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Regulatory Aspects of Mild Cognitive Impairment: Toward a Harmonized Perspective
No full textThe development of the concept of mild cognitive impairment (MCI) and its practical application have been intimately tied to attempts to produce therapeutic agents. Understanding the regulatory environment and determining the way in which it can be influenced are critical to the development of drugs and their eventual approval. In this article, we review some of the current challenges surrounding the concept of MCI relevant to drug development, summarize activities in various regions of the world, and conclude with some suggested next steps and an alternative framing for approving drugs for MCI and related conditions
Characterization of Active Electrode Yield for Intracortical Arrays: Awake versus Anesthesia
Get PDFIntracortical microelectrode arrays are used for recording neural signals at single-unit resolution and are promising tools for studying brain function and developing neuroprosthetics. Research is being done to increase the chronic performance and reliability of these probes, which tend to decrease or fail within several months of implantation. Although recording paradigms vary, studies focused on assessing the reliability and performance of these devices often perform recordings under anesthesia. However, anesthetics—such as isoflurane—are known to alter neural activity and electrophysiologic function. Therefore, we compared the neural recording performance under anesthesia (2% isoflurane) followed by awake conditions for probes implanted in the motor cortex of both male and female Sprague-Dawley rats. While the single-unit spike rate was significantly higher by almost 600% under awake compared to anesthetized conditions, we found no difference in the active electrode yield between the two conditions two weeks after surgery. Additionally, the signal-to-noise ratio was greater under anesthesia due to the noise levels being nearly 50% greater in awake recordings, even though there was a 14% increase in the peak-to-peak voltage of distinguished single units when awake. We observe that these findings are similar for chronic time points as well. Our observations indicate that either anesthetized or awake recordings are acceptable for studies assessing the chronic reliability and performance of intracortical microelectrode arrays
Testing Modified Gravity Theories with Numerical Solutions of the External Field Effect in Rotationally Supported Galaxies
Get PDFThe strong equivalence principle is violated by gravity theories of Milgromian dynamics [modified Newtonian dynamics (MOND)] through the action of the external field effect. We test two different Lagrangian theories Aquadratic-Lagrangian (AQUAL) and quasilinear MOND (QUMOND) based on their numerical solutions of the external field effect, by comparing two independent estimates of the mean external field strength of the nearby universe: a theory-deduced value from fitting the outer rotation curves of 114 galaxies and an empirical value from the large-scale distribution of cosmic baryons. The AQUAL-deduced external field strength from rotation curves agrees with that from the large-scale cosmic environment, while QUMOND-deduced value is somewhat higher. This suggests that AQUAL is likely to be preferred over QUMOND as an effective nonrelativistic limit of a potential relativistic modified gravity theory
The Effect of Adiabatic Compression on Dark Matter Halos and the Radial Acceleration Relation
Get PDFWe use a semiempirical model to investigate the radial acceleration relation (RAR) in a cold dark matter (CDM) framework. Specifically, we build 80 model galaxies covering the same parameter space as the observed galaxies in the SPARC database, assigning them to dark matter (DM) halos using abundance-matching and halo mass-concentration relations. We consider several abundance-matching relations, finding some to be a better match to the kinematic data than others. We compute the unavoidable gravitational interactions between baryons and their DM halos, leading to an overall compression of the original Navarro-Frenk-White (NFW) halos. Before halo compression, high-mass galaxies lie approximately on the observed RAR, whereas low-mass galaxies display up-bending hooks at small radii due to DM cusps, making them deviate systematically from the observed relation. After halo compression, the initial NFW halos become more concentrated at small radii, making larger contributions to rotation curves. This increases the total accelerations, moving all model galaxies away from the observed relation. These systematic deviations suggest that the CDM model with abundance matching alone cannot explain the observed RAR. Further effects (e.g., feedback) would need to counteract the compression with precisely the right amount of halo expansion, even in high-mass galaxies with deep potential wells where such effects are generally predicted to be negligible
Improving Feedforward Controls To Improve NPD Portfolio Performance – An Empirical Study
