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The present research is a preliminary investigation of the concurrent and temporal relationships between humility and two forms of well-being: emotional and psychological well-being. Humility, emotional well-being and psychological well-being were measured twice 6 weeks apart. Humility correlated positively with psychological well-being at both time-points, but was positively related to emotional well-being at only one time-point. In addition, we used structural equation modeling to perform cross-lagged panel analyses, and found that psychological well-being predicted an increase in humility over time, but humility did not predict changes in psychological well-being over time. In addition, there were no cross-lagged associations between emotional well-being and humility. The results suggest that humility does not necessarily lead to more pleasant or fulfilling experiences, but psychological well-being is conducive to cultivating humility.

In addition to the widespread availability of packaged cigarettes, the inhabitants of island nations of the Southwest Pacific frequently smoke commercially available loose tobacco using manufactured rolling papers, as well as locally grown tobacco rolled in manufactured rolling paper or wrapped in leaves, copybook paper, and newspaper. In this study, Vanuatu men who smoked local tobacco rolled in leaves, copybook paper, or newspaper showed significantly lower forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and FEV1/FVC ratios than men who smoked packaged cigarettes, store-bought tobacco rolled in manufactured rolling paper, or who smoked locally grown tobacco rolled in manufactured rolling papers. The addition of toxins from these unusual tobacco-wrapping media produces lung function deficits similar to the pattern noted among tobacco smokers who also inhale smoke from burning biomass. Thus, public health initiatives should consider including strategies addressing the use of wrapping media among smokers in South Pacific island societies.

The 27-bp deletion in the erythrocyte band 3 gene (B3Delta27) constitutes a genetic basis for Southeast Asian and Melanesian ovalocytosis. The distribution of B3Delta27 has been interpreted to reflect malaria selection or dispersal of the recent expansion of Austronesian-speaking populations. To explore these two hypotheses, we examined eight malarious populations of the East Sepik Province of Papua New Guinea (PNG) that speak both the Austronesian and Papuan languages. The B3Delta27 allele frequencies within populations were not positively correlated with malaria endemicities. In contrast, statistically significant geographical variations in the B3Delta27 allele distribution were observed. B3Delta27 was high (0.06-0.07) in the islands, intermediate (0.02-0.03) in coastal regions, but was absent or rare (0.00-0.01) in inland populations. Furthermore, the prevalence of the mitochondrial DNA region V 9-bp deletion, associated with the Austronesian expansion, was significantly correlated with that of B3Delta27. These results suggest that B3Delta27 was introduced by Austronesian-speaking people within the past 3,500 years and subsequently expanded to populations along the coasts and islands of PNG. This study highlights the contribution of population origins, patterns of gene flow, disease selection and genetic drift in determining the genetic compositions of present populations.

