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1. The 2022 symposium on dementia and brain aging in low‐ and middle‐income countries: Highlights on research, diagnosis, care, and impact

Author: Kalaria, Raj, Kalaria, Raj, Maestre, Gladys, Mahinrad, Simin, Acosta, Daisy M, Akinyemi, Rufus Olusola, Alladi, Suvarna, Allegri, Ricardo F, Arshad, Faheem, Babalola, David Oluwasayo, Baiyewu, Olusegun, Bak, Thomas H, Bellaj, Tarek, Brodie‐Mends, David K, Carrillo, Maria C, Celestin, Kaputu‐Kalala‐Malu, Damasceno, Albertino, de Silva, Ranil Karunamuni, de Silva, Rohan, Djibuti, Mamuka, Dreyer, Anna Jane, Ellajosyula, Ratnavalli, Farombi, Temitope H, Friedland, Robert P, Garza, Noe, Gbessemehlan, Antoine, Georgiou, Eliza Eleni‐Zacharoula, Govia, Ishtar, Grinberg, Lea T, Guerchet, Maëlenn, Gugssa, Seid Ali, Gumikiriza‐Onoria, Joy Louise, Hogervorst, Eef, Hornberger, Michael, Ibanez, Agustin, Ihara, Masafumi, Issac, Thomas Gregor, Jönsson, Linus, Karanja, Wambui M, Lee, Joseph H, Leroi, Iracema, Livingston, Gill, Manes, Facundo Francisco, Mbakile‐Mahlanza, Lingani, Miller, Bruce L, Musyimi, Christine Wayua, Mutiso, Victoria N, Nakasujja, Noeline, Ndetei, David M, Nightingale, Sam, Novotni, Gabriela, Nyamayaro, Primrose, Nyame, Solomon, Ogeng'o, Julius A, Ogunniyi, Adesola, de Oliveira, Maira Okada, Okubadejo, Njideka U, Orrell, Martin, Paddick, Stella‐Maria, Pericak‐Vance, Margaret A, Pirtosek, Zvezdan, Potocnik, Felix Claude Victor, Raman, Rema, Rizig, Mie, Rosselli, Mónica, Salokhiddinov, Marufjon, Satizabal, Claudia L, Sepulveda‐Falla, Diego, Seshadri, Sudha, Sexton, Claire E, Skoog, Ingmar, St George‐Hyslop, Peter H, Suemoto, Claudia Kimie, Thapa, Prekshy, Udeh‐Momoh, Chinedu Theresa, Valcour, Victor, Vance, Jeffery M, Varghese, Mathew, Vera, Jaime H, Walker, Richard W, Zetterberg, Henrik, Zewde, Yared Z, Ismail, Ozama, Kalaria, Raj, Kalaria, Raj, Maestre, Gladys, Mahinrad, Simin, Acosta, Daisy M, Akinyemi, Rufus Olusola, Alladi, Suvarna, Allegri, Ricardo F, Arshad, Faheem, Babalola, David Oluwasayo, Baiyewu, Olusegun, Bak, Thomas H, Bellaj, Tarek, Brodie‐Mends, David K, Carrillo, Maria C, Celestin, Kaputu‐Kalala‐Malu, Damasceno, Albertino, de Silva, Ranil Karunamuni, de Silva, Rohan, Djibuti, Mamuka, Dreyer, Anna Jane, Ellajosyula, Ratnavalli, Farombi, Temitope H, Friedland, Robert P, Garza, Noe, Gbessemehlan, Antoine, Georgiou, Eliza Eleni‐Zacharoula, Govia, Ishtar, Grinberg, Lea T, Guerchet, Maëlenn, Gugssa, Seid Ali, Gumikiriza‐Onoria, Joy Louise, Hogervorst, Eef, Hornberger, Michael, Ibanez, Agustin, Ihara, Masafumi, Issac, Thomas Gregor, Jönsson, Linus, Karanja, Wambui M, Lee, Joseph H, Leroi, Iracema, Livingston, Gill, Manes, Facundo Francisco, Mbakile‐Mahlanza, Lingani, Miller, Bruce L, Musyimi, Christine Wayua, Mutiso, Victoria N, Nakasujja, Noeline, Ndetei, David M, Nightingale, Sam, Novotni, Gabriela, Nyamayaro, Primrose, Nyame, Solomon, Ogeng'o, Julius A, Ogunniyi, Adesola, de Oliveira, Maira Okada, Okubadejo, Njideka U, Orrell, Martin, Paddick, Stella‐Maria, Pericak‐Vance, Margaret A, Pirtosek, Zvezdan, Potocnik, Felix Claude Victor, Raman, Rema, Rizig, Mie, Rosselli, Mónica, Salokhiddinov, Marufjon, Satizabal, Claudia L, Sepulveda‐Falla, Diego, Seshadri, Sudha, Sexton, Claire E, Skoog, Ingmar, St George‐Hyslop, Peter H, Suemoto, Claudia Kimie, Thapa, Prekshy, Udeh‐Momoh, Chinedu Theresa, Valcour, Victor, Vance, Jeffery M, Varghese, Mathew, Vera, Jaime H, Walker, Richard W, Zetterberg, Henrik, Zewde, Yared Z, and Ismail, Ozama
Abstract: Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
Published: 2024

2. Reduction of Chlorine Disinfection Dosage through Optimal Jet Design in the Hong Kong Harbor Area Treatment Scheme

Author: Lee, Joseph H. W., Qiao, Qingsong, Chan, Shu Ning, Choi, King Wah David, Chau, Henry K. M., Lee, Joseph H. W., Qiao, Qingsong, Chan, Shu Ning, Choi, King Wah David, and Chau, Henry K. M.
Abstract: Chlorine is commonly used in disinfection processes in wastewater treatment plants. The chlorine solution is typically dosed by turbulent mixing through multiport jet diffusers. The chlorine reacts with the inorganic and organic nitrogenous compounds at a fast rate (in the order of 1 s or less), and a significant portion of the dosed chlorine can be rapidly consumed by the reactions instead of destroying the pathogens. Despite extensive previous research, the chlorine consumption in the complex sewage flow remains an elusive problem. Field-scale experiments have been carried out to study the chlorine consumption in the turbulent mixing of dense chlorine jets with the primary treated sewage effluent of the Stonecutter's Island Sewage Treatment Works (serving a population of 5.7 million). Based on jet theory and the field tests, it is proposed to discharge the chlorine jets at a location of highest velocity to minimize the contact time of the sewage with high concentration chlorine. Full-scale in-plant experiments demonstrated that significant savings in chlorine can be achieved with optimal jet diffuser design and placement; at nominal applied chlorine dosages of 12 and 20 mg/L in winter and summer, respectively, the chlorine demand can be reduced by up to 30% compared with the conventional dosing design. The relatively simple dosing reconfiguration results in significant savings in chlorine and energy, reduces harmful impact to the environment, and improves plant operation reliability. The chlorine demands from daily operations are well-correlated with the results of the field-scale models. Predictions of the chlorine demand as a function of applied dosage and temperature were obtained from the collective field data.
Published: 2023

3. Dynamics of Algal Blooms as revealed by Continuous Machine- learning based Automatic Species Detection and Water Quality Monitoring in Sub-tropical Marine Fish Culture Zone

Author: Ma, Yaoyao, Chang, Lu, Lee, Joseph H. W., Ma, Yaoyao, Chang, Lu, and Lee, Joseph H. W.
Abstract: Algal blooms in coastal waters can cause harmful effects to marine ecosystems and pose threats to fisheries management. The formation of harmful algal blooms (HAB) involves the interaction of complex biological and physical processes; on the other hand, field observations of algal blooms are typically sparse and cannot capture the characteristic spatial and temporal variations of blooms. Continuous real time data on algal cell counts and water quality are necessary for the development of HAB early warning systems. We report recent findings of an integrated ecological monitoring system that has been successfully deployed in a subtropical coastal bay over a 3-year period. The system incorporates: (i) a submerged in-situ Imaging Flow Cytobot (IFCB) that is able to detect and classify up to 25 algal species with the use of a machine learning-based automatic classifier; (ii) a multi-parameter water quality monitor at two depths; and (iii) algal bloom risk prediction system based on antecedent environmental conditions. The algal cell count and relative species dominance (diatoms vs dinoflagellates) have been continuously monitored in a marine fish culture zone for the first time. The predicted algal bloom risks are found to correlate well with observed blooms; the changes in hydro-meteorological conditions, water temperature and salinity, water column stability, cell counts, chlorophyll, and dissolved oxygen (DO) throughout an algal bloom cycle are illustrated through field observations. © 2022 IAHR.
Published: 2022

4. Plasma Total-Tau and Neurofilament Light Chain as Diagnostic Biomarkers of Alzheimer's Disease Dementia and Mild Cognitive Impairment in Adults with Down Syndrome.

Author: Petersen, Melissa E, Petersen, Melissa E, Rafii, Michael S, Zhang, Fan, Hall, James, Julovich, David, Ances, Beau M, Schupf, Nicole, Krinsky-McHale, Sharon J, Mapstone, Mark, Silverman, Wayne, Lott, Ira, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Diana Rosas, H, Zaman, Shahid, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, Handen, Benjamin, Hartley, Sigan, Fortea, Juan, O'Bryant, Sid, Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS), Petersen, Melissa E, Petersen, Melissa E, Rafii, Michael S, Zhang, Fan, Hall, James, Julovich, David, Ances, Beau M, Schupf, Nicole, Krinsky-McHale, Sharon J, Mapstone, Mark, Silverman, Wayne, Lott, Ira, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Diana Rosas, H, Zaman, Shahid, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, Handen, Benjamin, Hartley, Sigan, Fortea, Juan, O'Bryant, Sid, and Alzheimer’s Biomarker Consortium –Down Syndrome (ABC-DS)
Abstract: BackgroundThe need for diagnostic biomarkers of cognitive decline is particularly important among aging adults with Down syndrome (DS). Growing empirical support has identified the utility of plasma derived biomarkers among neurotypical adults with mild cognitive impairment (MCI) and Alzheimer's disease (AD); however, the application of such biomarkers has been limited among the DS population.ObjectiveThis study aimed to investigate the cross-sectional diagnostic performance of plasma neurofilament light chain (Nf-L) and total-tau, individually and in combination among a cohort of DS adults.MethodsPlasma samples were analyzed from n = 305 (n = 225 cognitively stable (CS); n = 44 MCI-DS; n = 36 DS-AD) participants enrolled in the Alzheimer's Biomarker Consortium -Down Syndrome.ResultsIn distinguishing DS-AD participants from CS, Nf-L alone produced an AUC of 90%, total-tau alone reached 74%, and combined reached an AUC of 86%. When age and gender were included, AUC increased to 93%. Higher values of Nf-L, total-tau, and age were all shown to be associated with increased risk for DS-AD. When distinguishing MCI-DS participants from CS, Nf-L alone produced an AUC of 65%, while total-tau alone reached 56%. A combined model with Nf-L, total-tau, age, and gender produced an AUC of 87%. Both higher values in age and total-tau were found to increase risk for MCI-DS; Nf-L levels were not associated with increased risk for MCI-DS.ConclusionAdvanced assay techniques make total-tau and particularly Nf-L useful biomarkers of both AD pathology and clinical status in DS and have the potential to serve as outcome measures in clinical trials for future disease-modifying drugs.
Published: 2021

