Missing data in randomized clinical trials for weight loss: scope of the problem, state of the field, and performance of statistical methods.

BACKGROUND: Dropouts and missing data are nearly-ubiquitous in obesity randomized controlled trails, threatening validity and generalizability of conclusions. Herein, we meta-analytically evaluate the extent of missing data, the frequency with which various analytic methods are employed to accommodate dropouts, and the performance of multiple statistical methods. METHODOLOGY/PRINCIPAL FINDINGS: We searched PubMed and Cochrane databases (2000-2006) for articles published in English and manually searched bibliographic references. Articles of pharmaceutical randomized controlled trials with weight loss or weight gain prevention as major endpoints were included. Two authors independently reviewed each publication for inclusion. 121 articles met the inclusion criteria. Two authors independently extracted treatment, sample size, drop-out rates, study duration, and statistical method used to handle missing data from all articles and resolved disagreements by consensus. In the meta-analysis, drop-out rates were substantial with the survival (non-dropout) rates being approximated by an exponential decay curve (e(-lambdat)) where lambda was estimated to be .0088 (95% bootstrap confidence interval: .0076 to .0100) and t represents time in weeks. The estimated drop-out rate at 1 year was 37%. Most studies used last observation carried forward as the primary analytic method to handle missing data. We also obtained 12 raw obesity randomized controlled trial datasets for empirical analyses. Analyses of raw randomized controlled trial data suggested that both mixed models and multiple imputation performed well, but that multiple imputation may be more robust when missing data are extensive. CONCLUSION/SIGNIFICANCE: Our analysis offers an equation for predictions of dropout rates useful for future study planning. Our raw data analyses suggests that multiple imputation is better than other methods for handling missing data in obesity randomized controlled trials, followed closely by mixed models. We suggest these methods supplant last observation carried forward as the primary method of analysis.

Simulating one of the CIB W14 round robin test cases using the SMARTFIRE fire field model

Numerical predictions produced by the SMARTFIRE fire field model are compared with experimental data. The predictions consist of gas temperatures at several locations within the compartment over a 60 min period. The test fire, produced by a burning wood crib attained a maximum heat release rate of approximately 11MW. The fire is intended to represent a nonspreading fire (i.e. single fuel source) in a moderately sized ventilated room. The experimental data formed part of the CIB Round Robin test series. Two simulations are produced, one involving a relatively coarse mesh and the other with a finer mesh. While the SMARTFIRE simulations made use of a simple volumetric heat release rate model, both simulations were found capable of reproducing the overall qualitative results. Both simulations tended to overpredict the measured temperatures. However, the finer mesh simulation was better able to reproduce the qualitative features of the experimental data. The maximum recorded experimental temperature (12141C after 39 min) was over-predicted in the fine mesh simulation by 12%. (C) 2001 Elsevier Science Ltd. All rights reserved.

The study of flow and temperature fields in conducting droplets suspended in a DC/AC combination field

Electromagnetic Levitation (EML) is a valuable method for measuring the thermo-physical properties of metals - surface tensions, viscosity, thermal/electrical conductivity, specific heat, hemispherical emissivity, etc. – beyond their melting temperature. In EML, a small amount of the test specimen is melted by Joule heating in a suspended AC coil. Once in liquid state, a small perturbation causes the liquid envelope to oscillate and the frequency of oscillation is then used to compute its surface tension by the well know Rayleigh formula. Similarly, the rate at which the oscillation is dampened relates to the viscosity. To measure thermal conductivity, a sinusoidally varying laser source may be used to heat the polar axis of the droplet and the temperature response measured at the polar opposite – the resulting phase shift yields thermal conductivity. All these theoretical methods assume that convective effects due to flow within the droplet are negligible compared to conduction, and similarly that the flow conditions are laminar; a situation that can only be realised under microgravity conditions. Hence the EML experiment is the method favoured for Spacelab experiments (viz. TEMPUS). Under terrestrial conditions, the full gravity force has to be countered by a much larger induced magnetic field. The magnetic field generates strong flow within the droplet, which for droplets of practical size becomes irrotational and turbulent. At the same time the droplet oscillation envelope is no longer ellipsoidal. Both these conditions invalidate simple theoretical models and prevent widespread EML use in terrestrial laboratories. The authors have shown in earlier publications that it is possible to suppress most of the turbulent convection generated in the droplet skin layer, through use of a static magnetic field. Using a pseudo-spectral discretisation method it is possible compute very accurately the dynamic variation in the suspended fluid envelope and simultaneously compute the time-varying electromagnetic, flow and thermal fields. The use of a DC field as a dampening agent was also demonstrated in cold crucible melting, where suppression of turbulence was achieved in a much larger liquid metal volume and led to increased superheat in the melt and reduction of heat losses to the water-cooled walls. In this paper, the authors describe the pseudo-spectral technique as applied to EML to compute the combined effects of AC and DC fields, accounting for all the flow-induced forces acting on the liquid volume (Lorentz, Maragoni, surface tension, gravity) and show example simulations.

