| 1. |
|
|
| 2. |
- Thomas, HS, et al.
(author)
-
- 2019
-
swepub:Mat__t
|
|
| 3. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 4. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 5. |
|
|
| 6. |
- Wang, Z., et al.
(author)
-
Genome-wide association analyses of physical activity and sedentary behavior provide insights into underlying mechanisms and roles in disease prevention
- 2022
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 54:9, s. 1332-1344
-
Journal article (peer-reviewed)abstract
- Although physical activity and sedentary behavior are moderately heritable, little is known about the mechanisms that influence these traits. Combining data for up to 703,901 individuals from 51 studies in a multi-ancestry meta-analysis of genome-wide association studies yields 99 loci that associate with self-reported moderate-to-vigorous intensity physical activity during leisure time (MVPA), leisure screen time (LST) and/or sedentary behavior at work. Loci associated with LST are enriched for genes whose expression in skeletal muscle is altered by resistance training. A missense variant in ACTN3 makes the alpha-actinin-3 filaments more flexible, resulting in lower maximal force in isolated type IIA muscle fibers, and possibly protection from exercise-induced muscle damage. Finally, Mendelian randomization analyses show that beneficial effects of lower LST and higher MVPA on several risk factors and diseases are mediated or confounded by body mass index (BMI). Our results provide insights into physical activity mechanisms and its role in disease prevention. Multi-ancestry meta-analyses of genome-wide association studies for self-reported physical activity during leisure time, leisure screen time, sedentary commuting and sedentary behavior at work identify 99 loci associated with at least one of these traits.
|
|
| 7. |
- George, T. S., et al.
(author)
-
Organic phosphorus in the terrestrial environment : a perspective on the state of the art and future priorities
- 2018
-
In: Plant and Soil. - : Springer Netherlands. - 0032-079X .- 1573-5036. ; 427:1-2, s. 191-208
-
Journal article (peer-reviewed)abstract
- Background: The dynamics of phosphorus (P) in the environment is important for regulating nutrient cycles in natural and managed ecosystems and an integral part in assessing biological resilience against environmental change. Organic P (P-o) compounds play key roles in biological and ecosystems function in the terrestrial environment being critical to cell function, growth and reproduction.Scope: We asked a group of experts to consider the global issues associated with P-o in the terrestrial environment, methodological strengths and weaknesses, benefits to be gained from understanding the P-o cycle, and to set priorities for P-o research.Conclusions: We identified seven key opportunities for P-o research including: the need for integrated, quality controlled and functionally based methodologies; assessment of stoichiometry with other elements in organic matter; understanding the dynamics of P-o in natural and managed systems; the role of microorganisms in controlling P-o cycles; the implications of nanoparticles in the environment and the need for better modelling and communication of the research. Each priority is discussed and a statement of intent for the P-o research community is made that highlights there are key contributions to be made toward understanding biogeochemical cycles, dynamics and function of natural ecosystems and the management of agricultural systems.
|
|
| 8. |
|
|
| 9. |
- Stafoggia, M., et al.
(author)
-
Joint effect of heat and air pollution on mortality in 620 cities of 36 countries
- 2023
-
In: Environment International. - : Elsevier. - 0160-4120 .- 1873-6750. ; 181
-
Journal article (peer-reviewed)abstract
- Background: The epidemiological evidence on the interaction between heat and ambient air pollution on mor-tality is still inconsistent. Objectives: To investigate the interaction between heat and ambient air pollution on daily mortality in a large dataset of 620 cities from 36 countries. Methods: We used daily data on all-cause mortality, air temperature, particulate matter <= 10 mu m (PM10), PM <= 2.5 mu m (PM2.5), nitrogen dioxide (NO2), and ozone (O3) from 620 cities in 36 countries in the period 1995-2020. We restricted the analysis to the six consecutive warmest months in each city. City-specific data were analysed with over-dispersed Poisson regression models, followed by a multilevel random-effects meta-analysis. The joint association between air temperature and air pollutants was modelled with product terms between non-linear functions for air temperature and linear functions for air pollutants. Results: We analyzed 22,630,598 deaths. An increase in mean temperature from the 75th to the 99th percentile of city-specific distributions was associated with an average 8.9 % (95 % confidence interval: 7.1 %, 10.7 %) mortality increment, ranging between 5.3 % (3.8 %, 6.9 %) and 12.8 % (8.7 %, 17.0 %), when daily PM10 was equal to 10 or 90 mu g/m3, respectively. Corresponding estimates when daily O3 concentrations were 40 or 160 mu g/ m3 were 2.9 % (1.1 %, 4.7 %) and 12.5 % (6.9 %, 18.5 %), respectively. Similarly, a 10 mu g/m3 increment in PM10 was associated with a 0.54 % (0.10 %, 0.98 %) and 1.21 % (0.69 %, 1.72 %) increase in mortality when daily air temperature was set to the 1st and 99th city-specific percentiles, respectively. Corresponding mortality estimate for O3 across these temperature percentiles were 0.00 % (-0.44 %, 0.44 %) and 0.53 % (0.38 %, 0.68 %). Similar effect modification results, although slightly weaker, were found for PM2.5 and NO2. Conclusions: Suggestive evidence of effect modification between air temperature and air pollutants on mortality during the warm period was found in a global dataset of 620 cities.
|
|
| 10. |
- Ademuyiwa, Adesoji O., et al.
(author)
-
Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries
- 2016
-
In: BMJ Global Health. - : BMJ Publishing Group Ltd. - 2059-7908. ; 1:4
-
Journal article (peer-reviewed)abstract
- Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.
|
|
| 11. |
- Garland, N. T., et al.
(author)
-
A Miniaturized, Battery-Free, Wireless Wound Monitor That Predicts Wound Closure Rate Early
- 2023
-
In: Advanced Healthcare Materials. - : Wiley. - 2192-2640 .- 2192-2659. ; 12:28
-
Journal article (peer-reviewed)abstract
- Diabetic foot ulcers are chronic wounds that affect millions and increase the risk of amputation and mortality, highlighting the critical need for their early detection. Recent demonstrations of wearable sensors enable real-time wound assessment, but they rely on bulky electronics, making them difficult to interface with wounds. Herein, a miniaturized, wireless, battery-free wound monitor that measures lactate in real-time and seamlessly integrates with bandages for conformal attachment to the wound bed is introduced. Lactate is selected due to its multifaceted role in initiating healing. Studies in healthy and diabetic mice reveal distinct lactate profiles for normal and impaired healing wounds. A mathematical model based on the sensor data predicts wound closure rate within the first 3 days post-injury with ≈76% accuracy, which increases to ≈83% when pH is included. These studies underscore the significance of monitoring biomarkers during the inflammation phase, which can offer several benefits, including short-term use of wound monitors and their easy removal, resulting in lower risks of injury and infection at the wound site. Improvements in prediction accuracy can be achieved by designing mathematical models that build on multiple wound parameters such as pro-inflammatory and metabolic markers. Achieving this goal will require designing multi-analyte wound monitors.
|
|
| 12. |
|
|
| 13. |
- Watts, Eleanor L., et al.
