Assessment of Risk for Type 1 Diabetes in Children of Affected Families and in the General Population : Role of Immunological and Metabolic Markers

Background and aims. Type 1 diabetes (T1D), an autoimmune disease in which the insulin producing beta cells are gradually destroyed, is preceded by a prodromal phase characterized by appearance of diabetes-associated autoantibodies in circulation. Both the timing of the appearance of autoantibodies and their quality have been used in the prediction of T1D among first-degree relatives of diabetic patients (FDRs). So far, no general strategies for identifying individuals at increased disease risk in the general population have been established, although the majority of new cases originate in this population. The current work aimed at assessing the predictive role of diabetes-associated immunologic and metabolic risk factors in the general population, and comparing these factors with data obtained from studies on FDRs. Subjects and methods. Study subjects in the current work were subcohorts of participants of the Childhood Diabetes in Finland Study (DiMe; n=755), the Cardiovascular Risk in Young Finns Study (LASERI; n=3475), and the Finnish Type 1 Diabetes Prediction and Prevention Study (DIPP) Study subjects (n=7410). These children were observed for signs of beta-cell autoimmunity and progression to T1D, and the results obtained were compared between the FDRs and the general population cohorts. --- Results and conclusions. By combining HLA and autoantibody screening, T1D risks similar to those reported for autoantibody-positive FDRs are observed in the pediatric general population. Progression rate to T1D is high in genetically susceptible children with persistent multipositivity. Measurement of IAA affinity failed in stratifying the risk assessment in young IAA-positive children with HLA-conferred disease susceptibility, among whom affinity of IAA did not increase during the prediabetic period. Young age at seroconversion, increased weight-for-height, decreased early insulin response, and increased IAA and IA-2A levels predict T1D in young children with genetic disease susceptibility and signs of advanced beta-cell autoimmunity. Since the incidence of T1D continues to increase, efforts aimed at preventing T1D are important, and reliable disease prediction is needed both for intervention trials and for effective and safe preventive therapies in the future. Our observations confirmed that combined HLA-based screening and regular autoantibody measurements reveal similar disease risks in pediatric general population as those seen in prediabetic FDRs, and that risk assessment can be stratified further by studying glucose metabolism of prediabetic subjects. As these screening efforts are feasible in practice, the knowledge now obtained can be exploited while designing intervention trials aimed at secondary prevention of T1D.

The psychometric properties of the Kessler Psychological Distress Scale (K6) in a general population sample of adolescents

The 6-item Kessler Psychological Distress Scale (K6; Kessler et al., 2002) is a screener for psychological distress that has robust psychometric properties among adults. Given that a significant proportion of adolescents experience mental illness, there is a need for measures that accurately and reliably screen for mental disorders in this age group. This study examined the psychometric properties of the K6 in a large general population sample of adolescents (N = 4,434; mean age = 13.5 years; 44.6% male). Factor analyses were conducted to examine the dimensionality of the K6 in adolescents and to investigate sex-based measurement invariance. This study also evaluated the K6 as a predictor of scores on the Strengths and Difficulties Questionnaire (SDQ; Goodman, 1997). The K6 demonstrated high levels of internal consistency, with the 6 items loading primarily on 1 factor. Consistent with previous research, females reported higher mean levels of psychological distress when compared with males. The identification of sex-based measurement noninvariance in the item thresholds indicated that these mean differences most likely represented reporting bias in the K6 items rather than true differences in the underlying psychological distress construct. The K6 was a fair to good predictor of abnormal scores on the SDQ, but predictive utility was relatively low among males. Future research needs to focus on refining and augmenting the K6 scale to maximize its utility in adolescents. (PsycINFO Database Record (c) 2015 APA, all rights reserved)

Population genetics of the invasive plant species Impatiens glandulifera in Southern Finland

Biological invasions affect biodiversity worldwide, and, consequently, the invaded ecosystems may suffer from significant losses in economic and cultural values. Impatiens glandulifera Royle (Balsaminaceae) is an invasive annual herb, native to the western Himalayas and introduced into Europe in the 19th century as a garden ornamental plant. The massive invasion of I. glandulifera is due to its high reproductive output, rapid growth and its ability to outcompete native species. In Finland, the first observations regarding the presence of I. glandulifera date from the year 1947, and today it is considered a serious problem in riparian habitats. The aim of this master’s thesis research is to reveal the population genetic structure of I. glandulifera in Finland and to find out whether there have been one or multiple invasions in Finland. The study focuses on investigating the origin of I. glandulifera in Southern Finland, by comparing plant samples from the Helsinki region with those from its native region and other regions of invasion. Samples from four populations in Helsinki and from the United Kingdom, Canada, India and Pakistan were collected and genotyped using 11 microsatellite markers. The genetic analyses were evaluated using the programs Arlequin and Structure. The results of the genetic analyses suggested that I. glandulifera has been introduced to Finland more than once. Multiple introductions are supported by the higher level of genetic diversity detected within and among Finnish populations than would be expected for a single introduction. Results of the Bayesian Structure analysis divided the four Finnish populations into four clusters. This geographical structure was further supported by pairwise Fst values among populations. The causes and potential consequences of such multiple introductions of I. glandulifera in Finland and further perspectives are discussed.