Effect Of Temperature On The Respiration Rate Of Meiofauna

The effect of temperature on respiration rate has been established, using Cartesian divers, for the meiofaunal sabellid polychaeteManayunkia aestuarina, the free-living nematodeSphaerolaimus hirsutus and the harpacticoid copepodTachidius discipes from a mudflat in the Lynher estuary, Cornwall, U.K. Over the temperature range normally experienced in the field, i.e. 5–20° C the size-compensated respiration rate (R c) was related to the temperature (T) in °C by the equation Log10 R c=-0.635+0.0339T forManayunkia, Log10 R c=0.180+0.0069T forSphaerolaimus and Log10 R c=-0.428+0.0337T forTachidius, being equivalent toQ 10 values of 2.19, 1.17 and 2.17 respectively. In order to derive the temperature response forManayunkia a relationship was first established between respiration rate and body size: Log10 R=0.05+0.75 Log10 V whereR=respiration in nl·O2·ind-1·h-1 andV=body volume in nl. TheQ 10 values are compared with values for other species derived from the literature. From these limited data a dichotomy emerges: species with aQ 10≏2 which apparently feed on diatoms and bacteria, the abundance of which are subject to large short term variability, and species withQ 10≏1 apparently dependent on more stable food sources.

Simultaneous Determination Of Fluctuating Age Structure And Mortality From Field Data

The use of a Leslie matrix for analysis of a population normally implies that the age structure of the population is known. However, this restriction can be overcome if the population can be partitioned into recognisably different stages, and some information on stage duration and fecundity is available, in which case the age structure may be determined by the analysis itself. As an example of this approach we consider the estimation of the mortality rate applying to a population from a sequence of observed stage frequency vectors. The technique does not require that the population has attained a stable age structure nor that distinct cohorts can be recognised.

Ecological And Metabolic Studies On Free-Living Nematodes From An Estuarine Mud-Flat

Nematodes from a mud-flat in the river Lynher estuary, Cornwall, U.K., have a population density ranging between 8 and 9 × 106 m−2 in the winter months, corresponding to a dry weight of 1·4 and 1·6 g m−2. They reach a peak abundance of 22·86 × 106 m−2 (3·4 g) in May. About 40 species are present, and the species composition remained seasonally stable over the period of study. Analysis of age-structure suggests that the major species have continuous asynchronous reproduction. Respiration rates of 16 species have been determined at 20 °C using Cartesian diver respirometry. For five species, respiration/body size regressions were obtained in the form log10R = log10a+b log10V, where R = respiration in nl O2 ind−1 h−1 and V = body volume in nl: Mesotheristus setosus (log10a = −0·04,b = 0·74), Sphaerolaimus hirsutus (log10a = 0·11, b = 0·68), Axonolaimus paraspinosus (log10a = 0·00, b = 0·79), Metachromadora vivipara (log10a = −0·59, b = 1·07), Praeacanthonchus punctatus (log10a = 0·00, b = 0·55). For the remaining 11 species, several animals were used in each diver and, by assuming b = 0·75, log10a′ values were calculated: Viscosia viscosa (log10a′ = 0·188), Innocuonema tentabundum (−0·012), Ptycholaimellus ponticus (−0·081), Odontophora setosa (−0·092), Sphaerolaimus balticus (−0·112), Dichromadora cephalata (−0·133), Atrochromadora microlaima (−0·142), Cylindrotheristus normandicus (−0·150), Terschellingialongicaudata (−0·170), Sabatieria pulchra (−0·197), Terschellingia communis (−0·277). These values are compared with recalculated values for other species from the literature. Annual respiration of the nematode community is 28·01 O2 m−2, equivalent to 11·2 g carbon metabolised. Community respiration is compared with figures from N. American saltmarshes. At 20 °C, a respiration of about 61 O2 m−2 year−1 g−1 wet weight of nematodes appears to be typical. Annual production is estimated to be 6·6 g C m−2. The correlation between feeding-group, body-size, habitat and the repiration rate of individual species is discussed.

