FORECASTING THE GLOBAL BURDEN OF ALZHEIMER\u27S DISEASE

Background: The goal was to forecast the global burden of Alzheimer’s disease and evaluate the potential impact of interventions that delay disease onset or progression. Methods: A stochastic multi-state model was used in conjunction with U.N. worldwide population forecasts and data from epidemiological studies on risks of Alzheimer’s disease. Findings: In 2006 the worldwide prevalence of Alzheimer’s disease was 26.6 million. By 2050, prevalence will quadruple by which time 1 in 85 persons worldwide will be living with the disease. We estimate about 43% of prevalent cases need a high level of care equivalent to that of a nursing home. If interventions could delay both disease onset and progression by a modest 1 year, there would be nearly 9.2 million fewer cases of disease in 2050 with nearly all the decline attributable to decreases in persons needing high level of care. Interpretation: We face a looming global epidemic of Alzheimer’s disease as the world’s population ages. Modest advances in therapeutic and preventive strategies that lead to even small delays in Alzheimer’s onset and progression can significantly reduce the global burden of the disease

Caesium bis­(5-bromo­salicyl­aldehyde thio­semicarbazonato-κ3O,N,S)ferrate(III): supramolecular arrangement of low-spin FeIII complex anions mediated by Cs+ cations

The synthesis and crystal structure determination (at 293 K) of the title complex, Cs[Fe(C8H6BrN3OS)2], are reported. The compound is composed of two dianionic O,N,S-tridentate 5-bromo­salicyl­aldehyde thio­semicarbazonate(2-) ligands coord­inated to an FeIII cation, displaying a distorted octa­hedral geometry. The ligands are orientated in two perpendicular planes, with the O- and S-donor atoms in cis positions and the N-donor atoms in trans positions. The complex displays inter­molecular N-H...O and N-H...Br hydrogen bonds, creating R44(18) rings, which link the FeIII units in the a and b directions. The FeIII cation is in the low-spin state at 293 K

Inhibitors of SARS-CoV entry--identification using an internally-controlled dual envelope pseudovirion assay.

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV) emerged as the causal agent of an endemic atypical pneumonia, infecting thousands of people worldwide. Although a number of promising potential vaccines and therapeutic agents for SARS-CoV have been described, no effective antiviral drug against SARS-CoV is currently available. The intricate, sequential nature of the viral entry process provides multiple valid targets for drug development. Here, we describe a rapid and safe cell-based high-throughput screening system, dual envelope pseudovirion (DEP) assay, for specifically screening inhibitors of viral entry. The assay system employs a novel dual envelope strategy, using lentiviral pseudovirions as targets whose entry is driven by the SARS-CoV Spike glycoprotein. A second, unrelated viral envelope is used as an internal control to reduce the number of false positives. As an example of the power of this assay a class of inhibitors is reported with the potential to inhibit SARS-CoV at two steps of the replication cycle, viral entry and particle assembly. This assay system can be easily adapted to screen entry inhibitors against other viruses with the careful selection of matching partner virus envelopes

Otolith Microchemical Fingerprints of Age-0 Red Snapper, Lutjanus campechanus, from the Northern Gulf of Mexico

Red snapper, Lutjanus campechanus, in the northern Gulf of Mexico (Gulf) are believed to constitute a single stock. However, tagging and genetics studies suggest there is little mixing between populations of red snapper in the northern Gulf, and little is known about mixing rates of adult fish. The long-term goal of our work is to determine if age-0 red snapper from different nursery areas have unique microchemical fingerprints in their sagittal otoliths, and if so, can the microchemical fingerprints at the core of adult otoliths be used to determine retrospectively nursery area of origin. Ultimately, we hope to use the microchemical fingerprints at the core of adult snapper otoliths to estimate adults\u27 mixing rates and movement patterns. In this study, the objective was to determine if age-0 red snapper collected from different northern Gulf nursery areas in summer and fall 1995 did contain unique microchemical fingerprints. Sagittal otoliths of age-0 red snapper collected off the coasts of Alabama/Mississippi, Louisiana, and Texas were analyzed using inductively coupled plasma atomic emission spectrometry (ICP-AES). Twelve elements in the sagittae of age-0 snapper were analyzed with ICP-AES. Of these, eight were put into a stepwise discriminant function analysis with the best-fitted model including Mg, Se, As, Fe, and AI, entered in that order (MANOVA, P \u3c 0.001). Cross-validated classification accuracies were 92% for Texas fish, 91% for Louisiana fish, and 92% for Alabama/Mississippi fish. Therefore, it appears that otolith microchemistry can be used to infer nursery area of age-0 red snapper. Future work will focus on (1) establishing the temporal stability of age-0 red snapper otolith microchemical fingerprints and (2) inclusion of analyses of age-structured samples from adult red snapper otolith cores to estimate their nursery area of origin and mixing rates

