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1.
IEEE Trans Biomed Eng ; 71(4): 1151-1160, 2024 Apr.
Article in English | MEDLINE | ID: mdl-37910420

ABSTRACT

OBJECTIVE: To enhance visualization in pediatric Otolaryngology middle ear surgeries and reduce mastoidectomy instances, we introduce a novel Articulating Chip-on-Tip Endoscope (ACoT Endo). METHODS: The ACoT Endo incorporates a cable-driven distal end camera and off-the-shelf Chip-on-Tip camera to improve visualization. We compared its capabilities with standard endoscopes, evaluating its bending capacity (70 ° ± 2 °) and center axis rotation (360 °). To test the overall functionality of this device, a Mock Ear was created to simulate the anatomy of the human ear, and the ACoT Endo's ability to be used in this cavity is compared to a standard 0 ° Karl Storz endoscope through tests with the Mock Ear and respective endoscopes. RESULTS: The ACoT Endo accurately captured surgical details similar to standard endoscopes in the ENT field. Compared to the 0 ° Karl Storz endoscope, the ACoT Endo demonstrated an increased field of view by approximately 69% and captured area by approximately 249%. ACot Endo allowed the surgeon to effortlessly articulate the camera with the rotation of a finger, while an excision tool was inserted in the middle ear, a procedure that is currently extremely difficult with standard endoscopes. CONCLUSION: The ACoT Endo's dynamic viewing angle and Chip-on-Tip camera enable unparalleled surgical visualization within the middle ear using a single endoscope, offering potential benefits in Otolaryngology procedures. SIGNIFICANCE: By reducing the need for invasive mastoidectomies and providing better visualization tools, the ACoT Endo has significant potential to improve outcomes and safety in pediatric middle ear surgeries.


Subject(s)
Ear, Middle , Endoscopes , Humans , Child , Ear, Middle/surgery , Endoscopy
2.
Phys Rev Lett ; 131(2): 022501, 2023 Jul 14.
Article in English | MEDLINE | ID: mdl-37505957

ABSTRACT

The ß decays from both the ground state and a long-lived isomer of ^{133}In were studied at the ISOLDE Decay Station (IDS). With a hybrid detection system sensitive to ß, γ, and neutron spectroscopy, the comparative partial half-lives (logft) have been measured for all their dominant ß-decay channels for the first time, including a low-energy Gamow-Teller transition and several first-forbidden (FF) transitions. Uniquely for such a heavy neutron-rich nucleus, their ß decays selectively populate only a few isolated neutron unbound states in ^{133}Sn. Precise energy and branching-ratio measurements of those resonances allow us to benchmark ß-decay theories at an unprecedented level in this region of the nuclear chart. The results show good agreement with the newly developed large-scale shell model (LSSM) calculations. The experimental findings establish an archetype for the ß decay of neutron-rich nuclei southeast of ^{132}Sn and will serve as a guide for future theoretical development aiming to describe accurately the key ß decays in the rapid-neutron capture (r-) process.

3.
Phys Rev Lett ; 131(26): 262501, 2023 Dec 29.
Article in English | MEDLINE | ID: mdl-38215380

ABSTRACT

The excited states of unstable ^{20}O were investigated via γ-ray spectroscopy following the ^{19}O(d,p)^{20}O reaction at 8 AMeV. By exploiting the Doppler shift attenuation method, the lifetimes of the 2_{2}^{+} and 3_{1}^{+} states were firmly established. From the γ-ray branching and E2/M1 mixing ratios for transitions deexciting the 2_{2}^{+} and 3_{1}^{+} states, the B(E2) and B(M1) were determined. Various chiral effective field theory Hamiltonians, describing the nuclear properties beyond ground states, along with a standard USDB interaction, were compared with the experimentally obtained data. Such a comparison for a large set of γ-ray transition probabilities with the valence space in medium similarity renormalization group ab initio calculations was performed for the first time in a nucleus far from stability. It was shown that the ab initio approaches using chiral effective field theory forces are challenged by detailed high-precision spectroscopic properties of nuclei. The reduced transition probabilities were found to be a very constraining test of the performance of the ab initio models.

