Predictive structure or paradigm size? Investigating the effects of i-complexity and e-complexity on the learnability of morphological systems

Research on cross-linguistic differences in morphological paradigms reveals a wide range of variation on many dimensions, including the number of categories expressed, the number of unique forms, and the number of inflectional classes. However, in an influential paper, Ackerman and Malouf (2013) argue that there is one dimension on which languages do not differ widely: in predictive structure. Predictive structure in a paradigm describes the extent to which forms predict each other, called i-complexity. Ackerman and Malouf (2013) show that although languages differ according to measure of surface paradigm complexity, called e-complexity, they tend to have low i-complexity. They conclude that morphological paradigms have evolved under a pressure for low i-complexity. Here, we evaluate the hypothesis that language learners are more sensitive to i-complexity than e-complexity by testing how well paradigms which differ on only these dimensions are learned. This could result in the typological findings Ackerman and Malouf (2013) report if even paradigms with very high e-complexity are relatively easy to learn, so long as they have low i-complexity. First, we summarize a recent work by Johnson et al. (2020) suggesting that both neural networks and human learners may actually be more sensitive to e-complexity than i-complexity. Then we build on this work, reporting a series of experiments which confirm that, indeed, across a range of paradigms that vary in either e- or icomplexity, neural networks (LSTMs) are sensitive to both, but show a larger effect of e-complexity (and other measures associated with size and diversity of forms). In human learners, we fail to find any effect of i-complexity on learning at all. Finally, we analyse a large number of randomly generated paradigms and show that e- and i-complexity are negatively correlated: paradigms with high e-complexity necessarily show low i-complexity. We discuss what these findings might mean for Ackerman and Malouf’s hypothesis, as well as the role of ease of learning versus generalization to novel forms in the evolution of paradigms

Adherence and Tolerability of Alzheimer's Disease Medications: A Pragmatic Randomized Trial

BACKGROUND/OBJECTIVES: Post-marketing comparative trials describe medication use patterns in diverse, real-world populations. Our objective was to determine if differences in rates of adherence and tolerability exist among new users to acetylcholinesterase inhibitors (AChEI's). DESIGN: Pragmatic randomized, open label comparative trial of AChEI's currently available in the United States. SETTING: Four memory care practices within four healthcare systems in the greater Indianapolis area. PARTICIPANTS: Eligibility criteria included older adults with a diagnosis of possible or probable Alzheimer's disease (AD) who were initiating treatment with an AChEI. Participants were required to have a caregiver to complete assessments, access to a telephone, and be able to understand English. Exclusion criteria consisted of a prior severe adverse event from AChEIs. INTERVENTION: Participants were randomized to one of three AChEIs in a 1:1:1 ratio and followed for 18 weeks. MEASUREMENTS: Caregiver-reported adherence, defined as taking or not taking study medication, and caregiver-reported adverse events, defined as the presence of an adverse event. RESULTS: 196 participants were included with 74.0% female, 30.6% African Americans, and 72.9% who completed at least twelfth grade. Discontinuation rates after 18 weeks were 38.8% for donepezil, 53.0% for galantamine, and 58.7% for rivastigmine (P = .063) in the intent to treat analysis. Adverse events and cost explained 73.1% and 25.4% of discontinuation. No participants discontinued donepezil due to cost. Adverse events were reported by 81.2% of all participants; no between-group differences in total adverse events were statistically significant. CONCLUSIONS: This pragmatic comparative trial showed high rates of adverse events and cost-related non-adherence with AChEIs. Interventions improving adherence and persistence to AChEIs may improve AD management. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686 (https://clinicaltrials.gov/ct2/show/NCT01362686)

Antidepressant Use in the Elderly Is Associated With an Increased Risk of Dementia

A retrospective cohort study was conducted including 3688 patients age 60 years or older without dementia enrolled in a depression screening study in primary care clinics. Information on antidepressant use and incident dementia during follow-up was retrieved from electronic medical records. The Cox proportional hazard models were used to compare the risk for incident dementia among 5 participant groups: selective serotonin re-uptake inhibitors (SSRI) only, non-SSRI only (non-SSRI), mixed group of SSRI and non-SSRI, not on antidepressants but depressed, and not on antidepressants and not depressed. SSRI and non-SSRI users had significantly higher dementia risk than the nondepressed nonusers (hazard ratio [HR]=1.83, P=0.0025 for SSRI users and HR=1.50, P=0.004 for non-SSRI users). In addition, SSRIs users had significantly higher dementia risk than non-users with severe depression (HR=2.26, P=0.0005). Future research is needed to confirm our results in other populations and to explore potential mechanism underlying the observed association

