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The mining of sand resources from the inner continental shelf for beach nourishment may lead to impacts or increase stress on commercial and noncommercial living resources that utilize these areas. The objective of our work was to characterize benthos present in areas likely to be mined and to predict impacts of sand mining. In 1998 and 1999 we used a combination of methods (grab samples, sediment profile cameras, video sled, and trawl) to collect data on the benthos, both fishes and invertebrates, which utilized several potential sand mining areas. We found benthic communities and fish assemblages to be typical of middle Atlantic sandy inner continental shelf habitats. A sand mining scenario that removed the top meter of sand from Fenwick Shoal would disturb approximately 7.7 km2 with the potential acute impact on noncommercial sessile species being the loss of about 150 × 106 individuals representing 300 kg of wet weight biomass that could have functioned as trophic support to fishes. In additi...

Patterns of seafloor topography represent regions of geomorphological feature types and the physiography governing the spatial distributions of benthic habitats. Topographic variability can be considered seafloor texture and can be remotely sensed by acoustic and optical devices. Benthic habitat delineations often involve distinctions based upon seafloor morphology and composition based upon acoustic data maps that are ground-truthed by optical imaging tools. Habitat delineations can be done manually, however, automation of the procedure could provide more objectivity and reproducible map products. Recently a technique using Fourier transforms (FT) to produce texture features called local Fourier histograms (LFH) has been used successfully to classify standard textures in grayscale images and automatically retrieve digital images from archives according to texture content [Zhou, F., Feng, J., Shi, Q., 2001. Texture feature based on local Fourier transform, ICIP Conference Proceedings, IEEE 0-7803-6725-1/01.]. We implemented a modified form of that approach by varying the spatial scales at which local Fourier histograms were calculated. A modified LFH texture feature classification technique was applied to multibeam echosounder (MBES) data from Piscataqua River, New Hampshire, USA, for automatic delineation of a seafloor topographic map into regions of distinct geomorphology and apparent benthic habitats. Automated segmentations were done by the LFH method on 1-m gridded MBES data, applying the local Fourier transform, used to generate the LFH, at spatial scales from 1 to 5 m. Seven seafloor texture classes were identified, corresponding to the primary substrate types and configurations in the study area as well as some previously unidentified regions and transitional zones. The texture regions serve as a physical habitat model for the seafloor, a basis for predicting benthic faunal inhabitants, their areal distributions, and serving as sampling strata for ground-truthing efforts.

Fish-habitat relationships on the shallow inner continental shelf were quantified with video sled and metered beam trawl on Fenwick and Weaver shoals offshore of Maryland and Delaware, U.S. These areas provide megascale physical relief and habitat complexity, but for juvenile fishes, mesoscale and microscale habitat is very important particularly as refuge from predation. At these smaller scales, much of the relief on the inner continental shelf is contributed by bedforms or sand waves and biogenic structures such as tubes, shell beds, or pits. A quantitative association for juvenile fishes between and within benthic habitats was found and related primarily to bedform size and amount of biogenic structure. The incidence of fishes was about four-times higher for large bedforms (> 30 cm wavelength and about 10 cm crest height) relative to smaller bedforms (

Changes in hardware or image-processing settings are a common issue for large multicenter studies. To pool MRI data acquired under these changed conditions, it is necessary to demonstrate that the changes do not affect MRI-based measurements. In these circumstances, classical inference testing is inappropriate because it is designed to detect differences, not prove similarity. We used a method known as statistical equivalence testing to address this limitation. Equivalence testing was carried out on 3 datasets: (1) cortical thickness and automated hippocampal volume estimates obtained from healthy individuals imaged using different multichannel head coils; (2) manual hippocampal volumetry obtained using two readers; and (3) corpus callosum area estimates obtained using an automated method with manual cleanup carried out by two readers. Equivalence testing was carried out using the "two one-sided tests" (TOST) approach. Power analyses of the TOST were used to estimate sample sizes required for well-powered equivalence testing analyses. Mean and standard deviation estimates from the automated hippocampal volume dataset were used to carry out an example power analysis. Cortical thickness values were found to be equivalent over 61% of the cortex when different head coils were used (q.05, false discovery rate correction). Automated hippocampal volume estimates obtained using the same two coils were statistically equivalent (TOST P = 4.28 × 10(-15) ). Manual hippocampal volume estimates obtained using two readers were not statistically equivalent (TOST P = .97). The use of different readers to carry out limited correction of automated corpus callosum segmentations yielded equivalent area estimates (TOST P = 1.28 × 10(-14) ). Power analysis of simulated and automated hippocampal volume data demonstrated that the equivalence margin affects the number of subjects required for well-powered equivalence tests. We have presented a statistical method for determining if morphometric measures obtained under variable conditions can be pooled. The equivalence testing technique is applicable for analyses in which experimental conditions vary over the course of the study.

