| 1. |
- Hibar, Derrek P., et al.
(författare)
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Novel genetic loci associated with hippocampal volume
- 2017
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- The hippocampal formation is a brain structure integrally involved in episodic memory, spatial navigation, cognition and stress responsiveness. Structural abnormalities in hippocampal volume and shape are found in several common neuropsychiatric disorders. To identify the genetic underpinnings of hippocampal structure here we perform a genome-wide association study (GWAS) of 33,536 individuals and discover six independent loci significantly associated with hippocampal volume, four of them novel. Of the novel loci, three lie within genes (ASTN2, DPP4 and MAST4) and one is found 200 kb upstream of SHH. A hippocampal subfield analysis shows that a locus within the MSRB3 gene shows evidence of a localized effect along the dentate gyrus, subiculum, CA1 and fissure. Further, we show that genetic variants associated with decreased hippocampal volume are also associated with increased risk for Alzheimer's disease (r(g) = -0.155). Our findings suggest novel biological pathways through which human genetic variation influences hippocampal volume and risk for neuropsychiatric illness.
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| 2. |
- Mellhammar, Emma, et al.
(författare)
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An attenuation method for reducing count rate losses in preclinical PET during intratherapeutic imaging
- 2017
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Ingår i: 2016 IEEE Nuclear Science Symposium, Medical Imaging Conference and Room-Temperature Semiconductor Detector Workshop, NSS/MIC/RTSD 2016. - 9781509016426 ; 2017-January
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Konferensbidrag (refereegranskat)abstract
- In pre-clinical imaging, tumor response to radionuclide therapy can be monitored with PET imaging. Radionuclides used for therapy such as 177Lu emit a significant amount of low energy photons. These photons may have an energy high enough to penetrate the imaged object and are the prone to be detected. Although these phtons are likely to be rejected electronically, they add dead-time to the system since they need to be processed by the electronics. This is a problem in high-sensitivity pre-clinical PET system with a low number of readout channels, such as the Genisys G8 investigated in this work. The low energy gammas may also affect image quality due to increased probability of pulse pile-up. The use of high-attenuating shields designed to absorb most of the low energy photons emitted from the therapeutic radionuclide were investigated. Cylindrical led shields were constructed with thicknesses between 1 and 3 mm. A 3mm thick cylindrical shield was also constructed out of Rose metal (50% Bi, 28% Pb, and 22% Sn). The diameter of the shield was wide enough to accommodate a NEMA IQ phantom and a mouse. The attenuation of the shields for annihilation radiation was measured with a 22Na point source placed at the center of the FOV. Measurements of the coincidence rate were performed with the lead shields in place. At a of thicknesses of 1 and 3mm, the coincidence rate was reduced by a factor or 0.70 and 0.40, respectively. To study the effect of the presence of a background of low energy gammas on the coincidence count rate and the efficacy of the lead shields, 177Lu was added to a 1 cm diameter hollow sphere. In the presence of 100 MBq of 177Lu, the coincidence count rate was reduced by a factor 0.20 due to the detector dead-time. Although the count rate was reduced by a factor of 0.40 with the 3mm shield around the source, the dead-time effects due to the 177Lu background were less than 7%. 18F imaging of a NEMA phantom and a tumor bearing mouse showed dramatic image distortions in the presence of the 177Lu background. When imaging of with the 3mm shield in place, the image distortions were eliminated and were comparable in to the images acquired without the background activity.
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| 3. |
- Altena, Renske, et al.
(författare)
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Human Epidermal Growth Factor Receptor 2 (HER2) PET Imaging of HER2-Low Breast Cancer with [ 68 Ga]Ga-ABY-025 : Results from a Pilot Study
- 2024
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Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667. ; 65:5, s. 700-707
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Tidskriftsartikel (refereegranskat)abstract
- Patients with HER2-low metastatic breast cancer (mBC), defined as an immunohistochemistry (IHC) score of 1+ or 2+ without HER2 gene amplification, may benefit from HER2 antibody-drug conjugates. Identifying suitable candidates is a clinical challenge because of spatial and temporal heterogeneity in HER2 expression and discrepancies in pathologic reporting. We aimed to investigate the feasibility and safety of HER2-specific PET imaging with [ 68 Ga]Ga-ABY-025 for visualization of HER2-low mBC.Methods: A prospective pilot study was done with 10 patients who had HER2-low mBC, as part of a phase 2 basket imaging study with [ 68 Ga]Ga-ABY-025 in HER2-expressing solid tumors. Patients were recruited at the Breast Clinic at the Karolinska University Hospital, Stockholm, Sweden. PET/CT images were acquired 3 h after injection of 200 MBq of [ 68 Ga]Ga-ABY-025. The SUV max was used to quantify tracer uptake. Ultrasound-guided tumor biopsies were guided by results from the HER2 PET. The main outcome-the safety and feasibility of HER2 PET in patients with HER2low mBC, measured the occurrence of possible procedure -related adverse events.Results: Ten patients with HER2-low mBC underwent [ 68 Ga]Ga-ABY-025 PET/CT with paired tumor biopsies. No adverse events occurred. In all patients, [ 68 Ga]Ga-ABY-025-avid lesions with substantial intra- and interindividual heterogeneity in tracer uptake were noted. In 8 of 10 patients with ABY-025-avid lesions, the HER2low status of the corresponding lesions was confirmed by IHC or in situ hybridization. Two patients had an IHC score of 0 in the tumor biopsies:1 in a cutaneous lesion with a low SUV max and 1 in a liver metastasis with a high SUV max but a "cold" core.Conclusion: The visualization of HER2-low mBC with [ 68 Ga]Ga-ABY-025 PET/CT was feasible and safe. Areas of tracer uptake showed varying levels of HER2 expression on IHC. The observed intra- and interindividual heterogeneity in [ 68 Ga]Ga-ABY-025 uptake suggested that HER2 PET might be used as a tool for the noninvasive assessment of disease heterogeneity and has the potential to identify patients in whom HER2-targeted drugs can have a clinical benefit.
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| 4. |
- Alvez, Maria Bueno, et al.
(författare)
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Next generation pan-cancer blood proteome profiling using proximity extension assay
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- A comprehensive characterization of blood proteome profiles in cancer patients can contribute to a better understanding of the disease etiology, resulting in earlier diagnosis, risk stratification and better monitoring of the different cancer subtypes. Here, we describe the use of next generation protein profiling to explore the proteome signature in blood across patients representing many of the major cancer types. Plasma profiles of 1463 proteins from more than 1400 cancer patients are measured in minute amounts of blood collected at the time of diagnosis and before treatment. An open access Disease Blood Atlas resource allows the exploration of the individual protein profiles in blood collected from the individual cancer patients. We also present studies in which classification models based on machine learning have been used for the identification of a set of proteins associated with each of the analyzed cancers. The implication for cancer precision medicine of next generation plasma profiling is discussed.
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| 5. |
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| 6. |
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| 7. |
- Axelsson, Emma L., et al.
