Exponential Random Graph Modeling for Complex Brain Networks

Exponential random graph models (ERGMs), also known as p* models, have been utilized extensively in the social science literature to study complex networks and how their global structure depends on underlying structural components. However, the literature on their use in biological networks (especially brain networks) has remained sparse. Descriptive models based on a specific feature of the graph (clustering coefficient, degree distribution, etc.) have dominated connectivity research in neuroscience. Corresponding generative models have been developed to reproduce one of these features. However, the complexity inherent in whole-brain network data necessitates the development and use of tools that allow the systematic exploration of several features simultaneously and how they interact to form the global network architecture. ERGMs provide a statistically principled approach to the assessment of how a set of interacting local brain network features gives rise to the global structure. We illustrate the utility of ERGMs for modeling, analyzing, and simulating complex whole-brain networks with network data from normal subjects. We also provide a foundation for the selection of important local features through the implementation and assessment of three selection approaches: a traditional p-value based backward selection approach, an information criterion approach (AIC), and a graphical goodness of fit (GOF) approach. The graphical GOF approach serves as the best method given the scientific interest in being able to capture and reproduce the structure of fitted brain networks

Effects of a Single Intra-Articular Injection of a Microsphere-Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study

Background: Intra-articular corticosteroids relieve osteoarthritis pain, but rapid systemic absorption limits efficacy. FX006, a novel, microsphere-based, extended-release triamcinolone acetonide (TA) formulation, prolongs TA joint residence and reduces systemic exposure compared with standard TA crystalline suspension (TAcs). We assessed symptomatic benefits and safety of FX006 compared with saline-solution placebo and TAcs. Methods: In this Phase-3, multicenter, double-blinded, 24-week study, adults ≥40 years of age with knee osteoarthritis (Kellgren-Lawrence grade 2 or 3) and average-daily-pain (ADP)-intensity scores of ≥5 and ≤9 (0 to 10 numeric rating scale) were centrally randomized (1:1:1) to a single intra-articular injection of FX006 (32 mg), saline-solution placebo, or TAcs (40 mg). The primary end point was change from baseline to week 12 in weekly mean ADP-intensity scores for FX006 compared with saline-solution placebo. Secondary end points were area-under-effect (AUE) curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with saline-solution placebo, AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, change in weekly mean ADP-intensity scores from baseline to week 12 for FX006 compared with TAcs, and AUE curves of the change in weekly mean ADP-intensity scores from baseline to week 24 for FX006 compared with saline-solution placebo. Exploratory end points included week-12 changes in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Injury and Osteoarthritis Outcome Score Quality of Life (KOOS-QOL) subscale scores for FX006 compared with saline-solution placebo and TAcs. Adverse events were elicited at each inpatient visit. Results: The primary end point was met. Among 484 treated patients (n = 161 for FX006, n = 162 for saline-solution placebo, and n = 161 for TAcs), FX006 provided significant week-12 improvement in ADP intensity compared with that observed for saline-solution placebo (least-squares mean change from baseline: −3.12 versus −2.14; p < 0.0001) indicating ∼50% improvement. FX006 afforded improvements over saline-solution placebo for all secondary and exploratory end points (p < 0.05). Improvements in osteoarthritis pain were not significant for FX006 compared with TAcs using the ADP-based secondary measures. Exploratory analyses of WOMAC-A, B, and C and KOOS-QOL subscales favored FX006 (p ≤ 0.05). Adverse events were generally mild, occurring at similar frequencies across treatments. Conclusions: FX006 provided significant, clinically meaningful pain reduction compared with saline-solution placebo at week 12 (primary end point)

Impact on diarrhoeal illness of a community educational intervention to improve drinking water quality in rural communities in Puerto Rico

<p>Abstract</p> <p>Background</p> <p>Waterborne disease is a major risk for small water supplies in rural settings. This study was done to assess the impact of an educational intervention designed to improve water quality and estimate the contribution of water to the incidence of diarrhoeal disease in poor rural communities in Puerto Rico a two-part study was undertaken.</p> <p>Methods</p> <p>An educational intervention was delivered to communities relying on community water supplies. This intervention consisted of student operators and administrators supervising and assisting community members who voluntarily "operate" these systems. These voluntary operators had no previous training and were principally concerned with seeing that some water was delivered. The quality of that water was not something they either understood or addressed. The impact of this intervention was measured through water sampling for standard bacteriological indicators and a frank pathogen. In addition, face-to-face epidemiological studies designed to determine the base-line occurrence of diarrhoeal disease in the communities were conducted. Some 15 months after the intervention a further epidemiological study was conducted in both the intervention communities and in control communities that had not received any intervention.</p> <p>Results</p> <p>Diarrhoeal illness rates over a four week period prior to the intervention were 3.5%. <it>Salmonella </it>was isolated from all of 5 distributed samples prior to intervention and from only 2 of 12 samples after the intervention. In the 15 months follow-up study, illness rates were lower in the intervention compared to control communities (2.5% <it>vs </it>3.6%%) (RR = 0.70, 95%CI 0.43, 1.15), though this was not statistically significant. However, in the final Poisson regression model living in an intervention system (RR = 0.318; 95%CI 0.137 - 0.739) and owning a dog (RR = 0.597, 95%CI 0.145 - 0.962) was negatively associated with illness. Whilst size of system (RR = 1.006, 95%CI 1.001 - 1.010) and reporting problems with sewage system (RR = 2.973, 95%CI 1.539 - 5.744) were positively associated with illness.</p> <p>Conclusions</p> <p>Educational interventions directed both at identified individuals and the community in general in small communities with poor water quality is a way of giving communities the skills and knowledge to manage their own drinking water quality. This may also have important and sustainable health benefits, though further research preferably using a randomised control trial design is needed.</p