5. Proteomic profiles of prevalent mild cognitive impairment and Alzheimer's disease among adults with Down syndrome.

Author: Petersen, Melissa, Petersen, Melissa, Zhang, Fan, Krinsky-McHale, Sharon J, Silverman, Wayne, Lee, Joseph H, Pang, Deborah, Hall, James, Schupf, Nicole, O'Bryant, Sid E, Petersen, Melissa, Petersen, Melissa, Zhang, Fan, Krinsky-McHale, Sharon J, Silverman, Wayne, Lee, Joseph H, Pang, Deborah, Hall, James, Schupf, Nicole, and O'Bryant, Sid E
Abstract: IntroductionWe sought to determine if a proteomic profile approach developed to detect Alzheimer's disease (AD) in the general population would apply to adults with Down syndrome (DS).MethodsPlasma samples were obtained from 398 members of a community-based cohort of adults with DS. A total of n = 186 participants were determined to be non-demented and without mild cognitive impairment (MCI) at baseline and throughout follow-up; n = 50 had prevalent MCI; n = 42 had prevalent AD.ResultsThe proteomic profile yielded an area under the curve (AUC) of 0.92, sensitivity (SN) = 0.80, and specificity (SP) = 0.98 detecting prevalent MCI. For detecting prevalent AD, the proteomic profile yielded an AUC of 0.89, SN = 0.81, and SP = 0.97. The overall profile closely resembled our previously published profile of AD in the general population.DiscussionThese data provide evidence of the applicability of our blood-based algorithm for detecting MCI/AD among adults with DS.
Published: 2020

6. The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale and methodology.

Author: Handen, Benjamin L, Handen, Benjamin L, Lott, Ira T, Christian, Bradley T, Schupf, Nicole, OBryant, Sid, Mapstone, Mark, Fagan, Anne M, Lee, Joseph H, Tudorascu, Dana, Wang, Mei-Cheng, Head, Elizabeth, Klunk, William, Ances, Beau, Lai, Florence, Zaman, Shahid, Krinsky-McHale, Sharon, Brickman, Adam M, Rosas, H Diana, Cohen, Annie, Andrews, Howard, Hartley, Sigan, Silverman, Wayne, Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS), Handen, Benjamin L, Handen, Benjamin L, Lott, Ira T, Christian, Bradley T, Schupf, Nicole, OBryant, Sid, Mapstone, Mark, Fagan, Anne M, Lee, Joseph H, Tudorascu, Dana, Wang, Mei-Cheng, Head, Elizabeth, Klunk, William, Ances, Beau, Lai, Florence, Zaman, Shahid, Krinsky-McHale, Sharon, Brickman, Adam M, Rosas, H Diana, Cohen, Annie, Andrews, Howard, Hartley, Sigan, Silverman, Wayne, and Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS)
Abstract: IntroductionAdults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments.MethodsWe describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression.ResultsApproximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided.DiscussionThis represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population.
Published: 2020

7. Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study.

Author: Petersen, Melissa E, Petersen, Melissa E, Zhang, Fan, Schupf, Nicole, Krinsky-McHale, Sharon J, Hall, James, Mapstone, Mark, Cheema, Amrita, Silverman, Wayne, Lott, Ira, Rafii, Michael S, Handen, Benjamin, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Rosas, H Diana, Zaman, Shahid, Ances, Beau M, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, O'Bryant, Sid, Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS), Petersen, Melissa E, Petersen, Melissa E, Zhang, Fan, Schupf, Nicole, Krinsky-McHale, Sharon J, Hall, James, Mapstone, Mark, Cheema, Amrita, Silverman, Wayne, Lott, Ira, Rafii, Michael S, Handen, Benjamin, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Rosas, H Diana, Zaman, Shahid, Ances, Beau M, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, O'Bryant, Sid, and Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS)
Abstract: Introduction:Previously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS). Methods:Data were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS). Results:Distinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A , and FABP3 correlated fractions at r2 > = 0.90. Discussion:Proteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD.
Published: 2020

8. Proteomic profiles of prevalent mild cognitive impairment and Alzheimer's disease among adults with Down syndrome.

Author: Petersen, Melissa, Petersen, Melissa, Zhang, Fan, Krinsky-McHale, Sharon J, Silverman, Wayne, Lee, Joseph H, Pang, Deborah, Hall, James, Schupf, Nicole, O'Bryant, Sid E, Petersen, Melissa, Petersen, Melissa, Zhang, Fan, Krinsky-McHale, Sharon J, Silverman, Wayne, Lee, Joseph H, Pang, Deborah, Hall, James, Schupf, Nicole, and O'Bryant, Sid E
Abstract: IntroductionWe sought to determine if a proteomic profile approach developed to detect Alzheimer's disease (AD) in the general population would apply to adults with Down syndrome (DS).MethodsPlasma samples were obtained from 398 members of a community-based cohort of adults with DS. A total of n = 186 participants were determined to be non-demented and without mild cognitive impairment (MCI) at baseline and throughout follow-up; n = 50 had prevalent MCI; n = 42 had prevalent AD.ResultsThe proteomic profile yielded an area under the curve (AUC) of 0.92, sensitivity (SN) = 0.80, and specificity (SP) = 0.98 detecting prevalent MCI. For detecting prevalent AD, the proteomic profile yielded an AUC of 0.89, SN = 0.81, and SP = 0.97. The overall profile closely resembled our previously published profile of AD in the general population.DiscussionThese data provide evidence of the applicability of our blood-based algorithm for detecting MCI/AD among adults with DS.
Published: 2020

9. Proteomic profiles for Alzheimer's disease and mild cognitive impairment among adults with Down syndrome spanning serum and plasma: An Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS) study.

Author: Petersen, Melissa E, Petersen, Melissa E, Zhang, Fan, Schupf, Nicole, Krinsky-McHale, Sharon J, Hall, James, Mapstone, Mark, Cheema, Amrita, Silverman, Wayne, Lott, Ira, Rafii, Michael S, Handen, Benjamin, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Rosas, H Diana, Zaman, Shahid, Ances, Beau M, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, O'Bryant, Sid, Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS), Petersen, Melissa E, Petersen, Melissa E, Zhang, Fan, Schupf, Nicole, Krinsky-McHale, Sharon J, Hall, James, Mapstone, Mark, Cheema, Amrita, Silverman, Wayne, Lott, Ira, Rafii, Michael S, Handen, Benjamin, Klunk, William, Head, Elizabeth, Christian, Brad, Foroud, Tatiana, Lai, Florence, Rosas, H Diana, Zaman, Shahid, Ances, Beau M, Wang, Mei-Cheng, Tycko, Benjamin, Lee, Joseph H, O'Bryant, Sid, and Alzheimer's Biomarker Consortium – Down Syndrome (ABC‐DS)
Abstract: IntroductionPreviously generated serum and plasma proteomic profiles were examined among adults with Down syndrome (DS) to determine whether these profiles could discriminate those with mild cognitive impairment (MCI-DS) and Alzheimer's disease (DS-AD) from those cognitively stable (CS).MethodsData were analyzed on n = 305 (n = 225 CS; n = 44 MCI-DS; n = 36 DS-AD) enrolled in the Alzheimer's Biomarker Consortium-Down Syndrome (ABC-DS).ResultsDistinguishing MCI-DS from CS, the serum profile produced an area under the curve (AUC) = 0.95 (sensitivity [SN] = 0.91; specificity [SP] = 0.99) and an AUC = 0.98 (SN = 0.96; SP = 0.97) for plasma when using an optimized cut-off score. Distinguishing DS-AD from CS, the serum profile produced an AUC = 0.93 (SN = 0.81; SP = 0.99) and an AUC = 0.95 (SN = 0.86; SP = 1.0) for plasma when using an optimized cut-off score. AUC remained unchanged to slightly improved when age and sex were included. Eotaxin3, interleukin (IL)-10, C-reactive protein, IL-18, serum amyloid A , and FABP3 correlated fractions at r2 > = 0.90.DiscussionProteomic profiles showed excellent detection accuracy for MCI-DS and DS-AD.
Published: 2020

10. The Alzheimer's Biomarker Consortium-Down Syndrome: Rationale and methodology.

Author: Handen, Benjamin L, Handen, Benjamin L, Lott, Ira T, Christian, Bradley T, Schupf, Nicole, OBryant, Sid, Mapstone, Mark, Fagan, Anne M, Lee, Joseph H, Tudorascu, Dana, Wang, Mei-Cheng, Head, Elizabeth, Klunk, William, Ances, Beau, Lai, Florence, Zaman, Shahid, Krinsky-McHale, Sharon, Brickman, Adam M, Rosas, H Diana, Cohen, Annie, Andrews, Howard, Hartley, Sigan, Silverman, Wayne, Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS), Handen, Benjamin L, Handen, Benjamin L, Lott, Ira T, Christian, Bradley T, Schupf, Nicole, OBryant, Sid, Mapstone, Mark, Fagan, Anne M, Lee, Joseph H, Tudorascu, Dana, Wang, Mei-Cheng, Head, Elizabeth, Klunk, William, Ances, Beau, Lai, Florence, Zaman, Shahid, Krinsky-McHale, Sharon, Brickman, Adam M, Rosas, H Diana, Cohen, Annie, Andrews, Howard, Hartley, Sigan, Silverman, Wayne, and Alzheimer's Biomarker Consortium‐Down Syndrome (ABC‐DS)
Abstract: IntroductionAdults with Down syndrome (DS) are at exceptionally high risk for Alzheimer's disease (AD), with virtually all individuals developing key neuropathological features by age 40. Identifying biomarkers of AD progression in DS can provide valuable insights into pathogenesis and suggest targets for disease modifying treatments.MethodsWe describe the development of a multi-center, longitudinal study of biomarkers of AD in DS. The protocol includes longitudinal examination of clinical, cognitive, blood and cerebrospinal fluid-based biomarkers, magnetic resonance imaging and positron emission tomography measures (at 16-month intervals), as well as genetic modifiers of AD risk and progression.ResultsApproximately 400 individuals will be enrolled in the study (more than 370 to date). The methodological approach from the administrative, clinical, neuroimaging, omics, neuropathology, and statistical cores is provided.DiscussionThis represents the largest U.S.-based, multi-site, biomarker initiative of AD in DS. Findings can inform other multidisciplinary networks studying AD in the general population.
Published: 2020

