Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials

BACKGROUND AND PURPOSE Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

PEDro or Cochrane to Assess the Quality of Clinical Trials? A Meta-Epidemiological Study.

OBJECTIVE There is debate on how the methodological quality of clinical trials should be assessed. We compared trials of physical therapy (PT) judged to be of adequate quality based on summary scores from the Physiotherapy Evidence Database (PEDro) scale with trials judged to be of adequate quality by Cochrane Risk of Bias criteria. DESIGN Meta-epidemiological study within Cochrane Database of Systematic Reviews. METHODS Meta-analyses of PT trials were identified in the Cochrane Database of Systematic Reviews. For each trial PeDro and Cochrane assessments were extracted from the PeDro and Cochrane databases. Adequate quality was defined as adequate generation of random sequence, concealment of allocation, and blinding of outcome assessors (Cochrane criteria) or as trials with a PEDro summary score ≥5 or ≥6 points. We combined trials of adequate quality using random-effects meta-analysis. RESULTS Forty-one Cochrane reviews and 353 PT trials were included. All meta-analyses included trials with PEDro scores ≥5, 37 (90.2%) included trials with PEDro scores ≥6 and only 22 (53.7%) meta-analyses included trials of adequate quality according to the Cochrane criteria. Agreement between PeDro and Cochrane was poor for PeDro scores of ≥5 points (kappa = 0.12; 95% CI 0.07 to 0.16) and slight for ≥6 points (kappa 0.24; 95% CI 0.16-0.32). When combining effect sizes of trials deemed to be of adequate quality according to PEDro or Cochrane criteria, we found that a substantial difference in the combined effect size (≥0.15) was evident in 9 (22%) out of the 41 meta-analyses for PEDro cutoff ≥5 and 10 (24%) for cutoff ≥6. CONCLUSIONS The PeDro and Cochrane approaches lead to different sets of trials of adequate quality, and different combined treatment estimates from meta-analyses of these trials. A consistent approach to assessing RoB in trials of physical therapy should be adopted.

Addressing missing participant outcome data in dental clinical trials

Missing outcome data are common in clinical trials and despite a well-designed study protocol, some of the randomized participants may leave the trial early without providing any or all of the data, or may be excluded after randomization. Premature discontinuation causes loss of information, potentially resulting in attrition bias leading to problems during interpretation of trial findings. The causes of information loss in a trial, known as mechanisms of missingness, may influence the credibility of the trial results. Analysis of trials with missing outcome data should ideally be handled with intention to treat (ITT) rather than per protocol (PP) analysis. However, true ITT analysis requires appropriate assumptions and imputation of missing data. Using a worked example from a published dental study, we highlight the key issues associated with missing outcome data in clinical trials, describe the most recognized approaches to handling missing outcome data, and explain the principles of ITT and PP analysis.

The identification of child abuse in Harris County in 1998

Characteristics of child abuse cases are not well known. In this study I collected data on 70 child abuse cases that were reported to Children's Protective Services in Harris County in 1998. The purpose of this study was to determine the factors in Harris County that lead to the identification of physical and sexual abuse. In order to answer the questions of who, what, where and when relative to the discovery of abuse I applied the same questionnaire (see Appendix) to each of 35 Sexual Abuse case reports and to each of 35 Physical Abuse/Neglect case reports. Answers to the first four questions were arranged by frequency distribution to show the predominant reporter, the 10 most common indicators, the most common locale, and the most frequent timing. Tables of the age, sex, and ethnicity of the children indicate the identity of those whose victimization was most reported. In addition the relationship between the form questions and the characteristics of the children was explored. A comparison of Sexual Abuse cases with Physical Abuse/Neglect cases was conducted and the results were analyzed and recorded in the Tables. ^ Child maltreatment often has negative short and long term effects on children's mental health and development. Suicide, violence, delinquency, drug and alcohol abuse and other forms of criminality are frequently child abuse related. Early detection and treatment helps to alleviate the myriad mental and physical ailments that untreated victims present as adults. This translates into medical dollar savings. ^ The long term objectives of my research were to reduce the number of undetected and unreported child abuse cases in Harris County by formulating better educational programs and literature for medical professionals and other personnel who are in contact with children. ^