Summary Tumour necrosis factor-alpha (TNF-a) is one of the key cytokines that influence the pathology ofmicrobial infections. The genetic susceptibility to severe forms of falciparum malaria is differentiallyassociated with TNF-a promoter gene polymorphisms (TNFP alleles). In a previous study, we identified aTNFP-allele characterized by a C to T transition at position )857 (TNFP-D allele) as a marker forsusceptibility to cerebral malaria in Myanmar. The frequencies of TNFP alleles on six islands ofVanuatu, Melanesia (South-west Pacific) were estimated to investigate whether malaria selectionpressure on this susceptibility marker has influenced its prevalence. Within the archipelago of Vanuatuthere is a decreasing cline of parasite incidence from North to South. Of the four alleles of the TNFPgene detected in Vanuatu, the TNFP-D allele frequencies were inversely correlated with the parasiteincidence of islands; TNFP-D varied from 0.55 on the island with the lowest parasite incidence to 0.26on the island with the highest parasite incidence (r ¼ )0.855, P ¼ 0.03). We also observed a significantcorrelation between the frequencies of a-thalassaemia alleles, thought to protect against malaria andparasite incidence in the same populations. These data are consistent with a previously reportedcorrespondence between the frequencies of glucose 6-phosphate dehydrogenase (G6PD) deficiency andparasite incidences on the islands of Vanuatu (Kaneko et al. 1998) and indicate that the degree ofmalaria endemicity has influenced the allele frequencies of at least three loci that confer bothsusceptibility (TNFP-D) and protection (a-thalassaemias and G6PD deficiency).keywords malaria, selection, TNF-a, a-thalassaemia, MelanesiaIntroductionA number of studies have indicated that parasite incidencehas influenced the frequencies of susceptible or resistantgenes within populations. The loci thought to conferresistance to malaria include haemoglobin alleles such assickle cell trait in Africa (Allison 1954), a-thalassaemias inthe Mediterranean and in Asia (Beaven et al. 1961), andovalocytosis in South-east Asia (Baer et al. 1976). InMelanesia, a-thalassaemia allele frequencies were signifi-cantly correlated with altitude and latitude indicating long-term malaria selection pressure (Hill et al. 1985; Flint et al.1986; Roberts-Thomson et al. 1996). Genetic variants ofimmunity-related genes (e.g. major histocompatibilitycomplex, immunoglobulin, cytokine, chemokine, adhesionmolecule, and complements) have also been postulated toinfluence susceptibility to malaria (Gimenez et al. 2003).Of these immunity-related molecules, tumour necrosisfactor-alpha (TNF-a) is a pro-inflammatory cytokine thatplays an essential role in the protection against manyinfectious diseases, but is also fatal in excess (Beutler et al.1993; Knight et al. 1999). An association between singlenucleotide polymorphisms (SNPs) in the TNF-a promoterregion (TNFP) and susceptibility to malaria has beenobserved in several studies. In Africa, the severe form ofmalaria was associated with the TNFP )238A allele(McGuire et al. 1999) whereas cerebral malaria (CM) wasassociated with the TNFP )308A allele in the samepopulation (McGuire et al. 1994). In Myanmar patients,we reported a strong association between CM and TNFP-D(Ubalee et al. 2001). TNFP-D is characterized by a C to Ttransition at position )857, the location of an OCT-1binding site adjacent to a NF-jB binding site (position)863) (van Heel et al. 2002). The frequencies of glucose6-phosphate dehydrogenase (G6PD) deficiency of islandsof Vanuatu were significantly correlated with parasiteincidence (Kaneko et al. 1998). In this study, we investi-gated whether the frequencies of the TNFP-D allele

Aims We assessed the disposition of oral amodiaquine (AQ) and CYP2C8 polymorphism in 20 children with falciparum malaria. Methods AQ and DEAQ concentrations were determined with SPE-HPLC method. CYP2C8 genotypes were assessed by PCR-RFLP method. Results AQ was not detectable beyond day 3 postdose. Cmax for DEAQ was reached in 3.0 days. The mean values for t1/2, MRT, and AUCtotal were 10.1 days, 15.5 days and 4512.6 µg l−1 day, respectively. All the children were CYP2C8* homozygous. Conclusion Our data are consistent with those previously reported, and the AQ regimen seems pharmacokinetically adequate in the absence of CYP2C8 polymorphism.

The prevalence of a 9-base-pair (bp) deletion between the mitochondrial cytochrome oxidase II (MTCOX*2) and lysine tRNA (MTTK) genes (region V) has been used to estimate the genetic relationships among Asian and Pacific populations. Many East Asian and Pacific Island populations have been examined previously, but the mitochondrial DNA (mtDNA) diversity of the intervening Indonesian archipelago has not previously been systematically examined. The 17,500 islands of Indonesia currently contain nearly 213 million people and extensive cultural, linguistic, and, presumably, genetic diversity. This study of 1091 individuals representing 15 ethnic groups is the most extensive mtDNA survey to date of the Indonesian archipelago. Six distinct length polymorphisms in region V were observed within these 15 populations. The 9-bp deletion was found in every population examined at frequencies comparable to those of previously examined East Asian populations and substantially lower than those in most Pacific Island populations. Despite the inclusion of Austronesian-speaking populations and a Papuan-speaking population, there was no statistically significant heterogeneity in the frequency of the 9-bp deletion among the 15 populations (p = 0.09). These data indicate that substantial gene flow occurred among the populations at some time in the past. Our observations of no significant correlations between genetic and geographic distances (r = -0.04, p = 0.53) coupled with the extensive cultural and linguistic differences currently within the archipelago suggest that little gene flow among neighboring populations has occurred recently.

