Nevada State University

INTRODUCTION: Alzheimer's disease (AD) has few available treatments, and there is a high rate of failure in AD drug development programs. Study of the AD drug development pipeline can provide insight into the evolution of drug development and how best to optimize development practices. METHODS: We reviewed clinicaltrials.gov and identified all pharmacologic AD trials of all agents currently being developed for treatment of AD. RESULTS: There are 132 agents in clinical trials for the treatment of AD. Twenty-eight agents are in 42 phase 3 trials; 74 agents are in 83 phase 2 trials; and 30 agents are in 31 phase 1 trials. There is an increase in the number of agents in each phase compared with that in the 2018 pipeline. Nineteen agents in trials target cognitive enhancement, and 14 are intended to treat neuropsychiatric and behavioral symptoms. There are 96 agents in disease modification trials; of these, 38 (40%) have amyloid as the primary target or as one of several effects. Eighteen of the antiamyloid agents are small molecules, and 20 are monoclonal antibodies or biological therapies. Seven small molecules and ten biologics have tau as a primary or combination target (18%). Amyloid is the most common specific target in phase 3 and phase 2 disease modification trials. Novel biomarkers (e.g., neurofilament light), new outcomes (e.g., AD Composite Score [ADCOMS]), enrollment of earlier populations, and innovative trial designs (e.g., Bayesian adaptive designs) are new features in recent clinical trials. DISCUSSION: Drug development continues robustly at all phases despite setbacks in several programs in the recent past. Continuing unmet needs require a commitment to growing and accelerating the pipeline.

This article discusses the collaborative planning and co-teaching experiences of two college faculty who co-taught a second language acquisition course in an undergraduate teacher education program at an urban college. Three questions frame the activities and reflections of the authors’ experiences and provide insights into characteristics, planning, and strategies of co-teaching in teacher education. The course was structured using thematic units and weekly lesson plans. The authors agree the benefits of co-teaching outweigh the challenges.

The Onduo Virtual Diabetes Clinic (VDC) for people with type 2 diabetes (T2D) combines a mobile app, remote lifestyle coaching, connected devices, and live video consultations with board-certified endocrinologists. Adults with T2D ( n = 594) who were evaluated by a VDC endocrinologist, remotely prescribed and mailed a real-time continuous glucose monitoring (rtCGM) device and used ≥1 sensor completed a CGM satisfaction questionnaire. The CGM satisfaction score was 4.5 ± 0.8 out of 5. Most respondents (94.7%) agreed/strongly agreed that they were comfortable inserting the sensor remotely and that rtCGM use improved understanding of the impact of eating (97.0%), increased diabetes knowledge (95.7%), and helped improve diabetes control when not wearing the sensor (79.4%). HbA1c ( n = 372) decreased from 7.7% ± 1.6% to 7.1% ± 1.2% ( P < 0.001; 10.2 months). These data suggest that it is feasible to provide rtCGM directly to individuals with T2D through a VDC without in-office training. Intermittent use of rtCGM was well-received by adults with T2D and was associated with improvement in HbA1c.

Guided by photovoice, a form of participatory action research that uses documentary photography and storytelling, this study examines how Black gay men and lesbians view themselves in relation to White gay men and lesbians in South Africa. Participants were from 4 South African townships and included 4 women, and 3 men. Participants discussed interracial dating, a lack of education, and information regarding differing sexualities and health care. They reported being sexually and physically assaulted for challenging the heterosexual status quo. Other themes that emerged from this study were classism, cultural traditions of visiting African healers, and segregated social spaces. Amidst oppression and despair, participants showed signs of strength, hope, and optimism.

Novel agents addressing non-amyloid, non-tau targets in Alzheimer's Disease (AD) comprise 70% of the AD drug development pipeline of agents currently in clinical trials. Most of the target processes identified in the Common Alzheimer's Disease Research Ontology (CADRO) are represented by novel agents in trials. Inflammation and synaptic plasticity/neuroprotection are the CADRO categories with the largest number of novel candidate therapies. Within these categories, there are few overlapping targets among the test agents. Additional categories being evaluated include apolipoprotein E [Formula: see text] 4 (APOE4) effects, lipids and lipoprotein receptors, neurogenesis, oxidative stress, bioenergetics and metabolism, vascular factors, cell death, growth factors and hormones, circadian rhythm, and epigenetic regulators. We highlight current drugs being tested within these categories and their mechanisms. Trials will be informative regarding which targets can be modulated to produce a slowing of clinical decline. Possible therapeutic combinations of agents may be suggested by trial outcomes. Biomarkers are evolving in concert with new targets and novel agents, and biomarker outcomes offer a means of supporting disease modification by the putative treatment. Identification of novel targets and development of corresponding therapeutics offer an important means of advancing new treatments for AD.