The effects of weather and climate change on dengue

There is much uncertainty about the future impact of climate change on vector-borne diseases. Such uncertainty reflects the difficulties in modelling the complex interactions between disease, climatic and socioeconomic determinants. We used a comprehensive panel dataset from Mexico covering 23 years of province-specific dengue reports across nine climatic regions to estimate the impact of weather on dengue, accounting for the effects of non-climatic factors

Choice biases in no-sample and delay testing in pigeons (Columba livia)

In experimental tasks that involve stimuli that vary along a quantitative continuum, some choice biases are commonly found. Take, for instance, a matching-to-sample task where animals must, following the presentation of sample stimuli (that differ in duration), choose between two or more comparison stimuli. In tests where no sample is presented there is usually a bias towards the comparison that is correct following the shortest sample. To examine some aspects of these choice biases, pigeons were trained in a symbolic matching-to-sample task with two durations of keylight as samples, where key pecking had to be maintained during sample presentation. Firstly, even though animals were required to attend to the sample, a preference for the "short" comparison in no-sample testing was found. This result disproves an account where this effect was hypothesized to happen due to non-programmed learning resulting from the animals failing to attend to some trials. Secondly, even though a bias for "short" was found in both no-sample and delay testing, the extent of the biases differed between tasks, thus suggesting that forgetting the sample presented during a delay does not necessarily land the animal in a state similar to presenting no sample at all to begin with.The present study was supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds. It was also co-financed by the European Regional Development Fund (FEDER)-through COMPETE2020-under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653)

Denitrification and nitrous oxide emissions from riparian forests soils exposed to prolonged nitrogen runoff

Compared to upland forests, riparian forest soils have greater potential to remove nitrate (NO3) from agricultural run-off through denitrification. It is unclear, however, whether prolonged exposure of riparian soils to nitrogen (N) loading will affect the rate of denitrification and its end products. This research assesses the rate of denitrification and nitrous oxide (N2O) emissions from riparian forest soils exposed to prolonged nutrient run-off from plant nurseries and compares these to similar forest soils not exposed to nutrient run-off. Nursery run-off also contains high levels of phosphate (PO4). Since there are conflicting reports on the impact of PO4 on the activity of denitrifying microbes, the impact of PO4 on such activity was also investigated. Bulk and intact soil cores were collected from N-exposed and non-exposed forests to determine denitrification and N2O emission rates, whereas denitrification potential was determined using soil slurries. Compared to the non-amended treatment, denitrification rate increased 2.7- and 3.4-fold when soil cores collected from both N-exposed and non-exposed sites were amended with 30 and 60 μg NO3-N g-1 soil, respectively. Net N2O emissions were 1.5 and 1.7 times higher from the N-exposed sites compared to the non-exposed sites at 30 and 60 μg NO3-N g-1 soil amendment rates, respectively. Similarly, denitrification potential increased 17 times in response to addition of 15 μg NO3-N g-1 in soil slurries. The addition of PO4 (5 μg PO4–P g-1) to soil slurries and intact cores did not affect denitrification rates. These observations suggest that prolonged N loading did not affect the denitrification potential of the riparian forest soils; however, it did result in higher N2O emissions compared to emission rates from non-exposed forests

Опыт применения золадекса у больных эндометриозом и рецидивирующими гиперпластическими процессами эндометрия

ЭНДОМЕТРИОЗ /ЛЕК ТЕРЭНДОМЕТРИЯ ГИПЕРПЛАЗИЯ /ЛЕК ТЕРЗОЛАДЕК

The Two Faces of EU-NATO Cooperation:Counter-Piracy Operations off the Somali Coast

Maritime engagement in the Gulf of Aden is a puzzling case for anyone interested in the political and institutional problems underlying European Union–North Atlantic Treaty Organization (EU–NATO) cooperation. Although the EU’s operation NAVFOR ‘Atalanta’ and NATO’s ‘Ocean Shield’ operate in the same theatre and with similar mandates, there is no formal link between them. No joint planning has been envisaged, and no official task-sharing takes place. As this article aims to show, cooperation and coordination between EU and NATO forces at the operational and tactical levels have nevertheless worked surprisingly well. Two faces of EU–NATO cooperation become apparent: the political level is dominated by a permanent deadlock, while on the ground and at sea staff have developed a modus operandi that allows them to deliver fairly successfully in complementing yet detached operations. Based on 60 interviews with EU and NATO officials (2010–2013), this article illustrates how the operational and tactical levels have developed ways of coordinating efforts informally despite the lack of a formal framework. It aims to show to what extent and how they succeed at bypassing organizational boundaries and at overcoming political limitations. Although these practices are becoming increasingly institutionalized, it remains to be seen whether this will translate into formal changes