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The entorhinal cortex (EC) is the first cortical region affected by tau pathology in Alzheimer’s disease (AD), but its functions remain unclear. The EC is thought to support memory binding, which can be tested using the Visual Short-Term Memory Binding Test (VSTMBT). We aimed to test whether VSTMBT performance can identify individuals with preclinical AD before noticeable episodic memory impairment and whether these performances are related to amyloid (Aβ) pathology and/or EC tau burden.
Methods:
Ninety-four participants underwent the VSTMBT (including a shape-only condition (SOC) and a shape-color binding condition (SCBC)), standard neuropsychological assessment including the Preclinical Alzheimer Cognitive Composite (PACC5), an Aβ status examination, a 3D-T1 MRI and a [18F]-MK-6240 tau-PET scan. Participants were classified as follows: 54 Aβ-negative cognitively normal (Aβ − CN), 22 Aβ-positive CN (Aβ + CN, preclinical AD), and 18 Aβ + individuals with Mild Cognitive Impairment (Aβ + MCI, prodromal AD).
Results:
Aβ + CN individuals performed worse than Aβ-CN participants in the SCBC while the SOC only distinguished Aβ − CN from MCI participants. The SCBC performance was predicted by tau burden in the EC after adjusting for Aβ, white matter hypointensities, inferior temporal cortex (ITC) tau burden, age, sex, and education. The SCBC was more sensitive than the PACC5 in identifying CN individuals with a positive tau-PET scan.
Conclusion:
Impaired visual short-term memory binding performance was evident from the preclinical stage of sporadic AD and related to tau pathology in the EC, suggesting that SCBC performance could detect early tau pathology in the EC among CN individuals.
Vitamin D is crucial for normal organ function, vascular health and exercise performance, yet its deficiency is widespread. Patients with CHD often exhibit reduced exercise capacity. Limited research exists on vitamin D in CHD.
Methods:
This study investigates serum 25-hydroxy vitamin D levels in 55 adult CHD patients (median age 31 years) compared to 55 age- and gender-matched controls without cardiac disease and examines associations with exercise capacity, peripheral microvascular function, muscle strength and biventricular function in CHD. Therefore, patients underwent fingertip arterial tonometry, transthoracic echocardiography, muscle strength measurements and cardiopulmonary exercise testing.
Results:
Results indicated that 93% of CHD patients and 91% of controls had 25-hydroxy vitamin D levels <30 ng/ml, with both groups showing varying values depending on the season in which the studies were conducted. No significant difference in 25-hydroxy vitamin D levels was found between patients and controls. While vitamin D levels in CHD patients did not significantly correlate with age, body mass index, blood pressure, peripheral microvascular function, high-sensitivity C-reactive protein, cholesterol levels, N-terminal-pro hormone B-type natriuretic peptide, ventricular function or muscle strength, a significant correlation was found with percent-predicted peak oxygen consumption (ρ=0.41, p = 0.005 and ρ=0.34, p = 0.02 for reference values following Wasserman and the LowLands registry, respectively), even after adjusting for season (p = 0.03 and 0.05, respectively).
Conclusions:
In conclusion, vitamin D levels were similar between CHD patients and controls, but vitamin D insufficiency is common and linked to reduced exercise capacity in CHD. Further research is needed to determine whether vitamin D supplementation combined with exercise could be beneficial in CHD with vitamin D insufficiency.
To evaluate antibiotic prescribing behavior (APB) among physicians with various specialties in five Asian countries.
Design:
Survey of antibiotics prescribing behavior in three stages (initial, on-treatment, and de-escalation stages).
Methods:
Participants included internists, infectious diseases (ID) specialists, hematologists, intensivists, and surgeons. Participants’ characteristics, patterns of APB, and perceptions of antimicrobial stewardship were collected. A multivariate analysis was conducted to evaluate factors associated with appropriate APB.
Results:
There were 367 participants. The survey response rate was 82.5% (367/445). For the initial stage, different specialties had different choices for empiric treatment. For the on-treatment stage, if the patient does not respond to empiric treatment, most respondents will step up to broader-spectrum antibiotics (273/367: 74.39%). For the de-escalation stage, the rate of de-escalation was 10%–60% depending on the specialty. Most respondents would de-escalate antibiotics based on guidelines (250/367: 68.12%). De-escalation was mostly reported by ID specialists (66/106: 62.26%). Respondents who reported that they performed laboratory investigations prior to empirical antibiotic prescriptions (aOR = 2.83) were associated with appropriate use, while respondents who reported ID consultation were associated with appropriate antibiotic management for infections not responding to empiric treatment (aOR = 40.87); adherence with national guidelines (aOR = 2.57) was associated with reported successful carbapenem de-escalation.
