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Between 2018 and 2019, multiple clinical trials ended earlier than planned, resulting in calls to improve communication with and support for participants and their study partners ("dyads"). The multidisciplinary Participant Follow‐Up Improvement in Research Studies and Trials (Participant FIRST) Work Group met throughout 2021. Its goals were to identify best practices for communicating with and supporting dyads affected by early trial stoppage. The Participant FIRST Work Group identified 17 key recommendations spanning the pre‐trial, mid‐trial, and post‐trial periods. These focus on prospectively allocating sufficient resources for orderly closeout; developing dyad‐centered communication plans; helping dyads build and maintain support networks; and, if a trial stops, informing dyads rapidly. Participants and study partners invest time, effort, and hope in their research participation. The research community should take intentional steps toward better communicating with and supporting participants when clinical trials end early. The Participant FIRST recommendations are a practical guide for embarking on that journey. [ABSTRACT FROM AUTHOR]

Introduction: Apathy is common in neurocognitive disorders (NCD) but NCD‐specific diagnostic criteria are needed. Methods: The International Society for CNS Clinical Trials Methodology Apathy Work Group convened an expert group and sought input from academia, health‐care, industry, and regulatory bodies. A modified Delphi methodology was followed, and included an extensive literature review, two surveys, and two meetings at international conferences, culminating in a consensus meeting in 2019. Results: The final criteria reached consensus with more than 80% agreement on all parts and included: limited to people with NCD; symptoms persistent or frequently recurrent over at least 4 weeks, a change from the patient's usual behavior, and including one of the following: diminished initiative, diminished interest, or diminished emotional expression/responsiveness; causing significant functional impairment and not exclusively explained by other etiologies. Discussion: These criteria provide a framework for defining apathy as a unique clinical construct in NCD for diagnosis and further research. [ABSTRACT FROM AUTHOR]

Background: Diagnostic criteria for apathy (DCA) in neurocognitive disorders were developed in 2021. As next steps, we assessed whether commonly‐used validated apathy scales map onto the DCA and identified which scales map best. Method: Using a modified Delphi process, mapping of the Neuropsychiatric Inventory‐Clinician (NPI‐C) Apathy domain and the Apathy Evaluation Scale (AES) onto the DCA were assessed by surveying apathy experts. For each item on the scales, experts were asked to evaluate the degree of correspondence to the DCA globally, and the 3 DCA dimensions [diminished initiative, interest, and emotion]. Respondents voted "not at all" (scored as 0), "weakly" (scored as 1), or "strongly" (scored as 2). For each item, if the mean score was <0.5, the item was considered not mapped, for scores >1.5, the item was considered mapped, and items with scores 0.5‐1.5 were discussed further in a virtual consensus meeting. The surveys were then sent to other scientific community members, and the interrater reliability between the two groups was assessed using Cohen's kappa. Result: The surveys were completed by 12 experts. For NPI‐C apathy, 10/11 (90.9%) questions mapped primarily onto one dimension of the DCA: 2 onto "Initiative", 6 onto "Interest", and 2 onto "Emotion". Of NPI‐C Apathy domain items, 9/11 (81.8%) mapped globally onto the DCA. For the AES, 7/18 (38.9%) questions mapped onto different dimensions of the DCA: 4 onto "Initiative", 2 onto "Interest", and 1 onto "Emotion"; 6/18 (33.3%) items mapped globally onto the DCA. The mean mapping scores of NPI‐C were significantly higher than those of the AES (t (27) = 2.25, p = 0.032) indicating better performance of NPI‐C in this exercise. These findings were confirmed in a consensus discussion. There was substantial agreement (kappa = 0.621) between the experts and the community group regarding mapping of NPI‐C but only moderate agreement (kappa = 0.553) regarding mapping of AES on the DCA. Conclusion: More questions from the NPI‐C Apathy domain mapped strongly and uniquely both globally, and onto the 3 dimensions of the DCA, compared with the AES. Future research using the DCA, NPI‐C Apathy domain, and AES in clinical and research settings are needed to confirm these results. [ABSTRACT FROM AUTHOR]