(author)
-
Circulating sex hormones in relation to anthropometric, sociodemographic and behavioural factors in an international dataset of 12,300 men
- 2017
-
In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 12:12
-
Journal article (peer-reviewed)abstract
- Introduction: Sex hormones have been implicated in the etiology of a number of diseases. To better understand disease etiology and the mechanisms of disease-risk factor associations, this analysis aimed to investigate the associations of anthropometric, sociodemographic and behavioural factors with a range of circulating sex hormones and sex hormone-binding globulin.Methods: Statistical analyses of individual participant data from 12,330 male controls aged 25–85 years from 25 studies involved in the Endogenous Hormones Nutritional Biomarkers and Prostate Cancer Collaborative Group. Analysis of variance was used to estimate geometric means adjusted for study and relevant covariates.Results: Older age was associated with higher concentrations of sex hormone-binding globulin and dihydrotestosterone and lower concentrations of dehydroepiandrosterone sulfate, free testosterone, androstenedione, androstanediol glucuronide and free estradiol. Higher body mass index was associated with higher concentrations of free estradiol, androstanediol glucuronide, estradiol and estrone and lower concentrations of dihydrotestosterone, testosterone, sex hormone-binding globulin, free testosterone, androstenedione and dehydroepiandrosterone sulfate. Taller height was associated with lower concentrations of androstenedione, testosterone, free testosterone and sex hormone-binding globulin and higher concentrations of androstanediol glucuronide. Current smoking was associated with higher concentrations of androstenedione, sex hormone-binding globulin and testosterone. Alcohol consumption was associated with higher concentrations of dehydroepiandrosterone sulfate, androstenedione and androstanediol glucuronide. East Asians had lower concentrations of androstanediol glucuronide and African Americans had higher concentrations of estrogens. Education and marital status were modestly associated with a small number of hormones.Conclusion: Circulating sex hormones in men are strongly associated with age and body mass index, and to a lesser extent with smoking status and alcohol consumption.
|
|
| 14. |
- Garland, P., et al.
(author)
-
Haemoglobin causes neuronal damage in vivo which is preventable by haptoglobin
- 2020
-
In: Brain Communications. - : Oxford University Press (OUP). - 2632-1297. ; 2:1
-
Journal article (peer-reviewed)abstract
- After subarachnoid haemorrhage, prolonged exposure to toxic extracellular haemoglobin occurs in the brain. Here, we investigate the role of haemoglobin neurotoxicity in vivo and its prevention. In humans after subarachnoid haemorrhage, haemoglobin in cerebrospinal fluid was associated with neurofilament light chain, a marker of neuronal damage. Most haemoglobin was not complexed with haptoglobin, an endogenous haemoglobin scavenger present at very low concentration in the brain. Exogenously added haptoglobin bound most uncomplexed haemoglobin, in the first 2 weeks after human subarachnoid haemorrhage, indicating a wide therapeutic window. In mice, the behavioural, vascular, cellular and molecular changes seen after human subarachnoid haemorrhage were recapitulated by modelling a single aspect of subarachnoid haemorrhage: prolonged intrathecal exposure to haemoglobin. Haemoglobin-induced behavioural deficits and astrocytic, microglial and synaptic changes were attenuated by haptoglobin. Haptoglobin treatment did not attenuate large-vessel vasospasm, yet improved clinical outcome by restricting diffusion of haemoglobin into the parenchyma and reducing small-vessel vasospasm. In summary, haemoglobin toxicity is of clinical importance and preventable by haptoglobin, independent of large-vessel vasospasm.
|
|
| 15. |
- Silman, A. J., et al.
(author)
-
International variation in distribution of ASA class in patients undergoing total hip arthroplasty and its influence on mortality: data from an international consortium of arthroplasty registries
- 2021
-
In: Acta Orthopaedica. - : Medical Journals Sweden AB. - 1745-3674 .- 1745-3682. ; 92:3, s. 304-310
-
Journal article (peer-reviewed)abstract
- Background and purpose - A challenge comparing outcomes from total hip arthroplasty between countries is variation in preoperative characteristics, particularly comorbidity. Therefore, we investigated between-country variation in comorbidity in patients based on ASA class distribution, and determined any variation of ASA class to mortality risk between countries. Patients and methods - All arthroplasty registries collecting ASA class and mortality data in patients with elective primary THAs performed 2012-2016 were identified. Survival analyses of the influence of ASA class on 1-year mortality were performed by individual registries, followed by meta-analysis of aggregated data. Results - 6 national registries and 1 US healthcare organization registry with 418,916 THAs were included. There was substantial variation in the proportion of ASA class III/IV, ranging from 14% in the Netherlands to 39% in Finland. Overall, 1-year mortality was 0.93% (95% CI 0.87-1.01) and increased from 0.2% in ASA class I to 8.9% in class IV. The association between ASA class and mortality measured by hazard ratios (HR) was strong in all registries even after adjustment for age and sex, which reduced them by half in all registries. Combined adjusted HRs were 2.0, 6.1, and 22 for ASA class II-IV vs. I, respectively. Associations were moderately heterogeneous across registries. Interpretation - We observed large variation in ASA class distribution between registries, possibly explained by differences in background morbidity and/or international variation in access to surgery. The similar, strong mortality trends by ASA class between countries enhance the relevance of its use as an indicator of comorbidity in international registry studies.
|
|
| 16. |
- Brown, Darron R., et al.
(author)
-
The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Generally HPV-Naive Women Aged 16-26 Years
- 2009
-
In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 926-935
-
Conference paper (peer-reviewed)abstract
- Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of >= 6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for similar to 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type.
|
|
| 17. |
- Dillner, Joakim, et al.
(author)
-
Four year efficacy of prophylactic human papillomavirus quadrivalent vaccine against low grade cervical, vulvar, and vaginal intraepithelial neoplasia and anogenital warts: randomised controlled trial.
