| 1. |
- Franco, Irene, et al.
(författare)
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Whole genome DNA sequencing provides an atlas of somatic mutagenesis in healthy human cells and identifies a tumor-prone cell type
- 2019
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: The lifelong accumulation of somatic mutations underlies age-related phenotypes and cancer. Mutagenic forces are thought to shape the genome of aging cells in a tissue-specific way. Whole genome analyses of somatic mutation patterns, based on both types and genomic distribution of variants, can shed light on specific processes active in different human tissues and their effect on the transition to cancer. Results: To analyze somatic mutation patterns, we compile a comprehensive genetic atlas of somatic mutations in healthy human cells. High-confidence variants are obtained from newly generated and publicly available whole genome DNA sequencing data from single non-cancer cells, clonally expanded in vitro. To enable a well-controlled comparison of different cell types, we obtain single genome data (92% mean coverage) from multi-organ biopsies from the same donors. These data show multiple cell types that are protected from mutagens and display a stereotyped mutation profile, despite their origin from different tissues. Conversely, the same tissue harbors cells with distinct mutation profiles associated to different differentiation states. Analyses of mutation rate in the coding and non-coding portions of the genome identify a cell type bearing a unique mutation pattern characterized by mutation enrichment in active chromatin, regulatory, and transcribed regions. Conclusions: Our analysis of normal cells from healthy donors identifies a somatic mutation landscape that enhances the risk of tumor transformation in a specific cell population from the kidney proximal tubule. This unique pattern is characterized by high rate of mutation accumulation during adult life and specific targeting of expressed genes and regulatory regions.
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| 2. |
- Henriksson, Otto, 1976-, et al.
(författare)
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Protection against cold in prehospital care : wet clothing removal or addition of a vapor barrier
- 2015
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Ingår i: Wilderness & environmental medicine (Print). - : Elsevier. - 1080-6032 .- 1545-1534. ; 26:1, s. 11-20
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The purpose of this study was to evaluate the effect of wet clothing removal or the addition of a vapor barrier in shivering subjects exposed to a cold environment with only limited insulation available.METHODS: Volunteer subjects (n = 8) wearing wet clothing were positioned on a spineboard in a climatic chamber (-18.5°C) and subjected to an initial 20 minutes of cooling followed by 30 minutes of 4 different insulation interventions in a crossover design: 1) 1 woolen blanket; 2) vapor barrier plus 1 woolen blanket; 3) wet clothing removal plus 1 woolen blanket; or 4) 2 woolen blankets. Metabolic rate, core body temperature, skin temperature, and heart rate were continuously monitored, and cold discomfort was evaluated at 5-minute intervals.RESULTS: Wet clothing removal or the addition of a vapor barrier significantly reduced metabolic rate (mean difference ± SE; 14 ± 4.7 W/m(2)) and increased skin temperature rewarming (1.0° ± 0.2°C). Increasing the insulation rendered a similar effect. There were, however, no significant differences in core body temperature or heart rate among any of the conditions. Cold discomfort (median; interquartile range) was significantly lower with the addition of a vapor barrier (4; 2-4.75) and with 2 woolen blankets (3.5; 1.5-4) compared with 1 woolen blanket alone (5; 3.25-6).CONCLUSIONS: In protracted rescue scenarios in cold environments with only limited insulation available, wet clothing removal or the use of a vapor barrier is advocated to limit the need for shivering thermogenesis and improve the patient's condition on admission to the emergency department.
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| 3. |
- Henriksson, Otto, 1976-, et al.