A finite population model of mlecular evolution: theory and computation

This article is concerned with the evolution of haploid organisms that reproduce asexually. In a seminal piece of work, Eigen and coauthors proposed the quasispecies model in an attempt to understand such an evolutionary process. Their work has impacted antiviral treatment and vaccine design strategies. Yet, predictions of the quasispecies model are at best viewed as a guideline, primarily because it assumes an infinite population size, whereas realistic population sizes can be quite small. In this paper we consider a population genetics-based model aimed at understanding the evolution of such organisms with finite population sizes and present a rigorous study of the convergence and computational issues that arise therein. Our first result is structural and shows that, at any time during the evolution, as the population size tends to infinity, the distribution of genomes predicted by our model converges to that predicted by the quasispecies model. This justifies the continued use of the quasispecies model to derive guidelines for intervention. While the stationary state in the quasispecies model is readily obtained, due to the explosion of the state space in our model, exact computations are prohibitive. Our second set of results are computational in nature and address this issue. We derive conditions on the parameters of evolution under which our stochastic model mixes rapidly. Further, for a class of widely used fitness landscapes we give a fast deterministic algorithm which computes the stationary distribution of our model. These computational tools are expected to serve as a framework for the modeling of strategies for the deployment of mutagenic drugs.

Effects of Withania somnifera and Tinospora cordifolia Extracts on the Side Population Phenotype of Human Epithelial Cancer Cells: Toward Targeting Multidrug Resistance in Cancer

Recent reports suggest the existence of a subpopulation of stem-like cancer cells, termed as cancer stem cells (CSCs), which bear functional and phenotypic resemblance with the adult, tissue-resident stem cells. Side population (SP) assay based on differential efflux of Hoechst 33342 has been effectively used for the isolation of CSCs. The drug resistance properties of SP cells are typically due to the increased expression of ABC transporters leading to drug efflux. Conventionally used chemotherapeutic drugs may often leads to an enrichment of SP, revealing their inability to target the drug-resistant SP and CSCs. Thus, identification of agents that can reduce the SP phenotype is currently in vogue in cancer therapeutics. Withania somnifera (WS) and Tinospora cordifolia (TC) have been used in Ayurveda for treating various diseases, including cancer. In the current study, we have investigated the effects of ethanolic (ET) extracts of WS and TC on the cancer SP phenotype. Interestingly, we found significant decrease in SP on treatment with TC-ET, but not with WS-ET. The SP-inhibitory TC-ET was further fractionated into petroleum ether (TC-PET), dichloromethane (TC-DCM), and n-butyl alcohol (TC-nBT) fractions using bioactivity-guided fractionation. Our data revealed that TC-PET and TC-DCM, but not TC-nBT, significantly inhibited SP in a dose-dependent manner. Furthermore, flow cytometry-based functional assays revealed that TC-PET and TC-DCM significantly inhibited ABC-B1 and ABC-G2 transporters and sensitized cancer cells toward chemotherapeutic drug-mediated cytotoxicity. Thus, the TC-PET and TC-DCM may harbor phytochemicals with the potential to reverse the drug-resistant phenotype, thus improving the efficacy of cancer chemotherapy.

Does size matter? Comparative population genetics of two butterflies with different wingspans

The dispersal ability of a species is central to its biology, affecting other processes like local adaptation, population and community dynamics, and genetic structure. Among the intrinsic, species-specific factors that affect dispersal ability in butterflies, wingspan was recently shown to explain a high amount of variance in dispersal ability. In this study, a comparative approach was adopted to test whether a difference in wingspan translates into a difference in population genetic structure. Two closely related butterfly species from subfamily Satyrinae, family Nymphalidae, which are similar with respect to all traits that affect dispersal ability except for wingspan, were studied. Melanitis leda (wingspan 60-80 mm) and Ypthima baldus (wingspan 30-40 mm) were collected from the same areas along the Western Ghats of southern India. Amplified fragment length polymorphisms were used to test whether the species with a higher wingspan (M. leda) exhibited a more homogenous population genetic structure, as compared to a species with a shorter wingspan (Y. baldus). In all analyses, Y. baldus exhibited greater degree of population genetic structuring. This study is one of the few adopting a comparative approach to establish the relationship between traits that affect dispersal ability and population genetic structure.

