Utility of the Addenbrooke's Cognitive Examination III online calculator to differentiate the primary progressive aphasia variants.

The Addenbrooke's Cognitive Examination III is a brief cognitive screening tool that is widely used for the detection and monitoring of dementia. Recent findings suggest that the three variants of primary progressive aphasia can be distinguished based on their distinct profiles on the five subdomain scores of this test. Here, we investigated the utility of the Addenbrooke's Cognitive Examination III to differentiate the primary progressive aphasia variants based on their item-by-item performance profiles on this test. From these results, we created an interactive primary progressive aphasia Addenbrooke's Cognitive Examination III calculator which predicts the variant based on a patient's unique item-by-item profile. Twenty-eight logopenic variant, 25 non-fluent variant and 37 semantic variant primary progressive aphasia patients and 104 healthy controls completed the Addenbrooke's Cognitive Examination III at first clinical presentation. Multinomial regression analyses were conducted to establish performance profiles among groups, and R Shiny from RStudio was used to create the interactive Addenbrooke's Cognitive Examination III diagnostic calculator. To verify its accuracy, probability values of the regression model were derived based on a 5-fold cross-validation of cases. The calculator's accuracy was then verified in an independent sample of 17 logopenic, 19 non-fluent and 13 semantic variant primary progressive aphasia patients and 68 Alzheimer's disease patients who had completed the Addenbrooke's Cognitive Examination III (or an older version of this test: Revised) and had in vivo amyloid-PET imaging and/or brain autopsy pathological confirmation. Cross-validation of cases in the calculator model revealed different rates of sensitivity in classifying variants: semantic = 100%, non-fluent = 80.6% and logopenic = 79.9%; healthy controls were distinguished from primary progressive aphasia patients with 100% sensitivity. Verification of in vivo amyloid and/or autopsy-confirmed patients showed that the calculator correctly classified 10/13 (77%) semantic variant, 3/19 (16%) non-fluent variant and 4/17 (24%) logopenic variant patients. Importantly, for patients who were not classified, diagnostic probability values mostly pointed toward the correct clinical diagnosis. Furthermore, misclassified diagnoses of the primary progressive aphasia cohort were rare (1/49; 2%). Although 22 of the 68 Alzheimer's disease patients (32%) were misclassified with primary progressive aphasia, 19/22 were misclassified with the logopenic variant (i.e. falling within the same neuropathological entity). The Addenbrooke's Cognitive Examination III primary progressive aphasia diagnostic calculator demonstrates sound accuracy in differentiating the variants based on an item-by-item Addenbrooke's Cognitive Examination III profile. This calculator represents a new frontier in using data-driven approaches to differentiate the primary progressive aphasia variants.

Enhancing ultraviolet-to-visible rejection ratio by inserting an intrinsic NiO layer in p-NiO/n-Si heterojunction photodiodes.

Conventionally, p-NiO/n-Si (p-n) heterojunction photodiodes (HPDs) exhibit a larger visible response than the ultraviolet response due to the thick Si substrate; hence, it is used as a broadband photodetector with a poor ultraviolet (UV)-to-visible rejection ratio. Herein, an intrinsic NiO (i-NiO) layer is inserted between the p-NiO and the n-Si substrate to fabricate p-NiO/i-NiO/n-Si (p-i-n) HPDs, significantly suppressing leakage current and visible response. Compared with the conventional p-n HPDs, the insertion of the i-NiO layer significantly reduces leakage current by approximately 241 times and enhances the rectification ratio from 13.8 to 3228 for the p-n and p-i-n HPDs. The insertion of an i-NiO layer not only increases the UV-response but also suppresses the visible response. These issues enhance the UV-to-visible rejection ratio from 72.2 in p-n HPDs to 915.3 in p-i-n HPDs. The p-NiO reveals a poorer crystalline structure than the i-NiO film because the Ag dopants accumulate at the grain boundary and inhibit crystalline growth. The Ag diffusion in the Si substrate causes defect states within the Si bandgap, whereas it is retarded by the i-NiO layer in the p-i-n HPDs. The poor crystallinity in the p-NiO and defect states within the Si bandgap contributes to a high leakage current and visible response in p-n HPDs. The p-i-n HPDs demonstrate a higher UV-response due to absorption by the i-NiO layer. Because visible light cannot be absorbed by the i-NiO layer, visible response is suppressed in p-i-n HPDs.