(författare)
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Protection against cold in prehospital care : evaporative heat loss reduction by wet clothing removal or the addition of a vapour barrier - a thermal manikin study
- 2012
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Ingår i: Prehospital and Disaster Medicine. - 1049-023X .- 1945-1938. ; 26:6, s. 1-6
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the prehospital care of a cold and wet person, early application of adequate insulation is of utmost importance to reduce cold stress, limit body core cooling, and prevent deterioration of the patient’s condition. Most prehospital guidelines on protection against cold recommend the removal of wet clothing prior to insulation, and some also recommend the use of a waterproof vapor barrier to reduce evaporative heat loss. However, there is little scientific evidence of the effectiveness of these measures.Objective: Using a thermal manikin with wet clothing, this study was conducted to determine the effect of wet clothing removal or the addition of a vapor barrier on thermal insulation and evaporative heat loss using different amounts of insulation in both warm and cold ambient conditions.Methods: A thermal manikin dressed in wet clothing was set up in accordance with the European Standard for assessing requirements of sleeping bags, modified for wet heat loss determination, and the climatic chamber was set to -15 degrees Celsius (°C) for cold conditions and +10°C for warm conditions. Three different insulation ensembles, one, two or seven woollen blankets, were chosen to provide different levels of insulation. Five different test conditions were evaluated for all three levels of insulation ensembles: (1) dry underwear; (2) dry underwear with a vapor barrier; (3) wet underwear; (4) wet underwear with a vapor barrier; and (5) no underwear. Dry and wet heat loss and thermal resistance were determined from continuous monitoring of ambient air temperature, manikin surface temperature, heat flux and evaporative mass loss rate.Results: Independent of insulation thickness or ambient temperature, the removal of wet clothing or the addition of a vapor barrier resulted in a reduction in total heat loss of 19-42%. The absolute heat loss reduction was greater, however, and thus clinically more important in cold environments when little insulation is available. A similar reduction in total heat loss was also achieved by increasing the insulation from one to two blankets or from two to seven blankets.Conclusion: Wet clothing removal or the addition of a vapor barrier effectively reduced evaporative heat loss and might thus be of great importance in prehospital rescue scenarios in cold environments with limited insulation available, such as in mass-casualty situations or during protracted evacuations in harsh conditions.
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| 4. |
- Lundgren, Peter, 1977-
(författare)
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Protection and treatment of hypothermia in prehospital trauma care : with emphasis on active warming
- 2012
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: In prehospital trauma care active warming is recommended to aid in protection from further cooling. However, scientific evidence of the effectiveness of active warming in a clinical setting is scarce. Also, evaluating the effectiveness of active warming, especially in harsh ambient conditions, by objective measures, is difficult. Objective: To evaluate the effectiveness of field applicabe heat sources (I) and to evaluate active warming intervention in a prehospital clinical setting (II and III). To evaluate reliability and validity of the Cold Discomfort Scale (CDS), a subjective judgement scale for assessment of the thermal state of patients in a cold environment (IV). Methods: In a laboratory trial, non-shivering hypothermic subjects (n=5), were cooled in 8 ºC water followed by spontaneous warming, a charcoal heater, two flexible hot-water bags or two chemical heat pads, all applied to the chest and upper back (I). Oesophageal temperature, skin temperature, heat flux, oxygen consumption, respiratory rate and, heart rate were measured. In two clinical randomized trials, shivering patients during road and air ambulance transport (II) and during field treatment (III) were randomized to either passive warming alone (n=22 and n=9) or to passive warming with the addition of a chemical heat pad (n=26 and n=11). Body core temperature, respiratory rate, heart rate, blood pressure (II) and the patients’ subjective sensation of thermal comfort (II and III) were measured. In a laboratory trial, shivering subjects were exposed to – 20 ºC (n=22). The CDS was evaluated regarding reliability, defined as test-retest stability, and criterion validity, defined as the ability to detect changes in cold discomfort due to changes in cumulative cold stress (IV). Results: In non-shivering hypothermic subjects postcooling afterdrop was significantly less for the chemical heat pads, but not for the hot water bags and the charcoal heater, compared to spontaneous warming (I). Temperature drop during the entire warming phase was significantly less for all the heat sources respectively, compared to spontaneous warming (I). During road and air ambulance transport, ear canal temperature was significantly increased and cold discomfort significantly decreased, both in patients assigned to passive warming only, and in patients assigned to additional active warming (II). During field treatment, cold discomfort was significantly reduced in patients assigned to additional active warming, but remained the same in patients assigned to passive warming only (III). Weighted kappa coefficient, describing test-retest stability, was 0.84 (IV). CDS ratings were significantly increased during each 30 minutes interval (IV). Conclusion: In non-shivering hypothermic subjects, heat sources were effective to attenuate afterdrop, when providing high heat content over a large surface area and effective to continue to increase body core temperature when providing sustained high heat content. In shivering trauma patients, adequate passive warming were sufficient treatment to prevent afterdrop, to slowly increase body core temperature, and to reduce cold discomfort. If inadequate passive warming, additional active warming was required to reduce cold discomfort. The CDS, a subjective judgement scale for assessment of the thermal state of patients in a cold environment seemed to be reliable regarding test-retest stability and valid regarding ability to detect change in cumulative cold stress.