(författare)
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Humans' Pupillary Contagion Extends to Cats and Dogs
- 2021
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Ingår i: Social Cognitive & Affective Neuroscience. - : Oxford University Press (OUP). - 1749-5016 .- 1749-5024. ; 16:1-2, s. 153-166
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Tidskriftsartikel (refereegranskat)abstract
- When viewing pupil sizes change, our own pupil sizes change, a phenomenon known as pupillary contagion. This involuntary response is reliable between humans, but can be affected by familiarity and empathy. We investigated whether the pupillary contagion response occurs for humans viewing familiar species - cats and dogs - and whether it is modulated by preferences for particular species. Pupil sizes were measured while viewing cat, dog, and human images with small, medium, and large pupils. Trait empathy, cat and dog affiliation and experience were subsequently measured. There was an image pupil size effect, but this did not vary by species. There was greater pupil size change to cats and dogs than to humans, but this might have been due to the varying size and appearance of the cats and dogs. Greater dog affiliation was also associated with smaller overall pupil size change to dogs and larger change to humans, but this did not interact with image pupil size. Dog affiliation might be associated with less arousal to dog images. In sum, pupillary contagion responses indicate a spontaneous transfer of information about internal states and the findings suggest that humans are sensitive to this across species, regardless of individual preference.
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| 8. |
- Axelsson, Emma L, et al.
(författare)
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Mine, Mine, Mine : Self-Reference and Children’s Retention of Novel Words
- 2018
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Adults demonstrate enhanced memory for words encoded as belonging to themselves compared to those belonging to another. Known as the self-reference effect, there is evidence for the effect in children as young as three. Toddlers are efficient in linking novel words to novel objects, but have difficulties retaining multiple word-object associations. The aim here was to investigate the self-reference ownership paradigm on 3-year-old children’s retention of novel words. Following exposure to each of four novel word-object pairings, children were told that objects either belonged to them or another character. Children demonstrated significantly higher immediate retention of self-referenced compared to other-referenced items. Retention was also tested 4 h later and the following morning. Retention for self- and other-referenced words was significantly higher than chance at both delayed time points, but the difference between the self- and other-referenced words was no longer significant. The findings suggest that when it comes to toddlers’ retention of multiple novel words there is an initial memory enhancing effect for self- compared to other-referenced items, but the difference diminishes over time. Children’s looking times during the self-reference presentations were positively associated with retention of self-referenced words 4 h later. Looking times during the other-reference presentations were positively associated with proportional looking at other-referenced items during immediate retention testing. The findings have implications for children’s memory for novel words and future studies could test children’s explicit memories for the ownership manipulation itself and whether the effect is superior to other forms of memory supports such as ostensive naming.
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| 9. |
- Axelsson, Emma L., et al.
(författare)
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Napping and toddlers' memory for fast-mapped words
- 2018
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Ingår i: First language. - : SAGE Publications. - 0142-7237 .- 1740-2344. ; 38:6, s. 582-595
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Tidskriftsartikel (refereegranskat)abstract
- When toddlers hear a novel word, they quickly and independently link it with a novel object rather than known-name objects. However, they are less proficient in retaining multiple novel words. Sleep and even short naps can enhance declarative memory in adults and children and this study investigates the effect of napping on children’s memory for novel words. Forty two-and-a-half-year-old children were presented with referent selection trials for four novel nouns. Children’s retention of the words was tested immediately after referent selection, four hours later in the afternoon, and the following morning. Half of the toddlers napped prior to the afternoon retention test. Amongst the toddlers who napped, retention scores remained steady four hours after exposure and the following morning. In contrast, for the wake group, there was a steady decline in retention scores by the following morning and significantly lower retention scores compared to the nap group. Napping following exposure to novel word–object associations could help in maintaining memories and limiting decay. Nap duration was also associated with better retention scores, but there were no effects of sleep quality, habitual napping, or sleepiness. The findings have implications for the role of napping in children’s language acquisition.
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| 10. |
- Axelsson, Emma L., et al.
(författare)
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Near or far: The effect of spatial distance and vocabulary knowledge on word learning
- 2016
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Ingår i: Acta Psychologica. - : Elsevier BV. - 0001-6918 .- 1873-6297. ; 163, s. 81-87
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Tidskriftsartikel (refereegranskat)abstract
- The current study investigated the role of spatial distance in word learning. Two-year-old children saw three novel objects named while the objects were either in close proximity to each other or spatially separated. Children were then tested on their retention for the name-object associations. Keeping the objects spatially separated from each other during naming was associated with increased retention for children with larger vocabularies. Children with a lower vocabulary size demonstrated better retention if they saw objects in close proximity to each other during naming. This demonstrates that keeping a clear view of objects during naming improves word learning for children who have already learned many words, but keeping objects within close proximal range is better for children at earlier stages of vocabulary acquisition. The effect of distance is therefore not equal across varying vocabulary sizes. The influences of visual crowding, cognitive load, and vocabulary size on word learning are discussed.
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| 11. |
- Axelsson, Emma L., et al.
(författare)
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Sleep problems and language development in toddlers with Williams syndrome
- 2013
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 34, s. 3988-3996
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Tidskriftsartikel (refereegranskat)abstract
- Sleep and related maternal beliefs were assessed in a narrow age range of 18 children with Williams syndrome (WS) and 18 typically developing (TD) children. WS is a rare genetic disorder characterised by a complex physical, cognitive and behavioural phenotype. High prevalence of sleep difficulties in older children and adults with WS have been reported. Parents completed 6 questionnaires: the Brief Infant Sleep Questionnaire, Infant Sleep Vignettes Interpretation Scale, Pittsburgh Sleep Quality Index of Parents, Child Behaviour Checklist, MacArthur Communicative Development Inventory for Infants - Words and Gestures, and the Major (ICD-10) Depression Inventory. Compared to TD children, those with WS had shorter night sleep, more night wakings and wakefulness according to parental report. Regression analyses revealed that a proportion of the variance in language development scores in WS children could be explained by night sleep duration. Compared to control parents, the mothers of the WS group were more likely to describe their child’s sleep as problematic and had higher rates of involvement with child sleep, yet they had a lesser tendency to interpret sleep problems as signs of distress and a greater tendency to emphasise limit setting. Approximately half of both groups of mothers experienced poor sleep quality. This was also related to maternal mood, and night wakefulness in the children with WS. This is the first study to quantify sleep difficulties in young children with WS in a narrow age range using maternal report. The possible negative effects on maternal sleep and mood, and the link between night sleep and language development in young children with WS, requires further detailed investigation. ?? 2013 Elsevier Ltd.
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| 12. |
- Axelsson, Emma L., et al.
(författare)
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Testing a word is not a test of word learning
- 2013
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Ingår i: Acta Psychologica. - : Elsevier BV. - 0001-6918 .- 1873-6297. ; 144, s. 264-268
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Tidskriftsartikel (refereegranskat)abstract
- Although vocabulary acquisition requires children learn names for multiple things, many investigations of word learning mechanisms teach children the name for only one of the objects presented. This is problematic because it is unclear whether children’s performance reflects recall of the correct name-object association or simply selection of the only object that was singled out by being the only object named. Children introduced to one novel name may perform at ceiling as they are not required to discriminate on the basis of the name per se, and appear to rapidly learn words following minimal exposure to a single word. We introduced children to four novel objects. For half the children, only one of the objects was named and for the other children, all four objects were named. Only children introduced to one word reliably selected the target object at test. This demonstration highlights the over-simplicity of one-word learning paradigms and the need for a shift in word learning paradigms where more than one word is taught to ensure children disambiguate objects on the basis of their names rather than their degree of salience. ?? 2013.
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| 13. |
- Axelsson, Emma L., et al.
