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| 2. |
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| 3. |
- Jaffee, E. M., et al.
(författare)
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Future cancer research priorities in the USA: a Lancet Oncology Commission
- 2017
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Ingår i: Lancet Oncology. - 1470-2045. ; 18:11
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Forskningsöversikt (refereegranskat)abstract
- We are in the midst of a technological revolution that is providing new insights into human biology and cancer. In this era of big data, we are amassing large amounts of information that is transforming how we approach cancer treatment and prevention. Enactment of the Cancer Moonshot within the 21st Century Cures Act in the USA arrived at a propitious moment in the advancement of knowledge, providing nearly US$ 2 billion of funding for cancer research and precision medicine. In 2016, the Blue Ribbon Panel (BRP) set out a roadmap of recommendations designed to exploit new advances in cancer diagnosis, prevention, and treatment. Those recommendations provided a high-level view of how to accelerate the conversion of new scientific discoveries into effective treatments and prevention for cancer. The US National Cancer Institute is already implementing some of those recommendations. As experts in the priority areas identified by the BRP, we bolster those recommendations to implement this important scientific roadmap. In this Commission, we examine the BRP recommendations in greater detail and expand the discussion to include additional priority areas, including surgical oncology, radiation oncology, imaging, health systems and health disparities, regulation and financing, population science, and oncopolicy. We prioritise areas of research in the USA that we believe would accelerate efforts to benefit patients with cancer. Finally, we hope the recommendations in this report will facilitate new international collaborations to further enhance global efforts in cancer control.
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| 4. |
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| 5. |
- Frazier-Wood, Alexis C., et al.
(författare)
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Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
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Ingår i: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
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Tidskriftsartikel (refereegranskat)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
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| 6. |
- Adamson, R. E., et al.
(författare)
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In Vitro Primary Cell Culture as a Physiologically Relevant Method for Preclinical Testing of Human Oncolytic Adenovirus
- 2012
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Ingår i: Human Gene Therapy. - : Mary Ann Liebert Inc. - 1043-0342 .- 1557-7422. ; 23:2, s. 218-230
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Tidskriftsartikel (refereegranskat)abstract
- Ad[I/PPT-E1A] is an oncolytic adenovirus that specifically kills prostate cells via restricted replication by a prostate-specific regulatory element. Off-target replication of oncolytic adenoviruses would have serious clinical consequences. As a proposed ex vivo test, we describe the assessment of the specificity of Ad[I/PPT-E1A] viral cytotoxicity and replication in human nonprostate primary cells. Four primary nonprostate cell types were selected to mimic the effects of potential in vivo exposure to Ad[I/PPT-E1A] virus: bronchial epithelial cells, urothelial cells, vascular endothelial cells, and hepatocytes. Primary cells were analyzed for Ad[I/PPT-E1A] viral cytotoxicity in MTS assays, and viral replication was determined by hexon titer immunostaining assays to quantify viral hexon protein. The results revealed that at an extreme multiplicity of infection of 500, unlikely to be achieved in vivo, Ad[I/PPT-E1A] virus showed no significant cytotoxic effects in the nonprostate primary cell types apart from the hepatocytes. Transmission electron microscopy studies revealed high levels of Ad[I/PPT-E1A] sequestered in the cytoplasm of these cells. Adenoviral green fluorescent protein reporter studies showed no evidence for nuclear localization, suggesting that the cytotoxic effects of Ad[I/PPT-E1A] in human primary hepatocytes are related to viral sequestration. Also, hepatocytes had increased amounts of coxsackie adenovirus receptor surface protein. Active viral replication was only observed in the permissive primary prostate cells and LNCaP prostate cell line, and was not evident in any of the other nonprostate cells types tested, confirming the specificity of Ad[I/PPT-E1A]. Thus, using a relevant panel of primary human cells provides a convenient and alternative preclinical assay for examining the specificity of conditionally replicating oncolytic adenoviruses in vivo.
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| 7. |
- Buyanova, Irina, 1960-, et al.
