A new approach to disease-modifying drug trials in Parkinson's disease

Translating new findings in the laboratory into therapies for patients is a slow and expensive process. The development of therapies for neurodegenerative diseases is further complicated by the difficulty in determining whether the drug truly retards the slow degenerative process or provides only symptomatic benefit. In this issue, Aviles-Olmos et al. describe a first in Parkinson's disease (PD) patient study using a drug previously approved for diabetes treatment. In addition to suggesting that the drug may indeed be disease modifying in PD, their innovative approach suggests there may be more rapid and inexpensive avenues for testing novel therapies in PD

Community detection in temporal multilayer networks, with an application to correlation networks

Networks are a convenient way to represent complex systems of interacting entities. Many networks contain "communities" of nodes that are more densely connected to each other than to nodes in the rest of the network. In this paper, we investigate the detection of communities in temporal networks represented as multilayer networks. As a focal example, we study time-dependent financial-asset correlation networks. We first argue that the use of the "modularity" quality function---which is defined by comparing edge weights in an observed network to expected edge weights in a "null network"---is application-dependent. We differentiate between "null networks" and "null models" in our discussion of modularity maximization, and we highlight that the same null network can correspond to different null models. We then investigate a multilayer modularity-maximization problem to identify communities in temporal networks. Our multilayer analysis only depends on the form of the maximization problem and not on the specific quality function that one chooses. We introduce a diagnostic to measure \emph{persistence} of community structure in a multilayer network partition. We prove several results that describe how the multilayer maximization problem measures a trade-off between static community structure within layers and larger values of persistence across layers. We also discuss some computational issues that the popular "Louvain" heuristic faces with temporal multilayer networks and suggest ways to mitigate them.Comment: 42 pages, many figures, final accepted version before typesettin

Temporal Evolution of Financial Market Correlations

We investigate financial market correlations using random matrix theory and principal component analysis. We use random matrix theory to demonstrate that correlation matrices of asset price changes contain structure that is incompatible with uncorrelated random price changes. We then identify the principal components of these correlation matrices and demonstrate that a small number of components accounts for a large proportion of the variability of the markets that we consider. We then characterize the time-evolving relationships between the different assets by investigating the correlations between the asset price time series and principal components. Using this approach, we uncover notable changes that occurred in financial markets and identify the assets that were significantly affected by these changes. We show in particular that there was an increase in the strength of the relationships between several different markets following the 2007--2008 credit and liquidity crisis.Comment: 15 pages, 10 figures, 1 table. Accepted for publication in Phys. Rev. E. v2 includes additional section

Dynamic communities in multichannel data: An application to the foreign exchange market during the 2007--2008 credit crisis

We study the cluster dynamics of multichannel (multivariate) time series by representing their correlations as time-dependent networks and investigating the evolution of network communities. We employ a node-centric approach that allows us to track the effects of the community evolution on the functional roles of individual nodes without having to track entire communities. As an example, we consider a foreign exchange market network in which each node represents an exchange rate and each edge represents a time-dependent correlation between the rates. We study the period 2005-2008, which includes the recent credit and liquidity crisis. Using dynamical community detection, we find that exchange rates that are strongly attached to their community are persistently grouped with the same set of rates, whereas exchange rates that are important for the transfer of information tend to be positioned on the edges of communities. Our analysis successfully uncovers major trading changes that occurred in the market during the credit crisis.Comment: 8 pages, 6 figures, accepted for publication in Chao

MAX 4 and MAX 5 CMB anisotropy measurement constraints on open and flat-Lambda CDM cosmogonies

We account for experimental and observational uncertainties in likelihood analyses of cosmic microwave background (CMB) anisotropy data from the MAX 4 and MAX 5 experiments. These analyses use CMB anisotropy spectra predicted in open and spatially-flat Lambda cold dark matter cosmogonies. Amongst the models considered, the combined MAX data set is most consistent with the CMB anisotropy shape in Omega_0 ~ 0.1-0.2 open models and less so with that in old (t_0 >~ 15 - 16 Gyr, i.e., low h), high baryon density (Omega_B >~ 0.0175/h^2), low density (Omega_0 ~ 0.2 - 0.4), flat-Lambda models. The MAX data alone do not rule out any of the models we consider at the 2-sigma level. Model normalizations deduced from the combined MAX data are consistent with those drawn from the UCSB South Pole 1994 data, except for the flat bandpower model where MAX favours a higher normalization. The combined MAX data normalization for open models with Omega_0 ~ 0.1-0.2 is higher than the upper 2-sigma value of the DMR normalization. The combined MAX data normalization for old (low h), high baryon density, low-density flat-Lambda models is below the lower 2-sigma value of the DMR normalization. Open models with Omega_0 ~ 0.4-0.5 are not far from the shape most favoured by the MAX data, and for these models the MAX and DMR normalizations overlap. The MAX and DMR normalizations also overlap for Omega_0 = 1 and some higher h, lower Omega_B, low-density flat-Lambda models.Comment: Latex, 37 pages, uses aasms4 styl

