Changing temporal trends in non-AIDS cancer mortality among people diagnosed with AIDS: San Francisco,California, 1996–2013

BackgroundAntiretroviral therapy (ART) has reduced AIDS-defining cancer (ADC) mortality, but its effect on non-AIDS-defining cancer (NADC) mortality is unclear. To help inform cancer prevention and screening, we evaluated trends in NADC mortality among people with AIDS (PWA) in the ART era.MethodsThis retrospective cohort study analyzed AIDS surveillance data, including causes of death from death certificates, for PWA in San Francisco who died in 1996–2013. Proportional mortality ratios (PMRs), and year, age, race, sex-adjusted standardized mortality ratios (SMRs) were calculated for 1996–1999, 2000–2005, and 2006–2013, corresponding to advances in ART.ResultsThe study included 5822 deceased PWA of whom 90% were male and 68% were aged 35–54 at time of death. Over time, the PMRs significantly decreased for ADCs (2.6%, 1.4%, 1.2%) and increased for NADCs (4.3%, 7.0%, 12.3%). For all years combined (1996–2013) and compared to the California population, significantly elevated SMRs were observed for these cancers: all NADCs combined (2.1), anal (58.4), Hodgkin lymphoma (10.5), liver (5.2), lung/larynx (3.0), rectal (5.2), and tongue (4.7). Over time, the SMRs for liver cancer (SMR 19.8, 11.2, 5.0) significantly decreased while the SMRs remained significantly elevated over population levels for anal (SMR 123, 48.2, 45.5), liver (SMR 19.8, 11.2, 5.0), and lung/larynx cancer (SMR 5.3, 4.7, 3.6).ConclusionA decline in ADC PMRs and increase in NADC PMRs represent a shift in the cancer burden, likely due to ART use. Moreover, given their elevated SMRs, anal, liver, and lung/larynx cancer remain targets for improved cancer prevention, screening, and treatment.     

Nonparametric Evaluations of Familial Aggregation

Limitations of detection of familial aggregation, examined by nonparametric aggregate measures (e.g., SMR), or by parametric methods (e.g., segregation analysis) may involve: (1) heterogeneity of risk patterns in different kindreds, or (2) restricted choice of parametric models. Nonparametric approaches dealing with individual kindreds, on the contrary, involve sparce data for which large sample theory may not apply. When the expected risk schedules of individuals are known, some optimal test procedures may be developed. Nevertheless, the optimality criteria are shown to be satisfied for only restricted choice of alternatives, and large sample approximation are not warranted in analysis of individual kindreds. Truncations of points of entry and exit of individuals in the study are needed to avoid complications due to loss of followup, in presence of which expected risk calculations are not reliable. Covariances of components of a goodness-of-fit test criterion detect specific modes of aggregation. It is illustrated that this test statistic is not always less powerful than the aggregate measures in detecting aggregation, and the covariances of its components partitioned by relative classes are in conformity with the results of segregation analysis.     

The risk of cancer development in systemic sclerosis: A meta-analysis

Objectives: Systemic sclerosis is a multi-system disorder of connective tissue characterized by Raynaud's phenomenon and fibrosis of various organs. The risk of development of cancer in systemic sclerosis (SSc) has been extensively investigated with inconclusive results. To shed some light on the controversy, we conducted a meta-analysis of all published articles linking SSc to the risk of cancer development. Methods: Relevant electronic databases were searched for English-language studies characterizing the association of cancers in patients with SSc. Standardized incidence rate (SIR) with its 95% confidence interval (CI) of each study was combined using a fixed/random effect model. Results: A total of seven papers including 7183 SSc patients were identified, of which 7 reported the SIR for lung cancer, 4 for non-Hodgkin's lymphoma (NHL) and 4 for hematopoietic cancer and 7 for breast cancer. Compared with the general population, the combined SIR was 3.14 (95% CI: 2.02–4.89), 2.68 (95% CI: 1.58–4.56), 2.57 (95% CI: 1.79–3.68) and 1.09 (95% CI: 0.86–1.38), respectively. Significant heterogeneity was observed in lung cancer group (Q = 26.13, P < 0.001, I² = 77%). Potential publication bias was absent. Conclusions: This present meta-analysis demonstrated an increased risk of lung, non-Hodgkin's lymphoma and hematopoietic cancers among patients with SSc, but not for breast cancer. However, some of the available data were several decades old, and future studies taking new treatment strategies into account are required.     