Sensory Processing Abnormalities in Community-Dwelling Older Adults with Cognitive Impairment: A Mixed Methods Study

Mild cognitive impairment (MCI) or dementia often leads to behavioral and psychiatric symptoms of dementia (BPSD). Sensory processing abnormalities may be associated with BPSD. The purpose of this study was to explore relationships among sensory processing, behavior, and environmental features within the homes of people with MCI or dementia. This project used mixed methods to assess participants’ sensory processing, care partner perspectives on behaviors, and in situ observations of the home environment. Nine participants with cognitive impairment (MCI n = 8, early dementia = 1) and their care partners were included. Seven participants with cognitive impairment were reported to have abnormal sensory processing. Findings suggest that unique environmental adaptations, tailored to personal and sensory preferences for each participant, were associated with a decreased level of behavioral disruption during the observation periods. Implementing sensory-based approaches to maximize environment adaptation may be beneficial in reducing disruptive behaviors for adults with cognitive impairment

Jumping to Conclusions, a Lack of Belief Flexibility and Delusional Conviction in Psychosis: A Longitudinal Investigation of the Structure, Frequency, and Relatedness of Reasoning Biases

Two reasoning biases, jumping to conclusions (JTC) and belief inflexibility, have been found to be associated with delusions. We examined these biases and their relationship with delusional conviction in a longitudinal cohort of people with schizophrenia-spectrum psychosis. We hypothesized that JTC, lack of belief flexibility, and delusional conviction would form distinct factors, and that JTC and lack of belief flexibility would predict less change in delusional conviction over time. Two hundred seventy-three patients with delusions were assessed over twelve months of a treatment trial (Garety et al., 2008). Forty-one percent of the sample had 100% conviction in their delusions, 50% showed a JTC bias, and 50%–75% showed a lack of belief flexibility. Delusional conviction, JTC, and belief flexibility formed distinct factors although conviction was negatively correlated with belief flexibility. Conviction declined slightly over the year in this established psychosis group, whereas the reasoning biases were stable. There was little evidence that reasoning predicted the slight decline in conviction. The degree to which people believe their delusions, their ability to think that they may be mistaken and to consider alternative explanations, and their hastiness in decision making are three distinct processes although belief flexibility and conviction are related. In this established psychosis sample, reasoning biases changed little in response to medication or psychological therapy. Required now is examination of these processes in psychosis groups where there is greater change in delusion conviction, as well as tests of the effects on delusions when these reasoning biases are specifically targeted

Development of a Forage Evaluation System for Perennial Ryegrass Cultivar and Endophyte Combinations in New Zealand Dairy Systems

An economic index for perennial ryegrass (Lolium perenne L.) cultivars is a relatively new concept, although recently introduced in Ireland (McEvoy et al. 2011). By contrast, in dairy cattle breeding, the concept of an economic index rating animals and economic values underlying that index is well entrenched (Philipson et al. 1994; Veerkamp, 1998). Historically, forage evaluation data for individual cultivars were either displayed using absolute numbers for seasonal dry matter production within a season or across all seasons with a notation to indicate statistical differences, or percentage values where a reference cultivar is 100. The adoption of an economic index and routine evaluation approach for perennial ryegrass provides a method to identify traits of economic importance to focus plant breeding efforts better and to provide clarity for farmers around predicting cultivars that will maximise farm profit. It also allows for routine tracking of genetic gain of individual traits and the economic index. In this paper, the economic based forage evaluation techniques now used in New Zealand for perennial ryegrass cultivar/endophyte combinations are presented

Dosing regimen of meropenem for adults with severe burns : a population pharmacokinetic study with Monte Carlo simulations

