Cost-Effectiveness Analysis of Combination Therapies for Visceral Leishmaniasis in the Indian Subcontinent

Background

Visceral leishmaniasis is a systemic parasitic disease that is fatal unless treated. We assessed the cost and cost-effectiveness of alternative strategies for the treatment of visceral leishmaniasis in the Indian subcontinent. In particular we examined whether combination therapies are a cost-effective alternative compared to monotherapies.

Methods and Findings

We assessed the cost-effectiveness of all possible mono- and combination therapies for the treatment of visceral leishmaniasis in the Indian subcontinent (India, Nepal and Bangladesh) from a societal perspective using a decision analytical model based on a decision tree. Primary data collected in each country was combined with data from the literature and an expert poll (Delphi method). The cost per patient treated and average and incremental cost-effectiveness ratios expressed as cost per death averted were calculated. Extensive sensitivity analysis was done to evaluate the robustness of our estimations and conclusions. With a cost of US$92 per death averted, the combination miltefosine-paromomycin was the most cost-effective treatment strategy. The next best alternative was a combination of liposomal amphotericin B with paromomycin with an incremental cost-effectiveness of $652 per death averted. All other strategies were dominated with the exception of a single dose of 10mg per kg of liposomal amphotericin B. While strategies based on liposomal amphotericin B (AmBisome) were found to be the most effective, its current drug cost of US$20 per vial resulted in a higher average cost-effectiveness. Sensitivity analysis showed the conclusion to be robust to variations in the input parameters over their plausible range.

Conclusions

Combination treatments are a cost-effective alternative to current monotherapy for VL. Given their expected impact on the emergence of drug resistance, a switch to combination therapy should be considered once final results from clinical trials are available.     

Distribution and conservation of the Gaur Bos gaurus in the Indian Subcontinent

The Gaur Bos gaurus ranges from India to peninsular Malaysia. Its distribution, status and conservation in the Indian subcontinent are reviewed here on the basis of available information, both published papers and unpublished census reports of forest departments, and field survey data from north‐eastern India and parts of Bhutan and Nepal. The Gaur is found in three disjunct regions, south‐western India, central India and north‐eastern India (including Nepal, Bhutan and Bangladesh). Within these regions the distribution is highly fragmented and includes a number of small non‐viable isolated populations. The habitat in north‐eastern India is still contiguous with that in Bhutan, Myanmar and Bangladesh and to some extent with Nepal. Although the estimated population of the Gaur is 23 000–34 000, it is declining alarmingly. Populations outside the protected areas may not last long. An action plan has been proposed for its conservation.     

The origin and early evolution of whales: macroevolution documented on the Indian Subcontinent

The origin of whales (order Cetacea) from a four-footed land animal is one of the best understood examples of macroevolutionary change. This evolutionary transition has been substantially elucidated by fossil finds from the Indian subcontinent in the past decade and a half. Here, we review the first steps of whale evolution, i.e. the transition from a land mammal to obligate marine predators, documented by the Eocene cetacean families of the Indian subcontinent: Pakicetidae, Ambulocetidae, Remingtonocetidae, Protocetidae, and Basilosauridae, as well as their artiodactyl sister group, the Raoellidae. We also discuss the influence that the excellent fossil record has on the study of the evolution of organ systems, in particular the locomotor and hearing systems.     

Starvation Resistance in a Stenothermal Species from the Indian Subcontinent: Mechanistic Basis of Clinal Variation

Parallel clines for starvation resistance and lipid content are well documented among drosophilids on the Indian subcontinent. However, the mechanistic basis of these clines has not been investigated so far. Here, we investigate the utilization of lipids during starvation as a function of duration of stress in D. ananassae. We found higher lipid content responsible for high starvation resistance at lower latitudes. Lipids were utilized during starvation only; not during any other climatic stresses like desiccation or thermal stresses. We also found a cline for consumption of total body lipids; as more content (out of total amount of lipids) was utilized by flies at lower latitudes and lesser at higher latitudes. But, there was no latitudinal cline for threshold lipid amount in the case of females while for males there was a positive cline. Lastly, parallel clines have evolved under contrasting climatic conditions i.e. drier and colder northern localities have flies with lower lipid and reduced starvation resistance while hot and humid localities favor flies with higher lipid levels and greater starvation tolerance. Thus, the evolution of clines associated with starvation and lipid content might have resulted due to specific ecological conditions i.e. humidity gradient on the Indian subcontinent.     