A complete DNA sequence map of the ovine Major Histocompatibility Complex

<p>Abstract</p> <p>Background</p> <p>The ovine Major Histocompatibility Complex (MHC) harbors clusters of genes involved in overall resistance/susceptibility of an animal to infectious pathogens. However, only a limited number of ovine MHC genes have been identified and no adequate sequence information is available, as compared to those of swine and bovine. We previously constructed a BAC clone-based physical map that covers entire class I, class II and class III region of ovine MHC. Here we describe the assembling of a complete DNA sequence map for the ovine MHC by shotgun sequencing of 26 overlapping BAC clones.</p> <p>Results</p> <p>DNA shotgun sequencing generated approximately 8-fold genome equivalent data that were successfully assembled into a finished sequence map of the ovine MHC. The sequence map spans approximately 2,434,000 nucleotides in length, covering almost all of the MHC loci currently known in the sheep and cattle. Gene annotation resulted in the identification of 177 protein-coding genes/ORFs, among which 145 were not previously reported in the sheep, and 10 were ovine species specific, absent in cattle or other mammals. A comparative sequence analyses among human, sheep and cattle revealed a high conservation in the MHC structure and loci order except for the class II, which were divided into IIa and IIb subregions in the sheep and cattle, separated by a large piece of non-MHC autosome of approximately 18.5 Mb. In addition, a total of 18 non-protein-coding microRNAs were predicted in the ovine MHC region for the first time.</p> <p>Conclusion</p> <p>An ovine MHC DNA sequence map was successfully assembled by shotgun sequencing of 26 overlapping BAC clone. This makes the sheep the second ruminant species for which the complete MHC sequence information is available for evolution and functional studies, following that of the bovine. The results of the comparative analysis support a hypothesis that an inversion of the ancestral chromosome containing the MHC has shaped the MHC structures of ruminants, as we currently observed in the sheep and cattle. Identification of relative large numbers of microRNAs in the ovine MHC region helps to provide evidence that microRNAs are actively involved in the regulation of MHC gene expression and function.</p

Inhibition or Stimulation of Autophagy Affects Early Formation of Lipofuscin-Like Autofluorescence in the Retinal Pigment Epithelium Cell

The accumulation of lipofuscin in the retinal pigment epithelium (RPE) is dependent on the effectiveness of photoreceptor outer segment material degradation. This study explored the role of autophagy in the fate of RPE lipofuscin degradation. After seven days of feeding with either native or modified rod outer segments, ARPE-19 cells were treated with enhancers or inhibitors of autophagy and the autofluorescence was detected by fluorescence-activated cell sorting. Supplementation with different types of rod outer segments increased lipofuscin-like autofluorescence (LLAF) after the inhibition of autophagy, while the induction of autophagy (e.g., application of rapamycin) decreased LLAF. The effects of autophagy induction were further confirmed by Western blotting, which showed the conversion of LC3-I to LC3-II, and by immunofluorescence microscopy, which detected the lysosomal activity of the autophagy inducers. We also monitored LLAF after the application of several autophagy inhibitors by RNA-interference and confocal microscopy. The results showed that, in general, the inhibition of the autophagy-related proteins resulted in an increase in LLAF when cells were fed with rod outer segments, which further confirms the effect of autophagy in the fate of RPE lipofuscin degradation. These results emphasize the complex role of autophagy in modulating RPE autofluorescence and confirm the possibility of the pharmacological clearance of RPE lipofuscin by small molecules

Redefined blood pressure variability measure and its association with mortality in elderly primary care patients

Visit-to-visit blood pressure (BP) variability has received considerable attention recently. The objective of our study is to define a variability measure that is independent of change over time and determine the association between longitudinal summary measures of BP measurements and mortality risk. Data for the study came from a prospective cohort of 2906 adults, aged ≥60 years, in an urban primary care system with ≤15 years of follow-up. Dates of death for deceased participants were retrieved from the National Death Index. Systolic and diastolic BP measurements from outpatient clinic visits were extracted from the Regenstrief Medical Record System. For each patient, the intercept, regression slope, and root mean square error for visit-to-visit variability were derived using linear regression models and used as independent variables in Cox proportional hazards models for both all-cause mortality and mortality attributable to coronary heart disease or stroke. Rate of change was associated with mortality risk in a U-shaped relationship and that participants with little or no change in BP had the lowest mortality risk. BP variability was not an independent predictor of mortality risk. By separating change over time from visit-to-visit variability in studies with relatively long follow-up, we demonstrated in this elderly primary care patient population that BP changes over time, not variability, were associated with greater mortality risk. Future research is needed to confirm our findings in other populations