- 2010
-
In: BMJ: British Medical Journal. - : BMJ. - 1756-1833 .- 0959-8138 .- 1468-5833. ; 341
-
Journal article (peer-reviewed)abstract
- OBJECTIVES: To evaluate the prophylactic efficacy of the human papillomavirus (HPV) quadrivalent vaccine in preventing low grade cervical, vulvar, and vaginal intraepithelial neoplasias and anogenital warts (condyloma acuminata). DESIGN: Data from two international, double blind, placebo controlled, randomised efficacy trials of quadrivalent HPV vaccine (protocol 013 (FUTURE I) and protocol 015 (FUTURE II)). The trials were to be 4 years in length, and the results reported are from final study data of 42 months' follow-up. SETTING: Primary care centres and university or hospital associated health centres in 24 countries and territories around the world. PARTICIPANTS: 17 622 women aged 16-26 years enrolled between December 2001 and May 2003. Major exclusion criteria were lifetime number of sexual partners (>4), history of abnormal cervical smear test results, and pregnancy. INTERVENTION: Three doses of quadrivalent HPV vaccine (for serotypes 6, 11, 16, and 18) or placebo at day 1, month 2, and month 6. MAIN OUTCOME MEASURES: Vaccine efficacy against cervical, vulvar, and vaginal intraepithelial neoplasia grade I and condyloma in a per protocol susceptible population that included subjects who received all three vaccine doses, tested negative for the relevant vaccine HPV types at day 1 and remained negative through month 7, and had no major protocol violations. Intention to treat, generally HPV naive, and unrestricted susceptible populations were also studied. RESULTS: In the per protocol susceptible population, vaccine efficacy against lesions related to the HPV types in the vaccine was 96% for cervical intraepithelial neoplasia grade I (95% confidence interval 91% to 98%), 100% for both vulvar and vaginal intraepithelial neoplasia grade I (95% CIs 74% to 100%, 64% to 100% respectively), and 99% for condyloma (96% to 100%). Vaccine efficacy against any lesion (regardless of HPV type) in the generally naive population was 30% (17% to 41%), 75% (22% to 94%), and 48% (10% to 71%) for cervical, vulvar, and vaginal intraepithelial neoplasia grade I, respectively, and 83% (74% to 89%) for condyloma. CONCLUSIONS: Quadrivalent HPV vaccine provided sustained protection against low grade lesions attributable to vaccine HPV types (6, 11, 16, and 18) and a substantial reduction in the burden of these diseases through 42 months of follow-up. TRIAL REGISTRATIONS: NCT00092521 and NCT00092534.
|
|
| 18. |
- Joura, Elmar A., et al.
(author)
-
HPV antibody levels and clinical efficacy following administration of a prophylactic quadrivalent HPV vaccine
- 2008
-
In: Vaccine. - : Elsevier BV. - 1873-2518 .- 0264-410X. ; 26:52, s. 6844-6851
-
Journal article (peer-reviewed)abstract
- The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day I and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers. (C) 2008 Elsevier Ltd. All rights reserved.
|
|
| 19. |
- Kingma, B. R.M., et al.
(author)
-
Climapp—integrating personal factors with weather forecasts for individualised warning and guidance on thermal stress
- 2021
-
In: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:21
-
Journal article (peer-reviewed)abstract
- This paper describes the functional development of the ClimApp tool (available for free on iOS and Android devices), which combines current and 24 h weather forecasting with individual information to offer personalised guidance related to thermal exposure. Heat and cold stress assessments are based on ISO standards and thermal models where environmental settings and personal factors are integrated into the ClimApp index ranging from −4 (extremely cold) to +4 (extremely hot), while a range of −1 and +1 signifies low thermal stress. Advice for individuals or for groups is available, and the user can customise the model input according to their personal situation, including activity level, clothing, body characteristics, heat acclimatisation, indoor or outdoor situation, and geographical location. ClimApp output consists of a weather summary, a brief assessment of the thermal situation, and a thermal stress warning. Advice is provided via infographics and text depending on the user profile. ClimApp is available in 10 languages: English, Danish, Dutch, Swedish, Norwegian, Hellenic (Greek), Italian, German, Spanish and French. The tool also includes a research functionality providing a platform for worker and citizen science projects to collect individual data on physical thermal strain and the experienced thermal strain. The application may therefore improve the translation of heat and cold risk assessments and guidance for subpopulations. ClimApp provides the framework for personalising and downscaling weather reports, alerts and advice at the personal level, based on GPS location and adjustable input of individual factors.
|
|
| 20. |
- Kjaer, Susanne K., et al.
(author)
-
A Pooled Analysis of Continued Prophylactic Efficacy of Quadrivalent Human Papillomavirus (Types 6/11/16/18) Vaccine against High-grade Cervical and External Genital Lesions
- 2009
-
In: Cancer Prevention Research. - 1940-6207. ; 2:10, s. 868-878
-
Journal article (peer-reviewed)abstract
- Quadrivalent human papillomavirus (HPV) vaccine has been shown to provide protection from HPV 6/11/16/18-related cervical, vaginal, and vulvar disease through 3 years. We provide an update on the efficacy of the quadrivalent HPV vaccine against high-grade cervical, vaginal, and vulvar lesions based on end-of-study data from three clinical trials. Additionally, we stratify vaccine efficacy by several baseline characteristics, including age, smoking status, and Papanicolaou (Pap) test results. A total of 18,174 females ages 16 to 26 years were randomized and allocated into one of three clinical trials (protocols 007, 013, and 015). Vaccine or placebo was given at baseline, month 2, and month 6. Pap testing was conducted at regular intervals. Cervical and anogenital swabs were collected for HPV DNA testing. Examination for the presence of vulvar and vaginal lesions was also done. Endpoints included high-grade cervical, vulvar, or vaginal lesions (CIN 2/3, VIN 2/3, or VaIN 2/3). Mean follow-up time was 42 months post dose 1. Vaccine efficacy against HPV 6/11/16/18-related high-grade cervical lesions in the per-protocol and intention-to-treat populations was 98.2% [95% confidence interval (95% CI), 93.3-99.8] and 51.5% (95% CI, 40.6-60.6), respectively. Vaccine efficacy against HPV 6/11/16/18-related high-grade vulvar and vaginal lesions in the per-protocol and intention-to-treat populations was 100.0% (95% CI, 82.6-100.0) and 79.0% (95% CI, 56.4-91.0), respectively. Efficacy in the intention-to-treat population tended to be lower in older women, women with more partners, and women with abnormal Pap test results. The efficacy of quadrivalent HPV vaccine against high-grade cervical and external anogenital neoplasia remains high through 42 months post vaccination.
|
|
| 21. |
- Leo, P. J., et al.
(author)
-
Defining the genetic susceptibility to cervical neoplasia-A genome-wide association study
- 2017
-
In: PLoS Genetics. - : Public Library of Science (PLoS). - 1553-7404 .- 1553-7390. ; 13:8
-
Journal article (peer-reviewed)abstract
- A small percentage of women with cervical HPV infection progress to cervical neoplasia, and the risk factors determining progression are incompletely understood. We sought to define the genetic loci involved in cervical neoplasia and to assess its heritability using unbiased unrelated case/control statistical approaches. We demonstrated strong association of cervical neoplasia with risk and protective HLA haplotypes that are determined by the amino-acids carried at positions 13 and 71 in pocket 4 of HLA-DRB1 and position 156 in HLA-B. Furthermore, 36% (standard error 2.4%) of liability of HPV-associated cervical pre-cancer and cancer is determined by common genetic variants. Women in the highest 10% of genetic risk scores have approximately > 7.1% risk, and those in the highest 5% have approximately > 21.6% risk, of developing cervical neoplasia. Future studies should examine genetic risk prediction in assessing the risk of cervical neoplasia further, in combination with other screening methods.
|
|
| 22. |
- Muñoz, Nubia, et al.