细石叶工艺产品废弃的文化过程研究

细石叶工艺产品是如何废弃的、受哪些因素影响、又如何在考古遗存中得到表现,这些都是我们面临的课题。本文从考古遗存废弃一般过程的理论研究着手,确定影响细石叶工艺产品的因素包括史前狩猎采集者的生计策略、废弃过程中人们的行为选择两个方面;与此同时结合细石叶工艺性质预测细石叶工艺产品可能的废弃方式;然后回到对经验材料点(籍箕滩遗址)与面(华北地区主要细石叶工艺遗址)相结合的分析。整体而言,华北含细石叶工艺产品诸遗址的废弃呈现出多样的形态,有迅速而预期返回的废弃方式(籍箕滩遗址),有计划且不准备返回的废弃方式(如泗涧遗址),有人类经常光顾但不留宿的遗址(如孟家泉遗址),还有废弃迅速的临时营地(如柿子滩遗址)和狩猎动物的望点(如大岗遗址)。     

Evolution of Human Polyomavirus JC: Implications for the Population History of Humans

The polyomavirus JC virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy, is ubiquitous in the human population, infecting children asymptomatically, then persisting in the kidney. The main mode of transmission of JCV is from parents to children through long-term cohabitation. Twelve JCV subtypes that occupy unique domains in Europe, Africa, and Asia have been identified. Here, we attempted to elucidate the evolutionary relationships among JCV strains worldwide using the whole-genome approach with which a highly reliable phylogeny of JCV strains can be reconstructed. Sixty-five complete JCV DNA sequences, derived from various geographical regions and belonging to 11 of the 12 known subtypes, were subjected to phylogenetic analysis using three independent methods: the neighbor-joining, maximum parsimony, and maximum likelihood methods. The trees obtained with these methods consistently indicated that ancestral JCVs were divided into three superclusters, designated as Types A, B, and C. A split in Type A generated two subtypes, EU-a and -b, mainly containing European and Mediterranean strains. The first split in Type B generated Af2 (the major African subtype). Subsequent splits in Type B generated B1-c (a minor European subtype) and all seven Asian subtypes (B1-a, -b, -d, B2, MY, CY, and SC). Type C generated a single subtype (Af1), consisting of strains derived from western Africa. While the present findings provided a basis on which to classify JCV into types or subtypes, they have several implications for the divergence and migration of human populations. Received: 4 April 2001 / Accepted: 31 July 2001     

Home Range and Movement Patterns of Toucans: Implications for Seed Dispersal

Toucans (Ramphastidae) are highly frugivorous, widespread throughout the Neotropics, and travel long distances, thus likely providing dispersal for many tropical trees. Despite being large conspicuous members of the canopy and subcanopy bird community, their movement ecology has been little studied. To understand how these frugivores move through a lowland tropical forest, I tracked the movements of Ramphastos tucanus (White‐throated Toucan), Ramphastos vitellinus (Channel‐billed Toucan), and Pteroglossus pluricinctus (Many‐banded Araçari) in Yasuní National Park, Ecuador. The objectives of this study were to use radiotelemetry to estimate toucan home ranges, movement patterns, and potential seed dispersal distances. Using canopy nets, a total of 20 P. pluricinctus and three Ramphastos toucans were captured, radio‐tagged, and tracked over a 4‐yr period from 2001 to 2005. Average home range sizes were 191 and 86 ha for P. pluricinctus and Ramphastos toucans, respectively. The maximum travel distance in a single 30‐min tracking interval was 3665 m for P. pluricinctus and 3027 m for Ramphastos. Estimated dispersal distances of medium‐sized seeds ranged from 269 to 449 m. Large home range size and long‐distance movements indicate that toucans likely disperse seeds over a scale of hundreds of meters. This study is the first to estimate home range size of any toucan species in intact closed‐canopy forests. Abstract in Spanish is available at http://www.blackwell‐synergy.com/loi/btp .     