Introduction: The 2017 European Union‐North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician‐rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. Methods: In a modified Delphi process, Cohen‐Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory‐Clinician (NPI‐C) items were mapped to IPA agitation domains generating novel instruments, CMAI‐IPA and NPI‐C‐IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. Results: MCID was –17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8–32.6) for CMAI; –5 (OR = 9.3, 95% CI = 4.0–21.2) for CMAI‐IPA; –3 (OR = 11.9, 95% CI = 4.1–34.8) for NPI‐C‐A+A; and –5 (OR = 7.8, 95% CI = 3.4–17.9) for NPI‐C‐IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. Conclusion: Internal consistency and reliability analyses demonstrated better accuracy for the NPI‐C‐IPA than for the CMAI‐IPA and can be used for agitation clinical trial inclusion, and for response to intervention. [ABSTRACT FROM AUTHOR]

Molecular detection techniques are powerful tools used in ecological applications ranging from diet analyses to pathogen surveillance. Research partnerships that use these tools often involve collaboration among professionals with expertise in field biology, laboratory techniques, quantitative modeling, wildlife disease, and natural resource management. However, in many cases, each of these collaborators lacks specific knowledge about the approaches, decisions, methods, and terminology used by their research partners, which can impede effective communication and act as a barrier to the efficient use of molecular data for ecological inferences and subsequent conservation decision making. We outline a collaborative framework to assist colleagues with diverse types of expertise to effectively translate their scientific and management needs to research partners from other specialties. The molecular techniques used to detect organisms will continue to advance both in sophistication and in the breadth of ecological applications. Our objective is to enable ecologists to harness the full utility of these methods by developing effective collaborative partnerships. [ABSTRACT FROM AUTHOR]

Phosphorus (P) runoff from pastures can cause accelerated eutrophication of surface waters. However, few long‐term studies have been conducted on the effects of best management practices, such as rotational grazing and/or buffer strips on P losses from pastures. The objective of this study was to evaluate the long‐term effects of grazing management and buffer strips on P runoff from pastures receiving annual (5.6 Mg ha−1) poultry litter applications. A 14‐yr study was conducted on 15 small watersheds (0.14 ha) with five treatments: hayed (H), continuously grazed (CG), rotationally grazed (R), rotationally grazed with an unfertilized buffer strip (RB), and rotationally grazed with an unfertilized fenced riparian buffer (RBR). Runoff samples were collected using automatic samplers during runoff events. Average annual runoff volumes from H (40 mm yr−1) and RBR (48 mm yr−1) were lower than CG and RB, which were both 65 mm yr−1, and from R (67 mm yr−1). Rotational grazing alone did not reduce P loads compared with continuous grazing (1.88 and 1.71 kg P ha−1 for R and CG, respectively). However, compared with CG, total P losses from RB pastures were reduced 36% with unfertilized buffer strips (1.21 kg P ha−1), 60% in RBR watersheds with unfertilized fenced riparian buffer strips (0.74 kg P ha−1), and 49% by converting pastures to hayfields (0.97 kg P ha−1). Hence, the use of unfertilized buffer strips, unfertilized fenced riparian buffer strips, or converting pastures to hayfields are effective best management practices for reducing P runoff in U.S. pasture systems. [ABSTRACT FROM AUTHOR]