(author)
-
Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women.
- 2010
-
In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 325-339
-
Journal article (peer-reviewed)abstract
- Background The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). Methods This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. Results The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. Conclusions High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
|
|
| 23. |
- Olsson, Sven-Eric, et al.
(author)
-
Evaluation of quadrivalent HPV 6/11/16/18 vaccine efficacy against cervical and anogenital disease in subjects with serological evidence of prior vaccine type HPV infection
- 2009
-
In: Human Vaccines. - 1554-8600. ; 5:10, s. 696-704
-
Journal article (peer-reviewed)abstract
- Objective: In the quadrivalent (types 6/11/16/18) HPV vaccine (GARDASIL (R)/SILGARD (R)) clinical program, 73% of women aged 16-26 were naive to all vaccine HPV types. In these women, prophylactic administration of the vaccine was highly effective in preventing HPV 6/11/16/18-related cervical disease. Of the remaining women, 15% of had evidence of past infection with one or more vaccine HPV types (seropositive and DNA negative) at the time of enrollment. Here we present an analysis in this group of women to determine the efficacy of the HPV 6/11/16/18 vaccine against new cervical and external anogenital disease related to the same vaccine HPV type which had previously been cleared. Vaccine tolerability in this previously infected population was also assessed. Results: Subjects were followed for an average of 40 months. Seven subjects in the placebo group developed cervical disease, and eight subjects developed external genital disease related to a vaccine HPV type they had previously encountered. No subject receiving HPV 6/11/16/18 vaccine developed disease to a vaccine HPV type to which they were seropositive and DNA negative at enrollment. Methods: 18,174 women were enrolled into three clinical studies. The data presented comprise a subset of these subjects (n = 2,617) who were HPV seropositive and DNA negative at enrollment (for >= 1 vaccine type). In each study, subjects were randomized in a 1:1 ratio to receive HPV 6/11/16/18 vaccine or placebo at day 1, month 2 and month 6 (without knowledge of baseline HPV status). Procedures performed for efficacy data evaluation included detailed genital examination, Pap testing and collection of cervicovaginal and external genital specimens. Analyses of efficacy were carried out in a population stratified by HPV serology and HPV DNA status at enrollment. Conclusions: These results suggest that natural HPV infection-elicited antibodies may not provide complete protection over time, however the immune response to the HPV 6/11/16/18 vaccine appears to prevent reinfection or reactivation of disease with vaccine HPV types. Vaccine-related adverse experiences were higher among subjects receiving vaccine, mostly due to increased injection site adverse experiences.
|
|
| 24. |
- Poeschl, U., et al.
(author)
-
Rainforest Aerosols as Biogenic Nuclei of Clouds and Precipitation in the Amazon
- 2010
-
In: Science. - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 329:5998, s. 1513-1516
-
Journal article (peer-reviewed)abstract
- The Amazon is one of the few continental regions where atmospheric aerosol particles and their effects on climate are not dominated by anthropogenic sources. During the wet season, the ambient conditions approach those of the pristine pre-industrial era. We show that the fine submicrometer particles accounting for most cloud condensation nuclei are predominantly composed of secondary organic material formed by oxidation of gaseous biogenic precursors. Supermicrometer particles, which are relevant as ice nuclei, consist mostly of primary biological material directly released from rainforest biota. The Amazon Basin appears to be a biogeochemical reactor, in which the biosphere and atmospheric photochemistry produce nuclei for clouds and precipitation sustaining the hydrological cycle. The prevailing regime of aerosol-cloud interactions in this natural environment is distinctly different from polluted regions.
|
|
| 25. |
- Wheeler, Cosette M., et al.
(author)
-
The Impact of Quadrivalent Human Papillomavirus (HPV; Types 6, 11, 16, and 18) L1 Virus-Like Particle Vaccine on Infection and Disease Due to Oncogenic Nonvaccine HPV Types in Sexually Active Women Aged 16-26 Years
- 2009
-
In: Journal Of Infectious Diseases. - : Oxford University Press (OUP). - 0022-1899 .- 1537-6613. ; 199:7, s. 936-944
-
Conference paper (peer-reviewed)abstract
- Background. We evaluated the impact of a quadrivalent human papillomavirus (HPV) vaccine on infection and cervical disease related to 10 nonvaccine HPV types (31, 33, 35, 39, 45, 51, 52, 56, 58, and 59) associated with >20% of cervical cancers. The population evaluated included HPV-naive women and women with preexisting HPV infection and/or HPV-related disease at enrollment. Methods. Phase 3 efficacy studies enrolled 17,622 women aged 16-26 years. Subjects underwent cervicovaginal sampling and Pap testing on day 1 and then at 6-12-month intervals for up to 4 years. HPV typing was performed on samples from enrollment and follow-up visits, including samples obtained for diagnosis or treatment of HPV-related disease. All subjects who received >= 1 dose and returned for follow-up were included. Results. Vaccination reduced the rate of HPV-31/33/45/52/58 infection by 17.7% (95% confidence interval [CI], 5.1% to 28.7%) and of cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS) by 18.8% (95% CI, 7.4% to 28.9%). Vaccination also reduced the rate of HPV-31/58/59-related CIN1-3/AIS by 26.0% (95% CI, 6.7% to 41.4%), 28.1% (95% CI, 5.3% to 45.6%), and 37.6% (95% CI, 6.0% to 59.1%), respectively. Although a modest reduction in HPV-31/33/45/52/58-related CIN2 or worse was observed, the estimated reduction was not statistically significant. Conclusions. These cross-protection results complement the vaccine's prophylactic efficacy against disease associated with HPV-6, -11, -16, and - 18. Long-term monitoring of vaccinated populations are needed to fully ascertain the population-based impact and public health significance of these findings.
|
|
| 26. |
- Garland, Anne, et al.