Suicides among cancer patients in Lithuania: A population-based census-linked study

Background: This study aims to estimate suicide risk and its socio-demographic determinants among cancer patients in the country showing the highest suicide rates among developed countries. Methods: The study is based on a unique census-linked dataset based on the linkages between the records from death and cancer registers and the 2001 population census records. Standardized mortality ratios for suicide (SMRs) were calculated for patients diagnosed with cancer in Lithuania between April 6, 2001 and December 31, 2009, relative to suicide rates in the general population. Results: We found that the relative suicide risk was elevated for both males and females, with SMRs of 1.43 (95% CI 1.23–1.66) and 1.32 (95% CI 0.95–1.80), respectively. This relationship for females became statistically significant and stronger after excluding skin cancers. The highest suicide risks were observed at older ages and during the period shortly after the diagnosis. The groups showing an increased suicide risk include lower educated, non-married, and rural male patients. Conclusion: The results of our study point to inadequacies of the health care system in dealing with mental health problems of cancer patients. Interventions allowing early detection of depression or suicidal ideation may help to prevent suicide among cancer patients in Lithuania.     

Computing numerically the access resistance of a pore

The access resistance (AR) of a channel is an important component of the conductance of ion channels, particularly in wide and short channels, where it accounts for a substantial fraction of the total resistance to the movement of ions. The AR is usually calculated by using a classical and simple expression derived by Hall from electrostatics (J.E. Hall 1975 J. Gen. Phys. 66:531-532), though other expressions, both analytical and numerical, have been proposed. Here we report some numerical results for the AR of a channel obtained by solving the Poisson-Nernst-Planck equations at the entrance of a circular pore. Agreement is found between numerical calculations and analytical results from Hall's equation for uncharged pores in neutral membranes. However, for channels embedded in charged membranes, Hall's expression overestimates the AR, which is much lower and can even be neglected in some cases. The weak dependence of AR on the pore radius for charged membranes at low salt concentration can be exploited to separate the channel and the access contributions to the measured conductance.     

Electrostatics of Cytochrome-c assemblies

Electrostatic potentials along with computational mutagenesis are used to obtain atomic level insights into Cytochrome-c in order to design efficient bionanosensors. The electrostatic properties of wild type and mutant Cytochrome-c are examined in the context of their assembly, i.e. are examined in the absence and presence of neighboring molecules from the assembly. An intense increase in the positive potential ensues when the neighboring molecules are taken into account. This suggests that in the extrapolation of electric field effects upon the design of assemblies, considering the properties of only the central molecule may not be sufficient. Additionally, the influence of the uncharged residues becomes quite diminished when the molecule is considered in an assembly. This could pave the way for making mutants that might be more soluble in different media used in the construction of devices.FigureThe electrostatic potential, calculated using the program DELPHI [20] mapped on to the surface of Cytochrome-c when it is considered by itself (in the left column) and in the presence of the electrostatic field generated by the presence of the surrounding 4 molecules on the right (see Fig. 3). The potentials range from –10kT in red to +10kT in blue. The central figure shows the regions that have been mutated to positively charged residues by placing a unit positive charge at the terminal atom of the respective side chain. The figures range from the wild type in the first row, followed by the Gln12, Asn70, Asp50, Glu90 and Ala83 mutants.     