Population Recovery of Nicobar Long-Tailed Macaque Macaca fascicularis umbrosus following a Tsunami in the Nicobar Islands, India

Natural disasters pose a threat to isolated populations of species with restricted distributions, especially those inhabiting islands. The Nicobar long tailed macaque. Macaca fascicularis umbrosus, is one such species found in the three southernmost islands (viz. Great Nicobar, Little Nicobar and Katchal) of the Andaman and Nicobar archipelago, India. These islands were hit by a massive tsunami (Indian Ocean tsunami, 26 December 2004) after a 9.2 magnitude earthquake. Earlier studies Umapathy et al. 2003; Sivakumar, 2004] reported a sharp decline in the population of M. f. umbrosus after thetsunami. We studied the distribution and population status of M. f. umbrosus on thethree Nicobar Islands and compared our results with those of the previous studies. We carried out trail surveys on existing paths and trails on three islands to get encounter rate as measure of abundance. We also checked the degree of inundation due to tsunami by using Normalized Difference Water Index (NDWI) on landsat imageries of the study area before and after tsunami. Theencounter rate of groups per kilometre of M. f. umbrosus in Great Nicobar, Little Nicobar and Katchal was 0.30, 0.35 and 0.48 respectively with the mean group size of 39 in Great Nicobar and 43 in Katchal following the tsunami. This was higher than that reported in the two earlier studies conducted before and after the tsunami. Post tsunami, there was a significant change in the proportion of adult males, adult females and immatures, but mean group size did not differ as compared to pre tsunami. The results show that population has recovered from a drastic decline caused by tsunami, but it cannot be ascertained whether it has reached stability because of the altered group structure. This study demonstrates the effect of natural disasters on island occurring species.

Population Characteristics of Largemouth Bass Associated with Changes in Abundance of Submersed Aquatic Vegetation in Lake Seminole, Georgia

Population characteristics of largemouth bass ( Micropterus salmoides L.) including growth, body condition (relative weight), survival, and egg production were examined in relation to abundance of submersed aquatic vegetation (SAV) coverage (primarily hydrilla [ Hydrilla verticillata L.f. Royle]) in three embayments of Lake Seminole, GA, and compared to a previous study conducted in 1998. (PDF has 8 pages.)

Population Dynamics of Cyrtobagous salviniae on Common Salvinia in South Florida

Common salvinia (Salvinia minima Baker) is an exotic floating fern that has been in the U.S. from at least 1928(Small 1931). Its pest status in Florida is less clear perhaps due to the presence of the specialized herbivore Cyrtobagous salviniae (Coleoptera: Curculionidae). Our objective was to sample populations of adult C. salviniae in south Florida in order to assess temporal abundance and estimate density on common salvinia. (PDF has 4 pages.)

Do tissue carbon and nitrogen limit population growth of weevils introduced to control waterhyacinth at a site in the Sacramento-San Joaquin Delta, California?

Waterhyacinth (Eichhornia crassipes(Mart.) Solms), is a serious problem in the Sacramento Delta. Two weevil species (Neochetina bruchi Hustache and N. eichhorniae Warner) have been introduced as biological control agents. The purpose of this study was to test the hypothesis that nitrogen (N) in the tissue of waterhyacinth was not sufficient to support weevil growth and reproduction. Because it grows better on plants with high N content and because it has a greater impact on the growth of high N plants, N. bruchi may be a more effective biological control agent in the Sacramento Delta.

Population response of triploid grass carp to declining levels of hydrilla in the Santee Cooper Reservoirs, South Carolina

Approximately 768,500 triploid grass carp ( Ctenopharyngodon idella Valenciennes) were stocked into the Santee Cooper reservoirs, South Carolina between 1989 and 1996 to control hydrilla ( Hydrilla verticillata (L.f.) Royle). Hydrilla coverage was reduced from a high of 17,272 ha during 1994 to a few ha by 1998. During 1997, 1998 and 1999, at least 98 triploid grass carp were collected yearly for population monitoring. Estimates of age, growth, and mortality, as well as population models, were used in the study to monitor triploid grass carp and predict population trends. Condition declined from that measured during a previous study in 1994. The annual mortality rate was estimated at 28% in 1997, 32% in 1998 and 39% in 1999; however, only the 1999 mortality rate was significantly different. Few (2 out of 98) of the triploid grass carp collected during 1999 were older than age 9. We expect increased mortality due to an aging population and sparse hydrilla coverage. During 1999, we estimated about 63,000 triploid grass carp system wide and project less than 3,000 fish by 2004, assuming no future stocking. management, population size Ctenopharyngodon idella, Hydrilla

Toxic pollutants, health indices and population dynamics of Harbor Seals in San Francisco Bay, 1989-1992

(PDF contains 300 pages)

Population assessment of two stocks of white grunt, Haemulon plumieri, from the southeastern coast of the United States