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| 5. |
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| 6. |
- Lundgren, Peter, 1977-, et al.
(författare)
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Validity and reliability of the Cold Discomfort Scale : a subjective judgement scale for the assessment of patient thermal state in a cold environment.
- 2014
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Ingår i: Journal of clinical monitoring and computing. - : Springer Science and Business Media LLC. - 1387-1307 .- 1573-2614. ; 28:3, s. 287-291
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Tidskriftsartikel (refereegranskat)abstract
- Complementary measures for the assessment of patient thermoregulatory state, such as subjective judgement scales, might be of considerable importance in field rescue scenarios where objective measures such as body core temperature, skin temperature, and oxygen consumption are difficult to obtain. The objective of this study was to evaluate, in healthy subjects, the reliability of the Cold Discomfort Scale (CDS), a subjective judgement scale for the assessment of patient thermal state in cold environments, defined as test-retest stability, and criterion validity, defined as the ability to detect a difference in cumulative cold stress over time. Twenty-two healthy subjects performed two consecutive trials (test-retest). Dressed in light clothing, the subjects remained in a climatic chamber set to -20 °C for 60 min. CDS ratings were obtained every 5 min. Reliability was analysed by test-retest stability using weighted kappa coefficient that was 0.84 including all the 5-min interval measurements. When analysed separately at each 5-min interval the weighted kappa coefficients were was 0.48-0.86. Criterion validity was analysed by comparing median CDS ratings of a moving time interval. The comparison revealed that CDS ratings were significantly increased for every interval of 10, 15, and 30 min (p < 0.001) but not for every interval of 5 min. In conclusion, in a prehospital scenario, subjective judgement scales might be a valuable measure for the assessment of patient thermal state. The results of this study indicated that, in concious patients, the CDS may be both reliable and valid for such purpose.
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| 7. |
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| 8. |
- Furukawa, Toshi A., et al.
(författare)
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Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression : a systematic review and component network meta-analysis using individual data
- 2021
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Ingår i: Lancet psychiatry. - London, United Kingdom : Elsevier. - 2215-0374 .- 2215-0366. ; 8:6, s. 500-511
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Forskningsöversikt (refereegranskat)abstract
- Findings We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42.0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD -1.83 [95% credible interval (CrI) -2.90 to -0.80]) and that relaxation might be harmful (1.20 [95% CrI 0.17 to 2.27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0.32 [95% CrI 0.13 to 0.93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. 511
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| 9. |
- Henriksson, Otto, 1976-, et al.
