Plasticity, not genetic variation, drives infection success of a fungal parasite.

Hosts strongly influence parasite fitness. However, it is challenging to disentangle host effects on genetic vs plasticity-driven traits of parasites, since parasites can evolve quickly. It remains especially difficult to determine the causes and magnitude of parasite plasticity. In successive generations, parasites may respond plastically to better infect their current type of host, or hosts may produce generally 'good' or 'bad' quality parasites. Here, we characterized parasite plasticity by taking advantage of a system in which the parasite (the yeast Metschnikowia bicuspidata, which infects Daphnia) has no detectable heritable variation, preventing rapid evolution. In experimental infection assays, we found an effect of rearing host genotype on parasite infectivity, where host genotypes produced overall high or low quality parasite spores. Additionally, these plastically induced differences were gained or lost in just a single host generation. Together, these results demonstrate phenotypic plasticity in infectivity driven by the within-host rearing environment. Such plasticity is rarely investigated in parasites, but could shape epidemiologically important traits.

Differential host susceptibility to Batrachochytrium dendrobatidis, an emerging amphibian pathogen.

The amphibian fungal pathogen Batrachochytrium dendrobatidis (Bd) has received considerable attention due to its role in amphibian population declines worldwide. Although many amphibian species appear to be affected by Bd, there is little information on species-specific differences in susceptibility to this pathogen. We used a comparative experimental approach to examine Bd susceptibility in 6 amphibian species from the United States. We exposed postmetamorphic animals to Bd for 30 days and monitored mortality, feeding rates, and infection levels. In all species tested, Bd-exposed animals had higher rates of mortality than unexposed (control) animals. However, we found differences in mortality rates among species even though the amount of Bd detected on the different species' bodies did not differ. Of the species tested, southern toads (Anaxyrus terrestris) and wood frogs (Lithobates sylvaticus) had the highest rates of Bd-related mortality. Within species, we detected lower levels of Bd on individuals that survived longer and found that the relationship between body size and infection levels differed among species. Our results indicate that, even under identical conditions, amphibian species differ in susceptibility to Bd. This study represents a step toward identifying and understanding species variation in disease susceptibility, which can be used to optimize conservation strategies.

The genetic basis of colorectal cancer in a population-based incident cohort with a high rate of familial disease.

BACKGROUND AND AIMS: Colorectal cancer (CRC) is the second most frequent cancer in developed countries. Newfoundland has the highest incidence of CRC in Canada and the highest rate of familial CRC yet reported in the world. To determine the impact of mutations in known CRC susceptibility genes and the contribution of the known pathways to the development of hereditary CRC, an incident cohort of 750 patients with CRC (708 different families) from the Newfoundland population was studied. METHODS: Microsatellite instability (MSI) testing was performed on tumours, together with immunohistochemistry analysis for mismatch repair (MMR) genes. Where indicated, DNA sequencing and multiplex ligation-dependent probe amplifications of MMR genes and APC was undertaken. DNA from all patients was screened for MUTYH mutations. The presence of the BRAF variant, p.V600E, and of MLH1 promoter methylation was also tested in tumours. RESULTS: 4.6% of patients fulfilled the Amsterdam criteria (AC), and an additional 44.6% fulfilled the revised Bethesda criteria. MSI-high (MSI-H) was observed in 10.7% (n=78) of 732 tumours. In 3.6% (n=27) of patients, CRC was attributed to 12 different inherited mutations in six known CRC-related genes associated with chromosomal instability or MSI pathways. Seven patients (0.9%) carried a mutation in APC or biallelic mutations in MUTYH. Of 20 patients (2.7%) with mutations in MMR genes, 14 (70%) had one of two MSH2 founder mutations. 17 of 28 (61%) AC families did not have a genetic cause identified, of which 15 kindreds fulfilled the criteria for familial CRC type X (FCCTX). CONCLUSIONS: Founder mutations accounted for only 2.1% of cases and this was insufficient to explain the high rate of familial CRC. Many of the families classified as FCCTX may have highly penetrant mutations segregating in a Mendelian-like manner. These families will be important for identifying additional CRC susceptibility loci.