A categorical data analysis approach to estimation of demographic characteristics for Texas county populations

The need for timely population data for health planning and Indicators of need has Increased the demand for population estimates. The data required to produce estimates is difficult to obtain and the process is time consuming. Estimation methods that require less effort and fewer data are needed. The structure preserving estimator (SPREE) is a promising technique not previously used to estimate county population characteristics. This study first uses traditional regression estimation techniques to produce estimates of county population totals. Then the structure preserving estimator, using the results produced in the first phase as constraints, is evaluated.^ Regression methods are among the most frequently used demographic methods for estimating populations. These methods use symptomatic indicators to predict population change. This research evaluates three regression methods to determine which will produce the best estimates based on the 1970 to 1980 indicators of population change. Strategies for stratifying data to improve the ability of the methods to predict change were tested. Difference-correlation using PMSA strata produced the equation which fit the data the best. Regression diagnostics were used to evaluate the residuals.^ The second phase of this study is to evaluate use of the structure preserving estimator in making estimates of population characteristics. The SPREE estimation approach uses existing data (the association structure) to establish the relationship between the variable of interest and the associated variable(s) at the county level. Marginals at the state level (the allocation structure) supply the current relationship between the variables. The full allocation structure model uses current estimates of county population totals to limit the magnitude of county estimates. The limited full allocation structure model has no constraints on county size. The 1970 county census age - gender population provides the association structure, the allocation structure is the 1980 state age - gender distribution.^ The full allocation model produces good estimates of the 1980 county age - gender populations. An unanticipated finding of this research is that the limited full allocation model produces estimates of county population totals that are superior to those produced by the regression methods. The full allocation model is used to produce estimates of 1986 county population characteristics. ^

Family to Family: Child Welfare for the 21st Century

Child welfare services have undergone many revisions and transformations since their initiation. Some scholars trace the beginning of child welfare in the United States to events such as a 1655 Massachusetts conviction for maltreatment leading to the death of a 12-year-old boy (Watkins, 1990). The predominant philosophy of child welfare has shifted over time from an early emphasis on child saving, to child protection, to family preservation. Building on family preservation, one of the current transformations in child welfare that is taking place in isolated pockets to whole states, is family-centered, neighborhood-based services. One force behind implementation of this transformation is the Family to Family Initiative of the Annie E. Casey Foundation. This paper places family-centered, neighborhood-based child welfare services within the historical context of development of child welfare and within the recent move to reinvent human services (Adams & Nelson, 1995). Against this backdrop, a locality-based implementation of the Family to Family Initiative is described.

Eocene to Early Miocene palaeoclimate of Saxony, Germany (Table 4)

In the present study, proxy data concerning changes in atmospheric CO2 and climatic conditions from the Late Eocene to the Early Miocene were acquired by applying palaeobotanical methods. Fossil floras from 10 well-documented locations in Saxony, Germany, were investigated with respect to (1) stomatal density/index of fossil leaves from three different taxa (Eotrigonobalanus furcinervis, Laurophyllum pseudoprinceps and Laurophyllum acutimontanum), (2) the coexistence approach (CA) based on nearest living relatives (NLR) and (3) leaf margin analysis (LMA). Whereas the results of approach (1) indicate changes in atmospheric CO2 concentration, approaches (2) and (3) provide climate data. The results of the analysis of stomatal parameters indicate that the atmospheric CO2 concentration was higher during the Late Eocene than during the Early Oligocene and increased towards the Late Oligocene. A lower atmospheric pCO2 level after the Late Eocene is also suggested by an increase in marine palaeoproductivity at this time. From the Late Oligocene onwards, no changes in atmospheric CO2 concentration can be detected with the present data. For the considered sites, the results of the coexistence approach and of the leaf margin analysis document a significant cooling event from the Late Eocene to the Early Oligocene. The pCO2 decrease from the Late Eocene to the Early Oligocene indicated by the stomatal data raised in this study was thus coupled to a temperature decrease which is reflected by the present datasets. From the Early Oligocene onwards, however, no further fundamental climate change can be inferred for the considered locations. The pCO2 increase from the Early Oligocene to the Late Oligocene, which is indicated by the present data, is thus not accompanied by a climate change at the considered sites. A warming event during the Late Oligocene is, however, recorded by marine climate archives. According to the present data, no change in pCO2 occurred during the cooling event at the Oligocene/Miocene boundary, which is also indicated by marine data. The quality and validity of stomatal parameters as sensors for atmospheric CO2 concentration are discussed.