(författare)
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Optical study of spin injection dynamics in InGaN/GaN quantum wells with GaMnN injection layers
- 2004
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Ingår i: Journal of Vacuum Science & Technology B. - : American Vacuum Society. - 1071-1023 .- 1520-8567. ; 22:6, s. 2668-2672
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Tidskriftsartikel (refereegranskat)abstract
- The spin injection dynamics of GaMnN/InGaN multiquantum well (MQW) light emitting diodes (LEDs) grown by molecular beam epitaxy were examined using picosecond-transient and circularly polarized photoluminescence (PL) measurements. Even with the presence of a room temperature ferromagnetic GaMnN spin injector, the LEDs are shown to exhibit very low efficiency of spin injection. Based on resonant optical orientation spectroscopy, the spin loss in the structures is shown to be largely due to fast spin relaxation within the InGaN MQW, which itself destroys any spin polarization generated by optical spin orientation or electrical spin injection. Typical photoluminescence decay times were 20-40 ns in both commercial GaN MQW LEDs with emission wavelengths between 420-470 nm and in the GaMnN/InGaN multi-quantum well MQW LEDs. In the wurtzite InGaN/GaN system, biaxial strain at the interfaces give rise to large piezoelectric fields directed along the growth axis. This built-in piezofield breaks the reflection symmetry of confining potential leading to the presence of a large Rashba term in the conduction band Hamiltonian which is responsible for the short spin relaxation times.
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| 8. |
- Chen, Weimin, 1959-, et al.
(författare)
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Efficient spin relaxation in InGaN/GaN and InGaN/GaMnN quantum wells : An obstacle to spin detection
- 2005
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 87:19, s. 192107-
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Tidskriftsartikel (refereegranskat)abstract
- Transient magneto-optical spectroscopy of InGaNGaN and InGaNGaMnN quantum wells reveals a spin relaxation process with a characteristic time of 50 ps. We show that the observed spin relaxation is mediated by spin flips of individual carriers rather than by direct exciton spin flips, and is proposed to occur near the bottom of the exciton band (K=0). Nearly complete thermalization between spin sublevels of the excitons, observed immediately after the pulsed photoexcitation, is attributed to even faster spin relaxation of photogenerated hot carriers/excitons accompanying momentum and energy relaxation at high K vectors. © 2005 American Institute of Physics.
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| 9. |
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| 10. |
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| 11. |
- Chen, Weimin, 1959-, et al.
(författare)
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Spin relaxation in InGaN/Ga(Mn)N quantum wells
- 2005
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Ingår i: Bulletin of the American physical society. - 0003-0503. ; 50, s. 609-609
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Tidskriftsartikel (refereegranskat)abstract
- Proc. 2005 APS March Meeting, March 21-25, 2005; Los Angeles, CA, USA
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| 12. |
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| 13. |
- Kyrychenko, F.V., et al.
(författare)
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Investigation of a GaMnN/GaN/InGaN structure for spinLED
- 2005
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Ingår i: 27th Int. Conf. on the Physics of Semicond,2004. - : American Institute of Physics (AIP). - 0735402574 ; , s. 1319-1320
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Theoreticaland experimental studies of GaMnN/GaN/InGaN structure for a spin LEDdevice were performed. Strong electron spin relaxation was experimentally observedin a InGaN/GaN quantum well. It is shown that thestrong spin relaxation might result from the built-in piezoelectric fieldin strained wurzite heterostructures. A five level k · pmodel was used for microscopic calculations of the structure inversionasymmetry induced spin-orbit interaction. The magnitude of this interaction isshown to be comparable with that in InGaAs/GaAs quantum structures.©2005 American Institute of Physics
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| 14. |
- Polyakov, A. Y., et al.
(författare)
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Electrical and luminescent properties and the spectra of deep centers in GaMnN/InGaN light-emitting diodes
- 2004
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Ingår i: Journal of Electronic Materials. - : Springer Science and Business Media LLC. - 0361-5235 .- 1543-186X. ; 33:3, s. 241-247
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Tidskriftsartikel (refereegranskat)abstract
- Electrical and electroluminescent properties were studied for GaN/InGaN light-emitting diodes (LEDs) with the n-GaN layer up and with the top portion of the n layer made of undoped GaMnN to allow polarization modulation by applying an external magnetic field (so-called -spin-LEDs-). The contact annealing temperature was kept to 750°C, which is the thermal stability limit for retaining room-temperature magnetic ordering in the GaMnN layer. Measurable electroluminescence (EL) was obtained in these structures at threshold voltages of ∼15 V, with a lower EL signal compared to control LEDs without Mn. This is related to the existence of two parasitic junctions between the metal and the lower contact p-type layer and between the GaMnN and the n-GaN in the top contact layer.