The Status of Heligmosomoides americanus, Representative of an American Clade of Vole-Infecting Nematodes.

Heligmosomoides americanus is shown by molecular phylogenetic analysis of 3 nuclear (28S, ITS1, and ITS2) and 2 mitochondrial (cytochrome oxidase 1 and cytochrome b) loci to be a distinct species of heligmosomid nematode with a long-independent evolutionary history, and not a subspecies of Heligmosomoides polygyrus . Rather than being a recent arrival in North America, the species probably originated as a Beringian immigrant with the host vole Phenacomys, approximately 2 million years ago (MYA).

Responses of endoparasites in red-backed voles (Myodes gapperi) to natural forest fires.

We investigated the responses of endoparasites in red-backed voles (Myodes gapperi) to fire in a boreal forest ecosystem. Because fire affects the environmental conditions and biodiversity of the forest ecosystem, the life cycle of parasites may also be affected because of the absence of intermediate hosts in the environment. We hypothesized that the prevalence of endoparasites would be influenced by the parasites' life cycle and habitat characteristics (forest vs. burned). We found that prevalence of endoparasites was different between forested and burned habitats (chi(2)=37.49, P<0.001). Cestodes, nematodes, and coccidia showed different responses to habitat alteration (chi(2)=37.43, P<0.001). There was a higher prevalence of cestodes in forested (53.5%) than burned habitats (35.0%). However, there was higher prevalence of coccidia in burned (55.0%) than forested (42.9%) habitats. Furthermore, although prevalence of cestode infection was lower in burned than forested habitat, individuals in both habitats had similar intensities of cestodes. Our study showed that habitat can significantly affect the parasite communities, depending on specific parasite life cycles.

Seroprevalence of Toxoplasma gondii in mesocarnivores of the Canadian prairies.

The protozoon Toxoplasma gondii has a worldwide distribution and affects many species of warm-blooded animals. In the Canadian prairies, mesocarnivores such as striped skunks (Mephitis mephitis) and raccoons (Procyon lotor) have experienced an increase in density and distribution, and they are in close contact with human dwellings. However, there has been no systematic study on the seroprevalence of T. gondii in these mesocarnivore populations. The objectives of the current project were to determine the serum antibody prevalence of T. gondii in Canadian prairie mesocarnivores and to study the relationship between antibody prevalence and species, sex, age, location, and year of collection. Antibodies to T. gondii were found in 5 of 24 (20.8%) skunks from Saskatchewan trapped in 1999 and 5 of 40 (12.5%) in 2000. Seroprevalences for T. gondii in raccoons and skunks trapped in Manitoba were 2 of 10 (20%) raccoons trapped in 2002, 7 of 44 (15.9%) trapped in 2003, and 16 of 37 (43.2%) trapped in 2004; and in 13 of 99 (13.1%) skunks trapped in 2003, 29 of 131 (22.1%) trapped in 2004, 53 of 165 (32.1%) trapped in 2005, and 30 of 51 (58.8%) trapped in 2006. Age, location, and year, but not the host species, were important variables in the determining the seroprevalence of T. gondii in skunks and raccoons. Results confirm that T. gondii is endemic in the skunk and raccoon populations in the Canadian prairies.

Comparison of an interferon-gamma to a phospholipase D enzyme-linked immunosorbent assay for diagnosis of Corynebacterium pseudotuberculosis infection in experimentally infected goats.

