The complexity and heterogeneity of patients with multimorbidity and polypharmacy renders traditional disease‐oriented guidelines often inadequate and complicates clinical decision making. To address ...this challenge, guidelines have been developed on multimorbidity or polypharmacy. To systematically analyse their recommendations, we conducted a systematic guideline review using the Ariadne principles for managing multimorbidity as analytical framework. The information synthesis included a multistep consensus process involving 18 multidisciplinary experts from seven countries. We included eight guidelines (four each on multimorbidity and polypharmacy) and extracted about 250 recommendations. The guideline addressed (i) the identification of the target population (risk factors); (ii) the assessment of interacting conditions and treatments: medical history, clinical and psychosocial assessment including physiological status and frailty, reviews of medication and encounters with healthcare providers highlighting informational continuity; (iii) the need to incorporate patient preferences and goal setting: eliciting preferences and expectations, the process of shared decision making in relation to treatment options and the level of involvement of patients and carers; (iv) individualized management: guiding principles on optimization of treatment benefits over possible harms, treatment communication and the information content of medication/care plans; (v) monitoring and follow‐up: strategies in care planning, self‐management and medication‐related aspects, communication with patients including safety instructions and adherence, coordination of care regarding referral and discharge management, medication appropriateness and safety concerns. The spectrum of clinical and self‐management issues varied from guiding principles to specific recommendations and tools providing actionable support. The limited availability of reliable risk prediction models, feasible interventions of proven effectiveness and decision aids, and limited consensus on appropriate outcomes of care highlight major research deficits. An integrated approach to both multimorbidity and polypharmacy should be considered in future guidelines.
Content List – Read more articles from the symposium: “Multimorbidity research at the cross‐roads: developing the evidence for clinical practice and health policy”.
The ever increasing demand to develop highly fuel efficient engines coincides with the need to minimize air pollution originating from the exhaust gases of internal combustion engines. Dramatically ...improved fuel efficiency can be achieved at air-to-fuel ratios much higher than stoichiometric. In the presence of oxygen in large excess, however, traditional three-way catalysts are unable to reduce NO
x
. Among the number of lean-NO
x
reduction technologies, selective catalytic reduction (SCR) of NO
x
by NH
3
over Cu- and Fe-ion exchanged zeolite catalysts has been extensively studied over the past 30+ years. Despite the significant advances in developing a viable practical zeolite-based catalyst for lean NO
x
reduction, the insufficient hydrothermal stabilities of the zeolite structures considered cast doubts about their real-world applicability. During the past decade renewed interest in zeolite-based lean NO
x
reduction was spurred by the discovery of the very high activity of Cu-SSZ-13 (and the isostructural Cu-SAPO-34) in the NH
3
-SCR of NO
x
. These new, small-pore zeolite-based catalysts not only exhibited very high NO
x
conversion and N
2
selectivity, but also exhibited exceptionally high hydrothermal stability at high temperatures. In this review we summarize the key discoveries of the past ∼5 years that led to the introduction of these catalysts into practical applications. This review first briefly discusses the structure and preparation of the CHA structure-based zeolite catalysts, and then summarizes the key learnings of the rather extensive (but not complete) characterisation work. Then we summarize the key findings of reaction kinetic studies, and provide some mechanistic details emerging from these investigations. At the end of the review we highlight some of the issues that still need to be addressed in automotive exhaust control catalysis.
The current understanding of the structure-function relationship of small-pore microporous materials for NH
3
selective catalytic reduction of NO
x
is reviewed.