The UK national breast cancer screening programme for survivors of Hodgkin lymphoma detects breast cancer at an early stage.

BACKGROUND: Supradiaphragmatic radiotherapy (SRT) to treat Hodgkin's lymphoma (HL) at a young age increases the risk of breast cancer (BC). A national notification risk assessment and screening programme (NRASP) for women who were treated with SRT before the age of 36 years was instituted in the United Kingdom in 2003. In this study, we report the implementation and screening results from the largest English Cancer Network. METHODS: A total of 417 eligible women were identified through cancer registry/hospital databases and from follow-up (FU) clinics. Screening results were collated retrospectively, and registry searches were used to capture BC cases. RESULTS: Of the 417 women invited for clinical review, 243 (58%) attended. Of these 417 women, 23 (5.5%) have been diagnosed with BC, a standardised incidence ratio of 2.9 compared with the age-matched general population. Of five invasive BCs diagnosed within the NRASP, none involved axillary lymph nodes compared with 7 of 13 (54%) diagnosed outside the programme (P<0.10). The mean latency for BC cases was 19.5+/-8.35 years and the mean FU duration for those unaffected by BC was 14.6+/-9.11 years (P<0.01), suggesting that those unaffected by BC remain at high risk. Recall and negative biopsy rates were acceptable (10.5 and 0.8%, respectively). CONCLUSIONS: The NRASP appears to detect BC at an early stage with acceptable biopsy rates, although numbers are small. Determination of NRASP results on a national basis is required for the accurate evaluation of screening efficacy in women previously treated with SRT.

Photoemission Study of CO Adsorption on Gd.

Angle-resolved UV photoemission spectroscopy has been used to investigate the interaction of CO with Gd films, grown on W(110). The results suggest the CO absorbs dissociatively, initially forming Gd(2)O(3), with subsequent catalytic oxidation of CO to form carbonate.

Uncertainty and quality of life of adults hospitalized with life-threatening ventricular arrhythmias.

Advances in the management of ventricular arrhythmias have improved patient survival, but not the uncertainty faced by those living with these arrhythmias. Managing the uncertainty in illness is considered essential to the maintenance of well-being and, therefore, quality of life. The purpose of this study was to determine the relationship between uncertainty and quality of life for adults with recurrent ventricular arrhythmias. Using a descriptive correlational design, 22 adults hospitalized with life-threatening ventricular arrhythmias completed questionnaires prior to discharge from the hospital. Data were collected using a demographic questionnaire, the Mishel Uncertainty in Illness Scale, the Quality of Life Index-Cardiac Version, and a single item self-rating scale for amount of worry. Results from the study indicated that greater quality of life for the health and functioning domain was significantly correlated with lower overall uncertainty and less ambiguity. Greater worry about the arrhythmia was associated with increased uncertainty and ambiguity, and poorer quality of life for the health and functioning domain. The results provide support for the aversive nature and negative impact of uncertainty on quality of life for patients with ventricular arrhythmias. Conclusions address clinical and research implications of these findings.

Assessment of vision in infants and children.

An understanding of vision development is important in the assessment of visual problems. The authors look at this factor and outline testing procedures useful in the assessment of vision in the paediatric patient.

Time-domain analysis of auditory-nerve-fiber firing rates.