(författare)
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The Effect of Sleep on Children’s Word Retention and Generalization
- 2016
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 7, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- In the first few years of life children spend a good proportion of time sleeping as well as acquiring the meanings of hundreds of words. There is now ample evidence of the effects of sleep on memory in adults and the number of studies demonstrating the effects of napping and nocturnal sleep in children is also mounting. In particular, sleep appears to benefit children’s memory for recently-encountered novel words. The effect of sleep on children’s generalization of novel words across multiple items, however, is less clear. Given that sleep is polyphasic in the early years, made up of multiple episodes, and children’s word learning is gradual and strengthened slowly over time, it is highly plausible that sleep is a strong candidate in supporting children’s memory for novel words. Importantly, it appears that when children sleep shortly after exposure to novel word-object pairs retention is better than if sleep is delayed, suggesting that napping plays a vital role in long-term word retention for young children. Word learning is a complex, challenging, and important part of development, thus the role that sleep plays in children’s retention of novel words is worthy of attention. As such, ensuring children get sufficient good quality sleep and regular opportunities to nap may be critical for language acquisition.
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| 14. |
- Axelsson, Emma L., et al.
(författare)
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The Right Thing at the Right Time: Why Ostensive Naming Facilitates Word Learning
- 2012
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Ingår i: Frontiers in Psychology. - : Frontiers Media SA. - 1664-1078. ; 3
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Tidskriftsartikel (refereegranskat)abstract
- The current study examines how focusing children’s attention immediately after fast mapping improves their ability to retain novel names. Previous research suggests that young children can only retain novel names presented via referent selection if ostensive naming is provided and that such explicit naming works by increasing children’s attention to the target and decreasing their attention to the competitor objects (Horst and Samuelson, 2008). This explanation of the function of ostensive naming after referent selection trials was tested by drawing 24-month-old children’s attention to the target either by illuminating the target, covering the competitors, or both. A control group was given a social pragmatic cue (pointing). Children given social pragmatic cue support did not demonstrate retention. However, children demonstrated retention if the target object was illuminated, and also when it was illuminated and the competitors simultaneously dampened. This suggests that drawing children’s attention to the target object in a manner that helps focus children’s attention is critical for word learning via referent selection. Directing attention away from competitors while also directing attention toward a target also aids in the retention of novel words.
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| 15. |
- Axelsson, Emma L., et al.
(författare)
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The role of bodies in infants’ categorical representations of humans and non-human animals
- 2018
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Ingår i: Infant and Child Development. - : John Wiley & Sons. - 1522-7227 .- 1522-7219. ; 27:6
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether bodies are useful cues in infants' category formations, 7-month-old infants were familiarized to images of humans or non-human animals followed by test pairs comprising a familiar category image and a hybrid image with a novel category body. Infants familiarized to humans did not demonstrate a novelty preference for hybrid stimuli with non-human animal bodies. Infants familiarized with non-human animals demonstrated a novelty preference for hybrid stimuli with human bodies, suggesting that there is an asymmetry in infants' category formations of bodies. Compared with infants familiarized to non-human animals, the infants familiarized to humans had a higher proportional fixation count to bodies during familiarization, but the lack of preference for novel category bodies at test suggests that 7-month-old infants' representations of the features of human bodies are likely still developing and they are more likely to form a summary-based categorical representation of non-human animals.
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| 16. |
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| 17. |
- Dahlbom, Magnus, et al.
(författare)
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Effects of high photon fluence rate from therapeutic radionuclides on preclinical and clinical PET systems
- 2016
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Ingår i: 2014 IEEE Nuclear Science Symposium and Medical Imaging Conference, NSS/MIC 2014. - 9781479960972
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Konferensbidrag (refereegranskat)abstract
- Tumor response in radionuclide therapy can be monitored with PET/CT and/or PET/MR. A high background photon fluence from a therapy radionuclide may influence both image quality and quantification, when imaging is performed intra-therapeutically, i.e. with high activity of the therapeutic radionuclide present. Here, count losses and image distortion have been investigated for preclinical and clinical PET systems with different detector designs. The effect on the spatial resolution was studied with a point source of 22Na in a background of 99mTc, where 99mTc emulated the photon emission from a therapeutic radionuclide. An in-house made mouse phantom with silicon tubes filled with 99mTc with a centrally placed 22Na point source was used. For the clinical systems, a 70 cm long NEMA PET Scatter Phantom was used, with a 22Na point source placed at the center whereas the off-center silicon tube was filled with 99mTc. In addition, image quality was also evaluated in the presence of different levels of 99mTc with a 18F-filled NEMA image quality phantom on the preclinical systems and a 18F-filled Jaszczak phantom on the clinical system. Preclinical PET systems with different detector geometries showed that the addition of 99mTc affected the count rate capability considerably, especially those with a low number of read-out channels. The coincidence rate for was significantly reduced when high activities of 99mTc were present. The clinical PET system also showed an effect of reduced coincidence rate with increased photon fluence rate. At high 99mTc activities, the spatial resolution was degraded for both the preclinical and the clinical systems. The quantitative capability of PET systems used intra-therapeutically is significantly affected by the additional high photon fluence rate. The dead-time correction implemented on some of the investigated PET systems, was able to accurately compensate for the coincidence count losses. The reduced spatial resolution at high photon fluence rate, however, remains a potentially limiting factor.
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| 18. |
- Danielsson, Frida, et al.
(författare)
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Spatial Characterization of the Human Centrosome Proteome Opens Up New Horizons for a Small but Versatile Organelle
- 2020
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Ingår i: Proteomics. - : Wiley-VCH Verlag. - 1615-9853 .- 1615-9861.
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Tidskriftsartikel (refereegranskat)abstract
- After a century of research, the human centrosome continues to fascinate. Based on immunofluorescence and confocal microscopy, an extensive inventory of the protein components of the human centrosome, and the centriolar satellites, with the important contribution of over 300 novel proteins localizing to these compartments is presented. A network of candidate centrosome proteins involved in ubiquitination, including six interaction partners of the Kelch-like protein 21, and an additional network of protein phosphatases, together supporting the suggested role of the centrosome as an interactive hub for cell signaling, is identified. Analysis of multi-localization across cellular organelles analyzed within the Human Protein Atlas (HPA) project shows how multi-localizing proteins are particularly overrepresented in centriolar satellites, supporting the dynamic nature and wide range of functions for this compartment. In summary, the spatial dissection of the human centrosome and centriolar satellites described here provides a comprehensive knowledgebase for further exploration of their proteomes.
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| 19. |
- Eapen, Valsamma, et al.
(författare)
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"Are you available for the next 18 months?" - methods and aims of a longitudinal birth cohort study investigating a universal developmental surveillance program: the ’Watch Me Grow’ study
- 2014
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 14, s. 1-9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Universal developmental surveillance programs aimed at early identification and targeted early intervention significantly improve short-and long-term outcomes in children at risk of developmental disorders. However, a significant challenge remains in providing sufficiently rigorous research and robust evidence to inform policy and service delivery. This paper describes the methods of the ’Watch Me Grow’ study that aims to maximise accurate early detection of children with developmental disorders through a partnership formed between policy makers, service providers and researchers. Methods/Design: A mixed methods study design was developed consisting of: (1) a qualitative study of parents and health service providers to investigate barriers and enablers of developmental surveillance; (2) recruitment of a birth cohort and their longitudinal follow-up to 18 months of age to: a) assess risk factors for not accessing existing developmental surveillance programs and b) estimate the prevalence of children identified with developmental risk; (3) comparison of surveillance outcomes with a reference standard at 18 months of age to assess the diagnostic test accuracy of existing and alternative developmental surveillance tools; and (4) comparison of developmental surveillance models to inform policy recommendations. Data linkage will be used to determine the uptake and representativeness of the study participant group versus non-participants. Discussion: The Watch Me Grow study is expected to provide a collaborative opportunity to enhance universal developmental surveillance for early accurate identification of developmental risk. This will also provide quality evidence about identification of developmental risk and access to services to be embedded in existing practice with linkages to policy development.
