Regression analysis of longitudinal binary data with time-dependent environmental covariates: bias and efficiency

Generalized estimating equations (Liang and Zeger, 1986) is a widely used, moment-based procedure to estimate marginal regression parameters. However, a subtle and often overlooked point is that valid inference requires the mean for the response at time t to be expressed properly as a function of the complete past, present, and future values of any time-varying covariate. For example, with environmental exposures it may be necessary to express the response as a function of multiple lagged values of the covariate series. Despite the fact that multiple lagged covariates may be predictive of outcomes, researchers often focus interest on parameters in a 'cross-sectional' model, where the response is expressed as a function of a single lag in the covariate series. Cross-sectional models yield parameters with simple interpretations and avoid issues of collinearity associated with multiple lagged values of a covariate. Pepe and Anderson (1994), showed that parameter estimates for time-varying covariates may be biased unless the mean, given all past, present, and future covariate values, is equal to the cross-sectional mean or unless independence estimating equations are used. Although working independence avoids potential bias, many authors have shown that a poor choice for the response correlation model can lead to highly inefficient parameter estimates. The purpose of this paper is to study the bias-efficiency trade-off associated with working correlation choices for application with binary response data. We investigate data characteristics or design features (e.g. cluster size, overall response association, functional form of the response association, covariate distribution, and others) that influence the small and large sample characteristics of parameter estimates obtained from several different weighting schemes or equivalently 'working' covariance models. We find that the impact of covariance model choice depends highly on the specific structure of the data features, and that key aspects should be examined before choosing a weighting scheme.     

Phenotypic and evolutionary plasticity of organ masses in response to voluntary exercise in house mice

We used a novel mouse model to study the effects of selectivebreeding for high locomotor activity (14 generations) on relativeorgan sizes, hematocrit (Hct), and blood hemoglobin (Hb) concentration.We also examined effects of exercise training and genotype-by-environmentinteractions by housing animals for 8 weeks with wheels thatwere either free to rotate or locked. Mice from the four replicateHigh-Runner (HR) lines were smaller in total body mass but hadlarger body mass-adjusted kidneys relative to the four Controllines (P < 0.05). Control and HR lines did not differ significantlyfor mass-adjusted tail length or masses of the "triceps surae"hindlimb muscle group, heart (ventricle), spleen, liver, adrenalglands or gonads. Wheel access caused a reduction in body massand an increase in relative heart mass. In females only, wheelaccess caused a reduction in relative spleen mass. Wheel accessdid not affect relative tail length or relative mass of thetriceps surae, liver, adrenal gland or gonads. Significant interactionsbetween selection history and wheel access were observed infemales for spleen, liver, and gonad mass as well as Hct andHb. Wheel access caused increases in both Hct and Hb, mainlyin the HR lines. The mini-muscle phenotype, caused by a Mendelianrecessive allele that halves hindlimb muscle mass, was significantlyassociated with several other body composition traits, includingreduced body mass, increased tail length, increased heart mass,increased liver mass (females only), increased mean adrenalgland mass (females only), increased mean kidney mass (malesonly), and reduced Hct (wheel-access females only). Resultsare discussed in context of the beneficial acclimation hypothesis,genotype-by-environment interactions, and the potential for"nurture" to be self-reinforcing of "nature" in some complexbehavioral-physiological phenotypes.     

Taste, salience, and increased NaCl ingestion after repeated sodium depletions

Previous studies have shown that repeated sodium depletions using the natriuretic-diuretic furosemide induce progressive increases in NaCl ingestion. We investigated the role of taste in this behavioral sensitization in Sprague-Dawley rats using short-term lickometer testing along with 2-h stimulated intake tests. Our results show maximal licking across a range of NaCl concentrations after each of the three depletions, regardless of whether the solutions contained sucrose or were presented alone. Similarly, the presence of sucrose did not affect stimulated NaCl intake in long-term tests, although ingestion of NaCl solutions increased progressively with successive depletions. Finally, both licking and ingestion returned to baseline levels during need-free conditions. These results suggest that sodium imbalance acutely increases the salience of sodium taste and thereby the likelihood of NaCl ingestion, which may, in turn, contribute to progressive increases in NaCl intake that occur with multiple furosemide-induced sodium depletions.     