Results from a Phase 1 Study of Sodium Selenite in Combination with Palliative Radiation Therapy in Patients with Metastatic Cancer.

In preclinical studies, selenite had single agent activity and radiosensitized tumors in vivo. Here we report results from a Phase 1 trial in 15 patients with metastatic cancer treated with selenite (5.5 to 49.5 mg) orally as a single dose 2 hours before each radiation therapy (RT) treatment. Patients received RT regimens that were standard of care. The primary objective of the study was to assess the safety of this combination therapy. Secondary objectives included measurement of pharmacokinetics (PK) and evaluation of efficacy. Endpoints included assessment of PK, toxicity, tumor response, and pain before and after treatment. The half-life of selenite was 18.5 hours. There were no adverse events attributable to selenite until the 33 mg dose level, at which the primary toxicities were grade 1 GI side effects. One patient treated with 49.5 mg had grade 2 GI toxicity. Although this was not a DLT, it was felt that the highest acceptable dose in this patient population was 33 mg. Most patients had stabilization of disease within the RT fields, with some demonstrating objective evidence of tumor regression. Most patients had a marked improvement in pain and seven out of nine patients with prostate cancer had a decrease in PSA ranging from 11-78%. Doses up to 33 mg selenite were well tolerated in combination with RT. A randomized, well controlled study is needed at the 33 mg dose level to determine if selenite results in clinically meaningful improvements in the response to palliative RT

Loss of murine Paneth cell function alters the immature intestinal microbiome and mimics changes seen in neonatal necrotizing enterocolitis

Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal morbidity and mortality in premature infants. Human and animal studies suggest a role for Paneth cells in NEC pathogenesis. Paneth cells play critical roles in host-microbial interactions and epithelial homeostasis. The ramifications of eliminating Paneth cell function on the immature host-microbial axis remains incomplete. Paneth cell function was depleted in the immature murine intestine using chemical and genetic models, which resulted in intestinal injury consistent with NEC. Paneth cell depletion was confirmed using histology, electron microscopy, flow cytometry, and real time RT-PCR. Cecal samples were analyzed at various time points to determine the effects of Paneth cell depletion with and without Klebsiella gavage on the microbiome. Deficient Paneth cell function induced significant compositional changes in the cecal microbiome with a significant increase in Enterobacteriacae species. Further, the bloom of Enterobacteriaceae species that occurs is phenotypically similar to what is seen in human NEC. This further strengthens our understanding of the importance of Paneth cells to intestinal homeostasis in the immature intestine

Effects of Multivitamin Supplementation on Heart Rate Response in Aerobically Untrained College Aged Students

Multivitamin use is increasingly prevalent in the US among most every population. Yet, previous research noted no performance benefits among individuals following a supplementation period. This study focused on the potential physiological benefits from a three week multivitamin supplementation period using 24 (20.9 ± 2.6yr) aerobically untrained college aged students. Subjects were divided equally into three groups (placebo = PL, multivitamin = MV, control = CL) and asked to perform separate eight minute bouts of exercise, consisting of six min of moderate (60%VO2max) intensity followed immediately by two min of high (85%VO2max) intensity exercise on a cycle ergometer. Following the supplementation period, participants came back and performed the same exercise bout. Heart rates were measured with a POLAR Heart Rate monitor and recorded every two min. Data analysis, using ANOVA comparing the three groups, indicated a statistically significant HR interaction. Post hoc paired t-tests, comparing the pre/post supplementation tests of all groups, noted significant differences in HR between MV group during the 60% VO2 (p = 0.04) intensity bout, and approached significance at 85% VO2 (p = 0.10). No difference occurred for the CL group during either moderate or high intensity exercise. The results indicate that the introduction of a supplement, whether real or placebo, may have a physiological effect on the heart rate of aerobically untrained college students