Social Diversity in Humans: Implications and Hidden Consequences for Biological Research

Humans are both similar and diverse in such a vast number of dimensions that for human geneticists and social scientists to decide which of these dimensions is a worthy focus of empirical investigation is a formidable challenge. For geneticists, one vital question, of course, revolves around hypothesizing which kind of social diversity might illuminate genetic variation—and vice versa (i.e., what genetic variation illuminates human social diversity). For example, are there health outcomes that can be best explained by genetic variation—or for social scientists, are health outcomes mainly a function of the social diversity of lifestyles and social circumstances of a given population? Indeed, what is a “population,” how is it bounded, and are those boundaries most appropriate or relevant for human genetic research, be they national borders, religious affiliation, ethnic or racial identification, or language group, to name but a few? For social scientists, the matter of what constitutes the relevant borders of a population is equally complex, and the answer is demarcated by the goal of the research project. Although race and caste are categories deployed in both human genetics and social science, the social meaning of race and caste as pathways to employment, health, or education demonstrably overwhelms the analytic and explanatory power of genetic markers of difference between human aggregates.Two contradictory magnetic poles pull medical research on humans in opposite directions, producing a tension that will never be resolved. On the one hand, there is a universalizing impulse—based on a legitimate assumption that human bodies are sufficiently similar that vaccines, catheters, pasteurizing processes, and tranquilizers that work in one population will work in others. On the other hand, and unless and until research protocols establish and confirm specific similarities across populations, there is sufficient human variation that targeting medicines for specific populations can be a legitimate—even vital—empirically driven task. The theoretical question, of course, is why a particular population or subpopulation is to be so targeted? Because of folk theories about different groups’ biological difference, or because of their social and political standing? Age, gender, and race leap to the forefront. The history of research on ailments as disparate as breast and prostate cancer (Rothenberg 1997; Wailoo 2011), heart disease (Cooper et al. 2005), and syphilis (Jones 1981; Reverby 2009) provides strong evidence that the answer is not either/or but both. So, on what grounds do we choose one strategy over the other?And it is precisely on this point that Steven Epstein (2007) raises the most fundamental question:

Out of all the ways by which people differ from one another, why should it be assumed that sex and gender, race and ethnicity, and age are the attributes of identity that are most medically meaningful? Why these markers of identity and not others? (Epstein 2007, p. 10)

The answer is profoundly social and political, economic, and cultural. The United States is the only country in the world that, as public health policy, does not operate on the assumption of the single standard human.Moreover, by highlighting certain categories, there is the unassailable truth that other categories are thereby ignored. But more to the theoretical point, because each of the categories noted above has a potential or real biological base in either scientific or common sense understandings (Schutz 1962), when scientists report findings indicating differences, the danger is that these findings can seductively divert policymakers from seeking alternative interventions that could better address health disparities (Krieger 2011).The goal of Epstein’s monograph was to (a) better understand how ways of thinking about differences in human populations paved the way to try to “improve medical research by making it inclusive,” and (b) explain how and why the strategies of exclusiveness got institutionalized:

Academic researchers receiving federal funds, and pharmaceutical manufacturers hoping to win regulatory approval for their company''s products, are now enjoined to include women, racial and ethnic minorities, children, and the elderly as research subjects in many forms of clinical research … and question the presumption that findings derived from the study of any single group, such as middle-aged white men, might be generalized to other populations. (Epstein 2007, p. 5)

This shift has occurred only in the last two and a half decades, beginning with regulations that were developed first in 1986. Once again, it is important to restate the relatively unique feature of this development as it applies mainly to the United States (Epstein 2007, p. 7). The rest of the world has continued to act on the presupposition of the standard human, at least until now. As we shall see, that is about to change.     

