| 1. |
- Balestrino, R, et al.
(författare)
-
Applications of the European Parkinson's Disease Association sponsored Parkinson's Disease Composite Scale (PDCS)
- 2019
-
Ingår i: NPJ Parkinson's disease. - : Springer Science and Business Media LLC. - 2373-8057. ; 5, s. 26-
-
Tidskriftsartikel (refereegranskat)abstract
- This study was addressed to determine the presence of Parkinson disease (PD) manifestations, their distribution according to motor subtypes, and the relationships with health-related quality of life (QoL) using the recently validated European Parkinson’s Disease Association sponsored Parkinson’s Disease Composite Scale (PDCS). Frequency of symptoms was determined by the scores of items (present if >0). Using ROC analysis and Youden method, MDS-UPDRS motor subtypes were projected on the PDCS to achieve a comparable classification based on the PDCS scores. The same method was used to estimate severity levels from other measures in the study. The association between the PDCS and QoL (PDQ-39) was analyzed by correlation and multiple linear regression. The sample consisted of 776 PD patients. We found that the frequency of PD manifestations with PDCS and MDS-UPDRS were overlapping, the average difference between scales being 5.5% only. Using the MDS-UPDRS subtyping, 215 patients (27.7%) were assigned as Tremor Dominant (TD), 60 (7.7%) Indeterminate, and 501 (64.6%) Postural Instability and Gait Difficulty (PIGD) in this cohort. With this classification as criterion, the analogous PDCS-based ratio provided these cut-off values: TD subtype, ≥1.06; Indeterminate, <1.06 but >0.65; and PIGD, <0.65. The agreement between the two scales on this classification was substantial (87.6%; kappa = 0.69). PDCS total score cut-offs for PD severity were: 23/24 for mild/moderate and 41/42 for moderate/severe. Moderate to high correlations (r = 0.35–0.80) between PDCS and PDQ-39 were obtained, and the four PDCS domains showed a significant independent influence on QoL. The conclusions are: (1) the PDCS assessed the frequency of PD symptoms analogous to the MDS-UPDRS; (2) motor subtypes and severity levels can be determined with the PDCS; (3) a significant association between PDCS and QoL scores exists.
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Sjögren, Erik, 1977-, et al.
(författare)
-
Clinical testing of three novel transient receptor potential cation channel subfamily V member 1 antagonists in a pharmacodynamic intradermal capsaicin model
- 2018
-
Ingår i: European Journal of Pain. - : WILEY. - 1090-3801 .- 1532-2149. ; 22:7, s. 1214-1228
-
Tidskriftsartikel (refereegranskat)abstract
- Background The transient receptor potential cation channel subfamily V 1 (TRPV1) is involved in nociception and has thus been of interest for drug developers, as a target for novel analgesics. However, several oral TRPV1 antagonists have failed in development, and novel approaches to target TRPV1 with innovative chemistry are needed. Method This work describes an intradermal microdosing approach in humans for pharmacodynamic deductions and pharmacological profiling of compounds. First, a human capsaicin model was developed, to generate pharmacodynamic translational data (Study Part A, n=24). Then, three small molecule TRPV1 antagonists (AZ11760788, AZ12048189 and AZ12099548) were investigated in healthy volunteers (Study Part B, n=36), applying the established model. Pain and flare were assessed by Visual Analogue Score and laser Doppler, respectively. Results The developed model proved useful for pharmacologic deductions; all compounds caused a dose-dependent inhibition of capsaicin-induced pain and flare responses, with a rank order potency of AZ11760788>AZ12048189 >> AZ12099548. In addition, the dose-response data showed that the minimal antagonist concentrations needed to inhibit TRPV1 was 6-7 times the equilibrium dissociation constant for each compound. Conclusion With careful design of a pharmacodynamic translational human pain model, it was possible to rank order TRPV1 efficacy among three investigational TRPV1 antagonists, and to estimate human efficacious concentrations. SignificanceThis fast and cost-effective translational approach allows for generation of human target engagement information early in drug development. This could be of value for other development programmes where pharmacological targets are expressed in peripheral sensory nerves.
|
|
| 6. |
- Thust, S. C., et al.