The nutritional profiles of 37 children (aged 0.5-14.0 years) with chronic liver disease at the time of acceptance for orthotopic liver transplantation (OLTP) have been evaluated using clinical, biochemical and body composition methods. Nutritional progress while waiting for a donor has been related to outcome, whether transplanted or not. At the time of acceptance, most children were underweight (mean standard deviation (s.d.) weight = -1.4 +/- 0.2) and stunted (mean s.d. height = -2.2 +/- 0.4), had low serum albumin (27/35) and had reduced body fat and depleted body cell mass (measured by total body potassium--mean % expected for age = 58 +/- 5%, n = 15). Mean ad libitum nutrient intake was 63 +/- 5% of recommended daily intake (RDI). Those who died while waiting (n = 8) had significantly lower mean initial s.d. weight compared with those transplanted. The overall actuarial 1 year survival of those who were transplanted (mean waiting time = 75 days) was 81% but those who were initially well nourished (s.d. weight greater than -1.0) had an actuarial 1 year survival of 100%. There were no significant differences in actuarial survival in relationship to age, type of transplant (whole liver or segmental), liver biochemistry or the presence or absence of ascites. Of the total group accepted for OLTP, whether transplanted or not, the overall 1 year survival for those who were relatively well nourished was 88% and for those undernourished (initial s.d. weight less than -1.0) was 38% (P less than 0.003). Declining nutritional status during the waiting period also adversely affected outcome.(ABSTRACT TRUNCATED AT 250 WORDS)

This study reviewed the literature for the extent of neuroimaging findings in boxers, indicative of traumatic brain injury (TBI) as identified in magnetic resonance imaging (MRI). The study then utilized a systematic checklist approach to assess 100 unselected consecutive 1.5- and 3.0-Tesla MRI examinations of professional unarmed combatants to determine the extent of identifiable TBI findings. The percentage of positive findings and the localization of lesions were quantified using the checklist that included the MRI findings previously reported in the medical literature. Seventy-six percent of the unarmed combatants had at least one finding that may be associated with TBI: 59% hippocampal atrophy, 43% cavum septum pellucidum, 32% dilated perivascular spaces, 29% diffuse axonal injury, 24% cerebral atrophy, 19% increased lateral ventricular size, 14% pituitary gland atrophy, 5% arachnoid cysts, and 2% had contusions. Statistical relationships were found between number of bouts and lateral ventricular size (tau-b = 0.149, p = 0.0489), with years of fighting correlating with the presence of dilated perivascular spaces (tau-b = 0.167, p = 0.0388) and diffuse axonal injury (tau-b = 0.287, p = 0.0013) findings. The improved resolution and increased signal-to-noise ratio on 1.5- and 3.0-Tesla high-field MRI systems defines the range of pathological variations that may occur in professional unarmed combatants. Additionally, the use of a systematic checklist approach insures evaluation for all possible TBI-related abnormalities. This knowledge can be used to anticipate the regions of potential brain pathology for radiologists and emergency medicine physicians, and provides important information for evaluating unarmed combatants relative to their safety and long-term neurocognitive outcome.

Learning can be guided by unexpected success or failure, signaled via dopaminergic positive reward prediction error (+RPE) and negative reward-prediction error (-RPE) signals, respectively. Despite conflicting empirical evidence, RPE signaling is thought to be impaired in drug addiction. To resolve this outstanding question, we studied as a measure of RPE the feedback negativity (FN) that is sensitive to both reward and the violation of expectation. We examined FN in 25 healthy controls; 25 individuals with cocaine-use disorder (CUD) who tested positive for cocaine on the study day (CUD+), indicating cocaine use within the past 72 h; and in 25 individuals with CUD who tested negative for cocaine (CUD-). EEG was acquired while the participants performed a gambling task predicting whether they would win or lose money on each trial given three known win probabilities (25, 50, or 75%). FN was scored for the period in each trial when the actual outcome (win or loss) was revealed. A significant interaction between prediction, outcome, and group revealed that controls showed increased FN to unpredicted compared with predicted wins (i.e., intact +RPE) and decreased FN to unpredicted compared with predicted losses (i.e., intact -RPE). However, neither CUD subgroup showed FN modulation to loss (i.e., impaired -RPE), and unlike CUD+ individuals, CUD- individuals also did not show FN modulation to win (i.e., impaired +RPE). Thus, using FN, the current study directly documents -RPE deficits in CUD individuals. The mechanisms underlying -RPE signaling impairments in addiction may contribute to the disadvantageous nature of excessive drug use, which can persist despite repeated unfavorable life experiences (e.g., frequent incarcerations).