The optimal method of control of caseous lymphadenitis of goats caused by Corynebacterium pseudotuberculosis is eradication of infection by identification and removal of infected carrier animals. The objective of this study was to compare detection of C. pseudotuberculosis experimentally infected goats using a commercially available bovine interferon-gamma (IFN-gamma) whole blood enzyme-linked immunosorbent assay (ELISA) to serological response to a recombinant phospholipase D (PLD) ELISA. The tests were assessed repeatedly over 1 year in three infected and three non-infected goats. Using a IFN-gamma optical density cut-off at 0.10 as positive under the conditions used, the test accurately detected C. pseudotuberculosis experimentally infected goats over a 363 day period with a reliability of 89.2% and non-infected goats with a reliability of 97.1%. Using a cut-off value of the mean for negative samples plus two standard deviations, the PLD ELISA detected C. pseudotuberculosis experimentally infected goats over this period with a reliability of 81.0% and non-infected goats with a reliability of 97.0%. The PLD ELISA was however more predictive than the IFN-gamma ELISA of the presence of lesions observed at postmortem examination of infected goats.

An interferon-gamma assay for diagnosis of Corynebacterium pseudotuberculosis infection in adult sheep from a research flock.

The optimal method of control of caseous lymphadenitis of sheep caused by Corynebacterium pseudotuberculosis is eradication of infection by identification and removal of infected carrier animals. Current serological approaches to identification of infected sheep are generally hampered by low sensitivity and specificity of available tests. The objective of this study was to develop a whole blood assay for detection of C. pseudotuberculosis-infected sheep, based on detection of IFN-gamma response to whole cell C. pseudotuberculosis antigens, and to determine the reliability of the assay. A commercially available bovine interferon-gamma assay enzyme-linked immunosorbent assay was used and the test optimised using experimentally infected sheep. The assay was also tested on known CLA-negative sheep. Setting a IFN-gamma optical density cut-off at 0.100 as positive under the conditions used, the test detected C. pseudotuberculosis experimentally infected sheep over a 450-day period with a reliability of 95.7%. It identified known non-infected sheep with a reliability of 95.5%. Repeated vaccination of three uninfected sheep with a commercially available bacterin-toxoid vaccine did not interfere with the assay. The IFN-gamma response of sheep whole blood to C. pseudotuberculosis antigens offers promise for use in a test-and-removal approach to eradication of CLA in sheep.

Nurses' attitudes toward clinical trials at a comprehensive cancer center.

PURPOSE/OBJECTIVES: To identify nurses' attitudes and beliefs toward cancer clinical trials and their perceptions about factors influencing patients' participation in these trials. DESIGN: Descriptive. SETTING: National Cancer Institute-designated comprehensive cancer center. SAMPLE: 417 nurses employed at the cancer center were surveyed; 250 (60%) subjects responded. METHODS: 59-item questionnaire. MAIN RESEARCH VARIABLES: Nurses' attitudes toward clinical trials and perceptions of patient understanding of and influences on participation in clinical trials. FINDINGS: 96% of nurses reported that participation in clinical trials is important to improving standards of care; only 56% believed that patients should be encouraged to participate in trials if they had cancer. In multiple regression analyses, older age and being a research nurse were significant predictors of positive attitudes toward clinical trials. Work setting also was a significant predictor of nurses' perceptions of patients' understanding of treatment. Overall, nurses reported that an investigational therapy should have at least a 50% chance of success prior to being offered to patients. CONCLUSIONS: Nurses generally reported that clinical trials are important to improve standards of care; however, attitudes concerning patient participation in clinical trials and perceptions of patient understanding differed by work setting. Nurses have high expectations regarding the benefits of investigational therapy. IMPLICATIONS FOR NURSING PRACTICE: Nurses play a critical role in the care of participants in cancer clinical trials. Targeted interventions that involve nurses to enhance appropriate patient accrual, patient understanding, and patient decision making should result in improved patient care in centers conducting clinical trials.

Measuring and predicting surgeons' practice styles for breast cancer treatment in older women.