It is particularly difficult for healthcare providers to deliver optimal medical care to multimorbid middle-aged persons because patients' professional activities, family lives, and other everyday ...responsibilities hinder them from making necessary lifestyle changes. Our aim was to find out how patients and healthcare providers view and manage the problems of dealing with multimorbidity in middle age. This qualitative study consisted of three steps. First, we conducted semi-structured in-depth interviews with 15 purposively sampled middle-aged persons living with multimorbidity to explore the experiences of care in the context of their leisure time, family lives, and work. Second, further individual interviews were carried out to find out the views of 14 healthcare providers. Third, the results of the interviews with patients and healthcare providers were presented to and discussed with four healthcare providers at an interprofessional workshop. Interview data was coded using an inductive-deductive approach and analyzed using content analysis. While patients reflected on challenges in several life domains, healthcare providers differentiated between levels of challenges. Both shared recommendations for better care including i) helping patients cope, ii) providing relief in activities of daily living, iii) continuity of care, iv) interprofessional cooperation, v) health promotion/prevention, vi) expansion of health services and vii) general system-level changes. Furthermore, the healthcare provider workshop highlighted the importance of increasing patient-centeredness, reducing complexity through a care coordinator and promoting interprofessional cooperation/networking. To further improve the care of patients living with multimorbidity, barriers to managing multiple chronic conditions and facilitators to navigating complex care scenarios should be explored not only for people beyond working age, but for individuals in their mid-life specifically.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Numerous epidemiological studies have shown a significantly higher risk for development of Alzheimer's disease (AD) in patients affected by type 2 diabetes (T2D), but the molecular mechanism ...responsible for this association is presently unknown. Both diseases are considered protein misfolding disorders associated with the accumulation of protein aggregates; amyloid-beta (Aβ) and tau in the brain during AD, and islet amyloid polypeptide (IAPP) in pancreatic islets in T2D. Formation and accumulation of these proteins follows a seeding-nucleation model, where a misfolded aggregate or 'seed' promotes the rapid misfolding and aggregation of the native protein. Our underlying hypothesis is that misfolded IAPP produced in T2D potentiates AD pathology by cross-seeding Aβ, providing a molecular explanation for the link between these diseases. Here, we examined how misfolded IAPP affects Aβ aggregation and AD pathology in vitro and in vivo. We observed that addition of IAPP seeds accelerates Aβ aggregation in vitro in a seeding-like manner and the resulting fibrils are composed of both peptides. Transgenic animals expressing both human proteins exhibited exacerbated AD-like pathology compared with AD transgenic mice or AD transgenic animals with type 1 diabetes (T1D). Remarkably, IAPP colocalized with amyloid plaques in brain parenchymal deposits, suggesting that these peptides may directly interact and aggravate the disease. Furthermore, inoculation of pancreatic IAPP aggregates into the brains of AD transgenic mice resulted in more severe AD pathology and significantly greater memory impairments than untreated animals. These data provide a proof-of-concept for a new disease mechanism involving the interaction of misfolded proteins through cross-seeding events which may contribute to accelerate or exacerbate disease pathogenesis. Our findings could shed light on understanding the linkage between T2D and AD, two of the most prevalent protein misfolding disorders.
