ICA model order selection of task co-activation networks

Independent component analysis (ICA) has become a widely used method for extracting functional networks in the brain during rest and task. Historically, preferred ICA dimensionality has widely varied within the neuroimaging community, but typically varies between 20 and 100 components. This can be problematic when comparing results across multiple studies because of the impact ICA dimensionality has on the topology of its resultant components. Recent studies have demonstrated that ICA can be applied to peak activation coordinates archived in a large neuroimaging database (i.e., BrainMap Database) to yield whole-brain task-based co-activation networks. A strength of applying ICA to BrainMap data is that the vast amount of metadata in BrainMap can be used to quantitatively assess tasks and cognitive processes contributing to each component. In this study, we investigated the effect of model order on the distribution of functional properties across networks as a method for identifying the most informative decompositions of BrainMap-based ICA components. Our findings suggest dimensionality of 20 for low model order ICA to examine large-scale brain networks, and dimensionality of 70 to provide insight into how large-scale networks fractionate into sub-networks. We also provide a functional and organizational assessment of visual, motor, emotion, and interoceptive task co-activation networks as they fractionate from low to high model-orders

Factors associated with spontaneous clearance of chronic hepatitis C virus infection

Background & Aims: Spontaneous clearance of chronic hepatitis C virus (HCV) infection (CHC) is rare. We conducted a retrospective case-control study to identify rates and factors associated with spontaneous clearance of CHC. Methods: We defined cases as individuals who spontaneously resolved CHC, and controls as individuals who remained chronically infected. We used data obtained on HCV testing between 1994 and 2013 in the West of Scotland to infer case/control status. Specifically, untreated patients with ⩾2 sequential samples positive for HCV RNA ⩾6 months apart followed by ⩾1 negative test, and those with ⩾2 positive samples ⩾6 months apart with no subsequent negative samples were identified. Control patients were randomly selected from the second group (4/patient of interest). Case notes were reviewed and patient characteristics obtained. Results: 25,113 samples were positive for HCV RNA, relating to 10,318 patients. 50 cases of late spontaneous clearance were identified, contributing 241 person-years follow-up. 2,518 untreated, chronically infected controls were identified, contributing 13,766 person-years follow-up, from whom 200 controls were randomly selected. The incidence rate of spontaneous clearance was 0.36/100 person-years follow-up, occurring after a median 50 months’ infection. Spontaneous clearance was positively associated with female gender, younger age at infection, lower HCV RNA load and co-infection with hepatitis B virus. It was negatively associated with current intravenous drug use. Conclusions: Spontaneous clearance of CHC occurs infrequently but is associated with identifiable host and viral factors. More frequent HCV RNA monitoring may be appropriate in selected patient groups. Lay summary: Clearance of hepatitis C virus infection without treatment occurs rarely once chronic infection has been established. We interrogated a large Scottish patient cohort and found that it was more common in females, patients infected at a younger age or with lower levels of HCV in the blood, and patients co-infected with hepatitis B virus. Patients who injected drugs were less likely to spontaneously clear chronic infection

Axions In String Theory

In the context of string theory, axions appear to provide the most plausible solution of the strong CP problem. However, as has been known for a long time, in many string-based models, the axion coupling parameter F_a is several orders of magnitude higher than the standard cosmological bounds. We re-examine this problem in a variety of models, showing that F_a is close to the GUT scale or above in many models that have GUT-like phenomenology, as well as some that do not. On the other hand, in some models with Standard Model gauge fields supported on vanishing cycles, it is possible for F_a to be well below the GUT scale.Comment: 62 pages, v2; references, acknowledgements and minor corrections adde

Uptake of hepatitis C specialist services and treatment following diagnosis by dried blood spot in Scotland

