| 1. |
|
|
| 2. |
- Klint, Susanne, et al.
(författare)
-
Izokibep : Preclinical development and first-in-human study of a novel IL-17A neutralizing Affibody molecule in patients with plaque psoriasis
- 2023
-
Ingår i: mAbs. - : Taylor & Francis. - 1942-0862 .- 1942-0870. ; 15:1
-
Tidskriftsartikel (refereegranskat)abstract
- Psoriasis, an immune-mediated inflammatory disease, affects nearly 125 million people globally. The interleukin (IL)-17A homodimer is a key driver of psoriasis and other autoimmune diseases, including psoriatic arthritis, axial spondyloarthritis, hidradenitis suppurativa, and uveitis. Treatment with monoclonal antibodies (mAbs) against IL-17A provides an improvement in the Psoriasis Area and Severity Index compared to conventional systemic agents. In this study, the Affibody(CIRCLED LATIN CAPITAL LETTER R) technology was used to identify and optimize a novel, small, biological molecule comprising three triple helical affinity domains, izokibep (previously ABY-035), for the inhibition of IL-17A signaling. Preclinical studies show that izokibep, a small 18.6 kDa IL-17 ligand trap comprising two IL-17A-specific Affibody domains and one albumin-binding domain, selectively inhibits human IL-17A in vitro and in vivo with superior potency and efficacy relative to anti-IL-17A mAbs. A Phase 1 first-in-human study was conducted to establish the safety, pharmacokinetics, and preliminary efficacy of izokibep, when administered intravenously and subcutaneously as single doses to healthy subjects, and as single intravenous and multiple subcutaneous doses to patients with psoriasis (NCT02690142; EudraCT No: 2015-004531-13). Izokibep was well tolerated with no meaningful safety concerns identified in healthy volunteers and patients with psoriasis. Rapid efficacy was seen in all psoriasis patients after one dose which further improved in patients receiving multiple doses. A therapeutic decrease in joint pain was also observed in a single patient with concurrent psoriatic arthritis. The study suggests that izokibep has the potential to safely treat IL17A-associated diseases such as psoriasis, psoriatic arthritis, axial spondyloarthritis, hidradenitis suppurativa, and uveitis.
|
|
| 3. |
- Amour, Maryam A., et al.
(författare)
-
Determinants of COVID-19 Vaccine Uptake and Hesitancy among Healthcare Workers in Tanzania : A Mixed-Methods Study
- 2023
-
Ingår i: COVID. - : MDPI. - 2673-8112. ; 3:5, s. 777-791
-
Tidskriftsartikel (refereegranskat)abstract
- The novel Coronavirus disease 2019 (COVID-19) presents a major threat to public health but can be prevented by safe and effective COVID-19 vaccines. Vaccine acceptance among healthcare workers (HCWs) is essential to promote uptake. This study, aimed to determine the COVID-19 vaccination uptake and hesitancy and its associated factors among HCWs in Tanzania. We employed a convergent-parallel mixed-methods design among 1368 HCWs across health facilities in seven geographical zones in Tanzania in 2021. We collected quantitative data by using an interviewer-administered questionnaire and qualitative data, using in-depth interviews and focus group discussions. Participants in the quantitative aspect were conveniently selected whereas those in the qualitative aspect were purposively selected based on their role in patient care, management, and vaccine provision. Stata software version 16.1 was used in the analysis of quantitative data and thematic analysis for the qualitative data. Multiple logistic regression was used to assess the determinants of COVID-19 vaccine uptake. The median age of 1368 HCWs was 33, and the interquartile range was 28-43 years; 65.6% were aged 30+ years, and 60.1% were females. Over half (53.4%) of all HCWs received the COVID-19 vaccine, 33.6% completely refused, and 13% chose to wait. HCWs aged 40+ years, from lower-level facilities (district hospitals and health centers), who worked 6+ years, and with perceived high/very high risk of COVID-19 infection had significantly higher odds of vaccine uptake. The qualitative data revealed misinformation and inadequate knowledge about COVID-19 vaccine safety and efficacy as the key barriers to uptake. Nearly half of all HCWs in Tanzania are still unvaccinated against COVID-19. The predominance of contextual influence on COVID-19 vaccine uptake calls for interventions to focus on addressing contextual determinants, focusing on younger HCWs' population, short working duration, those working at different facility levels, and providing adequate vaccine knowledge.
|
|
| 4. |
- Basten, B., et al.
(författare)
-
Modular language implementation in Rascal - experience report
- 2015
-
Ingår i: Science of Computer Programming. - : Elsevier BV. - 0167-6423. ; 114, s. 7-19
-
Tidskriftsartikel (refereegranskat)abstract
- All software evolves, and programming languages and programming language tools are no exception. And just like in ordinary software construction, modular implementations can help ease the process of changing a language implementation and its dependent tools. However, the syntactic and semantic dependencies between language features make this a challenging problem. In this paper we detail how programming languages can be implemented in a modular fashion using the RASCAL meta-programming language. RASCAL supports extensible definition of concrete syntax, abstract syntax and operations on concrete and abstract syntax trees like matching, traversal and transformation. As a result, new language features can be added without having to change existing code. As a case study, we detail our solution of the LDTA'11 Tool Challenge: a modular implementation of OBERON-0, a relatively simple imperative programming language. The approach we sketch can be applied equally well to the implementation of domain-specific languages.
|
|
| 5. |
- Brooks, D. R., et al.
(författare)
-
Temporal trends in non-small cell lung cancer survival in Sweden
- 2007
-
Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 96:3, s. 519-522
-
Tidskriftsartikel (refereegranskat)abstract
- We modeled temporal trends in the 1- and 5-year survival of 32 499 patients with adenocarcinoma and squamous cell carcinoma of the lung in the Swedish Cancer Register between 1961 and 2000. The 1-year relative survival for adenocarcinoma improved from 37% for patients diagnosed 1961–1965 to 45% for those diagnosed 1996–2000 and from 39 to 45% for squamous cell carcinoma. The adjusted excess mortality ratios for the period 1996–2000 compared with 1961–1965 were 0.80 for adenocarcinoma and 0.81 for squamous cell carcinoma. Thus, a previous report in a Dutch study of a relatively worsening prognosis for adenocarcinoma over time could not be confirmed.
|
|
| 6. |
|
|
| 7. |
- Holmberg, Lars, et al.
(författare)
-
A comparison of prostate cancer survival in England, Norway and Sweden : A population-based study
- 2012
-
Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:1, s. e7-e12
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose The objective of the study was to compare patterns of survival 2001-2004 in prostate cancer patients from England, Norway and Sweden in relation to age and period of follow-up. Subjects and methods Excess mortality in men with prostate cancer was estimated using nation-wide cancer register data using a period approach for relative survival. 179,112 men in England, 23,192 in Norway and 59,697 in Sweden were included. Results In all age groups, England had the lowest survival, particularly so among men aged 80+. Overall age-standardised five-year survival was 76.4%, 80.3% and 83.0% for England, Norway and Sweden, respectively. The majority of the excess deaths in England were confined to the first year of follow-up. Conclusion The results indicate that a small but important group of older patients present at a late stage and succumb early to their cancers, possibly in combination with severe comorbidity, and this situation is more common in England than in Norway or Sweden.
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