Background: Activation of GRK2 requires interaction with agonist-occupied GPCRs. Results: Residues on the GRK2 N terminus and kinase domain extension collaborate to create a GPCR docking site. Conclusion: Three GRK subfamilies use similar determinants to create the putative docking site, but subtle differences may dictate selectivity. Significance: Mapping the GRK-GPCR interface is required to understand the mechanism and specificity of GRK activation, and, therefore, the regulation of GPCRs., G protein-coupled receptor kinases (GRKs) phosphorylate agonist-occupied receptors initiating the processes of desensitization and β-arrestin-dependent signaling. Interaction of GRKs with activated receptors serves to stimulate their kinase activity. The extreme N-terminal helix (αN), the kinase small lobe, and the active site tether (AST) of the AGC kinase domain have previously been implicated in mediating the allosteric activation. Expanded mutagenesis of the αN and AST allowed us to further assess the role of these two regions in kinase activation and receptor phosphorylation in vitro and in intact cells. We also developed a bioluminescence resonance energy transfer-based assay to monitor the recruitment of GRK2 to activated α2A-adrenergic receptors (α2AARs) in living cells. The bioluminescence resonance energy transfer signal exhibited a biphasic response to norepinephrine concentration, suggesting that GRK2 is recruited to Gβγ and α2AAR with EC50 values of 15 nm and 8 μm, respectively. We show that mutations in αN (L4A, V7E, L8E, V11A, S12A, Y13A, and M17A) and AST (G475I, V477D, and I485A) regions impair or potentiate receptor phosphorylation and/or recruitment. We suggest that a surface of GRK2, including Leu4, Val7, Leu8, Val11, and Ser12, directly interacts with receptors, whereas residues such as Asp10, Tyr13, Ala16, Met17, Gly475, Val477, and Ile485 are more important for kinase domain closure and activation. Taken together with data on GRK1 and GRK6, our data suggest that all three GRK subfamilies make conserved interactions with G protein-coupled receptors, but there may be unique interactions that influence selectivity.

BackgroundIn the main Digitalis Investigation Group (DIG) trial, digoxin reduced the risk of 30-day all-cause hospitalization in older systolic heart failure patients. However, this effect has not been studied in older diastolic heart failure patients.MethodsIn the ancillary DIG trial, of the 988 patients with chronic heart failure and preserved (> 45%) ejection fraction, 631 were age ≥ 65 years (mean age 73 years, 45% women, 12% non-whites), of whom 311 received digoxin.ResultsAll-cause hospitalization 30-day post randomization occurred in 4% of patients in the placebo group and 9% each among those in the digoxin group receiving 0.125 mg and ≥ 0.25 mg a day dosage (P = .026). Hazard ratios (HR) and 95% confidence intervals (CI) for digoxin use overall for 30-day, 3-month, and 12-month all-cause hospitalizations were 2.46 (1.25-4.83), 1.45 (0.96-2.20) and 1.14 (0.89-1.46), respectively. There was one 30-day death in the placebo group. Digoxin-associated HRs (95% CIs) for 30-day hospitalizations due to cardiovascular, heart failure, and unstable angina causes were 2.82 (1.18-6.69), 0.51 (0.09-2.79), and 6.21 (0.75-51.62), respectively. Digoxin had no significant association with 30-day all-cause hospitalization among younger patients (6% vs 7% for placebo; HR 0.80; 95% CI, 0.36-1.79).ConclusionsIn older patients with chronic diastolic heart failure, digoxin increased the risk of 30-day all-cause hospital admission, but not during longer follow-up. Although chance finding due to small sample size is possible, these data suggest that unlike in systolic heart failure, digoxin may not reduce 30-day all-cause hospitalization in older diastolic heart failure patients.