BACKGROUND: Few measures exist to assess physicians' practice style, and there are few data on physicians' practice styles and patterns of care. OBJECTIVES: To use clinical vignettes to measure surgeons' "propensity" for local treatments for early-stage breast cancer and to describe factors associated with propensity. RESEARCH DESIGN AND SUBJECTS: A cross-sectional mailed survey with telephone follow-up of a random sample of 1,000 surgeons treating Medicare beneficiaries in fee-for-service settings. MEASURES: Outcome measures include treatment propensity, self-reported practice, and actual treatment received by the surgeons' patients. RESULTS: Propensities were significantly associated with actual treatment, controlling for covariates. Area Medicare fees were the strongest predictor of propensity, followed by region, attitudes, volume, and gender. For instance, after other factors were considered, surgeons practicing in areas with the highest breast-conserving surgery (BCS) fees were 8.61 (95% CI 2.26-32.73) times more likely to have a BCS propensity than surgeons in areas with the lowest fees. Surgeons with the strongest beliefs in patient participation in treatment decisions were nearly 6 times (95% CI 1.67-20.84) more likely to have a BCS propensity than surgeons with the lowest such beliefs, controlling for covariates. Male surgeons were also independently more likely to have a mastectomy propensity than female surgeons. CONCLUSIONS: Surgeons' propensities explain some of the observed variations in breast cancer treatment patterns among older women. Standardized scenarios provide a practical method to measure practice style and could be used to evaluate physician contributions to shared decision making, practice patterns, costs and outcomes, and adherence to guidelines.

Constructs of burden of illness in older patients with breast cancer: a comparison of measurement methods.

OBJECTIVE: The burden of illness can influence treatment decisions, but there are limited data comparing the performance of different illness burden measures. We assessed the correlations between five previously validated measures of illness burden and global health and physical function and evaluated how each measure correlates with breast cancer treatment patterns in older women. DATA SOURCE: A cohort of 718 women > 67 years with early-stage breast cancer formed the study group. STUDY DESIGN/DATA COLLECTION METHODS: The study made a cross-sectional comparison of illness burden measures (Charlson index, Index of Co-existent Diseases, cardiopulmonary burden of illness, patient-specific life expectancy, and disease counts) and physical function and self-rated global health status. Data were collected from records and patient interviews. PRINCIPAL FINDINGS: All of the measures were significantly correlated with each other and with physical function and self-rated health (p < .001). After controlling for age and stage, life expectancy had the largest effect on surgical treatment, followed by self-rated physical function and health; life expectancy was also independent of physical function. For instance, women with higher life expectancy and better self-rated physical function and health were more likely to receive breast conservation and radiation than sicker women. Women with higher physical functioning were more likely to receive adjuvant chemotherapy than women with lower functioning. CONCLUSIONS: Several measures of illness burden were associated with breast cancer therapy, but each measure accounted for only a small amount of variance in treatment patterns. Future work is needed to develop and validate measures of burden of illness that are feasible, comprehensive, and relevant for diverse clinical and health services objectives.

Screening mammography and breast cancer treatment patterns in older women.

OBJECTIVE: To examine the impact of mammography screening on treatment options received by a cohort of older breast cancer patients. SETTING AND POPULATION: We studied 718 newly diagnosed breast cancer patients, 67 years and over, diagnosed with TNM Stage I and II disease between 1995 and 1997 at 29 hospitals in five regions. METHODS: Data were collected from patients, surgeons, and medical records. A breast cancer diagnosis was considered to have been by screening mammography if so reported by both patient and medical records. Bivariate and logistic regression were used to identify predictors of a women having her cancer detected by screening mammography and the relationships between mode of detection, stage of disease at diagnosis, and local treatment. RESULTS: Women with high school or greater education were 1.75 times (95%, CI 1.11-2.75) more likely to have their cancers diagnosed by screening mammography than women who had not completed high school, controlling for other factors. Screening found earlier stage disease: 96% of women with mammographically diagnosed cancer had T1 lesions, compared to 81% of women diagnosed by other means (p = 0.001). Women with mammography detected lesions were more likely to have ductal cancer, and to be referred to radiation oncologists more than women diagnosed by other means. Controlling for stage and histology, screening remained associated with a higher likelihood of receiving breast conserving surgery (BCS) with radiation (RT) (OR 1.56, 95%, CI 1.10-2.22) than other local therapies. CONCLUSIONS: Beyond the impact on stage, ductal cancers were more likely to be diagnosed by screening. Mammographically detected lesions were associated with referrals to radiation oncologists and higher rates of BCS and RT. Research is needed to explain the residual independent effects of mammography screening on breast cancer treatment.