Physiological-Responses Of Mytilus-Edulis L To Parasitic Infestation By Mytilicola-Intestinalis

Various levels of infestation by Mytilicola had no effect on the rates of oxygen consumption by Mytilus edulis in laboratory experiments. However, high levels of infestation (> 10 parasites per mussel) caused a depression in the feeding rate of the host at high temperatures (22° or 23° C) and low ration (maintenance or sub-maintenance). This depression of feeding resulted in a decline in the scope for growth, which would result in time in a decline in the “condition” of the host. It is concluded that similar effects may occur in the field when large numbers of small parasites are present at a time of high metabolic demand and low food availability.

High harmonic generation by halogen anions and noble gas atoms in a laser field

A comparative study of high harmonic generation (HHG) by atoms and ions with active p-electrons is carried out in the theoretical framework of the rescattering mechanism. The substate with m(l) = 0, i.e. zero orbital momentum projection along the electric vector of a linearly polarized laser wave, is found to give the major contribution to the HHG rate. Our calculations for HHG by an H atom in an excited 2p-state demonstrate that the rate for recombination into a final state with a different value of m(l) (= +/- 1), is higher for lower harmonic orders N, while for higher N (beyond the plateau domain) the difference vanishes. For species with closed electron shells, the m(l)-changing transitions are forbidden by the Pauli exclusion principle. We report absolute HHG rates for halogen ions and noble gas atoms at various intensities. These results demonstrate that the Coulomb binding potential of the atoms considerably enhances both the ionization and recombination steps in the rescattering process. However, the weak binding energy of the anions allows lower orders of HHG to be efficiently produced at relatively low intensities, from which we conclude that observation of HHG by an anion is experimentally feasible.

Resting and daily energy expenditures of free-living field voles are positively correlated but reflect extrinsic rather than intrinsic effects

Resting metabolic rates at thermoneutral (RMRts) are unexpectedly variable. One explanation is that high RMRts intrinsically potentiate a greater total daily energy expenditure (DEE), but recent work has suggested that DEE is extrinsically defined by the environment, which independently affects RMRt. This extrinsic effect could occur because expenditure is forced upwards in poor habitats or enabled to rise in good habitats. We provide here an intraspecific test for an association between RMRt and DEE that separates intrinsic from extrinsic effects and forcing from enabling effects. We measured the DEE and RMRt of 75 free-living short-tailed field voles at two time points in late winter. Across all sites, there was a positive link between individual variation in RMRt and DEE. This correlation, however, emerged only because of an effect across sites, rather than because of an intrinsic association within sites. We defined site quality from the survivorship of voles at the sites and the time at which they commenced breeding in spring. The associations between DEE/RMRt and site quality suggested that in February voles in poorer sites had higher energy demands, indicating that DEE was forced upwards, but in March the opposite was true, with higher demands in good sites, indicating that high expenditure was enabled. These data show that daily energy demands are extrinsically defined, with a link to RMRt that is secondary or independent. Both forcing and enabling effects of the environment may pertain at different times of year.