The Ecology and Evolution of Fruit Odor: Implications for Primate Seed Dispersal

Primates are now known to possess a keen sense of smell that serves them in various contexts, including feeding. Many primate species are frugivorous and provide essential seed dispersal services to a variety of plants. Studies of pollination ecology, and recently seed dispersal ecology, indicate that animal mutualist behavior exerts selection pressures that drive changes in flower and fruit traits. As a result, the use of olfaction in in primate feeding ecology may have affected the evolution of fruit odor in species that rely on primate seed dispersal. However, this hypothesis is seldom tested. Here, we summarize the available information on how primates may have affected the evolution of fruit odor. We ask what the chemistry of primate fruit odor may look like, what information fruit odor may convey, whether there are geographical differences in fruit odor, and what other factors may affect the odor of fruits consumed by primates. We identify many gaps in the available data and offer research questions, hypotheses, and predictions for future studies. Finally, to facilitate standardization in the field, we discuss methodological issues in the process of odor sampling and analysis.     

Population Genetics of Ceratitis capitata in South Africa: Implications for Dispersal and Pest Management

The invasive Mediterranean fruit fly (medfly), Ceratitis capitata, is one of the major agricultural and economical pests globally. Understanding invasion risk and mitigation of medfly in agricultural landscapes requires knowledge of its population structure and dispersal patterns. Here, estimates of dispersal ability are provided in medfly from South Africa at three spatial scales using molecular approaches. Individuals were genotyped at 11 polymorphic microsatellite loci and a subset of individuals were also sequenced for the mitochondrial cytochrome oxidase subunit I gene. Our results show that South African medfly populations are generally characterized by high levels of genetic diversity and limited population differentiation at all spatial scales. This suggests high levels of gene flow among sampling locations. However, natural dispersal in C. capitata has been shown to rarely exceed 10 km. Therefore, documented levels of high gene flow in the present study, even between distant populations (>1600 km), are likely the result of human-mediated dispersal or at least some form of long-distance jump dispersal. These findings may have broad applicability to other global fruit production areas and have significant implications for ongoing pest management practices, such as the sterile insect technique.     

Model-Based Investigations of Different Vector-Related Intervention Strategies to Eliminate Visceral Leishmaniasis on the Indian Subcontinent

The elimination of infectious diseases requires reducing transmission below a certain threshold. The Visceral Leishmaniasis (VL) Elimination Initiative in Southeast Asia aims to reduce the annual VL incidence rate below 1 case per 10,000 inhabitants in endemic areas by 2015 via a combination of case management and vector control. Using a previously developed VL transmission model, we investigated transmission thresholds dependent on measures reducing the sand fly density either by killing sand flies (e.g., indoor residual spraying and long-lasting insecticidal nets) or by destroying breeding sites (e.g., environmental management).Model simulations suggest that elimination of VL is possible if the sand fly density can be reduced by 67% through killing sand flies, or if the number of breeding sites can be reduced by more than 79% through measures of environmental management.These results were compared to data from two recent cluster randomised controlled trials conducted in India, Nepal and Bangladesh showing a 72% reduction in sand fly density after indoor residual spraying, a 44% and 25% reduction through the use of long-lasting insecticidal nets and a 42% reduction after environmental management.Based on model predictions, we identified the parameters within the transmission cycle of VL that predominantly determine the prospects of intervention success. We suggest further research to refine model-based predictions into the elimination of VL.     