Conclusion:
This study highlights the variation in practices and gaps in appropriate APB on three stages of antibiotic prescription among different specialties. Education on appropriate investigation, partnership with ID specialist, and availability and adherence with national guidelines are critical to help guide appropriate APB among different specialties.
User Experience is becoming an increasing centre of interest both in the academic and industrial worlds. Design agencies are no strangers to this phenomenon and are willing to shift from product-oriented design toward user experience design. However, their design process is often loose which may explain a lack of final UX quality or proof of quality, and does not allow to diagnose misuses and improvement opportunities due to a lack of UX formulation and traceability. We propose in this paper to retrospectively represent a design project and its specified, designed and validated UX, in the perspective to conduct a posterior collective diagnosis of UX design in a design agency. The proposed representation model is used to analyse one design project. Results show that only a few UX traces are found in the presented project, and that many dimensions are not considered (like perceptions or affects). Finally, we discuss the next steps of this tool's deployment to create a shared mental model of the design process among the design players.
Amid the emergence of modern warfare at the end of the nineteenth century, states agreed on a model to regulate armed conflicts centered on a body of internationally agreed norms known as international humanitarian law (IHL). While states have always been the sole law makers and are ultimately responsible for the implementation of the laws of war, the International Committee of the Red Cross placed itself at the very center of the new model, as the champion of IHL, filling the gaps in terms of sponsoring new rules, promoting the law, and monitoring its application in war zones. This unique model of governance was composed of states and independent humanitarian actors and combines features of a hierarchy and a network. While the model saved countless numbers of lives, it has been perpetually challenged, criticized, and violated. The model stood the test of time nonetheless and survived the conflicts of the twentieth century. It is still enduring today. This chapter analyses the reasons for the longevity of the model, looking at its evolution over time in terms of key moments, efficacy and legitimacy, changing composition, and growing complexity.
The in vitro effects of four nutraceuticals, catechin hydrate, gallic acid, α-tocopherol and ascorbic acid, on the ability of human osteoarthritic chondrocytes of two female obese groups to form articular cartilage (AC) tissues and to reduce inflammation were investigated. Group 1 represented thirteen females in the 50–69 years old range, an average weight of 100 kg and an average body mass index (BMI) of 34⋅06 kg/m2. Group 2 was constituted of three females in the 70–80 years old range, an average weight of 75 kg and an average BMI of 31⋅43 kg/m2. The efficacy of nutraceuticals was assessed in monolayer cultures using histological, colorimetric and mRNA gene expression analyses. AC engineered tissues of group 1 produced less total collagen and COL2A1 (38-fold), and higher COL10A1 (2⋅7-fold), MMP13 (50-fold) and NOS2 (15-fold) mRNA levels than those of group 2. In comparison, engineered tissues of group 1 had a significant decrease in NO levels from day 1 to day 21 (2⋅6-fold), as well as higher mRNA levels of FOXO1 (2-fold) and TNFAIP6 (16-fold) compared to group 2. Catechin hydrate decreased NO levels significantly in group 1 (1⋅5-fold) while increasing NO levels significantly in group 2 (3⋅8-fold). No differences from the negative control were observed in the presence of other nutraceuticals for either group. In conclusion, engineered tissues of the younger but heavier patients responded better to nutraceuticals than those from the older but leaner study participants. Finally, cells of group 2 formed better AC tissues with less inflammation and better extracellular matrix than cells of group 1.
Terrestrial laser scanning (TLS) provides a means of rapid and highly accurate survey of archaeological excavations and structures at landscape scales, and is particularly valuable for documenting tidal environments. Here, the authors use TLS to record tidal fixed fishing structures and a tide mill within the Léguer Estuary at Le Yaudet, in north-west France. As part of a comprehensive resource-exploitation system, the early medieval (sixth to eighth centuries AD) structures lie within, and exploit different parts of, the tidal frame. The results are used to quantify production within an estuarine landscape associated with seignorial or monastic control of environmental resources.
The aim of this study is to assess prevalence of major depressive disorder (MDD), generalized anxiety disorder (GAD), and posttraumatic stress disorder (PTSD) in students of Keyano College 18 months after a wildfire and to determine the predictors of likely MDD, GAD, and PTSD in the respondents.
Methods:
A quantitative cross-sectional survey was used to collect data through self-administered, paper-based questionnaires to determine likely MDD, GAD, and PTSD using the PHQ 9, GAD-7, and the PTSD Checklist for DSM 5, Part 3, respectively. Data were analyzed with SPSS version 20 (IBM Corp, Armonk, NY) using univariate analysis with chi-square tests.
Results:
Eighteen months after the wildfire, the 1-month prevalence rates for MDD, GAD, and PTSD among the college students were 23.4%, 18.7%, and 11.0%, respectively. There were statistically significant associations between multiple sociodemographic variables and the likelihood respondents presented with MDD, GAD, and PTSD 18 months after the wildfire. There were also associations between the likely MDD, GAD, and PTSD and abuse/dependence on alcohol and substances in respondents at 18 months.