4.
PLoS One ; 17(12): e0278412, 2022.
Article in English | MEDLINE | ID: mdl-36454969

ABSTRACT

Non-invasive Gamma ENtrainment Using Sensory stimulation (GENUS) at 40Hz reduces Alzheimer's disease (AD) pathology such as amyloid and tau levels, prevents cerebral atrophy, and improves behavioral testing performance in mouse models of AD. Here, we report data from (1) a Phase 1 feasibility study (NCT04042922, ClinicalTrials.gov) in cognitively normal volunteers (n = 25), patients with mild AD dementia (n = 16), and patients with epilepsy who underwent intracranial electrode monitoring (n = 2) to assess safety and feasibility of a single brief GENUS session to induce entrainment and (2) a single-blinded, randomized, placebo-controlled Phase 2A pilot study (NCT04055376) in patients with mild probable AD dementia (n = 15) to assess safety, compliance, entrainment, and exploratory clinical outcomes after chronic daily 40Hz sensory stimulation for 3 months. Our Phase 1 study showed that 40Hz GENUS was safe and effectively induced entrainment in both cortical regions and other cortical and subcortical structures such as the hippocampus, amygdala, insula, and gyrus rectus. Our Phase 2A study demonstrated that chronic daily 40Hz light and sound GENUS was well-tolerated and that compliance was equally high in both the control and active groups, with participants equally inaccurate in guessing their group assignments prior to unblinding. Electroencephalography recordings show that our 40Hz GENUS device safely and effectively induced 40Hz entrainment in participants with mild AD dementia. After 3 months of daily stimulation, the group receiving 40Hz stimulation showed (i) lesser ventricular dilation and hippocampal atrophy, (ii) increased functional connectivity in the default mode network as well as with the medial visual network, (iii) better performance on the face-name association delayed recall test, and (iv) improved measures of daily activity rhythmicity compared to the control group. These results support further evaluation of GENUS in a pivotal clinical trial to evaluate its potential as a novel disease-modifying therapeutic for patients with AD.


Subject(s)
Alzheimer Disease , Dementia , Animals , Mice , Alzheimer Disease/therapy , Pilot Projects , Feasibility Studies , Atrophy
5.
Phys Rev Lett ; 129(17): 172701, 2022 Oct 21.
Article in English | MEDLINE | ID: mdl-36332266

ABSTRACT

The ß-delayed one- and two-neutron emission probabilities (P_{1n} and P_{2n}) of 20 neutron-rich nuclei with N≥82 have been measured at the RIBF facility of the RIKEN Nishina Center. P_{1n} of ^{130,131}Ag, ^{133,134}Cd, ^{135,136}In, and ^{138,139}Sn were determined for the first time, and stringent upper limits were placed on P_{2n} for nearly all cases. ß-delayed two-neutron emission (ß2n) was unambiguously identified in ^{133}Cd and ^{135,136}In, and their P_{2n} were measured. Weak ß2n was also detected from ^{137,138}Sn. Our results highlight the effect of the N=82 and Z=50 shell closures on ß-delayed neutron emission probability and provide stringent benchmarks for newly developed macroscopic-microscopic and self-consistent global models with the inclusion of a statistical treatment of neutron and γ emission. The impact of our measurements on r-process nucleosynthesis was studied in a neutron star merger scenario. Our P_{1n} and P_{2n} have a direct impact on the odd-even staggering of the final abundance, improving the agreement between calculated and observed Solar System abundances. The odd isotope fraction of Ba in r-process-enhanced (r-II) stars is also better reproduced using our new data.

6.
Front Chem ; 10: 976635, 2022.
Article in English | MEDLINE | ID: mdl-36092655

ABSTRACT

Flerovium (Fl, element 114) is the heaviest element chemically studied so far. To date, its interaction with gold was investigated in two gas-solid chromatography experiments, which reported two different types of interaction, however, each based on the level of a few registered atoms only. Whereas noble-gas-like properties were suggested from the first experiment, the second one pointed at a volatile-metal-like character. Here, we present further experimental data on adsorption studies of Fl on silicon oxide and gold surfaces, accounting for the inhomogeneous nature of the surface, as it was used in the experiment and analyzed as part of the reported studies. We confirm that Fl is highly volatile and the least reactive member of group 14. Our experimental observations suggest that Fl exhibits lower reactivity towards Au than the volatile metal Hg, but higher reactivity than the noble gas Rn.