Time-domain analysis of firing-rate data from over 200 fibers from the auditory nerve of cat has been used to estimate the formants of the synthetic-syllable stimuli. Distinct groups of fibers are identified based on intervals between peaks in the fiber firing rates. The large extent of some of these groups--over an octave in terms of characteristic frequency--and the lack of short intervals in the longer-interval groups suggest that the behavior of the nonlinear cochlear filters for these signals is effectively wideband with steep high-frequency cutoffs. The measured intervals within each group are very similar, and correspond to the period of the formant that dominates the group's response. These intervals are used to estimate the dynamic speech formants. The overall formant estimates are better than those of the previous spectral analyses of the neural data, and the details of lower-formant dynamics are tracked more precisely. The direct temporal representation of the formant in contrasted with the diffuse spectral representation, the dependence of spectral peaks on nonformant parameters, and the distortion of the spectrum by rectification. It is concluded that a time-domain analysis of the responses to complex stimuli can be an important addition to frequency-domain analysis for neural data, cochlear models, and machine processing of speech.

Prevalence of human papillomavirus infections in term pregnancy.

The prevalence of human papillomavirus (HPV) infections in the lower genital tracts of pregnant and nonpregnant women was studied. Cervical and vaginal exfoliated cells were obtained during a routine pelvic examination in 45 pregnant women in early labor, and in 44 nonpregnant women. A detailed questionnaire with emphasis on sexual history and sexually transmitted diseases was administered. The two groups of women were comparable with respect to mean age, prior pregnancy experiences, and number of lifetime sexual partners. Compared with pregnant women, the nonpregnant women had a more frequent history of sexually transmitted diseases (61% versus 39%; p = 0.06), and of genital warts (16% versus 0%; p = 0.01). Utilizing Southern transfer and hybridization with 32P-labeled viral DNA probes for HPV types 6, 11, 16, 18, and 31, DNAs extracted from cervicovaginal exfoliated cells were assessed for HPV genomic sequences. HPV genomic sequences were identified in 25% of nonpregnant women compared with 13.5% of term pregnant women. This difference was not statistically significant (p = 0.26). Six HPV isolates identified in pregnant women were distributed as follows: type 6/11, 1; type 16, 1, type 31, 1; and unknown type, 3. Eleven isolates were identified in nonpregnant women and were distributed as follows: type 6/11, 2; type 16, 6; type 18, 2; and type 31, 1. HPV type 6/11, the type responsible for laryngeal papillomatosis of juvenile onset, was identified in 2% of the pregnant population and accounted for only one of six isolates. HPV DNA-positive pregnant and nonpregnant women were predominantly asymptomatic and had normal Papanicolaou smears and normal clinical examinations.

Human papillomavirus and epithelial ovarian neoplasia.

In contrast to the strong association between human papillomavirus (HPV) and squamous cell carcinoma of the lower female genital tract, no viral DNA had been found in epithelial ovarian carcinoma. Recently, however, R. H. Kaufman, J. Bornstein, A. N. Gordon, E. Adam, A. L. Kaplan, and K. Adler-Storthy [Gynecol. Oncol. 27, 340-349 (1987)] reported the detection of HPV-6 DNA by in situ hybridization in 10 of 12 patients with advanced epithelial ovarian carcinoma. To further investigate the possible association between HPV and epithelial ovarian neoplasia, tumor from 12 patients with epithelial ovarian adenocarcinoma, 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian tumors of low malignant potential, and 3 with epithelial ovarian adenomas was examined for HPV DNA by the Southern hybridization technique. All the tissues were tested under low stringency for HPV-6 and under high stringency for HPV-6, HPV-16, HPV-18, HPV-31, and HPV-35. In addition, all tissues were tested by polymerase chain reaction for the presence of HPV-6 and HPV-11. Of the 12 patients with adenocarcinoma, 5 were poorly differentiated, 4 serous, 1 endometrioid, 1 mucinous, and 1 mixed. The neoplasms were of grades 2-4 with a predominance of stages III and IV (83%). Of the 3 patients with tumors of low malignant potential, all were serous and stage I. Of the 3 patients with adenomas, 1 was mucinous, 1 serous, and 1 Brenner. We were unable to detect HPV-related sequences in any of the specimens. On the basis of these findings, there appears to be no association between HPV and epithelial ovarian neoplasia.