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| 20. |
- Eapen, Valsamma, et al.
(författare)
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Maternal help-seeking for child developmental concerns: Associations with socio-demographic factors
- 2017
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Ingår i: Journal of Paediatrics and Child Health. - : Wiley. - 1034-4810 .- 1440-1754. ; 53, s. 963-969
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To examine socio-demographic factors associated with maternal help-seeking for child developmental concerns in a longitudinal birth cohort study. An understanding of these factors is critical to improving uptake of services to maximise early identification and intervention for developmental concerns. Methods: A birth cohort was recruited from the post-natal wards of two teaching hospitals and through community nurses in South Western Sydney, Australia, between November 2011 and April 2013. Of the 4047 mothers approached, 2025 consented to participate (response rate = 50%). Socio-demographic and service use information was collected after the child’s birth and when the child was 18 months of age. Sources of help were divided into three categories (formal health services, other formal services and informal supports) and compound variables were created by summing the number of different sources identified by mothers. Results: Significantly more sources of help were intended to be used and/or actually accessed by mothers born in Australia, whose primary language was English, with higher levels of education and annual household income, and among mothers of first-born children. Conclusions: Developmental concerns are known to increase with increased psychosocial adversity. Our findings of reduced intent to access and use of services by socio-economically disadvantaged families and those from culturally and linguistically diverse backgrounds suggests that an inverse care effect is in operation whereby those children with the greatest health needs may have the least access to services. Possible explanations for this, and recommendations for improving service accessibility for these populations through targeted and culturally appropriate services, are discussed. Copyright © 2017 Paediatrics and Child Health Division (The Royal Australasian College of Physicians)
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| 21. |
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| 22. |
- Gandaglia, Giorgio, et al.
(författare)
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Clinical Characterization of Patients Diagnosed with Prostate Cancer and Undergoing Conservative Management : A PIONEER Analysis Based on Big Data
- 2024
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Ingår i: European Urology. - 0302-2838. ; 85:5, s. 457-465
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Tidskriftsartikel (refereegranskat)abstract
- Background: Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics. Objective: To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data. Design, setting, and participants: From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146). Outcome measurements and statistical analysis: Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data. Results and limitations: The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent. Conclusions: Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data. Patient summary: Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
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| 23. |
- Gnann, Christian, et al.
(författare)
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An image-based map of the mitochondrial proteome reveals widespread metabolic heterogeneity
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Mitochondria are involved in a wide range of cellular functions beyond their role in energy metabolism. Defining the human mitochondrial proteome is crucial to understand the mitochondria’s diverse functions and role in disease. Here, we present an image-based map of the human mitochondrial proteome containing 1,121 proteins with subcellular resolution. Our analysis shows that 48.3% (n=542) of the proteins localize to additional cellular compartments, further contributing to the diverse cellular functions of mitochondria and connectivity to other organelles. Furthermore, the mitochondrial proteome reveals tissue specific clustering, suggesting tissue specific functions and physiology. Strikingly, the single cell resolution of our dataset revealed extensive heterogeneity for as much as 33.5% (n=376) of the mitochondrial proteome which could not be explained by cell cycle progression. By performing a high throughput immunofluorescence screen, we conclude that heterogeneity in mitochondria protein expression can establish metabolic states in cell populations. This map of the mitochondrial proteome, part of the Human Protein Atlas database (www.proteinatlas.org), provides a valuable knowledge resource for studies of mitochondria function, dysfunction and disease.
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| 24. |
- Gnann, Christian, et al.
(författare)
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Widespread enzyme expression variations underlie diverse metabolic capacities within cell types
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Metabolic enzymes perform life-sustaining functions in various compartments of the cell. Recent studies have shown some enzymes to exhibit varied expression or localization between genetically identical cells and that this heterogeneity impacts drug resistance, metastasis, differentiation, and immune cell activation. However, no systematic analysis of metabolic cellular heterogeneity has been performed. Here, we leverage imaging-based single-cell spatial proteomic data to reveal the extent of non-genetic partitioning of the metabolic proteome. Over half of all enzymes localize to multiple cellular compartments, hinting at moonlighting potential. In addition, nearly two fifths of metabolic enzymes exhibit cell-to-cell variable expression. We demonstrate that individual cells reproduce these highly heterogeneous cell populations using clonal expansion, establishing that cells recapitulate myriad metabolic phenotypes over just a few cell divisions. To identify multifunctional moonlighting enzymes, we mine protein-protein interaction datasets to find interacting proteins with distinct functional roles, and using a timeresolved transcriptomic dataset, we find that metabolic heterogeneity arises largely independently of cell cycle progression and is established mostly post-transcriptionally or posttranslationally. Taken together, our data suggest that the heterogeneity of metabolic enzymes establish diverse cellular phenotypes, which are reflected in tissues, and which may ultimately allow targeted studies of their roles in health and disease.
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| 25. |
- Gyllensten, Ulf B., et al.
(författare)
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Next Generation Plasma Proteomics Identifies High-Precision Biomarker Candidates for Ovarian Cancer
- 2022
-
Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 14:7
-
Tidskriftsartikel (refereegranskat)abstract
- Simple Summary Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. The aim of our study was to broadly measure protein biomarkers to find tests for the early detection of ovarian cancer. We found that combinations of 4-7 protein biomarkers can provide highly accurate detection of early- and late-stage ovarian cancer compared to benign conditions. The performance of the tests was then validated in a second independent cohort. Background: Ovarian cancer is the eighth most common cancer among women and has a 5-year survival of only 30-50%. The survival is close to 90% for patients in stage I but only 20% for patients in stage IV. The presently available biomarkers have insufficient sensitivity and specificity for early detection and there is an urgent need to identify novel biomarkers. Methods: We employed the Explore PEA technology for high-precision analysis of 1463 plasma proteins and conducted a discovery and replication study using two clinical cohorts of previously untreated patients with benign or malignant ovarian tumours (N = 111 and N = 37). Results: The discovery analysis identified 32 proteins that had significantly higher levels in malignant cases as compared to benign diagnoses, and for 28 of these, the association was replicated in the second cohort. Multivariate modelling identified three highly accurate models based on 4 to 7 proteins each for separating benign tumours from early-stage and/or late-stage ovarian cancers, all with AUCs above 0.96 in the replication cohort. We also developed a model for separating the early-stage from the late-stage achieving an AUC of 0.81 in the replication cohort. These models were based on eleven proteins in total (ALPP, CXCL8, DPY30, IL6, IL12, KRT19, PAEP, TSPAN1, SIGLEC5, VTCN1, and WFDC2), notably without MUCIN-16. The majority of the associated proteins have been connected to ovarian cancer but not identified as potential biomarkers. Conclusions: The results show the ability of using high-precision proteomics for the identification of novel plasma protein biomarker candidates for the early detection of ovarian cancer.
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| 26. |
- Hovén, Emma, et al.
