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  • 1
    In: Bioorganic & Medicinal Chemistry, Elsevier BV, Vol. 29 ( 2021-01), p. 115859-
    Type of Medium: Online Resource
    ISSN: 0968-0896
    RVK:
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 1501507-5
    SSG: 15,3
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  • 2
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2023-05-15)
    Abstract: Narcolepsy type 1 (NT1) is caused by a loss of hypocretin/orexin transmission. Risk factors include pandemic 2009 H1N1 influenza A infection and immunization with Pandemrix®. Here, we dissect disease mechanisms and interactions with environmental triggers in a multi-ethnic sample of 6,073 cases and 84,856 controls. We fine-mapped GWAS signals within HLA (DQ0602, DQB1*03:01 and DPB1*04:02) and discovered seven novel associations (CD207, NAB1, IKZF4-ERBB3, CTSC, DENND1B, SIRPG, PRF1). Significant signals at TRA and DQB1*06:02 loci were found in 245 vaccination-related cases, who also shared polygenic risk. T cell receptor associations in NT1 modulated TRAJ*24, TRAJ*28 and TRBV*4-2 chain-usage. Partitioned heritability and immune cell enrichment analyses found genetic signals to be driven by dendritic and helper T cells. Lastly comorbidity analysis using data from FinnGen, suggests shared effects between NT1 and other autoimmune diseases. NT1 genetic variants shape autoimmunity and response to environmental triggers, including influenza A infection and immunization with Pandemrix®.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 2553671-0
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  • 3
    In: European Archives of Oto-Rhino-Laryngology, Springer Science and Business Media LLC
    Abstract: To investigate 2-year post-operative hearing performance, safety, and patient-reported outcomes of hearing-impaired adults treated with the Osia ® 2 System, an active osseointegrated bone-conduction hearing implant that uses piezoelectric technology. Methods A prospective, multicenter, open-label, single-arm, within-subject clinical study conducted at three tertiary referral clinical centers located in Melbourne, Sydney and Hong Kong. Twenty adult recipients of the Osia 2 System were enrolled and followed up between 12 and 24 months post-implantation: 17 with mixed or conductive hearing loss and 3 with single-sided sensorineural deafness. Safety data, audiological thresholds, speech recognition thresholds in noise, and patient-reported outcomes were collected and evaluated. In addition, pre-and 6-month post-implantation data were collected retrospectively for this recipient cohort enrolled into the earlier study (ClinicalTrials.gov NCT04041700). Results Between 6- and 24-month follow-up, there was no statistically significant change in free-field hearing thresholds or speech reception thresholds in noise ( p  =   〉  0.05), indicating that aided improvements were maintained up to 24 months of follow-up. Furthermore, improvements in health-related quality of life and daily hearing ability, as well as clinical and subjective measures of hearing benefit remained stable over the 24-month period. No serious adverse events were reported during extended follow-up. Conclusions These study results provide further evidence to support the longer term clinical safety, hearing performance, and patient-related benefits of the Osia 2 System in patients with either a conductive hearing loss, mixed hearing loss, or single-sided sensorineural deafness. Trial Registration ClinicalTrials.gov Identifier: NCT04754477. First posted: February 15, 2021.
    Type of Medium: Online Resource
    ISSN: 0937-4477 , 1434-4726
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    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1459042-6
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  • 4
    Online Resource
    Online Resource
    American Society for Pharmacology & Experimental Therapeutics (ASPET) ; 2022
    In:  Pharmacological Reviews Vol. 74, No. 4 ( 2022-10), p. 1051-1135
    In: Pharmacological Reviews, American Society for Pharmacology & Experimental Therapeutics (ASPET), Vol. 74, No. 4 ( 2022-10), p. 1051-1135
    Type of Medium: Online Resource
    ISSN: 0031-6997 , 1521-0081
    RVK:
    Language: English
    Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
    Publication Date: 2022
    detail.hit.zdb_id: 1471698-7
    SSG: 15,3
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  • 5
    In: Geoscientific Model Development, Copernicus GmbH, Vol. 15, No. 17 ( 2022-09-01), p. 6567-6579
    Abstract: Abstract. We describe an idealized primitive-equation model for studying mesoscale turbulence and leverage a hierarchy of grid resolutions to make eddy-resolving calculations on the finest grids more affordable. The model has intermediate complexity, incorporating basin-scale geometry with idealized Atlantic and Southern oceans and with non-uniform ocean depth to allow for mesoscale eddy interactions with topography. The model is perfectly adiabatic and spans the Equator and thus fills a gap between quasi-geostrophic models, which cannot span two hemispheres, and idealized general circulation models, which generally include diabatic processes and buoyancy forcing. We show that the model solution is approaching convergence in mean kinetic energy for the ocean mesoscale processes of interest and has a rich range of dynamics with circulation features that emerge only due to resolving mesoscale turbulence.
