Evaluating Acquisition Time of rfMRI in the Human Connectome Project for Early Psychosis. How Much Is Enough?

Resting-state functional MRI (rfMRI) correlates activity across brain regions to identify functional connectivity networks. The Human Connectome Project (HCP) for Early Psychosis has adopted the protocol of the HCP Lifespan Project, which collects 20 min of rfMRI data. However, because it is difficult for psychotic patients to remain in the scanner for long durations, we investigate here the reliability of collecting less than 20 min of rfMRI data. Varying durations of data were taken from the full datasets of 11 subjects. Correlation matrices derived from varying amounts of data were compared using the Bhattacharyya distance, and the reliability of functional network ranks was assessed using the Friedman test. We found that correlation matrix reliability improves steeply with longer windows of data up to 11–12 min, and ≥14 min of data produces correlation matrices within the variability of those produced by 18 min of data. The reliability of network connectivity rank increases with increasing durations of data, and qualitatively similar connectivity ranks for ≥10 min of data indicates that 10 min of data can still capture robust information about network connectivities

Heritability Estimation of Reliable Connectomic Features*

Brain imaging genetics is an emerging research field to explore the underlying genetic architecture of brain structure and function measured by different imaging modalities. However, not all the changes in the brain are a consequential result of genetic effect and it is usually unknown which imaging phenotypes are promising for genetic analyses. In this paper, we focus on identifying highly heritable measures of structural brain networks derived from diffusion weighted imaging data. Using the twin data from the Human Connectome Project (HCP), we evaluated the reliability of fractional anisotropy measure, fiber length and fiber number of each edge in the structural connectome and seven network level measures using intraclass correlation coefficients. We then estimated the heritability of those reliable network measures using SOLAR-Eclipse software. Across all 64,620 network edges between 360 brain regions in the Glasser parcellation, we observed ~5% of them with significantly high heritability in fractional anisotropy, fiber length or fiber number. All the tested network level measures, capturing the network integrality, segregation or resilience, are highly heritable, with variance explained by the additive genetic effect ranging from 59% to 77%

Mimotope ELISA for Detection of Broad Spectrum Antibody against Avian H5N1 Influenza Virus

Science and Technology Foundation of Fujian Province [2009YZ0002]; National Natural Science Foundation of China [30901077]; National High Technology Research and Development Program [2010AA022801]Background: We have raised a panel of broad spectrum neutralizing monoclonal antibodies against the highly pathogenic H5N1 avian influenza virus, which neutralize the infectivity of, and afford protection against infection by, most of the major genetic groups of the virus evolved since 1997. Peptide mimics reactive with one of these broad spectrum H5N1 neutralizing antibodies, 8H5, were identified from random phage display libraries. Method: The amino acid residues of the most reactive 12mer peptide, p125 (DTPLTTAALRLV), were randomly substituted to improve its mimicry of the natural 8H5 epitope. Result: 133 reactive peptides with unique amino acid sequences were identified from 5 sub-libraries of p125. Four residues (2,4,5.9) of the parental peptide were preserved among all the derived peptides and probably essential for 8H5 binding. These are interspersed among four other residues (1,3,8,10), which exhibit restricted substitution and probably could contribute to binding, and another four (6,7,11,12) which could be randomly substituted and probably are not essential for binding. One peptide, V-1b, derived by substituting 5 of the latter residues is the most reactive and has a binding constant of 3.16x10(-9) M, which is 38 fold higher than the affinity of the parental p125. Immunoassay produced with this peptide is specifically reactive with 8H5 but not also the other related broad spectrum H5N1 avian influenza virus neutralizing antibodies. Serum samples from 29 chickens infected with H5N1 avian influenza virus gave a positive result by this assay and those from 12 uninfected animals gave a negative test result. Conclusion: The immunoassay produced with the 12 mer peptide, V1-b, is specific for the natural 8H5 epitope and can be used for detection of antibody against the broad spectrum neutralization site of H5N1 avian influenza virus

Systemic inflammatory response predicts outcome in patients undergoing resection for ductal adenocarcinoma head of pancreas

The aim of the present study was to examine the relationship between the clinicopathological status, the pre- and postoperative systemic inflammatory response and survival in patients undergoing potentially curative resection for ductal adenocarcinoma of the head of the pancreas. Patients (n=65) who underwent resection of ductal adenocarcinoma of the head of pancreas between 1993 and 2001, and had pre- and postoperative measurements of C-reactive protein, were included in the study. The majority of patients had stage III disease (International Union Against Cancer Criteria, IUCC), positive circumferential margin involvement (R1), tumour size greater than 25 mm with perineural and lymph node invasion and died within the follow-up period. On multivariate analysis, tumour size (hazard ratio (HR) 2.10, 95% confidence interval (CI) 1.20–3.68, P=0.009), vascular invasion (HR 2.58, 95% CI 1.48–4.50, P<0.001) and postoperative C-reactive protein (HR 2.00, 95% CI 1.14–3.52, P=0.015) retained independent significance. Those patients with a postoperative C-reactive protein ⩽10 mg l−1 had a median survival of 21.5 months compared with 8.4 months in those patients with a C-reactive protein >10 mg l−1 (P<0.001). The results of the present study indicate that, in patients who have undergone potentially curative resection for ductal adenocarcinoma of the head of pancreas, the presence of a systemic inflammatory response predicts poor outcome

Asymmetric Dimethylarginine, Endothelial Nitric Oxide Bioavailability and Mortality in Sepsis