The myth of “minima” and “maxima”, the species of Physalis in the Indian Subcontinent

The status of the names, Physalis minima L. and P. maxima Mill. (Solanaceae), and their alleged presence on the Indian subcontinent are discussed. The issues of nativity and identity of Linnaean Physalis minima are long-debated while the use of the name P. maxima Mill. and its report from India are recent. The available evidence indicates that the name "P. minima L." is misapplied to two different elements, viz., P. angulata L. and P. lagascae Roem. & Schult. The name Physalis minima L. may be rejected as nomen confusum, for which the paper provides the primary information. As on today, it is submerged under the synonymy of P. angulata L. The correct name for the widely known P. minima is P. lagascae. The name "P. maxima Mill." applied to the escape and naturalized weed in the Indian subcontinent and elsewhere is to be substituted by P. pruinosa L., a name misapplied to P. grisea (Waterf.) M. Martínez.     

Sex-Linked Inheritance in Macaque Monkeys: Implications for Effective Population Size and Dispersal to Sulawesi

Sex-specific differences in dispersal, survival, reproductive success, and natural selection differentially affect the effective population size (N_e) of genomic regions with different modes of inheritance such as sex chromosomes and mitochondrial DNA. In papionin monkeys (macaques, baboons, geladas, mandrills, drills, and mangabeys), for example, these factors are expected to reduce N_e of paternally inherited portions of the genome compared to maternally inherited portions. To explore this further, we quantified relative N_e of autosomal DNA, X and Y chromosomes, and mitochondrial DNA using molecular polymorphism and divergence information from pigtail macaque monkeys (Macaca nemestrina). Consistent with demographic expectations, we found that N_e of the Y is lower than expected from a Wright–Fisher idealized population with an equal proportion of males and females, whereas N_e of mitochondrial DNA is higher. However, N_e of 11 loci on the X chromosome was lower than expected, a finding that could be explained by pervasive hitchhiking effects on this chromosome. We evaluated the fit of these data to various models involving natural selection or sex-biased demography. Significant support was recovered for natural selection acting on the Y chromosome. A demographic model with a skewed sex ratio was more likely than one with sex-biased migration and explained the data about as well as an ideal model without sex-biased demography. We then incorporated these results into an evaluation of macaque divergence and migration on Borneo and Sulawesi islands. One X-linked locus was not monophyletic on Sulawesi, but multilocus data analyzed in a coalescent framework failed to reject a model without migration between these islands after both were colonized.THE effective size of a population (N_e) determines the relative impact of genetic drift and natural selection on mutations with mild effects on fitness (Charlesworth 2009). Differences in N_e are hypothesized to affect virtually every aspect of genome evolution, including rates of molecular evolution, abundance of introns and transposable elements, and persistence of duplicate genes, and this has important implications for the evolution of complexity via both adaptive and degenerative processes (Lynch 2007). Of relevance are not only the number of different individuals in a population, but also the number of copies of a gene within each individual. In diploid species with separate sexes, sex chromosomes and mitochondrial DNA (mtDNA) differ in copy number from autosomal DNA (aDNA): both sexes have two alleles at autosomal loci whereas in species with male heterogamy, males have one X and one Y chromosome, females have two Xs, and a female/male pair has effectively only one copy of mtDNA due to maternal inheritance. Sex-specific differences in demographic parameters such as migration, adult sex ratio, and variance in reproductive success also affect relative copy number and associated levels of neutral polymorphism at mtDNA, aDNA, the X chromosome (xDNA), and the Y chromosome (yDNA) (Hedrick 2007).The effective population size is the number of individuals in a Wright–Fisher idealized population (Fisher 1930; Wright 1931) that have the same magnitude of genetic drift as an observed population, where ideal individuals are diploid, and have discrete (nonoverlapping) generations, constant population size, and random mating. N_e can be quantified in terms of variance in allele frequency over generations (variance N_e) or variance in inbreeding over time (inbreeding N_e). If population size is constant with random mating, these approaches for quantifying N_e produce identical results (Kimura and Crow 1963; Whitlock and Barton 1997). At mutation–drift equilibrium with an equal number of males and females and a Poisson distributed number of offspring with a mean of two offspring per individual, N_e-aDNA and N_e-xDNA are expected to be four and three times as large, respectively, as N_e-yDNA and N_e-mtDNA; we refer to this as the “ideal expectation with an equal proportion of males and females.”Demography can alter relationships between N_e of different parts of the genome. For example, extreme skew in adult sex ratio can cause N_e of uniparentally inherited portions of the genome to exceed N_e of biparentally inherited portions (Figure 1A; Nunney 1993; Caballero 1994; Hoelzer 1997; Hedrick 2007). With a skewed sex ratio, the more common sex has a higher variance in reproductive success than the rare one, and this causes the overall variance in reproductive success to increase as the sex-ratio bias increases (Nunney 1993). Sex-biased dispersal such as female philopatry also alters relationships between N_e-aDNA, N_e-xDNA, N_e-yDNA, and N_e-mtDNA (Figure 1B), causing N_e of portions of the genome that disperse less to increase (Nei and Takahata 1993; Hoelzer 1997; Wang and Caballero 1999).Open in a separate windowFigure 1.