Changes in the age structure and population size of white grunt, Haemulon plumieri, from North Carolina through the Florida Keys were examined using records of landings and size frequencies of fish from commercial, re~reational, and headboat fisheries from 1986-1998. Data were stratified into two geographical areas: North Carolina and South Carolina; and southeast Florida. Population size in numbers at age was estimated for each year and geographical area by applying an uncalibrated separable virtual population analysis (SVPA) to the landings in numbers at age. A calibrated virtual population analysis, FADAPT, was also run for data from North Carolina and South Carolina. SVPA and FADAPT were used to estimate annual, age-specific fishing mortality (F) for four levels of natural mortality (M = 0.20, 0.25, 0.30, and 0.35). The best estimate of M for white grunt is 0.30. Landings of white grunt in the Carolinas for the three fisheries have generally decreased in recent years, but have held fairly steady for the species in southeast Florida. Age at entry and age at full recruitment were age-1 and age-4 for the Carolinas, and age-l and age-3 for southeast Florida. With M = 0.30, levels of fishing mortality (F) on the fully-recruited ages were 0.23 for the Carolinas and 0.33 for southeast Florida. Spawning potential ratio (SPR) at M = 0.30 was 57% for the Carolinas and 61% for southeast Florida, which indicates that the species, by definition, has not been over-exploited by fishing. The results of this assessment of the white grunt population off the Carolinas agree with the recent F/FMSY analysis of white grunt (Anonymous, 1999). (PDF contaons 72 pages)

Population assessment of the vermilion snapper, Rhomboplites aurorubens, from the Southeastern United States

Changes in the age structure and population size of vermilion snapper, Rhornboplites aurorubens, from North Carolina through the Florida Keys were examined using records of landings and size frequencies of fish from commercial, recreational, and headboat fisheries from 1986-1996. Population size in numbers at age was estimated for each year by applying separable virtual population analysis (SVPA) to the landings in numbers at age. SVPA was used to estimate annual, age-specific fishing mortality (F) for four levels of natural mortality (M = 0.20, 0.25, 0.30, and 0.35). Although landings of vermilion snapper for the three fisheries have declined, minimum fish size regulations have resulted in an increase in the mean size of fish landed. Age at entry and age at full recruitment were age-1 andage-3 fDr 1986-1991, compared with age-1 and age-4, respectively, for 1992-1996. Levels of mortality from fishing (F) ranged from 0.38 - 0.61 for the entire period. Current spawning potential ratio (SPR) is 21% or 27% depending on the natural mortality estimate. SPR could be raised to 30% or 40% with a reduction in F, or by increasing the age at entry to the fisheries. The latter could be enhanced now if fishermen, particularly recreational, comply with minimum size regulations. However, released fish mortality, modeled in the assessment at 27%, will continue to make the achievement of 30% and 40% SPR more difficult. (PDF contains 63 pages)

Population characteristics of gulf menhaden, Brevoortia patronus

The status of the Gulf menhaden, Brevoortia patronus, fishery was assessed with purse-seine landings data from 1946 to 1997 and port sampling data from 1964 to 1997. These data were analyzed to determine growth rates, biological reference points for fi shing mortality from yield per recruit and maximum spawning potential analyses, spawner-recruit relationships, and maximum sustainable yield (MSY). The separable virtual population approach was used for the period 1976–97 (augmented by earlier analyses for 1964–75) to obtain point estimates of stock size, recruits to age 1, spawning stock size, and fishing mortality rates. Exploitation rates for age-1 fi sh ranged between 11% and 45%, for age-2 fi sh between 32% and 72%, and for age-3 fi sh between 32% and 76%. Biological reference points from yield per recruit (F0.1: 1.5–2.5/yr) and spawning potential ratio (F20: 1.3–1.9/yr and F30: 0.8–1.2/yr) were obtained for comparison with recent estimates of F (0.6–0.8/yr). Recent spawning stock estimates (as biomass or eggs) are above the long-term average, while recent recruits to age 1 are comparable to the long-term average. Parameters from Ricker-type spawner-recruit relations were estimated, although considerable unexplained variability remained. Recent survival to age-1 recruitment has generally been below that expected based on the Ricker spawner-recruit relation. Estimates of long-term MSY from PRODFIT and ASPIC estimation of production model ranged between 717,000 t and 753,000 t, respectively. Declines in landings between 1988 and 1992 raised concerns about the status of the Gulf menhaden stock. Landings have fl uctuated without trend since 1992, averaging about 571,000 t. However, Gulf menhaden are short lived and highly fecund. Thus, variation in recruitment to age 1, largely mediated by environmental conditions, infl uences fi shing success over the next two years (as age-1 and age-2 fi sh). Comparisons of recent estimates of fi shing mortality to biological reference points do not suggest overfishing. (PDF file contains 22 pages.)