.     

Mutants of Arabidopsis lacking starch branching enzyme II substitute plastidial starch synthesis by cytoplasmic maltose accumulation

Three genes, BE1, BE2, and BE3, which potentially encode isoforms of starch branching enzymes, have been found in the genome of Arabidopsis thaliana. Although no impact on starch structure was observed in null be1 mutants, modifications in amylopectin structure analogous to those of other branching enzyme II mutants were detected in be2 and be3. No impact on starch content was found in any of the single mutant lines. Moreover, three double mutant combinations were produced (be1 be2, be1 be3, and be2 be3), and the impact of the mutations on starch content and structure was analyzed. Our results suggest that BE1 has no apparent function for the synthesis of starch in the leaves, as both be1 be2 and be1 be3 double mutants display the same phenotype as be2 and be3 separately. However, starch synthesis was abolished in be2 be3, while high levels of alpha-maltose were assayed in the cytosol. This result indicates that the functions of both BE2 and BE3, which belong to class II starch branching enzymes, are largely redundant in Arabidopsis. Moreover, we demonstrate that maltose accumulation depends on the presence of an active ADP-glucose pyrophosphorylase and that the cytosolic transglucosidase DISPROPORTIONATING ENZYME2, required for maltose metabolization, is specific for beta-maltose.     

CHANGING EPIDEMIOLOGIC ASPECTS OF TYPHOID FEVER IN CALIFORNIA

Typhoid fever in California is no longer a major public health problem. The previously high incidence of water- and milk-borne infections has been greatly reduced. Human carriers now are the source of most infections.Chloramphenicol has proven to be a valuable aid in the therapy of the acutely ill patient, but it has not as yet solved the therapeutic or public health problems of typhoid fever. It continues to be vital for the protection of the public that every suspected case of typhoid fever be definitely established by appropriate public health laboratory procedures, that thorough investigation be carried out to determine the source of infection, and that careful follow-up examinations be done so that if a carrier state develops, proper measures can be taken.     

The determination of 'best interests' in relation to childhood vaccinations

There are many different ethical arguments that might be advanced for and against childhood vaccinations. In this paper I will explore one particular argument that focuses on the idea that childhood vaccinations are justifiable because they are held to be in the best interests of a particular child. Two issues arise from this idea. The first issue is how best interests are to be determined in the case of childhood vaccinations. The second issue is what follows from this to justify potential interventions within the family in relation to such vaccinations. I argue that best interests must be characterised objectively in such situations and that this means that, in at least some cases, parental decision-making about vaccinating their children may be overridden.     

Block Fitness

There are three related criteria that a concept of fitness should be able to meet: it should render the principle of natural selection non-tautologous and it should be explanatory and predictive. I argue that for fitness to be able to fulfill these criteria, it cannot be a property that changes over the course of an individual's life. Rather, I introduce a fitness concept--Block Fitness--and argue that an individual's genes and environment fix its fitness in such a way that each individual's fitness has a fixed value over its lifetime.     

Phylogeny of the fish leeches (Oligochaeta, Hirudinida, Piscicolidae) based on nuclear and mitochondrial genes and morphology

The phylogeny of the Piscicolidae was analysed from combined 18S rDNA, cytochrome c oxidase subunit I (CO-I), nicotinamide adenine dinucleotide dehydrogenase subunit I (ND-I) and morphological data using parsimony. A worldwide distribution of Piscicolidae was represented for the first time. While the family Piscicolidae was supported as a monophyletic group, the traditional subfamilies based on morphology were not supported. The Platybdellinae was polyphyletic and formed four distinct clades, and Bathybdella sawyeri did not group with any other platybdellins. The Piscicolinae was also polyphyletic, also forming four distinct clades. The pontobdellin genus Stibarobdella was shown to be the basal taxon within the Piscicolidae; however, the Pontobdellinae was found to be paraphyletic if Oxytonostoma was included. The genera Aestabdella , Austrobdella, and Malmiana were found to be paraphyletic; the genera Calliobdella, Cystobranchus, and Platybdella were found to be polyphyletic. The species Myzobdella lugubris was not found to be monophyletic. It is proposed that Oxytonostoma be transferred out of the Pontobdellinae, that Aestabdella be synonymized with Pterobdella , that Calliobdella vivida be returned to Cystobranchus , that Gonimosobdella be synonymized with Cystobranchus , and that Piscicolaria be synonymized with Myzobdella . The synonymy of Malmiana and Heptacyclus is confirmed, with Heptacyclus having priority. Piscicola milneri is confirmed to be a separate species from Piscicola geometra .