| 1. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 2. |
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| 4. |
- Campbell, PJ, et al.
(författare)
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Pan-cancer analysis of whole genomes
- 2020
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
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| 5. |
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| 6. |
- Blanken, M. A. J. T., et al.
(författare)
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Sex-specifics of ECT outcome
- 2023
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Ingår i: Journal of Affective Disorders. - : ELSEVIER. - 0165-0327 .- 1573-2517. ; 326, s. 243-248
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Electroconvulsive therapy (ECT) is the most effective treatment for patients with severe major depressive disorder (MDD). Given the known sex differences in MDD, improved knowledge may provide more sex-specific recommendations in clinical guidelines and improve outcome. In the present study we examine sex differences in ECT outcome and its predictors. Methods: Clinical data from 20 independent sites participating in the Global ECT-MRI Research Collaboration (GEMRIC) were obtained for analysis, totaling 500 patients with MDD (58.6 % women) with a mean age of 54.8 years. Severity of depression before and after ECT was assessed with validated depression scales. Remission was defined as a HAM-D score of 7 points or below after ECT. Variables associated with remission were selected based on literature (i.e. depression severity at baseline, age, duration of index episode, and presence of psychotic symptoms). Results: Remission rates of ECT were independent of sex, 48.0 % in women and 45.7 % in men (X2(1) = 0.2, p = 0.70). In the logistic regression analyses, a shorter index duration was identified as a sex-specific predictor for ECT outcome in women (X2(1) = 7.05, p = 0.01). The corresponding predictive margins did show overlapping confidence intervals for men and women. Conclusion: The evidence provided by our study suggests that ECT as a biological treatment for MDD is equally effective in women and men. A shorter duration of index episode was an additional sex-specific predictor for remission in women. Future research should establish whether the confidence intervals for the corresponding predictive margins are overlapping, as we find, or not.
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| 8. |
- Cresswell, J. A., et al.
(författare)
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Measurement of maternal functioning during pregnancy and postpartum: findings from the cross-sectional WHO pilot study in Jamaica, Kenya, and Malawi
- 2020
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Ingår i: BMC Pregnancy and Childbirth. - : Springer Science and Business Media LLC. - 1471-2393. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundThe World Health Organization's definition of maternal morbidity refers to "a negative impact on the woman's wellbeing and/or functioning". Many studies have documented the, mostly negative, effects of maternal ill-health on functioning. Although conceptually important, measurement of functioning remains underdeveloped, and the best way to measure functioning in pregnant and postpartum populations is unknown.MethodsA cross-sectional study among women presenting for antenatal (N=750) and postpartum (N=740) care in Jamaica, Kenya and Malawi took place in 2015-2016. Functioning was measured through the World Health Organization Disability Assessment Schedule (WHODAS-12). Data on health conditions and socio-demographic characteristics were collected through structured interview, medical record review, and clinical examination. This paper presents descriptive data on the distribution of functioning status among pregnant and postpartum women and examines the relationship between functioning and health conditions.ResultsWomen attending antenatal care had a lower level of functioning than those attending postpartum care. Women with a health condition or associated demographic risk factor were more likely to have a lower level of functioning than those with no health condition. However, the absolute difference in functioning scores typically remained modest.ConclusionsFunctioning is an important concept which integrates a woman-centered approach to examining how a health condition affects her life, and ultimately her return to functioning after delivery. However, the WHODAS-12 may not be the optimal tool for use in this population and additional components to capture pregnancy-specific issues may be needed. Challenges remain in how to integrate functioning outcomes into routine maternal healthcare at-scale and across diverse settings.
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| 9. |
- Rudman, S. M., et al.
(författare)
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What genomic data can reveal about eco-evolutionary dynamics
- 2018
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Ingår i: Nature Ecology & Evolution. - : Springer Science and Business Media LLC. - 2397-334X. ; 2:1, s. 9-15
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Tidskriftsartikel (refereegranskat)abstract
- Recognition that evolution operates on the same timescale as ecological processes has motivated growing interest in eco-evolutionary dynamics. Nonetheless, generating sufficient data to test predictions about eco-evolutionary dynamics has proved challenging, particularly in natural contexts. Here we argue that genomic data can be integrated into the study of eco-evolutionary dynamics in ways that deepen our understanding of the interplay between ecology and evolution. Specifically, we outline five major questions in the study of eco-evolutionary dynamics for which genomic data may provide answers. Although genomic data alone will not be sufficient to resolve these challenges, integrating genomic data can provide a more mechanistic understanding of the causes of phenotypic change, help elucidate the mechanisms driving eco-evolutionary dynamics, and lead to more accurate evolutionary predictions of eco-evolutionary dynamics in nature.
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| 10. |
- Wasmann, Jan-Willem A., et al.
