Calculation of Disease Dynamics in a Population of Households

Early mathematical representations of infectious disease dynamics assumed a single, large, homogeneously mixing population. Over the past decade there has been growing interest in models consisting of multiple smaller subpopulations (households, workplaces, schools, communities), with the natural assumption of strong homogeneous mixing within each subpopulation, and weaker transmission between subpopulations. Here we consider a model of SIRS (susceptible-infectious-recovered-susceptible) infection dynamics in a very large (assumed infinite) population of households, with the simplifying assumption that each household is of the same size (although all methods may be extended to a population with a heterogeneous distribution of household sizes). For this households model we present efficient methods for studying several quantities of epidemiological interest: (i) the threshold for invasion; (ii) the early growth rate; (iii) the household offspring distribution; (iv) the endemic prevalence of infection; and (v) the transient dynamics of the process. We utilize these methods to explore a wide region of parameter space appropriate for human infectious diseases. We then extend these results to consider the effects of more realistic gamma-distributed infectious periods. We discuss how all these results differ from standard homogeneous-mixing models and assess the implications for the invasion, transmission and persistence of infection. The computational efficiency of the methodology presented here will hopefully aid in the parameterisation of structured models and in the evaluation of appropriate responses for future disease outbreaks.     

Dynamics and persistence of Dead Sea microbial populations as shown by high-throughput sequencing of rRNA

16S rRNA amplicon libraries from a haloarchaeal bloom in the hypersaline Dead Sea in 1992 were analyzed together with the 2007 residual population and simulated blooms in experimental mesocosms. Significant population shifts were observed during the bloom, and surprisingly a signature from the bloom was retained 15 years later.     

Geobiological analysis using whole genome-based tree building applied to the Bacteria, Archaea, and Eukarya

We constructed genomic trees based on the presence and absence of families of protein‐encoding genes observed in 55 prokaryotic and five eukaryotic genomes. There are features of the genomic trees that are not congruent with typical rRNA phylogenetic trees. In the bacteria, for example, Deinococcus radiodurans associates with the Gram‐positive bacteria, a result that is also seen in some other phylogenetic studies using whole genome data. In the Archaea, the methanogens plus Archaeoglobus form a united clade and the Euryarchaeota are divided with the two Thermoplasma genomes and Halobacterium sp. falling below the Crenarchaeota. While the former appears to be an accurate representation of methanogen‐relatedness, the misplacement of Halobacterium may be an artefact of parsimony. These results imply the last common ancestor of the Archaea was not a methanogen, leaving sulphur reduction as the most geochemically plausible metabolism for the base of the archaeal crown group. It also suggests that methanogens were not a component of the Earth's earliest biosphere and that their origin occurred sometime during the Archean. In the Eukarya, the parsimony analysis of five Eukaryotes using the Crenarchaeota as an outgroup seems to counter the Ecdysozoa hypothesis, placing Caenorhabditis elegans (Nematoda) below the common ancestor of Drosophila melanogaster (Arthropoda) and Homo sapiens (Chordata) even when efforts are made to counter the possible effects of a faster rate of sequence evolution for the C. elegans genome. Further analysis, however, suggests that the gene loss of ‘animal’ genes is highest in C. elegans and is obscuring the relationships of these organisms.     

Simultaneous determination of 5-fluorouracil and uracil by high-performance liquid chromatography using four serial columns

A sensitive assay was developed for the quantitation of 5-fluorouracil (5-FU) and uracil using liquid–liquid extraction (LLE) and HPLC with UV detection. Analyses were performed with four μBondapak C₁₈ columns connected in series using 20 mM acetic acid with 1% ACN as mobile phase. The calibration curves were linear across the range of 26–1000 ng ml⁻¹ (0.21–7.8 μM) for 5-FU and 1.0–14.0 μg ml⁻¹ (0.01–110 μM) for uracil. This assay has been implemented to determine the plasma concentrations for pharmacokinetic studies for 5-FU and uracil in conjunction with clinical trials.     

Nonbinomial distributions of relative neurite outgrowth in PC-12 cells

Previously we reported the results of a series of experimental tests using PC-12 cells to examine the biological effects of prescribed combinations of both nerve growth factor and magnetic fields. Because our assay of the PC-12 cells is based on a binary classification of the cells following treatment, our data might be expected to have a binomial distribution. However, our data consistently show a smaller variability than that predicted by the binomial distribution model. In this paper, we examine some possible reasons for this reduction in variability in our results. © 1996 Wiley-Liss, Inc.     

Deliberate self harm: systematic review of efficacy of psychosocial and pharmacological treatments in preventing repetition

Objective: To identify and synthesise the findings from all randomised controlled trials that have examined the effectiveness of treatments of patients who have deliberately harmed themselves. Design: Systematic review of randomised controlled trials of psychosocial and physical treatments. Studies categorised according to type of treatment. When there was more than one investigation in a particular category a summary odds ratio was estimated with the Mantel-Haenszel method. Setting: Randomised trials available in electronic databases in 1996, in the Cochrane Controlled Trials Register in 1997, and from hand searching of journals to 1997. Subjects: Patients who had deliberately harmed themselves shortly before entry into the trials with information on repetition of behaviour. The included trials comprised 2452 randomised participants with outcome data. Main outcome measure: Repetition of self harm. Results: 20 trials reported repetition of self harm as an outcome variable, classified into 10 categories. Summary odds ratio (all for comparison with standard aftercare) indicated reduced repetition for problem solving therapy (0.73; 95% confidence interval 0.45 to 1.18) and for provision of an emergency contact card in addition to standard care (0.45; 0.19 to 1.07). The summary odds ratios were 0.83 (0.61 to 1.14) for trials of intensive aftercare plus outreach and 1.19 (0.53 to 2.67) for antidepressant treatment compared with placebo. Significantly reduced rates of further self harm were observed for depot flupenthixol versus placebo in multiple repeaters (0.09; 0.02 to 0.50) and for dialectical behaviour therapy versus standard aftercare (0.24; 0.06 to 0.93). Conclusion: There remains considerable uncertainty about which forms of psychosocial and physical treatments of patients who harm themselves are most effective. Further larger trials of treatments are needed.