Evolution of the Isd11-IscS complex reveals a single alpha-proteobacterial endosymbiosis for all eukaryotes

Giardia and Trichomonas are eukaryotes without standard mitochondria but contain mitochondrial-type alpha-proteobacterium-derived iron-sulfur cluster (ISC) assembly proteins, located to mitosomes in Giardia and hydrogenosomes in Trichomonas. Although these data suggest a single common endosymbiotic ancestry for mitochondria, mitosomes, and hydrogenosomes, separate origins are still being proposed. Here, we present a bioinformatic analysis of Isd11, a recently described essential component of the mitochondrial ISC assembly pathway. Isd11 is unique to eukaryotes but functions closely with the alpha-proteobacterium-derived cysteine desulfurase IscS. We demonstrate the presence of homologues of Isd11 in all 5 eukaryotic supergroups sampled, including hydrogenosomal and mitosomal lineages. The eukaryotic invention of Isd11 as a functional partner to IscS directly implies a single shared alpha-proteobacterial endosymbiotic ancestry for all eukaryotes. This pinpoints the alpha-proteobacterial endosymbiosis to before the last common ancestor of all eukaryotes without ambiguity.     

A Raman-scattering study on the net orientation of biomacromolecules in the outer epidermal walls of mature wheat stems (Triticum aestivum)

BACKGROUND AND AIMS: Raman spectroscopy can be used to examine the orientation of biomacromolecules using relatively thick samples of material, whereas more traditional means of analysing molecular structure require prior isolation of the components, which often destroys morphological features. In this study, Raman spectroscopy was used to examine the outer epidermal cell walls of wheat stems. METHODS: Polarized Raman spectra from the epidermal cell walls of wheat stem were obtained using near-infrared-Fourier transform Raman scattering. By comparing spectra taken with Raman light polarized perpendicular or parallel to the longitudinal axis of the cell, the orientation of macromolecules in the cell wall was investigated. KEY RESULTS: The net orientation of macromolecules varies in the epidermal cell walls of the different components of wheat stem. The net orientation of cellulose is parallel to the longitudinal axis of the cells, whereas the xylan and the phenylpropane units of lignin tend to lie perpendicular to the longitudinal axis of the cells, i.e. perpendicular to the net orientation of cellulose in the epidermal cell walls. CONCLUSIONS: The results imply that cellulose, lignin and xylan form a relatively ordered network that defines the mechanical and structural properties of the cell wall. Such results are likely to have a significant impact on the formulation of definitive models for the static and growing cell wall.     

A multi-species assessment of post-dispersal seed predation in the central Chilean Andes

BACKGROUND AND AIMS: Post-dispersal seed predation in alpine communities has received little attention despite evidence that seeds removed by granivores can decrease plant recruitment into ecosystems. Moreover, few studies have assessed the effects of removal of seeds of a range of species after dispersal on the seeds remaining in ecosystems. A comparison was made of the magnitude of seed removal by ants and birds of nine different shrubby-, herbaceous- and cushion-plant species in the central Chilean Andes in order to assess the interactions between birds, ants and wind, and the types of seeds. METHODS: A total of 324 soil-covered plates, each containing 50 seeds of one species, were placed in the field at an altitude of 2700 m and assigned to one of four treatments: control, exclusion of ants, birds, and both. The design also allowed the effects of wind to be assessed. Seed removal from plates was monitored over 20 d. KEY RESULTS: Mean accumulative seed removal by granivores averaged over all nine species combined was 25%. However, large differences between species were evident, with limited seed removal (3-11%) in three herbaceous species (Alstroemeria pallida, Sisyrinchium arenarium, Pozoa coriacea), moderate (18-33%) in five species, including a shrub (Chuquiraga oppositifolia), two herbs (Taraxacum officinale, Rhodophiala rhodolirion), and two cushion-plants (Laretia acaulis, Azorella monantha), and substantial (78%) in the shrub Anarthrophyllum cumingii. The magnitudes of losses caused by birds compared with ants did not differ for the majority of species, although removal by birds was greater than by ants in A. cumingii, and smaller for C. oppositifolia. CONCLUSIONS: Post-dispersal seed removal is shown to be an important cause of decreased potential plant species recruitment into alpine ecosystems. The substantial differences in the magnitude of seed losses to ants and birds demonstrate the need for evaluation of seed removal on a wide range of species in any given ecosystem.     