Get PDFManagers making crucial project selections in large, fast-changing project portfolios face the challenge of balancing the tension between control (performance) and creativity (experimentation/innovation). To better manage this challenge and to improve performance, some practitioners and scholars have considered the application of more sophisticated feedforward controls in new product development portfolio project selections. However, empirical studies of changes in the sophistication of such controls and of their influence on performance are lacking. We use an engaged scholarship approach and an action research methodology in a large international organization with multiple business units to study the post-intervention changes in applied controls and changes in portfolio performance. Our findings identify the underlying generative mechanisms influencing the changes in the applied sophistication of feedforward controls, how these changes enable portfolio managers to better balance the tension between control and creativity in project selection, and the performance outcomes
Palliative Stenting of the Venous Duct in a Premature Neonate with Obstructed Infradiaphragmatic Total Anomalous Pulmonary Venous Connection
Get PDFIn infracardiac, infradiaphragmatic total anomalous pulmonary venous connection, all four pulmonary veins connect to a descending vertical vein that usually drains to the portal vein or one of its tributaries. Obstruction is common, and definitive treatment is surgical repair. We present a case of late-diagnosed infradiaphragmatic total anomalous pulmonary venous connection in a premature neonate who was too high risk for surgery and underwent palliative stenting of the venous duct. We demonstrate the feasibility of a transhepatic approach when umbilical access is no longer available
The Longitudinal Relationship Between Broken Windows and Sexual Behaviors Among African American Girls in Juvenile Detention: The Moderating Effects of Sexual Sensation Seeking and Parental Monitoring
Get PDFObjective: Broken windows theory has been applied in public health to understand how neighborhood disadvantage contributes to health risk and disparities. This longitudinal study examined the relationship between a broken windows index (i.e., a proxy for neighborhood disadvantage) and sexual behaviors and whether sexual sensation-seeking behaviors and parental monitoring moderated that relationship. Method: Participants were 188 African American adolescent girls incarcerated in a short-term detention facility in Atlanta, GA. Participants completed audio computer-assisted self-interviews at baseline, 3, and 6 months; interviews assessed neighborhood disadvantage, sexual risk behaviors, sexual sensation seeking, parental monitoring, and demographics. Results: Longitudinal findings indicate that the broken windows index was associated with risky sexual behaviors (e.g., condomless sex and sex while using drugs). Parental monitoring (i.e., knowledge of child activities and friends) moderated the relationship between broken windows and sexual risk behaviors. Conclusion: Future interventions should address underlying mechanisms linking structural disadvantage to sexual behaviors
Using mHealth to Improve Adherence and Reduce Blood pressure in Individuals With Hypertension and Bipolar Disorder (iTAB-CV): Study Protocol for a 2-Stage Randomized Clinical Trial
No full textBackground: Cardiovascular disease in individuals with mental health conditions such as bipolar disorder is highly prevalent and often poorly managed. Individuals with bipolar disorder face significant medication adherence barriers, especially when they are prescribed multiple medications for other health conditions including hypertension. Poor adherence puts them at a disproportionate risk for poor health outcomes. As such, there is a need for effective interventions to improve hypertension medication adherence, particularly in patients that struggle with adherence due to mental health comorbidity. Methods: This 5-year project uses a 2-stage randomized controlled trial design to evaluate a brief, practical adherence intervention delivered via interactive text messaging (iTAB-CV) along with self-monitoring of medication taking, mood, and home blood pressure (N = 100) compared to self-monitoring alone (N = 100). Prior to randomization, all participants will view an educational video that emphasizes the importance of medication for the treatment of hypertension and bipolar disorder. Those randomized to the texting intervention will receive daily text messages with predetermined content to address 11 salient domains as well as targeted customized messages for 2 months. This group will then be re-randomized to receive either a high (gradual taper from daily to weekly texts) or low booster (weekly texts) phase for an additional 2 months. All participants will be monitored for 52 weeks. The primary outcomes are systolic blood pressure and adherence to antihypertensive medication as determined by a self-reported questionnaire and validated with an automated pill-monitoring device. Secondary outcomes include adherence to bipolar disorder medications, psychiatric symptoms, health status, self-efficacy for medication-taking behavior, illness beliefs, medication attitudes, and habit strength. Discussion: This study specifically targets blood pressure and mental health symptom control in people with bipolar and includes implementation elements in the study design intended to inform future scale-up. Promising pilot data and a theoretical model, which views sustained medication-taking behavior in the context of habit formation, suggests that this remotely delivered intervention may help advance care for this high-risk population and is amenable to both scale up and easy adaptation for other groups with poor medication adherence. Trial registration: The study was registered at ClinicalTrials.gov (NCT04675593) on December 19, 2020