(author)
-
Prediction of 90-day mortality after total hip arthroplasty A SIMPLIFIED AND EXTERNALLY VALIDATED MODEL BASED ON OBSERVATIONAL REGISTRY DATA FROM SWEDEN, ENGLAND, AND WALES
- 2021
-
In: Bone & Joint Journal. - : BRITISH EDITORIAL SOC BONE & JOINT SURGERY. - 2049-4394 .- 2049-4408. ; 103B:3, s. 469-478
-
Journal article (peer-reviewed)abstract
- Aims To develop and externally validate a parsimonious statistical prediction model of 90-day mortality after elective total hip arthroplasty (THA), and to provide a web calculator for clinical usage. Methods We included 53,099 patients with cemented THA due to osteoarthritis from the Swedish Hip Arthroplasty Registry for model derivation and internal validation, as well as 125,428 patients from England and Wales recorded in the National Joint Register for England, Wales, Northern Ireland, the Isle of Man, and the States of Guernsey (NJR) for external model validation. A model was developed using a bootstrap ranking procedure with a least absolute shrinkage and selection operator (LASSO) logistic regression model combined with piecewise linear regression. Discriminative ability was evaluated by the area under the receiver operating characteristic curve (AUC). Calibration belt plots were used to assess model calibration. Results A main effects model combining age, sex, American Society for Anesthesiologists (ASA) class, the presence of cancer, diseases of the central nervous system, kidney disease, and diagnosed obesity had good discrimination, both internally (AUC = 0.78, 95% confidence interval (CI) 0.75 to 0.81) and externally (AUC = 0.75, 95% CI 0.73 to 0.76). This model was superior to traditional models based on the Charlson (AUC = 0.66, 95% CI 0.62 to 0.70) and Elixhauser (AUC = 0.64, 95% CI 0.59 to 0.68) comorbidity indices. The model was well calibrated for predicted probabilities up to 5%. Conclusion We developed a parsimonious model that may facilitate individualized risk assessment prior to one of the most common surgical interventions. We have published a web calculator to aid clinical decision-making.
|
|
| 27. |
|
|
| 28. |
- Kaviani, Sepideh, et al.
(author)
-
Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique
- 2018
-
In: Nutrition in Clinical Practice. - : Wiley. - 0884-5336. ; 33:2, s. 206-216
-
Journal article (peer-reviewed)abstract
- Background: Several indirect calorimetry (IC) instruments are commercially available, but comparative validity and reliability data are lacking. Existing data are limited by inconsistencies in protocols, subject characteristics, or single-instrument validation comparisons. The aim of this study was to compare accuracy and reliability of metabolic carts using methanol combustion as the cross-laboratory criterion. Methods: Eight 20-minute methanol burn trials were completed on 12 metabolic carts. Respiratory exchange ratio (RER) and percent O2 and CO2 recovery were calculated. Results: For accuracy, 1 Omnical, Cosmed Quark CPET (Cosmed), and both Parvos (Parvo Medics trueOne 2400) measured all 3 variables within 2% of the true value; both DeltaTracs and the Vmax Encore System (Vmax) showed similar accuracy in measuring 1 or 2, but not all, variables. For reliability, 8 instruments were shown to be reliable, with the 2 Omnicals ranking best (coefficient of variation [CV] < 1.26%). Both Cosmeds, Parvos, DeltaTracs, 1 Jaeger Oxycon Pro (Oxycon), Max-II Metabolic Systems (Max-II), and Vmax were reliable for at least 1 variable (CV ≤ 3%). For multiple regression, humidity and amount of combusted methanol were significant predictors of RER (R2 = 0.33, P <.001). Temperature and amount of burned methanol were significant predictors of O2 recovery (R2 = 0.18, P <.001); only humidity was a predictor for CO2 recovery (R2 = 0.15, P <.001). Conclusions: Omnical, Parvo, Cosmed, and DeltaTrac had greater accuracy and reliability. The small number of instruments tested and expected differences in gas calibration variability limits the generalizability of conclusions. Finally, humidity and temperature could be modified in the laboratory to optimize IC conditions.
|
|
| 29. |
- Kaviani, Sepideh, et al.
(author)
-
Determining the Accuracy and Reliability of Indirect Calorimeters Utilizing the Methanol Combustion Technique
- 2017
-
In: The FASEB Journal. - 0892-6638 .- 1530-6860. ; 31:S1
-
Journal article (peer-reviewed)abstract
- ObjectiveThere are several indirect calorimetry (IC) instruments commercially available but validity and reliability data is lacking. Site-to-site inconsistencies in protocols and subject characteristics, and comparisons to a “gold standard” instrument or method which may no longer be accurate enough, have put restraints on drawing conclusions about instruments' performance.PurposeTo compare the accuracy and reliability of different metabolic carts using the methanol combustion technique as the criterion measure.MethodsA total of eight, 20-minute methanol burn trials were completed on 12 metabolic carts (2 Cosmed Quark CPET, 2 DeltaTrac II, 2 Parvo Medics TrueOne 2400, 2 Iaeger Oxycon Pros, 2 Omnicals, a Vmax Encore, and a Max-II Metabolic System) at 11 international study sites. Methanol tests were performed at 0700, 1000, 1300, and 1600 hours on 2 consecutive days. Respiratory Exchange Ratio (RER) and percent (%) recovery of O2 and CO2 were calculated after each test.ResultsAccuracy – 1 Omnical, Cosmed, and Parvo were accurate in measuring RER and % recovery O2, while 1 DeltaTrac was also accurate for % recovery O2. The same Cosmed and Parvo, and the other DeltaTrac were accurate in measuring % recovery CO2. Reliability – 8 instruments were shown to be reliable with the two Omnicals ranking best based on the smallest coefficient of variation (CV) (all CV(s) 1.26%). Both Cosmeds, Parvos, DeltaTracs and 1 Vmax were the reliable instruments for at least one variable (CV(s) 3%). Multiple Regression– Humidity, amount of methanol combusted, and temperature were tested as predictors of IC outcomes. Humidity and amount of combusted methanol were significant predictors of RER (F (2, 60) =10.91, p<0.001, R2=0.33). Temperature and amount of burned methanol were significant predictors of % recovery O2 (F (2, 60) =8.32, p<0.001, R2=0.18) while only humidity was a predictor for % recovery CO2 (F (1, 61) =21.10, p<0.001, R2=0.15).ConclusionOmnical, Cosmed, and Parvo showed superior accuracy and reliability; however, accuracy was only found at one of two study sites. Exogenous factors such as humidity and temperature may be influencing instrument performance and could be modified in the lab to optimize IC conditions.
|
|
| 30. |
|
|
| 31. |
- Lehtinen, Matti, et al.
