A comparison of missing data methods for hypothesis tests of the treatment effect in substance abuse clinical trials: a Monte-Carlo simulation study

<p>Abstract</p> <p>Background</p> <p>Missing data due to attrition are rampant in substance abuse clinical trials. However, missing data are often ignored in the presentation of substance abuse clinical trials. This paper demonstrates missing data methods which may be used for hypothesis testing.</p> <p>Methods</p> <p>Methods involving stratifying and weighting individuals based on missing data pattern are shown to produce tests that are robust to missing data mechanisms in terms of Type I error and power. In this article, we describe several methods of combining data that may be used for testing hypotheses of the treatment effect. Furthermore, illustrations of each test's Type I error and power under different missing data percentages and mechanisms are quantified using a Monte-Carlo simulation study.</p> <p>Results</p> <p>Type I error rates were similar for each method, while powers depended on missing data assumptions. Specifically, power was greatest for the weighted, compared to un-weighted methods, especially for greater missing data percentages.</p> <p>Conclusion</p> <p>Results of this study as well as extant literature demonstrate the need for standards of design and analysis specific to substance abuse clinical trials. Given the known substantial attrition rates and concern for the missing data mechanism in substance abuse clinical trials, investigators need to incorporate missing data methods a priori. That is, missing data methods should be specified at the outset of the study and not after the data have been collected.</p

Subanesthetic ketamine treatment promotes abnormal interactions between neural subsystems and alters the properties of functional brain networks

Acute treatment with subanesthetic ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, is widely utilized as a translational model for schizophrenia. However, how acute NMDA receptor blockade impacts on brain functioning at a systems level, to elicit translationally relevant symptomatology and behavioral deficits, has not yet been determined. Here, for the first time, we apply established and recently validated topological measures from network science to brain imaging data gained from ketamine-treated mice to elucidate how acute NMDA receptor blockade impacts on the properties of functional brain networks. We show that the effects of acute ketamine treatment on the global properties of these networks are divergent from those widely reported in schizophrenia. Where acute NMDA receptor blockade promotes hyperconnectivity in functional brain networks, pronounced dysconnectivity is found in schizophrenia. We also show that acute ketamine treatment increases the connectivity and importance of prefrontal and thalamic brain regions in brain networks, a finding also divergent to alterations seen in schizophrenia. In addition, we characterize how ketamine impacts on bipartite functional interactions between neural subsystems. A key feature includes the enhancement of prefrontal cortex (PFC)-neuromodulatory subsystem connectivity in ketamine-treated animals, a finding consistent with the known effects of ketamine on PFC neurotransmitter levels. Overall, our data suggest that, at a systems level, acute ketamine-induced alterations in brain network connectivity do not parallel those seen in chronic schizophrenia. Hence, the mechanisms through which acute ketamine treatment induces translationally relevant symptomatology may differ from those in chronic schizophrenia. Future effort should therefore be dedicated to resolve the conflicting observations between this putative translational model and schizophrenia

Investigating the effects of external fields polarization on the coupling of pure magnetic waves in the human body in very low frequencies

In this paper we studied the effects of external fields' polarization on the coupling of pure magnetic fields into human body. Finite Difference Time Domain (FDTD) method is used to calculate the current densities induced in a 1 cm resolution anatomically based model with proper tissue conductivities. Twenty different tissues have been considered in this investigation and scaled FDTD technique is used to convert the results of computer code run in 15 MHz to low frequencies which are encountered in the vicinity of industrial induction heating and melting devices. It has been found that external magnetic field's orientation due to human body has a pronounced impact on the level of induced currents in different body tissues. This may potentially help developing protecting strategies to mitigate the situations in which workers are exposed to high levels of external magnetic radiation