An important goal of addiction research and treatment is to predict behavioural responses to drug-related stimuli. This goal is especially important for patients with impaired insight, which can interfere with therapeutic interventions and potentially invalidate self-report questionnaires. This research tested (i) whether event-related potentials, specifically the late positive potential, predict choice to view cocaine images in cocaine addiction; and (ii) whether such behaviour prediction differs by insight (operationalized in this study as self-awareness of image choice). Fifty-nine cocaine abusers and 32 healthy controls provided data for the following laboratory components that were completed in a fixed-sequence (to establish prediction): (i) event-related potential recordings while passively viewing pleasant, unpleasant, neutral and cocaine images, during which early (400-1000 ms) and late (1000-2000 ms) window late positive potentials were collected; (ii) self-reported arousal ratings for each picture; and (iii) two previously validated tasks: one to assess choice for viewing these same images, and the other to group cocaine abusers by insight. Results showed that pleasant-related late positive potentials and arousal ratings predicted pleasant choice (the choice to view pleasant pictures) in all subjects, validating the method. In the cocaine abusers, the predictive ability of the late positive potentials and arousal ratings depended on insight. Cocaine-related late positive potentials better predicted cocaine image choice in cocaine abusers with impaired insight. Another emotion-relevant event-related potential component (the early posterior negativity) did not show these results, indicating specificity of the late positive potential. In contrast, arousal ratings better predicted respective cocaine image choice (and actual cocaine use severity) in cocaine abusers with intact insight. Taken together, the late positive potential could serve as a biomarker to help predict drug-related choice--and possibly associated behaviours (e.g. drug seeking in natural settings, relapse after treatment)--when insight (and self-report) is compromised.

The physician-patient relationship is important to the successful delivery of health care. Health locus of control (HLOC) of the patient, the extent to which individuals attribute their health to their own actions or to external agents, may affect the patient-provider relationship. This study examined the influences of HIV and HLOC on trust in physician among a population of predominantly minority women and their family members. Powerful others HLOC demonstrated a positive relationship with trust in physician and chance HLOC had a negative relationship with trust in physician. HIV moderated both of these relationships.

Focuses on a study about major innovation in the ISO 9000:2000 registration process. Shows that the application of the behavioural science field is an excellent strategy for businesses to use to help improve investment return on ISO 9001:2000. Reckons that, in order to maximise benefits from implementing ISO 9001:2000, companies should approach the process using an organizational behaviour strategy, to ensure motivation involving the workforce.

Abstract Spatial patterns in carbon (C) and nitrogen (N) cycles of high‐latitude catchments have been linked to climate and permafrost and used to infer potential changes in biogeochemical cycles under climate warming. However, inconsistent spatial patterns across regions indicate that factors in addition to permafrost and regional climate may shape responses of C and N cycles to climate change. We hypothesized that physical attributes of catchments modify responses of C and N cycles to climate and permafrost. We measured dissolved organic C (DOC) and nitrate (NO 3 − ) concentrations, and composition of dissolved organic matter (DOM) in 21 streams spanning boreal to arctic Alaska, and assessed permafrost, topography, and attributes of soils and vegetation as predictors of stream chemistry. Multiple regression analyses indicated that catchment slope is a primary driver, with lower DOC and higher NO 3 − concentration in streams draining steeper catchments, respectively. Depth of the active layer explained additional variation in concentration of DOC and NO 3 − . Vegetation type explained regional variation in concentration and composition of DOM, which was characterized by optical methods. Composition of DOM was further correlated with attributes of soils, including moisture, temperature, and thickness of the organic layer. Regional patterns of DOC and NO 3 − concentrations in boreal to arctic Alaska were driven primarily by catchment topography and modified by permafrost, whereas composition of DOM was driven by attributes of soils and vegetation, suggesting that predicting changes to C and N cycling from permafrost‐influenced regions should consider catchment setting in addition to dynamics of climate and permafrost.