—N_e of aDNA, xDNA, mtDNA, and yDNA as a function of (A) sex ratio skew and (B) the probability of female dispersal. In B, a finite island model of subdivided populations of constant size is assumed with a population size of 10,000 individuals, 10 subpopulations, and a male probability of migration equal to 0.1.At least five factors related to natural selection also can cause the relative N_e of aDNA, xDNA, yDNA, and mtDNA to depart from expectations: (1) very low or absent recombination in mtDNA and a portion of yDNA, (2) haploidy of mtDNA and yDNA, (3) hemizygosity of xDNA in males, (4) sexual selection and differences in gene content, and (5) differences in the rate and variance of mutation. “Selective sweeps” in which an advantageous mutation is fixed by natural selection, reduces N_e of linked sites (Maynard Smith and Haigh 1974) and this can affect the entire mitochondrial genome and nonrecombining portion of the Y chromosome. Nonrecombining portions of yDNA and mtDNA are also affected by stochastic loss of alleles containing the fewest deleterious mutations (“Muller''s ratchet”; Muller 1964; Felsenstein 1974), which results in a gradual decline of fitness of these chromosomes over time. N_e of nonrecombining DNA is further reduced by elimination of variation linked to substantially deleterious mutations (“background selection”; Charlesworth et al. 1993), by interference between linked polymorphisms that impedes fixation of advantageous alleles and extinction of deleterious ones (the “Hill–Robertson effect”; Hill and Robertson 1966; McVean and Charlesworth 2000), and by increased frequency of deleterious mutations linked to advantageous ones during a selective sweep (“genetic hitchhiking”; Rice 1987). Hemizygous X-linked and haploid Y-linked loci in males and mtDNA loci in both sexes are more vulnerable to recessive deleterious mutations because they are not masked by a second allele (Otto and Goldstein 1992). Hemizygosity on the X chromosome can also increase the rate of selective sweeps when advantageous mutations are recessive (Charlesworth et al. 1987). Similarly, these loci are also susceptible to recessive species incompatibilities—a factor that at least partially accounts for Haldane''s rule for hybrid sterility (Haldane 1922; Orr 1997). Sexual selection differentially influences the probability of fixation of mutations depending on mode of inheritance (Wade and Shuster 2004), especially mutations with antagonistic fitness effects between the sexes (Gibson et al. 2002). Additionally, the rate of evolution of animal mtDNA is much higher than aDNA, xDNA, and yDNA (Haag-Liautard et al. 2008) and this presumably contributes to variation in the frequency of nonneutral mutations in different parts of the genome.Differences among N_e of mtDNA, yDNA, xDNA, and aDNA are thought to be particularly pronounced in papionin monkeys (macaques, baboons, geladas, mandrills, drills, and mangabeys). These monkeys have a highly sex-biased adult demography; females form stable philopatric groups of close relatives, whereas males generally change social groups and disperse more widely (Dittus 1975). Often adult sex ratio of papionins is female biased (Dittus 1975; Melnick and Pearl 1987; O''Brien and Kinnard 1997; Okamoto and Matsumura 2001), and males have higher variance in reproductive success than females (Dittus 1975; de Ruiter et al. 1992; Keane et al. 1997; Van Noordwijk and Van Schaik 2002; Widdig et al. 2004). These sex differences predict strong population subdivision of mtDNA with little or no subdivision of aDNA, deep mtDNA coalescence times, and frequent mtDNA paraphyly among species, and discordant genealogical relationships between mtDNA and yDNA—and this has been observed in multiple studies (Melnick and Pearl 1987; Melnick 1988; Melnick and Hoelzer 1992; Melnick et al. 1993; Hoelzer et al. 1994; Evans et al. 1999, 2001, 2003; Tosi et al. 2000, 2002, 2003; Newman et al. 2004). Female philopatry and obligate male migration is a common social system in mammals (Greenwood 1980; Dobson 1982; Johnson 1986), though less so in humans (Seielstad et al. 1998), and molecular variation provides an effective tool for exploring the impact of natural selection and demography on aDNA, the sex chromosomes, and mtDNA (Nachman 1997; Bachtrog and Charlesworth 2002; Stone et al. 2002; Berlin and Ellegren 2004; Hellborg and Ellegren 2004; Wilder et al. 2004; Hammer et al. 2008).We explored the genetic effects of demography and linked selection in structuring sequence polymorphism of a papionin monkey—the macaques—at two levels. We first tested whether levels of polymorphism in aDNA, xDNA, yDNA, and mtDNA in a Bornean population of the pigtail macaque, Macaca nemestrina, match expectations under scenarios involving natural selection and also whether the data might be explained by simple demographic models with sex-specific dispersal or a biased sex ratio. We then explored demography on a larger, inter-island scale by estimating the time of divergence between macaques on Borneo and Sulawesi islands and by testing for evidence of ongoing migration between these islands.     