7.
Chembiochem ; 23(3): e202100614, 2022 02 04.
Article in English | MEDLINE | ID: mdl-34881485

ABSTRACT

Cycles of dehydration and rehydration could have enabled formation of peptides and RNA in otherwise unfavorable conditions on the early Earth. Development of the first protocells would have hinged upon colocalization of these biopolymers with fatty acid membranes. Using atomic force microscopy, we find that a prebiotic fatty acid (decanoic acid) forms stacks of membranes after dehydration. Using LC-MS-MS (liquid chromatography-tandem mass spectrometry) with isotope internal standards, we measure the rate of formation of serine dipeptides. We find that dipeptides form during dehydration at moderate temperatures (55 °C) at least as fast in the presence of decanoic acid membranes as in the absence of membranes. Our results are consistent with the hypothesis that protocells could have formed within evaporating environments on the early Earth.


Subject(s)
Decanoic Acids/chemistry , Peptides/chemical synthesis , Dehydration , Peptides/chemistry , Protein Conformation , Temperature
8.
Front Chem ; 9: 753738, 2021.
Article in English | MEDLINE | ID: mdl-34917588

ABSTRACT

Nihonium (Nh, element 113) and flerovium (Fl, element 114) are the first superheavy elements in which the 7p shell is occupied. High volatility and inertness were predicted for Fl due to the strong relativistic stabilization of the closed 7p 1/2 sub-shell, which originates from a large spin-orbit splitting between the 7p 1/2 and 7p 3/2 orbitals. One unpaired electron in the outermost 7p 1/2 sub-shell in Nh is expected to give rise to a higher chemical reactivity. Theoretical predictions of Nh reactivity are discussed, along with results of the first experimental attempts to study Nh chemistry in the gas phase. The experimental observations verify a higher chemical reactivity of Nh atoms compared to its neighbor Fl and call for the development of advanced setups. First tests of a newly developed detection device miniCOMPACT with highly reactive Fr isotopes assure that effective chemical studies of Nh are within reach.

9.
Article in English | MEDLINE | ID: mdl-34500309

ABSTRACT

Lipid bioactivity is a result of direct action and the action of lipid mediators including oxylipins, endocannabinoids, bile acids and steroids. Understanding the factors contributing to biological variation in lipid mediators may inform future approaches to understand and treat complex metabolic diseases. This research aims to determine the contribution of genetic and environmental influences on lipid mediators involved in the regulation of inflammation and energy metabolism. This study recruited 138 monozygotic (MZ) and dizygotic (DZ) twins aged 18-65 years and measured serum oxylipins, endocannabinoids, bile acids and steroids using liquid chromatography mass-spectrometry (LC-MS). In this classic twin design, the similarities and differences between MZ and DZ twins are modelled to estimate the contribution of genetic and environmental influences to variation in lipid mediators. Heritable lipid mediators included the 12-lipoxygenase products 12-hydroxyeicosatetraenoic acid [0.70 (95% CI: 0.12,0.82)], 12-hydroxyeicosatetraenoic acid [0.73 (95% CI: 0.30,0.83)] and 14­hydroxy-docosahexaenoic acid [0.51 (95% CI: 0.07,0.71)], along with the endocannabinoid docosahexaenoy-lethanolamide [0.52 (95% CI: 0.15,0.72)]. For others such as 13-hydroxyoctadecatrienoic acid and lithocholic acid the contribution of environment to variation was stronger. With increased understanding of lipid mediator functions in health, it is important to understand the factors contributing to their variance. This study provides a comprehensive analysis of lipid mediators and extends pre-existing knowledge of the genetic and environmental influences on the human lipidome.


Subject(s)
Bile Acids and Salts/blood , Endocannabinoids/blood , Fatty Acids, Omega-3/blood , Lipid Metabolism/genetics , Oxylipins/blood , Steroids/blood , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/blood , 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid/genetics , Adolescent , Adult , Aged , Bile Acids and Salts/genetics , Dehydroepiandrosterone/blood , Dehydroepiandrosterone/genetics , Docosahexaenoic Acids/blood , Docosahexaenoic Acids/genetics , Eicosapentaenoic Acid/analogs & derivatives , Eicosapentaenoic Acid/blood , Eicosapentaenoic Acid/genetics , Endocannabinoids/genetics , Fatty Acids, Omega-3/genetics , Female , Gene-Environment Interaction , Humans , Male , Middle Aged , Twins, Dizygotic/genetics , Twins, Monozygotic/genetics , Young Adult
10.
Public Health ; 198: 146-155, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34428607

