Beyond health care reform: immigrants and the future of medicine

Abstract

I first discuss the fundamental responsibilities of physicians and relate them to an increasingly fragmented medical system made even more complex by government regulations. I focus on trust as a vital component in the doctor–patient relationship, and note the difficult conditions surrounding the treatment of poor and marginal populations. Subsequently, I sketch the elements of a new vision to extend medical services to neglected populations. In that pursuit, the part played by physicians is only as important as the willingness of neighbourhoods and communities to support health as a public good.     

Cross‐species discovery of syncretic drug combinations that potentiate the antifungal fluconazole

Resistance to widely used fungistatic drugs, particularly to the ergosterol biosynthesis inhibitor fluconazole, threatens millions of immunocompromised patients susceptible to invasive fungal infections. The dense network structure of synthetic lethal genetic interactions in yeast suggests that combinatorial network inhibition may afford increased drug efficacy and specificity. We carried out systematic screens with a bioactive library enriched for off‐patent drugs to identify compounds that potentiate fluconazole action in pathogenic Candida and Cryptococcus strains and the model yeast Saccharomyces. Many compounds exhibited species‐ or genus‐specific synergism, and often improved fluconazole from fungistatic to fungicidal activity. Mode of action studies revealed two classes of synergistic compound, which either perturbed membrane permeability or inhibited sphingolipid biosynthesis. Synergistic drug interactions were rationalized by global genetic interaction networks and, notably, higher order drug combinations further potentiated the activity of fluconazole. Synergistic combinations were active against fluconazole‐resistant clinical isolates and an in vivo model of Cryptococcus infection. The systematic repurposing of approved drugs against a spectrum of pathogens thus identifies network vulnerabilities that may be exploited to increase the activity and repertoire of antifungal agents.     

Microclimatic adaptation and differences in food consumption and assimilation efficiency of different shell colour morphs of the land snail Arianta arbustorum

Food consumption and assimilation efficiency of different shell colour morphs adapted to various microclimatic conditions were determined. Five-factor analysis of variance (adaptation temperature, relative humidity, phenotypic shell colour, age class and time of acclimatization) was used. There are differences between different levels of adaptation temperature and relative humidity in the effect on food consumption in the two morphs. The interaction of these two factors is also significant. There is no effect of the phenotypic shell colour on the food consumption, but there is a relation between shell colour and adaptation temperature. Food consumption is greater in the juveniles. The interactions between age class and adaptation temperature or relative humidity are relevant. Acclimatization to these conditions shows a highly significant effect on the food consumption. The brown and yellow morphs of Arianta arbustorum consumed different amounts of food in relation to the adaptation temperature.
Assimilation efficiency is independent of temperature but declines at high relative humidity. There is a relation between adaptation temperature and relative humidity, but not between the phenotypic shell colour and age class factors. The yellow morphs show higher assimilation efficiencies than the brown morphs during cold adaptation to 5 °C and at the highest level of relative humidity (98%).     

The cost to plants of different strategies of adaptation to stress and the alleviation of stress by increasing assimilation

Summary The fitter of two species that use different strategies to overcome the same stress may be the one that expends the least resources to cope with this stress. However, this concept has proven difficult to quantify. It is proposed here that the increase in maintenance respiration in response to stress factors such as high temperature, salinity or a high-oxygen atmosphere (one indirect effect of which is nitrogen deficiency) may provide a measure of the cost of adaptation, in terms of expenditure of assimilated carbon. A corrolary to this is that, where it can be shown that an adaptive strategy results in the expenditure of assimilates, adaptation may be enhanced by increasing carbon assimilation. Results are presented supporting the hypothesis and its corrolary.     

The impact of growing-season length variability on carbon assimilation and evapotranspiration over 88 years in the eastern US deciduous forest

 Recent research suggests that increases in growing-season length (GSL) in mid-northern latitudes may be partially responsible for increased forest growth and carbon sequestration. We used the BIOME-BGC ecosystem model to investigate the impacts of including a dynamically regulated GSL on simulated carbon and water balance over a historical 88-year record (1900–1987) for 12 sites in the eastern USA deciduous broadleaf forest. For individual sites, the predicted GSL regularly varied by more than 15 days. When grouped into three climatic zones, GSL variability was still large and rapid. There is a recent trend in colder, northern sites toward a longer GSL, but not in moderate and warm climates. The results show that, for all sites, prediction of a long GSL versus using the mean GSL increased net ecosystem production (NEP), gross primary production (GPP), and evapotranspiration (ET); conversely a short GSL is predicted to decrease these parameters. On an absolute basis, differences in GPP between the dynamic and mean GSL simulations were larger than the differences in NEP. As a percentage difference, though, NEP was much more sensitive to changes in GSL than were either GPP or ET. On average, a 1-day change in GSL changed NEP by 1.6%, GPP by 0.5%, and ET by 0.2%. Predictions of NEP and GPP in cold climates were more sensitive to changes in GSL than were predictions in warm climates. ET was not similarly sensitive. First, our results strongly agree with field measurements showing a high correlation between NEP and dates of spring growth, and second they suggest that persistent increases in GSL may lead to long-term increases in carbon storage. Received: 26 May 1998 / Accepted: 6 July 1998     