    Type of Medium: Online Resource
    ISSN: 1991-9603
    Language: English
    Publisher: Copernicus GmbH
    Publication Date: 2022
    detail.hit.zdb_id: 2456725-5
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  • 6
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Objective: We previously reported long term effectiveness of a very low carbohydrate intervention including nutritional ketosis (VLCI) delivered via continuous remote care (CRC) for improving weight and glycemia at 2 years in people with type 2 diabetes (T2D) . We assessed 5-year changes to determine if the intervention is sustainable, durable, and effective over a longer period of time. Research Design and Methods: Patients with T2D who were initially enrolled in a 2 year non-randomized, controlled clinical trial received a CRC emphasizing a VLCI. These patients were offered to continue for an additional 3 years of prospective follow-up. Of the 200 patients completing 2 years, 169 (84.5%) patients consented to the extension and 122 (72.2%) were retained at 5 years. Among those who extended, baseline versus 5 year differences in weight and glycemic outcomes were assessed using linear mixed effects models in an intent-to-treat analysis. P-values were adjusted using Holm-Bonferroni correction. Results: At five years, there were persistent improvements in weight from 116.4 to 107.6 kg (-8.8 kg, 95%CI [-11.0, -6.6]) , fasting insulin from 25.8 to 24.5 mIU/L (-7.9 mIU/L, 95%CI [-10.0, -5.8] ) , and HOMA-IR from 9.1 to 6.6 (-2.5, 95%CI [-3.5, -1.5]) (all adjusted p-values & lt;0.05) . Total diabetes medications were reduced 46.6%, and 59.9% excluding metformin were deprescribed. The percent of patients prescribed diabetes medications significantly decreased at 5 years (from 85.2% to 71.3%; p & lt;0.01) , including patients taking sulfonylureas (from 27.0% to 4.9%) , insulin (from 26.2% to 13.1%) , and SGLT2i (from 10.7% to 2.5%) . Despite less medication use, HbA1c improved from 7.5 to 7.2% (-0.3%, 95%CI [-0.6, 0.0], unadjusted p-value & lt;0.05) . Conclusions: Over 5 years follow-up, the VLCI with CRC showed excellent retention, sustained clinically significant weight loss, and stable glycemic control with reduced dependency on antidiabetes medications. Disclosure S.J.Athinarayanan: Employee; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 7
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: Objective: To address the long-term effectiveness of VLCI for T2D, we report changes in lipids, inflammatory, hepatic, and renal markers at 5y. Research Design and Methods: Of the 200 subjects with T2D reaching 2-years in a non-randomized, controlled trial of CRC emphasizing VLCI, 169 (84.5%) consented to 3-year extension and 122 (61%) completed 5y. Metabolic changes from baseline (BL) to 5y were assessed with linear mixed effect models as an intent-to-treat analysis (n=169) . Holm-Bonferroni adjusted p-values are & lt;0.05 unless otherwise noted. Results: At 5y, there were significant changes in HDLc from 43.0 mg/dl to 50.6 mg/dl (+17.7%) , apoA-I from 146.9 mg/dl to 153.5 mg/dl (+4.5%) , and no changes in Total Cholesterol, LDLc, apoB. There were marginal improvements in non-HDLc from 139.2 mg/dl to 128.9 mg/dl (-7.4%, unadjusted p-value & lt;0.01) , and triglycerides from 202.3 mg/dl to 165.1 mg/dl (-18.4%, unadjusted p-value & lt;0.01) . Inflammatory markers significantly improved: hs-CRP from 7.8 nmol/L to 4.4 nmol/L (-43.6%) , white blood cell count from 7.2 k/mm3 to 6.4 k/mm3 (-11.1%) . At all time points, liver markers have been in the normal range. There were no changes in renal biomarkers. eGFR was stable at CKD2. Subcohort completers’ analysis of those with eGFR & lt;60 ml/min/1.73m2 (n=10) showed an increase from 47.8 to 57.1 ml/min/1.73m2 (p=0.01). Six of the subjects (60%) with BL CKD3 who completed 5y rose to CKD2. Of the 107 subjects with BL CKD2, 7 (6.5%) progressed to CKD3. Conclusions: People with T2D following VLCI for 5y show improvements in diabetic dyslipidemia and inflammation. Notably, there is no change in LDLc. There is no significant deterioration in liver and renal labs, although regression from CKD3 to 2 is possible with a VLCI and warrants further investigation. Disclosure C.G.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 8
    In: Diabetes, American Diabetes Association, Vol. 71, No. Supplement_1 ( 2022-06-01)