Key messages

• A systematic review of the effectiveness of psychosocial and drug treatments of patients who deliberately harm themselves identified 20 randomised controlled trials in which repetition of self harm was reported as an outcome
• Promising results were found for problem solving therapy, provision of a card to allow patients to make emergency contact with services, depot flupenthixol for recurrent self harm, and long term psychological therapy for female patients with borderline personality disorder and recurrent self harm
• Assertive outreach can help to keep patients in treatment
• Nearly all the trials included too few patients to detect clinically significant differences in repetition of self harm, and even synthesis of results by meta-analysis did not have the power to detect such differences
• There is an urgent need for large trials of promising therapies for this substantial clinical population

     

Sedimentary and faunal changes across the frasnian/famennian boundary in the canning basin of Western Australia

The Canning Basin of northwestern Australia is a key area for understanding global changes at the “Kellwasser Events” and the Frasnian‐Famennian boundary. Frasnian stromatoporoid‐coral‐cyanobacterial reef platforms stretched out for enormous distances along the palaeoshelf but in the early Famennian they were completely replaced by cyanobacterial reef platforms. An iridium anomaly in the sequence was formerly believed to be at or close to the boundary and was interpreted as possible evidence for an asteroid impact. Recent field work and detailed biostratigraphy in the area east and southeast of Fitzroy Crossing has given dating relevant to the timing and extent of sea level changes, hypoxic incursions and reef backstepping. Goniatites and conodonts provide correlations with the international biostratigraphy.

In the Horse Spring area the stage boundary falls within the Virgin Hills Formation which normally has a rich pelagic goniatite, nautiloid and conodont fauna. In the latest Frasnian (Zone 13 of Klapper 1989; regional Sphaeromanticoceras lindneri Zone) large allochthonous reef blocks moved downslope into the open marine basin. A diverse gastropod fauna is associated with the last atrypid brachiopods. The faunal record at the immediate boundary is obscured by dolomitisation but manticoceratid goniatites range into this level. There is no evidence for the organic‐rich dark Kellwasser limestone facies.

In the McWhae Ridge area two Frasnian goniatite horizons with Beloceras trilobites and the giant Mamicoceras guppyi and Sphaeromanticoceras lindneri transgress over the reef slope. Stromatolitic cyanobacterial beds mark condensations. Again there is no trace of the oxygen‐depleted Kellwasser facies. However, as at Horse Spring, manticoceratids persisted into dolomitic marker beds that have no other preserved macrofauna. The iridium anomaly associated with Frutexites postdates the Frasnian‐Famennian boundary and was formed by cyanobacterial concentration.     

Unsymmetric nonpeptidic HIV protease inhibitors containing anthranilamide as a P2′ ligand

A series of novel unsymmetrical anthranilamide-containing HIV protease inhibitors was designed. The structure-activity studies revealed a series of potent P2–P3′ inhibitors that incorporate an anthranilamide group at the P2′ position. A reduction in molecular weight and lipophilicity is achieved by a judicious choice of P2 ligands (i.e., aromatic, heteroaromatic, carbamate, and peptidic). A systematic investigation led to the 5-thiazolyl carbamate analog 8m, which exhibited a favorable C_max/EC₅₀ ratio (>30), plasma half-life (>8 h), and potent in vitro antiviral activity (EC₅₀ = 0.2 uM).     

Effects of surfactant adsorption and biodegradability on the distribution of bacteria between sediments and water in a freshwater microcosm.

A microcosm containing resuspended river sediment was used to investigate the effect of anionic surfactants on the distribution of bacteria between planktonic and attached populations. Freshwater river sediment containing viable bacteria was preequilibrated in the microcosm, which was subsequently supplemented with biodegradable or recalcitrant surfactants and a non-surface-active carbon and energy source. Population dynamics of both free-living and attached bacteria were measured by epifluorescence microscopy with simultaneous analysis of the residual solution concentration of the xenobiotic carbon source. The addition of the readily biodegradable anionic surfactants sodium decyl sulfate and sodium dodecyl sulfate in separate experiments caused an increase in the number of attached bacteria and a concomitant decrease in the number of free-living bacteria. As biodegradation of the surfactants progressed, these trends reversed and the bacterial populations had returned to their preaddition values by the time when biodegradation was completed. In contrast, sodium tetradecyl sulfate or sodium dodecane sulfonate did not stimulate bacterial association with sediment, nor were they biodegraded in the microcosm. Sodium pyruvate, a non-surface-active carbon and energy source, was readily utilized but caused no bacterial attachment to the sediment. These results indicate that for an anionic surfactant to induce bacterial attachment to river sediment, it must be biodegradable. The bacterial attachment to the sediment appears to be reversible and may be dependent on the accumulation of the surfactant at the surface or as a result of alteration of the surface free energies.