11. Alzheimer-Related Cerebrovascular Disease in Down Syndrome.

Author: Lao, Patrick J, Lao, Patrick J, Gutierrez, José, Keator, David, Rizvi, Batool, Banerjee, Arit, Igwe, Kay C, Laing, Krystal K, Sathishkumar, Mithra, Moni, Fahmida, Andrews, Howard, Krinsky-McHale, Sharon, Head, Elizabeth, Lee, Joseph H, Lai, Florence, Yassa, Michael A, Rosas, H Diana, Silverman, Wayne, Lott, Ira T, Schupf, Nicole, Brickman, Adam M, Lao, Patrick J, Lao, Patrick J, Gutierrez, José, Keator, David, Rizvi, Batool, Banerjee, Arit, Igwe, Kay C, Laing, Krystal K, Sathishkumar, Mithra, Moni, Fahmida, Andrews, Howard, Krinsky-McHale, Sharon, Head, Elizabeth, Lee, Joseph H, Lai, Florence, Yassa, Michael A, Rosas, H Diana, Silverman, Wayne, Lott, Ira T, Schupf, Nicole, and Brickman, Adam M
Abstract: ObjectiveAdults with Down syndrome (DS) develop Alzheimer disease (AD) pathology by their 5th decade. Compared with the general population, traditional vascular risks in adults with DS are rare, allowing examination of cerebrovascular disease in this population and insight into its role in AD without the confound of vascular risk factors. We examined in vivo magnetic resonance imaging (MRI)-based biomarkers of cerebrovascular pathology in adults with DS, and determined their cross-sectional relationship with age, beta-amyloid pathology, and mild cognitive impairment or clinical AD diagnostic status.MethodsParticipants from the Biomarkers of Alzheimer's Disease in Down Syndrome study (n = 138, 50 ± 7 years, 39% women) with MRI data and a subset (n = 90) with amyloid positron emission tomography (PET) were included. We derived MRI-based biomarkers of cerebrovascular pathology, including white matter hyperintensities (WMH), infarcts, cerebral microbleeds, and enlarged perivascular spaces (PVS), as well as PET-based biomarkers of amyloid burden. Participants were characterized as cognitively stable (CS), mild cognitive impairment-DS (MCI-DS), possible AD dementia, or definite AD dementia based on in-depth assessments of cognition, function, and health status.ResultsThere were detectable WMH, enlarged PVS, infarcts, and microbleeds as early as the 5th decade of life. There was a monotonic increase in WMH volume, enlarged PVS, and presence of infarcts across diagnostic groups (CS < MCI-DS < possible AD dementia < definite AD dementia). Higher amyloid burden was associated with a higher likelihood of an infarct.InterpretationThe findings highlight the prevalence of cerebrovascular disease in adults with DS and add to a growing body of evidence that implicates cerebrovascular disease as a core feature of AD and not simply a comorbidity. ANN NEUROL 2020;88:1165-1177.
Published: 2020

12. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author: Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renström, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., and Morrison, Alanna C.
Abstract: Elevated blood pressure (BP), a leading cause of global morbidity and mortality, is influenced by both genetic and lifestyle factors. Cigarette smoking is one such lifestyle factor. Across five ancestries, we performed a genome-wide gene–smoking interaction study of mean arterial pressure (MAP) and pulse pressure (PP) in 129 913 individuals in stage 1 and follow-up analysis in 480 178 additional individuals in stage 2. We report here 136 loci significantly associated with MAP and/or PP. Of these, 61 were previously published through main-effect analysis of BP traits, 37 were recently reported by us for systolic BP and/or diastolic BP through gene–smoking interaction analysis and 38 were newly identified (P < 5 × 10−8, false discovery rate < 0.05). We also identified nine new signals near known loci. Of the 136 loci, 8 showed significant interaction with smoking status. They include CSMD1 previously reported for insulin resistance and BP in the spontaneously hypertensive rats. Many of the 38 new loci show biologic plausibility for a role in BP regulation. SLC26A7 encodes a chloride/bicarbonate exchanger expressed in the renal outer medullary collecting duct. AVPR1A is widely expressed, including in vascular smooth muscle cells, kidney, myocardium and brain. FHAD1 is a long non-coding RNA overexpressed in heart failure. TMEM51 was associated with contractile function in cardiomyocytes. CASP9 plays a central role in cardiomyocyte apoptosis. Identified only in African ancestry were 30 novel loci. Our findings highlight the value of multi-ancestry investigations, particularly in studies of interaction with lifestyle factors, where genomic and lifestyle differences may contribute to novel findings.
Published: 2019
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13. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions

Author: de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., Morrison, Alanna C., de Vries, Paul S., Brown, Michael R., Bentley, Amy R., Sung, Yun J., Winkler, Thomas W., Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T., Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E., Musani, Solomon K., Li, Changwei, Feitosa, Mary F., Richard, Melissa A., Noordam, Raymond, Aschard, Hugues, Bartz, Traci M., Bielak, Lawrence F., Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K., Manning, Alisa K., Rankinen, Tuomo, Smith, Albert V., Tajuddin, Salman M., Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Laguzzi, Federica, Lee, Joseph H., Luan, Jian'an, Lyytikainen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M., Pietzner, Maik, Riaz, Muhammad, Said, M. Abdullah, Scott, Robert A., Sofer, Tamar, Stancakova, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O., van der Most, Peter J., Varga, Tibor V., Wang, Yajuan, Ware, Erin B., Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E., Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickael, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M., de Faire, Ulf, de las Fuentes, Lisa, de Mutsert, Renee, de Silva, H. Janaka, Ding, Jingzhong, Dominiczak, Anna F., Duan, Qing, Eaton, Charles B., Eppinga, Ruben N., Faul, Jessica D., Fisher, Virginia, Forrester, Terrence, Franco, Oscar H., Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, Grabe, Hans J., Grove, Megan L., Gu, C. Charles, Harris, Tamara B., Heikkinen, Sami, Heng, Chew-Kiat, Hirata, Makoto, Hixson, James E., Howard, Barbara V., Ikram, M. Arfan, Jacobs, David R., Jr., Johnson, Craig, Jonas, Jost Bruno, Kammerer, Candace M., Katsuya, Tomohiro, Khor, Chiea Chuen, Kilpelainen, Tuomas O., Koh, Woon-Puay, Koistinen, Heikki A., Kolcic, Ivana, Kooperberg, Charles, Krieger, Jose E., Kritchevsky, Steve B., Kubo, Michiaki, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lehne, Benjamin, Lemaitre, Rozenn N., Li, Yize, Liang, Jingjing, Liu, Jianjun, Liu, Kiang, Loh, Marie, Louie, Tin, Magi, Reedik, Manichaikul, Ani W., McKenzie, Colin A., Meitinger, Thomas, Metspalu, Andres, Milaneschi, Yuri, Milani, Lili, Mohlke, Karen L., Mosley, Thomas H., Jr., Mukamal, Kenneth J., Nalls, Mike A., Nauck, Matthias, Nelson, Christopher P., Sotoodehnia, Nona, O'Connell, Jeff R., Palmer, Nicholette D., Pazoki, Raha, Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Poulter, Neil, Raffel, Leslie J., Raitakari, Olli T., Reiner, Alex P., Rice, Treva K., Rich, Stephen S., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Shi, Yuan, Sidney, Stephen, Sims, Mario, Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tan, Nicholas, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., van Heemst, Diana, Vuckovic, Dragana, Waldenberger, Melanie, Wang, Lihua, Wang, Yujie, Wang, Zhe, Wei, Wen Bin, Williams, Christine, Wilson, Gregory, Sr., Wojczynski, Mary K., Yao, Jie, Yu, Bing, Yu, Caizheng, Yuan, Jian-Min, Zhao, Wei, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Deary, Ian J., Esko, Tonu, Farrall, Martin, Franks, Paul W., Freedman, Barry I., Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo L., Kamatani, Yoichiro, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Leander, Karin, Lehtimaki, Terho, Magnusson, Patrik K. E., Penninx, Brenda, Pereira, Alexandre C., Rauramaa, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van der Harst, Pim, Wagenknecht, Lynne E., Wang, Ya Xing, Wareham, Nicholas J., Watkins, Hugh, Weir, David R., Wickremasinghe, Ananda R., Zheng, Wei, Elliott, Paul, North, Kari E., Bouchard, Claude, Evans, Michele K., Gudnason, Vilmundur, Liu, Ching-Ti, Liu, Yongmei, Psaty, Bruce M., Ridker, Paul M., van Dam, Rob M., Kardia, Sharon L. R., Zhu, Xiaofeng, Rotimi, Charles N., Mook-Kanamori, Dennis O., Fornage, Myriam, Kelly, Tanika N., Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Liu, Jingmin, Rotter, Jerome I., Gauderman, W. James, Province, Michael A., Munroe, Patricia B., Rice, Kenneth, Chasman, Daniel I., Cupples, L. Adrienne, Rao, Dabeeru C., and Morrison, Alanna C.
Abstract: A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
Published: 2019
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14. Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Author: Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., Perola, Markus, Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., and Perola, Markus
Abstract: Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of
Published: 2019
Full Text: View/download PDF

15. Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Author: Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., Perola, Markus, Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., and Perola, Markus
Abstract: Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of
Published: 2019
Full Text: View/download PDF

16. Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions.

Author: de Vries, Paul S, de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, Giulianini, Franco, de Vries, Paul S, de Vries, Paul S, Brown, Michael R, Bentley, Amy R, Sung, Yun J, Winkler, Thomas W, Ntalla, Ioanna, Schwander, Karen, Kraja, Aldi T, Guo, Xiuqing, Franceschini, Nora, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Huffman, Jennifer E, Musani, Solomon K, Li, Changwei, Feitosa, Mary F, Richard, Melissa A, Noordam, Raymond, Aschard, Hugues, Bartz, Traci M, Bielak, Lawrence F, Deng, Xuan, Dorajoo, Rajkumar, Lohman, Kurt K, Manning, Alisa K, Rankinen, Tuomo, Smith, Albert V, Tajuddin, Salman M, Evangelou, Evangelos, Graff, Mariaelisa, Alver, Maris, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Goel, Anuj, Hagemeijer, Yanick, Harris, Sarah E, Hartwig, Fernando P, He, Meian, Horimoto, Andrea RVR, Hsu, Fang-Chi, Jackson, Anne U, Kasturiratne, Anuradhani, Komulainen, Pirjo, Kühnel, Brigitte, Laguzzi, Federica, Lee, Joseph H, Luan, Jian'an, Lyytikäinen, Leo-Pekka, Matoba, Nana, Nolte, Ilja M, Pietzner, Maik, Riaz, Muhammad, Said, M Abdullah, Scott, Robert A, Sofer, Tamar, Stančáková, Alena, Takeuchi, Fumihiko, Tayo, Bamidele O, van der Most, Peter J, Varga, Tibor V, Wang, Yajuan, Ware, Erin B, Wen, Wanqing, Yanek, Lisa R, Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Amin, Najaf, Amini, Marzyeh, Arking, Dan E, Aung, Tin, Ballantyne, Christie, Boerwinkle, Eric, Broeckel, Ulrich, Campbell, Archie, Canouil, Mickaël, Charumathi, Sabanayagam, Chen, Yii-Der Ida, Connell, John M, de Faire, Ulf, de Las Fuentes, Lisa, de Mutsert, Renée, de Silva, H Janaka, Ding, Jingzhong, Dominiczak, Anna F, Duan, Qing, Eaton, Charles B, Eppinga, Ruben N, Faul, Jessica D, Fisher, Virginia, Forrester, Terrence, Franco, Oscar H, Friedlander, Yechiel, Ghanbari, Mohsen, and Giulianini, Franco
Abstract: A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 × 10-6) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 × 10-8 using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
Published: 2019

17. Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Author: Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., Perola, Markus, Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., and Perola, Markus
Abstract: Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of
Published: 2019
Full Text: View/download PDF

18. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author: Kraja, Aldi T., Liu, Chunyu, Fetterman, Jessica L., Graff, Mariaelisa, Have, Christian Theil, Gu, Charles, Yanek, Lisa R., Feitosa, Mary F., Arking, Dan E., Chasman, Daniel, I, Young, Kristin, Ligthart, Symen, Hill, W. David, Weiss, Stefan, Luan, Jian'an, Giulianini, Franco, Li-Gao, Ruifang, Hartwig, Fernando P., Lin, Shiow J., Wang, Lihua, Richardson, Tom G., Yao, Jie, Fernandez, Eliana P., Ghanbari, Mohsen, Wojczynski, Mary K., Lee, Wen-Jane, Argos, Maria, Armasu, Sebastian M., Barve, Ruteja A., Ryan, Kathleen A., An, Ping, Baranski, Thomas J., Bielinski, Suzette J., Bowden, Donald W., Broeckel, Ulrich, Christensen, Kaare, Chu, Audrey Y., Corley, Janie, Cox, Simon R., Uitterlinden, Andre G., Rivadeneira, Fernando, Cropp, Cheryl D., Daw, E. Warwick, van Heemst, Diana, de las Fuentes, Lisa, Gao, He, Tzoulaki, Ioanna, Ahluwalia, Tarunveer S., de Mutsert, Renee, Emery, Leslie S., Erzurumluoglu, A. Mesut, Perry, James A., Fu, Mao, Forouhi, Nita G., Gu, Zhenglong, Hai, Yang, Harris, Sarah E., Hemani, Gibran, Hunt, Steven C., Irvin, Marguerite R., Jonsson, Anna E., Justice, Anne E., Kernson, Nicola D., Larson, Nicholas B., Lin, Keng-Hung, Love-Gregory, Latisha D., Mathias, Rasika A., Lee, Joseph H., Nauck, Matthias, Noordam, Raymond, Ong, Ken K., Pankow, James, Patki, Amit, Pattie, Alison, Petersmann, Astrid, Qi, Qibin, Ribel-Madsen, Rasmus, Rohde, Rebecca, Sandow, Kevin, Schnurr, Theresia M., Sofer, Tamar, Starr, John M., Taylor, Adele M., Teumer, Alexander, Timpson, Nicholas J., de Haan, Hugoline G., Wang, Yujie, Weeke, Peter E., Williams, Christine, Wu, Hongsheng, Yang, Wei, Zeng, Donglin, Witte, Daniel R., Weir, Bruce S., Wareham, Nicholas J., Vestergaard, Henrik, Turner, Stephen T., Torp-Pedersen, Christian, Stergiakouli, Evie, Sheu, Wayne Huey-Hemg, Rosendaal, Frits R., Ikram, M. Arfan, Franco, Oscar H., Ridker, Paul M., Perls, Thomas T., Pedersen, Oluf, Nohr, Ellen A., Newman, Anne B., Linneberg, Allan, Langenberg, Claudia, Kilpelainen, Tuomas O., Kardia, Sharon L. R., Jørgensen, Marit E., Jørgensen, Torben, Sorensen, Thorkild I. A., Homuth, Georg, Hansen, Torben, Goodarzi, Mark O., Deary, Ian J., Christensen, Cramer, Chen, Yii-Der Ida, Chakravarti, Aravinda, Brandslund, Ivan, Bonnelykke, Klaus, Taylor, Kent D., Wilson, James G., Rodriguez, Santiago, Davies, Gail, Horta, Bernardo L., Thyagarajan, Bharat, Rao, D. C., Grarup, Niels, Davila-Roman, Victor G., Hudson, Gavin, Guo, Xiuqing, Arnett, Donna K., Hayward, Caroline, Vaidya, Dhananjay, Mook-Kanamori, Dennis O., Tiwari, Hemant K., Levy, Daniel, Loos, Ruth J. F., Dehghan, Abbas, Elliott, Paul, Malik, Afshan N., Scott, Robert A., Becker, Diane M., de Andrade, Mariza, Province, Michael A., Meigs, James B., Rotter, Jerome, I, North, Kari E., Kraja, Aldi T., Liu, Chunyu, Fetterman, Jessica L., Graff, Mariaelisa, Have, Christian Theil, Gu, Charles, Yanek, Lisa R., Feitosa, Mary F., Arking, Dan E., Chasman, Daniel, I, Young, Kristin, Ligthart, Symen, Hill, W. David, Weiss, Stefan, Luan, Jian'an, Giulianini, Franco, Li-Gao, Ruifang, Hartwig, Fernando P., Lin, Shiow J., Wang, Lihua, Richardson, Tom G., Yao, Jie, Fernandez, Eliana P., Ghanbari, Mohsen, Wojczynski, Mary K., Lee, Wen-Jane, Argos, Maria, Armasu, Sebastian M., Barve, Ruteja A., Ryan, Kathleen A., An, Ping, Baranski, Thomas J., Bielinski, Suzette J., Bowden, Donald W., Broeckel, Ulrich, Christensen, Kaare, Chu, Audrey Y., Corley, Janie, Cox, Simon R., Uitterlinden, Andre G., Rivadeneira, Fernando, Cropp, Cheryl D., Daw, E. Warwick, van Heemst, Diana, de las Fuentes, Lisa, Gao, He, Tzoulaki, Ioanna, Ahluwalia, Tarunveer S., de Mutsert, Renee, Emery, Leslie S., Erzurumluoglu, A. Mesut, Perry, James A., Fu, Mao, Forouhi, Nita G., Gu, Zhenglong, Hai, Yang, Harris, Sarah E., Hemani, Gibran, Hunt, Steven C., Irvin, Marguerite R., Jonsson, Anna E., Justice, Anne E., Kernson, Nicola D., Larson, Nicholas B., Lin, Keng-Hung, Love-Gregory, Latisha D., Mathias, Rasika A., Lee, Joseph H., Nauck, Matthias, Noordam, Raymond, Ong, Ken K., Pankow, James, Patki, Amit, Pattie, Alison, Petersmann, Astrid, Qi, Qibin, Ribel-Madsen, Rasmus, Rohde, Rebecca, Sandow, Kevin, Schnurr, Theresia M., Sofer, Tamar, Starr, John M., Taylor, Adele M., Teumer, Alexander, Timpson, Nicholas J., de Haan, Hugoline G., Wang, Yujie, Weeke, Peter E., Williams, Christine, Wu, Hongsheng, Yang, Wei, Zeng, Donglin, Witte, Daniel R., Weir, Bruce S., Wareham, Nicholas J., Vestergaard, Henrik, Turner, Stephen T., Torp-Pedersen, Christian, Stergiakouli, Evie, Sheu, Wayne Huey-Hemg, Rosendaal, Frits R., Ikram, M. Arfan, Franco, Oscar H., Ridker, Paul M., Perls, Thomas T., Pedersen, Oluf, Nohr, Ellen A., Newman, Anne B., Linneberg, Allan, Langenberg, Claudia, Kilpelainen, Tuomas O., Kardia, Sharon L. R., Jørgensen, Marit E., Jørgensen, Torben, Sorensen, Thorkild I. A., Homuth, Georg, Hansen, Torben, Goodarzi, Mark O., Deary, Ian J., Christensen, Cramer, Chen, Yii-Der Ida, Chakravarti, Aravinda, Brandslund, Ivan, Bonnelykke, Klaus, Taylor, Kent D., Wilson, James G., Rodriguez, Santiago, Davies, Gail, Horta, Bernardo L., Thyagarajan, Bharat, Rao, D. C., Grarup, Niels, Davila-Roman, Victor G., Hudson, Gavin, Guo, Xiuqing, Arnett, Donna K., Hayward, Caroline, Vaidya, Dhananjay, Mook-Kanamori, Dennis O., Tiwari, Hemant K., Levy, Daniel, Loos, Ruth J. F., Dehghan, Abbas, Elliott, Paul, Malik, Afshan N., Scott, Robert A., Becker, Diane M., de Andrade, Mariza, Province, Michael A., Meigs, James B., Rotter, Jerome, I, and North, Kari E.
Published: 2019

19. Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Author: Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., Perola, Markus, Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., and Perola, Markus
Abstract: Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of
Published: 2019
Full Text: View/download PDF

20. Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Author: Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., Perola, Markus, Sarin, Heikki V., Gudelj, Ivan, Honkanen, Jarno, Ihalainen, Johanna K., Vuorela, Arja, Lee, Joseph H., Jin, Zhenzhen, Terwilliger, Joseph D., Isola, Ville, Ahtiainen, Juha P., Häkkinen, Keijo, Juric, Julija, Lauc, Gordan, Kristiansson, Kati, Hulmi, Juha J., and Perola, Markus
Abstract: Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., "semi-starvation") leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 +/- 4.0 years, body mass index 23.4 +/- 1.7 kg/m(2)) volunteered into either a diet group (n = 25) or a control group (n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline (PRE), at the end of the weight loss period (MID 21.1 +/- 3.1 weeks after PRE), and at the end of the weight regain period (POST 18.4 +/- 2.9 weeks after MID). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters-white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of
Published: 2019
Full Text: View/download PDF