(author)
-
Chlamydia trachomatis infection and risk of cervical intraepithelial neoplasia
- 2011
-
In: Sexually Transmitted Infections. - : BMJ. - 1368-4973 .- 1472-3263. ; 87:5, s. 372-376
-
Journal article (peer-reviewed)abstract
- Objectives High-risk human papillomavirus (hrHPV) is the primary cause of cervical cancer. As Chlamydia trachomatis is also linked to cervical cancer, its role as a potential co-factor in the development of cervical intraepithelial neoplasia (CIN) grade 2 or higher was examined. Methods The placebo arms of two large, multinational, clinical trials of an HPV6/11/16/18 vaccine were combined. A total of 8441 healthy women aged 15-26 years underwent cervicovaginal cytology (Papanicolaou (Pap) testing) sampling and C trachomatis testing at day 1 and every 12 months thereafter for up to 4 years. Protocol-specified guidelines were used to triage participants with Pap abnormalities to colposcopy and definitive therapy. The main outcome measured was CIN. Results At baseline, 2629 (31.1%) tested positive for hrHPV DNA and 354 (4.2%) tested positive for C trachomatis. Among those with HPV16/18 infection (n = 965; 11.4%) or without HPV16/18 infection (n = 7382, 87.5%), the hazard ratios (HRs) associated with development of any CIN grade 2 according to baseline C trachomatis status were 1.82 (95% CI: 1.06 to 3.14) and 1.74 (95% CI 1.05 to 2.90), respectively. The results were comparable when only the 12 most common hrHPV infections were considered, but the excess risk disappeared when the outcome was expanded to include CIN grade 3 or worse. Conclusion Further studies based on larger cohorts with longitudinal follow-up in relation to the C trachomatis acquisition and a thorough evaluation of temporal relationships of infections with hrHPV types, C trachomatis and cervical neoplasia are needed to demonstrate whether and how in some situations C trachomatis sets the stage for cervical carcinogenesis. Trial registration NCT00092521 and NCT00092534.
|
|
| 32. |
- Lightfoot, J. Timothy, et al.
(author)
-
Biological/Genetic Regulation of Physical Activity Level : Consensus From Genbiopac
- 2018
-
In: Medicine & Science in Sports & Exercise. - 0195-9131 .- 1530-0315. ; 50:4, s. 863-873
-
Research review (peer-reviewed)abstract
- Purpose: Physical activity unquestionably maintains and improves health; however, physical activity levels globally are low and not rising despite all the resources devoted to this goal. Attention in both the research literature and the public policy domain has focused on social-behavioral factors; however, a growing body of literature suggests that biological determinants play a significant role in regulating physical activity levels. For instance, physical activity level, measured in various manners, has a genetic component in both humans and nonhuman animal models. This consensus article, developed as a result of an American College of Sports Medicine-sponsored round table, provides a brief review of the theoretical concepts and existing literature that supports a significant role of genetic and other biological factors in the regulation of physical activity.Conclusions: Future research on physical activity regulation should incorporate genetics and other biological determinants of physical activity instead of a sole reliance on social and other environmental determinants.
|
|
| 33. |
- Machalek, Dorothy A., et al.
(author)
-
Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium : a systematic review and meta-analysis
- 2020
-
In: The Lancet - Infectious diseases. - : Elsevier. - 1473-3099 .- 1474-4457. ; 20:11, s. 1302-1314
-
Research review (peer-reviewed)abstract
- BACKGROUND: Mycoplasma genitalium is now recognised as an important bacterial sexually transmitted infection. We summarised data from studies of mutations associated with macrolide and fluoroquinolone resistance in M genitalium to establish the prevalence of resistance. We also investigated temporal trends in resistance and aimed to establish the association between resistance and geographical location.METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and MEDLINE for studies that included data for the prevalence of mutations associated with macrolide and fluoroquinolone resistance in M genitalium published in any language up to Jan 7, 2019. We defined prevalence as the proportion of M genitalium samples positive for key mutations associated with azithromycin resistance (23S rRNA gene, position 2058 or 2059) or moxifloxacin resistance (S83R, S83I, D87N, or D87Y in parC), or both, among all M genitalium samples that were successfully characterised. We used random-effects meta-analyses to calculate summary estimates of prevalence. Subgroup and meta-regression analyses by WHO region and time period were done. This study was registered with PROSPERO, number CRD42016050370.RESULTS: Overall, 59 studies from 21 countries met the inclusion criteria for our study: 57 studies of macrolide resistance (8966 samples), 25 of fluoroquinolone resistance (4003 samples), and 22 of dual resistance to macrolides and fluoroquinolones (3280 samples). The summary prevalence of mutations associated with macrolide resistance among M genitalium samples was 35·5% (95% CI 28·8-42·5); prevalence increased from 10·0% (95% CI 2·6-20·1%) before 2010, to 51·4% (40·3-62·4%) in 2016-17 (p<0·0001). Prevalence of mutations associated with macrolide resistance was significantly greater in samples in the WHO Western Pacific and Americas regions than in those from the WHO European region. The overall prevalence of mutations associated with fluoroquinolone resistance in M genitalium samples was 7·7% (95% CI 4·5-11·4%). Prevalence did not change significantly over time, but was significantly higher in the Western Pacific region than in the European region. Overall, the prevalence of both mutations associated with macrolide resistance and those associated with fluoroquinolone resistance among M genitalium samples was 2·8% (1·3-4·7%). The prevalence of dual resistance did not change significantly over time, and did not vary significantly by geographical region.INTERPRETATION: Global surveillance and measures to optimise the efficacy of treatments-including resistance-guided strategies, new antimicrobials, and antimicrobial combination approaches-are urgently needed to ensure cure in a high proportion of M genitalium infections and to prevent further spread of resistant strains.
|
|
| 34. |
|
|
| 35. |
- Rysinska, A., et al.
(author)
-
Aseptic loosening after total hip arthroplasty and the risk of cardiovascular disease: A nested case-control study
- 2018
-
In: Plos One. - : Public Library of Science (PLoS). - 1932-6203. ; 13:11
-
Journal article (peer-reviewed)abstract
- Background Patients with surgically treated osteoarthritis of the hip have an increased risk of cardiovascular morbidity and mortality many years after the operation compared with controls. Our hypothesis is that this increased risk after total hip arthroplasty (THA) is mediated by development of periprosthetic osteolysis leading to aseptic loosening of the implant. Methods We conducted a nation-wide, nested, case-control study consisting of patients receiving a cemented THA due to osteoarthritis between the years 1992 and 2005. Our study population included a total of 14,430 subjects identified in the Swedish hip arthroplasty register and linked to the Swedish National Patient Register. The case group consisted of patients (n = 2,886) who underwent reoperation of the treated hip due to osteolysis or aseptic loosening at any time within five years after the index surgery. Each case was matched with four controls (n = 11,544) who had not undergone reoperation. The main outcomes were cardiovascular events i.e. myocardial infarction, heart failure and cerebral infarction according to ICD-codes and time to the first cardiovascular event during the exposure period. Outcomes were subgrouped into cardiac and cerebral events. We used regression models to calculate the incidence rates and adjusted our results for confounders. Findings Overall, 5.1% of patients had cardiac events, with slightly more overall cardiovascular events occurring in the control group (8.1% vs. 6.7%, odds ratio 0.8, 95% confidence interval (CI) 0.7 to 1.0). After adjusting for confounders, the case group had an increased relative risk of 1.3 (95% confidence interval (CI) 1.1 to 1.3) for total number of cardiovascular events. Similar effect sizes were observed for time to first event. Interpretation Patients with osteoarthritis who received THA and subsequently underwent a revision operation due to loosening had a higher relative risk of developing cardiovascular events than controls. Thus there is an association which could be explained by a common inflammatory disease pathway that requires further experimental research. Copyright: © 2018 Rysinska et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|
|
| 36. |
|
|
| 37. |
- Bance, Manohar, et al.