Background: We have previously identified a large proportion of subjects (> 10%) entering clinical trials in early Alzheimer's disease to possibly suffer from Baseline inflation (Kott, 2023). Without useful predictive markers, the identification of these subjects happens only when these subjects are already randomized into the trial. Our prior analyses showed an almost linear relationship between MMSE interview duration and MMSE total score (Kott, 2022). To be able to identify possible subjects with MMSE score inflation at Screening, we wanted to test the hypothesis that those subjects with likely inflated MMSE scores had significantly longer scale administration times, possibly corresponding to increased symptom severity below the MMSE inclusionary threshold. Method: Data from 6,922 subjects were pooled from 6 early AD clinical trials. We restricted the analysis to interviews between 3 and 30 minutes long, shorter interviews are technically not possible and longer interviews likely indicate user error. This decreased the sample to 6,717 subjects. Subjects were dichotomized into subjects meeting Screening MMSE criteria at Baseline and subjects who dropped below the Screening MMSE criteria at Baseline. A generalized linear model was fitted to the data with the Screening MMSE duration used as the predicted variable and type of subject (drops below criteria yes/no) as the predictor variable correcting for the MMSE score at Screening. Result: 937 subjects no longer met MMSE inclusion criteria at Baseline. For those subjects, MMSE interview duration increased significantly (∼40 seconds). Conclusion: Our post‐hoc analysis found significantly longer Screening MMSE interview durations in subjects who no longer met MMSE inclusion cutoffs at Baseline. The increase was consistent with our hypothesis and likely reflects that these subjects had their Screening MMSE scores inflated in order to meet inclusion criteria. We suggest including prolonged MMSE durations in analytical programs as a marker of possible MMSE score inflation alongside other markers, like MMSE vs ADAS‐Cog discordance. We plan additional analyses to better understand this problem. [ABSTRACT FROM AUTHOR]

Background: The success of any clinical trial begins with ensuring that participants entering the trial meet the inclusion criteria and disease severity. Score manipulation to meet eligibility criteria may contribute to loss of signal in clinical trials. Based on our prior analyses of early Alzheimer's disease (AD) clinical trials, over 10% of randomized participants likely had inflated MMSE scores at inclusion determination. In addition to 'traditional' instruments such as the MMSE or CDR, other 'diagnostic' instruments such as the RBANS, FCSRT and Wechsler Memory Scale are often used to select the study population. In the current analysis we explore the relationship between the performance on the diagnostic tests and the likely inflation in MMSE. Method: Baseline MMSE scores and Screening diagnostic tests results were pooled from 6,387 subjects from multiple clinical trials in early AD. Within each trial, participants' performance on the diagnostic tests was broken into quartiles – best performers, second best, second worst and worst performers. Participants were also classified by their Baseline MMSE score as either meeting or being below the Screening MMSE inclusion criteria. A logistic regression was used to explore the association of the diagnostic test performance quartiles and Baseline MMSE score categories correcting for Screening MMSE score. Result: 1223 (19.2%) participants comprised the best performing quartile on the diagnostic tests. Comparatively, with each subsequent quartile, the odds of not meeting the Screening inclusion criteria at Baseline increased significantly ‐ by 1.4x in the 1666 participants (26.1%) in the second best, by 2.0x in the 1696 (26.6%) in the second worst, and by 2.4x in the 1800 (28.2%) in the worst quartile. Conclusion: This post‐hoc analysis identified increasingly significant odds of not meeting Screening MMSE related inclusion criteria at Baseline for each progressive quartile of worsening diagnostic test performance, when correcting for the Screening MMSE score. We suggest that despite the limitations of this post‐hoc analysis, outlying poor performance on the diagnostic tests should be considered a risk marker for possible score inflation and assessed in the whole context of the available data. Further work is necessary. [ABSTRACT FROM AUTHOR]

Adding alum to poultry litter is a best management practice used to stabilize P in less soluble forms, reducing nonpoint-source P runoff. However, little research has been conducted on how alum additions to litter affect subsequent leaching of P from soil. The objective of this study was to evaluate the effects of alumtreated versus untreated poultry litter on P leaching from soil cores receiving long-term poultry litter applications. Two intact soil cores were taken from each of 52 plots in a long-term study with 13 treatments: a control, four rates each of untreated and alum-treated litter (2.24, 4.49, 6.72, and 8.96 Mg ha-1), and four rates of ammonium nitrate (65, 130, 195, and 260 kg N ha-1). One core from each plot received the same fertilizer as for the previous 20 yr, whereas the other was unfertilized in the study year, resulting in a total of 25 treatments. Cores were exposed to natural rainfall, and P leaching was measured for 1 yr. The average soluble reactive P concentrations in the leachate varied from 0.16 to 0.44 mg P L-1 in fertilized alum-treated cores, whereas leachate from cores fertilized with untreated litter ranged from 0.40 to 2.64 mg P L-1. At the highest litter rate (8.96 Mg ha-1), alum reduced total dissolved P and total P concentrations in leachate by 83 and 80%, respectively, compared with untreated litter. These results indicate that alum additions to poultry litter significantly reduced soluble and total P fractions in leachate. [ABSTRACT FROM AUTHOR]