21. A multi-ancestry genome-wide study incorporating gene-smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure

Author: Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renstrom, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., Oskari Kilpeläinen, Tuomas, Sung, Yun Ju, de Las Fuentes, Lisa, Winkler, Thomas W., Chasman, Daniel, I, Bentley, Amy R., Kraja, Aldi T., Ntalla, Ioanna, Warren, Helen R., Guo, Xiuqing, Schwander, Karen, Manning, Alisa K., Brown, Michael R., Aschard, Hugues, Feitosa, Mary F., Franceschini, Nora, Lu, Yingchang, Cheng, Ching-Yu, Sim, Xueling, Vojinovic, Dina, Marten, Jonathan, Musani, Solomon K., Kilpelainen, Tuomas O., Richard, Melissa A., Aslibekyan, Stella, Bartz, Traci M., Dorajoo, Rajkumar, Li, Changwei, Liu, Yongmei, Rankinen, Tuomo, Smith, Albert Vernon, Tajuddin, Salman M., Tayo, Bamidele O., Zhao, Wei, Zhou, Yanhua, Matoba, Nana, Sofer, Tamar, Alver, Maris, Amini, Marzyeh, Boissel, Mathilde, Chai, Jin Fang, Chen, Xu, Divers, Jasmin, Gandin, Ilaria, Gao, Chuan, Giulianini, Franco, Goel, Anuj, Harris, Sarah E., Hartwig, Fernando P., He, Meian, Horimoto, Andrea R. V. R., Hsu, Fang-Chi, Jackson, Anne U., Kammerer, Candace M., Kasturiratne, Anuradhani, Komulainen, Pirjo, Kuehnel, Brigitte, Leander, Karin, Lee, Wen-Jane, Lin, Keng-Hung, Luan, Jian'an, Lyytikainen, Leo-Pekka, McKenzie, Colin A., Nelson, Christopher P., Noordam, Raymond, Scott, Robert A., Sheu, Wayne H. H., Stancakova, Alena, Takeuchi, Fumihiko, van Der Most, Peter J., Varga, Tibor V., Waken, Robert J., Wang, Heming, Wang, Yajuan, Ware, Erin B., Weiss, Stefan, Wen, Wanqing, Yanek, Lisa R., Zhang, Weihua, Zhao, Jing Hua, Afaq, Saima, Alfred, Tamuno, Amin, Najaf, Arking, Dan E., Aung, Tin, Barr, R. Graham, Bielak, Lawrence F., Boerwinkle, Eric, Bottinger, Erwin P., Braund, Peter S., Brody, Jennifer A., Broeckel, Ulrich, Cade, Brian, Campbell, Archie, Canouil, Mickael, Chakravarti, Aravinda, Cocca, Massimiliano, Collins, Francis S., Connell, John M., de Mutsert, Renee, de Silva, H. Janaka, Doerr, Marcus, Duan, Qing, Eaton, Charles B., Ehret, Georg, Evangelou, Evangelos, Faul, Jessica D., Forouhi, Nita G., Franco, Oscar H., Friedlander, Yechiel, Gao, He, Gigante, Bruna, Gu, C. Charles, Gupta, Preeti, Hagenaars, Saskia P., Harris, Tamara B., He, Jiang, Heikkinen, Sami, Heng, Chew-Kiat, Hofman, Albert, Howard, Barbara, V, Hunt, Steven C., Irvin, Marguerite R., Jia, Yucheng, Katsuya, Tomohiro, Kaufman, Joel, Kerrison, Nicola D., Khor, Chiea Chuen, Koh, Woon-Puay, Koistinen, Heikki A., Kooperberg, Charles B., Krieger, Jose E., Kubo, Michiaki, Kutalik, Zoltan, Kuusisto, Johanna, Lakka, Timo A., Langefeld, Carl D., Langenberg, Claudia, Launer, Lenore J., Lee, Joseph H., Lehne, Benjamin, Levy, Daniel, Lewis, Cora E., Li, Yize, Lim, Sing Hui, Liu, Ching-Ti, Liu, Jianjun, Liu, Jingmin, Liu, Yeheng, Loh, Marie, Lohman, Kurt K., Louie, Tin, Magi, Reedik, Matsuda, Koichi, Meitinger, Thomas, Metspalu, Andres, Milani, Lili, Momozawa, Yukihide, Mosley, Thomas H., Jr., Nalls, Mike A., Nasri, Ubaydah, O'Connell, Jeff R., Ogunniyi, Adesola, Palmas, Walter R., Palmer, Nicholette D., Pankow, James S., Pedersen, Nancy L., Peters, Annette, Peyser, Patricia A., Polasek, Ozren, Porteous, David, Raitakari, Olli T., Renstrom, Frida, Rice, Treva K., Ridker, Paul M., Robino, Antonietta, Robinson, Jennifer G., Rose, Lynda M., Rudan, Igor, Sabanayagam, Charumathi, Salako, Babatunde L., Sandow, Kevin, Schmidt, Carsten O., Schreiner, Pamela J., Scott, William R., Sever, Peter, Sims, Mario, Sitlani, Colleen M., Smith, Blair H., Smith, Jennifer A., Snieder, Harold, Starr, John M., Strauch, Konstantin, Tang, Hua, Taylor, Kent D., Teo, Yik Ying, Tham, Yih Chung, Uitterlinden, Andre G., Waldenberger, Melanie, Wang, Lihua, Wang, Ya Xing, Wei, Wen Bin, Wilson, Gregory, Wojczynski, Mary K., Xiang, Yong-Bing, Yao, Jie, Yu, Caizheng, Yuan, Jian-Min, Zonderman, Alan B., Becker, Diane M., Boehnke, Michael, Bowden, Donald W., Chambers, John C., Chen, Yii-Der Ida, Weir, David R., de Faire, Ulf, Deary, Ian J., Esko, Tonu, Farrall, Martin, Forrester, Terrence, Freedman, Barry, I, Froguel, Philippe, Gasparini, Paolo, Gieger, Christian, Horta, Bernardo Lessa, Hung, Yi-Jen, Jonas, Jost Bruno, Kato, Norihiro, Kooner, Jaspal S., Laakso, Markku, Lehtimaki, Terho, Liang, Kae-Woei, Magnusson, Patrik K. E., Oldehinkel, Albertine J., Pereira, Alexandre C., Perls, Thomas, Rauramaa, Rainer, Redline, Susan, Rettig, Rainer, Samani, Nilesh J., Scott, James, Shu, Xiao-Ou, van Der Harst, Pim, Wagenknecht, Lynne E., Wareham, Nicholas J., Watkins, Hugh, Wickremasinghe, Ananda R., Wu, Tangchun, Kamatani, Yoichiro, Laurie, Cathy C., Bouchard, Claude, Cooper, Richard S., Evans, Michele K., Gudnason, Vilmundur, Hixson, James, Kardia, Sharon L. R., Kritchevsky, Stephen B., Psaty, Bruce M., van Dam, Rob M., Arnett, Donna K., Mook-Kanamori, Dennis O., Fornage, Myriam, Fox, Ervin R., Hayward, Caroline, van Duijn, Cornelia M., Tai, E. Shyong, Wong, Tien Yin, Loos, Ruth J. F., Reiner, Alex P., Rotimi, Charles N., Bierut, Laura J., Zhu, Xiaofeng, Cupples, L. Adrienne, Province, Michael A., Rotter, Jerome, I, Franks, Paul W., Rice, Kenneth, Elliott, Paul, Caulfield, Mark J., Gauderman, W. James, Munroe, Patricia B., Rao, Dabeeru C., Morrison, Alanna C., and Oskari Kilpeläinen, Tuomas
Published: 2019

22. Associations of Mitochondrial and Nuclear Mitochondrial Variants and Genes with Seven Metabolic Traits

Author: Kraja, Aldi T., Liu, Chunyu, Fetterman, Jessica L., Graff, Mariaelisa, Have, Christian Theil, Gu, Charles, Yanek, Lisa R., Feitosa, Mary F., Arking, Dan E., Chasman, Daniel, I, Young, Kristin, Ligthart, Symen, Hill, W. David, Weiss, Stefan, Luan, Jian'an, Giulianini, Franco, Li-Gao, Ruifang, Hartwig, Fernando P., Lin, Shiow J., Wang, Lihua, Richardson, Tom G., Yao, Jie, Fernandez, Eliana P., Ghanbari, Mohsen, Wojczynski, Mary K., Lee, Wen-Jane, Argos, Maria, Armasu, Sebastian M., Barve, Ruteja A., Ryan, Kathleen A., An, Ping, Baranski, Thomas J., Bielinski, Suzette J., Bowden, Donald W., Broeckel, Ulrich, Christensen, Kaare, Chu, Audrey Y., Corley, Janie, Cox, Simon R., Uitterlinden, Andre G., Rivadeneira, Fernando, Cropp, Cheryl D., Daw, E. Warwick, van Heemst, Diana, de las Fuentes, Lisa, Gao, He, Tzoulaki, Ioanna, Ahluwalia, Tarunveer S., de Mutsert, Renee, Emery, Leslie S., Erzurumluoglu, A. Mesut, Perry, James A., Fu, Mao, Forouhi, Nita G., Gu, Zhenglong, Hai, Yang, Harris, Sarah E., Hemani, Gibran, Hunt, Steven C., Irvin, Marguerite R., Jonsson, Anna E., Justice, Anne E., Kernson, Nicola D., Larson, Nicholas B., Lin, Keng-Hung, Love-Gregory, Latisha D., Mathias, Rasika A., Lee, Joseph H., Nauck, Matthias, Noordam, Raymond, Ong, Ken K., Pankow, James, Patki, Amit, Pattie, Alison, Petersmann, Astrid, Qi, Qibin, Ribel-Madsen, Rasmus, Rohde, Rebecca, Sandow, Kevin, Schnurr, Theresia M., Sofer, Tamar, Starr, John M., Taylor, Adele M., Teumer, Alexander, Timpson, Nicholas J., de Haan, Hugoline G., Wang, Yujie, Weeke, Peter E., Williams, Christine, Wu, Hongsheng, Yang, Wei, Zeng, Donglin, Witte, Daniel R., Weir, Bruce S., Wareham, Nicholas J., Vestergaard, Henrik, Turner, Stephen T., Torp-Pedersen, Christian, Stergiakouli, Evie, Sheu, Wayne Huey-Hemg, Rosendaal, Frits R., Ikram, M. Arfan, Franco, Oscar H., Ridker, Paul M., Perls, Thomas T., Pedersen, Oluf, Nohr, Ellen A., Newman, Anne B., Linneberg, Allan, Langenberg, Claudia, Kilpelainen, Tuomas O., Kardia, Sharon L. R., Jørgensen, Marit E., Jørgensen, Torben, Sorensen, Thorkild I. A., Homuth, Georg, Hansen, Torben, Goodarzi, Mark O., Deary, Ian J., Christensen, Cramer, Chen, Yii-Der Ida, Chakravarti, Aravinda, Brandslund, Ivan, Bonnelykke, Klaus, Taylor, Kent D., Wilson, James G., Rodriguez, Santiago, Davies, Gail, Horta, Bernardo L., Thyagarajan, Bharat, Rao, D. C., Grarup, Niels, Davila-Roman, Victor G., Hudson, Gavin, Guo, Xiuqing, Arnett, Donna K., Hayward, Caroline, Vaidya, Dhananjay, Mook-Kanamori, Dennis O., Tiwari, Hemant K., Levy, Daniel, Loos, Ruth J. F., Dehghan, Abbas, Elliott, Paul, Malik, Afshan N., Scott, Robert A., Becker, Diane M., de Andrade, Mariza, Province, Michael A., Meigs, James B., Rotter, Jerome, I, North, Kari E., Kraja, Aldi T., Liu, Chunyu, Fetterman, Jessica L., Graff, Mariaelisa, Have, Christian Theil, Gu, Charles, Yanek, Lisa R., Feitosa, Mary F., Arking, Dan E., Chasman, Daniel, I, Young, Kristin, Ligthart, Symen, Hill, W. David, Weiss, Stefan, Luan, Jian'an, Giulianini, Franco, Li-Gao, Ruifang, Hartwig, Fernando P., Lin, Shiow J., Wang, Lihua, Richardson, Tom G., Yao, Jie, Fernandez, Eliana P., Ghanbari, Mohsen, Wojczynski, Mary K., Lee, Wen-Jane, Argos, Maria, Armasu, Sebastian M., Barve, Ruteja A., Ryan, Kathleen A., An, Ping, Baranski, Thomas J., Bielinski, Suzette J., Bowden, Donald W., Broeckel, Ulrich, Christensen, Kaare, Chu, Audrey Y., Corley, Janie, Cox, Simon R., Uitterlinden, Andre G., Rivadeneira, Fernando, Cropp, Cheryl D., Daw, E. Warwick, van Heemst, Diana, de las Fuentes, Lisa, Gao, He, Tzoulaki, Ioanna, Ahluwalia, Tarunveer S., de Mutsert, Renee, Emery, Leslie S., Erzurumluoglu, A. Mesut, Perry, James A., Fu, Mao, Forouhi, Nita G., Gu, Zhenglong, Hai, Yang, Harris, Sarah E., Hemani, Gibran, Hunt, Steven C., Irvin, Marguerite R., Jonsson, Anna E., Justice, Anne E., Kernson, Nicola D., Larson, Nicholas B., Lin, Keng-Hung, Love-Gregory, Latisha D., Mathias, Rasika A., Lee, Joseph H., Nauck, Matthias, Noordam, Raymond, Ong, Ken K., Pankow, James, Patki, Amit, Pattie, Alison, Petersmann, Astrid, Qi, Qibin, Ribel-Madsen, Rasmus, Rohde, Rebecca, Sandow, Kevin, Schnurr, Theresia M., Sofer, Tamar, Starr, John M., Taylor, Adele M., Teumer, Alexander, Timpson, Nicholas J., de Haan, Hugoline G., Wang, Yujie, Weeke, Peter E., Williams, Christine, Wu, Hongsheng, Yang, Wei, Zeng, Donglin, Witte, Daniel R., Weir, Bruce S., Wareham, Nicholas J., Vestergaard, Henrik, Turner, Stephen T., Torp-Pedersen, Christian, Stergiakouli, Evie, Sheu, Wayne Huey-Hemg, Rosendaal, Frits R., Ikram, M. Arfan, Franco, Oscar H., Ridker, Paul M., Perls, Thomas T., Pedersen, Oluf, Nohr, Ellen A., Newman, Anne B., Linneberg, Allan, Langenberg, Claudia, Kilpelainen, Tuomas O., Kardia, Sharon L. R., Jørgensen, Marit E., Jørgensen, Torben, Sorensen, Thorkild I. A., Homuth, Georg, Hansen, Torben, Goodarzi, Mark O., Deary, Ian J., Christensen, Cramer, Chen, Yii-Der Ida, Chakravarti, Aravinda, Brandslund, Ivan, Bonnelykke, Klaus, Taylor, Kent D., Wilson, James G., Rodriguez, Santiago, Davies, Gail, Horta, Bernardo L., Thyagarajan, Bharat, Rao, D. C., Grarup, Niels, Davila-Roman, Victor G., Hudson, Gavin, Guo, Xiuqing, Arnett, Donna K., Hayward, Caroline, Vaidya, Dhananjay, Mook-Kanamori, Dennis O., Tiwari, Hemant K., Levy, Daniel, Loos, Ruth J. F., Dehghan, Abbas, Elliott, Paul, Malik, Afshan N., Scott, Robert A., Becker, Diane M., de Andrade, Mariza, Province, Michael A., Meigs, James B., Rotter, Jerome, I, and North, Kari E.
Published: 2019

23. Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.

Author: Miranda, Andre M, Miranda, Andre M, Herman, Mathieu, Cheng, Rong, Nahmani, Eden, Barrett, Geoffrey, Micevska, Elizabeta, Fontaine, Gaelle, Potier, Marie-Claude, Head, Elizabeth, Schmitt, Frederick A, Lott, Ira T, Jiménez-Velázquez, Ivonne Z, Antonarakis, Stylianos E, Di Paolo, Gilbert, Lee, Joseph H, Hussaini, S Abid, Marquer, Catherine, Miranda, Andre M, Miranda, Andre M, Herman, Mathieu, Cheng, Rong, Nahmani, Eden, Barrett, Geoffrey, Micevska, Elizabeta, Fontaine, Gaelle, Potier, Marie-Claude, Head, Elizabeth, Schmitt, Frederick A, Lott, Ira T, Jiménez-Velázquez, Ivonne Z, Antonarakis, Stylianos E, Di Paolo, Gilbert, Lee, Joseph H, Hussaini, S Abid, and Marquer, Catherine
Abstract: The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD.
Published: 2018

24. 3D Numerical Modeling of Geyser Formation by Release of Entrapped Air From Horizontal Pipe Into Vertical Shaft

Author: Chan, Shu Ning CIVL, Cong, Jing, Lee, Joseph H W, Chan, Shu Ning CIVL, Cong, Jing, and Lee, Joseph H W
Abstract: Geysers are explosive eruptions of air-water mixture from manholes in drainage systems. When the design capacity of urban storm water drainage systems is exceeded during extreme rainfall, rapid inflows into the drainage network can lead to air-water interactions that give rise to geysers—causing damage to the water infrastructure and threatening human lives. Although extensive research has revealed the role of entrapped air in causing large pressure transients in drainage tunnels, the mechanism of geyser formation remains elusive. In this study, an unsteady three-dimensional (3D) computational fluid dynamics (CFD) model is developed to simulate the pressure transients and air-water interactions during geyser events using the volume-of-fluid (VOF) technique. Extensive numerical simulations are conducted to study the air-pocket dynamics caused by release of trapped air from a horizontal tunnel into a vertical riser. Model predictions of the air-water interface in the vertical shaft are in good agreement with laboratory measurements by a high-speed camera; the mechanism for the formation of geysers is elucidated. It is found that during a geyser event, compression of the air pocket in the riser can lead to rapid acceleration of the overlying water column and its expulsion from the riser; the air-pocket pressure is significantly higher than the hydrostatic pressure of the overlying water column, and the velocity is greater than that of a Taylor bubble. Comprehensive numerical modeling has been conducted to study the effect of the vertical shaft diameter, the upstream pressure head and the air-pocket volume on the air-pocket dynamics; the results show that geyser formation is primarily controlled by the riser to tunnel diameter ratio, Dr/DDr/D. 3D CFD simulations have also been carried out for an idealized prototype drainage system; it is shown that the geyser behavior can be characterized by extremely large vertical air velocities that result in dispersed air
Published: 2018

25. 3D Numerical Modeling of Geyser Formation by Release of Entrapped Air From Horizontal Pipe Into Vertical Shaft

Author: Chan, Shu Ning CIVL, Cong, Jing, Lee, Joseph H W, Chan, Shu Ning CIVL, Cong, Jing, and Lee, Joseph H W
Abstract: Geysers are explosive eruptions of air-water mixture from manholes in drainage systems. When the design capacity of urban storm water drainage systems is exceeded during extreme rainfall, rapid inflows into the drainage network can lead to air-water interactions that give rise to geysers—causing damage to the water infrastructure and threatening human lives. Although extensive research has revealed the role of entrapped air in causing large pressure transients in drainage tunnels, the mechanism of geyser formation remains elusive. In this study, an unsteady three-dimensional (3D) computational fluid dynamics (CFD) model is developed to simulate the pressure transients and air-water interactions during geyser events using the volume-of-fluid (VOF) technique. Extensive numerical simulations are conducted to study the air-pocket dynamics caused by release of trapped air from a horizontal tunnel into a vertical riser. Model predictions of the air-water interface in the vertical shaft are in good agreement with laboratory measurements by a high-speed camera; the mechanism for the formation of geysers is elucidated. It is found that during a geyser event, compression of the air pocket in the riser can lead to rapid acceleration of the overlying water column and its expulsion from the riser; the air-pocket pressure is significantly higher than the hydrostatic pressure of the overlying water column, and the velocity is greater than that of a Taylor bubble. Comprehensive numerical modeling has been conducted to study the effect of the vertical shaft diameter, the upstream pressure head and the air-pocket volume on the air-pocket dynamics; the results show that geyser formation is primarily controlled by the riser to tunnel diameter ratio, Dr/DDr/D. 3D CFD simulations have also been carried out for an idealized prototype drainage system; it is shown that the geyser behavior can be characterized by extremely large vertical air velocities that result in dispersed air
Published: 2018

26. Excess Synaptojanin 1 Contributes to Place Cell Dysfunction and Memory Deficits in the Aging Hippocampus in Three Types of Alzheimer's Disease.

Author: Miranda, Andre M, Miranda, Andre M, Herman, Mathieu, Cheng, Rong, Nahmani, Eden, Barrett, Geoffrey, Micevska, Elizabeta, Fontaine, Gaelle, Potier, Marie-Claude, Head, Elizabeth, Schmitt, Frederick A, Lott, Ira T, Jiménez-Velázquez, Ivonne Z, Antonarakis, Stylianos E, Di Paolo, Gilbert, Lee, Joseph H, Hussaini, S Abid, Marquer, Catherine, Miranda, Andre M, Miranda, Andre M, Herman, Mathieu, Cheng, Rong, Nahmani, Eden, Barrett, Geoffrey, Micevska, Elizabeta, Fontaine, Gaelle, Potier, Marie-Claude, Head, Elizabeth, Schmitt, Frederick A, Lott, Ira T, Jiménez-Velázquez, Ivonne Z, Antonarakis, Stylianos E, Di Paolo, Gilbert, Lee, Joseph H, Hussaini, S Abid, and Marquer, Catherine
Abstract: The phosphoinositide phosphatase synaptojanin 1 (SYNJ1) is a key regulator of synaptic function. We first tested whether SYNJ1 contributes to phenotypic variations in familial Alzheimer's disease (FAD) and show that SYNJ1 polymorphisms are associated with age of onset in both early- and late-onset human FAD cohorts. We then interrogated whether SYNJ1 levels could directly affect memory. We show that increased SYNJ1 levels in autopsy brains from adults with Down syndrome (DS/AD) are inversely correlated with synaptophysin levels, a direct readout of synaptic integrity. We further report age-dependent cognitive decline in a mouse model overexpressing murine Synj1 to the levels observed in human sporadic AD, triggered through hippocampal hyperexcitability and defects in the spatial reproducibility of place fields. Taken together, our findings suggest that SYNJ1 contributes to memory deficits in the aging hippocampus in all forms of AD.
Published: 2018

27. 3D Numerical Modeling of Geyser Formation by Release of Entrapped Air From Horizontal Pipe Into Vertical Shaft

Author: Chan, Shu Ning CIVL, Cong, Jing, Lee, Joseph H W, Chan, Shu Ning CIVL, Cong, Jing, and Lee, Joseph H W
Abstract: Geysers are explosive eruptions of air-water mixture from manholes in drainage systems. When the design capacity of urban storm water drainage systems is exceeded during extreme rainfall, rapid inflows into the drainage network can lead to air-water interactions that give rise to geysers—causing damage to the water infrastructure and threatening human lives. Although extensive research has revealed the role of entrapped air in causing large pressure transients in drainage tunnels, the mechanism of geyser formation remains elusive. In this study, an unsteady three-dimensional (3D) computational fluid dynamics (CFD) model is developed to simulate the pressure transients and air-water interactions during geyser events using the volume-of-fluid (VOF) technique. Extensive numerical simulations are conducted to study the air-pocket dynamics caused by release of trapped air from a horizontal tunnel into a vertical riser. Model predictions of the air-water interface in the vertical shaft are in good agreement with laboratory measurements by a high-speed camera; the mechanism for the formation of geysers is elucidated. It is found that during a geyser event, compression of the air pocket in the riser can lead to rapid acceleration of the overlying water column and its expulsion from the riser; the air-pocket pressure is significantly higher than the hydrostatic pressure of the overlying water column, and the velocity is greater than that of a Taylor bubble. Comprehensive numerical modeling has been conducted to study the effect of the vertical shaft diameter, the upstream pressure head and the air-pocket volume on the air-pocket dynamics; the results show that geyser formation is primarily controlled by the riser to tunnel diameter ratio, Dr/DDr/D. 3D CFD simulations have also been carried out for an idealized prototype drainage system; it is shown that the geyser behavior can be characterized by extremely large vertical air velocities that result in dispersed air
Published: 2018