The islands of Micronesia and Polynesia collectively comprise the last major region of the globe to be settled by humans. Both of these groups of islands were colonized within the last 4,000 years by Austronesian-speaking agriculturists. Based on biogeographic and linguistic patterns, central-eastern Micronesia and Polynesia are included by many in a single category called Remote Oceania. Similarities of biologic, linguistic, and cultural traits within Remote Oceania highlight a question central to Oceanic studies: Are similarities among islands due to a common origin of isolated communities, to ongoing interactions among islands, or both? Analyses of mitochondrial DNA (mtDNA) sequences reveal that most remote Oceanic populations are polyphyletic. These polyphyletic populations violate the assumptions of many genetic distance and population demography models and so are problematic to interpret. The majority of mtDNA sequences from Micronesian and Polynesian populations are derived from Asia, whereas others are inferred to have originated in New Guinea. These data support an Island Southeast Asian origin and a colonization route along the north coast of New Guinea. The Marianas and Yap proper (main island) appear to have been independently settled directly from Island Southeast Asia, and both have received migrants from Central-Eastern Micronesia since then. Palau clearly demonstrates a complex prehistory including a significant influx of lineages from New Guinea. Thus genetic similarities among Micronesian and Polynesian populations result, in some cases, from a common origin, and in others, from extensive gene flow.

The origins and genetic affinities of the more than 500 tribal populations living in South Asia are widely disputed. This may reflect differential contributions that continental populations have made to tribal groups in South Asia. We assayed for the presence of the intergenic COII/tRNALys 9-bp deletion in human mtDNA in 646 individuals from 12 caste and 14 tribal populations of South India and compared them to individuals from Africa, Europe, and Asia. The 9-bp deletion is observed in four South Indian tribal populations, the Irula, Yanadi, Siddi, and Maria Gond, and in the Nicobarese. Length polymorphisms of the 9-bp motif are present in the Santal, Khonda Dora, and Jalari, all of whom live in a circumscribed region on the eastern Indian coast. Phylogenetic analyses of mtDNA control region sequence from individuals with the 9-bp deletion indicate that it has arisen independently in some Indian tribal populations. Other 9-bp deletion haplotypes are likely to be of Asian and African origin, implying multiple origins of the 9-bp deletion in South India. These results demonstrate varying genetic affinities of different South Indian tribes to continental populations and underscore the complex histories of the tribal populations living in South Asia.

SummarymtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations.

The origins and relationships among Micronesians, Polynesians, and Melanesians were investigated. Five different mtDNA region V length polymorphisms from 873 individuals representing 24 Oceanic and Asian populations were analyzed. The frequency cline of a common deletion and the distributions of a rare expanded length polymorphism support the origin of both Micronesians and Polynesians in Island Southeast Asia. Genetic, linguistic, and geographic distances were compared to assess the relative importance of isolation and gene flow during the prehistory of 19 Austronesian-speaking populations subdivided into five potential spheres of interaction. We observed significant correlations (P0.05) between genetic and linguistic distances in four of five comparisons. These data indicate extensive gene flow throughout much of Micronesia, but substantial isolation in other Pacific regions. Although recent advancements in our understanding of intentional voyaging within Remote Oceania have challenged the existence of the "myth of the primitive isolate," we caution against the adoption of panmictic alternatives.

The 4000-year-old human population expansion into Remote Oceania has been studied from a variety of genetic perspectives. Here, we report the discovery that Polynesians, traditionally considered to be a single cohesive linguistic and cultural unit, exhibit at least three distinct mitochondrial DNA (mtDNA) groups that probably shared a common maternal ancestor more than 85,000 years ago. The major lineage groups were first identified by PCR amplification of the mitochondrial region V deletion marker, known to be present at high frequency in Polynesian populations. Sequence analysis of mtDNA hypervariable control regions reveals a surprising number of lineages in Polynesia. We also note high sequence divergence between lineage groups deleted and not deleted in region V. Major group I lineages are common in Remote Oceania and include about 95% of the Native Hawaiian, 90% of the Samoan, and 100% of the Tongan donors in our sample. They contain the region V deletion and generally share three control region transition substitutions. This group also contains non-Polynesian individuals, such as Indonesians, Native Americans, Micronesians, Malaysians, Japanese, and Chinese. The group I Polynesians differ by 4.4% in sequence identity from major lineage group II Polynesians, who do not have the region V deletion and who share among themselves four distinct single-base substitutions. Group II individuals are seen at low frequency (10%) in Hawaii, Samoa, and the Cook Islands and may represent the predominant maternal lineage group of Papuan Melanesia. Major lineage group III, not found in Hawaii, tentatively links Samoa to Indonesia. Our observation of deep maternal genetic branches in Polynesia today confirms the notion that during the colonization of the Pacific, mainland Asian immigrants mixed with Melanesian peoples already inhabiting Near Oceania and carried a complex assortment of maternal genotypes derived from two distinct geographic sources to isolated island archipelagoes.