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxidesynthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelialdysfunction, but the role of ADMA in acute inflammatory states is less well defined.Methods and Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digitalmicrovascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2&ndash;4 dayslater. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baselineplasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45&ndash;103]) than in hospital controls(143 [123&ndash;166], p,0.0001) and correlated with microvascular reactivity (r = 0.34, R2 = 0.12, p = 0.02). Baseline plasma ADMAwas independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile($0.66 mmol/L) = 20.8 [2.2&ndash;195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase inADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.Conclusions: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potentialmechanism linking increased plasma ADMA with organ failure and death in sepsis

Molecular characterization and antiviral activity test of common drugs against echovirus 18 isolated in Korea

Genetic diversity and antiviral activity for five common antiviral drugs of echovirus (ECV) 5 isolated in Korea have been described. The present study extended these tests to a Korean ECV 18 isolate. An outbreak of aseptic meningitis caused by the ECV 18 isolate was reported in Korea in 2005, marking the first time this virus had been identified in the country since enterovirus surveillance began in 1993. Using a sample isolated from stool specimen of a 5-year-old male patient with aseptic meningitis, the complete genome sequence was obtained and was compared it with the Metcalf prototype strain. Unlike the ECV5 isolate, the 3' untranslated region had the highest identity value (94.2%) at the nucleotide level, while, at the amino acid level, the P2 region displayed the highest identity value (96.9%). These two strains shared all cleavage sites, with the exception of the 2B/2C site, which was RQ/NN in the Metcalf strain but RQ/NS in the Korean ECV 18 isolate. In Vero cells infected with the Korean ECV 18 isolate, no cytotoxicity was observed in the presence of azidothymidine, acyclovir, amantadine, lamivudine, or ribavirin, when the drugs were administered at a CC50 value >100 μg/mL. Of the five drugs, only amantadine (IC50: 4.97 ± 0.77 μg/mL, TI: 20.12) and ribavirin (IC50: 7.63 ± 0.87 μg/mL, TI: 13.11) had any antiviral activity against the Korean ECV 18 isolate in the five antiviral drugs. These antiviral activity effects were similar with results of the Korean ECV5 isolate

Evaluation of applying IHC4 as a prognostic model in the translational study of Intergroup Exemestane Study (IES): PathIES

Background: Intergroup Exemestane Study (IES) was a randomised study that showed a survival benefit of switching adjuvant endocrine therapy after 2–3 years from tamoxifen to exemestane. This PathIES aimed to assess the role of immunohistochemical (IHC)4 score in determining the relative sensitivity to either tamoxifen or sequential treatment with tamoxifen and exemestane. Patients and methods: Primary tumour samples were available for 1274 patients (27% of IES population). Only patients for whom the IHC4 score could be calculated (based on oestrogen receptor, progesterone receptor, HER2 and Ki67) were included in this analysis (N = 430 patients). The clinical score (C) was based on age, grade, tumour size and nodal status. The association of clinicopathological parameters, IHC4(+C) scores and treatment effect with time to distant recurrence-free survival (TTDR) was assessed in univariable and multivariable Cox regression analyses. A modified clinical score (PathIEscore) (N = 350) was also estimated. Results: Our results confirm the prognostic importance of the original IHC4, alone and in conjunction with clinical scores, but no significant difference with treatment effects was observed. The combined IHC4 + Clinical PathIES score was prognostic for TTDR (P < 0.001) with a hazard ratio (HR) of 5.54 (95% CI 1.29–23.70) for a change from 1st quartile (Q1) to Q1–Q3 and HR of 15.54 (95% CI 3.70–65.24) for a change from Q1 to Q4. Conclusion: In the PathIES population, the IHC4 score is useful in predicting long-term relapse in patients who remain disease-free after 2–3 years. This is a first trial to suggest the extending use of IHC4+C score for prognostic indication for patients who have switched endocrine therapies at 2–3 years and who remain disease-free after 2–3 years

Pyoderma gangrenosum – a review

Pyoderma gangrenosum (PG) is a rare noninfectious neutrophilic dermatosis. Clinically it starts with sterile pustules that rapidly progress and turn into painful ulcers of variable depth and size with undermined violaceous borders. The legs are most commonly affected but other parts of the skin and mucous membranes may also be involved. Course can be mild or malignant, chronic or relapsing with remarkable morbidity. In many cases PG is associated with an underlying disease, most commonly inflammatory bowel disease, rheumatic or haematological disease and malignancy. Diagnosis of PG is based on history of an underlying disease, typical clinical presentation, histopathology, and exclusion of other diseases that would lead to a similar appearance. The peak of incidence occurs between the ages of 20 to 50 years with women being more often affected than men. Aetiology has not been clearly determined yet. The treatment of PG is a challenge. Randomized, double-blinded prospective multicenter trials for PG are not available. The best documented treatments are systemic corticosteroids and ciclosporin A. Combinations of steroids with cytotoxic drugs are used in resistant cases. The combination of steroids with sulfa drugs or immunosuppressants has been used as steroid-sparing modalities. Anti-tumor necrosis alpha therapy in Crohn's disease showed a rapid response of PG. Skin transplants and the application of bioengineered skin is useful in selected cases as a complement to the immunosuppressive treatment. Topical therapy with modern wound dressings is useful to minimize pain and the risk of secondary infections. Despite recent advances in therapy, the prognosis of PG remains unpredictable

Economic and Environmental Impacts of Harmful Non-Indigenous Species in Southeast Asia

10.1371/journal.pone.0071255PLoS ONE88-POLN