| 3251. |
- Muth, C., et al.
(författare)
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Evidence supporting the best clinical management of patients with multimorbidity and polypharmacy : a systematic guideline review and expert consensus
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 285:3, s. 272-288
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Forskningsöversikt (refereegranskat)abstract
- 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.
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| 3252. |
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| 3253. |
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| 3254. |
- Naeem, Aishath, et al.
(författare)
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Pirtobrutinib targets BTK C481S in ibrutinib-resistant CLL but second-site BTK mutations lead to resistance
- 2023
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 7:9, s. 1929-1943
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Tidskriftsartikel (refereegranskat)abstract
- Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtobrutinib is a highly selective, noncovalent BTKi with substantial clinical activity in patients whose disease has progressed on covalent BTKi, regardless of BTK mutation status. Using in vitro ibrutinib-resistant models and cells from patients with CLL, we show that pirtobrutinib potently inhibits BTK-mediated functions including B-cell receptor (BCR) signaling, cell viability, and CCL3/CCL4 chemokine production in both BTK wild-type and C481S mutant CLL cells. We demonstrate that primary CLL cells from responding patients on the pirtobrutinib trial show reduced BCR signaling, cell survival, and CCL3/CCL4 chemokine secretion. At time of progression, these primary CLL cells show increasing resistance to pirtobrutinib in signaling inhibition, cell viability, and cytokine production. We employed longitudinal whole-exome sequencing on 2 patients whose disease progressed on pirtobrutinib and identified selection of alternative-site BTK mutations, providing clinical evidence that secondary BTK mutations lead to resistance to noncovalent BTKis.
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| 3255. |
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| 3256. |
- Naiini, Maziar M., et al.
(författare)
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Embedded Graphene Photodetectors for Silicon Photonics
- 2014
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Ingår i: Device Research Conference (DRC), 2014 72nd Annual. - : IEEE conference proceedings. - 9781479954056 ; , s. 43-44
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Konferensbidrag (refereegranskat)abstract
- Graphene has extraordinary electronic and optoelectronic properties such as high carrier mobility, large charge-carrier concentrations, tunability via electrostatic doping, wavelength-independent absorption, and relatively low dissipation rates [1]. The combination of its electro-optical properties with its manufacturability and CMOS integrability makes graphene an extremely promising candidate for active photonic devices [2,3]. Because of its two-dimensional appearance, graphene has a limited light absorption, which is not enough to fulfill the requirements of silicon photonics technology. Recently, the integration of graphene with silicon waveguides [4,5] has been shown for on-chip applications [6]. In these solutions graphene is placed on top and outside of the waveguide yielding only limited light-graphene interaction. We introduce novel photo-detector architecture by embedding CVD-graphene inside the slot layer of deposited high-k slot waveguides that are compatible with back-end-of-the-line manufacturing of photonic integrated circuits (PICs). This approach leads to a high light-graphene interaction due to the high mode concentration in the slot region[7]. This results in enhanced absorption and enables a very compact photodetector design.
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| 3257. |
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| 3258. |
- Nashef, SAM, et al.
(författare)
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EuroSCORE II
- 2012
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Ingår i: European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. - : Oxford University Press (OUP). - 1873-734X. ; 41:4, s. 734-745
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Tidskriftsartikel (refereegranskat)
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| 3259. |
- Navara, E., et al.
(författare)
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Investigation of microstructural changes occurring during warm working of manganese partitioned dual phase steel
- 1990
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Ingår i: Materials Science and Technology. - : Informa UK Limited. - 0267-0836 .- 1743-2847. ; 6:2, s. 151-155
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents results from studies using transmission and high resolution electron microscopy of as-received and warm worked manganese partitioned dual phase steel. A growing manganese enriched austenite grain shares two different boundaries with ferrite: (a) a stationary coherent boundary, replacing a stretch of the original ferrite/ferrite boundary, and (b) a migrating non-coherent boundary. This finding gives support to a previously described mechanism of the nucleation and growth of the manganese enriched austenite. The structure of the warm worked steel consists of recovered ferrite strengthened by substructure, and fine martensitic lathes separated by low angle boundaries which resulted from the transformation of deformed non-recrystallised austenite grains
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| 3260. |
- Nduva, George M., et al.
(författare)
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Phylogeographic Assessment Reveals Geographic Sources of HIV-1 Dissemination Among Men Who Have Sex With Men in Kenya
- 2022
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Ingår i: Frontiers in Microbiology. - : Frontiers Media SA. - 1664-302X. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- HIV-1 transmission dynamics involving men who have sex with men (MSM) in Africa are not well understood. We investigated the rates of HIV-1 transmission between MSM across three regions in Kenya: Coast, Nairobi, and Nyanza. We analyzed 372 HIV-1 partial pol sequences sampled during 2006–2019 from MSM in Coast (N = 178, 47.9%), Nairobi (N = 137, 36.8%), and Nyanza (N = 57, 15.3%) provinces in Kenya. Maximum-likelihood (ML) phylogenetics and Bayesian inference were used to determine HIV-1 clusters, evolutionary dynamics, and virus migration rates between geographic regions. HIV-1 sub-subtype A1 (72.0%) was most common followed by subtype D (11.0%), unique recombinant forms (8.9%), subtype C (5.9%), CRF 21A2D (0.8%), subtype G (0.8%), CRF 16A2D (0.3%), and subtype B (0.3%). Forty-six clusters (size range 2–20 sequences) were found—half (50.0%) of which had evidence of extensive HIV-1 mixing among different provinces. Data revealed an exponential increase in infections among MSM during the early-to-mid 2000s and stable or decreasing transmission dynamics in recent years (2017–2019). Phylogeographic inference showed significant (Bayes factor, BF > 3) HIV-1 dissemination from Coast to Nairobi and Nyanza provinces, and from Nairobi to Nyanza province. Strengthening HIV-1 prevention programs to MSM in geographic locations with higher HIV-1 prevalence among MSM (such as Coast and Nairobi) may reduce HIV-1 incidence among MSM in Kenya.
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