ABSTRACT

OBJECTIVES: This study aimed to investigate the extent and key characteristics of academic research and scholarship on the public health community's use of social media for policy advocacy purposes. This will enable an evaluation of extant research and provide insight into directions for future research. STUDY DESIGN: This study was a scoping review of academic literature. METHODS: A scoping review of academic literature published between 1 January 2011 and 31 December 2020 was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework. Boolean searches were conducted using a university library platform, which included databases, such as EBSCO host, Informit, Scopus, and ScienceDirect. Data were extracted using an a priori code frame, and publication, content, and disciplinary characteristics were analysed. The results of coding and screening comparison checks were within acceptable limits. RESULTS: In total, 2672 works from around the world were identified and screened for inclusion. Twenty-two English language articles were included in the final analysis. The public health community's use of social media for policy advocacy purposes has largely been approached from a health perspective, despite research and scholarship about social media in communication and policy disciplines (among others). Reported research aims or questions emphasised functional rather than theoretical contributions. Most analysed works used empirical or case study-based methods and were produced by authors in Western geographies. Among the health issues discussed, tobacco and tobacco control were discussed most frequently. While recognising issues with social media, most publications framed social media as more of an opportunity than a problem. CONCLUSIONS: The public health community's use of social media for policy advocacy purposes is an emerging field. There is considerable potential to expand scholarship and research in this field internationally, especially by integrating transdisciplinary knowledge and perspectives and by applying social media to foster policy change around identified global health challenges. Greater representation of authors from institutions in the Global South is also encouraged, as are applied and theoretical contributions.


Subject(s)
Social Media , Delivery of Health Care , Global Health , Humans , Policy , Public Health
11.
Phys Rev Lett ; 125(19): 192501, 2020 Nov 06.
Article in English | MEDLINE | ID: mdl-33216605

ABSTRACT

The ß decay of ^{208}Hg into the one-proton hole, one neutron-particle _{81}^{208}Tl_{127} nucleus was investigated at CERN-ISOLDE. Shell-model calculations describe well the level scheme deduced, validating the proton-neutron interactions used, with implications for the whole of the N>126, Z<82 quadrant of neutron-rich nuclei. While both negative and positive parity states with spin 0 and 1 are expected within the Q_{ß} window, only three negative parity states are populated directly in the ß decay. The data provide a unique test of the competition between allowed Gamow-Teller and Fermi, and first-forbidden ß decays, essential for the understanding of the nucleosynthesis of heavy nuclei in the rapid neutron capture process. Furthermore, the observation of the parity changing 0^{+}→0^{-}ß decay where the daughter state is core excited is unique, and can provide information on mesonic corrections of effective operators.

12.
J Dent Res ; 99(2): 168-174, 2020 02.
Article in English | MEDLINE | ID: mdl-31944893

ABSTRACT

The purpose of this study was to determine the efficacy of a dental nurse-delivered intervention-the Dental RECUR Brief Negotiated Interview for Oral Health (DR-BNI)-in reducing the recurrence of dental caries in children who have a primary tooth extracted. It was based on a 2-arm multicenter randomized controlled trial with blinded outcome assessment. Participants were 5- to 7-y-old children (n = 241) scheduled to have primary teeth extracted in 12 UK centers. Test intervention parents (n = 119) received DR-BNI led by trained dental nurses. DR-BNI is a 30-min structured conversation informed by motivational interviewing with a forward focus to prevent future caries. Preventive goals are agreed, and a review appointment is made with child's general dental practitioner, who is advised to treat the child as being at high caries risk. The control intervention (n = 122) was a parent-nurse conversation about child's future tooth eruption, with advice given to visit a general dental practitioner as usual. At baseline, the DR-BNI group's mean dmft was 6.8, and the control group's was 6.3. A median of 5 teeth were extracted, mainly under general anesthesia. Final dental assessments were conducted by a single examiner visiting 189 schools 2 y after intervention; 193 (80%) of 241 children were examined. In the control group, 62% developed new caries in teeth that were caries-free or unerupted at baseline, as compared with 44% in the test group, a significant reduction (P = 0.021). The odds of new caries experience occurring were reduced by 51% in the DR-BNI group as compared with control. There was a 29% decrease in the relative risk of new caries experience in the DR-BNI group as compared with control. This single low-cost, low-intensity intervention was successful in significantly reducing the risk of recurrence of dental caries in children. This trial has implications for changing pediatric dental practice internationally. Training in and implementation of a motivational interviewing-informed brief intervention provides opportunities for dental nurses to facilitate behavior change improving the oral health of children at high caries risk (ISRCTN 24958829).


