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  • Holmström, Pontus, et al. (författare)
  • The effects of high altitude ascent on splenic contraction and the diving response during voluntary apnea
  • 2021
  • Ingår i: Experimental Physiology. - 0958-0670 .- 1469-445X. ; 106:1, s. 160-174
  • Tidskriftsartikel (refereegranskat)abstract
    • Voluntary apnea causes splenic contraction and reductions in heart rate (HR; bradycardia), and subsequent transient increases in hemoglobin concentration ([Hb]). Ascent to high altitude (HA) induces systemic hypoxia and reductions in oxygen saturation (SpO2 ), which may cause tonic splenic contraction, which may contribute to hematological acclimatization associated with HA ascent. We measured resting cardiorespiratory variables (HR, SpO2 , [Hb]) and resting splenic volume (via ultrasound) during incremental ascent from 1400 m (day 0), to 3440 m (day 3), 4240 m (day 7), and 5160 m (day 10) in non-acclimatized native lowlanders during assent to HA in the Nepal Himalaya. In addition, apnea-induced responses in HR, SpO2 and splenic volume were measured before and after two separate voluntary maximal apneas (A1-A2) at 1400 m, 3440 m and 4240 m. Resting spleen volume decreased -14.3% (-15.2 mL)/1000 m with ascent, from 140±41 mL (1400 m), to 108±28 mL (3440 m; P > 0.99), 94±22 mL (4240 m; P = 0.009) and 84±28 mL (5160 m; P = 0.029), with concomitant increases in [Hb] from 125±18.3 g/L (1400 m) to 128±10.4 g/L (3440 m), 138.8±12.7 g/L (4240 m) and 157.5±8 g/L (5160 m; P = 0.021). Apnea-induced splenic contraction was 50±15 mL (1400 m), 44±17 mL (3440 m; P > 0.99) and 26±8 mL (4240 m; P = 0.002), but was not consistently associated with increases in [Hb]. The apnea-induced bradycardia was more pronounced at 3440 m (A1:P = 0.04; A2:P = 0.094) and at 4240 m (A1:P = 0.037 A2:P = 0.006) compared to values at 1400 m. We conclude that hypoxia-induced splenic contraction at rest (a) may contribute to restoring arterial oxygen content through its [Hb]-enhancing contractile function and (b) eliminates further apnea-induced [Hb] increases in hypoxia. We suggest that tonic splenic contraction may contribute to hematological acclimatization early in HA ascent in humans.
  • Johansson, Ronnie, et al. (författare)
  • On the Definition and Scope of Information Fusion as a Field of Research
  • 2022
  • Ingår i: Perspectives. - : International Society of Information Fusion (ISIF). - 2831-4824 .- 2831-4832. ; 5:1, s. 3-12
  • Tidskriftsartikel (refereegranskat)abstract
    • A definition of information fusion (IF) as a field of research can benefit researchers within the field, who may use such a definition when motivating their own work and evaluating the contributions of others. Moreover, it can enable researchers and practitioners outside the field to more easily relate their own work to the field and more easily understand the scope of IF techniques and methods. Based on strengths and weaknesses of existing definitions, a definition is proposed that is argued to effectively fulfill the requirements that can be put on a definition of IF as a field of research. Although the proposed definition aims to be precise, it does not fully capture the richness and versatility of the IF field. To address that limitation, we highlight some topics to explore the scope of IF, covering the systems perspective of IF and its relation to ma-chine learning, optimization, robot behavior, opinion aggregation, and databases.
  • Kilpeläinen, Tuomas O, et al. (författare)
  • Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels.
  • 2016
  • Ingår i: Nature Communications. - : Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Leptin is an adipocyte-secreted hormone, the circulating levels of which correlate closely with overall adiposity. Although rare mutations in the leptin (LEP) gene are well known to cause leptin deficiency and severe obesity, no common loci regulating circulating leptin levels have been uncovered. Therefore, we performed a genome-wide association study (GWAS) of circulating leptin levels from 32,161 individuals and followed up loci reaching P<10(-6) in 19,979 additional individuals. We identify five loci robustly associated (P<5 × 10(-8)) with leptin levels in/near LEP, SLC32A1, GCKR, CCNL1 and FTO. Although the association of the FTO obesity locus with leptin levels is abolished by adjustment for BMI, associations of the four other loci are independent of adiposity. The GCKR locus was found associated with multiple metabolic traits in previous GWAS and the CCNL1 locus with birth weight. Knockdown experiments in mouse adipose tissue explants show convincing evidence for adipogenin, a regulator of adipocyte differentiation, as the novel causal gene in the SLC32A1 locus influencing leptin levels. Our findings provide novel insights into the regulation of leptin production by adipose tissue and open new avenues for examining the influence of variation in leptin levels on adiposity and metabolic health.
