The effect of heterogeneous variance on efficiency and power of cluster randomized trials with a balanced 2x2 factorial design

Sample size calculation for cluster randomized trials (CRTs) with a 2x2 factorial design is complicated due to the combination of nesting (of individuals within clusters) with crossing (of two treatments). Typically, clusters and individuals are allocated across treatment conditions in a balanced fashion, which is optimal under homogeneity of variance. However, the variance is likely to be heterogeneous if there is a treatment effect. An unbalanced allocation is then more efficient, but impractical because the optimal allocation depends on the unknown variances. Focusing on CRTs with a 2x2 design, this paper addresses two questions: How much efficiency is lost by having a balanced design when the outcome variance is heterogeneous? How large must the sample size be for a balanced allocation to have sufficient power under heterogeneity of variance? We consider different scenarios of heterogeneous variance. Within each scenario, we determine the relative efficiency of a balanced design, as a function of the level (cluster, individual, both) and amount of heterogeneity of the variance. We then provide a simple correction of the sample size for the loss of power due to heterogeneity of variance when a balanced allocation is used. The theory is illustrated with an example of a published 2x2 CRT

On the interior geometry of a typical black hole microstate

We argue that the region behind the horizon of a one-sided black hole can be probed by an analogue of the double-trace deformation protocol of Gao-Jafferis-Wall. This is achieved via a deformation of the CFT Hamiltonian by a term of the form ${\cal O} \widetilde{\cal O}$, where $\widetilde{\cal O}$ denote the state-dependent "mirror operators". We argue that this deformation creates negative energy shockwaves in the bulk, which allow particles inside the horizon to escape and to get directly detected in the CFT. This provides evidence for the smoothness of the horizon of black holes dual to typical states. We argue that the mirror operators allow us to perform an analogue of the Hayden-Preskill decoding protocol. Our claims rely on a technical conjecture about the chaotic behavior of out-of-time-order correlators on typical pure states at scrambling time.Comment: 5 page

Probing typical black hole microstates

We investigate the possibility that the geometry dual to a typical AdS black hole microstate corresponds to the extended AdS-Schwarzschild geometry, including a region spacelike to the exterior. We argue that this region can be described by the mirror operators, a set of state-dependent operators in the dual CFT. We probe the geometry of a typical state by considering state-dependent deformations of the CFT Hamiltonian, which have an interpretation as a one-sided analogue of the Gao-Jafferis-Wall traversable wormhole protocol for typical states. We argue that the validity of the conjectured bulk geometry requires that out-of-time-order correlators of simple CFT operators on typical pure states must exhibit the same chaotic effects as thermal correlators at scrambling time. This condition is related to the question of whether the product of operators separated by scrambling time obey the Eigenstate Thermalization Hypothesis. We investigate some of these statements in the SYK model and discuss similarities with state-dependent perturbations of pure states in the SYK model previously considered by Kourkoulou and Maldacena. Finally, we discuss how the mirror operators can be used to implement an analogue of the Hayden-Preskill protocol.Comment: 77 page

The clinical effectiveness of evidence-based interventions for depression: A pragmatic trial in routine practice

Abstract BACKGROUND: Controversy persists about how effectively empirically-supported treatments for major depression work in actual clinical practice as well as how patients choose among them. We examined the acute phase effectiveness of cognitive therapy (CT), interpersonal psychotherapy (IPT), and combined psychotherapy-pharmacotherapy (PHT) in a naturalistic setting, allowing patients their choice of treatment. METHODS: The study compared CT (n=63), IPT (n=56), CT-PHT (n=34), and IPT-PHT (n=21) for 174 subjects with major depression in a secondary care mood disorders clinic. Patient preference, rather than randomization, determined treatment selection. The Beck Depression Inventory-II (BDI) was the primary outcome variable. Exclusion criteria were minimal. RESULTS: All treatments were associated with a reduction in depressive symptoms, with a 35% remission rate by week 26. Overall improvement was well within ranges reported in efficacy trials. On average, treatment effects of the different interventions straddled the same range, but moderation analyses revealed that BDI scores dropped faster in the first 16 weeks in patients who received CT alone than patients who received CT and pharmacotherapy, a pattern not found in patients who received IPT (with or without pharmacotherapy). LIMITATIONS: Limitations consist of a modest sample size, choice of treatment was made by participants which may have been influenced by many sources, and the absence of a non-active control group. CONCLUSIONS: This study supports the effectiveness of empirically-supported antidepressant treatments selected by patients in routine settings, and provides an indication that speed of therapeutic response may vary amongst treatments

JMASM45: A Computer Program for Bayesian D-Optimal Binary Repeated Measurements Designs (Matlab)

Planners of longitudinal studies of binary responses in applied sciences have not yet benefitted from optimal designs, which have been shown to improve precision of model parameter estimates, due to absence of a computer program. An interactive computer program for Bayesian optimal binary repeated measurements designs is presented for this purpose

Paclitaxel for malignant pleural mesothelioma: a phase II study of the EORTC Lung Cancer Cooperative Group.