BACKGROUND: Lumbar spinal stenosis (LSS) can lead to compression of neural elements and manifest as low back and leg pain. LSS has traditionally been treated with a variety of conservative (pain medications, physical therapy, epidural spinal injections) and invasive (surgical decompression) options. Recently, several minimally invasive procedures have expanded the treatment options. METHODS: The Lumbar Spinal Stenosis Consensus Group convened to evaluate the peer-reviewed literature as the basis for making minimally invasive spine treatment (MIST) recommendations. Eleven consensus points were clearly defined with evidence strength, recommendation grade, and consensus level using U.S. Preventive Services Task Force criteria. The Consensus Group also created a treatment algorithm. Literature searches yielded 9 studies (2 randomized controlled trials [RCTs]; 7 observational studies, 4 prospective and 3 retrospective) of minimally invasive spine treatments, and 1 RCT for spacers. RESULTS: The LSS treatment choice is dependent on the degree of stenosis; spinal or anatomic level; architecture of the stenosis; severity of the symptoms; failed, past, less invasive treatments; previous fusions or other open surgical approaches; and patient comorbidities. There is Level I evidence for percutaneous image-guided lumbar decompression as superior to lumbar epidural steroid injection, and 1 RCT supported spacer use in a noninferiority study comparing 2 spacer products currently available. CONCLUSIONS: MISTs should be used in a judicious and algorithmic fashion to treat LSS, based on the evidence of efficacy and safety in the peer-reviewed literature. The MIST Consensus Group recommend that these procedures be used in a multimodal fashion as part of an evidence-based decision algorithm.

ABSTRACT Improvement in engineering properties of expansive soils by mixing ground granulated blast furnace slag (GGBFS) is the main focus of this research. For this purpose two expansive soil samples were collected from DG Khan and Sialkot areas (Pakistan). Classification tests revealed that DG Khan sample belonged to fat clay (CH) while Sialkot soil was lean clay (CL) as classified by Unified Soil Classification System. GGBFS has been added in varying proportions between 0 and 55% in these soil samples to study its role in stabilizing these expansive soils. Based on the laboratory test performed on composite soil samples, it was observed that maximum dry unit weight increased up to 10 % by adding 50% GGBFS in both samples. California bearing ratio (CBR) value showed an increase from 3.2 % to 11.5% for DG Khan soil while CBR values varied from 2.4% to 10.7% for Sialkot soil by mixing 50% GGBFS. Addition of 30 % GGBFS to DG Khan soil reduced swell potential from 8 % to 2 % while in Sialkot soil, 20 % addition of GGBFS reduced swell potential from 5 % to 2 %. Unconfined compressive strength of remoulded sample cured for 28 days increased by about 35% with the addition of 30%GGBFS. The results indicated that mixing of GGBFS in the expansive soil samples have a marked increase in their engineering properties. Also, it is an affective and environmental friendly means to dispose waste of steel industry.

Teramoto, M, Cross, CL, Rieger, RH, Maak, TG, and Willick, SE. Predictive validity of national basketball association draft combine on future performance. J Strength Cond Res 32(2): 396-408, 2018-The National Basketball Association (NBA) Draft Combine is an annual event where prospective players are evaluated in terms of their athletic abilities and basketball skills. Data collected at the Combine should help NBA teams select right the players for the upcoming NBA draft; however, its value for predicting future performance of players has not been examined. This study investigated predictive validity of the NBA Draft Combine on future performance of basketball players. We performed a principal component analysis (PCA) on the 2010-2015 Combine data to reduce correlated variables (N = 234), a correlation analysis on the Combine data and future on-court performance to examine relationships (maximum pairwise N = 217), and a robust principal component regression (PCR) analysis to predict first-year and 3-year on-court performance from the Combine measures (N = 148 and 127, respectively). Three components were identified within the Combine data through PCA (= Combine subscales): length-size, power-quickness, and upper-body strength. As per the correlation analysis, the individual Combine items for anthropometrics, including height without shoes, standing reach, weight, wingspan, and hand length, as well as the Combine subscale of length-size, had positive, medium-to-large-sized correlations (r = 0.313-0.545) with defensive performance quantified by Defensive Box Plus/Minus. The robust PCR analysis showed that the Combine subscale of length-size was a predictor most significantly associated with future on-court performance (p ≤ 0.05), including Win Shares, Box Plus/Minus, and Value Over Replacement Player, followed by upper-body strength. In conclusion, the NBA Draft Combine has value for predicting future performance of players.