(författare)
-
Glioma imaging in Europe : A survey of 220 centres and recommendations for best clinical practice
- 2018
-
Ingår i: European Radiology. - : Springer Science and Business Media LLC. - 0938-7994 .- 1432-1084. ; 28:8, s. 3306-3317
-
Tidskriftsartikel (refereegranskat)abstract
- Objectives: At a European Society of Neuroradiology (ESNR) Annual Meeting 2015 workshop, commonalities in practice, current controversies and technical hurdles in glioma MRI were discussed. We aimed to formulate guidance on MRI of glioma and determine its feasibility, by seeking information on glioma imaging practices from the European Neuroradiology community. Methods: Invitations to a structured survey were emailed to ESNR members (n=1,662) and associates (n=6,400), European national radiologists’ societies and distributed via social media. Results: Responses were received from 220 institutions (59% academic). Conventional imaging protocols generally include T2w, T2-FLAIR, DWI, and pre- and post-contrast T1w. Perfusion MRI is used widely (85.5%), while spectroscopy seems reserved for specific indications. Reasons for omitting advanced imaging modalities include lack of facility/software, time constraints and no requests. Early postoperative MRI is routinely carried out by 74% within 24–72 h, but only 17% report a percent measure of resection. For follow-up, most sites (60%) issue qualitative reports, while 27% report an assessment according to the RANO criteria. A minority of sites use a reporting template (23%). Conclusion: Clinical best practice recommendations for glioma imaging assessment are proposed and the current role of advanced MRI modalities in routine use is addressed. Key Points: • We recommend the EORTC-NBTS protocol as the clinical standard glioma protocol.• Perfusion MRI is recommended for diagnosis and follow-up of glioma.• Use of advanced imaging could be promoted with increased education activities.• Most response assessment is currently performed qualitatively.• Reporting templates are not widely used, and could facilitate standardisation.
|
|
| 7. |
- Broitman, E., et al.
(författare)
-
Mechanical and tribological properties of CNx films deposited by reactive magnetron sputtering
- 2001
-
Ingår i: Wear. - 0043-1648 .- 1873-2577. ; 248:1-2, s. 55-64
-
Tidskriftsartikel (refereegranskat)abstract
- The hardness, elasticity, wear rate and friction coefficient of carbon nitride (CNx) films of defined microstructure and composition are presented. CNx films were deposited by dc reactive magnetron sputtering from a C target in N2/Ar plasma. Films were grown on Si (001), Ni, and HSS substrates to thickness of ~0.5 µm at a total pressure of 3 mTorr with the N2 fraction varied from 0 to 1, and the substrate temperature Ts, varied from ambient to 350°C. The mechanical and tribological properties of the coatings were evaluated by nanoindentation and dry ball-on-disk test. For CNx (0 = x = 0.35) films deposited below 200°C (amorphous structure), the elastic recovery and hardness do not change significantly with increasing N concentration, however, the friction coefficient increases from 0.19 to 0.45, while the coating wear rate is low. For CNx (0 = x = 0.15) films grown at Ts = 350°C, where a transition from a graphite-like to a "fullerene-like" phase occurs, a dramatic increase in hardness and elasticity is observed. Furthermore, the rms surface roughness decreases from 15.0 to 0.4 nm. For 0.15 = x = 0.20, CNx films deposited at Ts = 350°C (fullerene-like phase) exhibit a smooth surface, high hardness and elasticity (~90% recovery), and a coefficient of friction against hard steel of ~0.25. For all substrates, film friction coefficient tends to increase as the nitrogen content in the film is increased. Results also indicate the formation of a transfer layer which improves the tribological properties of the films. © 2001 Elsevier Science B.V. All rights reserved.
|
|
| 8. |
- Coorevits, Pascal, et al.
