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      • SCOPUS

        Effects of ultraviolet radiation on pigmentation, photoenzymatic repair, behavior, and community ecology of zooplankton

        Hansson, Lars-Anders,Hylander, Samuel Korean Society of Photoscience 2009 Photochemical & photobiological sciences Vol.8 No.9

        In this report, we provide a perspective on how zooplankton are able to respond to present and future levels of ultraviolet (UV) radiation, a threat that has been present throughout evolutionary time. To cope with this threat, zooplankton have evolved several adaptations including behavioral responses, repair systems, and accumulation of photoprotective compounds. Common photoprotective compounds include melanins and carotenoids, which are true pigments, but also mycosporine-like amino acids (MAAs) and several other substances, and different taxa use different blends of these compounds. It is not only the level of UV radiation, however, that determines the amount of photoprotective compounds incorporated by the zooplankton, but also other environmental factors, such as predation and supply rate of the compounds. Furthermore, compared to taxa that are less pigmented, those taxa with ample pigmentation are generally less likely to exhibit diel migration. The photoenzymatic repair of UV damages seems to be more efficient at intermediate temperature than at low and high temperatures, suggesting that it is less useful at high and low latitudes, where UV radiation is often extremely high. While predicted future increases in UV radiation are expected to substantially affect many processes, recent studies show that most zooplankton taxa are well adapted to cope with such increases, either by UV avoidance behavior or by incorporation of photoprotective compounds. Hence, we conclude that future increase in UV radiation will have only moderate direct effects on zooplankton biomass and community dynamics.

      • KCI등재후보

        The Future Work-Life Balance Attitudes Scale: Assessing Attitudes on Work-Life Balance in Millennial College Women

        Megan Hyland Tajlili,Stanley B. Baker 한국상담학회 2018 Journal of Asia Pacific counseling Vol.8 No.2

        The goal of this study was to construct a reliable and valid scale that assesses the work-life balance attitudes of millennial college women. The items that created the Future Work-Life Balance Attitudes Scale (FWLBAS) were based on the Kaleidoscope Career Model and proved similar to findings from a previous qualitative pilot study. The scale was administered to an online sample of 508 millennial college women in their senior year of college. The data were then analyzed via exploratory and confirmatory factor analyses, and internal consistency reliability estimates were generated. The scale showed high reliability. The exploratory and confirmatory factor analyses led to the development of three subscales, namely “defining working motherhood,” “work-life balance strategies,” and “influence of college personnel,” and revisions of the item content of the FWLBAS. This scale is the first work-life balance instrument of its kind focusing on the population of millennial college women.

      • Ledipasvir/Sofosbuvir for 12 or 24 Weeks Is Safe and Effective in Kidney-transplant Recipients with Genotype 1 or 4 HCV Infection

        ( Massimo Colombo ),( Alessio Aghemo ),( Lin Liu ),( Robert H. Hyland ),( Chohee Yun ),( Diana M. Brainard ),( John G. Mchutchison ),( Sunjin Hwang ),( Marc Bourliere ),( Markus Peck-radosavljevic ),( 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Methods: Kidney transplant recipients with chronic GT1 or GT4 HCV infection, treatment-naive and treatment-experienced, with or without compensated cirrhosis were randomized 1:1 at 5 sites in Europe to receive LDV/SOF (90 mg/400 mg) for 12 or 24 weeks. Randomization was stratified by HCV genotype, treatment history and presence or absence of cirrhosis. Cirrhosis was determined by liver biopsy (Metavir score = 4 or Ishak score ≥5), Fibroscan® >12.5 kPa, or Fibrotest® >0.75 and APRI >2. A pretreatment creatinine clearance <40 mL/min was an exclusionary criterion. The primary endpoint was SVR12. Results: 114 patients were randomized and treated; median age was 53, 58% were male, 94% were white, 72% carried the non-CC IL28B allele, 91% had GT 1 infection, 69% were treatment-naive, and 15% had compensated cirrhosis. The median eGFR was 56ml/min (range 35-135ml/min). All 92 patients with SVR4 data available achieved SVR4 including a patient discontinuing treatment at Week 4 due to an AE. SAEs were reported in 12 (11%) patients; 3 were assessed as treatment related: syncope, pulmonary embolism, and blood creatinine increased. The most frequent AEs were headache (19%), asthenia (13%), and fatigue (10%). Conclusions: Administration of LDV/SOF for 12 or 24 weeks in patients with chronic HCV genotype 1 or 4 patients who have undergone kidney transplant was safe and highly effective with an SVR4 rate of 100%. Treatment was well-tolerated. SVR12 data for all patients will be presented.