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| 15. |
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| 16. |
- Blenckner, Thorsten, et al.
(författare)
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The Baltic Health Index (BHI): Assessing the social-ecological status of the Baltic Sea
- 2021
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Ingår i: People and Nature. - : Wiley. - 2575-8314. ; 3:2, s. 359-375
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Tidskriftsartikel (refereegranskat)abstract
- Improving the health of coastal and open sea marine ecosystems represents a substantial challenge for sustainable marine resource management, since it requires balancing human benefits and impacts on the ocean. This challenge is often exacerbated by incomplete knowledge and lack of tools that measure ocean and coastal ecosystem health in a way that allows consistent monitoring of progress towards predefined management targets. The lack of such tools often limits capabilities to enact and enforce effective governance. We introduce the Baltic Health Index (BHI) as a transparent, collaborative and repeatable assessment tool. The Index complements existing, more ecological-oriented, approaches by including a human dimension on the status of the Baltic Sea, an ecosystem impacted by multiple anthropogenic pressures and governed by a multitude of comprehensive national and international policies. Using a large amount of social-ecological data available, we assessed the health of the Baltic Sea for nine goals that represent the status towards set targets, for example, clean waters, biodiversity, food provision, natural products extraction and tourism. Our results indicate that the overall health of the Baltic Sea is suboptimal (a score of 76 out of 100), and a substantial effort is required to reach the management objectives and associated targets. Subregionally, the lowest BHI scores were measured for carbon storage, contaminants and lasting special places (i.e. marine protected areas), albeit with large spatial variation. Overall, the likely future status of all goals in the BHI averaged for the entire Baltic Sea is better than the present status, indicating a positive trend towards a healthier Baltic Sea. However, in some Baltic Sea basins, the trend for specific goals was decreasing, highlighting locations and issues that should be the focus of management priorities. The BHI outcomes can be used to identify both pan-Baltic and subregional scale management priorities and to illustrate the interconnectedness between goals linked by cumulative pressures. Hence, the information provided by the BHI tool and its further development will contribute towards the fulfilment of the UN Agenda 2030 and its Sustainability Development Goals. A free Plain Language Summary can be found within the Supporting Information of this article. A free Plain Language Summary can be found within the Supporting Information of this article.
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| 17. |
- Ding, Ming, et al.
(författare)
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Dairy consumption, systolic blood pressure, and risk of hypertension : Mendelian randomization study
- 2017
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Ingår i: The BMJ. - : BMJ Publishing Group Ltd. - 1756-1833 .- 0959-8138. ; 356
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE To examine whether previous observed inverse associations of dairy intake with systolic blood pressure and risk of hypertension were causal. DESIGN Mendelian randomization study using the single nucleotide polymorphism rs4988235 related to lactase persistence as an instrumental variable. SETTING CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium. PARTICIPANTS Data from 22 studies with 171 213 participants, and an additional 10 published prospective studies with 26 119 participants included in the observational analysis. MAIN OUTCOME MEASURES The instrumental variable estimation was conducted using the ratio of coefficients approach. Using metaanalysis, an additional eight published randomized clinical trials on the association of dairy consumption with systolic blood pressure were summarized. RESULTS Compared with the CC genotype (CC is associated with complete lactase deficiency), the CT/TT genotype (TT is associated with lactose persistence, and CT is associated with certain lactase deficiency) of LCT-13910 (lactase persistence gene) rs4988235 was associated with higher dairy consumption (0.23 (about 55 g/day), 95% confidence interval 0.17 to 0.29) serving/day; P<0.001) and was not associated with systolic blood pressure (0.31, 95% confidence interval -0.05 to 0.68 mm Hg; P=0.09) or risk of hypertension (odds ratio 1.01, 95% confidence interval 0.97 to 1.05; P=0.27). Using LCT-13910 rs4988235 as the instrumental variable, genetically determined dairy consumption was not associated with systolic blood pressure (beta=1.35, 95% confidence interval -0.28 to 2.97 mm Hg for each serving/day) or risk of hypertension (odds ratio 1.04, 0.88 to 1.24). Moreover, meta-analysis of the published clinical trials showed that higher dairy intake has no significant effect on change in systolic blood pressure for interventions over one month to 12 months (intervention compared with control groups: beta=-0.21, 95% confidence interval -0.98 to 0.57 mm Hg). In observational analysis, each serving/day increase in dairy consumption was associated with -0.11 (95% confidence interval -0.20 to -0.02 mm Hg; P=0.02) lower systolic blood pressure but not risk of hypertension (odds ratio 0.98, 0.97 to 1.00; P=0.11). CONCLUSION The weak inverse association between dairy intake and systolic blood pressure in observational studies was not supported by a comprehensive instrumental variable analysis and systematic review of existing clinical trials.