(author)
-
Effects of tensor tympani muscle contraction on the middle ear and markers of a contracted muscle.
- 2013
-
In: The Laryngoscope. - : Wiley. - 1531-4995 .- 0023-852X. ; 123:4, s. 1021-1027
-
Journal article (peer-reviewed)abstract
- OBJECTIVES/HYPOTHESIS: Many otologic disorders have been attributed to dysfunction of the tensor tympani muscle, including tinnitus, otalgia, Meniere's disease and sensorineural hearing loss. The objective of this study was to determine adequate stimuli for tensor tympani contraction in humans and determine markers of the hypercontracted state that could be used to detect this process in otologic disease. STUDY DESIGN: Multiple types of studies. METHODS: Studies included 1) measuring middle ear impedance changes in response to orbital puffs of air, facial stroking, and self-vocalization; 2) measuring changes in stapes and eardrum vibrations and middle ear acoustic impedance in response to force loading of the tensor tympani in fresh human cadaveric temporal bones; 3) measuring changes in acoustic impedance in two subjects who could voluntarily contract their tensor tympani, and performing an audiogram with the muscle contracted in one of these subjects; and 4) developing a lumped parameter computer model of the middle ear while simulating various levels of tensor tympani contraction. RESULTS: Orbital jets of air are the most effective stimuli for eliciting tensor tympani contraction. As markers for tensor tympani contraction, all investigations indicate that tensor tympani hypercontraction should result in a low-frequency hearing loss, predominantly conductive, with a decrease in middle ear compliance. CONCLUSIONS: These markers should be searched for in otologic pathology states where the tensor tympani is suspected of being hypercontracted.
|
|
| 38. |
- Berglund, Anders, et al.
(author)
-
ProVal : A protein-scoring function for the selection of native and near-native folds
- 2004
-
In: Proteins. - : Wiley-Liss, Inc. - 0887-3585 .- 1097-0134. ; 54:2, s. 289-302
-
Journal article (peer-reviewed)abstract
- A low-resolution scoring function for the selection of native and near-native structures from a set of predicted structures for a given protein sequence has been developed. The scoring function, ProVal (Protein Validate), used several variables that describe an aspect of protein structure for which the proximity to the native structure can be assessed quantitatively. Among the parameters included are a packing estimate, surface areas, and the contact order. A partial least squares for latent variables (PLS) model was built for each candidate set of the 28 decoy sets of structures generated for 22 different proteins using the described parameters as independent variables. The C(alpha) RMS of the candidate structures versus the experimental structure was used as the dependent variable. The final generalized scoring function was an average of all models derived, ensuring that the function was not optimized for specific fold classes or method of structure generation of the candidate folds. The results show that the crystal structure was scored best in 64% of the 28 test sets and was clearly separated from the decoys in many examples. In all the other cases in which the crystal structure did not rank first, it ranked within the top 10%. Thus, although ProVal could not distinguish between predicted structures that were similar overall in fold quality due to its inherently low resolution, it can clearly be used as a primary filter to eliminate approximately 90% of fold candidates generated by current prediction methods from all-atom modeling and further evaluation. The correlation between the predicted and actual C(alpha) RMS values varies considerably between the candidate fold sets.
|
|
| 39. |
- Cnudde, Peter, 1970, et al.
(author)
-
Do Patients Live Longer After THA and Is the Relative Survival Diagnosis-specific?
- 2018
-
In: Clinical orthopaedics and related research. - : Ovid Technologies (Wolters Kluwer Health). - 1528-1132 .- 0009-921X. ; 476, s. 1166-1175
-
Journal article (peer-reviewed)abstract
- Hip replacements are successful in restoring mobility, reducing pain, and improving quality of life. However, the association between THA and the potential for increased life expectancy (as expressed by mortality rate) is less clear, and any such association could well be influenced by diagnosis and patient-related, socioeconomic, and surgical factors, which have not been well studied.(1) After controlling for birth year and sex, are Swedish patients who underwent THA likely to survive longer than individuals in the general population? (2) After controlling for relevant patient-related, socioeconomic/demographic factors and surgical factors, does relative survival differ across the various diagnoses for which THAs were performed in Sweden?Data from the Swedish Hip Arthroplasty Register, linked to administrative health databases, were used for this study. We identified 131,808 patients who underwent THA between January 1, 1999, and December 31, 2012. Of these, 21,755 had died by the end of followup. Patient- and surgery-specific data in combination with socioeconomic data were available for analysis. We compared patient survival (relative survival) with age- and sex-matched survival data in the entire Swedish population according to Statistics Sweden. We used multivariable modeling proceeded with a Cox proportional hazards model in transformed time.Patients undergoing elective THA had a slightly improved survival rate compared with the general population for approximately 10 years after surgery. At 1 year after surgery, the survival in patients undergoing THA was 1% better than the expected survival (r = 1.01; 95% confidence interval [CI], 1.01-1.02; p < 0.001); at 5 years, this increased to 3% (r = 1.03; 95% CI, 1.03-1.03; p < 0.001); at 10 years, the difference was 2% (r = 1.02; 95% CI, 1.02-1.03; p < 0.001); and by 12 years, there was no difference between patients undergoing THA and the general population (r = 1.01; 95% CI, 0.99-1.02; p = 0.13). Using the diagnosis of primary osteoarthritis as a reference, hip arthroplasties performed for sequelae of childhood hip diseases had a similar survival rate (hazard ratio [HR], 1.02; 95% CI, 0.88-1.18; p = 0.77). Patients undergoing surgery for osteonecrosis of the femoral head (HR, 1.69; 95% CI, 1.60-1.79; p < 0.001), inflammatory arthritis (HR, 1.49; 95% CI, 1.38-1.61; p < 0.001), and secondary osteoarthritis (HR, 2.46; 95% CI, 2.03-2.99; p < 0.001) all had poorer relative survival. Comorbidities and the Elixhauser comorbidity index had a negative association with relative survival. Level of achieved education (middle level of education: HR, 0.90, 95% CI, 0.87-0.93, p < 0.001; high level: 0.76, 95% CI, 0.73-0.80, p < 0.001) and marital status (single status: HR, 1.33; 95% CI, 1.28-1.38; p < 0.001) were also negatively associated with survival.Whereas it has been known that in most patients, THA improves quality of life, this study demonstrates that it also is associated with a slightly increased life expectancy that lasts for approximately 10 years after surgery, especially among patients whose diagnosis was primary osteoarthritis. This adds further proof of a health-economic value for this surgical intervention. The reasons for the increase in relative survival are unknown but are probably multifactorial.Level III, therapeutic study.
|
|
| 40. |
- Didion, JP, et al.