Dynamics of nonlinearly coupled magnetic-field-aligned electromagnetic electron-cyclotron waves near the zero-group-dispersion point in magnetized plasmas

The nonlinear coupling between two magnetic-field-aligned electromagnetic electron-cyclotron (EMEC) waves in plasmas is considered. Evaluating the ponderomotive coupling between the EMEC waves and quasistationary plasma density perturbations, a pair of coupled nonlinear Schrodinger equations (CNLSEs) is obtained. The CNLSEs are then used to investigate the occurrence of modulational instability in magnetized plasmas. Waves in the vicinity of the zero-group-dispersion point are considered, so that the group dispersion terms may either bear the same or different signs. It is found that a stable EMEC wave can be destabilized due to its nonlinear interactions with an unstable one, while a pair of unstable EMEC waves yields an increased instability growth rate. Individually stable waves remain stable while interacting with one another. Stationary nonlinear solutions of the coupled equations are presented. The relevance of our investigation to nonlinear phenomena in space plasmas is discussed. (c) 2005 American Institute of Physics.

The level playing field: the impact of assessment practice on professional development

Context: The effects of assessment practice on students’ learning are unclear, particularly regarding professional development. Corralling in objective structured clinical examinations (OSCEs) is designed to reduce illicit passing of examination information. Candidates completing an examination are kept secluded until the next cohort of examinees has begun. We used the introduction of corralling as a context in which to explore social influences on examination misconduct, with the aims of improving understanding of the hidden effects of assessment, and evaluating the acceptability of corralling from the student perspective.

Methods: A questionnaire was administered to students corralled post-OSCE for the first time. Eleven semi-structured interviews were subsequently conducted. Questionnaire data were analysed for descriptive statistics and thematic analysis of interview transcripts was carried out.

Results: The questionnaire response rate was 95.4% (251/263). Before corralling, 80.9% (203/251) of students were aware of the sharing of information among peers and 78.5% (197/251) agreed that such misconduct was unprofessional. The majority were in favour of corralling (90.8%, 228/251). Four themes emerged from the semi-structured interviews: the student network versus the individual; assessment-driven culture; the deferring of professionalism, and the ‘level playing field’. Students saw interaction within the student network, on a background of assessment-driven culture, as the key driver in examination misconduct. Conforming to the rules of the social network was prioritised over individual agency, although the mismatch between the rules of the network and the dominant professional discourse caused some conflict for individuals. Deferred professionalism (described as the practice of taking on the norms of professional behaviour only when qualified) was a rationalisation used to minimise this conflict. Corralling provided a ‘level playing field’ in which the influences of the network were minimised.

Conclusions: Examination misconduct is thus a complex social construction with implications for individual learners in terms of professional development. Corralling is one mechanism for addressing misconduct that is acceptable to students, but assessment processes have important hidden effects which educators should acknowledge.

A Monte Carlo model of DNA double-strand break clustering and rejoining kinetics for the analysis of pulsed-field gel electrophoresis data

In studies of radiation-induced DNA fragmentation and repair, analytical models may provide rapid and easy-to-use methods to test simple hypotheses regarding the breakage and rejoining mechanisms involved. The random breakage model, according to which lesions are distributed uniformly and independently of each other along the DNA, has been the model most used to describe spatial distribution of radiation-induced DNA damage. Recently several mechanistic approaches have been proposed that model clustered damage to DNA. In general, such approaches focus on the study of initial radiation-induced DNA damage and repair, without considering the effects of additional (unwanted and unavoidable) fragmentation that may take place during the experimental procedures. While most approaches, including measurement of total DNA mass below a specified value, allow for the occurrence of background experimental damage by means of simple subtractive procedures, a more detailed analysis of DNA fragmentation necessitates a more accurate treatment. We have developed a new, relatively simple model of DNA breakage and the resulting rejoining kinetics of broken fragments. Initial radiation-induced DNA damage is simulated using a clustered breakage approach, with three free parameters: the number of independently located clusters, each containing several DNA double-strand breaks (DSBs), the average number of DSBs within a cluster (multiplicity of the cluster), and the maximum allowed radius within which DSBs belonging to the same cluster are distributed. Random breakage is simulated as a special case of the DSB clustering procedure. When the model is applied to the analysis of DNA fragmentation as measured with pulsed-field gel electrophoresis (PFGE), the hypothesis that DSBs in proximity rejoin at a different rate from that of sparse isolated breaks can be tested, since the kinetics of rejoining of fragments of varying size may be followed by means of computer simulations. The problem of how to account for background damage from experimental handling is also carefully considered. We have shown that the conventional procedure of subtracting the background damage from the experimental data may lead to erroneous conclusions during the analysis of both initial fragmentation and DSB rejoining. Despite its relative simplicity, the method presented allows both the quantitative and qualitative description of radiation-induced DNA fragmentation and subsequent rejoining of double-stranded DNA fragments. (C) 2004 by Radiation Research Society.