The best spectrographs are limited in stability by their calibration light source. Laser frequency combs are the ideal calibrators for astronomical spectrographs. They emit a spectrum of lines that ...are equally spaced in frequency and that are as accurate and stable as the atomic clock relative to which the comb is stabilized. Absolute calibration provides the radial velocity of an astronomical object relative to the observer (on Earth). For the detection of Earth-mass exoplanets in Earth-like orbits around solar-type stars, or of cosmic acceleration, the observable is a tiny velocity change of less than 10 cm s(-1), where the repeatability of the calibration--the variation in stability across observations--is important. Hitherto, only laboratory systems or spectrograph calibrations of limited performance have been demonstrated. Here we report the calibration of an astronomical spectrograph with a short-term Doppler shift repeatability of 2.5 cm s(-1), and use it to monitor the star HD 75289 and recompute the orbit of its planet. This repeatability should make it possible to detect Earth-like planets in the habitable zone of star or even to measure the cosmic acceleration directly.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aims. We investigate the photometric modulation induced by magnetic activity cycles and study the relationship between rotation period and activity cycle(s) in late-type (FGKM) stars. Methods. We ...analysed light curves, spanning up to nine years, of 125 nearby stars provided by the All Sky Automated Survey (ASAS). The sample is mainly composed of low-activity, main-sequence late-A to mid-M-type stars. We performed a search for short (days) and long-term (years) periodic variations in the photometry. We modelled the light curves with combinations of sinusoids to measure the properties of these periodic signals. To provide a better statistical interpretation of our results, we complement our new results with results from previous similar works. Results. We have been able to measure long-term photometric cycles of 47 stars, out of which 39 have been derived with false alarm probabilities (FAP) of less than 0.1 per cent. Rotational modulation was also detected and rotational periods were measured in 36 stars. For 28 stars we have simultaneous measurements of activity cycles and rotational periods, 17 of which are M-type stars. We measured both photometric amplitudes and periods from sinusoidal fits. The measured cycle periods range from 2 to 14 yr with photometric amplitudes in the range of 5−20 mmag. We found that the distribution of cycle lengths for the different spectral types is similar, as the mean cycle is 9.5 yr for F-type stars, 6.7 yr for G-type stars, 8.5 yr for K-type stars, 6.0 yr for early M-type stars, and 7.1 yr for mid-M-type stars. On the other hand, the distribution of rotation periods is completely different, trending to longer periods for later type stars, from a mean rotation of 8.6 days for F-type stars to 85.4 days in mid-M-type stars. The amplitudes induced by magnetic cycles and rotation show a clear correlation. A trend of photometric amplitudes with rotation period is also outlined in the data. The amplitudes of the photometric variability induced by activity cycles of main-sequence GK stars are lower than those of early- and mid-M dwarfs for a given activity index. Using spectroscopic data, we also provide an update in the empirical relationship between the level of chromospheric activity as given by log10R 'HK and the rotation periods.
A three-dimensional network solid composed of FeIII centers and paramagnetic semiquinoid linkers, (NBu4)2FeIII 2(dhbq)3 (dhbq2–/3– = 2,5-dioxidobenzoquinone/1,2-dioxido-4,5-semiquinone), is ...shown to exhibit a conductivity of 0.16 ± 0.01 S/cm at 298 K, one of the highest values yet observed for a metal–organic framework (MOF). The origin of this electronic conductivity is determined to be ligand mixed-valency, which is characterized using a suite of spectroscopic techniques, slow-scan cyclic voltammetry, and variable-temperature conductivity and magnetic susceptibility measurements. Importantly, UV–vis–NIR diffuse reflectance measurements reveal the first observation of Robin–Day Class II/III mixed valency in a MOF. Pursuit of stoichiometric control over the ligand redox states resulted in synthesis of the reduced framework material Na0.9(NBu4)1.8FeIII 2(dhbq)3. Differences in electronic conductivity and magnetic ordering temperature between the two compounds are investigated and correlated to the relative ratio of the two different ligand redox states. Overall, the transition metal–semiquinoid system is established as a particularly promising scaffold for achieving tunable long-range electronic communication in MOFs.
•Reduction wind power forecasting uncertainty for day ahead and intraday markets.•Statistical relationship between total load and wind power generation.•Accurately forecast expected revenues from ...wind producer’s perspective.
The growing share of electricity production from variable renewable energy sources increases the stochastic nature of the power system. This has repercussions on the markets for electricity. Deviations from forecasted production schedules require balancing of a generator’s position within a day. Short term products that are traded on power and/or reserve markets have been developed for this purpose, providing opportunities to actors who can offer flexibility in the short term. The value of flexibility is typically modelled using stochastic scenario extensions of dispatch models which requires, as a first step, understanding the nature of forecast uncertainties. This study provides a new approach for determining the forecast errors of wind power generation in the time period between the closure of the day ahead and the opening of the first intraday session using Spain as an example. The methodology has been developed using time series analysis for the years 2010–2013 to find the explanatory variables of the wind error variability by applying clustering techniques to reduce the range of uncertainty, and regressive techniques to forecast the probability density functions of the intra-day price. This methodology has been tested considering different system actions showing its suitability for developing intra-day bidding strategies and also for the generation of electricity generated from Renewable Energy Sources scenarios. This methodology could help a wind power producer to optimally bid into the intraday market based on more accurate scenarios, increasing their revenues and the system value of wind.