(author)
-
R2d2 Drives Selfish Sweeps in the House Mouse
- 2016
-
In: Molecular biology and evolution. - : Oxford University Press (OUP). - 1537-1719 .- 0737-4038. ; 33:6, s. 1381-1395
-
Journal article (peer-reviewed)
|
|
| 41. |
|
|
| 42. |
|
|
| 43. |
- Garland, SM, et al.
(author)
-
Imiquimod 5% cream is a safe and effective self-applied treatment for anogenital warts--results of an open-label, multicentre Phase IIIB trial
- 2001
-
In: International journal of STD & AIDS. - : SAGE Publications. - 0956-4624 .- 1758-1052. ; 12:11, s. 722-729
-
Journal article (peer-reviewed)abstract
- Our objective was to determine the efficacy and safety of imiquimod 5% cream in the treatment of external genital/perianal warts in an open-label Phase IIIB trial. Patients applied imiquimod 5% cream 3 times per week, for up to 16 weeks. Those who cleared their warts were monitored during a 6-month follow-up period. If their warts recurred, or new warts developed during this time, patients could be re-treated for up to 16 additional weeks. Patients who experienced partial clearance during the initial treatment period entered an extended treatment period of up to an additional 16 weeks. A total of 943 patients from 114 clinic sites in 20 countries participated in this study. Complete clinical clearance was observed in 451/943 (47.8%) patients (intent-to-treat (ITT) analysis) during the initial treatment period, with clearance in an additional 52 (5.5%) patients during the extended treatment period beyond 16 weeks. The overall clearance rate for the combined treatment periods was 53.3%. In a treatment failure analysis, the overall clearance rate was 65.5%; a greater proportion of female patients (75.5%) experienced complete clearance than male patients (56.9%). Low recurrence rates, of 8.8% and 23.0%, were observed at the end of the 3- and 6-month follow-up periods, respectively. The sustained clearance rates (patients who cleared during treatment and remained clear at the end of the follow-up period) after 3 and 6 months were 41.6% and 33.0% (ITT analysis), respectively. Local erythema occurred in 67% of patients. In the majority of patients local skin reactions were of mild to moderate severity. In conclusion, imiquimod 5% cream is an effective self-applied treatment for external genital/perianal warts when applied for up to 16 weeks and is well tolerated for up to 32 weeks.
|
|
| 44. |
|
|
| 45. |
|
|
| 46. |
|
|
| 47. |
- Lunt, Daniel J., et al.
(author)
-
The DeepMIP contribution to PMIP4 : experimental design for model simulations of the EECO, PETM, and pre-PETM (version 1.0)
- 2017
-
In: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 10:2, s. 889-901
-
Journal article (peer-reviewed)abstract
- Past warm periods provide an opportunity to evaluate climate models under extreme forcing scenarios, in particular high (>800 ppmv) atmospheric CO2 concentrations. Although a post hoc intercomparison of Eocene (similar to 50 Ma) climate model simulations and geological data has been carried out previously, models of past high-CO2 periods have never been evaluated in a consistent framework. Here, we present an experimental design for climate model simulations of three warm periods within the early Eocene and the latest Paleocene (the EECO, PETM, and pre-PETM). Together with the CMIP6 pre-industrial control and abrupt 4 x CO2 simulations, and additional sensitivity studies, these form the first phase of DeepMIP - the Deep-time Model Intercomparison Project, itself a group within the wider Paleo-climate Modelling Intercomparison Project (PMIP). The experimental design specifies and provides guidance on boundary conditions associated with palaeogeography, greenhouse gases, astronomical configuration, solar constant, land surface processes, and aerosols. Initial conditions, simulation length, and output variables are also specified. Finally, we explain how the geological data sets, which will be used to evaluate the simulations, will be developed.
|
|
| 48. |
- Mesher, David, et al.
(author)
-
Population-level effects of human papillomavirus vaccination programs on infections with nonvaccine genotypes
- 2016
-
In: Emerging Infectious Diseases. - : Centers for Disease Control and Prevention (CDC). - 1080-6040 .- 1080-6059. ; 22:10, s. 1732-1740
-
Journal article (peer-reviewed)abstract
- We analyzed human papillomavirus (HPV) prevalences during prevaccination and postvaccination periods to consider possible changes in nonvaccine HPV genotypes after introduction of vaccines that confer protection against 2 high-risk types, HPV16 and HPV18. Our meta-analysis included 9 studies with data for 13,886 girls and women ≤19 years of age and 23,340 women 20–24 years of age. We found evidence of cross-protection for HPV31 among the younger age group after vaccine introduction but little evidence for reductions of HPV33 and HPV45. For the group this same age group, we also found slight increases in 2 nonvaccine high-risk HPV types (HPV39 and HPV52) and in 2 possible high-risk types (HPV53 and HPV73). However, results between age groups and vaccines used were inconsistent, and the increases had possible alternative explanations; consequently, these data provided no clear evidence for type replacement. Continued monitoring of these HPV genotypes is important.
|
|
| 49. |
- Pettersson-Kymmer, Ulrika, et al.
(author)
-
HLA and KIR Associations of Cervical Neoplasia
- 2018
-
In: Journal of Infectious Diseases. - : Oxford University Press. - 0022-1899 .- 1537-6613. ; 218:12, s. 2006-2015
-
Journal article (peer-reviewed)abstract
- Background: Cervical cancer is the fourth most common cancer in women, and we recently reported human leukocyte antigen (HLA) alleles showing strong associations with cervical neoplasia risk and protection. HLA ligands are recognised by killer immunoglobulin-like receptors (KIRs) expressed on a range of immune cell subsets, governing their proinflammatory activity. We hypothesized that the inheritance of particular HLA-KIR combinations would increase cervical neoplasia risk.Methods: Here, we used HLA and KIR dosages imputed from SNP genotype data from 2,143 cervical neoplasia cases and 13,858 healthy controls of European decent.Results: Four novel HLA alleles were identified in association with cervical neoplasia: HLA-DRB3*9901 (OR=1.24, P=2.49×10-9), HLA-DRB5*0101 (OR=1.29, P=2.26×10-8), HLA-DRB5*9901 (OR=0.77, P=1.90×10-9) and HLA-DRB3*0301 (OR=0.63, P=4.06×10-5), due to their linkage disequilibrium with known cervical neoplasia-associated HLA-DRB1 alleles. We also found homozygosity of HLA-C1 group alleles is a protective factor for HPV16-related cervical neoplasia (C1/C1, OR=0.79, P=0.005). This protective association was restricted to carriers of either KIR2DL2 (OR=0.67, P=0.00045) or KIR2DS2 (OR=0.69, P=0.0006).Conclusions: Our findings suggest that HLA-C1 group alleles play a role in protecting against HPV16-related cervical neoplasia, mainly through a KIR-mediated mechanism.
|
|
| 50. |
|
|