      • Sofosbuvir/Velpatasvir/Voxilaprevir for 12 Weeks is a Safe and Effective Salvage Regimen in NS5A Inhibitor-Experienced Patients with Genotype1-6 Infection: The POLARIS-1 Study

        ( Edward J. Gane ),( Marc Bourliere ),( Stuart C. Gordon ),( Alnoor Ramji ),( Natarajan Ravendhran ),( Tram T. Tran ),( Rob H. Hyland ),( Jie Zhang ),( Hadas Dvory-sobol ),( Luisa M. Stamm ),( Diana M 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

        Aims: NS5A inhibitors are potent DAAs which are key components of HCV treatment regimens. In combination with other DAAs, NS5A inhibitors provide cure to over 90% of patients. For patients who have failed a regimen with an NS5A inhibitor, there is concern about long-lasting NS5A RASs and currently no approved retreatment option. Sofosbuvir (SOF) and velpatasvir (VEL) are pangenotypic inhibitors of the NS5B and NS5A proteins, respectively, and voxilaprevir (VOX) is a pangenotypic NS3/4A protease inhibitor. This study evaluates treatment with a SOF/VEL/VOX for 12 weeks in patients who previously received an NS5A inhibitor. Methods: Eligible patients received at least 4 weeks of a prior NS5A inhibitor-containing. Those with HCV GT1 were randomized 1:1 to receive SOF/VEL/VOX (400mg/100 mg/100 mg) or matching placebo daily for 12 weeks, stratified by the presence or absence of cirrhosis. Patients of all other GTs were assigned to receive SOF/VEL/VOX for 12 weeks. Those patients assigned to receive placebo were offered deferred treatment with SOF/VEL/VOX for 12 weeks. The primary endpoint evaluated the superiority of SVR12 to a performance goal of 85%. Results: Of 415 patients enrolled and treated with SOF/VEL/VOX, 76% were male, 80% were white, 46% had compensated cirrhosis, and 57% had GT 1infection. The majority of patients had DAA experience with an NS5A inhibitor given in combination with an NS5B inhibitor, and the most common prior NS5A inhibitor was ledipasvir (50%). Treatment with SOF/VEL/VOX was well tolerated. No serious adverse events attributed to study medication were reported. Overall, 253/263 (96%) of patients treated with SOF/VEL/VOX achieved SVR12, which was superior to the prespecified goal of 85% (p<0.001). High SVR12 was achieved across HCV GTs and regardless of selected baseline factors such as cirrhosisand RASs at any position. Conclusions: SOF/VEL/VOX for 12 weeks is a safe, well-tolerated and effective treatment for patients previously failed an NS5A inhibitor-containing DAA regimen, a group that currently has no retreatment option.