Objectives To develop a population model to describe the pharmacokinetics (PK) of intravenous meropenem in adult patients with severe burns and investigate potential relationships between dosage regimens and antimicrobial efficacy.Patients and methods A dose of 1 g every 8 h was administered to adult patients with total body surface area burns of ≥15%. Doses for subsequent courses were determined using results from the initial course and the patient's clinical condition. Five plasma meropenem concentrations were typically measured over the dosage interval on one to four occasions. An open, two-compartment PK model was fitted to the meropenem concentrations using NONMEM and the effect of covariates on meropenem PK was investigated. Monte Carlo simulations investigated dosage regimens to achieve a target T>MIC for ≥40%, ≥60% or ≥80% of the dose interval.Results Data comprised 113 meropenem concentration measurements from 20 dosage intervals in 12 patients. The parameters were CL (L/h) = 0.196 L/h/kg × [1 − 0.023 × (age − 46)] × [1 − 0.049 × (albumin − 15)], V1 = 0.273 L/kg × [1 − 0.049 × (albumin − 15)], Q = 0.199 L/h/kg and V2 = 0.309 L/kg × [1 – 0.049 × (albumin − 15)]. For a target of ≥80% T>MIC, the breakpoint was 8 mg/L for doses of 1 g every 4 h and 2 g every 8 h given over 3 h, but only 4 mg/L if given over 5 min.Conclusions Although 1 g 8 hourly should be effective against Escherichia coli and CoNS, higher doses, ideally with a longer infusion time, would be more appropriate for empirical therapy, mixed infections and bacteria with MIC values ≥4 mg/L

Grazing in a megagrazer-dominated savanna does not reduce soil carbon stocks, even at high intensities

Recent studies suggest that wild animals can promote ecosystem carbon sinks through their impacts on vegetation and soils. However, livestock studies show that intense levels of grazing reduce soil organic carbon (SOC), leading to concerns that rewilding with large grazers may compromise ecosystem carbon storage. Furthermore, wild grazers can both limit and promote woody plant recruitment and survival on savanna grasslands, with both positive and negative impacts on SOC, depending on the rainfall and soil texture contexts. We used grazing lawns in one of the few African protected savannas that are still dominated by megagrazers (> 1000 kg), namely white rhinoceros Ceratotherium simum, as a model to study the impact of prolonged and intense wild grazing on SOC stocks. We contrasted SOC stocks between patches of varying grazing intensity and woody plant encroachment in sites across different rhino habitat types. We found no differences in SOC stocks between the most- and least grazed plots in any of the habitats. Intermediately grazed plots, however, had higher SOC stocks in the top 5 cm compared to most and least grazed plots, but only in the closed-canopy woodland habitat and not in the open habitats. Importantly, we found no evidence to support the hypothesis that wild grazing reduces SOC, even at high grazing intensities by the world's largest megagrazer. Compared to the non-encroached reference plots, woody encroached plots had higher SOC stocks in soils with low clay content and lower SOC stocks in soils with high clay content, although only in the top 5 cm. Accordingly, our study highlights that wild grazers may influence SOC indirectly through their impact on tree-grass ratios in grassy ecosystems. Our study thus provides important insights for future natural climate solutions that focus on wild grazer conservation and restoration.Keywords: fire, grazing impact, rewilding, soil carbon, white rhinoceros, woody encroachmen

Serum Midkine, estimated glomerular filtration rate and chronic kidney disease-related events in elderly women: Perth Longitudinal Study of Aging Women

© 2020, The Author(s). Midkine (MDK), a heparin-binding growth factor cytokine, is involved in the pathogenesis of kidney diseases by augmenting leukocyte trafficking and activation. Animal models and small case control studies have implicated MDK as a pathological biomarker in chronic kidney diseases (CKD), however this is yet to be confirmed in prospective human studies. In a prospective study of 499 elderly, predominantly Caucasian women aged over 70 years the association between serum MDK collected in 1998, and renal function change and the risk of CKD-related hospitalisations and deaths at 5 and 14.5 years, respectively, was examined. Baseline serum MDK was not associated with 5-year change in estimated glomerular filtration rate using the CKD Epidemiology Collaboration creatinine and cystatin C equation (Standardised β = − 0.09, 95% confidence interval − 3.76–0.48, p = 0.129), 5-year rapid decline in renal function (odds ratio = 0.97, 95% confidence interval 0.46–2.02, p = 0.927) or the risk of 14.5-year CKD-related hospitalisations and deaths (hazard ratio = 1.27, 95% confidence interval.66–2.46, p = 0.470) before or after adjusting for major risk factors. In conclusion, in this cohort of elderly women with normal or mildly impaired renal function, serum MDK was not associated with renal function change or future CKD-related hospitalisations and deaths, suggesting that MDK may not be an early biomarker for progression of CKD