  • Leidermark, Erik, et al. (författare)
  • Estimating the risk for secondary cancer following targeted alpha therapy with astatine-211 intraperitoneal radioimmunotherapy.
  • 2022
  • Ingår i: Journal of nuclear medicine : official publication, Society of Nuclear Medicine. - 1535-5667.
  • Tidskriftsartikel (refereegranskat)abstract
    • Intraperitoneal 211At-based targeted alpha therapy (TAT) may hold most promise as an adjuvant therapy following surgery and chemotherapy in epithelial ovarian cancer to eradicate any remaining undetectable disease. This implies it will also be delivered to patients possibly already cured by the primary treatment. An estimate of long-term risks is therefore sought whether to justify the treatment. Methods: Baseline data for risk estimates of alpha-particle irradiation were collected from published studies on excess cancer induction and mortality for subjects exposed to either 224Ra treatments or Thorotrast contrast agent (25% ThO2 colloid, containing 232Th). Organ dosimetry for 224Ra and Thorotrast irradiation were taken from the literature. These organ-specific risks were then applied for our previously reported dosimetry for intraperitoneal (i.p.) 211At-TAT patients. Results: Risk could be estimated for 10 different organ or organ groups. The calculated excess relative risk per Gray (ERR/Gy) could be sorted into two groups. In the lower ERR/Gy group, up to approx. 5, were: Trachea, bronchus and lung 0.52 (CI 95% 0.21-0.82), Stomach 1.4 (CI 95% -5.0-7.9), Lymphoid and hematopoietic system 2.17 (CI 95% 1.7-2.7), Bone and articular cartilage 2.6 (CI 95% 2.0-3.3), Breast 3.45 (CI 95% -10-17) and Colon 4.5 (CI 95% -3.5-13). In the higher ERR/Gy group, ranging from approx. 10 to 15 were: Urinary bladder 10.1 (CI 95% 1.4-23), Liver 14.2 (CI 95% 13-16), Kidney 14.9 (CI 95% 3.9-26) and Lip, oral cavity and pharynx 15.20 (CI 95% 2.73-27.63). Applying a typical candidate patient (female, age 65 years) and correcting for reference population mortality rate, a total estimated excess mortality of an i.p. 211At-mAb treatment amounted to 1.13 per 100 treated. More than half of this excess originated from urinary bladder and kidney, 0.29 and 0.34 respectively. Depending on various adjustments in calculation and assumptions on competing risks excess mortality could range from 0.11 - 1.84 per 100 treated. Conclusion: Published epidemiological data on life-long detriment following alpha-particle irradiation and its dosimetry allowed calculations to estimate the risk for secondary cancer following 211At-based i.p. TAT. Measures to reduce dose to the urinary organs may further decrease the estimated relative low risk for secondary cancer from 211At-mAb based i.p. TAT.
  • Lindegren, Sture, 1960, et al. (författare)
  • Synthesis and biodistribution of 211At-labeled, biotinylated, and charge-modified poly-L-lysine: evaluation for use as an effector molecule in pretargeted intraperitoneal tumor therapy.
  • 2002
  • Ingår i: Bioconjugate chemistry. - 1043-1802 .- 1520-4812. ; 13:3, s. 502-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Poly-L-lysine (7, 21, and 204 kDa) has been evaluated as an effector carrier for use in pretargeted intraperitoneal tumor therapy. For the synthesis, the epsilon-amino groups on the poly-L-lysine were modified in three steps utilizing conjugate biotinylation with biotin amidocaproate N-hydroxysuccinimide ester (BANHS), conjugate radiolabeling with (211)At using the intermediate reagent N-succinimidyl 3-(trimethylstannyl)benzoate (m-MeATE), and charge modification using succinic anhydride, resulting in an increase in the molecular weight of approximately 80% of the final product. The labeling of the m-MeATE reagent and subsequent conjugation of the polymer were highly efficient with overall radiochemical yields in the range of 60-70%. The in vitro avidin binding ability of the modified polymer was almost complete (90-95%), as determined by binding to avidin beads using a convenient filter tube assay. Following intraperitoneal (ip) injection in athymic mice, the 13 kDa polymer product was cleared mainly via the kidneys with fast kinetics (biological half-live T(b) approximately 2 h) and with low whole-body retention. The clearance of the 38 kDa polymer was distributed between kidneys and liver, and the 363 kDa polymer was mainly sequestered by the liver with a T(b) of 8 h. Increased tissue uptake in the thyroid, lungs, stomach, and spleen following the distribution of the large effector molecules (38 and 363 kDa) suggests that degradation of the polymers by the liver may release some of the label as free astatine/astatide.
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