Objectives To study natural weight changes and to develop a weight classification system that can identify weight maintainers, gainers, and losers. Design/outcome A prospective, observational study in which weight changes over five annual measurements were evaluated. In the weight classification system used, changes greater than 5lb defined weight maintenance, gain, or loss. Subjects/settings Subjects were healthy, normal-weight and overweight, men and women (mean age=44.1+14.1 years) in the Relationships of Energy, Nutrition, and Obesity to Cardiovascular Disease Risk Study. Prospective data for 385 of the original 508 subjects for whom actual weights were available for each of the 5 years (1985 to 1990) were used to classify and characterize subjects by weight-change categories. Statistical analyses Cross-tabulations (with χ 2 tests) and hierarchical log-linear analyses (with partial χ 2 tests) to examine the relationships of categorical variables; analyses of variance (with F tests) for continuous measures. Results Over the 4-year interval, 46% of subjects were classified as maintainers, 34% as gainers, and 20% as losers. Over shorter 1-year epochs, more subjects were maintainers (62%) and fewer subjects were gainers (22%) or losers (16%). Maintainers had fewer and smaller magnitudes of weight fluctuations and showed fewer deleterious changes in health risk factors than gainers. Applications Weight changes of greater than ±5lb can classify a person as a weight maintainer, gainer, or loser. Although annual weight changes were used in this study, a weight change of more than 5lb between any two points in time may suggest nonmaintenance of weight or weight instability that needs further evaluation.

The objective of this study is to determine if change in acetylcholine receptor antibody (AChR-ab) levels reflects change in clinical severity in patients with myasthenia gravis (MG).We reviewed results from a prospective trial in MG and from all 85 patients in an MG Clinic who had AChR-ab determinations performed at least twice by the same commercial laboratory.Change in AChR-ab levels correlated only weakly with change in clinical severity. AChR-ab levels fell in 92% of patients who improved and in 63% who did not. A fall in AChR-ab level had a positive predictive value for clinical improvement of 83% and a negative predictive value of only 59%.AChR-ab levels fell in almost all patients who improved, but also in most patients who did not. Thus, we do not recommend commercially available AChR-ab levels as a biomarker of improvement in MG. However, antibody levels might be useful as a marker for inadequate immunotherapy.

Complement activation at the neuromuscular junction is a primary cause of acetylcholine receptor loss and failure of neuromuscular transmission in myasthenia gravis (MG). Eculizumab, a humanized monoclonal antibody, blocks the formation of terminal complement complex by specifically preventing the enzymatic cleavage of complement 5 (C5).This study was a randomized, double-blind, placebo-controlled, crossover trial involving 14 patients with severe, refractory generalized MG (gMG).Six of 7 patients treated with eculizumab for 16 weeks (86%) achieved the primary endpoint of a 3-point reduction in the quantitative myasthenia gravis (QMG) score. Examining both treatment periods, the overall change in mean QMG total score was significantly different between eculizumab and placebo (P = 0.0144). After assessing data obtained from all visits, the overall change in mean QMG total score from baseline was found to be significantly different between eculizumab and placebo (P0.0001). Eculizumab was well tolerated.The data suggest that eculizumab may have a role in treating severe, refractory MG.

Background Multiple sclerosis (MS) can affect virtually every neurological function which complicates the conceptualization and assessment of disability. Similar challenges are encountered in other medical fields including child cognitive development and psychiatry, for instance. In these disciplines progress in diagnosis and outcome measurement has been recently achieved by capitalizing on the concept of bifactor model. Objective To present in accessible terms an application of bifactor confirmatory factor analysis to study the clinical disability outcomes in MS. Methods Data included 480 assessments on 301 patients with relapsing–remitting MS who participated in the North American interferon beta-1a clinical trial (Avonex). Measures consisted of the Expanded Disability Status Scale (EDSS), the three components of the Multiple Sclerosis Functional Composite (MSFC), and five other clinical measures of neurological functions. We determined which of three confirmatory factor analysis models (unidimensional, multidimensional, and bifactor) best described the structure of the data. Results EDSS scores ranged from 0 to 8 (94% between 0 and 4). The final bifactor model fitted the data well, explained 59.4% of total variance, and provided the most useful representation of the data. In this model, the nine measures defined a scoring dimension of global neurological function (63.1% of total composite score variance) and two auxiliary dimensions of extra variability in leg and cognitive function (17.1% and 9% of total composite score variance). Conclusion Bifactor modeling is a promising approach to further understanding of the structure of disability in MS and for refining composite measures of global disability.