The Alzheimer's Association's Research Roundtable met in November 2017 to explore the new National Institute on Aging and the Alzheimer's Association Research Framework for Alzheimer's disease. The meeting allowed experts in the field from academia, industry, and government to provide perspectives on the new National Institute on Aging and the Alzheimer's Association Research Framework. This review will summarize the "A, T, N System" (Amyloid, Tau, and Neurodegeneration) using biomarkers and how this may be applied to clinical research and drug development. In addition, challenges and barriers to the potential adoption of this new framework will be discussed. Finally, future directions for research will be proposed. [ABSTRACT FROM AUTHOR]

Disentangling the role that multiple interacting factors have on species responses to shifting climate poses a significant challenge. However, our ability to do so is of utmost importance to predict the effects of climate change on species distributions. We examined how populations of three species of wetland-breeding amphibians, which varied in life history requirements, responded to a six-year period of extremely variable precipitation. This interval was punctuated by both extensive drought and heavy precipitation and flooding, providing a natural experiment to measure community responses to environmental perturbations. We estimated occurrence dynamics using a discrete hidden Markov modeling approach that incorporated information regarding habitat state and predator-prey interactions. This approach allowed us to measure how metapopulation dynamics of each amphibian species was affected by interactions among weather, wetland hydroperiod, and co-occurrence with fish predators. The pig frog, a generalist, proved most resistant to perturbations, with both colonization and persistence being unaffected by seasonal variation in precipitation or co-occurrence with fishes. The ornate chorus frog, an ephemeral wetland specialist, responded positively to periods of drought owing to increased persistence and colonization rates during periods of low-rainfall. Low probabilities of occurrence of the ornate chorus frog in long-duration wetlands were driven by interactions with predators due to low colonization rates when fishes were present. The mole salamander was most sensitive to shifts in water availability. In our study area, this species never occurred in short-duration wetlands and persistence probabilities decreased during periods of drought. At the same time, negative effects occurred with extreme precipitation because flooding facilitated colonization of fishes to isolated wetlands and mole salamanders did not colonize wetlands once fishes were present. We demonstrate that the effects of changes in water availability depend on interactions with predators and wetland type and are influenced by the life history of each of our species. The dynamic species occurrence modeling approach we used offers promise for other systems when the goal is to disentangle the complex interactions that determine species responses to environmental variability. [ABSTRACT FROM AUTHOR]

Alzheimer's Association Research Roundtable Fall 2015—Tau: From research to clinical development. Tau pathology is recognized as the key driver of disease progression in Alzheimer's and other neurodegenerative diseases. Although this makes tau an attractive target for the development of novel diagnostic and therapeutic strategies, the mechanisms underlying the onset and progression of tau-related neurotoxicity remain elusive. Recent strides in the development of sophisticated preclinical models and the emergence of tau PET imaging and fluid biomarkers provide new opportunities to increase our understanding of tau biology, overcome translational challenges, and accelerate the advancement of tau therapeutics from bench to bedside. With this in mind, the Alzheimer's Association convened a Research Roundtable in October 2015, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of tau pathogenic pathways and review the evolution of tau therapeutics and biomarkers currently in development. The meeting provided a forum to share experience and expertise with the common goal of advancing the discovery and development of new treatment strategies and expediting the design and implementation of efficient clinical trials. [ABSTRACT FROM AUTHOR]

Neuropsychiatric symptoms (NPS) are common in dementia and in predementia syndromes such as mild cognitive impairment (MCI). NPS in MCI confer a greater risk for conversion to dementia in comparison to MCI patients without NPS. NPS in older adults with normal cognition also confers a greater risk of cognitive decline in comparison to older adults without NPS. Mild behavioral impairment (MBI) has been proposed as a diagnostic construct aimed to identify patients with an increased risk of developing dementia, but who may or may not have cognitive symptoms. We propose criteria that include MCI in the MBI framework, in contrast to prior definitions of MBI. Although MBI and MCI can co-occur, we suggest that they are different and that both portend a higher risk of dementia. These MBI criteria extend the previous literature in this area and will serve as a template for validation of the MBI construct from epidemiologic, neurobiological, treatment, and prevention perspectives. [ABSTRACT FROM AUTHOR]