广西地区脑血管病城乡抽样对比分析

本文着重分析了广西城市和农村脑血管病发病情况的差异。我们发现城市CVD发病率、患病率明显高于农村,但是农村CVD的死亡率高于城市,其中我们对其原因作了初步的探讨。     

Kinetic study of racemization of aspartyl residues in synthetic elastin peptides

Summary. We previously reported that biologically uncommon D-aspartyl residues are present in sun-damaged skin from elderly people, possibly in elastin. Here, we report the kinetics of Asp racemization in model peptides corresponding to elastin sequences from exons 6 and 26. We estimated the activation energy (E) of racemization of Asp residues, the racemization rates (RR) at 37°C and the time (t) required for the D/L ratio of Asp to approximate to 1.0 (D/L ratio of Asp=0.99) at 37°C. For an exon 6 peptide, E=29.0kcal/mol, RR=2.59×10^–2/yr and t=101.0yr. For an exon 26A peptide E=26.2kcal/mol, RR=4.27×10^–2/yr and t=61.3yr; and for a second exon 26A peptide E=25.7kcal/mol, RR=5.55×10^–2/yr and t=47.0yr. These results suggest that racemization of Asp residues in elastin could occur within a human life span. We propose that D-Asp could be a useful molecular indicators of aging.     

Models for integrated pest control and their biological implications

Successful integrated pest management (IPM) control programmes depend on many factors which include host-parasitoid ratios, starting densities, timings of parasitoid releases, dosages and timings of insecticide applications and levels of host-feeding and parasitism. Mathematical models can help us to clarify and predict the effects of such factors on the stability of host-parasitoid systems, which we illustrate here by extending the classical continuous and discrete host-parasitoid models to include an IPM control programme. The results indicate that one of three control methods can maintain the host level below the economic threshold (ET) in relation to different ET levels, initial densities of host and parasitoid populations and host-parasitoid ratios. The effects of host intrinsic growth rate and parasitoid searching efficiency on host mean outbreak period can be calculated numerically from the models presented. The instantaneous pest killing rate of an insecticide application is also estimated from the models. The results imply that the modelling methods described can help in the design of appropriate control strategies and assist management decision-making. The results also indicate that a high initial density of parasitoids (such as in inundative releases) and high parasitoid inter-generational survival rates will lead to more frequent host outbreaks and, therefore, greater economic damage. The biological implications of this counter intuitive result are discussed.     

Simulating the SARS outbreak in Beijing with limited data

We propose a mathematical model to simulate the SARS outbreak in Beijing. The model consists of six subpopulations, namely susceptible, exposed, quarantined, suspect, probable and removed, as China started to report SARS cases as suspect and probable separately from April 27 and cases transferred from suspect class to probable class from May 2. By simplifying the model to a two-compartment suspect-probable model and a single-compartment probable model and using limited data, we are able to simulate the SARS outbreak in Beijing. We estimate that the reproduction number varies from 1.0698 to 3.2524 and obtain certain important epidemiological parameters.     

Combining capture–recapture data and pedigree information to assess heritability of demographic parameters in the wild

Quantitative genetic analyses have been increasingly used to estimate the genetic basis of life‐history traits in natural populations. Imperfect detection of individuals is inherent to studies that monitor populations in the wild, yet it is seldom accounted for by quantitative genetic studies, perhaps leading to flawed inference. To facilitate the inclusion of imperfect detection of individuals in such studies, we develop a method to estimate additive genetic variance and assess heritability for binary traits such as survival, using capture–recapture (CR) data. Our approach combines mixed‐effects CR models with a threshold model to incorporate discrete data in a standard ‘animal model’ approach. We employ Markov chain Monte Carlo sampling in a Bayesian framework to estimate model parameters. We illustrate our approach using data from a wild population of blue tits (Cyanistes caeruleus) and present the first estimate of heritability of adult survival in the wild. In agreement with the prediction that selection should deplete additive genetic variance in fitness, we found that survival had low heritability. Because the detection process is incorporated, capture–recapture animal models (CRAM) provide unbiased quantitative genetics analyses of longitudinal data collected in the wild.     

Tumor necrosis factor-alpha in serum of macaques during SIVmac251 acute infection

TNF secretion was explored in sera during acute SIV-infection of cynomolgus macaques. A peak of TNF was detected in sera of animals in concomitance with SIV replication. Likewise, AZT treatment delayed and reduced peaks of viral replication and TNF production. Thus, SIVmac251-infected monkey could be an excellent model to explore the interdigitation existing between HIV and TNF in acute and chronic infection and to develop new therapeutic strategies that target the production of this cytokine or its inductive effects.