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| 18. |
- Frazier, I., et al.
(författare)
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Older Adults Show More Trust Than Younger Adults Post-Betrayal in Trust/Lottery Game
- 2017
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Konferensbidrag (refereegranskat)abstract
- Older adults comprise both the fastest growing population segment in industrialized nations and the majority of political and industry leaders. Regardless of social status, older adults face a constant flow of highly consequential decisions. These decisions are often social in nature, even when they primarily concern health, finance, or politics; in particular, they often require putting trust in others. However, older adults’ social decision making processes relating to trust have not been well researched yet. Trust is an important aspect of maintaining social supports and maintenance of social supports is health protective. This is of particular concern in older adults as aging is linked to increased social loss, isolation, and loneliness. Evidence has indicated that the neuropeptide oxytocin (OT) is linked to several aspects of socioemotional functioning including trust. There is emerging evidence of a possible deficit in OT in older, specifically male, adults. Intranasally administered OT before a trust game has resulted in young adults acting in a more trusting, but not gullible manner. However, the potential effects of OT administration on trust game performance in older adults is unknown. We compared older (N = 54, 56% female) and younger adults’ (N = 48, 48% female) performance on a Trust/Lottery game after intranasal administration of either OT or placebo (P). Participants played the role of investors with ostensible same age social partners (trust) or a computer (lottery). At the beginning of each game investors received monetary units to invest in increments. They were instructed that if money was sent it would be tripled and then the investee (ostensible social partner) would be able to send an amount, or none, back or the lottery would be played (in the lottery condition). The probabilities of the trustee returning behavior in both the trust and lottery conditions were drawn from the same probability distributions, thus the participants faced the same objective risk but only interacted socially in the trust condition. Twelve trust and 12 lottery games were played in a pseudo-randomly, counterbalanced fashion. After half of the trust and lottery trials were played, a feedback screen was presented informing participants that in both the trust and lottery conditions only 50% of their investments bore returns, signifying 50% chance of trust breach or lottery success. While no effects of OT were detected, trust trials older adults increased their investments post betrayal while younger adults decreased their investments (F = 5.53, p = .021). No such differences were found in the lottery game. These results may indicate that older adults are more forgiving of breaching trust than younger adults. However, these results may also indicate vulnerability to being taken advantage of in a social context. To address these interpretations, research examining older adults’ goals in social decision making contexts is warranted.
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| 19. |
- Graham, J. B., et al.
(författare)
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The Malmo polymorphism of coagulation factor IX, an immunologic polymorphism due to dimorphism of residue 148 that is in linkage disequilibrium with two other F.IX polymorphisms
- 1988
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 42:4, s. 573-580
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Tidskriftsartikel (refereegranskat)abstract
- A mouse monoclonal antibody (MAB 9,9) to coagulation factor IX (F.IX) detects a polymorphism in the plasma of normal people. Its epitope has been narrowed down to <6 amino acids in the activation peptide of the X-linked F.IX protein. The activation peptide contains a dimorphism - Thr:Ala - at position 148 of the protein. Using synthetic oligonucleotides, we have demonstrated that (1) the F.IX which reacts with 9.9 has Thr at position 148 and (2) that which does not has Ala. Positive reactors (148(thr)) are designated Malmo A, and negative reactors (148(ala)) are designated Malmo B. The plasma levels of AA women are indistinguishable from those of A men, and both B men and BB women are null against MAB 9.9. The plasma level of Malmo A in AB women is approximately half that of AA women, and 'lyonization' is clearly operating in the heterozygotes. The dimorphism is in strong linkage disequilibrium with two other intragenic RFLPs, TaqI and XmnI. Furthermore, intragenic crossing-over - including double crossing-over - appears to have occurred between the three sites. Seven of the eight possible haplotypes have been identified, five in men and two others in women. The immunoassay that identifies ~50% of the AB women in the pool of Malmo A females with 95% confidence identifies men unambiguously as A or B. The assay would be very useful for population-genetic studies of the Malmo epitope if the studies were limited to men.