(författare)
-
Electronic health records : new opportunities for clinical research
- 2013
-
Ingår i: Journal of Internal Medicine. - : Wiley-Blackwell. - 0954-6820 .- 1365-2796. ; 274:6, s. 547-60
-
Tidskriftsartikel (refereegranskat)abstract
- Clinical research is on the threshold of a new era in which electronic health records (EHRs) are gaining an important novel supporting role. Whilst EHRs used for routine clinical care have some limitations at present, as discussed in this review, new improved systems and emerging research infrastructures are being developed to ensure that EHRs can be used for secondary purposes such as clinical research, including the design and execution of clinical trials for new medicines. EHR systems should be able to exchange information through the use of recently published international standards for their interoperability and clinically validated information structures (such as archetypes and international health terminologies), to ensure consistent and more complete recording and sharing of data for various patient groups. Such systems will counteract the obstacles of differing clinical languages and styles of documentation as well as the recognized incompleteness of routine records. Here, we discuss some of the legal and ethical concerns of clinical research data reuse and technical security measures that can enable such research while protecting privacy. In the emerging research landscape, cooperation infrastructures are being built where research projects can utilize the availability of patient data from federated EHR systems from many different sites, as well as in international multilingual settings. Amongst several initiatives described, the EHR4CR project offers a promising method for clinical research. One of the first achievements of this project was the development of a protocol feasibility prototype which is used for finding patients eligible for clinical trials from multiple sources.
|
|
| 9. |
- Fjalldal, S., et al.
(författare)
-
Detailed assessment of hypothalamic damage in craniopharyngioma patients with obesity
- 2019
-
Ingår i: International Journal of Obesity. - : Springer Science and Business Media LLC. - 0307-0565 .- 1476-5497. ; 43:3, s. 533-544
-
Tidskriftsartikel (refereegranskat)abstract
- Background/objectives: Hypothalamic obesity (HO) occurs in 50% of patients with the pituitary tumor craniopharyngioma (CP). Attempts have been made to predict the risk of HO based on hypothalamic (HT) damage on magnetic resonance imaging (MRI), but none have included volumetry. We performed qualitative and quantitative volumetric analyses of HT damage. The results were explored in relation to feeding related peptides and body fat. Subjects/methods: A cross-sectional study of childhood onset CPs involving 3 Tesla MRI, was performed at median 22 years after first operation; 41 CPs, median age 35 (range: 17–56), of whom 23 had HT damage, were compared to 32 controls. After exclusions, 35 patients and 31 controls remained in the MRI study. Main outcome measures were the relation of metabolic parameters to HT volume and qualitative analyses of HT damage. Results: Metabolic parameters scored persistently very high in vascular risk particularly among HT damaged patients. Patients had smaller HT volumes compared to controls 769 (35–1168) mm3 vs. 879 (775–1086) mm3; P < 0.001. HT volume correlated negatively with fat mass and leptin among CP patients (rs = −0.67; P <.001; rs = −0.53; P = 0.001), and explained 39% of the variation in fat mass. For every 100 mm3 increase in HT volume fat mass decreased by 2.7 kg (95% CI: 1.5–3.9; P < 0.001). Qualitative assessments revealed HT damage in three out of six patients with normal volumetry, but HT damage according to operation records. Conclusions: A decrease in HT volume was associated with an increase in fat mass and leptin. We present a method with a high inter-rater reliability (0.94) that can be applied by nonradiologists for the assessment of HT damage. The method may be valuable in the risk assessment of diseases involving the HT.
|
|
| 10. |
- Fjalldal, S., et al.
(författare)
-
Microstructural white matter alterations and hippocampal volumes are associated with cognitive deficits in craniopharyngioma
- 2018
-
Ingår i: European Journal of Endocrinology. - : BIOSCIENTIFICA LTD. - 0804-4643 .- 1479-683X. ; 178:6, s. 577-587
-
Tidskriftsartikel (refereegranskat)abstract
- Context: Patients with craniopharyngioma (CP) and hypothalamic lesions (HL) have cognitive deficits. Which neural pathways are affected is unknown. Objective: To determine whether there is a relationship between microstructural white matter (WM) alterations detected with diffusion tensor imaging (DTI) and cognition in adults with childhood-onset CP. Design: A cross-sectional study with a median follow-up time of 22 (6-49) years after operation. Setting: The South Medical Region of Sweden (2.5 million inhabitants). Participants: Included were 41 patients (24 women, amp;gt;= 17 years) surgically treated for childhood-onset CP between 1958-2010 and 32 controls with similar age and gender distributions. HI was found in 23 patients. Main outcome measures: Subjects performed cognitive tests and magnetic resonance imaging, and images were analyzed using DTI of uncinate fasciculus, fornix, cingulum, hippocampus and hypothalamus as well as hippocampal volumetry. Results: Right uncinate fasciculus was significantly altered (P amp;lt;= 0.01) Microstructural WM alterations in left ventral cingulum were significantly associated with worse performance in visual episodic memory, explaining approximately 50% of the variation. Alterations in dorsal cingulum were associated with worse performance in immediate, delayed recall and recognition, explaining 26-38% of the variation, and with visuospatial ability and executive function, explaining 19-29%. Patients who had smaller hippocampal volume had worse general knowledge (P = 0.028), and microstructural WM alterations in hippocampus were associated with a decline in general knowledge and episodic visual memory. Conclusions: A structure to function relationship is suggested between microstructural WM alterations in cingulum and in hippocampus with cognitive deficits in CP.