      • Patterning droplets with durotaxis

        Style, Robert W.,Che, Yonglu,Park, Su Ji,Weon, Byung Mook,Je, Jung Ho,Hyland, Callen,German, Guy K.,Power, Michael P.,Wilen, Larry A.,Wettlaufer, John S.,Dufresne, Eric R. National Academy of Sciences 2013 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.110 No.31

        <P>Numerous cell types have shown a remarkable ability to detect and move along gradients in stiffness of an underlying substrate—a process known as durotaxis. The mechanisms underlying durotaxis are still unresolved, but generally believed to involve active sensing and locomotion. Here, we show that simple liquid droplets also undergo durotaxis. By modulating substrate stiffness, we obtain fine control of droplet position on soft, flat substrates. Unlike other control mechanisms, droplet durotaxis works without imposing chemical, thermal, electrical, or topographical gradients. We show that droplet durotaxis can be used to create large-scale droplet patterns and is potentially useful for many applications, such as microfluidics, thermal control, and microfabrication.</P>

      • Long-term Follow-up of Patients with Chronic HCV Following Treatment with DAAs: Maintenance of SVR, Persistence of Resistance and Clinical Outcomes

        ( W. Ray Kim ),( Eric J. Lawitz ),( Peter Ruane ),( Catherine Stedman ),( Graham Foster ),( Robert H. Hyland ),( Sarah Coogan ),( Stephanie Moody ),( Hadas Dvory-sobo ),( Steven J. Knox ),( Diana M. B 대한간학회 2016 춘·추계 학술대회 (KASL) Vol.2016 No.1

        Aims: Significant advances in the treatment of chronic hepatitis C have been made with direct acting antiviral (DAA) regimens. While SVR rates may now be achieved in the majority of patients, data describing long-term virologic and clinical outcomes with these regimens are needed. Methods: We report interim data from two 3-year registry studies capturing long-term outcomes in patients with chronic hepatitis C treated with DAAs. Subjects are enrolled into two registries according to SVR status; SVR (SVR registry) versus non-SVR (Sequence registry). We determined the durability of SVR, relapse and reinfection rates. The persistence of resistance associated variants (RAVs) in treatment failures is followed. Liver disease progression is assessed by periodic clinical & labroratory evaluations. Results: 5433 patients enrolled in the SVR registry with a median (range) follow-up of 71 (0-156) weeks. 536 patients enrolled in the Sequence registry with a median (range) of follow-up of 44 (0-159) weeks. Demographic and disease characteristics are described below. In the SVR registry, at the time of data analysis, 99.7% (5414/5433) of patients have maintained SVR with 0.3% (19/5433) having emergent virus (6 relapses, 8 new infections, 5 to be confirmed). Viral emergence occurred by Week 96 in all patients. In the Sequence registry of 89 patients who received an NS5A inhibitor and had baseline sequencing data, 91.0% (81/89) had NS5A RAVs at Week 96. HCC was reported in 0.3% (16/5433) and 0.9% (5/536) of patients in the SVR and Sequence registries through Week 96 respectively. There were no significant changes in laboratory evaluations or liver disease assessments. Conclusions: SVR achieved following treatment with DAA regimens is durable. In patients failing NS5A-containing regimens, treatment- emergent NS5A RAVs persist. Rates of clinical disease progression and HCC are low. Ongoing reporting from these registry studies will be required to confirm these findings.

      • KCI등재

        The Stressed Gut: Region-specific Immune and Neuroplasticity Changes in Response to Chronic Psychosocial Stress

        Beatriz Lobo,Mónica Tramullas,Beate-C Finger,Kevin W Lomasney,Caroll Beltran,Gerard Clarke,Javier Santos,Niall P Hyland,Timothy G Dinan,John F Cryan 대한소화기 기능성질환∙운동학회 2023 Journal of Neurogastroenterology and Motility (JNM Vol.29 No.1