(författare)
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Computational Audiology: New Approaches to Advance Hearing Health Care in the Digital Age
- 2021
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Ingår i: Ear and Hearing. - : LIPPINCOTT WILLIAMS & WILKINS. - 0196-0202 .- 1538-4667. ; 42:6, s. 1499-1507
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Tidskriftsartikel (refereegranskat)abstract
- The global digital transformation enables computational audiology for advanced clinical applications that can reduce the global burden of hearing loss. In this article, we describe emerging hearing-related artificial intelligence applications and argue for their potential to improve access, precision, and efficiency of hearing health care services. Also, we raise awareness of risks that must be addressed to enable a safe digital transformation in audiology. We envision a future where computational audiology is implemented via interoperable systems using shared data and where health care providers adopt expanded roles within a network of distributed expertise. This effort should take place in a health care system where privacy, responsibility of each stakeholder, and patients safety and autonomy are all guarded by design.
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| 13. |
- Barratt, Jonathan, et al.
(författare)
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Phase 2 Trial of Cemdisiran in Adult Patients with IgA Nephropathy: A Randomized Controlled Trial
- 2024
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Ingår i: American Society of Nephrology. Clinical Journal. - : AMER SOC NEPHROLOGY. - 1555-9041 .- 1555-905X. ; 19:4, s. 452-462
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Tidskriftsartikel (refereegranskat)abstract
- Background IgA nephropathy is the most common primary GN. Clinical features of IgA nephropathy include proteinuria, which is the strongest known surrogate of progression to kidney failure. Complement pathway activation is a critical driver of inflammation and tissue injury in IgA nephropathy. Cemdisiran is an investigational RNA interference therapeutic that suppresses hepatic production of complement component 5 (C5), thereby potentially reducing proteinuria in IgA nephropathy. We evaluated the efficacy and safety of cemdisiran in adult patients with IgA nephropathy at high risk of kidney disease progression. Methods In this phase 2, 36-week, double-blind study, adult patients with IgA nephropathy and urine protein >= 1 g/24 hours were randomized (2:1) to subcutaneous cemdisiran 600 mg or placebo every 4 weeks in combination with the standard of care. The primary end point was percentage change from baseline at week 32 in urine protein-to-creatinine ratio (UPCR) measured by 24-hour urine collection. Additional end points included change from baseline in UPCR measured by spot urine, serum C5 level, and safety assessments. Results Thirty-one patients were randomized (cemdisiran, N=22; placebo, N=9). Cemdisiran-treated patients had a placebo-adjusted geometric mean change in 24-hour UPCR of -37.4% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.69 [0.10]) at week 32. Spot UPCR was consistent with 24-hour UPCR placebo-adjusted change of -45.8% (cemdisiran-adjusted geometric mean ratio to baseline [SEM], 0.73 [0.11]). Mean (SD) change in serum C5 level from baseline at week 32 was -98.7% (1.2) with cemdisiran and 25.2% (57.7) with placebo. Over 36 weeks, most adverse events were mild or moderate and transient; the most common adverse event after cemdisiran treatment was injection-site reaction (41%). Conclusions These findings indicate that treatment with cemdisiran resulted in a reduction of proteinuria at week 32 and was well tolerated.
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| 15. |
- Bunikis, Jonas, et al.
(författare)
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Sequence typing reveals extensive strain diversity of the Lyme borreliosis agents Borrelia burgdorferi in North America and Borrelia afzelii in Europe.
- 2004
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Ingår i: Microbiology. - : Microbiology Society. - 1350-0872 .- 1465-2080. ; 150:6, s. 1741-1755
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Tidskriftsartikel (refereegranskat)abstract
- The genetic polymorphism of Borrelia burgdorferi and Borrelia afzelii, two species that cause Lyme borreliosis, was estimated by sequence typing of four loci: the rrs-rrlA intergenic spacer (IGS) and the outer-membrane-protein gene p66 on the chromosome, and the outer-membrane-protein genes ospA and ospC on plasmids. The major sources of DNA for PCR amplification and sequencing were samples of the B. burgdorferi tick vector Ixodes scapularis, collected at a field site in an endemic region of the north-eastern United States, and the B. afzelii vector Ixodes ricinus, collected at a similar site in southern Sweden. The sequences were compared with those of reference strains and skin biopsy isolates, as well as database sequences. For B. burgdorferi, 10-13 alleles for each of the 4 loci, and a total of 9 distinct clonal lineages with linkage of all 4 loci, were found. For B. afzelii, 2 loci, ospC and IGS, were examined, and 11 IGS genotypes, 12 ospC alleles, and a total of 9 linkage groups were identified. The genetic variants of B. burgdorferi and B. afzelii among samples from the field sites accounted for the greater part of the genetic diversity previously reported from larger areas of the north-eastern United States and central and northern Europe. Although ospC alleles of both species had higher nucleotide diversity than other loci, the ospC locus showed evidence of intragenic recombination and was unsuitable for phylogenetic inference. In contrast, there was no detectable recombination at the IGS locus of B. burgdorferi. Moreover, beyond the signature nucleotides that specified 10 IGS genotypes, there were additional nucleotide polymorphisms that defined a total of 24 subtypes. Maximum-likelihood and parsimony cladograms of B. burgdorferi aligned IGS sequences revealed the subtype sequences to be terminal branches of clades, and the existence of at least three monophyletic lineages within B. burgdorferi. It is concluded that B. burgdorferi and B. afzelii have greater genetic diversity than had previously been estimated, and that the IGS locus alone is sufficient for strain typing and phylogenetic studies.