Introduction As drug development research efforts move toward studying patients earlier in the course of Alzheimer's disease (AD), it is important to incorporate the patient's perspective into measurement of outcomes. Methods This article summarizes the qualitative work of the Patient-Reported Outcome Consortium's Cognition Working Group in the development of a new self-reported outcome measure in persons with mild cognitive impairment (MCI) due to suspected AD, herein referred to as MCI. Results The draft measure captures the patient's voice for two functional domains, complex activities of daily living and interpersonal functioning. Discussion This work represents a series of initial steps in the development of this rating scale. The next steps are to conduct psychometric analysis and evaluate the role of insight. [ABSTRACT FROM AUTHOR]

Several lines of evidence from Alzheimer's disease (AD) research continue to support the notion that the biological changes associated with AD are occurring possibly several decades before an individual will experience the cognitive and functional changes associated with the disease. The National Institute on Aging—Alzheimer's Association revised criteria for AD provided a framework for this new thinking. As a result of this growing understanding, several research efforts have launched or will be launching large secondary prevention trials in AD. These and other efforts have clearly demonstrated a need for better measures of cognitive and functional change in people with the earliest changes associated with AD. Recent draft guidance from the US Food and Drug Administration further elevated the importance of cognitive and functional assessments in early stage clinical trials by proposing that even in the pre-symptomatic stages of the disease, approval will be contingent on demonstrating clinical meaningfulness. The Alzheimer's Association's Research Roundtable addressed these issues at its fall meeting October 28–29, 2013, in Washington, D.C. The focus of the discussion included the need for improved cognitive and functional outcome measures for clinical of participants with preclinical AD and those diagnosed with Mild Cognitive Impairment due to AD. [ABSTRACT FROM AUTHOR]

With its long‐standing culture of excellence and exemplary leadership in the drinking water industry, New Hampshire's Manchester Water Works (MWW) has been recognized as an award‐winning Partnership for Safe Water member utility and remains proactive in protecting public health. [ABSTRACT FROM AUTHOR]

Abstract: Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS-PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome-specific synthetic reviews and recommendations prepared by NPS-PIA workgroups on depression, apathy, sleep, agitation, and psychosis. [Copyright &y& Elsevier]

Abstract: In 2011, the National Institute on Aging and the Alzheimer's Association (NIA-AA) proposed revising the criteria for diagnosing Alzheimer's disease (AD), which had been established more than 25 years earlier by the National Institute on Neurologic and Communicative Disorders and Stroke (NINCDS) and the Alzheimer's Disease and Related Disorders Association (ADRDA), now called the Alzheimer's Association. The NIA-AA initiative also built upon research criteria for AD proposed by the International Working Group (IWG) in 2007 and updated in 2010. These efforts to revise the criteria reflect the need to improve diagnostic accuracy, facilitate clinical trials, and establish a common set of criteria that are universally accepted across domains of clinical practice, research, and drug development. To ensure that the proposed NIA-AA criteria remain as current as possible, the Alzheimer's Association Research Roundtable convened a meeting in Washington, DC, on October 1 and 2, 2012, bringing together international stakeholders from industry, academia, and regulatory agencies to identify areas of agreement and research gaps respective of NIA-AA criteria and IWG recommendations. [Copyright &y& Elsevier]

The article presents a study regarding the false positive errors in occurrence surveys for auditory species. The study made use of 31 observers to record detections for 12 species during 180 calling trials. The result of the study shows that false positives were an important component of species occurrence data obtained by auditory methods.