Lumbar spinal stenosis (LSS) functionally impacts significant numbers of Americans per year. Current estimates place the number of Americans suffering from senescent lumbar spinal stenosis at 400,000. The prevalence of this disorder in patients ranging from 60 to 69 years of age is very high. Forty-seven percent of this age group have mild to moderate stenosis, and 19.7% have severe stenosis. As the baby boomer generation gets older, 10,000 individuals attain the age of 65 years every day in United States. LSS is becoming very common and will be a major healthcare issue as the population ages. Although LSS is not life threatening, it can cause substantial disability with limitations to performing daily activities, and thus, the associated negative impact on quality of life (QOL). This article reviews the pathophysiology and current treatment options for LSS, focusing on evidence-based treatment options.

Two studies used response latency measures to assess automatic attitudes that individuals are unwilling or unable to reveal about their partners. In Study 1, participants (n = 51) in dating relationships completed two response latency measures (Time 1) and several relationship self-reports (Times 1 and 2). Participants who faced high barriers to exiting (BTE) their relationship generally showed a negative association between their relationship self-reports and automatic attitudes, and there was some evidence that automatic attitudes at Time 1 predicted relationship satisfaction at Time 2. Study 2 (n = 41 couples) replicated the BTE finding and showed that image-based response latency measures may assess automatic attitudes more effectively than word-based measures. A negative correlation between self-reported and automatic attitudes among high-BTE participants suggests that they may overreport relationship positivity to quell feelings of doubt about a relationship they cannot feasibly dissolve.

Abstract We evaluated variation in dissolved organic matter (DOM) export as a function of hydrology and land use from a large arid river basin in northwestern China. Two soil‐derived, humic‐like (C1 and C2) and three protein‐like fluorescence components (C3, C4, and C5) were identified. During high discharges, river water DOM had higher values of DOC concentration, percent humic fluorescence, and humification index, but lower values of fluorescence index and percent protein fluorescence than found at base flow, suggesting that flow paths shifted to shallower depths flushing out topsoil organic matter. Loading of DOC and soil‐derived humic fluorescence were driven largely by discharge, with values over 10 times higher during high discharges than at base flow. Furthermore, both δ 13 C‐DOC and C1 at high flows positively correlated with %agricultural lands within 1 km river buffers, demonstrating that near‐river agricultural activities enhanced storm export of soil DOM. At base flow, C4 positively correlated with %agricultural lands, showing stimulation of aquatic bacterial carbon production as a result of elevated nutrient inputs from agricultural lands. Percent contributions of humic fluorescence in groundwater varied with well depths in shallow wells, but this pattern was not observed for deeper groundwater, suggesting that humic DOM could serve as a water source tracer indicating deeper aquifers were isolated from river water and shallow groundwater. Together, our data demonstrate that hydrology and land use controlled the sources and amount of riverine DOM in this large agricultural basin and that regulating storm runoff and near‐river agricultural activities should be incorporated in ecosystem‐based management of water resources.

Knowledge about the brain and the impact of trauma has increased significantly in recent years. Counselors must understand brain functioning and the effects of trauma in order to choose the most effective methods for working with clients. Creative arts therapies offer a nonthreatening way for clients to access and express their trauma, creating a corrective experience in the brain. Activities that incorporate body movement can be particularly helpful by providing a corrective emotional experience for those clients with an immobilized response to a traumatic event. This article offers a model for the assessment and treatment of trauma through the use of creative arts.

Despite its importance in the nitrogen cycle, little is known about nitrite oxidation at high temperatures. To bridge this gap, enrichment cultures were inoculated with sediment slurries from a variety of geothermal springs. While nitrite-oxidizing bacteria (NOB) were successfully enriched from seven hot springs located in US Great Basin, south-western China, and Armenia at ≤ 57.9 °C, all attempts to enrich NOB from > 10 hot springs at ≥ 61 °C failed. The stoichiometric conversion of nitrite to nitrate, chlorate sensitivity, and sensitivity to autoclaving all confirmed biological nitrite oxidation. Regardless of origin, all successful enrichments contained organisms with high 16S rRNA gene sequence identity (≥ 97%) with Nitrospira calida. In addition, Armenian enrichments also contained close relatives of Nitrospira moscoviensis. Physiological properties of all enrichments were similar, with a temperature optimum of 45-50 °C, yielding nitrite oxidation rates of 7.53 ± 1.20 to 23.0 ± 2.73 fmoles cell(-1) h(-1), and an upper temperature limit between 60 and 65 °C. The highest rates of NOB activity occurred with initial NO2 - concentrations of 0.5-0.75 mM; however, lower initial nitrite concentrations resulted in shorter lag times. The results presented here suggest a possible upper temperature limit of 60-65 °C for Nitrospira and demonstrate the wide geographic range of Nitrospira species in geothermal environments.