The EORTC Lung Cancer Cooperative Group undertook a phase II study of paclitaxel in 25 chemotherapy-naive patients with malignant pleural mesothelioma. Paclitaxel was given intravenously at a dose of 200 mg m-2 as a 3 h infusion every 3 weeks, after standard premedication with corticosteroids and antihistamines. This regimen was well tolerated, with < 4% of cycles resulting in severe toxicity. No major objective responses were observed and ten patients had stable disease. Median survival time was 39 weeks and the 1 year survival rate was 30%. In conclusion, paclitaxel at the dose and schedule investigated in this trial had no major activity in the treatment of malignant pleural mesothelioma

Multi-object spectroscopy of low-redshift EIS clusters IV. Reliability of matched-filter results at z~0.3-0.4

abridged) In this paper we present new redshifts for 747 galaxies in 23 ESO Imaging Survey (EIS) cluster fields. We use the "gap"-technique to search for significant overdensities in redshift space for identifying groups/clusters of galaxies. In this way we spectroscopically confirm systems in 10 of the 23 cluster candidate fields with a matched-filter estimated redshift z_MF=0.3-0.4 and with spectroscopic redshifts in the range from z=0.158 to z=0.534. We find that the systems identified in the present paper span a broad range of one-dimensional velocity dispersion (175-497 km/s) and richness (12L*<=L<=65L*). Both undersampling and contamination by substructures contribute to the uncertainty of these measurements. From the analysis of the colours of the galaxy populations we find that ~60% of the spectroscopically confirmed systems have a "significant" red sequence with a colour matching passive stellar evolution models. With this paper we complete our spectroscopic survey of the fields of 58 EIS cluster candidates with estimated redshifts z<=0.4. We have measured a total of 1954 galaxy redshifts in the range z=0.0065 to z=0.6706. Of the 58 systems we confirm 42 (~75%) with redshifts between z=0.095 and z=0.534.Comment: Accepted for publication in A&A, 19 pages, 11 figure

Removal of bacterial plant pathogens in columns filled with quartz and natural sediments under anoxic and oxygenated conditions

Irrigation with surface water carrying plant pathogens poses a risk for agriculture. Managed aquifer recharge enhances fresh water availability while simultaneously it may reduce the risk of plant diseases by removal of pathogens during aquifer passage. We compared the transport of three plant pathogenic bacteria with Escherichia coli WR1 as reference strain in saturated laboratory column experiments filled with quartz sand, or sandy aquifer sediments. E. coli showed the highest removal, followed by Pectobacterium carotovorum, Dickeya solani and Ralstonia solanacearum. Bacterial and non-reactive tracer breakthrough curves were fitted with Hydrus-1D and compared with colloid filtration theory (CFT). Bacterial attachment to fine and medium aquifer sand under anoxic conditions was highest with attachment rates of max. katt1 = 765 day-1 and 355 day-1, respectively. Attachment was the least to quartz sand under oxic conditions (katt1 = 61 day-1). In CFT, sticking efficiencies were higher in aquifer than in quartz sand but there was no differentiation between fine and medium aquifer sand. Overall removal ranged between < 6.8 log10 m−1 in quartz and up to 40 log10 m−1 in fine aquifer sand. Oxygenation of the anoxic aquifer sediments for two weeks with oxic influent water decreased the removal. The results highlight the potential of natural sand filtration to sufficiently remove plant pathogenic bacteria during aquifer storage

Natuurkwaliteit en biodiversiteit van de Nederlandse zoute wateren

Van de biodiversiteit in de Nederlandse zoute wateren is momenteel nog ongeveer 40% aanwezig van de biodiversiteit die zou bestaan in een oorspronkelijke, meer natuurlijke situatie. Deze conclusie is gebaseerd op een grote hoeveelheid gegevens over kenmerkende soorten en eigenschappen van de Nederlandse mariene ecosysteme