Abstract: Neuropsychiatric symptoms (NPS) are core features of Alzheimer’s disease and related dementias. Once thought to emerge primarily in people with late-stage disease, these symptoms are currently known to manifest commonly in very early disease and in prodromal phases, such as mild cognitive impairment. Despite decades of research, reliable treatments for dementia-associated NPS have not been found, and those that are in widespread use present notable risks for people using these medications. An Alzheimer’s Association Research Roundtable was convened in the spring of 2010 to review what is known about NPS in Alzheimer’s disease, to discuss classification and underlying neuropathogenesis and vulnerabilities, and to formulate recommendations for new approaches to tailored therapeutics. [Copyright &y& Elsevier]

Abstract: The number of clinical trials for Alzheimer’s disease conducted outside the United States in a broad array of countries is increasing. As the number of compounds ready for clinical testing increases, and as trials become longer and more complex, this trend is expected to grow. The cultural and ethical context of global clinical trials, potential benefits for those involved, and practical approaches to obstacles generated by these global trials were discussed at a meeting of the Alzheimer’s Association Research Roundtable. Regulatory issues, including regional differences in study registration procedures, rules for collecting and reporting serious adverse events, requirements for national identity of study populations, and regulatory audits were also discussed by individuals who are knowledgeable about global clinical trials for Alzheimer’s disease. [Copyright &y& Elsevier]

Abstract: The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimer''s disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an increasing number of trials are focusing on potential disease-modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimer''s Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross-cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo-treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics. [Copyright &y& Elsevier]

Background: We previously presented the impact of protocol design on the MMSE changes observed in the screening period. Protocols requiring inclusion criteria be met at Screening alone had significantly more large MMSE changes between Screening and Baseline than did protocols where the criteria needed to be met at both Screening and Baseline. [Kott,2020]. In the current analysis we explore the impact of protocol design on the presence of between scale change discrepancies at Baseline and 6 months after randomization. Method: Data were pulled from multi‐national clinical trials in early Alzheimer's Disease (AD) where MMSE and ADAS‐Cog and/or CDR were collected at Screening, Baseline and 6 months after baseline. Subjects were categorized into 2 groups depending on whether inclusion criteria were required at Screening alone or at Screening and Baseline. We defined discordance as occurring when at least 2 of the 3 instruments showed a clinically meaningful change from the prior visit but the changes were in opposite directions. Chi‐square test was used to compare the distribution of discordances between the protocols at Baseline and at month 6. Result: Our dataset consisted of 4,237 subjects with data available from Screening, Baseline and month 6. At Baseline, we saw significantly more instances of discordance from Screening in studies requiring criteria be met at Screening alone (5%) vs 2% when the requirement needed to be met at both Screen and Baseline (chi2 = 12.5, P < 0.001). At month 6, no difference between the protocol types was identified – (12.2% vs. 12.4%, chi2 = 0.01, p = 0.912). Conclusion: Our analyses indicate a significant impact of protocol design on the presence of between scale change discrepancies. Protocols requiring criteria be met at Screening only had a significantly increased number of discordances at Baseline but this difference disappeared by month 6. Among the potential explanations for such between scale discordances, score manipulations to comply with inclusion criteria needs to be considered. These findings should be considered when designing protocol inclusion criteria. Further research is necessary to understand the impact of these discrepancies on drug‐placebo separation. [ABSTRACT FROM AUTHOR]

Background: We have observed numerous apparent inconsistencies in direction of scale (eg – MMSE, ADAS‐Cog and CDR) change between visits across multiple dementia clinical trials. While all instruments are not expected to move in the same direction, clinically meaningful changes in opposite directions may signal scoring and/or administration errors in one or more scales. In this analysis, we explore a) the extent to which such discordances between the MMSE, ADAS‐Cog and CDR occur in dementia clinical trials, and b) whether any associations between the presence of such discordances and scoring and/or administration errors exist. Method: Blinded data were obtained from multi‐national dementia clinical trials in early AD. Visit‐to‐visit point change was calculated for the MMSE, ADAS‐Cog and CDR‐sb. Clinically meaningful changes were defined as ≥ 4 points for the ADAS‐Cog, 3 points for the MMSE and 1 point for the CDR‐sb. We defined discordance occurring when at least 2 of 3 instruments showed clinically meaningful change, but in opposite directions. We also evaluated data from the corresponding Endpoint Quality reviews of both the worksheet and audio recordings of these assessments. These were performed by calibrated, independent Clinicians and assessed whether there were any administration and/or scoring errors. Descriptive statistics and logistic regression analyses were used to address our questions. Result: Data were collected from 4,892 randomized subjects. Visit‐to‐visit discordances were identified in 1,732 out of 15,321(11.30%) collected visits. Discordances were significantly less likely at baseline than after randomization (OR=0.54; CI=0.49‐0.61). The presence of baseline discordances significantly increased the odds of post‐baseline discordances (OR = 1.7; CI=1.4‐2.1). No association between the presence of discordances and administration or scoring errors was identified. Conclusion: We have identified over 11% of study visits affected by clinically meaningful discordances between the visit‐to‐visit changes between the MMSE, ADAS‐cog and CDR‐SB. Despite the expected lower presence of baseline than post‐baseline discordances, discordances at baseline affected over 8% of randomized subjects. The lack of association between the discordances and administration or scoring errors is surprising and we plan further analyses to understand this phenomenon better. [ABSTRACT FROM AUTHOR]