28. Internal Hydraulics of a Chlorine Jet Diffuser

Author: Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, Lee, Joseph H. W., Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, and Lee, Joseph H. W.
Abstract: Multiport diffusers are used in many environmental applications to distribute a discharge flow uniformly through a number of jet nozzles into the same or another fluid. For example, a sewage diffuser can be designed to achieve approximately equal port discharges along the diffuser to maximize environmental benefit, i.e., approximately the same port discharge to achieve similar dilutions for all ports. When the effluent density is smaller than that of the ambient receiving water (i.e., positively buoyant), the energy head increases with elevation (in the inshore direction); as the total diffuser flow varies, the relative port discharge distribution remains similar. However, for dense (negatively buoyant) discharges, this may not be the case. This paper presents an experimental and theoretical study of the internal hydraulics of a diffuser used for dosing sodium hypochlorite solution (specific gravity 1.2) for sewage disinfection. Because of the significant density difference, the jet discharge undergoes a flow switching (reversal of relative discharge distribution) as the total discharge decreases. The predictions were validated with full scale experiments carried out with water jets into air; the design implications for plant operation are discussed. The findings are of general interest to the design of diffuser manifolds for dense effluents. (C) 2017 American Society of Civil Engineers.
Published: 2017

29. Internal Hydraulics of a Chlorine Jet Diffuser

Author: Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, Lee, Joseph H. W., Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, and Lee, Joseph H. W.
Abstract: Multiport diffusers are used in many environmental applications to distribute a discharge flow uniformly through a number of jet nozzles into the same or another fluid. For example, a sewage diffuser can be designed to achieve approximately equal port discharges along the diffuser to maximize environmental benefit, i.e., approximately the same port discharge to achieve similar dilutions for all ports. When the effluent density is smaller than that of the ambient receiving water (i.e., positively buoyant), the energy head increases with elevation (in the inshore direction); as the total diffuser flow varies, the relative port discharge distribution remains similar. However, for dense (negatively buoyant) discharges, this may not be the case. This paper presents an experimental and theoretical study of the internal hydraulics of a diffuser used for dosing sodium hypochlorite solution (specific gravity 1.2) for sewage disinfection. Because of the significant density difference, the jet discharge undergoes a flow switching (reversal of relative discharge distribution) as the total discharge decreases. The predictions were validated with full scale experiments carried out with water jets into air; the design implications for plant operation are discussed. The findings are of general interest to the design of diffuser manifolds for dense effluents. (C) 2017 American Society of Civil Engineers.
Published: 2017

30. Internal Hydraulics of a Chlorine Jet Diffuser

Author: Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, Lee, Joseph H. W., Qiao, Qingsong CIVL, Choi, King Wah David, Chan, Shu Ning, and Lee, Joseph H. W.
Abstract: Multiport diffusers are used in many environmental applications to distribute a discharge flow uniformly through a number of jet nozzles into the same or another fluid. For example, a sewage diffuser can be designed to achieve approximately equal port discharges along the diffuser to maximize environmental benefit, i.e., approximately the same port discharge to achieve similar dilutions for all ports. When the effluent density is smaller than that of the ambient receiving water (i.e., positively buoyant), the energy head increases with elevation (in the inshore direction); as the total diffuser flow varies, the relative port discharge distribution remains similar. However, for dense (negatively buoyant) discharges, this may not be the case. This paper presents an experimental and theoretical study of the internal hydraulics of a diffuser used for dosing sodium hypochlorite solution (specific gravity 1.2) for sewage disinfection. Because of the significant density difference, the jet discharge undergoes a flow switching (reversal of relative discharge distribution) as the total discharge decreases. The predictions were validated with full scale experiments carried out with water jets into air; the design implications for plant operation are discussed. The findings are of general interest to the design of diffuser manifolds for dense effluents. (C) 2017 American Society of Civil Engineers.
Published: 2017

31. Association of Long Runs of Homozygosity With Alzheimer Disease Among African American Individuals.

Author: Ghani, Mahdi, Ghani, Mahdi, Reitz, Christiane, Cheng, Rong, Vardarajan, Badri Narayan, Jun, Gyungah, Sato, Christine, Naj, Adam, Rajbhandary, Ruchita, Wang, Li-San, Valladares, Otto, Lin, Chiao-Feng, Larson, Eric B, Graff-Radford, Neill R, Evans, Denis, De Jager, Philip L, Crane, Paul K, Buxbaum, Joseph D, Murrell, Jill R, Raj, Towfique, Ertekin-Taner, Nilufer, Logue, Mark, Baldwin, Clinton T, Green, Robert C, Barnes, Lisa L, Cantwell, Laura B, Fallin, M Daniele, Go, Rodney CP, Griffith, Patrick A, Obisesan, Thomas O, Manly, Jennifer J, Lunetta, Kathryn L, Kamboh, M Ilyas, Lopez, Oscar L, Bennett, David A, Hendrie, Hugh, Hall, Kathleen S, Goate, Alison M, Byrd, Goldie S, Kukull, Walter A, Foroud, Tatiana M, Haines, Jonathan L, Farrer, Lindsay A, Pericak-Vance, Margaret A, Lee, Joseph H, Schellenberg, Gerard D, St George-Hyslop, Peter, Mayeux, Richard, Rogaeva, Ekaterina, Alzheimer’s Disease Genetics Consortium, Ghani, Mahdi, Ghani, Mahdi, Reitz, Christiane, Cheng, Rong, Vardarajan, Badri Narayan, Jun, Gyungah, Sato, Christine, Naj, Adam, Rajbhandary, Ruchita, Wang, Li-San, Valladares, Otto, Lin, Chiao-Feng, Larson, Eric B, Graff-Radford, Neill R, Evans, Denis, De Jager, Philip L, Crane, Paul K, Buxbaum, Joseph D, Murrell, Jill R, Raj, Towfique, Ertekin-Taner, Nilufer, Logue, Mark, Baldwin, Clinton T, Green, Robert C, Barnes, Lisa L, Cantwell, Laura B, Fallin, M Daniele, Go, Rodney CP, Griffith, Patrick A, Obisesan, Thomas O, Manly, Jennifer J, Lunetta, Kathryn L, Kamboh, M Ilyas, Lopez, Oscar L, Bennett, David A, Hendrie, Hugh, Hall, Kathleen S, Goate, Alison M, Byrd, Goldie S, Kukull, Walter A, Foroud, Tatiana M, Haines, Jonathan L, Farrer, Lindsay A, Pericak-Vance, Margaret A, Lee, Joseph H, Schellenberg, Gerard D, St George-Hyslop, Peter, Mayeux, Richard, Rogaeva, Ekaterina, and Alzheimer’s Disease Genetics Consortium
Abstract: ImportanceMutations in known causal Alzheimer disease (AD) genes account for only 1% to 3% of patients and almost all are dominantly inherited. Recessive inheritance of complex phenotypes can be linked to long (>1-megabase [Mb]) runs of homozygosity (ROHs) detectable by single-nucleotide polymorphism (SNP) arrays.ObjectiveTo evaluate the association between ROHs and AD in an African American population known to have a risk for AD up to 3 times higher than white individuals.Design, setting, and participantsCase-control study of a large African American data set previously genotyped on different genome-wide SNP arrays conducted from December 2013 to January 2015. Global and locus-based ROH measurements were analyzed using raw or imputed genotype data. We studied the raw genotypes from 2 case-control subsets grouped based on SNP array: Alzheimer's Disease Genetics Consortium data set (871 cases and 1620 control individuals) and Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set (279 cases and 1367 control individuals). We then examined the entire data set using imputed genotypes from 1917 cases and 3858 control individuals.Main outcomes and measuresThe ROHs larger than 1 Mb, 2 Mb, or 3 Mb were investigated separately for global burden evaluation, consensus regions, and gene-based analyses.ResultsThe African American cohort had a low degree of inbreeding (F ~ 0.006). In the Alzheimer's Disease Genetics Consortium data set, we detected a significantly higher proportion of cases with ROHs greater than 2 Mb (P = .004) or greater than 3 Mb (P = .02), as well as a significant 114-kilobase consensus region on chr4q31.3 (empirical P value 2 = .04; ROHs >2 Mb). In the Chicago Health and Aging Project-Indianapolis Ibadan Dementia Study data set, we identified a significant 202-kilobase consensus region on Chr15q24.1 (empirical P value 2 = .02; ROHs >1 Mb) and a cluster of 13 significant genes on Chr3p21.31 (empirical P value 2 = .03; ROHs >3
Published: 2015