High apex predator biomass on remote Pacific islands

Author Posting. © The Author(s), 2006. This is the author's version of the work. It is posted here by permission of Springer for personal use, not for redistribution. The definitive version was published in Coral Reefs 26 (2007): 47-51, doi:10.1007/s00338-006-0158-x.On coral reefs in Palmyra—a central Pacific atoll with limited fishing pressure—total fish biomass is 428 and 299% greater than on reefs in nearby Christmas and Fanning Islands. Large apex predators –groupers, sharks, snappers, and jacks larger than 50 cm in length- account for 56% of total fish biomass in Palmyra on average, but only 7% and 3% on Christmas and Fanning. These biomass proportions are remarkably similar to those previously reported for the remote and uninhabited Northwest Hawaiian Islands (NWHI) and densely populated Main Hawaiian Islands (MHI), although Palmyra’s reefs are dominated in biomass by sharks (44% of the total), whereas the NWHI by jacks (39%). Herbivorous fish biomass was also greater on Palmyra than on Christmas and Fanning (343% and 207%, respectively). These results and previous findings indicate that remote, uninhabited islands support high levels of consumers, and highlight the importance of healthy coral reef ecosystems as reference points for assessment of human impacts and establishment of restoration goals

Strong Double Higgs Production at the LHC

The hierarchy problem and the electroweak data, together, provide a plausible motivation for considering a light Higgs emerging as a pseudo-Goldstone boson from a strongly-coupled sector. In that scenario, the rates for Higgs production and decay differ significantly from those in the Standard Model. However, one genuine strong coupling signature is the growth with energy of the scattering amplitudes among the Goldstone bosons, the longitudinally polarized vector bosons as well as the Higgs boson itself. The rate for double Higgs production in vector boson fusion is thus enhanced with respect to its negligible rate in the SM. We study that reaction in pp collisions, where the production of two Higgs bosons at high pT is associated with the emission of two forward jets. We concentrate on the decay mode hh -> WW^(*)WW^(*) and study the semi-leptonic decay chains of the W's with 2, 3 or 4 leptons in the final states. While the 3 lepton final states are the most relevant and can lead to a 3 sigma signal significance with 300 fb^{-1} collected at a 14 TeV LHC, the two same-sign lepton final states provide complementary information. We also comment on the prospects for improving the detectability of double Higgs production at the foreseen LHC energy and luminosity upgrades.Comment: 54 pages, 26 figures. v2: typos corrected, a few comments and one table added. Version published in JHE

Protocol: does sodium nitrite administration reduce ischaemia-reperfusion injury in patients presenting with acute ST segment elevation myocardial infarction? Nitrites in acute myocardial infarction (NIAMI)

BACKGROUND: Whilst advances in reperfusion therapies have reduced early mortality from acute myocardial infarction, heart failure remains a common complication, and may develop very early or long after the acute event. Reperfusion itself leads to further tissue damage, a process described as ischaemia-reperfusion-injury (IRI), which contributes up to 50% of the final infarct size. In experimental models nitrite administration potently protects against IRI in several organs, including the heart. In the current study we investigate whether intravenous sodium nitrite administration immediately prior to percutaneous coronary intervention (PCI) in patients with acute ST segment elevation myocardial infarction will reduce myocardial infarct size. This is a phase II, randomised, placebo-controlled, double-blinded and multicentre trial. METHODS AND OUTCOMES: The aim of this trial is to determine whether a 5 minute systemic injection of sodium nitrite, administered immediately before opening of the infarct related artery, results in significant reduction of IRI in patients with first acute ST elevation myocardial infarction (MI). The primary clinical end point is the difference in infarct size between sodium nitrite and placebo groups measured using cardiovascular magnetic resonance imaging (CMR) performed at 6-8 days following the AMI and corrected for area at risk (AAR) using the endocardial surface area technique. Secondary end points include (i) plasma creatine kinase and Troponin I measured in blood samples taken pre-injection of the study medication and over the following 72 hours; (ii) infarct size at six months; (iii) Infarct size corrected for AAR measured at 6-8 days using T2 weighted triple inversion recovery (T2-W SPAIR or STIR) CMR imaging; (iv) Left ventricular (LV) ejection fraction measured by CMR at 6-8 days and six months following injection of the study medication; and (v) LV end systolic volume index at 6-8 days and six months. FUNDING,ETHICS AND REGULATORY APPROVALS: This study is funded by a grant from the UK Medical Research Council. This protocol is approved by the Scotland A Research Ethics Committee and has also received clinical trial authorisation from the Medicines and Healthcare products Regulatory Agency (MHRA) (EudraCT number: 2010-023571-26)