|
|
| 11. |
|
|
| 12. |
- Hammar, M., et al.
(författare)
-
1300-nm GaAs-based vertical-cavity lasers
- 2002
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - Brugge : SPIE. ; , s. 137-149
-
Konferensbidrag (refereegranskat)abstract
- We compare GaInNAs and highly strained InGaAs quantum-wells (QWs) for applications in metal-organic vapor-phase epitaxy (MOVPE)-grown GaAs-based 1300-nm vertical-cavity lasers (VCLs). While the peak wavelength of InGaAs QWs can be extended by a small fraction of N, the luminescence efficiency degrades strongly with wavelength. On the other hand, using highly strained InGaAs QWs in combination with a large VCL detuning it is also possible to push the emission wavelength towards 1.3 ÎŒm. The optimized MOVPE growth conditions for such QW and VCL structures are discussed in some detail. It is noted that GaInNAs and InGaAs QWs preferably are grown at low temperature, but with quite different V/III ratios and growth rates. We also point out the importance of reduced doping concentration and growth temperature of the n-doped bottom distributed Bragg reflector to minimize optical loss and for compatibility with GaInNAs QWs. InGaAs VCLs with emission wavelengths beyond 1260 nm are demonstrated. This includes mW-range output power, mA-range threshold current and 10 Gb/s data transmission.
|
|
| 13. |
- Lehmann, Patrick M, et al.
(författare)
-
A numerical human brain phantom for dynamic glucose-enhanced (DGE) MRI : On the influence of head motion at 3T
- 2023
-
Ingår i: Magnetic Resonance in Medicine. - : Wiley. - 1522-2594 .- 0740-3194. ; 89:5, s. 1871-1887
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: Dynamic glucose-enhanced (DGE) MRI relates to a group of exchange-based MRI techniques where the uptake of glucose analogues is studied dynamically. However, motion artifacts can be mistaken for true DGE effects, while motion correction may alter true signal effects. The aim was to design a numerical human brain phantom to simulate a realistic DGE MRI protocol at 3T that can be used to assess the influence of head movement on the signal before and after retrospective motion correction.METHODS: MPRAGE data from a tumor patient were used to simulate dynamic Z-spectra under the influence of motion. The DGE responses for different tissue types were simulated, creating a ground truth. Rigid head movement patterns were applied as well as physiological dilatation and pulsation of the lateral ventricles and head-motion-induced B 0 -changes in presence of first-order shimming. The effect of retrospective motion correction was evaluated. RESULTS: Motion artifacts similar to those previously reported for in vivo DGE data could be reproduced. Head movement of 1 mm translation and 1.5 degrees rotation led to a pseudo-DGE effect on the order of 1% signal change. B 0 effects due to head motion altered DGE changes due to a shift in the water saturation spectrum. Pseudo DGE effects were partly reduced or enhanced by rigid motion correction depending on tissue location. CONCLUSION: DGE MRI studies can be corrupted by motion artifacts. Designing post-processing methods using retrospective motion correction including B 0 correction will be crucial for clinical implementation. The proposed phantom should be useful for evaluation and optimization of such techniques.
|
|
| 14. |
- Mogg, S., et al.