        Background/AimsChronic psychological stress affects gastrointestinal physiology which may underpin alterations in the immune response and epithelial transport, both functions are partly regulated by enteric nervous system. However, its effects on enteric neuroplasticity are still unclear. This study aims to investigate the effects of chronic unpredictable psychological stress on intestinal motility and prominent markers of enteric function. MethodsAdult male C57BL/6J mice were exposed to 19 day of unpredictable stress protocol schedule of social defeat and overcrowding. We investigated the effects on plasma corticosterone, food intake, and body weight. In vivo gastrointestinal motility was assessed by fecal pellet output and by whole-gastrointestinal transit (using the carmine red method). Tissue monoamine level, neural and glial markers, neurotrophic factors, monoamine signaling, and Toll-like receptor expression in the proximal and distal colon, and terminal ileum were also assessed. ResultsFollowing chronic unpredictable psychological stress, stressed mice showed increased food intake and body weight gain (P < 0.001), and reduced corticosterone levels (P < 0.05) compared to control mice. Stressed mice had reduced stool output without differences in water content, and showed a delayed gastrointestinal transit compared to control mice (P < 0.05). Stressed mice exhibited decreased mRNA expression of tyrosine hydroxylase (Th), brain-derived neurotrophic factor (Bdnf) and glial cell-derived neurotrophic factor (Gdnf), as well as Toll-like receptor 2 (Tlr2) compared to control (P < 0.05), only proximal colon. These molecular changes in proximal colon were associated with higher levels of monoamines in tissue. ConclusionUnpredictable psychological chronic stress induces region-specific impairment in monoamine levels and neuroplasticity markers that may relate to delayed intestinal transit.

      • SOF/VEL/VOX for 12 Weeks is a Safe and Effective Salvage Regimen for NS5A Inhibitor-experienced Patients with Genotype 1-6 HCV Infection

        ( Eric Lawitz ),( Michael Manns ),( Marc Bourliere ),( Sooji Lee ),( Nelson Cheinquer ),( Luisa Stamm ),( Robert H. Hyland ),( Liyun Ni ),( Hadas Dvory-sobol ),( Diana Brainard ),( Mani Subramanian ) 대한간학회 2018 춘·추계 학술대회 (KASL) Vol.2018 No.1

        Aims: The pangenotypic fixed-dose combination (FDC) of sofosbuvir (SOF), a HCV NS5B inhibitor, velpatasvir (VEL), a HCV NS5A inhibitor, and voxilaprevir (VOX), a HCV NS3/4A protease inhibitor, is an salvage regimen for direct acting antiviral (DAA)-experienced patients based on the safety and efficacy demonstrated in Phase 2 and Phase 3 trials in this population. Methods: This was a retrospective analysis of data from 454 NS5A inhibitor-experienced patients treated with SOF/VEL FDC+VOX or SOF/VEL/VOX FDC in the Phase 2 and Phase 3 trials. Efficacy was assessed by SVR12 and relapse rates. Safety was assessed by treatment-emergent adverse events (AEs) and laboratory abnormalities. Results: Of 454 NS5A inhibitor-experienced patients treated, 77% were male, 41% had compensated cirrhosis, 86% had NS5A and NS3 baseline resistance-associated substitutions (RASs), 74% had genotype 1 HCV infection. Most patients (53%) had previously been exposed to NS5A inhibitor+NS5B inhibitor, with 39% exposed to NS5A inhibitor+NS3/4A protease inhibitor±NS5B inhibitor and 8% exposed to NS5A inhibitor±another DAA. Overall, the SVR12 rate was 97% with a relapse rate of 2%. The SVR12 rate in patients with compensated cirrhosis was 95% and in patients with baseline RASs was 97%. The SVR12 rates by prior regimen were: NS5A inhibitor+NS5B inhibitor 95%; NS5A inhibitor+NS3/4A protease inhibitor±NS5B inhibitor 99%; and NS5A inhibitor±another DAA 100%. Treatment-emergent RASs were uncommon, present in 3 of 10 patients who relapsed. Only 1 patient (0.2%) discontinued treatment due to an AE. No serious adverse events attributed to study medication were reported. Conclusions: Results in over 450 NS5A inhibitor-experienced patients enrolled in Phase 2 or Phase 3 trials demonstrate that the 3-DAA combination of SOF, VEL and VOX for 12 weeks is a safe, well tolerated and effective treatment for patients who previously failed an NS5A inhibitor-containing regimen, irrespective of the other drugs in the prior treatment.

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