A trade-off between guerrilla and phalanx growth forms in Leymus secalinus under different nutrient supplies

BACKGROUND AND AIMS: A phalanx growth form enables clonal plants to make better use of resource-rich patches, whereas a guerrilla growth form provides them with opportunities to escape from resource-poor sites. Leymus secalinus produces both spreading (guerrilla form) and clumping ramets (phalanx form). Here, the hypothesis that a trade-off between the two growth forms in L. secalinus exists under different resource levels is tested. METHODS: Ramets of L. secalinus were grown under three levels of nutrient supply. KEY RESULTS: With increasing nutrient supply, the proportion of clumping ramets (in total number of ramets) increased, whereas that of spreading ramets decreased. With increasing nutrient supply, the number of buds increased, whereas biomass per bud decreased. A trade-off between bud number and size further supports the above hypothesis because larger buds were more likely to develop into spreading ramets, and smaller buds into clumping ramets. Mean spacer length between spreading ramets was significantly smaller under the high than under the medium nutrient supply. CONCLUSIONS: The results suggest that a trade-off between the two growth forms in L. secalinus exists under different nutrient supplies. Such a trade-off together with plasticity in spacer morphology may enable L. secalinus to make better use of small-scale heterogeneity in resource supply.     

Colocalization studies of Arp1 and p150Glued to spindle microtubules during mitosis: the effect of cytochalasin on the organization of microtubules and motor proteins in PtK1 cells

Motor proteins play a fundamental role in the congression and segregation of chromosomes in mitosis as well as the formation of the mitotic spindle. In particular, the dynein/dynactin complex is involved in the maintenance of the spindle, formation of astral microtubules, chromosome motion, and chromosome segregation. Dynactin is a multisubunit, high molecular weight protein that is responsible for the attachment of cargo to dynein. There are a number of major subunits in dynactin that are presumed to be important during mitosis. Arp1 is thought to be the attachment site for cargo to the complex while p150(Glued), a side arm of this complex regulates binding to MTs and the binding of dynactin to dynein. We performed colocalization studies of Arp1 and p150(Glued) to spindle microtubules. Both Arp1 and p150(Glued) colocalize with spindle MTs as well as cytoplasmic components. When treated with cytochalasin J, Arp1 concentrates at the centrosomes and is less co-localized with spindle MTs. Cytochalasin J has less of an effect on the colocalization of p150(Glued) with spindle MTs, suggesting that Arp1 may have a cytochalasin J sensitive site.     

Low serum PON1 activity: an independent risk factor for coronary artery disease in North-West Indian type 2 diabetics

Posttranslational modifications of proteins have profound effects on many aspects of their function and have received much attention due to the importance of these processes in epigenetic regulation. In this study, we report that deleted azoospermia associated protein 1 (DAZAP1)/proline-rich RNA binding protein (Prrp), a multifunctional RNA binding protein which is essential for spermatogenesis and normal cell growth, is acetylated at Lysine 150 within its RNA binding domain. The acetylation is predominantly observed in nuclear Prrp, and the nonacetylated form is in cytoplasm. Considering that Prrp is a shuttling protein, we suggest that the acetylation cycle at Prrp K150 regulates nucleocytoplasmic transport in cells.     

老年患者就医流向及影响因素调查研究

??????? 目的 分析老年患者就医流向的原因与因素,为合理引导老年患者适宜就医、提高医疗有效利用率、缓解医疗供需矛盾提出参考建议。方法 利用SPSS20.0描述性统计和X²检验对数据进行分析。结果 老年患者在生病时首选三级医院就医的比例最高,其次为社区卫生服务中心,二级医院比例最低。就医流向的影响因素有：年龄、医疗保障情况、文化程度、家庭平均月收入。结论 应通过加强宣教、合理引导,强化社区医疗机构服务能力建设,畅通双向转诊/转查渠道,积极推进二级医院的转型发展,来吸引老年就医群,优化老年人群就医流向,提高医疗资源的有效使用效率。