This article discusses the concentrations of particulate matter in dust plumes emitted during harvesting and tilling in an irrigated cotton field near Las Cruces, New Mexico. The authors compared remote lidar measurements with air samplers. They found strong agreement between the two techniques for concentrations of particulate matter and total suspended particulates. Plume movement was impacted by atmospheric stability and wind field. They concluded that there is a potential exposure risk to people in and around farming operations based on the measured concentrations of particulate matter.

Describes the balance between the agricultural nutrient inputs and removals for nine geographical districts within Arkansas from 1997 to 2001. Transport of excess nutrients; Development of nutrient management strategies; Predominance of row-crop agriculture and animal agriculture.

An index of biological integrity (IBI) was developed for streams in the Hudson, Delaware, and Susquehanna River drainages in the northeastern United States based on fish assemblage data from the Mohawk River drainage of New York. The original IBI, developed for streams in the U.S. Midwest, was modified to reflect the assemblage composition and structure present in Mid-Atlantic Slope drainages. We replaced several of the Midwestern IBI metrics and criteria scores because fishes common to the Midwest are absent from or poorly represented in the Northeast and because stream fish assemblages in the Northeast are less rich than those in the Midwest. For all replacement metrics we followed the ecology-based rationale used in the development of each of the metrics of the Midwestern IBI so that the basic theoretical underpinnings of the IBI remained unchanged. The validity of this modified IBI is demonstrated by examining the quality of streams in the Hudson, Delaware, and lower Susquehanna River basins. The relationships between the IBI and other indicators of environmental quality are examined using data on assemblages of fish and benthic macroinvertebrates and on chemical and physical stream characteristics obtained during 1993-2000 by the U.S. Geological Survey's National Water Quality Assessment Program in these three river basins. A principal components analysis (PCA) of chemical and physical variables from 27 sites resulted in an environmental quality gradient as the primary PCA axis (eigenvalue, 0.41). Principal components analysis site scores were significantly correlated with such benthic macroinvertebrate metrics as the percentage of Ephemeroptera, Plecoptera, and Trichoptera taxa (Spearman R = −0.66, P < 0.001). Index of biological integrity scores for sites in these three river basins were significantly correlated with this environmental quality gradient (Spearman R = −0.78, P = 0.0001). The northern Mid-Atlantic Slope IBI appears to be sensitive to environmental degradation in all three of the river basins addressed in this study. Adjustment of metric scoring criteria may be warranted, depending on composition of fish species in streams in the study area and on the relative effort used in the collection of fish assemblage data. [ABSTRACT FROM AUTHOR]

Task level animation of articulated figures, such as the human body, requires the ability to generate collision-free goal-directed motion of individual limbs in the presence of obstacles. This paper describes a new articulated limb motion planner for goal-directed point-to-point reaching motions. The produced motion avoids obstacles while optimizing an objective function. This two-phase algorithm uses heuristic guided Monte Carlo techniques to create a consistent underlying paradigm. The first phase consists of an existing potential field based random path planner which generates a population of candidate paths. This initial population is fed into the second phase, a genetic algorithm, which iteratively refines the population as it optimizes with respect to the objective function. The refinement process works on the principle of path coherency, the idea that a family of closely related collision-free paths lies in the vicinity of a given collision-free path. This paper focuses on seven different optimization functions. Optimized trajectories produced by the new motion planner are compared to those generated solely by the random path planner. The presented algorithm is flexible in that a wide range of objective functions can be optimized. Applications of the algorithm include task level animation, ergonomics and robotics. [ABSTRACT FROM AUTHOR]