(författare)
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Sexual dysfunction in young adult survivors of childhood cancer : A population-based study
- 2021
-
Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049 .- 1879-0852. ; 154, s. 147-156
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the prevalence of sexual dysfunction and to identify the factors associated with sexual dysfunction in young adult childhood cancer survivors.METHODS: All survivors of childhood cancer (aged 19-40 years) in Sweden were invited to this population-based study, and 2546 men and women (59%) participated. Sexual function was examined with the PROMIS Sexual Function and Satisfaction Measure. Logistic regression was used to assess the differences between survivors and a general population sample (n = 819) and to identify the factors associated with sexual dysfunction in survivors.RESULTS: Sexual dysfunction in at least one domain was reported by 57% of female and 35% of male survivors. Among females, dysfunction was most common for Sexual interest (36%), Orgasm - ability (32%) and Vulvar discomfort - labial (19%). Among males, dysfunction was most common for the domains satisfaction with sex life (20%), Sexual interest (14%) and Erectile function (9%). Compared with the general population, male survivors more frequently reported sexual dysfunction in ≥2 domains (OR = 1.67, 95% CI: 1.03-2.71), with an increased likelihood of dysfunction regarding Orgasm - ability (OR = 1.82; 95% CI: 1.01-3.28) and Erectile function (OR = 2.30; 95% CI: 1.18-4.49). Female survivors reported more dysfunction regarding Orgasm - pleasure (9% versus 5%, OR = 1.86; 95% CI: 1.11-3.13). A more intensive cancer treatment, emotional distress and body image disturbance were associated with sexual dysfunction in survivors.CONCLUSIONS: The findings underscore the need for routine assessment of sexual health in follow-up care of childhood cancer survivors and highlight that those treated with more intensive cancer treatment and who experience concurrent psychological concerns may benefit from targeted screening and interventions.
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| 27. |
- Kullgren, Anders, 1963, et al.
(författare)
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The potential of vehicle and road infrastructure interventions in fatal bicyclist accidents on Swedish roads—What can in-depth studies tell us?
- 2019
-
Ingår i: Traffic Injury Prevention. - : Informa UK Limited. - 1538-9588 .- 1538-957X. ; 20:sup1, s. S7-S12
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: The objective of this article is to describe the characteristics of fatal crashes with bicyclists on Swedish roads in rural and urban areas and to investigate the potential of bicycle helmets and different vehicle and road infrastructure interventions to prevent them. The study has a comprehensive approach to provide road authorities and vehicle manufacturers with recommendations for future priorities. Methods: The Swedish Transport Administration’s (STA) in-depth database of fatal crashes was used for case-by-case analysis of fatal cycling accidents (2006–2016) on rural (n = 82) and urban (n = 102) roads. The database consists of information from the police, medical journals, autopsy reports, accident analyses performed by STA, and witness statements. The potential of helmet use and various vehicle and road infrastructure safety interventions was determined retrospectively for each case by analyzing the chain of events leading to the fatality. The potential of vehicle safety countermeasures was analyzed based on prognoses on their implementation rates in the Swedish vehicle fleet. Results: The most common accident scenario on rural roads was that the bicyclist was struck while cycling along the side of the road. On urban roads, the majority of accidents occurred in intersections. Most accidents involved a passenger car, but heavy trucks were also common, especially in urban areas. Most accidents occurred in daylight conditions (73%). Almost half (46%) of nonhelmeted bicyclists would have survived with a helmet. It was assessed that nearly 60% of the fatal accidents could be addressed by advanced vehicle safety technologies, especially autonomous emergency braking with the ability to detect bicyclists. With regard to interventions in the road infrastructure, separated paths for bicyclists and bicycle crossings with speed calming measures were found to have the greatest safety potential. Results indicated that 91% of fatally injured bicyclists could potentially be saved with known techniques. However, it will take a long time for such technologies to be widespread. Conclusions: The majority of fatally injured bicyclists studied could potentially be saved with known techniques. A speedy implementation of important vehicle safety systems is recommended. A fast introduction of effective interventions in the road infrastructure is also necessary, preferably with a plan for prioritization.
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| 28. |
- Kushnerenko, Elena, et al.
(författare)
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Brain responses to audiovisual speech mismatch in infants are associated with individual differences in looking behaviour
- 2013
-
Ingår i: European Journal of Neuroscience. - : Wiley. - 0953-816X .- 1460-9568.
-
Tidskriftsartikel (refereegranskat)abstract
- Research on audiovisual speech integration has reported high levels of individual variability, especially among young infants. In the present study we tested the hypothesis that this variability results from individual differences in the maturation of audiovisual speech processing during infancy. A developmental shift in selective attention to audiovisual speech has been demonstrated between 6 and 9 months with an increase in the time spent looking to articulating mouths as compared to eyes (Lewkowicz & Hansen-Tift. (2012) Proc. Natl Acad. Sci. USA, 109, 1431-1436; Tomalski et al. (2012) Eur. J. Dev. Psychol., 1-14). In the present study we tested whether these changes in behavioural maturational level are associated with differences in brain responses to audiovisual speech across this age range. We measured high-density event-related potentials (ERPs) in response to videos of audiovisually matching and mismatched syllables /ba/ and /ga/, and subsequently examined visual scanning of the same stimuli with eye-tracking. There were no clear age-specific changes in ERPs, but the amplitude of audiovisual mismatch response (AVMMR) to the combination of visual /ba/ and auditory /ga/ was strongly negatively associated with looking time to the mouth in the same condition. These results have significant implications for our understanding of individual differences in neural signatures of audiovisual speech processing in infants, suggesting that they are not strictly related to chronological age but instead associated with the maturation of looking behaviour, and develop at individual rates in the second half of the first year of life.
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| 29. |
- Le, Trang, et al.
(författare)
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Analysis of the Human Protein Atlas Weakly Supervised Single-Cell Classification competition
- 2022
-
Ingår i: Nature Methods. - : Springer Nature. - 1548-7091 .- 1548-7105. ; 19:10, s. 1221-1229
-
Tidskriftsartikel (refereegranskat)abstract
- While spatial proteomics by fluorescence imaging has quickly become an essential discovery tool for researchers, fast and scalable methods to classify and embed single-cell protein distributions in such images are lacking. Here, we present the design and analysis of the results from the competition Human Protein Atlas – Single-Cell Classification hosted on the Kaggle platform. This represents a crowd-sourced competition to develop machine learning models trained on limited annotations to label single-cell protein patterns in fluorescent images. The particular challenges of this competition include class imbalance, weak labels and multi-label classification, prompting competitors to apply a wide range of approaches in their solutions. The winning models serve as the first subcellular omics tools that can annotate single-cell locations, extract single-cell features and capture cellular dynamics.
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| 30. |
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| 31. |
- Mahdessian, Diana, et al.