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| 16. |
- Bunikis, J, et al.
(författare)
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Surface exposure and species specificity of an immunoreactive domain of a 66-kilodalton outer membrane protein (P66) of the Borrelia spp. that cause Lyme disease
- 1996
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Ingår i: Infection and Immunity. - 0019-9567 .- 1098-5522. ; 64:12, s. 5111-5116
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Tidskriftsartikel (refereegranskat)abstract
- A chromosomally encoded 66-kDa protein (P66) of Borrelia spp. that cause Lyme disease has previously been shown to be associated with the spirochetal outer membrane. A topological model of P66 predicts a surface-exposed fragment which links the N- and C-terminal intramembranous domains of the protein (J. Bunikis, L. Noppa, and S. Bergström, FEMS Microbiol. Lett. 131:139-145, 1995). In the present study, an immunogenic determinant of P66 was identified by a comparison of the immunoreactivities of different fragments of P66 generated either by proteolytic treatment of intact spirochetes or as recombinant proteins expressed in Escherichia coli. The immune response to P66 during natural infection was found to be directed against the predicted surface domain which comprises amino acids at positions 454 through 491. A sequence comparison revealed considerable polymorphism of the surface domains of P66 proteins of different Lyme disease-causing Borrelia species. Five sequence patterns of this domain were observed in the B. garinii strains studied. In contrast, sequences of the relevant part of P66 of the B. afzelii and B. burgdorferi sensu stricto isolates studied were identical within the respective species. In immunoblotting, 5 of 17 (29.4%) sera from North American patients with early disseminated or persistent Lyme disease reacted against P66 of B. burgdorferi sensu stricto B31. These sera, however, failed to recognize P66 of B. afzelii and B. garinii, as well as an analog of P66 in the relapsing fever agent, B. hermsii. In conclusion, the topological model of P66 is supported by the demonstration of an apparent surface localization of an immunoreactive domain of this protein. Furthermore, analogous to the plasmid-encoded borrelial outer surface proteins, the predicted surface-exposed portion of chromosomally encoded P66 appears to be antigenically heterogenous.
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| 17. |
- Bunikis, Jonas, et al.
(författare)
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Typing of Borrelia relapsing fever group strains.
- 2004
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Ingår i: Emerging Infectious Diseases. - 1080-6040 .- 1080-6059. ; 10:9, s. 1661-1664
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Tidskriftsartikel (refereegranskat)abstract
- Partial sequencing of the 16S-23S rDNA intergenic spacer showed two to four genotypes each for Borrelia hermsii and B. turicatae, both relapsing fever agents transmitted by argasid ticks, and for B. miyamotoi and B. lonestari, transmitted by ixodid ticks. Field surveys of Ixodes ticks in Connecticut and Sweden showed limited local diversity for B. miyamotoi.
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| 19. |
- Clark, K, et al.
(författare)
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Stigma, displacement stressors and psychiatric morbidity among displaced Syrian men who have sex with men (MSM) and transgender women: a cross-sectional study in Lebanon
- 2021
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Ingår i: BMJ open. - : BMJ. - 2044-6055. ; 11:5, s. e046996-
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Tidskriftsartikel (refereegranskat)abstract
- Displaced Syrians face psychiatric morbidity often resulting from displacement-related stressors (eg, resource scarcity). Both men who have sex with men (MSM) and transgender women among the displaced Syrians are particularly vulnerable to mental health challenges given that they also often face stigma-related stressors (eg, discrimination).MethodsBetween January and December 2019 in greater Beirut, 258 Lebanese-born MSM and transgender women and 230 displaced Syrian MSM and transgender women were recruited via respondent-driven sampling to complete an in-person survey assessing displacement-related stressors, stigma-related stressors, depression, anxiety and post-traumatic stress disorder. In the total sample, we first documented the prevalence of psychiatric morbidity among the displaced Syrians; we then assessed associations among displacement-related and stigma-related stressors and each psychiatric outcome.ResultsSixty-three per cent of Syrian participants met criteria for depression compared with 43.8% of Lebanese participants (p<0.001); 21.3% of Syrians met criteria for severe anxiety compared with 13.1% of Lebanese participants (p<0.05) and 33.0% of Syrians met criteria for post-traumatic stress disorder compared with 18.4% of Lebanese participants (p<0.001). Among Syrian MSM and transgender women, sociodemographic characteristics, displacement-related stressors and stigma-related stressors were uniquely associated with psychiatric morbidity.ConclusionDisplaced Syrian MSM and transgender women experience higher levels of psychiatric comorbidities than Lebanese MSM and transgender women in part due to compounding exposure to displacement-related stressors and stigma-related stressors. Informed by tenets of minority stress theory and intersectionality theory, we discuss mental health intervention implications and future directions.