Conclusion:
Our study has established prevalence rates for MDD, GAD, and PTDS among college students 18 months after the Fort McMurray wildfires. Further studies are needed to explore the impact of college-based mental health interventions on the long-term mental health effects of the wildfires.
Cerro Charquini, Bolivia (Cordillera Real, 5392 ma.s.l.) was selected as a site to reconstruct glacier recession since the maximum of the Little Ice Age (LIA) in the central Andes. Five glaciers, located on differently exposed slopes, present comprehensive and well-preserved morainic systems attributed to former centuries. The moraines were dated by lichenometry and show a consistent organization on the different slopes. The past geometry of the glaciers was reconstructed using ground topography and aerophotogrammetry. Lichenometric dating shows that the LIA maximum occurred in the second half of the 17th century, after which the glaciers have receded nearly continuously. Over the last decades of the 20th century (1983–97), recession rates increased by a factor of four. On the northern and western slopes, glaciers receded more than on the southern and eastern slopes (by 78% and 65% of their LIA maximum area, respectively). The mean equilibrium-line altitude (ELA) rose by about 160 m between the LIA maximum and 1997. Recession rates were analysed in terms of climatic signal, suggesting that glacier recession since the LIA maximum was mainly due to a change in precipitation and that the 19th century may have been drier. For the 20th century, a temperature rise of about 0.6°C appears to be the main cause of glacier recession. Recent climatic conditions from 1983 to 1997 correspond to a mass deficit of about 1.36m w.e.a–1. If such conditions persist, the small glaciers below 5300ma.s.l. in the Cordillera Real should disappear completely in the near future.
The supply of glacier water to La Paz city, Bolivia, between 1963 and 2006 was assessed at annual and seasonal timescales based on the mass-balance quantification of 70 glaciers located within the drainage basins of La Paz. Glaciers contributed ∼15% of water resources at an annual scale (14% in the wet season, 27% in the dry season). Uncertainties in our estimation are related to the assumed constant precipitation (∼0.5% for ice-free areas and up to 6.5% for glaciated areas), the constant runoff coefficient (∼1%), the surface areas of the glaciers and catchments (∼5%) and the mean mass-balance uncertainty of the 21 glaciers used to obtain the mass balance of the 70 glaciers (12% of the total discharge). Despite the loss of 50% of the glacierized area during the study period, runoff at La Paz did not change significantly, showing that increase in ice melt rates compensated for reduction in the surface area of the glaciers. In the future, assuming complete disappearance of the glaciers and no change in precipitation, runoff should diminish by ∼12% at an annual scale, 9% during the wet season and 24% during the dry season.
Dating moraines by lichenometry enabled us to reconstruct glacier recession in the Bolivian Andes since the Little Ice Age maximum. On the 15 proglacial margins studied, we identified a system of ten principal moraines that marks the successive positions of glaciers over the last four centuries. Moraines were dated by performing statistical analysis of lichen measurements based on the extreme values theory. Like glaciers in many mid-latitude mountain areas, Bolivian glaciers reached their maximal extent during the second half of the 17th century. This glacier maximum coincides with the Maunder minimum of solar irradiance. By reconstructing the equilibrium-line altitude and changes in mass-balance, we think the glacier maximum may be due to a 20 to 30% increase in precipitation and a 1.1 to 1.2 °C decrease in temperature compared with present conditions. In the early 18th century, glaciers started to retreat at varying rates until the late 19th to early 20th century; this trend was generally associated with decreasing accumulation rates. By contrast, glacier recession in the 20th century was mainly the consequence of an increase in temperature and humidity. These results are consistent with observations made in the study region based on other proxies.
In the classical optimal dividends problem, dividend decisions are allowed to be made at any point in time — according to a continuous strategy. Depending on the surplus process that is considered and whether dividend payouts are bounded or not, optimal strategies are generally of a band, barrier or threshold type. In reality, while surpluses change continuously, dividends are generally paid on a periodic basis. Because of this, the actuarial literature has recently considered strategies where dividends are only allowed to be distributed at (random) discrete times — according to a periodic strategy.
In this paper, we focus on the Brownian risk model. In this context, the optimal continuous and periodic strategies have previously been shown (independently of one another) to be of barrier type. For the first time, we consider a model where both strategies are used. In such a hybrid strategy, decisions are allowed to be made either at any time (continuously), or periodically at a lower cost. This proves optimal in some cases. We also determine under which combination of parameters a pure continuous, pure periodic or hybrid (including both continuous and periodic dividend payments) barrier strategy is optimal. Interestingly, the hybrid strategy lies in-between periodic and continuous strategies, which provides some interesting insights. Results are illustrated.