(författare)
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Spatiotemporal dissection of the cell cycle with single-cell proteogenomics
- 2021
-
Ingår i: Nature. - : Springer Nature. - 0028-0836 .- 1476-4687. ; 590:7847
-
Tidskriftsartikel (refereegranskat)abstract
- Spatial and temporal variations among individual human cell proteomes are comprehensively mapped across the cell cycle using proteomic imaging and transcriptomics. The cell cycle, over which cells grow and divide, is a fundamental process of life. Its dysregulation has devastating consequences, including cancer(1-3). The cell cycle is driven by precise regulation of proteins in time and space, which creates variability between individual proliferating cells. To our knowledge, no systematic investigations of such cell-to-cell proteomic variability exist. Here we present a comprehensive, spatiotemporal map of human proteomic heterogeneity by integrating proteomics at subcellular resolution with single-cell transcriptomics and precise temporal measurements of individual cells in the cell cycle. We show that around one-fifth of the human proteome displays cell-to-cell variability, identify hundreds of proteins with previously unknown associations with mitosis and the cell cycle, and provide evidence that several of these proteins have oncogenic functions. Our results show that cell cycle progression explains less than half of all cell-to-cell variability, and that most cycling proteins are regulated post-translationally, rather than by transcriptomic cycling. These proteins are disproportionately phosphorylated by kinases that regulate cell fate, whereas non-cycling proteins that vary between cells are more likely to be modified by kinases that regulate metabolism. This spatially resolved proteomic map of the cell cycle is integrated into the Human Protein Atlas and will serve as a resource for accelerating molecular studies of the human cell cycle and cell proliferation.
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| 32. |
- Melander, Claes, et al.
(författare)
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Determination of reducing ends with flow injection analysis with amperometric detection: application to enzyme-hydrolysed methyl cellulose
- 2007
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Ingår i: Analytical and Bioanalytical Chemistry. - : Springer Science and Business Media LLC. - 1618-2642 .- 1618-2650. ; 387:7, s. 2585-2593
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Tidskriftsartikel (refereegranskat)abstract
- A novel method for detection of reducing ends of sugars is proposed, based on the use of Fe(CN)(6)(3-) as the oxidant in combination with amperometric detection and flow injection analysis (FIA). The method is very sensitive, giving values of < 10 mu M for the limit of detection for a series of mono- and oligosaccharides. Samples can be analysed every 30 s, and injection can be made fully automated, making it possible to perform on-line analysis of polysaccharide samples subjected to hydrolysis. Three methylcelluloses (MC) of different qualities were hydrolysed with three different glucanases, and the concentrations of reducing ends prior to, during and after hydrolysis were determined. Differences were observed between the results obtained using different combinations of enzymes and MCs, which revealed different selectivities of the various enzymes for the different substrates. One MC was also hydrolysed and analysed in real-time for three hours. The method proposed is superior to many of the standard methods used today, which require manual labour and have a lower sensitivity.
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| 33. |
- Mellhammar, Emma Matilda, et al.
(författare)
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Count rate characteristics and image distortion in preclinical PET systems during intratherapeutic radiopharmaceutical therapy imaging
- 2016
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 57:12, s. 1964-1970
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Tidskriftsartikel (refereegranskat)abstract
- Positron emission tomography (PET) may provide important information on the therapeutic response of radiopharmaceutical therapy (RPT) during therapy. The radiation emission from the RPT radionuclide may disturb the coincidence detection and impair the image resolution. In this study we tested the feasibility to perform intratherapeutic PET on three preclinical PET systems.METHODS: Using (22)Na point sources and phantoms filled with (18)F, and a phantom filled with either (99m)Tc or (177)Lu, the coincidence count rate and the spatial resolution when both a PET and a therapeutic radionuclide were present in the PET camera, were evaluated. (99m)Tc was used as a substitute for a generic therapeutic radioisotope, since it has a suitable half-life and is easy obtainable.RESULTS: High activities of (99m)Tc deteriorated the coincidence count rate from the (18)F-filled phantom with a (22)Na point source on all three systems evaluated. One of the systems could to a high degree correct the count rate with its dead time correction. The spatial resolution was degraded at high activities of (99m)Tc for all systems. On one of the systems (177)Lu increased the coincidence count rate and slightly affected the spatial resolution. The results for high activities of (177)Lu were similar to those for (99m)Tc.CONCLUSION: Intratherapeutic imaging might be a feasible method to study RPT treatment response. However, some sensitive preclinical PET systems, unable to handle high count rates, suffer count losses and may also introduce image artifacts.
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| 34. |
- Mellhammar, Emma, et al.
(författare)
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Preserving Preclinical PET Quality During Intratherapeutic Imaging in Radionuclide Therapy with Rose Metal Shielding Reducing Photon Flux
- 2019
-
Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine. - 0161-5505 .- 2159-662X. ; 60:5, s. 710-715
-
Tidskriftsartikel (refereegranskat)abstract
- Performing PET imaging during ongoing radionuclide therapy can be a promising method to follow tumor response in vivo. However, the high therapeutic activity can interfere with the PET camera performance and degrade both image quality and quantitative capabilities. As a solution, low-energy photon emissions from the therapeutic radionuclide can be highly attenuated, still allowing sufficient detection of annihilation photons in coincidence. Methods: Hollow Rose metal cylinders with walls 2-4 mm thick were used to shield a 22Na point source and a uniform phantom filled with 18F as they were imaged on a preclinical PET camera with increasing activities of 177Lu. A mouse with a subcutaneous tumor was injected with 18F-FDG and imaged with an additional 120 MBq of 177Lu and repeated with shields surrounding the animal. Results: The addition of 177Lu to the volume imaged continuously degraded the image quality with increasing activity. The image quality was improved when shielding was introduced. The shields showed a high ability to produce stable and reproducible results for both spatial resolution and quantification of up to 120 MBq of 177Lu activity (maximum activity tested). Conclusion: Without shielding, the activity quantification will be inaccurate for time points at which therapeutic activities are high. The suggested method shows that the shields reduce the noise induced by the 177Lu and therefore enable longitudinal quantitative intratherapeutic imaging studies.
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| 35. |
- Moore, Derek G, et al.
(författare)
-
During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption, but continue to smoke tobacco and cannabis: initial findings from the Development and Infancy Study
- 2010
-
Ingår i: Journal of Psychopharmacology. - : SAGE Publications. - 0269-8811 .- 1461-7285. ; 24, s. 1403-1410
-
Tidskriftsartikel (refereegranskat)abstract
- While recreational drug use in UK women is prevalent, to date there is little prospective data on patterns of drug use in recreational drug-using women immediately before and during pregnancy. A total of 121 participants from a wide range of backgrounds were recruited to take part in the longitudinal Development and Infancy Study (DAISY) study of prenatal drug use and outcomes. Eighty-six of the women were interviewed prospectively while pregnant and/or soon after their infant was born. Participants reported on use immediately before and during pregnancy and on use over their lifetime. Levels of lifetime drug use of the women recruited were high, with women reporting having used at least four different illegal drugs over their lifetime. Most users of cocaine, 3,4-methylenedioxy-N-methylamphetamine (MDMA) and other stimulants stopped using these by the second trimester and levels of use were low. However, in pregnancy, 64% of the sample continued to use alcohol, 46% tobacco and 48% cannabis. While the level of alcohol use reduced substantially, average tobacco and cannabis levels tended to be sustained at pre-pregnancy levels even into the third trimester (50 cigarettes and/or 11 joints per week). In sum, while the use of ‘party drugs’ and alcohol seems to reduce, levels of tobacco and cannabis use are likely to be sustained throughout pregnancy. The data provide polydrug profiles that can form the basis for the development of more realistic animal models.
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| 36. |
- Moore, Derek G., et al.