Sulfate assimilation and glutathione synthesis in C<Subscript>4</Subscript> plants

Sulfate assimilation and glutathione synthesis were traditionally believed to be differentially compartmentalised in C₄ plants with the synthesis of cysteine and glutathione restricted to bundle sheath and mesophyll cells, respectively. Recent studies, however, showed that although ATP sulfurylase and adenosine 5′ phosphosulfate reductase, the key enzymes of sulfate assimilation, are localised exclusively in bundle sheath in maize and other C₄ monocot species, this is not true for the dicot C₄ species of Flaveria. On the other hand, enzymes of glutathione biosynthesis were demonstrated to be active in both types of maize cells. Therefore, in this review the recent findings on compartmentation of sulfate assimilation and glutathione metabolism in C₄ plants will be summarised and the consequences for our understanding of sulfate metabolism and C₄ photosynthesis will be discussed.     

Transformations in the sociocultural values and meanings of reefs and resources on Mwoakilloa

People have been living on Mwoakilloa, a coral atoll in the Federated States of Micronesia (FSM), for well over a millennium. Foreign interlopers, colonial governments, global commerce, and a host of internal and external forces have all played a role in shaping the uses, values, and meanings assigned to the atoll, its reefs, and its resources. This paper explores the changing relationships among the people and reefs of Mwoakilloa, highlighting the multiple, co-existing, and sometimes competing meanings and values assigned to atoll resources. It emphasizes the point that even in a small, ethnically homogeneous population there exists a diversity of meanings associated with reef resources that are dependent upon wider socioeconomic contexts. Identifying the sources of these cultural meanings is critical for understanding behaviors toward and uses of reef resources, the status and application of traditional ecological knowledge, and the success and failure of local management measures on Mwoakilloa.

Local adaptation and the geometry of host–parasite coevolution

Metapopulation dynamics can strongly affect the ecological and evolutionary processes involved in host–parasite interactions. Here, I analyse a deterministic host–parasite coevolutionary model and derive analytic approximations for the level of local adaptation as a function of (1) host migration rate, (2) parasite migration rate, (3) parasite specificity and (4) parasite virulence. This analysis confirms the results of previous simulation studies: the difference between host and parasite migration rates may explain the level of local adaptation of both species. I also show that both higher specificity and higher virulence generally lead to higher levels of local adaptation of the species which is already ahead in the coevolutionary arms race. The present analysis also provides a simple geometric interpretation for local adaptation which captures the complexity of the temporal dynamics of host–parasite coevolution.     

Height and BMI of Italian immigrants to the USA, 1908–1970

We analyze self-reported anthropometric data pertaining to 2140 adults who emigrated to the United States, mainly from southern Italy, between 1908-1928 and 1960-1970. The mean height of immigrant men was 165.5 cm: they were taller than contemporary southern Italian men by 0.5-7.3 cm in different periods. The mean height of the Italian immigrant women born before 1952 was 157.6 cm, less than the national average. At the end of the 1990s, national women average height was 162 cm, 159.5 cm for southern women. There were age-related increases of weight and BMI: overweight was more prevalent in the 40-49 years age category. In the male sample, the mean values of BMI were within the overweight range in all age classes. The prevalence of obesity was higher in the male sample than among US men, whereas it was virtually identical in the women's sample and much higher than the values reported for several European countries for the period 1970-1980.     

Individuals and groups in evolution: Darwinian pluralism and the multilevel selection debate

Outlined here is an updated review of the long-standing ‘kin selection vs group selection’ debate. Group selection is a highly contentious concept, scientifically and philosophically. In 2012, Dawkins’ attack against Wilson’s latest book about eusociality concentrated all the attention on group selection and its mutual exclusivity with respect to inclusive fitness theory. Both opponents seem to be wrong, facing the general consensus in the field, which favours a pluralistic approach. Historically, despite some misunderstandings in current literature, such a perspective is clearly rooted in Darwin’s writings, which suggested a plurality of levels of selection and a general view that we propose to call ‘imperfect selfishness’. Today, the mathematically updated hypothesis of group selection has little to do with earlier versions of ‘group selection’. It does not imply ontologically unmanageable notions of ‘groups’. We propose here population structure as the main criterion of compatibility between kin selection and group selection. The latter is now evidently a pattern among others within a more general ‘multilevel selection’ theory. Different explanations and patterns are not mutually exclusive. Such a Darwinian pluralism is not a piece of the past, but a path into the future. A challenge in philosophy of biology will be to figure out the logical structure of this emerging pluralistic theory of evolution in such contentious debates.     