Belowground DNA-based techniques: untangling the network of plant root interactions

Contains fulltext : 91591.pdf (publisher's version ) (Closed access)7 p

Loss of circadian rhythm of blood pressure following acute stroke

BACKGROUND: Epidemiology of acute stroke in developing countries differs from that in the developed world, for example, the age at stroke, risk factors, subtypes of stroke and prognosis. Hypertension remains a dominant risk factor and prognostic indicator in patients with stroke in all communities. The risk of stroke is directly related to elevations of blood pressure. A number of clinical studies have shown that the control of hypertension leads to a reduction in the incidence of stroke in a community. However there is still considerable controversy surrounds the changes in blood pressure in various subtypes of strokes and problem of management of elevated BP after stroke. We studied the circadian rhythm of blood pressure in patients following acute stroke. METHODS: To study the circadian rhythm of blood pressure, fifty consecutive patients with an acute stroke who were admitted to medical emergency within 120 hours of onset were included in the study. After a detailed history and clinical examination, a continuous blood pressure monitor (Spacelab 90207) was attached on the side ipsilateral to intracranial lesion (unaffected arm). The blood pressure was recorded for 24 hours at 15 minutes interval during daytime (6.00 am–6.00 pm) and 20 minutes interval overnight (6 pm to 6 am). RESULTS: Risk factors for stroke in 50 patients included hypertension in 31(62%), diabetes mellitus in 4 (8%), smoking in 13 (26%) and previous history of transient ischemic attack in 7 (14%) patients. Mean systolic pressure and diastolic pressure at admission were higher in patients with hemorrhagic stroke -29 patients (177 ± 24 mmHg and 105 ± 19 mmHg respectively) compared to patients with ischemic strokes-21 patients (150 ± 36 mm Hg and 89 ± 18 mm Hg respectively, p value <0.01 in both comparisons). The normal diurnal variation in blood pressure (night time dipping of more than 10%) was abolished in 44 (88%) of patients. Out of 44 nondippers, 29 patients showed reverse dipping i.e. rise of BP during night time compared to day time levels. None of the risk factors, clinical or laboratory variables, type of stroke or blood pressure changes differed significantly between these two groups. CONCLUSIONS: Therefore, we showed a pathologically reduced or abolished circadian BP variation after stroke. Absence of normal dipping results in a higher 24 hour blood pressure load and may have more target organ damage than those with normal diurnal variation of blood pressure

Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)

The hierarchical organization of important sites for the conservation or the restoration of fish communities is a great challenge for managers, especially because of financial or time constraints. In this perspective, we developed a methodology, which is easy to implement in different locations. Based on the fish assemblage characteristics of the Loire basin (France), we created a synthetic conservation value index including the rarity, the conservation status and the species origin. The relationship between this new synthetic index and the Fish-Based Index allowed us to establish a classification protocol of the sites along the Loire including fish assemblages to be restored or conserved. Sites presenting disturbed fish assemblages, a low rarity index, few threatened species, and a high proportion of non-native species were considered as important for the restoration of fish biodiversity. These sites were found mainly in areas where the assemblages are typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic species. On the contrary, important sites for conservation were defined as having an important conservation potential (high RI, a lot of threatened species, and few nonnatives fish species) and an undisturbed fish assemblage similar to the expected community if habitats are undisturbed. Important sites for conservation were found in the Loire basin’s medium reaches which host assemblages typical for the grayling and the barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to management priorities and capacities

A Case Study of Crowdsourcing Imagery Coding in Natural Disasters

Crowdsourcing and open licensing allow more people to participate in research and humanitarian activities. Open data, such as geographic information shared through OpenStreetMap and image datasets from disasters, can be useful for disaster response and recovery work. This chapter shares a real-world case study of humanitarian-driven imagery analysis, using open-source crowdsourcing technology. Shared philosophies in open technologies and digital humanities, including remixing and the wisdom of the crowd, are reflected in this case study.This research was funded through the European Commission FP7-ICT project: Citizen Cyberlab: Technology Enhanced Creative Learning in the field of Citizen Cyberscience