Field fluxes and speciation of arsines emanating from soils

The biogeochemical cycle of arsenic (As) has been extensively studied over the past decades because As is an environmentally ubiquitous, nonthreshold carcinogen, which is often elevated in drinking water and food. It has been known for over a century that micro-organisms can volatilize inorganic As salts to arsines (arsine AsH(3), mono-, di-, and trimethylarsines, MeAsH(2), Me(2)AsH, and TMAs, respectively), but this part of the As cycle, with the exception of geothermal environs, has been almost entirely neglected because of a lack of suited field measurement approaches. Here, a validated, robust, and low-level field-deployable method employing arsine chemotrapping was used to quantify and qualify arsines emanating from soil surfaces in the field. Up to 240 mg/ha/y arsines was released from low-level polluted paddy soils (11.3 ± 0.9 mg/kg As), primarily as TMAs, whereas arsine flux below method detection limit was measured from a highly contaminated mine spoil (1359 ± 212 mg/kg As), indicating that soil chemistry is vital in understanding this phenomenon. In microcosm studies, we could show that under reducing conditions, induced by organic matter (OM) amendment, a range of soils varied in their properties, from natural upland peats to highly impacted mine-spoils, could all volatilize arsines. Volatilization rates from 0.5 to 70 µg/kg/y were measured, and AsH(3), MeAsH(2), Me(2)AsH, and TMAs were all identified. Addition of methylated oxidated pentavalent As, namely monomethylarsonic acid (MMAA) and dimethylarsinic acid (DMAA), to soil resulted in elevated yearly rates of volatilization with up to 3.5% of the total As volatilized, suggesting that the initial conversion of inorganic As to MMAA limits the rate of arsine and methylarsines production by soils. The nature of OM amendment altered volatilization quantitatively and qualitatively, and total arsines release from soil showed correlation between the quantity of As and the concentration of dissolved organic carbon (DOC) in the soil porewater. The global flux of arsines emanating from soils was estimated and placed in the context of As atmospheric inputs, with arsines contributing from 0.9 to 2.6% of the global budget.

Seasonal differences in the effects of oscillatory and uni-directional flow on the growth and nitrate-uptake rates of juvenile Laminaria digitata (Phaeophyceae)

The influence of oscillatory versus unidirectional flow on the growth and nitrate-uptake rates of juvenile kelp, Laminaria digitata, was determined seasonally in experimental treatments that simulated as closely as possible natural environmental conditions. In winter, regardless of flow condition (oscillatory and unidirectional) or water velocity, no influence of water motion was observed on the growth rate of L. digitata. In summer, when ambient nitrate concentrations were low, increased water motion enhanced macroalgal growth, which is assumed to be related to an increase in the rate of supply of nutrients to the blade surface. Nitrate-uptake rates were significantly influenced by water motion and season. Lowest nitrate-uptake rates were observed for velocities <5 cm · s−1 and nitrate-uptake rates increased by 20%–50% under oscillatory motion compared to unidirectional flow at the same average speed. These data further suggested that the diffusion boundary layer played a significant role in influencing nitrate-uptake rates. However, while increased nitrate-uptake in oscillatory flow was clear, this was not reflected in growth rates and further work is required to understand the disconnection of nitrate-uptake and growth by L. digitata in oscillatory flow. The data obtained support those from related field-based studies, which suggest that in summer, when insufficient nitrogen is available in the water to saturate metabolic demand, the growth rate of kelps will be influenced by water motion restricting mass transfer of nitrogen.