Subject(s)
Dental Assistants , Dental Caries , Motivational Interviewing , Child , Child, Preschool , Dental Caries/prevention & control , Dentists , Humans , Parents , Professional Role , Recurrence , Tooth Extraction
13.
Sci Rep ; 9(1): 5797, 2019 Apr 03.
Article in English | MEDLINE | ID: mdl-30940838

ABSTRACT

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

14.
Transfusion ; 59(4): 1246-1251, 2019 04.
Article in English | MEDLINE | ID: mdl-30592057

ABSTRACT

BACKGROUND: Platelet inventory constraints can result in minor ABO incompatibility and possible hemolysis. The aims of this study were to determine the reduction of isoagglutinin in titers of platelets stored in additive solution (PAS) and compare its safety, efficiency, and cost-effectiveness with full-volume and plasma-reduced platelets. STUDY DESIGN AND METHODS: Isoagglutinin titers were performed in paired whole blood donor samples and apheresis platelets collected in PAS (PAS-PLT) aliquot samples by the tube method. RESULTS: A total of 149 pairs of donor/platelet samples were tested: 75 group O, 59 group A, and 15 group B. For group O donor samples, the median anti-A IgG and IgM were 64 and 16, respectively, and the median anti-B IgG and IgM were 64 and 16, respectively. For group O PAS-PLT samples the mean anti-A IgG and IgM, and anti-B IgG and IgM were 32 and 8, and 16 and 8, respectively. For group A donor samples, the mean anti-B IgG and IgM was 8 in both cases; and both titers decreased to 2 in PAS-PLT. For group B donor samples, mean anti-A IgG and IgM was 16 in both cases; and both titers decreased to 4 in PAS-PLT. PAS-PLT demonstrated a net reduction in cost and improved efficiency when compared to plasma reduction. The use of PAS-PLT resulted in a 40% reduction of allergic transfusion reactions. CONCLUSION: The use of PAS decreases plasma isoagglutinin titers, transfusion reactions, and is cost-effective when compared to routine plasma reduction as a strategy to mitigate hemolysis risk from minor incompatible platelet transfusion.


Subject(s)
Blood Group Incompatibility/prevention & control , Blood Preservation/methods , Hemolysis , Platelet Transfusion/adverse effects , Transfusion Reaction/prevention & control , ABO Blood-Group System/immunology , Cost-Benefit Analysis , Hemagglutinins/blood , Humans , Platelet Transfusion/economics
15.
Phys Rev Lett ; 121(14): 142701, 2018 Oct 05.
Article in English | MEDLINE | ID: mdl-30339438

ABSTRACT

The ^{12}C(α,γ)^{16}O reaction plays a central role in astrophysics, but its cross section at energies relevant for astrophysical applications is only poorly constrained by laboratory data. The reduced α width, γ_{11}, of the bound 1^{-} level in ^{16}O is particularly important to determine the cross section. The magnitude of γ_{11} is determined via sub-Coulomb α-transfer reactions or the ß-delayed α decay of ^{16}N, but the latter approach is presently hampered by the lack of sufficiently precise data on the ß-decay branching ratios. Here we report improved branching ratios for the bound 1^{-} level [b_{ß,11}=(5.02±0.10)×10^{-2}] and for ß-delayed α emission [b_{ßα}=(1.59±0.06)×10^{-5}]. Our value for b_{ßα} is 33% larger than previously held, leading to a substantial increase in γ_{11}. Our revised value for γ_{11} is in good agreement with the value obtained in α-transfer studies and the weighted average of the two gives a robust and precise determination of γ_{11}, which provides significantly improved constraints on the ^{12}C(α,γ) cross section in the energy range relevant to hydrostatic He burning.