Assembly of the triangular, organic radical‐bridged complexes Cp*6Ln3(μ3‐HAN) (Cp*=pentamethylcyclopentadienyl; Ln=Gd, Tb, Dy; HAN=hexaazatrinaphthylene) proceeds through the reaction of Cp*2Ln(BPh4) ...with HAN under strongly reducing conditions. Significantly, magnetic susceptibility measurements of these complexes support effective magnetic coupling of all three LnIII centers through the HAN3−. radical ligand. Thorough investigation of the DyIII congener through both ac susceptibility and dc magnetic relaxation measurements reveals slow relaxation of the magnetization, with an effective thermal relaxation barrier of Ueff=51 cm−1. Magnetic coupling in the DyIII complex enables a large remnant magnetization at temperatures up to 3.0 K in the magnetic hysteresis measurements and hysteresis loops that are open at zero‐field up to 3.5 K.
A DyIII HAT Trick: Magnetic coupling between three lanthanide ions is established through a central organic radical bridging ligand in Cp*6Ln3(μ3‐HAN) (Cp*=pentamethylcyclopentadienyl; Ln=Gd, Tb, Dy; HAN=hexaazatrinaphthylene). Coupling in the DyIII congener enables a large remnant magnetization up to 3.0 K in the magnetic hysteresis measurements and hysteresis loops that are open at zero‐field up to 3.5 K.
Half the US population uses drugs with anticholinergic properties. Their potential harms may outweigh their benefits. Amitriptyline is among the most frequently prescribed anticholinergic medicinal ...products, is used for multiple indications, and rated as strongly anticholinergic. Our objective was to explore and quantify (anticholinergic) adverse drug reactions (ADRs) in patients taking amitriptyline vs. placebo in randomized controlled trials (RCTs) involving adults and healthy individuals.
We searched electronic databases from their inception until 09/2022, and clinical trial registries from their inception until 09/2022. We also performed manual reference searches. Two independent reviewers selected RCTs with ≥100 participants of ≥18 years, that compared amitriptyline (taken orally) versus placebo for all indications. No language restrictions were applied. One reviewer extracted study data, ADRs, and assessed study quality, which two others verified. The primary outcome was frequency of anticholinergic ADRs as a binary outcome (absolute number of patients with/without anticholinergic ADRs) in amitriptyline vs. placebo groups.
Twenty-three RCTs (mean dosage 5mg to 300mg amitriptyline/day) and 4217 patients (mean age 40.3 years) were included. The most frequently reported anticholinergic ADRs were dry mouth, drowsiness, somnolence, sedation, fatigue, constitutional, and unspecific anticholinergic ADRs. Random-effects meta-analyses showed anticholinergic ADRs had a higher odd's ratio for amitriptyline versus placebo (OR = 7.41; 95% CI, 4.54 to 12.12). Non-anticholinergic ADRs were as frequent for amitriptyline as placebo. Meta-regression analysis showed anticholinergic ADRs were not dose-dependent.
The large OR in our analysis shows that ADRs indicative of anticholinergic activities can be attributed to amitriptyline. The low average age of participants in our study may limit the generalizability of the frequency of anticholinergic ADRs in older patients. A lack of dose-dependency may reflect limited reporting of the daily dosage when the ADRs occurred. The exclusion of small studies (<100 participants) decreased heterogeneity between studies, but may also have reduced our ability to detect rare events. Future studies should focus on older people, as they are more susceptible to anticholinergic ADRs.
PROSPERO: CRD42020111970.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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