Despite its fundamental importance, Spanish colonial law, derecho indiano, has remained something of a mystery to modern scholars. Perhaps the great chronological and ideological distance between us and the antiguo régimen plays a role. We often listen more sympathetically to those who espouse political ideas similar to our own, and we make assumptions based on the institutions with which we are familiar. As a result, modern historians often have joined with nineteenth-century patriots and foreign observers in denouncing the colonial legal system. Judicial administration is still depicted as ponderous, tyrannical, arbitrary, and corrupt. Clearly, many scholars have failed to appreciate the essential qualities of derecho indiano. A more careful scrutiny of the historical record reveals an intricate legal system that proved to be adaptable to the peculiar needs of the diverse regions of empire. Local modification of Hispanic law–derecho vulgar–was an important element of this flexibility and constituted a legitimate expression of local self-governance.

BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory. DESIGN/METHODS: Individual-patient data meta-analysis included randomized controlled trials of preterm infants ( RESULTS: Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92–1.01]; P = .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98–1.28]; P = .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of >5 vs ≤5 ppm there was evidence of improved outcome (interaction P = .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74–0.98]) was found. CONCLUSIONS: Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.

Tumors have heterogeneous properties, which could be explained by the existence of hierarchically and biologically distinct tumor cells such as tumor-initiating cells (TICs). This model is clinically important, as TICs are promising targets for cancer therapies. However, TICs in spontaneous B-cell lymphoma have not been conclusively identified.Tumor cells with a progenitor phenotype exist in B-cell lymphoma, reflecting a hierarchical organization.Twenty-eight client-owned dogs with previously untreated B-cell lymphoma and 6 healthy dogs.This was a prospective study. Flow cytometry was used to identify lymphoid progenitor cells (LPCs) that coexpressed hematopoietic progenitor antigens CD34, CD117, and CD133, with lymphoid differentiation markers CD21 and/or CD22 in B-cell lymphoma. The polymerase chain reaction for antigen receptor rearrangements was used to analyze clonality and relatedness of tumor populations. A xenograft model with NOD/SCID/IL-2Rγ(-/-) mice was adapted to expand and serially transplant primary canine B-cell lymphoma.LPCs were expanded in lymph nodes from 28 dogs with B-cell lymphoma compared with 6 healthy dogs (P= .0022). LPCs contained a clonal antigen receptor gene rearrangement identical to that of the bulk of tumor cells. Canine B-cell lymphoma xenografts in recipient mice that maintained LPCs in the tumors were recurrently observed.These results suggest the presence of a hierarchy of tumor cells in B-cell lymphoma as has been demonstrated in other cancers. These findings have the potential to impact not only the understanding of lymphoma pathogenesis but also the development of lymphoma therapies by providing novel targets for therapy.

Background Low cerebrospinal fluid (CSF) amyloid-β 1-42 concentration and high total-tau/Aβ 1-42 ratio have been recommended to support the diagnosis of prodromal Alzheimer's disease (AD) in patients with amnestic mild cognitive impairment (aMCI) and also to select patients for clinical trials (Shaw et al, Ann Neurol 2009;65:403–13; Dubois et al, Lancet Neurol 2007;6:734–46). Methods We tested this recommendation with clinical trials simulations using patients from the Alzheimer Disease Neuroimaging Initiative who fulfilled the following entry criteria: (1) aMCI, (2) aMCI with CSF Aβ 1-42 ≤192 mg/mL, (3) and aMCI with total-tau/Aβ 1-42 >0.39. For each criterion, we randomly resampled the database obtaining samples for 1000 trials for each trial scenario, planning for 1 or 2 year trials with samples from 50 to 400 patients per treatment or placebo group, with up to 40% dropouts, outcomes after using the AD assessment scale-cognitive subscale and clinical dementia rating scale with effect sizes ranging from 0.15 to 0.75, and calculated statistical power. Findings Approximately 70% to 74% of aMCI patients with CSF measures met biomarker criteria. The addition of the low Aβ 1-42 or high tau/Aβ 1-42 requirement resulted in minimal or no increase in the power of the trials compared with enrolling aMCI without requiring the biomarker criteria. Slightly larger mean differences between the placebo and treatment groups fulfilling biomarker criteria were offset by increased outcome variability within the groups. Interpretations Although patients with aMCI or patients with prodromal AD meeting CSF biomarkers criteria were slightly more cognitively impaired and showed greater decline than patients with aMCI diagnosed without considering the biomarkers, the requirement of biomarker-positive patients would most likely not result in more efficient clinical trials, and trials would take longer because fewer patients would be available. A CSF Aβ 1-42 marker, however, could be useful as an explanatory variable or covariate when warranted by the action of a drug.