Background: Dried blood spot (DBS) testing for hepatitis C (HCV) was introduced to Scotland in 2009. This minimally invasive specimen provides an alternative to venipuncture and can overcome barriers to testing in people who inject drugs (PWID). Objectives: The objective of this study was to determine rates and predictors of: exposure to HCV, attendance at specialist clinics and anti-viral treatment initiation among the DBS tested population in Scotland. Study design: DBS testing records were deterministically linked to the Scottish HCV Clinical database prior to logistic regression analysis. Results: In the first two years of usage in Scotland, 1322 individuals were tested by DBS of which 476 were found to have an active HCV infection. Linkage analysis showed that 32% had attended a specialist clinic within 12 months of their specimen collection date and 18% had begun anti-viral therapy within 18 months of their specimen collection date. A significantly reduced likelihood of attendance at a specialist clinic was evident amongst younger individuals (<35 years), those of unknown ethnic origin and those not reporting injecting drug use as a risk factor. Conclusion: We conclude that DBS testing in non-clinical settings has the potential to increase diagnosis and, with sufficient support, treatment of HCV infection among PWID

Mortality in hepatitis C patients who achieve a sustained viral response compared to the general population

Background & Aims: The number of people living with previous hepatitis C infection that have attained a sustained viral response (SVR) is expected to grow rapidly. So far, the prognosis of this group relative to the general population is unclear. Methods: Individuals attaining SVR in Scotland in 1996–2011 were identified using a national database. Through record-linkage, we obtained cause-specific mortality data complete to Dec 2013. We calculated standardised mortality ratios (SMRs) to compare the frequency of mortality in SVR patients to the general population. In a parallel analysis, we used Cox regression to identify modifiable patient characteristics associated with post-SVR mortality. Results: We identified 1824 patients, followed on average for 5.2 years after SVR. In total, 78 deaths were observed. Overall, all-cause mortality was 1.9 times more frequent for SVR patients than the general population (SMR: 1.86; 95% confidence interval (CI): 1.49–2.32). Significant cause-specific elevations were seen for death due to primary liver cancer (SMR: 23.50; 95% CI: 12.23–45.16), and death due to drug-related causes (SMR: 6.58, 95% CI: 4.15–10.45). Together these two causes accounted for 66% of the total excess death observed. All of the modifiable characteristics associated with increased mortality were markers either of heavy alcohol use or injecting drug use. Individuals without these behavioural markers (32.8% of cohort) experienced equivalent survival to the general population (SMR: 0.70; 95% CI: 0.41–1.18) Conclusions: Mortality in Scottish SVR patients is higher overall than the general population. The excess was driven by death from drug-related causes and liver cancer. Health risk behaviours emerged as important modifiable determinants of mortality in this population. Lay summary: Patients cured of hepatitis C through treatment had a higher mortality rate overall than the general population. Most of the surplus mortality was due to drug-related causes and death from liver cancer. A history of heavy alcohol and injecting drug use were associated with a higher mortality risk

Shared genetic variance between obesity and white matter integrity in Mexican Americans.

peer reviewedObesity is a chronic metabolic disorder that may also lead to reduced white matter integrity, potentially due to shared genetic risk factors. Genetic correlation analyses were conducted in a large cohort of Mexican American families in San Antonio (N = 761, 58% females, ages 18-81 years; 41.3 +/- 14.5) from the Genetics of Brain Structure and Function Study. Shared genetic variance was calculated between measures of adiposity [(body mass index (BMI; kg/m(2)) and waist circumference (WC; in)] and whole-brain and regional measurements of cerebral white matter integrity (fractional anisotropy). Whole-brain average and regional fractional anisotropy values for 10 major white matter tracts were calculated from high angular resolution diffusion tensor imaging data (DTI; 1.7 x 1.7 x 3 mm; 55 directions). Additive genetic factors explained intersubject variance in BMI (heritability, h (2) = 0.58), WC (h (2) = 0.57), and FA (h (2) = 0.49). FA shared significant portions of genetic variance with BMI in the genu (rhoG = -0.25), body (rhoG = -0.30), and splenium (rhoG = -0.26) of the corpus callosum, internal capsule (rhoG = -0.29), and thalamic radiation (rhoG = -0.31) (all p's = 0.043). The strongest evidence of shared variance was between BMI/WC and FA in the superior fronto-occipital fasciculus (rhoG = -0.39, p = 0.020; rhoG = -0.39, p = 0.030), which highlights region-specific variation in neural correlates of obesity. This may suggest that increase in obesity and reduced white matter integrity share common genetic risk factors