Eocene to Quaternary benthic foraminifers from the Izu-Bonin Arc

The benthic foraminifer fauna at Sumisu Rift Sites 790 and 791 indicates that a deep open-ocean (>2300 m) or a basin with open-ocean access existed between 1.1 and 0.7 Ma at the time of the initiation of rifting. The appearance of a low- to medium-oxygen fauna (1600-2300 m) between 0.7 and 0.5 Ma suggests that the open-ocean access may have been terminated at this time because of the development of volcanoes and rift flank uplifts around the basin. The occurrence of low-oxygen faunas at 0.03 Ma suggests a secondary closing of the basin. The lower bathyal benthic faunas from lower Pliocene sediments of rift margin Site 788 suggest about 0.6-1.6 km of total basement uplift. This uplift may have led to the formation of the major hiatus between 2.3 and <0.3 Ma. The faunal changes of benthic foraminifers at Sites 792 and 793 in the forearc basin document a shallowing water depth from below the carbonate compensation depth (CCD) (about 3.5 km) in the late early Oligocene to the present depths of 1800 and 2975 m, respectively. These data suggest about 1 km of total basement uplift in the inner part of the forearc basin (Site 792) and about 0.6 km total basement subsidence in the central part of the forearc basin (Site 793) since about 31 Ma. The former uplift led to a thinner sediment accumulation (800 m) and the latter subsidence to a thicker sediment accumulation (1400 m) at these sites. Faunal changes of benthic foraminifers observed in Sites 782 and 786 sequences drilled at the outer-arc high document a deepening water depth from 1.3 to 2.1 km in late Eocene to the present depth of about 3 km. These data suggest about 1.1-1.9 and 1.3-2.1 km of total basement subsidence at Sites 786 and 782, respectively. These results indicate total basement uplift in the inner part of the Bonin arc-trench system since late Oligocene and total basement subsidence in the outer part of the system since late Eocene. The last occurrence (LO) of Stilostomella spp. and Pleurostomella spp. and the first occurrence (F0) of Bulimina aculeata d'Orbigny occurred consistently at 0.7 Ma at all three arc proximal sites (790,791, and 792). This fact is taken to suggest a change of water mass, from one originating from the central part of the ocean to that originating from ocean-margin areas at that time.

Late Miocene to Early Pliocene radiolarians from ODP Hole 178-1095B

Early Pliocene to middle late Miocene hemipelagic and distal turbidite sediments from Hole 1095B, near the Antarctic Peninsula, yield moderately abundant, moderately well preserved radiolarian faunas and other biosiliceous material (diatoms, silicoflagellates, and sponge spicules). Preservation characteristics, however, vary strongly even between closely related samples, and there are many intervals of poor preservation. In the 140- to 460-meters below seafloor interval studied, it was possible to identify the following standard Southern Ocean radiolarian zones: Upsilon, Tau, Amphymenium challengerae, Acrosphaera? labrata, Siphonosphaera vesuvius, and upper Acrosphaera australis (total age range ~4-10 Ma). Some normally common radiolarian groups, such as actinommids, are unusually rare in the studied material, and the relative ranges of several individual species, such as Acrosphaera labrata vs. A. australis, appear to be somewhat anomalous. These observations imply that the ranges of taxa in this section may be somewhat diachronous, due to either local ecologic factors and/or the highly variable preservation of the faunas. Thus, the ages of events reported are probably only approximate, although they are still useful for constraining the age of sediments in this section.