The aim of this study was to determine the reproducibility of individual versus pooled plaque sampling of permanent first molars (PFM) to quantitate Streptococcus mutans (SM)/total streptococci (TS). Ten individual and pooled plaque samples were collected from 35 subjects, randomly assigned to individual-first or pooled-first group. Plaque samples were processed and quantified for SM and TS. SM/TS ratio was used to determine the reproducibility within two group samples. Mean percentage of SM/TS in both methods were not significantly different. However, within subject detection of SM was found to be significantly more sensitive for individual sampling method. Despite the lack of a difference between both methods for SM/TS quantitation, the difference in SM detection suggests that individual sampling is more sensitive.

We assessed the performance of items from the Quantitative Myasthenia Gravis (QMG), MMT (Manual Muscle Test), and MG-ADL (Myasthenia Gravis - Activities of Daily Living) scales, using data from two recently completed treatment trials of generalized MG. Items were selected that were relevant to manifestations of MG, meaningful to both the physician and the patient, and responsive to clinical change. After the 10 items were chosen, they were weighted based on input from MG experts from around the world, considering factors such as quality of life, disease severity, risk, prognosis, validity, and reliability. The MG Composite is easy to administer, takes less than 5 minutes to complete, and requires no equipment. Weighting of the response options of the 10 items should result in ordinal scores that better represent MG status and are more responsive to meaningful clinical change. To better determine its suitability for clinical use and for treatment trials, the MG Composite will be tested prospectively at several academic medical centers and will be used as a secondary measure of efficacy in pending clinical trials of MG.

We present our experience planning and launching a multinational, NIH/NINDS funded study of thymectomy in myasthenia gravis. We highlight the additional steps required for international sites and analyze and contrast the time investment required to bring U.S. and non-U.S. sites into full regulatory compliance. Results show the mean time for non-U.S. centers to achieve regulatory approval was significantly longer (mean 13.4+/0.96 [corrected] months) than for U.S. sites (9.67+/0.74 [corrected] months; p=0.003, [corrected] t-test). The delay for non-U.S. sites was mainly attributable to Federalwide Assurance certification and State Department clearance.

RT-RiboSyn measures the specific rate of ribosome synthesis in distinct microbial populations by measuring the generation rate of precursor 16S rRNA relative to that of mature 16S rRNA when precursor 16S rRNA processing is inhibited. Good agreement was demonstrated between specific rate of ribosome synthesis and specific growth rate of Acinetobacter calcoaceticus .

Unprotected and excessive exposure to ultraviolet radiation (UVR) is the primary risk factor for skin cancer.A pair-matched, group-randomized, pre-test/post-test, quasi-experimental design, with ski resorts as the unit of randomization, tested the effectiveness of Go Sun Smart, a multi-channel skin cancer prevention program. Independent samples of guests were taken at baseline (2001) and follow-up (2002); data were analyzed in 2006.A total of 6516 adult guests at 26 ski areas in the western U.S. and Canada were recruited, consented, and interviewed on chairlifts. This study was nested within an occupational intervention for ski area workers.Ski areas were pair-matched and randomized to receive Go Sun Smart, which consisted of print, electronic, visual, and interpersonal skin cancer prevention messages.Sun-protection behaviors, sunburning, recall of sun-protection messages, and the association of message exposure to sun protection.The difference in recall of all sun-protection messages, messages on signs and posters, and the Go Sun Smart logo was significant between the intervention and control resorts. Reported use of sun-protection practices was higher by guests at intervention ski areas using more (a higher dose of) Go Sun Smart materials. Intervention-group guests who recalled a sun-safety message were more likely to practice sun safety than intervention-group guests who did not recall a message and control-group guests.While the mere implementation of Go Sun Smart did not produce sun-safety improvements, Go Sun Smart appeared to be effective for guests who encountered and remembered it. Many factors can work against message exposure. Signage seemed to produce the greatest increase in exposure to sun-safety messages.