Similar Mortality among United States Veterans with Invasive and Noninvasive Pneumonia due to Group B Streptococcus
Get PDFBackground: The nosology of noninvasive pneumonia due to group B Streptococcus (GBS) is not well defined. This study compared clinical characteristics and outcomes of patients with invasive pneumonia and noninvasive pneumonia caused by GBS. Methods: We conducted a retrospective cohort study among Veterans Affairs (VA) healthcare users between 2008 and 2017. Using data from electronic health records, we identified patients who had blood or respiratory cultures that grew GBS and had invasive pneumonia or noninvasive pneumonia. We analyzed patient and infection characteristics associated with all-cause mortality, including among the subset of patients with cultures that were monomicrobial for GBS. Results: Among 1791 patients with GBS pneumonia, 646 (36%) cases were invasive and 1145 (64%) were noninvasive. Among those, 535 and 424 cases of invasive and noninvasive pneumonia, respectively, had cultures that were monomicrobial for GBS. All-cause 30-day mortality among those with monomicrobial GBS pneumonia was 15% for both those with invasive and noninvasive disease, respectively. Increasing age, severity of illness, healthcare exposure in the previous 90 days, and polymicrobial infection with Staphylococcus aureus were independently associated with all-cause mortality at 30 days. Conclusions: In this large cohort, even when considering cases for which GBS was the only pathogen recovered, \u3e40% of GBS pneumonia cases were noninvasive. All-cause mortality was comparable for invasive and noninvasive pneumonia. These findings suggest that the burden of GBS pneumonia may be greater than previously recognized by surveillance of invasive GBS disease and may inform treatment and prevention efforts
Urban Expansion of Energiewende in Germany: A Systematic Bibliometric Analysis and Literature Study
Get PDFBackground: Despite Germany’s world leadership of Energiewende, there have been mounting challenges, such as the slowdown of German renewable energy growth since 2017, when the Merkel administration dramatically changed the German renewable energy promotion policy from feed-in tariffs to competitive auctions. These challenges pose important research questions about whether and how an emerging urban expansion of Energiewende can serve as a vital solution to counteract the challenges to the energy transition. Answering these research questions provides a unique opportunity to explore the academic and historic foundations of the energy transition and its urban expansion, the emerging events that exemplify urban expansion, and the viable solutions this growing trend of urban expansion might be able to provide to the challenges to the German energy transition. Methods: This paper conducted visual and manual bibliometric analyses, examined the results of case studies, and reviewed secondary literature and data on urban expansion of German Energiewende. Results: By analyzing the bibliometric and investigative results, this paper identified political, socioeconomic, and technological challenges to Energiewende and a new trend of solar energy expansion in German cities aimed at meeting Germany’s carbon neutrality targets by 2045. The new trend of the urban expansion of the German energy transition manifests itself in the focused research efforts on identifying the vast untapped potential on new building rooftop areas in most populous German cities and/or detached and two-family houses in Germany and the recent booming of building-related solar PV and heating mandates in German cities and states, the expanding solar heating and cooling systems, and the government policy support at various levels in this urban expansion through aggressively strengthening climate and renewable energy targets. Conclusions: In search for answers to the recent challenges of Energiewende in Germany, this paper conducted both visual and manual bibliometric analyses and applied desk research and reviews of secondary literature and data. This paper found an emerging trend of the urban expansion of Energiewende, including the awareness of the vast potential and gap of urban solarization and the enhanced urban municipal policies, actors, actions, and accomplishments of exploiting this potential. These findings were based on academic knowledge on the German energy transition and contribute to expanding this academic knowledge. To help more effectively exploit the vast potential in solarizing all German cities, especially the largest ones, this study recommends that further research more closely track the progress of this trend and apply more quantitative tools and approaches in future tracking
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