更新世东亚人群连续演化的考古证据及相关问题论述

本文从考古文化的角度论证中国乃至东亚古人类演化的连续性。通过对石制品原料特点及开发利用方式、石器制作技术、石制品类型、形态与组合特点、区域文化传统演变等方面的分析,提出这里的旧石器时代文化一脉相承,古人群生生不息、连续演化。通过对中国旧石器文化体系中勒瓦娄哇技术制品、具有阿舍利风格的组合和石叶技术产品这些具有"西方元素"特点的文化成分的辨识与分析,指出更新世期间该地区石器生产基本维持在奥杜威模式内,来自西方的文化因素间或出现过,但从来没有成为主流,更没有发生对土著文化的置换,说明这一地区没有发生过大规模移民和人群更替事件;基因混合与文化交流可能发生过,但其过程是融合而非替代。秦岭诸遗址、北窑、大地湾、徐家城、乌兰木伦、织机洞、井水湾、黄龙洞等遗址的地层和测年数据表明东亚不存在距今10~4万年间的材料空白,人类演化的链条没有中断过。古气候和古生物信息也对末次冰期导致本土人群灭绝的论断提出否定。这些考古材料与信息对中国乃至东亚古人群连续演化及现代人类"连续进化附带杂交"的理论提供了强有力的论证和支持。"综合行为模式"等学说的提出强化了对本土人群生存能力的论述。对人类独特的行为特点与社会属性的观察和思考,也对本土人群与西方同类的隔离问题及不同地区人群长时期维持在同一物种内的可能性与动因提供了有益的启示。