Background: Audio recording of eCOA MMSE administration enables identification of both administration and scoring errors. Either can result in incorrect MMSE scores, potentially leading to inclusion of inappropriate subjects and/or biased assessment of change after randomization. Our current analysis explores the effect of protocol design, MMSE scores close to inclusion criteria and visit type on MMSE scoring and/or administration errors. Method: Data were pooled from 2 types of early dementia protocols – Type A where MMSE inclusion criteria need only be met at screening, and type B where they needed to be met at both screening and baseline. All assessments were audio recorded and reviewed by independent clinicians for the presence of administration and scoring errors. Operationally, subjects were defined as close to inclusion criteria if their MMSE scores were within 2 points of specified thresholds. Logistic regression with 3‐way interaction was used to explore the hypotheses. Result: 11,391 MMSE assessments were reviewed, and 2,706 (23.8%) had either an administration and/or scoring error. In both protocol types, administration errors were significantly less likely at baseline than screening, regardless of MMSE score proximity to inclusion threshold. In type A protocols, administration errors were more likely if scores were close to inclusion criteria. For type B protocols this was true only at screening. Scoring errors were significantly less likely at baseline, if MMSE scores were close to inclusion (both protocol types) or not (type A). Scoring errors were significantly more likely at screening but not baseline when scores were close to inclusion (only type A). No direct effect of protocol design was observed on the likelihood of either scoring or administration errors. Conclusion: Our data indicate that scoring and administration errors occur more frequently at screening and in subjects with scores close to inclusion criteria. Despite some differences, the effect of protocol design seems less likely to result in errors to the same extent as the other 2 parameters. Given that data coming from subjects close to inclusion criteria at screening are at the highest risk of having a scoring or administration error indicates that data may be manipulated to meet inclusion criteria. [ABSTRACT FROM AUTHOR]

Background: Anecdotally, we have observed subgroups of subjects who in the screening period of clinical trials in early Alzheimer's disease exhibit unexpectedly large changes in MMSE scores. Such changes could be explained by a number of reasons, such as learning effects, regression to the mean, measurement error, or intentional score manipulation. If the latter was the case, differences in MMSE changes between screening and baseline should be observed between protocols where MMSE inclusion criteria are required to be met at screening only and protocols requiring the criteria be met at screening and baseline. We hypothesized that MMSE changes would be larger in protocols with criteria required only at screening. Method: Data were pooled from multi‐national dementia clinical trials in early AD where MMSE was collected at screening and baseline. Subjects were categorized into 2 groups depending on whether the inclusion criteria were applied to screening alone or to both the screen and baseline visits. T‐test was used to compare the change between screening and baseline between the two groups of subjects. Additionally we compared the distribution of subjects changing by a) 3 and b) 5 MMSE points in either direction between screening and baseline between the two protocol groups using a chi‐square test. Result: Data were collected from 1,409 subjects. The MMSE change in subjects with criteria required at screening only was ‐1.2 points compared to ‐.05 points in subjects with criteria required at screening and baseline (t(1,407) = 5.99, p < 0.001). MMSE changes of 3 or 5 points were seen significantly more often in studies where the requirement was applied at screen alone (chi2(1)=18.2, p < 0.001 and chi2(1)=13.1, p < 0.001, respectively). Conclusion: Our analyses indicate that protocol design has a significant impact on the MMSE change observed in the screening period. Given the only difference between the two groups was the absence of inclusion criteria at baseline, we hypothesize that the MMSE score change observed differences can most likely be explained by score manipulation happening at either screening only or screening and baseline, depending on protocol type. We plan to replicate these results in larger datasets. [ABSTRACT FROM AUTHOR]