    Abstract: The national Diabetes Prevention Program (nDPP) failed to translate the efficacy of the Diabetes Prevention Program (DPP) into real world effectiveness. We initiated a prevention program, previously publishing outcomes on 96 patients with prediabetes over two years with 75% retention. This single center observational trial examines the effectiveness of a very low carbohydrate intervention (VLCI) including nutritional ketosis delivered via a continuous remote care (CRC) model; here, we report sustainability and durability at 5 years. At completion of the 2-year trial, 58 of the original cohort (80%) renewed consent and 78% completed the 5 year follow-up. At baseline, all had prediabetes, with mean weight 109 kg and mean BMI 38.9 kg/m2. Using intention to treat analysis at 5 years, 22% regressed to normoglycemia, 13% progressed to diabetes, and 65% remained prediabetes. A1c remained unchanged (mean 5.9%) , and mean fasting glucose fell from 112 to 108 mg/dl (p=NS). Weight fell from 1 to 103 kg (p & lt;0.001) , with insulin resistance falling from a HOMA-IR of 6.1 to 4.7 (p & lt;0.05) . The nDPP utilizes 5% weight loss as a surrogate outcome for prevention. Forty-eight percent of the sample met that criteria at 5 years, with 19% achieving a 5-9.9% weight loss, 19% a 10-19.9% weight loss, and 10% with at least 20% weight loss. There was a 30% reduction in class 3 obesity (BMI ≥40) , contributing to a 2.7 fold increase in those now overweight (BMI 25-29.9). These results show that a VLCI delivered via CRC is sustainable in prediabetes, resulting in normalization of A1c without medication in over 20% with limited glycemic deterioration to the diabetes threshold. No other real world intervention has presented glycemic data on diabetes prevention, but only reported surrogate weight change as an outcome. Over 5 years, almost half of the cohort achieved that surrogate with significant population shifts to lower obesity classes. The promise of the DPP is met via telehealth-supported VLCI and is sustainable over the long term. Disclosure A.L.Mckenzie: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.Phinney: Employee; Virta Health Corp. S.Hallberg: Advisory Panel; Atkins Nutritionals Inc., Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. S.J.Athinarayanan: Employee; Virta Health Corp. M.Vantieghem: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.M.Volk: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.N.Adams: Employee; Virta Health Corp. C.G.P.Roberts: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. B.Fell: Employee; Virta Health Corp., Stock/Shareholder; Virta Health Corp. R.E.Ratner: Employee; Virta Health Corp. J.Volek: Advisory Panel; Abbott Diagnostics, Simply Good Foods, Stock/Shareholder; Virta Health Corp.
    Type of Medium: Online Resource
    ISSN: 0012-1797
    Language: English
    Publisher: American Diabetes Association
    Publication Date: 2022
    detail.hit.zdb_id: 1501252-9
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  • 9
    In: Journal of Advances in Modeling Earth Systems, American Geophysical Union (AGU), Vol. 12, No. 3 ( 2020-03)
    Abstract: Development and performance of the next generation GFDL seasonal to decadal prediction model is documented The response of this model to realistic radiative forcing changes is shown via a large ensemble of climate simulations for 1921–2100 The influence of the Antarctic surface energy balance on the world ocean was crucial in model development as shown via sensitivity tests
    Type of Medium: Online Resource
    ISSN: 1942-2466 , 1942-2466
    Language: English
    Publisher: American Geophysical Union (AGU)
    Publication Date: 2020
    detail.hit.zdb_id: 2462132-8
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  • 10
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 12 ( 2021-10-7)
    Abstract: Objective: The aim of this study was to investigate emotional processing as a potential mediator in therapist-guided, internet-based Emotional Awareness and Expression Therapy (I-EAET) for somatic symptom disorder, using data from a previously published pilot study. Methods: Participants ( N = 52) engaged in a 9-week I-EAET treatment. Before treatment and each week during treatment (i.e., 10 weekly measurements), emotional processing was assessed with the Emotional Processing Scale-25 (EPS-25), which contains five subscales, and somatic symptoms were assessed with the Patient Health Questionnaire-15 (PHQ-15). Results: Mediation analyses using linear mixed models showed that two EPS-25 subscales—Signs of Unprocessed Emotions and Impoverished Emotional Experience—were uniquely associated with somatic symptom reduction. The proportion of the mediated effect was 0.49, indicating that about half of the total association of the PHQ-15 with symptoms was accounted for by the two EPS-25 subscales. Conclusion: This preliminary mediation analysis suggests that improved emotional processing is associated with change in somatic symptoms in I-EAET. However, randomized controlled and comparison trials are needed to establish that I-EAET creates the change in emotional processing and that such changes are specific to I-EAET.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
    detail.hit.zdb_id: 2563826-9
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