(författare)
-
1.3-ÎŒm InGaAs(N)/GaAs vertical-cavity lasers
- 2003
-
Ingår i: Proceedings of SPIE - The International Society for Optical Engineering. - San Jose, CA : SPIE. ; , s. 139-151
-
Konferensbidrag (refereegranskat)abstract
- In this work we present performance characteristics of metalorganic vapor-phase epitaxy grown GaInNAs and InGaAs quantum-well (QW) vertical-cavity lasers (VCLs) for 1.3-Όm applications. The InGaAs VCLs emit in a wavelength range from 1200 to somewhat above 1260 nm, while the GaInNAs VCLs operate from 1265 to 1303 nm. The InGaAs VCLs are based on highly strained InGaAs double QWs, with photoluminescence (PL) maximum at around 1190 nm, and extensive negative gain-cavity detuning. As a consequence, these devices are strongly temperature sensitive and the minimum threshold current is found at very high temperature (∌90-100°C). Both kind of VCLs work continuous-wave well above 100°C, and while the InGaAs VCLs reach slightly higher light output power, they show significantly larger threshold currents. In addition, the large device detuning also has profound effects on the high-frequency response. Nevertheless, for a 1260-nm device, 10 Gb/s transmission is demonstrated in a back-to-back configuration. We also show that by further optimization of the InGaAs QWs the PL peak wavelength can be extended to at least 1240 nm. The incorporation of such QWs in the present VCL structure should considerably improve the device performance, resulting in higher light output power, lower threshold current, and reduced temperature sensitivity with a shift of the minimum threshold current towards room temperature, thus approaching standard VCL tuning.
|
|
| 15. |
- Mogg, S., et al.
(författare)
-
High-performance 1.2-ÎŒm Highly strained InGaAs/GaAs quantum well lasers
- 2002
-
Ingår i: Conference Proceedings - International Conference on Indium Phosphide and Related Materials. - Stockholm. ; , s. 107-110
-
Konferensbidrag (refereegranskat)abstract
- The growth and characterisation of high-performance 1.2-Όm highly strained InGaAs/GaAs single quantum well (SQW) laser diodes is reported. High output power in excess of 200 mW per facet was obtained from ridge-waveguide (RWG) lasers at an emission wavelength of 1230 nm. These lasers operate CW to at least 145°C and show a high characteristic temperature of 150 K. The net modal gain was measured using the method described by Hakki and Paoli.
|
|
| 16. |
- Seidemo, Anina, et al.
(författare)
-
Towards robust glucose chemical exchange saturation transfer imaging in humans at 3 T: Arterial input function measurements and the effects of infusion time
- 2022
-
Ingår i: NMR in Biomedicine. - : Wiley. - 0952-3480 .- 1099-1492. ; 35:2, s. 4624-4624
-
Tidskriftsartikel (refereegranskat)abstract
- Dynamic glucose-enhanced (DGE) magnetic resonance imaging (MRI) has shown potential for tumor imaging using D-glucose as a biodegradable contrast agent. The DGE signal change is small at 3 T (around 1 and accurate detection is hampered by motion. The intravenous D-glucose injection is associated with transient side effects that can indirectly generate subject movements. In this study, the aim was to study DGE arterial input functions (AIFs) in healthy volunteers at 3 T for different scanning protocols, as a step towards making the glucose chemical exchange saturation transfer (glucoCEST) protocol more robust. Two different infusion durations (1.5 and 4.0 min) and saturation frequency offsets (1.2 and 2.0 ppm) were used. The effect of subject motion on the DGE signal was studied by using motion estimates retrieved from standard retrospective motion correction to create pseudo-DGE maps, where the apparent DGE signal changes were entirely caused by motion. Furthermore, the DGE AIFs were compared with venous blood glucose levels. A significant difference (p = 0.03) between arterial baseline and postinfusion DGE signal was found after D-glucose infusion. The results indicate that the measured DGE AIF signal change depends on both motion and blood glucose concentration change, emphasizing the need for sufficient motion correction in glucoCEST imaging. Finally, we conclude that a longer infusion duration (e.g. 3–4 min) should preferably be used in glucoCEST experiments, because it can minimize the glucose infusion side effects without negatively affecting the DGE signal change.
|
|
| 17. |
- Sjögren, Erik, 1977-, et al.