Effects of exonuclease activity and nucleotide selectivity of the herpes simplex virus DNA polymerase on the fidelity of DNA replication in vivo.

A mutagenesis system was developed for the in vivo study of the fidelity of DNA replication mediated by wild-type herpes simplex virus type 1 (HSV-1) strain KOS and its polymerase (Pol) mutant derivatives PAAr5, Y7, and YD12. The pHOS1 shuttle plasmid, which contained the SupF mutagenesis marker gene and the HSV oris sequence, was used for analysis of the mutation frequency and the mutation spectrum. All three Pol mutants induced significant increases in the mutation frequencies of the target gene, despite the fact that PAAr5 was previously shown to have an antimutator phenotype by the thymidine kinase mutagenesis assay (J. D. Hall, D. M. Coen, B. L. Fisher, M. Weisslitz, S. Randall, R. E. Almy, P. Gelep, and P. A. Schaffer, Virology 132:26-37, 1984; C. B. C. Hwang and J.-H. Chen, Gene 152:191-193, 1995). Altered spectra of mutated target genes induced by these three mutants were also observed. The relative frequencies of both deletion and complex mutations found in mutants induced by exonuclease-proficient Pols were significantly higher than those induced by exonuclease-deficient Pols. On the other hand, the exonuclease-deficient Pols induced significant increases in the frequency of base substitutions, which comprised predominantly G. C-to-T. A transversions, as well as mutations at additional hot spots. These results suggest that the HSV-1 DNA Pol can incorporate purine-purine or pyrimidine-pyrimidine mispaired bases which may be preferentially proofread by its intrinsic exonuclease activity. Furthermore, the effects of the sequence context of the target gene and the assay method should also be considered carefully in any analysis of replication fidelity.

Mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene can confer altered drug sensitivities.

Two herpes simplex virus mutants containing mutated residues within the conserved Exo III motif of the polymerase gene were previously shown to be defective in 3'-5' exonuclease activity and exhibited extremely high mutation frequencies. In this study, we have shown that these mutants also exhibited higher resistance to phosphonoacetic acid and sensitivity to aphidicolin and all nucleoside analogs tested, including acyclovir and gangciclovir, compared to wild-type virus. Marker transfer experiments and sequencing analyses demonstrated that these altered phenotypes were the result of mutations within the Exo III motif. The data indicate that, aside from leading to exonuclease deficiency, mutations in the Exo III motif may also affect interaction of nucleoside triphosphates with the catalytic sites of polymerase activity.

Effects of mutations in the Exo III motif of the herpes simplex virus DNA polymerase gene on enzyme activities, viral replication, and replication fidelity.

The herpes simplex virus DNA polymerase catalytic subunit, which has intrinsic polymerase and 3'-5' exonuclease activities, contains sequence motifs that are homologous to those important for 3'-5' exonuclease activity in other polymerases. The role of one such motif, Exo III, was examined in this study. Mutated polymerases containing either a single tyrosine-to-histidine change at residue 577 or this change plus an aspartic acid-to-alanine at residue 581 in the Exo III motif exhibited defective or undetectable exonuclease activity, respectively, yet retained substantial polymerase activity. Despite the defects in exonuclease activity, the mutant polymerases were able to support viral replication in transient complementation assays, albeit inefficiently. Viruses replicated via the action of these mutant polymerases exhibited substantially increased frequencies of mutants resistant to ganciclovir. Furthermore, when the Exo III mutations were incorporated into the viral genome, the resulting mutant viruses displayed only modestly defect in replication in Vero cells and exhibited substantially increased mutation frequencies. The results suggest that herpes simplex virus can replicate despite severely impaired exonuclease activity and that the 3'-5' exonuclease contributes substantially to the fidelity of viral DNA replication.

Transmission of hepatitis C virus between spouses: the important role of exposure duration.