The active reduction of noise is an application of the principle of superposition in which an unwanted noise signal is detected by a microphone and processed by an electronic controller to produce an equal amplitude, 180° out-of-phase cancellation signal. The signal is then appropriately amplified and injected back into the space by a loudspeaker. This paper describes an electronic controller based on a digital implementation of transversal filters using a modification of the Widrow-Hoff Least-Mean-Squared Algorithm. In the case of active noise reduction there is no signal to enhance and all of the detected input must be cancelled. Further, the time required for the physical acoustic wave must be taken into consideration for the system to work.

This paper discusses a proposed processing technique for combining video imagery with auxiliary sensor information. The latter greatly simplifies image processing by reducing complexity of the transformation model. The mosaics produced by this technique are adequate for many applications, in particular habitat mapping. The algorithm is demonstrated through simulations and hardware configuration is described.

Summary Background Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease. Methods We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age ⩽34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age. Findings The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0·03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0·65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2–4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%). Interpretation Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

Clinical outcome assessment in Multiple Sclerosis (MS) is challenging due to the diversity and fluctuating nature of MS symptoms. Traditional clinical scales such as the EDSS are inadequate in their assessment of key clinical dimensions of MS (e.g. , cognitive function), and they have psychometric limitations as well. Based on analyses of pooled data from natural history studies and from placebo groups in clinical trials, the National MS Society's Clinical Outcomes Assessment Task Force recently proposed a new multidimensional clinical outcome measure, the MS Functional Composite (MSFC). The MSFC comprises quantitative functional measures of three key clinical dimensions of MS: leg function/ambulation, arm/hand function, and cognitive function. Scores on component measures are converted to standard scores (z-scores), which are averaged to form a single MSFC score. Preliminary analyses confirm that: (1) the three clinical dimensions of the MSFC are relatively independent; (2) the MSFC is sensitive to clinical changes over 1- and 2-year intervals; and (3) the MSFC has acceptable criterion validity (i.e., predicts both concurrent and subsequent EDSS change). The advantages and potential limitations of incorporating quantitative functional outcome measures such as the MSFC into collaborative databases are discussed.

The seafloor in the mouth of the Piscataqua River Estuary, near Portsmouth, New Hampshire, contains several geomorphological regions that are evident in bathymetric data from multibeam sonar soundings. Those morphological regions generally are associated with surficial sediment type classes previously identified from sediment samples. We demonstrate that the morphologies are distinguishable using parameters from models of spatial variation for gridded depth soundings and backscatter values. Ground‐truth seafloor‐video transects data suggest that apparent facies and morphological regions are associated with different surficial sediment classes and rates of facies transitions. We show that the spatial variability of depth and backscatter is associated with the substrate transition rate, the number of microhabitats (microfacies), and distribution of certain epifauna identified using video. We show that, in some cases, a single region defined based upon spatial morphological attributes from depth data and apparent sedimentological attributes from backscatter data represented several benthic habitats. The results suggest that although we can use spatial variability of depth or backscatter to segment the seafloor into apparent facies or habitat class regions, some of the regions will have unpredicted associated microhabitats and organisms. The results have implications for habitat‐specific assessment of organisms.

To determine whether there is a relationship between exposure to heparin and an increased risk of intraventricular hemorrhage (IVH), we analyzed data from a cohort of infants who had been subjects in a randomized clinical trial of umbilical artery catheter placement. Data from 862 infants who survived the first 6 days of life were used for analysis. The incidence of IVH (grades 1 through 4) was 28.6%. The mean (SD) birth weight for infants with IVH was 954 gm (247 gm) compared with 1053 gm (253 gm) among infants without IVH (p0.01). The mean (SD) heparin intake among infants with an IVH was 83.5 units/kg/day (48.7) compared with 59.4 units/kg/day (48.7) among infants without an IVH (p0.01). With the use of logistic regression modeling to adjust for a number of potentially confounding variables, including fluid intake and birth weight, we observed an odds ratio for an IVH of 1.96 (95% confidence interval = 1.32, 2.91) for infants with second through fourth quartile intakes of heparin compared with that for infants with first quartile heparin intakes. Although we cannot rule out the possibility that the observations from this model may be confounded by factors associated with the severity of illness of the infant, these data support the findings of previous reports of an association between heparin exposure and the risk for an IVH.