16.
Sci Rep ; 8(1): 14568, 2018 10 01.
Article in English | MEDLINE | ID: mdl-30275458

ABSTRACT

The menstrual cycle is an essential life rhythm governed by interacting levels of progesterone, estradiol, follicular stimulating, and luteinizing hormones. To study metabolic changes, biofluids were collected at four timepoints in the menstrual cycle from 34 healthy, premenopausal women. Serum hormones, urinary luteinizing hormone and self-reported menstrual cycle timing were used for a 5-phase cycle classification. Plasma and urine were analyzed using LC-MS and GC-MS for metabolomics and lipidomics; serum for clinical chemistries; and plasma for B vitamins using HPLC-FLD. Of 397 metabolites and micronutrients tested, 208 were significantly (p < 0.05) changed and 71 reached the FDR 0.20 threshold showing rhythmicity in neurotransmitter precursors, glutathione metabolism, the urea cycle, 4-pyridoxic acid, and 25-OH vitamin D. In total, 39 amino acids and derivatives and 18 lipid species decreased (FDR < 0.20) in the luteal phase, possibly indicative of an anabolic state during the progesterone peak and recovery during menstruation and the follicular phase. The reduced metabolite levels observed may represent a time of vulnerability to hormone related health issues such as PMS and PMDD, in the setting of a healthy, rhythmic state. These results provide a foundation for further research on cyclic differences in nutrient-related metabolites and may form the basis of novel nutrition strategies for women.


Subject(s)
Biological Factors/analysis , Menstrual Cycle , Metabolome , Periodicity , Adult , Blood Chemical Analysis , Chromatography, Gas , Chromatography, Liquid , Female , Healthy Volunteers , Humans , Mass Spectrometry , Metabolomics , Urinalysis , Young Adult
17.
Genes Nutr ; 13: 14, 2018.
Article in English | MEDLINE | ID: mdl-29861790

ABSTRACT

Biomarkers of food intake (BFIs) are a promising tool for limiting misclassification in nutrition research where more subjective dietary assessment instruments are used. They may also be used to assess compliance to dietary guidelines or to a dietary intervention. Biomarkers therefore hold promise for direct and objective measurement of food intake. However, the number of comprehensively validated biomarkers of food intake is limited to just a few. Many new candidate biomarkers emerge from metabolic profiling studies and from advances in food chemistry. Furthermore, candidate food intake biomarkers may also be identified based on extensive literature reviews such as described in the guidelines for Biomarker of Food Intake Reviews (BFIRev). To systematically and critically assess the validity of candidate biomarkers of food intake, it is necessary to outline and streamline an optimal and reproducible validation process. A consensus-based procedure was used to provide and evaluate a set of the most important criteria for systematic validation of BFIs. As a result, a validation procedure was developed including eight criteria, plausibility, dose-response, time-response, robustness, reliability, stability, analytical performance, and inter-laboratory reproducibility. The validation has a dual purpose: (1) to estimate the current level of validation of candidate biomarkers of food intake based on an objective and systematic approach and (2) to pinpoint which additional studies are needed to provide full validation of each candidate biomarker of food intake. This position paper on biomarker of food intake validation outlines the second step of the BFIRev procedure but may also be used as such for validation of new candidate biomarkers identified, e.g., in food metabolomic studies.

18.
Transl Psychiatry ; 7(9): e1240, 2017 09 26.
Article in English | MEDLINE | ID: mdl-28949339

ABSTRACT

The identification of an early biomarker of psychotic disorder is important as early treatment is associated with improved patient outcome. Metabolomic and lipidomic approaches in combination with multivariate statistical analysis were applied to identify plasma alterations in children (age 11) (38 cases vs 67 controls) and adolescents (age 18) (36 cases vs 117 controls) preceeding or coincident with the development of psychotic disorder (PD) at age 18 in the Avon Longitudinal Study of Parents and Children (ALSPAC). Overall, 179 lipids were identified at age 11, with 32 found to be significantly altered between the control and PD groups. Following correction for multiple comparisons, 8 of these lipids remained significant (lysophosphatidlycholines (LPCs) LPC(18:1), LPC(18:2), LPC(20:3); phosphatidlycholines (PCs) PC(32:2; PC(34:2), PC(36:4), PC(0-34-3) and sphingomyelin (SM) SM(d18:1/24:0)), all of which were elevated in the PD group. At age 18, 23 lipids were significantly different between the control and PD groups, although none remained significant following correction for multiple comparisons. In conclusion, the findings indicate that the lipidome is altered in the blood during childhood, long before the development of psychotic disorder. LPCs in particular are elevated in those who develop PD, indicating inflammatory abnormalities and altered phospholipid metabolism. These findings were not found at age 18, suggesting there may be ongoing alterations in the pathophysiological processes from prodrome to onset of PD.