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| 23. |
- Veenstra, M M K, et al.
(författare)
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Complications and survival after hybrid and fully minimally invasive oesophagectomy
- 2021
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Ingår i: BJS Open. - : John Wiley & Sons. - 2474-9842. ; 5:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Minimally invasive oesophagectomy (MIO) is reported to produce fewer respiratory complications than open oesophagectomy. This study assessed differences in postoperative complications between MIO and hybrid MIO (HMIO) employing thoracoscopy and laparotomy, along with the influence of co-morbidities on postoperative outcomes.METHODS: Patients with oesophageal cancer undergoing three-stage MIO or three-stage HMIO between 1999 and 2018 were identified from a prospectively developed database, which included patient demographics, co-morbidities, preoperative therapies, and cancer stage. The primary outcome was postoperative complications in the two groups. Secondary outcomes included duration of operation, blood transfusion requirement, duration of hospital stay, and overall survival.RESULTS: There were 828 patients, of whom 722 had HMIO and 106 MIO, without significant baseline differences. Median duration of operation was longer for MIO (325 versus 289 min; P < 0.001), but with less blood loss (median 250 versus 300 ml; P < 0.001) and a shorter hospital stay (median 12 versus 13 days; P = 0.006). Respiratory complications were not associated with operative approach (31.1 versus 35.2 per cent for MIO and HMIO respectively; P = 0.426). Anastomotic leak rates (10.4 versus 10.2 per cent) and 90-day mortality (1.0 versus 1.7 per cent) did not differ. Cardiac co-morbidity was associated with more medical and surgical complications. Overall survival was associated with AJCC stage and co-morbidities, but not operative approach.CONCLUSION: MIO had a small benefit in terms of blood loss and hospital stay, but not in operating time. Oncological outcomes were similar in the two groups. Postoperative complications were associated with pre-existing cardiorespiratory co-morbidities rather than operative approach.
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| 24. |
- Wilkinson, Jack, et al.
(författare)
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Protocol for the development of a tool (INSPECT-SR) to identify problematic randomised controlled trials in systematic reviews of health interventions
- 2024
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Ingår i: BMJ Open. - : BMJ Publishing Group Ltd. - 2044-6055. ; 14:3
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Tidskriftsartikel (refereegranskat)abstract
- Introduction Randomised controlled trials (RCTs) inform healthcare decisions. It is now apparent that some published RCTs contain false data and some appear to have been entirely fabricated. Systematic reviews are performed to identify and synthesise all RCTs that have been conducted on a given topic. While it is usual to assess methodological features of the RCTs in the process of undertaking a systematic review, it is not usual to consider whether the RCTs contain false data. Studies containing false data therefore go unnoticed and contribute to systematic review conclusions. The INveStigating ProblEmatic Clinical Trials in Systematic Reviews (INSPECT-SR) project will develop a tool to assess the trustworthiness of RCTs in systematic reviews of healthcare-related interventions.Methods and analysis The INSPECT-SR tool will be developed using expert consensus in combination with empirical evidence, over five stages: (1) a survey of experts to assemble a comprehensive list of checks for detecting problematic RCTs, (2) an evaluation of the feasibility and impact of applying the checks to systematic reviews, (3) a Delphi survey to determine which of the checks are supported by expert consensus, culminating in, (4) a consensus meeting to select checks to be included in a draft tool and to determine its format and (5) prospective testing of the draft tool in the production of new health systematic reviews, to allow refinement based on user feedback. We anticipate that the INSPECT-SR tool will help researchers to identify problematic studies and will help patients by protecting them from the influence of false data on their healthcare.Ethics and dissemination The University of Manchester ethics decision tool was used, and this returned the result that ethical approval was not required for this project (30 September 2022), which incorporates secondary research and surveys of professionals about subjects relating to their expertise. Informed consent will be obtained from all survey participants. All results will be published as open-access articles. The final tool will be made freely available.
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