Dental morphology and odontometry of the Tibetan immigrants

Dental features such as size, shape, cusp number and groove pattern, deflecting wrinkle, protostylid, form and size of dental arch and occlusion pattern, as well as crown diameters of maxillary and mandibular dentition of the Tibetan immigrants in India are described. Sex differences in various measurements are also noted. Overall reduction in size, presence of hypodontia of the third molar, and absence of Carabelli's trait are a distinct progressive/evolutionary trend in the Tibetan dentition, while presence of a shovel-shaped lingual surface of central and lateral incisors is a retrogressive/primitive condition. In some of the dental features Tibetans resemble Caucasoid and modern populations, in certain others they resemble other Mongoloid populations, and in still other features they resemble aboriginal populations and fossil hominids.     

Genetic assimilation in the evolution of bipedalism

The evolution of the bipedal habit and its attendant anatomical specializations constitute the hallmark of our taxonomic family, but aside from numerous adaptive (ultimate cause) scenarios, no discussion of a genetic proximate cause can be found in the literature. On the surface, the evolution of obligate bipedalism involves the inheritance of an acquired character, since the descendants of facultative bipeds who chose to walk bipedally are hypothesized to have become obligate bipeds. This paper attempts to explain the Lamarckian origin of human bipedalism in a neo-Darwinian manner, by recourse to the adaptability of organisms, and the concept of genetic assimilation.     

Insularity and adaptation in coupled victim–enemy associations

Employing a mathematical model we show how insularity, genotypic interactions and victim life‐history/demography can influence adaptation in a simple enemy–victim interaction where genotypes migrate between a large source and a smaller, initially unoccupied, isolated habitat. We find that when there are explicit costs to heightened enemy virulence and victim resistance, large/close islands resemble their immigration sources, whereas small and/or distant islands tend to be occupied only by the least defended victims and least virulent enemies. In a model with no explicit cost to genotypic identity, frequencies do not differ on average between source and island. Despite these trends in genotype frequencies, for a range of realistic conditions, both cost and cost‐free genotypic interactions yield an increase in the frequency of resistant encounters as a function of isolation. Moreover, in models with explicit costs, maximal island to island variation in genotypic frequencies is found on islands of intermediate distance from the source. In contrast, the model without explicit costs produces more variable communities, attaining maximum variability in genotypic frequencies at the most isolated islands. We hypothesize that adaptive patterns in mainland–island comparisons may differ substantially from those generated by centre‐periphery comparisons in continental systems.     

Variation of female and male lineages in sub-Saharan populations: the importance of sociocultural factors

In this paper, we present a study of genetic variation in sub-Saharan Africa, which is based on published and unpublished data on fast-evolving (hypervariable region 1 of mitochondrial DNA and six microsatellites of Y chromosome) and slow-evolving (haplogroup frequencies) polymorphisms of mtDNA and Y chromosome. Our study reveals a striking difference in the genetic structure of food-producer (Bantu and Sudanic speakers) and hunter-gatherer populations (Pygmies, Kung, and Hadza). In fact, the ratio of mtDNA to Y-chromosome Nupsilon is substantially higher in food producers than in hunter-gatherers as determined by fast-evolving polymorphisms (1.76 versus 0.11). This finding indicates that the two population groups differ substantially in female and male migration rate and/or effective size. The difference also persists when linguistically homogeneous populations are used and outlier populations are eliminated (1.78 vs 0.19) or when the jacknife procedure is applied to a paired population data set (1.32 to 7.84 versus 0.14 to 0.66). The higher ratio of mtDNA to Y-chromosome Nnu in food producers than in hunter-gatherers is further confirmed by the use of slow-evolving polymorphisms (1.59 to 7.91 versus 0.12 to 0.35). To explain these results, we propose a model that integrates demographic and genetic aspects and incorporates ethnographic knowledge. In such a model, the asymmetric gene flow, polyginy, and patrilocality play an important role in differentiating the genetic structure of sub-Saharan populations. The existence of an asymmetric gene flow is supported by the phylogeographic features of mtDNA and Y-chromosome haplogroups found in the two population groups. The role of polyginy and patrilocality is sustained by the evidence of a differential pressure of genetic drift and gene flow on maternal and paternal lineages of food producers and hunter-gatherers that is revealed through the analysis of mitochondrial and Y-chromosomal intrapopulational variation.