Extinction times and phase transitions for spatially structured closed epidemics

This paper considers the time to extinction for a stochastic epidemic model of SEIR form without replacement of susceptibles. It first shows how previous rigorous results can be heuristically explained in terms of the more transparent dynamics of an approximating deterministic system. The model is then extended to include a host population structured into patches, with weak nearest-neighbour mixing of infection. It is shown, by considering the approximating deterministic system, that the expected time to extinction in a population of n + 1 patches each of size N is of the form a log N + bn, provided that N > N _c where N _c is a critical patch size below which transits are unlikely to occur. This corresponds to the simple decomposition of the time of an epidemic into the time it takes to spread through one patch plus the time it takes to transit to each of n successive patches. Expressions for this threshold and the coefficients of the time to extinction are given in terms of the transmission parameters of infection and the coupling strength between patches. These expressions are compared with numerical results using parameters relevant to a study of phocine distemper virus in North Sea seals, and the agreement is found to be good for large and small N. In the region when N ≈ N _c , where transits may or may not occur, interesting transitional behaviour is seen, leading to a non-monotonicity of the extinction time as a function of N.     

The Interleukin-17 Gene of Herpesvirus Saimiri

In comparison to wild-type herpesvirus saimiri, viral interleukin-17 gene knockout mutants have unaltered behavior regarding viral replication, T-cell transformation in vitro, and pathogenicity in cottontop tamarins. Thus, this gene is not required for T-cell lymphoma induction but may contribute to apathogenic viral persistence in the natural host, the squirrel monkey.     

What factors influence primary care physicians' charges for their services? An exploratory study using standardized patients

OBJECTIVE: To determine the extent of variation in physicians'' charges for health care encounters with unannounced standardized patients and factors associated with the variation. DESIGN: Cross-sectional study. SETTING: Family practices open to new patients within 1 hour''s drive of Hamilton, Ont. PARTICIPANTS: A stratified random sample of 125 physicians who had responded to an earlier survey regarding preventive care were invited to participate. Of the 125, 44 (35.2%) declined to participate, and an additional 19 (15.2%) initially consented but later withdrew because they closed their practices to new patients. Sixty-two physicians thus participated in the study. INTERVENTION: Unannounced standardized patients posing as new patients to the practice visited study physicians'' practices between September 1994 and August 1995, portraying 4 scenarios: 28-year-old woman, 52-year-old woman, 48-year-old man and 70-year-old man. OUTCOME MEASURES: Physician characteristics, encounter characteristics and charges made for services. RESULTS: The 62 physicians had 246 encounters with the standardized patients. Charges were made to the health insurance plan for services by 59 physicians for up to 4 encounters (215 encounters in all). Charges varied considerably both within and across patient scenarios. Time spent with the patient was an important factor predicting charges made (p < 0.01), although the effect of time spent on charges varied across scenarios (p < 0.01). Fee-for-service physicians charged more for their services than physicians who usually had alternative billing arrangements (p < 0.01). Female physicians charged more for their services than their male colleagues (p = 0.03). No relation was found between quality of preventive care and charges made (p = 0.15). CONCLUSIONS: Physician-related factors are better able to account for the variability in charges for their services than patient-related factors. Physicians seeing comparable patients may earn much more or less than their colleagues because of differences in the services they provide and the way they apply the fee schedule. Quality-assurance techniques are likely needed to reduce the variability in charges seen and increase value for money spent in health care.     

Ski slope vegetation at Snoqualmie Pass, Washington State, USA, and a comparison with ski slope vegetation in temperate coniferous forest zones

Ski slope vegetation at Snoqualmie Pass in Washington State, USA, was surveyed in order to identify community types and to compare it with vegetation development patterns in Japan. Ski slopes in Japan, most of which were constructed after 1960, underwent heavy land recontouring, while those at Snoqualmie Pass were constructed before 1950 with less modification. Three points apply to Japanese ski slope vegetation and differentiate these slopes from those at Snoqualmie Pass: (i) grasslands of introduced species are widespread and persistent; (ii) unvegetated patches are uncommon; and (iii) wetland vegetation has developed. These differences are mainly derived from the intensity of human impact, history of the slope and its scale: namely, ski slopes in Washington are older and larger than those in Japan. Ski slope vegetation in Washington was primarily differentiated by a soil moisture gradient. The large size of Washington ski slopes permitted the inclusion and development of wetland habitats, whereas most ski slopes in Japan are constructed on ridges and do not contain wetlands. Most introduced species in Japan are eliminated soon after seeding. In contrast, the long-term management of ski slopes decreased soil erosion and/or unvegetated patches in Washington and created relatively permanent grasslands composed of introduced species. Tsuga heterophylla and Abies amabilis were found established on the ski slopes in Washington, whereas in Japan the pioneer tree species are shade-intolerant broadleaved species. These differences may be a result of the different disturbance histories of ski slopes in the two countries. In addition, along with the conifers, early successional forbs such as Anaphalis margaritacea and Epilobium angustifolium are well established on Washington ski slopes. Results show that disturbances created by ski slope development greatly affect the vegetation, even on older, less heavily impacted ski slopes.     