A nucleolar protein related to ribosomal protein L7 is required for an early step in large ribosomal subunit biogenesis

The Saccharomyces cerevisiae Rlp7 protein has extensive identity and similarity to the large ribosomal subunit L7 proteins and shares an RNA-binding domain with them. Rlp7p is not a ribosomal protein; however, it is encoded by an essential gene and therefore must perform a function essential for cell growth. In this report, we show that Rlp7p is a nucleolar protein that plays a critical role in processing of precursors to the large ribosomal subunit RNAs. Pulse–chase labeling experiments with Rlp7p-depleted cells reveal that neither 5.8SS, 5.8SL, nor 25S is produced, indicating that both the major and minor processing pathways are affected. Analysis of processing intermediates by primer extension indicates that Rlp7p-depleted cells accumulate the 27SA3 precursor RNA, which is normally the major substrate (85%) used to produce the 5.8S and 25S rRNAs, and the ratio of 27SBL to 27SBS precursors changes from approximately 1:8 to 8:1 (depleted cells). Because 27SA3 is the direct precursor to 27SBS, we conclude that Rlp7p is specifically required for the 5′ to 3′ exonucleolytic trimming of the 27SA3 into the 27SBS precursor. As it is essential for processing in both the major and minor pathways, we propose that Rlp7p may act as a specificity factor that binds precursor rRNAs and tethers the enzymes that carry out the early 5′ to 3′ exonucleolytic reactions that generate the mature rRNAs. Rlp7p may also be required for the endonucleolytic cleavage in internal transcribed spacer 2 that separates the 5.8S rRNA from the 25S rRNA.

Differential Control of Xanthophylls and Light-Induced Stress Proteins, as Opposed to Light-Harvesting Chlorophyll a/b Proteins, during Photosynthetic Acclimation of Barley Leaves to Light Irradiance

Barley (Hordeum vulgare L.) plants were grown at different photon flux densities ranging from 100 to 1800 μmol m−2 s−1 in air and/or in atmospheres with reduced levels of O2 and CO2. Low O2 and CO2 partial pressures allowed plants to grow under high photosystem II (PSII) excitation pressure, estimated in vivo by chlorophyll fluorescence measurements, at moderate photon flux densities. The xanthophyll-cycle pigments, the early light-inducible proteins, and their mRNA accumulated with increasing PSII excitation pressure irrespective of the way high excitation pressure was obtained (high-light irradiance or decreased CO2 and O2 availability). These findings indicate that the reduction state of electron transport chain components could be involved in light sensing for the regulation of nuclear-encoded chloroplast gene expression. In contrast, no correlation was found between the reduction state of PSII and various indicators of the PSII light-harvesting system, such as the chlorophyll a-to-b ratio, the abundance of the major pigment-protein complex of PSII (LHCII), the mRNA level of LHCII, the light-saturation curve of O2 evolution, and the induced chlorophyll-fluorescence rise. We conclude that the chlorophyll antenna size of PSII is not governed by the redox state of PSII in higher plants and, consequently, regulation of early light-inducible protein synthesis is different from that of LHCII.

Midwife's testimony, Bristol Co. Massachusetts, 1727

Manuscript testimony, dated April 11, 1727, regarding the declaration of the paternity of a child out of wedlock born to Charity Caswell, probably in January of 1727. Signed by midwife Mary Crossman; also by Sarah Dean and Elizabeth Caswell.

Papers of Theophilus Parsons, 1778-1811

Bill to Timothy T. Ford for legal services performed from September 1778 to June 1779; letter to Judge Thomas Dawes regarding a probate case (1802); Parsons' report and opinion in the case of the proprietors of the Kennebec Purchase v. Boulton, et al. (1807); a statement of facts in the case of Brooks v. Dorr (1807); a note to Joseph Allen regarding a case (1810); and a letter to Foster regarding the Massachusetts Circuit Court of Common Pleas (1811).

Account book, ca. 1783-1820

Oblong notebook recording payments by William Bridge to various parties in Chelmsford, Tyngsborough, Groton and Dunstable, in Middlesex County, Massachusetts in the early 19th century. Bridge also records legal duties such as serving writs, and activities such as making hay and slaughtering livestock for or with other individuals which may indicate debt and payment. Elsewhere he records the birthdates of himself and his siblings and the deaths of his parents. Also included is a recipe to cure an ailing horse.

Warrant to attach goods of Abel Taylor, 1783

A warrant to seize nine pounds, the equal in property, or the body of Abel Taylor of Stow, to answer charges of debt brought by Nathan Smith of Weston.