(författare)
-
Preclinical characterization of three transient receptor potential vanilloid receptor 1 antagonists for early use in human intradermal microdose analgesic studies
- 2018
-
Ingår i: European Journal of Pain. - : Wiley. - 1090-3801 .- 1532-2149. ; 22:5, s. 889-903
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe transient receptor potential vanilloid receptor 1 (TRPV1) is a nonselective cation channel involved in the mediation of peripheral pain to the central nervous system. As such, the TRPV1 is an accessible molecular target that lends itself well to the understanding of nociceptive signalling. This study encompasses preclinical investigations of three molecules with the prospect to establish them as suitable analgesic model compounds in human intradermal pain relief studies.MethodsThe inhibitory effectiveness was evaluated by means of invitro assays, TRPV1 expressing Chinese hamster ovary cells (CHO-K1) and rat dorsal root ganglion cultures in fluorescent imaging plate reader and whole cell patch clamp systems, as well as invivo by capsaicin-evoked pain-related behavioural response studies in rat. Secondary pharmacology, pharmacokinetics and preclinical safety were also assessed.ResultsIn vitro, all three compounds were effective at inhibiting capsaicin-activated TRPV1. The concentration producing 50% inhibition (IC50) determined was in the range of 3-32nmol/L and 10-501nmol/L using CHO-K1 and dorsal root ganglion cultures, respectively. In vivo, all compounds showed dose-dependent reduction in capsaicin-evoked pain-related behavioural responses in rat. None of the three compounds displayed any significant activity on any of the secondary targets tested. The compounds were also shown to be safe from a toxicological, drug metabolism and pharmacokinetic perspective, for usage in microgram doses in the human skin.ConclusionThe investigated model compounds displayed ideal compound characteristics as pharmacological and translational tools to address efficacy on the human native TRPV1 target in human skin insitu.SignificanceThis work details the pharmaceutical work-up of three TRPV1-active investigational compounds, to obtain regulatory approval, for subsequent use in humans. This fast and cost-effective preclinical development path may impact research beyond the pain management area, as it allows human target engagement information gathering early in drug development.
|
|
| 18. |
- Sundgren, M, et al.
(författare)
-
Does Information from the Parkinson KinetiGraph™ (PKG) Influence the Neurologist's Treatment Decisions?-An Observational Study in Routine Clinical Care of People with Parkinson's Disease
- 2021
-
Ingår i: Journal of personalized medicine. - : MDPI AG. - 2075-4426. ; 11:6
-
Tidskriftsartikel (refereegranskat)abstract
- Management of Parkinson’s disease traditionally relies solely on clinical assessment. The PKG objectively measures affected persons’ movements in daily life. The present study evaluated how often PKG data changed treatment decisions in routine clinical care and to what extent the clinical assessment and the PKG interpretation differed. PKG recordings were performed before routine visits. The neurologist first made a clinical assessment without reviewing the PKG. Signs and symptoms were recorded, and a treatment plan was documented. Afterward, the PKG was evaluated. Then, the neurologist decided whether to change the initial treatment plan or not. PKG review resulted in a change in the initial treatment plan in 21 of 66 participants (31.8%). The clinical assessment and the PKG review differed frequently, mainly regarding individual overall presence of motor problems (67%), profile of bradykinesia/wearing off (79%), dyskinesia (35%) and sleep (55%). PKG improved the dialogue with the participant in 88% of cases. PKG and clinical variables were stable when they were repeated after 3–6 months. In conclusion, PKG information changes treatment decisions in nearly a third of people with Parkinson’s disease in routine care. Standard clinical assessment and PKG evaluation are often non-identical. Objective measurements in people living with Parkinson’s disease can add therapeutically relevant information.
|
|
| 19. |
- Abul-Kasim, Kasim, et al.
(författare)
-
Intradural spinal tumors: current classification and MRI features
- 2008
-
Ingår i: Neuroradiology. - : Springer Science and Business Media LLC. - 1432-1920 .- 0028-3940. ; 50:4, s. 301-314
-
Tidskriftsartikel (refereegranskat)abstract
- The differential diagnosis of intradural spinal tumors is primarily based on location, but the clinical presentation, age, and gender of the patient are also important factors in determining the diagnosis. This comprehensive review focuses on the current classification, clinical symptoms, and MRI features of the more common intradural extramedullary and intramedullary neoplastic lesions. This review does not include extradural lesions.
|
|
| 20. |
|
|
| 21. |
- Bakker, Elisabeth, et al.