Dark Matter attempts for CoGeNT and DAMA

Recently, the CoGeNT collaboration presented a positive signal for an annual modulation in their data set. In light of the long standing annual modulation signal in DAMA/LIBRA, we analyze the compatibility of both of these signal within the hypothesis of dark matter (DM) scattering on nuclei, taking into account existing experimental constraints. We consider the cases of elastic and inelastic scattering with either spin-dependent or spin-independent coupling to nucleons. We allow for isospin violating interactions as well as for light mediators. We find that there is some tension between the size of the modulation signal and the time-integrated event excess in CoGeNT, making it difficult to explain both simultaneously. Moreover, within the wide range of DM interaction models considered, we do not find a simultaneous explanation of CoGeNT and DAMA/LIBRA compatible with constraints from other experiments. However, in certain cases part of the data can be made consistent. For example, the modulation signal from CoGeNT becomes consistent with the total rate and with limits from other DM searches at 90% CL (but not with the DAMA/LIBRA signal) if DM scattering is inelastic spin-independent with just the right couplings to protons and neutrons to reduce the scattering rate on xenon. Conversely the DAMA/LIBRA signal (but not CoGeNT) can be explained by spin-dependent inelastic DM scattering.Comment: 20 pages, 9 figure

The risk of hepatocellular carcinoma in cirrhotic patients with hepatitis C and sustained viral response:role of the treatment regimen

Background & Aims: Previous studies have reported a high frequency of hepatocellular carcinoma (HCC) occurrence in patients with advanced liver disease, after receipt of interferon (IFN)-free therapy for hepatitis C virus (HCV) infection. Our objective was to verify and account for this phenomenon using data from the Scottish HCV clinical database. Methods: We identified HCC-naïve individuals with liver cirrhosis receiving a course of antiviral therapy in Scotland from 1997–2016 resulting in a sustained virologic response. Patients were followed-up from their treatment start date to the earliest of: date of death, date of HCC occurrence, or 31 January 2017. We used Cox regression to compare the risk of HCC occurrence according to treatment regimen after adjusting for relevant co-factors (including: demographic factors; baseline liver disease stage; comorbidities/health behaviours, virology, and previous treatment experience). HCC occurrence was ascertained through both the HCV clinical database and medical chart review. For our main analysis, treatment regimen was defined as IFN-free vs. IFN-containing. Results: A total of 857 patients met the study criteria, of whom 31.7% received an IFN-free regimen. Individuals receiving IFN-free therapy were more likely to be: older; of white ethnicity, Child-Turcotte-Pugh B/C vs. Child-Turcotte-Pugh A; thrombocytopenic; non-genotype 3; and treatment experienced. HCC occurrence was observed in 46 individuals during follow-up. In univariate analysis, IFN-free therapy was associated with a significantly increased risk of HCC (HR: 2.48; p = 0.021). However, after multivariate adjustment for baseline factors, no significant risk attributable to IFN-free therapy persisted (aHR: 1.15, p = 0.744). Conclusion: These findings suggest that the higher incidence of HCC following sustained virologic response with IFN-free therapy relates to baseline risk factors/patient selection, and not the use of IFN-free therapy per se. Lay summary: We examined the risk of liver cancer in 857 patients with cirrhosis in Scotland who received hepatitis C antiviral therapy and achieved a cure. We compared the risk of first-time liver cancer in patients treated with the newest interferon-free regimens, to patients treated with interferon. After accounting for the different characteristics of these two treatment groups, we found no evidence that interferon-free therapy is associated with a higher risk of liver cancer