Unlike distributed data entry, which is used in many large epidemiologic studies and multicenter clinical trials, distributed data analysis is a relatively new concept. This paper reports on the usefulness of such a system in the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA distributes the entire examination dataset to participating centers soon after completion of each round of data collection. The process was designed to encourage more numerous, diverse, and rapid publications, and to allow for more efficient use of the manpower and expertise in centers. Responsibilities of the coordinating center have changed from a conventional coordinating center but remain substantial due to the need for collating, monitoring, verifying, and documenting the distributed data analysis (DDA) system. DDA is successful from the standpoint of implementation and operation—21 manuscripts representing work analyzed at six participating centers had been submitted for publication within 3.5 years of the completion of the baseline examination.

A recently‐developed statistical‐spectral approach to acoustic‐target identification (SSID) incorporates information contained in the frequency‐dependent signal amplitudes and their variances. In addition to identifying biological targets, the SSID has demonstrated utility for estimating fish aggregation densities, abundances, and behaviors, and detecting and classifying the seabed (e.g., accurate depth, within‐beam slope, hardness and roughness, and the height of the unresolved boundary region, and the so‐called dead zone). Further, the related multi‐frequency, bi‐planar, interferometric technique (MBI) allows much higher‐resolution measurements of the seabed and sub‐beam measures of slope, hardness, and roughness. Here we extend the utilities of the SSID and MBI methods, with explicit consideration of the single‐frequency signal phases and their variances, and frequency‐dependent split‐aperture phases and their variances, for improved estimations of pelagic‐target sizes, and their aggregation densities,...

Acoustic classifications of fish and estimations of their orientation distributions are possible using multi‐frequency or broad bandwidth measurements of their acoustic target strengths (TSs) with knowledge of their scattering directivity pattern and size distributions. To measure TS of in situ fish, single‐frequency interferometric methods provide information to detect resolvable single targets and estimate their location within the acoustic beam. This technique is compromised by multiple targets that are unresolvable because of their spacing, but this situation can be mitigated with the use of multi‐frequency interferometry. The ambiguity caused by coincident echoes can also be substantially reduced using single‐frequency, multiple‐aperture interferometry. This method uses phase differences from multiple sub‐arrays of a single‐frequency (200‐kHz) multibeam echosounder to estimate robustly when echoes originate from a resolvable single target and its position within the acoustic beams. Results provide accurate measures of beam‐compensated TS and, in cases of low‐density scatterers, estimates of their volume density. Multiple‐aperture interferometry can significantly improve the utility of single‐frequency multibeam echosounders for quantitative measures of fish and zooplankton, and seabed‐range detections.

Acoustic backscatter measurements from aggregations of Antarctic krill were collected over two field seasons (2006 and 2007) in the waters north of Livingston Island using two 5.5‐m inflatable vessels. One was equipped with a dual‐frequency (38‐ and 200‐kHz) single‐beam echosounder, while the other used a 200‐kHz multi‐beam system. In addition to independent survey operations, both vessels participated in joint survey operations where the two boats followed the same trackline separated by a small distance (10–40 m). These data allow us to compare how the two echosounder systems “see” the same (or very similar) krill aggregations. During 2006, some tracklines were also occupied by a large (300‐ft) vessel although vessel separation distances were larger during these operations. The combination of measurements from single‐ and multi‐beam echosounders (and nearby net tows) provides the opportunity to characterize krill aggregation size, shape, numerical density, and overall biomass. Observations of krill pred...

Fish dispersion and abundance are commonly estimated from volume backscattering coefficients (sv) of animals located directly beneath the survey vessel, inside a narrow transducer beamwidth. Fish density (♯/m2) is estimated from a ratio of integrated sv and a representative backscattering cross‐sectional area. Fish biomass is estimated from the product of fish density and the area sampled. Uncertainty in biomass estimates can arise from small sampling volumes, and the scattering directivities of the fish coupled with their orientations relative to the acoustic beam. Multibeam sonars can be used to increase the observational volumes, but add the complexity of a wider range of incident angles. If fish size and packing density are constant throughout a school, then the variation in sv versus aspect angle can be attributed to fish orientation. With modeling and multibeam sonar measurements, the following null hypotheses are explored: (1) The variability of sv versus roll angle is nearly uniform; (2) For measurements made with beams at or near vertical, sv variability is primarily due to the pitch angle; (3) For measurements with nonvertical beams, such as the outer beams of multibeam echosounders, sv variability is primarily due to the yaw angle.