(författare)
-
Perspectives on a Way Forward to Implementation of Precision Medicine in Patients With Diabetic Kidney Disease; Results of a Stakeholder Consensus-Building Meeting
- 2021
-
Ingår i: Frontiers in Pharmacology. - : Frontiers Media SA. - 1663-9812. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- Aim: This study aimed to identify from different stakeholders the benefits and obstacles of implementing precision medicine in diabetic kidney disease (DKD) and to build consensus about a way forward in order to treat, prevent, or even reverse this disease. Methods: As part of an ongoing effort of moving implementation of precision medicine in DKD forward, a two-day consensus-building meeting was organized with different stakeholders involved in drug development and patient care in DKD, including patients, patient representatives, pharmaceutical industry, regulatory agencies representatives, health technology assessors, healthcare professionals, basic scientists, and clinical academic researchers. The meeting consisted of plenary presentations and discussions, and small group break-out sessions. Discussion topics were based on a symposium, focus groups and literature search. Benefits, obstacles and potential solutions toward implementing precision medicine were discussed. Results from the break-out sessions were presented in plenary and formed the basis of a broad consensus discussion to reach final conclusions. Throughout the meeting, participants answered several statement and open-ended questions on their mobile device, using a real-time online survey tool. Answers to the statement questions were analyzed descriptively. Results of the open-ended survey questions, the break-out sessions and the consensus discussion were analyzed qualitatively. Results and conclusion: Seventy-one participants from 26 countries attended the consensus-building meeting in Amsterdam, April 2019. During the opening plenary on the first day, the participants agreed with the statement that precision medicine is the way forward in DKD (n = 57, median 90, IQR [75–100]). Lack of efficient tools for implementation in practice and generating robust data were identified as significant obstacles. The identified benefits, e.g., improvement of the benefit-risk ratio of treatment, offer substantive incentives to find solutions for the identified obstacles. Earlier and increased multi-stakeholder collaboration and specific training may provide solutions to alter clinical and regulatory guidelines that lie at the basis of both obstacles and solutions. At the end of the second day, the opinion of the participants toward precision medicine in DKD was somewhat more nuanced (n = 45, median 83, IQR [70–92]) and they concluded that precision medicine is an important way forward in improving the treatment of patients with DKD.
|
|
| 22. |
- Bernabé, S., et al.
(författare)
-
Highly integrated VCSEL-based 10Gb/s miniature optical sub-assembly
- 2005
-
Ingår i: Proceedings - Electronic Components and Technology Conference. - Lake Buena Vista, FL : IEEE. ; , s. 1333-1338
-
Konferensbidrag (refereegranskat)abstract
- In order to fit with the present and future needs of the Datacom transceiver market, newly designed high rate transmitter optical subassemblies (TOSAs) have to be compact, low cost and compatible with mass production. We propose here an innovative design strategy that reaches all these targets by integrating a 10Gbps 850nmVCSEL laser diode and its laser driver with other functionalities (e.g. power monitoring and thermal monitoring) in a small form factor package. Taking advantages of the optical properties of the VCSEL and using flip-chip techniques, the transmitter exhibits excellent hyperfrequency performances and compatibility with mass production due to the use of collective manufacturing technologies and passive optical alignment. This versatile approach is also applicable to high rate receivers, parallel optics emitters, and singlemode low cost transmitter integrating long wavelength VCSELs.