(författare)
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Infants perceive human point-light displays as solid forms
- 2007
-
Ingår i: Cognition. - : Elsevier BV. - 0010-0277 .- 1873-7838. ; 104, s. 377-396
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Tidskriftsartikel (refereegranskat)abstract
- While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and material objects. To explore these issues we tested whether infants would selectively apply the principle of solidity to upright human displays. In the first experiment infants aged six and nine months were repeatedly shown a human point-light display walking across a computer screen up to 10 times or until habituated. Next, they were repeatedly shown the walking display passing behind an in-depth representation of a table, and finally they were shown the human display appearing to pass through the table top in violation of the solidity of the hidden human form. Both six- and nine-month-old infants showed significantly greater recovery of attention to this final phase. This suggests that infants are able to bind a solid vertical form to human motion. In two further control experiments we presented displays that contained similar patterns of motion but were not perceived by adults as human. Six- and nine-month-old infants did not show recovery of attention when a scrambled display or an inverted human display passed through the table. Thus, the binding of a solid human form to a display in only seems to occur for upright human motion. The paper considers the implications of these findings in relation to theories of infants’ developing conceptions of objects, humans and animals. ?? 2006 Elsevier B.V. All rights reserved.
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| 37. |
- Mähler, Emma, et al.
(författare)
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Detecting small liver tumors with In-111-Pentetreotide SPECT-A Collimator study based on Monte Carlo simulations
- 2012
-
Ingår i: IEEE Transactions on Nuclear Science. - : IEEE. - 0018-9499 .- 1558-1578. ; 59:1, s. 47-53
-
Tidskriftsartikel (refereegranskat)abstract
- In In-111- pentetreotide single-photon emission computed tomography (SPECT), the tumor-to-background-uptake ratio is generally high. The noise is, however, also usually on a high level, and in combination with the low spatial resolution of SPECT, this may lead to difficulties in the detection of small tumors. This is especially the case in regions with a relatively high background activity, such as in the liver, which is a common region for somatostatin-positive metastases. Visually detecting the small tumors is important for a successful treatment of the cancer disease. In this paper, we compare three different parallel-hole collimators for In-111-pentetreotide SPECT regarding contrast as a function of image noise for a phantom simulating small tumors in liver background. The corresponding contrast-to-noise ratios are also presented. All raw-data projections are produced using Monte Carlo simulations. The collimators are of type low-energy general-purpose (LEGP), extended LEGP (ELEGP), and medium-energy general-purpose (MEGP). Reconstructions were performed with OSEM both with and without model-based compensation. Of the investigated collimators, the ELEGP collimator proved to be the most optimal for the smallest tumors, both with and without model-based compensation included in the reconstruction. It is also shown that model-based compensation outperforms the conventional reconstruction technique.
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| 38. |
- Nittérus, Karolina, 1972, et al.
(författare)
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Insects reared from logging residue on clear-cuts
- 2004
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Ingår i: Entomologica Fennica. - 0785-8760. ; 15:1, s. 53-61
-
Tidskriftsartikel (refereegranskat)abstract
- Coniferous and deciduous logging residue ("slash") was collected from six 1-year old and six 4-year old clear-cuts in South-West Sweden during the spring of 2002. In the laboratory, insects were emerged under standardised conditions. Insects emerged in 41% of the rearing-tubes with 1-year old slash. In 4-year old slash, 54% of the tubes contained insects. The most successfully emerged order was Coleoptera, represented by 10 families, 22 species and 425 individuals. The second most abundant order was Hymenoptera. The most abundant Coleoptera family was Curculionidae that comprised 48% of all the beetles. Four distinct species groups among Coleoptera. were found, each group being separated by slash age and tree category (deciduous/coniferous). Significantly more species were found in the 4-year old deciduous slash, compared to the 1-year old. In coniferous slash, there was a tendency for more species in the 1-year old slash than in the 4-year old. The results suggest that slash is valuable as breeding substrate and/or food supply to the beetle fauna on clear-cuts.
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| 39. |
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| 40. |
- Peden, John F., et al.
(författare)
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A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:4, s. 339-344
-
Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with similar to 575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 x 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
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| 41. |
- Perry, Lynn K, et al.
(författare)
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Learning What to Remember: Vocabulary Knowledge and Children’s Memory for Object Names and Features
- 2016
-
Ingår i: Infant and Child Development. - : Wiley. - 1522-7227 .- 1522-7219. ; 25, s. 247-258
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Tidskriftsartikel (refereegranskat)abstract
- Although young children can map a novel name to a novel object, it remains unclear what they actually remember about objects when they initially make such a name–object association. In the current study we investigated (1) what children remembered after they were initially introduced to name–object associations and (2) how their vocabulary size and vocabulary structure influenced what they remembered. As a group, children had difficulty remembering each of the features of the original novel objects. Further analyses revealed that differences in vocabulary structure predicted children’s ability to remember object features. Specifically, children who produced many names for categories organized by similarity in shape (e.g. ball, cup) had the best mem-ory for newly-learned objects’ features—especially their shapes. In addition, the more features children remembered, the more likely they were to retain the newly learned name–object associa-tions. Vocabulary size, however, was not predictive of children’s feature memory or retention. Taken together, these findings dem-onstrate that children’s existing vocabulary structure, rather than simply vocabulary size, influences what they attend to when en-countering a new object and subsequently their ability to remem-ber new name–object associations.
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| 42. |
- Rajwa, Pawel, et al.
(författare)
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Research protocol for an observational health data analysis on the adverse events of systemic treatment in patients with metastatic hormone-sensitive prostate cancer : big data analytics using the PIONEER platform
- 2024
-
Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 63, s. 81-88
-
Tidskriftsartikel (refereegranskat)abstract
- Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in “real-life” patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies.
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| 43. |
- Seersholm, Frederik Valeur, et al.
(författare)
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Repeated plague infections across six generations of Neolithic Farmers
- 2024
-
Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 632:8023, s. 114-121
-
Tidskriftsartikel (refereegranskat)abstract
- In the period between 5,300 and 4,900 calibratedyears before present (cal. bp), populations across large parts of Europe underwent a period of demographic decline1,2. However, the cause of this so-called Neolithic decline is still debated. Some argue for an agricultural crisis resulting in the decline3, others for the spread of an early form of plague4. Here we use population-scale ancient genomics to infer ancestry, social structure and pathogen infection in 108 Scandinavian Neolithic individuals from eight megalithic graves and a stone cist. We find that the Neolithic plague was widespread, detected in at least 17% of the sampled population and across large geographical distances. We demonstrate that the disease spread within the Neolithic community in three distinct infection events within a period of around 120 years. Variant graph-based pan-genomics shows that the Neolithic plague genomes retained ancestral genomic variation present in Yersinia pseudotuberculosis, including virulence factors associated with disease outcomes. In addition, we reconstruct four multigeneration pedigrees, the largest of which consists of 38 individuals spanning six generations, showing a patrilineal social organization. Lastly, we document direct genomic evidence for Neolithic female exogamy in a woman buried in a different megalithic tomb than her brothers. Taken together, our findings provide a detailed reconstruction of plague spread within a large patrilineal kinship group and identify multiple plague infections in a population dated to the beginning of the Neolithic decline.
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| 44. |
- Škerlep, Martin, et al.