The "prismane" protein resolved: X-ray structure at 1.7 Å and multiple spectroscopy of two novel 4Fe clusters

The three-dimensional structure of the native "putative prismane" protein from Desulfovibrio vulgaris (Hildenborough) has been solved by X-ray crystallography to a resolution of 1.72?Å. The molecule does not contain a [6Fe-6S] prismane cluster, but rather two 4Fe clusters some 12?Å apart and situated close to the interfaces formed by the three domains of the protein. Cluster 1 is a conventional [4Fe-4S] cubane bound, however, near the N-terminus by an unusual, sequential arrangement of four cysteine residues (Cys 3, 6, 15, 21). Cluster 2 is a novel 4Fe structure with two μ₂-sulfido bridges, two μ₂-oxo bridges, and a partially occupied, unidentified μ₂ bridge X. The protein ligands of cluster 2 are widely scattered through the second half of the sequence and include three cysteine residues (Cys 312, 434, 459), one persulfido-cysteine (Cys 406), two glutamates (Glu 268, 494), and one histidine (His 244). With this unusual mixture of bridging and external type of ligands, cluster 2 is named the "hybrid" cluster, and its asymmetric, open structure suggests that it could be the site of a catalytic activity. X-ray absorption spectroscopy at the Fe K-edge is readily interpretable in terms of the crystallographic model when allowance is made for volume contraction at 10?K; no Fe··Fe distances beyond 3.1?Å could be identified. EPR, Mössbauer and MCD spectroscopy have been used to define the oxidation states and the magnetism of the clusters in relation to the crystallographic structure. Reduced cluster 1 is a [4Fe-4S]¹⁺ cubane with S?=?3/2; it is the first biological example of a "spin-admixed" iron-sulfur cluster. The hybrid cluster 2 has four oxidation states from (formally) all Fe^III to three Fe^II plus one Fe^III. The four iron ions are exchange coupled resulting in the system spins S?=?0, 9/2, 0 (and 4), 1/2, respectively, for the four redox states. Resonance Raman spectroscopy suggests that the bridging ligand X which could not be identified unambiguously in the crystal structure is a solvent-exchangeable oxygen.     

Conformation, stability, and active-site cysteine titrations of Escherichia coli D26A thioredoxin probed by Raman spectroscopy.

The active-site cysteines (Cys 32 and Cys 35) of Escherichia coli thioredoxin are oxidized to a disulfide bridge when the protein mediates substrate reduction. In reduced thioredoxin, Cys 32 and Cys 35 are characterized by abnormally low pKa values. A conserved side chain, Asp 26, which is sterically accessible to the active site, is also essential to oxidoreductase activity. pKa values governing cysteine thiol-thiolate equilibria in the mutant thioredoxin, D26A, have been determined by direct Raman spectrophotometric measurement of sulfhydryl ionizations. The results indicate that, in D26A thioredoxin, both sulfhydryls titrate with apparent pKa values of 7.5+/-0.2, close to values measured previously for wild-type thioredoxin. Sulfhydryl Raman markers of D26A and wild-type thioredoxin also exhibit similar band shapes, consistent with minimal differences in respective cysteine side-chain conformations and sulfhydryl interactions. The results imply that neither the Cys 32 nor Cys 35 SH donor is hydrogen bonded directly to Asp 26 in the wild-type protein. Additionally, the thioredoxin main-chain conformation is largely conserved with D26A mutation. Conversely, the mutation perturbs Raman bands diagnostic of tryptophan (Trp 28 and Trp 31) orientations and leads to differences in their pH dependencies, implying local conformational differences near the active site. We conclude that, although the carboxyl side chain of Asp 26 neither interacts directly with active-site cysteines nor is responsible for their abnormally low pKa values, the aspartate side chain may play a role in determining the conformation of the enzyme active site.     

Seedling establishment in different microsites on Mount St. Helens,Washington, USA

On the volcanically devastated Pumice Plain of Mount St. Helens, plant species colonized microsites differentially. Peak colonization did not occur in the same microsites as peak establishment and growth. In addition, observed microsite colonization patterns differed between years. Two studies were conducted. The first assessed seedling establishment and growth from seeds sown at different microsites. The second assessed colonization into four microsite types that were constructed on the Pumice Plain. Hypochaeris radicata was the most common species to survive when the same number of seeds of four species were planted; however, Anaphalis margaritacea was the most common colonizer of microsites. Microsites with the largest biomass plants in the first study generally had the highest colonization in the second study. Sites that do not possess features to trap seeds, such as flats and ridges, are not opportune places for a plant to grow since there is little microclimatic or substrate amelioration. Thus, flat microsites had low biomass in the establishment experiment due to the lack of amelioration and contained few plants in the colonization experiment due to a lack of seed trapping mechanisms. These results show that in the primary successional landscape of Mount St. Helens microsites are critical to revegetation dynamics. Changes in the pattern of microsite colonization between years emphasizes the dynamic nature of the landscape and the important influences of climate, substrate amelioration and seed rain to plant establishment.