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| 20. |
- McKeown, Nicola M., et al.
(författare)
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Sugar-sweetened beverage intake associations with fasting glucose and insulin concentrations are not modified by selected genetic variants in a ChREBP-FGF21 pathway : a meta-analysis
- 2018
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 61:2, s. 317-330
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis: Sugar-sweetened beverages (SSBs) are a major dietary contributor to fructose intake. A molecular pathway involving the carbohydrate responsive element-binding protein (ChREBP) and the metabolic hormone fibroblast growth factor 21 (FGF21) may influence sugar metabolism and, thereby, contribute to fructose-induced metabolic disease. We hypothesise that common variants in 11 genes involved in fructose metabolism and the ChREBP-FGF21 pathway may interact with SSB intake to exacerbate positive associations between higher SSB intake and glycaemic traits. Methods: Data from 11 cohorts (six discovery and five replication) in the CHARGE (Cohorts for Heart and Aging Research in Genomic Epidemiology) Consortium provided association and interaction results from 34,748 adults of European descent. SSB intake (soft drinks, fruit punches, lemonades or other fruit drinks) was derived from food-frequency questionnaires and food diaries. In fixed-effects meta-analyses, we quantified: (1) the associations between SSBs and glycaemic traits (fasting glucose and fasting insulin); and (2) the interactions between SSBs and 18 independent SNPs related to the ChREBP-FGF21 pathway. Results: In our combined meta-analyses of discovery and replication cohorts, after adjustment for age, sex, energy intake, BMI and other dietary covariates, each additional serving of SSB intake was associated with higher fasting glucose (β ± SE 0.014 ± 0.004 [mmol/l], p = 1.5 × 10−3) and higher fasting insulin (0.030 ± 0.005 [loge pmol/l], p = 2.0 × 10−10). No significant interactions on glycaemic traits were observed between SSB intake and selected SNPs. While a suggestive interaction was observed in the discovery cohorts with a SNP (rs1542423) in the β-Klotho (KLB) locus on fasting insulin (0.030 ± 0.011 loge pmol/l, uncorrected p = 0.006), results in the replication cohorts and combined meta-analyses were non-significant. Conclusions/interpretation: In this large meta-analysis, we observed that SSB intake was associated with higher fasting glucose and insulin. Although a suggestive interaction with a genetic variant in the ChREBP-FGF21 pathway was observed in the discovery cohorts, this observation was not confirmed in the replication analysis. Trial registration: Trials related to this study were registered at clinicaltrials.govas NCT00005131 (Atherosclerosis Risk in Communities), NCT00005133 (Cardiovascular Health Study), NCT00005121 (Framingham Offspring Study), NCT00005487 (Multi-Ethnic Study of Atherosclerosis) and NCT00005152 (Nurses’ Health Study).
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| 21. |
- Myers, T. M., et al.
(författare)
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Hemodynamic Evaluation of the Jarvik 2000 Heart During Heart Failure
- 2001
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Ingår i: ASAIO journal (1992). - : Wolters Kluwer. - 1058-2916 .- 1538-943X. ; 46:2, s. 167-
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Tidskriftsartikel (refereegranskat)abstract
- The Jarvik 2000 Heart is an axial flow left ventricular assist system designed for long-term circulatory support. Purpose: To assess the level of hemodynamic support provided by the Jarvik 2000 in an animal model, with acute, severe heart failure. Methods: Heart failure (HF) was induced in 5 calves by progressively ligating the LAD coronary artery. A continuous infusion of esmolol hydrochloride was given to maintain the stability of HF. Compared to normal baseline values, during heart failure CI decreased by 33% (p < 0.02), LAP increased by 16% (p < 0.03), and BP decreased by 28% (p < 0.13). Once stable HF was established, the pump was turned on, and hemodynamic measurements were obtained at pump speed settings that ranged from 8,000 to 12,000 rpm. Results: Selected, mean hemodynamic values are presented in the table, CI, LAP, and BP improved significantly (p < 0.05) at pump speeds >9000 rpm. Pulse pressure (PP) narrowed by 64% (p < 0.009), and the PAP remained unchanged.Image ToolsBlood flow in the femoral artery increased but was not statistically significant. Other hemodynamic parameters such as HR, SVR, PVR, and CVP did not change significantly. Conclusions: The Jarvik 2000 Heart can provide a level of cardiac output support that normalizes the CI and LAP, while maintaining some arterial pressure pulsatility during HF. Systemic perfusion is increased while the left heart is unloaded.