Antihypertensive Medication and Dementia Risk in Older Adult African Americans with Hypertension: A Prospective Cohort Study

BACKGROUND: African Americans are especially at risk of hypertension and dementia. Antihypertensive medications reduce the risk of cardiovascular events, but may also reduce the risk of dementia. OBJECTIVE: To assess the longitudinal effects of antihypertensive medications and blood pressure on the onset of incident dementia in a cohort of African Americans. DESIGN: Prospective cohort. PARTICIPANTS: 1236 community-dwelling patients from an inner-city public health care system, aged 65 years and older, with a history of hypertension but no history of dementia, and who had at least three primary care visits and a prescription filled for any medication. MAIN MEASURES: Blood pressure was the average of three seated measurements. Dementia was diagnosed using a two-stage design, with a screening evaluation every 2 to 3 years followed by a comprehensive in-home clinical evaluation for those with a positive screen. Laboratory, inpatient and outpatient encounter data, coded diagnoses and procedures, and medication records were derived from a health information exchange. KEY RESULTS: Of the 1236 hypertensive participants without dementia at baseline, 114 (9%) developed incident dementia during follow-up. Individuals prescribed any antihypertensive medication (n = 816) were found to have a significantly reduced risk of dementia (HR = 0.57, 95% CI 0.37-0.88, p = 0.0114) compared to untreated hypertensive participants (n = 420). When this analysis was repeated including a variable indicating suboptimally treated blood pressure (> 140 mmHg systolic or >90 mmHg diastolic), the effect of antihypertensive medication was no longer statistically significant (HR = 0.65, 95% CI 0.32-1.30, p = 0.2217). CONCLUSIONS: Control of blood pressure in older adult African American patients with hypertension is a key intervention for preventing dementia, with similar benefits from most of the commonly available antihypertensive medications

Mild Cognitive Impairment, Incidence, Progression, and Reversion: Findings from a Community-based Cohort of Elderly African Americans

Objective To examine the long-term outcomes of community-based elderly African Americans by following their transitions from normal cognition to mild cognitive impairment (MCI), and to dementia. Methods Participants were from the community-based Indianapolis Dementia Project. A total of 4104 African Americans were enrolled in 1992 or 2001 and followed until 2009 with regularly scheduled evaluation of cognitive assessment. A two-stage sampling was used at each evaluation to select individuals for extensive clinical assessment following the results of stage one cognitive testing. Age and gender specific incidence, progression and reversion rates for MCI were derived using the person-year method in a dynamic cohort and predicted probabilities from weighted multinomial logistic models of transitional probabilities among normal cognition, MCI and dementia. Results Annual overall incidence rate for MCI is 5.6% (95% CI: 4.6–6.6%). Annual progression rate from MCI to dementia is 5.9% (95% CI: 5.3–6.5%) and annual reversion rate from MCI to normal is 18.6% (95% CI: 16.7–20.4%). Both MCI incidence rates and MCI to dementia progression rates increase with age, while reversion rates from MCI to normal decrease with age. Conclusion MCI progression to dementia is much more frequent in the older age groups than in the younger participants where reversion to normal cognition is more common. Future research is needed to determine factors related to the heterogeneous outcomes in MCI individuals

Comorbidity Profile and Health Care Utilization in Elderly Patients with Serious Mental Illnesses

Objectives Patients with serious mental illness are living longer. Yet there remain few studies that focus on health care utilization and its relationship to comorbidities in these elderly mentally ill patients. Design Comparative study. Information on demographics, comorbidities and health care utilization were taken from an electronic medical record system. Setting Wishard Health Services senior care and community mental health clinics. Participants Patients age 65 years and over-255 patients with serious mental illness (schizophrenia, major recurrent depression and bipolar illness) attending a mental health clinic and a representative sample of 533 non-demented patients without serious mental illness attending primary care clinics. Results Patients having serious mental illness had significantly higher rates of medical emergency room visits (p=0.0027) and significantly longer lengths of medical hospitalizations (p<0.0001) than did the primary care control group. The frequency of medical comorbidities such as diabetes, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, thyroid disease, and cancer were not significantly different between the groups. Hypertension was lower in the mentally ill group (p<0.0001). Reported falls (p<0.0001), diagnoses of substance abuse (p=0.02), and alcoholism (p=0.0016) were higher in the seriously mentally ill. The differences in health care utilization between the groups remained significant after adjusting for comorbidity levels, lifestyle factors, and attending primary care. Conclusions Our findings of higher rates of emergency care, longer hospitalizations, and increased frequency of falls, substance abuse, and alcoholism suggest the elderly seriously mentally ill remain a vulnerable population requiring an integrated model of health care