OBJECTIVES: Although interspousal transmission of hepatitis C virus (HCV) has been studied, the factors responsible for it remain unclear. METHODS: To investigate the transmission of HCV between spouses and the related risk factors, 100 anti-HCV-positive index patients and their spouses were studied. RESULTS: Overall, anti-HCV was detected in 17 (17%) spouses, 15 of whom were also positive for HCV RNA, and 11 couples were infected with the same genotype. The anti-HCV-positive rate was higher in spouses married longer than 20 yr compared with those married less than 20 yr (22 vs 6%, p < 0.05), and the infection was correlated with the duration of their actual exposure to the index patients but not with serum HCV titers. The infected couples had more frequent sexual contacts and more commonly shared tooth-brushes than those with uninfected spouses. CONCLUSION: Spouses of patients with chronic hepatitis C have a higher risk of acquiring HCV that increases with longer marriage and duration of exposure, and they should be educated about how to avoid contracting HCV infection from their spouses.

Rapid hepatic failure associated with a contracted liver mimicking cirrhosis in a case of nasopharyngeal carcinoma with liver metastasis.

A 46-year-old women had an undifferentiated nonkeratinizing nasopharyngeal carcinoma, locally controlled by radiotherapy. Initially, she had normal liver function tests and normal hepatic ultrasonography. Seven months later, she experienced a rapidly progressive hepatic failure manifested by the development of ascites, elevation of serum bilirubin level, and prolongation of prothrombin time. Imaging studies showed a contracted liver and serum biochemical tests were compatible with chronic liver disease, except for an increase of alkaline phosphatase and gamma-glutamyl transpeptidase levels. An endoscopic retrograde cholangiogram ws compatible with changes of sclerosing cholangitis. The patient died of hepatic decompensation within two months. A liver necropsy disclosed diffuse infiltration of carcinoma cells into the hepatic sinusoids and obliterative angio-invasion of the tumor cells with massive fibrotic stroma replacing almost all hepatocytes. In situ hybridization demonstrated expression of Epstein-Barr virus transcripts EBER1 in the tumor cells and proved a metastatic nasopharyngeal carcinoma. The contracted liver is likely to be explained by the tumor-associated desmoplastic change and the obliterative angio-invasion of the tumor. It is important to be aware that, although rare, such an unusual pattern of liver metastasis may mimick cirrhosis clinically and cause rapid hepatic failure in patients with nasopharyngeal carcinoma.

Hemosuccus pancreaticus from a splenic artery pseudoaneurysm: an unusual cause of upper gastrointestinal bleeding.

Hemorrhage through the pancreatic duct into the duodenum, so called "hemosuccus pancreaticus", is a rare cause of gastrointestinal bleeding with diagnostic difficulties. We report a 60-year-old man with recurrent upper gastrointestinal bleeding due to rupture of a splenic artery pseudoaneurysm into the pancreatic duct. Initial upper gastrointestinal endoscopy failed to identify the site of the hemorrhage. Abdominal computed tomography disclosed a cystic mass containing a well-enhanced spherical area at the pancreatic tail. Arterial blood flow was demonstrated in the lesion by Doppler ultrasound. Celiac angiography demonstrated a saccular pseudoaneurysm arising from the splenic artery. Bleeding from the ampulla of Vater located in a big duodenal diverticulum was found on repeat endoscopy. Surgical resection of the pseudoaneurysm with distal pancreatectomy and splenectomy was successfully performed. The patient remained symptom-free 5 months after the operation. Hemosuccus pancreaticus, although rare, remains important in the differential diagnosis of upper gastrointestinal bleeding of obscure origin.

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay.

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be, further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.

Biliary ascariasis: report of a case.

A 64-year-old female aborigine presented with acute cholangitis and obstructive jaundice for three days. Abdominal ultrasonography showed dilatation of the common bile duct, intrahepatic ducts and a linear tubular structure in the common bile duct. Duodenoscopy showed a live Ascaris protruding through the papilla of Vater, which was retracted endoscopically. Cholangitis improved dramatically after worm extraction and nasobiliary drainage. Endoscopic retrograde cholangiography revealed another worm retained in the common bile duct. It disappeared spontaneously from the common bile duct one week later. The barium study of the intestine showed multiple filling defects in the terminal ileum. A total of five worms passed into the stool after treatment with pyrantel pamoate.