(författare)
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Protection against cold in prehospital care — thermal insulation properties of blankets and rescue bags in different wind conditions
- 2009
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Ingår i: Journal of Prehospital and Disaster Medicine. ; 24:5, s. 408-415
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In a cold,wet, or windy environment, cold exposure can be considerable for an injured or ill person. The subsequent autonomous stress response initially will increase circulatory and respiratory demands, and as body core temperature declines, the patient’s condition might deteriorate. Therefore, the application of adequate insulation to reduce cold exposure and prevent body core cooling is an important part of prehospital primary care, but recommendations for what should be used in the field mostly depend on tradition and experience, not on scientific evidence. Objective: The objective of this study was to evaluate the thermal insulation properties in different wind conditions of 12 different blankets and rescue bags commonly used by prehospital rescue and ambulance services. Methods: The thermal manikin and the selected insulation ensembles were setup inside a climatic chamber in accordance to the modified European Standard for assessing requirements of sleeping bags. Fans were adjusted to provide low (< 0.5 m/s), moderate (2–3 m/s) and high (8–9 m/s) wind conditions. During steady state thermal transfer, the total resultant insulation value, Itr (m2 °C/Wclo; where °C = degrees Celcius, and W = watts), was calculated from ambient air temperature (°C), manikin surface temperature (°C), and heat flux (W/m2). Results: In the low wind condition, thermal insulation of the evaluated ensembles correlated to thickness of the ensembles, ranging from 2.0 to 6.0 clo (1 clo = 0.155 m2 °C/W), except for the reflective metallic foil blankets that had higher values than expected. In moderate and high wind conditions, thermal insulation was best preserved for ensembles that were windproof and resistant to the compressive effect of the wind, with insulation reductions down to about 60–80% of the original insulation capacity, whereas wind permeable and/or lighter materials were reduced down to about 30–50% of original insulation capacity. Conclusions: The evaluated insulation ensembles might all be used for prehospital protection against cold, either as single blankets or in multiple layer combinations, depending on ambient temperatures. However, with extended outdoor, on-scene durations, such as during prolonged extrications or in multiple casualty situations, the results of this study emphasize the importance of using a windproof and compression resistant outer ensemble to maintain adequate insulation capacity.
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| 10. |
- Johansson, Peter, 1962-, et al.
(författare)
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An internet-based cognitive behavioral therapy program adapted to patients with cardiovascular disease and depression : Randomized controlled trial
- 2019
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Ingår i: Journal of Medical Internet Research. - Toronto, Canada : Journal of Medical Internet Research. - 1438-8871. ; 21:10, s. 1-14
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Tidskriftsartikel (refereegranskat)abstract
- Background: Depression is a common cause of reduced well-being and prognosis in patients with cardiovascular disease (CVD). However, there is a lack of effective intervention strategies targeting depression.Objective: The study aimed to evaluate the effects of a nurse-delivered and adapted internet-based cognitive behavioral therapy (iCBT) program aimed at reducing depression in patients with CVD.Methods: A randomized controlled trial was conducted. A total of 144 patients with CVD with at least mild depression (Patient Health Questionnaire–9 [PHQ-9] score ≥5) were randomized 1:1 to a 9-week program of iCBT (n=72) or an active control participating in a Web-based discussion forum (online discussion forum [ODF], n=72). The iCBT program, which included 7 modules, was adapted to fit patients with CVD. Nurses with an experience of CVD care provided feedback and a short introduction to cognitive behavioral therapy. The primary outcome, depression, was measured using PHQ-9. Secondary outcomes were depression measured using the Montgomery-Åsberg Depression Rating Scale–self-rating version (MADRS-S), health-related quality of life (HRQoL) measured using Short Form 12 (SF-12) survey and EuroQol Visual Analogue Scale (EQ-VAS), and the level of adherence. An intention-to-treat analysis with multiple imputations was used. Between-group differences in the primary and secondary outcomes were determined by the analysis of covariance, and a sensitivity analysis was performed using mixed models. Results: Compared with ODF, iCBT had a significant and moderate treatment effect on the primary outcome depression (ie, PHQ-9; mean group difference=−2.34 [95% CI −3.58 to −1.10], P<.001, Cohen d=0.62). In the secondary outcomes, compared with ODF, iCBT had a significant and large effect on depression (ie, MADRS-S; P<.001, Cohen d=0.86) and a significant and moderate effect on the mental component scale of the SF-12 (P<.001, Cohen d=0.66) and the EQ-VAS (P<.001, Cohen d=0.62). Overall, 60% (n=43) of the iCBT group completed all 7 modules, whereas 82% (n=59) completed at least half of the modules. No patients were discontinued from the study owing to a high risk of suicide or deterioration in depression.Conclusions: Nurse-delivered iCBT can reduce depression and improve HRQoL in patients with CVD, enabling treatment for depression in their own homes and at their preferred time.
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