(författare)
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Afforestation driving long-term surface water browning
- 2020
-
Ingår i: Global Change Biology. - : Wiley. - 1354-1013 .- 1365-2486. ; 26:3, s. 1390-1399
-
Tidskriftsartikel (refereegranskat)abstract
- Increase in surface water color (browning), caused by rising dissolved organic carbon (DOC) and iron concentrations, has been widely reported and studied in the last couple of decades. This phenomenon has implications to aquatic ecosystem function and biogeochemical carbon cycling. While recovery from acidification and changes in climate-related variables, such as precipitation and length of growing season, are recognized as drivers behind browning, land-use change has received less attention. In this study, we include all of the above factors and aim to discern their individual and combined contribution to water color variation in an unprecedentedly long (1940–2016) and highly resolved dataset (~20 times per month), from a river in southern Sweden. Water color showed high seasonal variability and a marked long-term increase, particularly in the latter half of the dataset (~1980). Short-term and seasonal variations were best explained by precipitation, with temperature playing a secondary role. All explanatory variables (precipitation, temperature, S deposition, and land-use change) contributed significantly and together predicted 75% of the long-term variation in water color. Long-term change was best explained by a pronounced increase in Norway spruce (Picea abies Karst) volume—a measure of land-use change and a proxy for buildup of organic soil layers—and by change in atmospheric S deposition. When modeling water color with a combination of explanatory variables, Norway spruce showed the highest contribution to explaining long-term variability. This study highlights the importance of considering land-use change as a factor behind browning and combining multiple factors when making predictions in water color and DOC.
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| 45. |
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| 46. |
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| 47. |
- Tomalski, Przemyslaw, et al.
(författare)
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Socioeconomic status and functional brain development - associations in early infancy
- 2013
-
Ingår i: Developmental Science. - : Wiley. - 1363-755X .- 1467-7687. ; 16, s. 676-687
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Tidskriftsartikel (refereegranskat)abstract
- Socioeconomic status (SES) impacts on both structural and functional brain development in childhood, but how early its effects can be demonstrated is unknown. In this study we measured resting baseline EEG activity in the gamma frequency range in awake 6-9-month-olds from areas of East London with high socioeconomic deprivation. Between-subjects comparisons of infants from low- and high-income families revealed significantly lower frontal gamma power in infants from low-income homes homes. Similar power differences were found when comparing infants according to maternal occupation, with lower occupational status groups yielding lower power. Infant sleep, maternal education, length of gestation, and birth weight, as well as smoke exposure and bilingualism, did not explain these differences. Our results show that the effects of socioeconomic disparities on brain activity can already be detected in early infancy, potentially pointing to very early for language and attention difficulties. This is the first study to reveal region-selective differences in functional brain development associated with early infancy in low-income families.
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| 48. |
- Winsnes, Casper F., et al.
(författare)
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A proteome map of the micronucleus reveals a diversity of nuclear functions
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Annan publikation (övrigt vetenskapligt/konstnärligt)abstract
- Micronuclei are small nuclei-like structures, commonly associated with cancer, that have long been used as biomarkers of DNA damage and chromosomal instability. They are caused by lagging chromosomes or chromosome fragments that fail to be incorporated into primary nuclei during mitosis. Until recently, they were thought to be inert but recent studies have shown that micronuclei may be playing an active role in cellular biology, particularly in the context of cancer and chromothripsis. However, the precise ways that micronuclei perform these functions remain unknown.In this study, we perform the first comprehensive mapping and functional analysis of the micronuclear proteome. We demonstrate that micronuclei are involved in several known cellular processes, showing high enrichment for proteins involved in gene expression, cell cycle checkpoints, and DNA damage repair among other things. Furthermore, we show that several poorly categorized proteins also localize to micronuclei, hinting towards unknown functionality beyond the already known. Our results indicate that micronuclei are more involved in cellular activity than previously thought and that .We anticipate this resource to be a starting point for further investigation into the functions of micronuclei, particularly for their role in DNA damage and the chromothripsis phenomenon. Additionally, we believe that it can be used for investigation into errors in mitosis and new ways of treating diseases.
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| 49. |
- Witt, Sofia, et al.
(författare)
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Mismatch between risk factors and preventive interventions? A register study of fall prevention among older people in one Swedish county
- 2018
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Ingår i: International Journal of Older People Nursing. - : John Wiley & Sons. - 1748-3735 .- 1748-3743. ; 13:4
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Falls are a common and often a devastating health hazard for older people, causing suffering, morbidity and mortality. Falls are costly for society in terms of both resources and direct medical costs. Although knowledge about falls and fall prevention is well known, falls among older people are still a major problem. AIM AND OBJECTIVES: The aim was to estimate the prevalence of the risk of falls among older people receiving municipal health care. A further aim was to investigate the consistency between fall risk factors and preventive nursing interventions. DESIGN: A cross-sectional register study. METHODS: Data containing risk assessments based on the Downton Fall Risk Index (DFRI) and planned interventions by the municipal health care were collected from the Swedish national quality registry, Senior Alert. Data were analysed using descriptive and analytic statistics. RESULTS: In the sample of 5,427 older people, the prevalence of the risk of falling was 79%. There was a difference in prevalence between the different types of municipal health care, sex and age. The most common preventive intervention was environment adjustments, and the least planned intervention was information/education about falls. Physical activity as an intervention was planned among 13.2% of the participants. Approximately 27% of the older people did not have any planned interventions despite being at risk of falling. Planned interventions did not always correspond with the risk factors; for instance, only 35.4% of those at risk of falling due to medication obtained pharmaceutical reviews as a preventive measure to decrease the risk. CONCLUSION: The risk of falling is common among older people, and the preventive interventions do not sufficiently follow current evidence. This implies that systematic implementation of fall-prevention guidelines is needed in municipal care. IMPLICATION FOR PRACTICE: A better match between identified risk factors and preventive interventions is warranted.
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| 50. |
- Woolfenden, Susan, et al.
(författare)
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Prevalence and factors associated with parental concerns about development detected by the Parents’ Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks in a birth cohort
- 2016
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Early identification of developmental vulnerability is vital. This study aimed to estimate the prevalence of moderate or high developmental risk on the Parents’ Evaluation of Developmental Status (PEDS) at 6-month, 12-month and 18-month well-child checks; identify associated risk factors; and examine documentation of the PEDS at well-child checks. Design, participants: A prospective birth cohort of 2025 children with 50% of those approached agreeing to participate. Demographic data were obtained via questionnaires and linked electronic medical records. Telephone interviews were conducted with parents to collect PEDS data. Primary and secondary outcomes: Multiple logistic regression analyses identified risk factors for moderate or high developmental risk on the PEDS. A Cumulative Risk Index examined the impact of multiple risk factors on developmental risk and documentation of the PEDS at the well-child checks. Results: Of the original cohort, 792 (39%) had 6-month, 649 (32%) had 12-month and 565 (28%) had 18-month PEDS data. Parental concerns indicating moderate or high developmental risk on the PEDS were 27% (95% CI 24 to 30) at 6 months, 27% (95% CI 24 to 30) at 12 months and 33% (95% CI 29 to 37) at 18 months. Factors associated with moderate or high developmental risk were perinatal risk (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); maternal Middle Eastern or Asian nationality (OR 6 months: 1.6 (95% CI 1.1 to 2.4)), (OR 12 months: 1.7 (95% CI 1.1 to 2.7)); and household disadvantage (OR 6 months: 1.5 (95% CI 1.0 to 2.2). As the number of risk factors increased the odds increased for high or moderate developmental risk and no documentation of the PEDS at well-child checks. Conclusions: Children with multiple risk factors are more likely to have parental concerns indicating developmental vulnerability using the PEDS and for these concerns to not be documented.
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