Subject(s)
Psychotic Disorders/blood , Psychotic Disorders/diagnosis , Adolescent , Biomarkers/blood , Child , Humans , Lipids/blood , Longitudinal Studies , Metabolomics , Multivariate Analysis , Psychotic Disorders/metabolism
19.
Stat Med ; 36(28): 4548-4569, 2017 Dec 10.
Article in English | MEDLINE | ID: mdl-28664564

ABSTRACT

The LIPGENE-SU.VI.MAX study, like many others, recorded high-dimensional continuous phenotypic data and categorical genotypic data. LIPGENE-SU.VI.MAX focuses on the need to account for both phenotypic and genetic factors when studying the metabolic syndrome (MetS), a complex disorder that can lead to higher risk of type 2 diabetes and cardiovascular disease. Interest lies in clustering the LIPGENE-SU.VI.MAX participants into homogeneous groups or sub-phenotypes, by jointly considering their phenotypic and genotypic data, and in determining which variables are discriminatory. A novel latent variable model that elegantly accommodates high dimensional, mixed data is developed to cluster LIPGENE-SU.VI.MAX participants using a Bayesian finite mixture model. A computationally efficient variable selection algorithm is incorporated, estimation is via a Gibbs sampling algorithm and an approximate BIC-MCMC criterion is developed to select the optimal model. Two clusters or sub-phenotypes ('healthy' and 'at risk') are uncovered. A small subset of variables is deemed discriminatory, which notably includes phenotypic and genotypic variables, highlighting the need to jointly consider both factors. Further, 7 years after the LIPGENE-SU.VI.MAX data were collected, participants underwent further analysis to diagnose presence or absence of the MetS. The two uncovered sub-phenotypes strongly correspond to the 7-year follow-up disease classification, highlighting the role of phenotypic and genotypic factors in the MetS and emphasising the potential utility of the clustering approach in early screening. Additionally, the ability of the proposed approach to define the uncertainty in sub-phenotype membership at the participant level is synonymous with the concepts of precision medicine and nutrition. Copyright © 2017 John Wiley & Sons, Ltd.


Subject(s)
Cluster Analysis , Factor Analysis, Statistical , Genotype , Phenotype , Algorithms , Bayes Theorem , European Union , Humans , Markov Chains , Metabolic Syndrome/classification , Metabolic Syndrome/genetics , Monte Carlo Method , Polymorphism, Single Nucleotide , Prospective Studies , Risk Factors
20.
Phys Rev Lett ; 118(16): 162501, 2017 Apr 21.
Article in English | MEDLINE | ID: mdl-28474951

ABSTRACT

Prompt γ-ray spectroscopy of the neutron-rich ^{96}Kr, produced in transfer- and fusion-induced fission reactions, has been performed using the combination of the Advanced Gamma Tracking Array and the VAMOS++ spectrometer. A second excited state, assigned to J^{π}=4^{+}, is observed for the first time, and a previously reported level energy of the first 2^{+} excited state is confirmed. The measured energy ratio R_{4/2}=E(4^{+})/E(2^{+})=2.12(1) indicates that this nucleus does not show a well-developed collectivity contrary to that seen in heavier N=60 isotones. This new measurement highlights an abrupt transition of the degree of collectivity as a function of the proton number at Z=36, of similar amplitude to that observed at N=60 at higher Z values. A possible reason for this abrupt transition could be related to the insufficient proton excitations in the g_{9/2}, d_{5/2}, and s_{1/2} orbitals to generate strong quadrupole correlations or to the coexistence of competing different shapes. An unexpected continuous decrease of R_{4/2} as a function of the neutron number up to N=60 is also evidenced. This measurement establishes the Kr isotopic chain as the low-Z boundary of the island of deformation for N=60 isotones. A comparison with available theoretical predictions using different beyond mean-field approaches shows that these models fail to reproduce the abrupt transitions at N=60 and Z=36.

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