|
|
| 23. |
- Birch, Jens
(författare)
-
Single-crystal Mo/V superlattices : growth, structure, and hydrogen uptake
- 1994
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Fundamental studies concerning the growth, structural characterization and hydrogen uptake of single-crystal (00 l )-oriented Mo/V superlattices have been performed. The superlattices were grown by dual-target magnetron sputtering in pure Ar-atmosphere < 6·10-3 Torr on (001)-oriented MgO substrates. X-ray diffraction (XRD), X-ray and neutron reflectivity, high resolution (HR) as well as ordinary crosssectional transmission electron microscopy (XTEM) and selected area electron diffraction (SAED) were used for the structural characterization. Hydrogen depth-profiling was performed by the 15N method.For growth of periodic Mo/V superlattices, it is shown that substrate temperatures in the range of 600-700 °C is feasible for epitaxy. At higher growth temperatures substantial interdiffusion occurred. Furthermore, simulations of XRDpatterns gave the width of the interfaces to be ±1 monolayer (±0,154 nm) which was confirmed by XRD and HRXTEM analyses of a superlattice grown with layer thicknesses DMo=Dv=0,31 nm (2 monolayers). A transition from smooth to wavy V-layers was found to occur at a critical V-layer thickness Dc. In superlattices where the relative amount of V is large, De is large and vice versa for superlattices containing thin V-layers. In superlattices with equally thick Mo- and V-layers Dc was found to be ~2,5 nm. Mo was found to grow with a uniform thickness following the surface of the V-layers. The layer thickness fluctuations are non-accumulative and disappear if the periodicity of a growing Mo/V superlattice is changed so that Dv becomes smaller than Dc. The origin of the 3D evolution is explained in terms of surface strain and the roughening transition. The interfaces of Mo/V superlattices grown under the influence of energetic ion bombardment ranging from about 15 eV to 250 eV was studied by HRXTEM and XRD. Both techniques indicated a continous deterioration of the interface quality and an increasing amount of defects with increasing ion energy.The diffraction peaks from a clas of quasi-periodic superlattices which can be generated by the inflation rules A→AmB, B→A (m = positive integer) was analytically, experimentally and numerically found to be located at the wavevectors q = 2πɅ-1rγ(m)k where r and k are integers and A is an average superlattice period. The ratios, γ(m), between the thicknesses of the two superlattice building blocks, A and B, must be chosen such that γ(m) = (m + (m2 + 4) 1/2 )/2.The uptake of hydrogen in the superlattices is found to decrease with decreasing A and for ≤5,5 nm the transition between α-VHx and β-VHx is not observed. A model is proposed which explains the A-dependent behaviour of the hydrogen uptake by a transfer of interstitial electrons from Mo to V, creating a 0,49 nm wide H-free interface layer. The existence of this layer is shown both by the 15N method performed on samples containing several A:s and by combining simulations of X-ray and neutron reflectivities with measurements on superlattices loaded with either hydrogen or deuterium. The structural change of Mo/V(OOl) superlattices upon H-loading was measured by a method derived in this work which utilises a combination of X-ray reflectivity and reciprocal space mapping by XRD. The lattice parameters in the layers are measured in the growth direction as well a in the plane of the sample. It is found that the V lattice expands in the growth direction and that the hydrogenation process is associated with relaxation of coherency strain.
|
|
| 24. |
- Birch, J., et al.
(författare)
-
Structural characterization of precious-mean quasiperiodic Mo/V single-crystal superlattices grown by dual-target magnetron sputtering
- 1990
-
Ingår i: Physical Review B. - 1098-0121. ; 41:15, s. 10398-10407
-
Tidskriftsartikel (refereegranskat)abstract
- A class of quasiperiodic superlattice structures, which can be generated by the concurrent inflation rule A→AmB and B→A (where m=positive integer), has been studied both theoretically and experimentally. Given that the ratios between the thicknesses of the two superlattice building blocks, A and B, are chosen to be γ(m)=[m+(m2+4)1/2]/2 (known as the ‘‘precious means’’), then the x-ray- and electron-diffraction peak positions are analytically found to be located at the wave vectors q=2πΛ−1r[γ(m)]k, where r and k are integers and Λ is an average superlattice wavelength. The analytically obtained results have been compared to experimental results from single-crystalline Mo/V superlattice structures, generated with m=1, 2, and 3. The superlattices were grown by dual-target dc-magnetron sputtering on MgO(001) substrates kept at 700 °C. X-ray diffraction (XRD) and selected-area electron diffraction (SAED) showed that the analytical model mentioned above predicts the peak positions of the experimental XRD and SAED spectra with a very high accuracy. Furthermore, numerical calculations of the diffraction intensities based on a kinematical model of diffraction showed good agreement with the experimental data for all three cases. In addition to a direct verification of the quasiperiodic modulation, both conventional and high-resolution cross-sectional transmission electron microscopy (XTEM) showed that the superlattices are of high crystalline quality with sharp interfaces. Based on lattice resolution images, the width of the interfaces was determined to be less than two (002) lattice-plane spacings (≊0.31 nm).
|
|
| 25. |
- Björkman-Burtscher, Isabella M., et al.
(författare)
-
Detailed anatomy at 7T
- 2017
-
Ingår i: Neuroimaging : Anatomy Meets Function - Anatomy Meets Function. - Cham : Springer International Publishing. - 9783319574264 - 9783319574271 ; , s. 69-80
-
Bokkapitel (refereegranskat)
|
|