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| 22. |
- Papautsky, I, et al.
(författare)
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Micromachined pipette arrays
- 2000
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Ingår i: IEEE transactions on bio-medical engineering. - : Institute of Electrical and Electronics Engineers (IEEE). - 0018-9294. ; 47:6, s. 812-819
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Tidskriftsartikel (refereegranskat)
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| 23. |
- Siegenthaler, MP, et al.
(författare)
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Mechanical reliability of the Jarvik 2000 Heart - Discussion
- 2006
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Ingår i: Annals of Thoracic Surgery. - : Elsevier BV. - 1552-6259 .- 0003-4975. ; 81:5, s. 1752-1759
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Tidskriftsartikel (refereegranskat)abstract
- Background. Device failure is a limitation of permanent mechanical circulatory support. We studied the mechanical reliability of the Jarvik 2000 Heart, an axial flow pump with ceramic bearings designed to provide more than 10 years' durability. Methods. The Jarvik 2000 Heart was implanted in 102 patients between April 2000 and December 2004. Eighty-three pumps with an abdominal driveline were implanted as a bridge-to-transplantation, and 19 with post-auricular power supply as lifetime therapy. Eighteen pumps were recovered intact after clinical use and run continuously on the bench to further assess durability. Results. No implantable component failure occurred either in patients or during bench testing. The cumulative pump run-time was 110 years: 59 years overall in vivo and 51 years in vitro. The mean support time for bridge-to-transplant recipients was 159 days, and for discharged lifetime-therapy recipients 551 days. Six recipients were supported moer than 2 years, with the longest ongoing approaching 5 years. External cables caused three system failures, with a 95% freedom from system failure at 4 years. Device malfunctions, related to external cables ( 9) and lack of a backup battery ( 1), caused no adverse consequences. Before introduction of noncorrosive, gold-plated stainless steel connectors, corrosion was observed on three connectors to the retroauricular power supply. Conclusions. The Jarvik 2000 Heart has had no implantable component failure. Meaningful durability data and failure mode can only be established by real-time testing in patients. The reliability and dependability of this device, in addition to the exchangeability of external components, give promise for long-term circulatory support in critically ill heart failure patients.
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| 24. |
- Smith, Caren E., et al.
(författare)
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Genome-Wide Interactions with Dairy Intake for Body Mass Index in Adults of European Descent
- 2018
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Ingår i: Molecular Nutrition & Food Research. - : Wiley. - 1613-4125. ; 62:3
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Tidskriftsartikel (refereegranskat)abstract
- Scope: Body weight responds variably to the intake of dairy foods. Genetic variation may contribute to inter-individual variability in associations between body weight and dairy consumption. Methods and results: A genome-wide interaction study to discover genetic variants that account for variation in BMI in the context of low-fat, high-fat and total dairy intake in cross-sectional analysis was conducted. Data from nine discovery studies (up to 25 513 European descent individuals) were meta-analyzed. Twenty-six genetic variants reached the selected significance threshold (p-interaction <10−7), and six independent variants (LINC01512-rs7751666, PALM2/AKAP2-rs914359, ACTA2-rs1388, PPP1R12A-rs7961195, LINC00333-rs9635058, AC098847.1-rs1791355) were evaluated meta-analytically for replication of interaction in up to 17 675 individuals. Variant rs9635058 (128 kb 3’ of LINC00333) was replicated (p-interaction = 0.004). In the discovery cohorts, rs9635058 interacted with dairy (p-interaction = 7.36 × 10−8) such that each serving of low-fat dairy was associated with 0.225 kg m−2 lower BMI per each additional copy of the effect allele (A). A second genetic variant (ACTA2-rs1388) approached interaction replication significance for low-fat dairy exposure. Conclusion: Body weight responses to dairy intake may be modified by genotype, in that greater dairy intake may protect a genetic subgroup from higher body weight.
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