32. Large-scale meta-analysis of genome-wide association data identifies six new risk loci for Parkinson's disease.

Author: Nalls, Mike A, Nalls, Mike A, Pankratz, Nathan, Lill, Christina M, Do, Chuong B, Hernandez, Dena G, Saad, Mohamad, DeStefano, Anita L, Kara, Eleanna, Bras, Jose, Sharma, Manu, Schulte, Claudia, Keller, Margaux F, Arepalli, Sampath, Letson, Christopher, Edsall, Connor, Stefansson, Hreinn, Liu, Xinmin, Pliner, Hannah, Lee, Joseph H, Cheng, Rong, International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Ashkenazi Jewish Dataset Investigator, Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC), Greek Parkinson's Disease Consortium, Alzheimer Genetic Analysis Group, Ikram, M Arfan, Ioannidis, John PA, Hadjigeorgiou, Georgios M, Bis, Joshua C, Martinez, Maria, Perlmutter, Joel S, Goate, Alison, Marder, Karen, Fiske, Brian, Sutherland, Margaret, Xiromerisiou, Georgia, Myers, Richard H, Clark, Lorraine N, Stefansson, Kari, Hardy, John A, Heutink, Peter, Chen, Honglei, Wood, Nicholas W, Houlden, Henry, Payami, Haydeh, Brice, Alexis, Scott, William K, Gasser, Thomas, Bertram, Lars, Eriksson, Nicholas, Foroud, Tatiana, Singleton, Andrew B, Nalls, Mike A, Nalls, Mike A, Pankratz, Nathan, Lill, Christina M, Do, Chuong B, Hernandez, Dena G, Saad, Mohamad, DeStefano, Anita L, Kara, Eleanna, Bras, Jose, Sharma, Manu, Schulte, Claudia, Keller, Margaux F, Arepalli, Sampath, Letson, Christopher, Edsall, Connor, Stefansson, Hreinn, Liu, Xinmin, Pliner, Hannah, Lee, Joseph H, Cheng, Rong, International Parkinson's Disease Genomics Consortium (IPDGC), Parkinson's Study Group (PSG) Parkinson's Research: The Organized GENetics Initiative (PROGENI), 23andMe, GenePD, NeuroGenetics Research Consortium (NGRC), Hussman Institute of Human Genomics (HIHG), Ashkenazi Jewish Dataset Investigator, Cohorts for Health and Aging Research in Genetic Epidemiology (CHARGE), North American Brain Expression Consortium (NABEC), United Kingdom Brain Expression Consortium (UKBEC), Greek Parkinson's Disease Consortium, Alzheimer Genetic Analysis Group, Ikram, M Arfan, Ioannidis, John PA, Hadjigeorgiou, Georgios M, Bis, Joshua C, Martinez, Maria, Perlmutter, Joel S, Goate, Alison, Marder, Karen, Fiske, Brian, Sutherland, Margaret, Xiromerisiou, Georgia, Myers, Richard H, Clark, Lorraine N, Stefansson, Kari, Hardy, John A, Heutink, Peter, Chen, Honglei, Wood, Nicholas W, Houlden, Henry, Payami, Haydeh, Brice, Alexis, Scott, William K, Gasser, Thomas, Bertram, Lars, Eriksson, Nicholas, Foroud, Tatiana, and Singleton, Andrew B
Abstract: We conducted a meta-analysis of Parkinson's disease genome-wide association studies using a common set of 7,893,274 variants across 13,708 cases and 95,282 controls. Twenty-six loci were identified as having genome-wide significant association; these and 6 additional previously reported loci were then tested in an independent set of 5,353 cases and 5,551 controls. Of the 32 tested SNPs, 24 replicated, including 6 newly identified loci. Conditional analyses within loci showed that four loci, including GBA, GAK-DGKQ, SNCA and the HLA region, contain a secondary independent risk variant. In total, we identified and replicated 28 independent risk variants for Parkinson's disease across 24 loci. Although the effect of each individual locus was small, risk profile analysis showed substantial cumulative risk in a comparison of the highest and lowest quintiles of genetic risk (odds ratio (OR) = 3.31, 95% confidence interval (CI) = 2.55-4.30; P = 2 × 10(-16)). We also show six risk loci associated with proximal gene expression or DNA methylation.
Published: 2014

33. Fostering Indigenous Leadership through Redefining Christian Relationship at Southlands Christian Schools

Author: Lee, Joseph H., Arn, Charles, Lee, Joseph H., and Arn, Charles
Abstract: Doctor of Ministry (DMin), The goal of this project was to pioneer a class which would nurture indigenous leadership among high school students in a Christian school by redefining leadership and Christian relationships, focusing on power relationships. This project was meant to encourage students to re-imagine what healthy power relationships should look like and how healthy ministry could be done by adolescents. The laboratory for this experiment took the form of a ministry focus class that was first offered during the 2009-2010 academic year at Southlands Christian Schools in Walnut, California. The class focused on the theological themes of theologia crucis, missio Dei, priesthood of all believers and spiritual gifts. These topics were discussed to lay a foundation of what healthy relationships and power dynamics among Christians might look like. Surveys were taken of this class and also of the school at large. The students then embarked on ministry projects within the school in order to get a taste of leadership and also to see how healthy power relationships might operate. At the conclusion of these projects, the students were asked to reflect upon their thoughts of leadership and power relationships. This project illustrated that a majority of the students in the class saw that their ideas of power and relationships were not Christian but more corporate or religious. It demonstrated that a better way to practice relationships and leadership existed. While the first year of this class did not completely change the culture at Southlands Christian Schools, it did start the discussion of how to continue this shift and to sustain such a shift in the culture of the school. Content Reader: Dr. Charles Arn, Ed.D.
Published: 2011

34. Fostering Indigenous Leadership through Redefining Christian Relationship at Southlands Christian Schools

Author: Lee, Joseph H. and Lee, Joseph H.
Abstract: Doctor of Ministry (DMin), The goal of this project was to pioneer a class which would nurture indigenous leadership among high school students in a Christian school by redefining leadership and Christian relationships, focusing on power relationships. This project was meant to encourage students to re-imagine what healthy power relationships should look like and how healthy ministry could be done by adolescents. The laboratory for this experiment took the form of a ministry focus class that was first offered during the 2009-2010 academic year at Southlands Christian Schools in Walnut, California. The class focused on the theological themes of theologia crucis, missio Dei, priesthood of all believers and spiritual gifts. These topics were discussed to lay a foundation of what healthy relationships and power dynamics among Christians might look like. Surveys were taken of this class and also of the school at large. The students then embarked on ministry projects within the school in order to get a taste of leadership and also to see how healthy power relationships might operate. At the conclusion of these projects, the students were asked to reflect upon their thoughts of leadership and power relationships. This project illustrated that a majority of the students in the class saw that their ideas of power and relationships were not Christian but more corporate or religious. It demonstrated that a better way to practice relationships and leadership existed. While the first year of this class did not completely change the culture at Southlands Christian Schools, it did start the discussion of how to continue this shift and to sustain such a shift in the culture of the school. Content Reader: Dr. Charles Arn, Ed.D.
Published: 2011

35. Temporal and spatial variations in nutrient stoichiometry and regulation of phytoplankton biomass in Hong Kong waters : influence of the Pearl River outflow and sewage inputs

Author: Xu, Jie, Ho, Alvin Y. T., Yin, Kedong, Yuan, Xiangcheng, Anderson, Donald M., Lee, Joseph H. W., Harrison, Paul J., Xu, Jie, Ho, Alvin Y. T., Yin, Kedong, Yuan, Xiangcheng, Anderson, Donald M., Lee, Joseph H. W., and Harrison, Paul J.
Abstract: Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 57 (2008): 335-348, doi:10.1016/j.marpolbul.2008.01.020., In 2001, the Hong Kong government implemented the Harbor Area Treatment Scheme (HATS) under which 70% of the sewage that had been formerly discharged into Victoria Harbor is now collected and sent to Stonecutters Island Sewage Works where it receives chemically enhanced primary treatment (CEPT), and is then discharged into waters west of the Harbor. The relocation of the sewage discharge will possibly change the nutrient dynamics and phytoplankton biomass in this area. Therefore, there is a need to examine the factors that regulate phytoplankton growth in Hong Kong waters in order to understand future impacts. Based on a historic nutrient data set (1986-2001), a comparison of ambient nutrient ratios with the Redfield ratio (N:P:Si=16:1:16) showed clear spatial variations in the factors that regulate phytoplankton biomass along a west (estuary) to east (coastal/oceanic) transect through Hong Kong waters. Algal biomass was constrained by a combination of low light conditions, a rapid change in salinity, and strong turbulent mixing in western waters throughout the year. Potential stoichiometric Si limitation (up to 94% of the cases in winter) occurred in Victoria Harbor due to the contribution of sewage effluent with high N and P enrichment all year, except for summer when the frequency of stoichiometric Si limitation (48%) was the same as P, owing to the influence of the high Si in the Pearl River discharge. In the eastern waters, potential N limitation and N and P co-limitation occurred in autumn and winter respectively, because of the dominance of coastal/oceanic water with low nutrients and low N:P ratios. In contrast, potential Si limitation occurred in spring and a switch to potential N, P and Si limitation occurred in eastern waters in summer. In southern waters, there was a shift from P limitation (80%) in summer due to the influence of the N-rich Pearl River discharge, to N limitation (68%) in autumn, and to N and P co-limitation in winter due to the dominance, Financial support for this research was provided by the University Grants Council of Hong Kong AoE project (AoE/P-04/0401), and RGC project HKUST6478/05M. Support was also provided (to DMA) by U.S. National Science Foundation grants OCE-0402707 and OCE-0430724 and by NIEHS grant 1 P50-ES01274201.
Published: 2008

36. Temporal and spatial variations in nutrient stoichiometry and regulation of phytoplankton biomass in Hong Kong waters : influence of the Pearl River outflow and sewage inputs

Author: Xu, Jie, Ho, Alvin Y. T., Yin, Kedong, Yuan, Xiangcheng, Anderson, Donald M., Lee, Joseph H. W., Harrison, Paul J., Xu, Jie, Ho, Alvin Y. T., Yin, Kedong, Yuan, Xiangcheng, Anderson, Donald M., Lee, Joseph H. W., and Harrison, Paul J.
Abstract: Author Posting. © Elsevier B.V., 2008. This is the author's version of the work. It is posted here by permission of Elsevier B.V. for personal use, not for redistribution. The definitive version was published in Marine Pollution Bulletin 57 (2008): 335-348, doi:10.1016/j.marpolbul.2008.01.020., In 2001, the Hong Kong government implemented the Harbor Area Treatment Scheme (HATS) under which 70% of the sewage that had been formerly discharged into Victoria Harbor is now collected and sent to Stonecutters Island Sewage Works where it receives chemically enhanced primary treatment (CEPT), and is then discharged into waters west of the Harbor. The relocation of the sewage discharge will possibly change the nutrient dynamics and phytoplankton biomass in this area. Therefore, there is a need to examine the factors that regulate phytoplankton growth in Hong Kong waters in order to understand future impacts. Based on a historic nutrient data set (1986-2001), a comparison of ambient nutrient ratios with the Redfield ratio (N:P:Si=16:1:16) showed clear spatial variations in the factors that regulate phytoplankton biomass along a west (estuary) to east (coastal/oceanic) transect through Hong Kong waters. Algal biomass was constrained by a combination of low light conditions, a rapid change in salinity, and strong turbulent mixing in western waters throughout the year. Potential stoichiometric Si limitation (up to 94% of the cases in winter) occurred in Victoria Harbor due to the contribution of sewage effluent with high N and P enrichment all year, except for summer when the frequency of stoichiometric Si limitation (48%) was the same as P, owing to the influence of the high Si in the Pearl River discharge. In the eastern waters, potential N limitation and N and P co-limitation occurred in autumn and winter respectively, because of the dominance of coastal/oceanic water with low nutrients and low N:P ratios. In contrast, potential Si limitation occurred in spring and a switch to potential N, P and Si limitation occurred in eastern waters in summer. In southern waters, there was a shift from P limitation (80%) in summer due to the influence of the N-rich Pearl River discharge, to N limitation (68%) in autumn, and to N and P co-limitation in winter due to the dominance, Financial support for this research was provided by the University Grants Council of Hong Kong AoE project (AoE/P-04/0401), and RGC project HKUST6478/05M. Support was also provided (to DMA) by U.S. National Science Foundation grants OCE-0402707 and OCE-0430724 and by NIEHS grant 1 P50-ES01274201.
Published: 2008

37. Waste disposal in the ocean

Author: Jirka, Gerhard H., Lee, Joseph H W, Jirka, Gerhard H., and Lee, Joseph H W
Abstract: This review is structured into four main sections. First, the three major types of discharge into coastal receiving water are discussed: by means of a single submerged pipe outfall; a multiple port (multiport) submerged diffuser outfall; and surface discharge by means of a canal at the shoreline. All of these discharges produce jet-like motions that are modified in various ways by buoyancy, ambient geometry, and ambient currents. The emphasis in these three sections is to provide a classification of the behaviour of these discharges and to present simple methods for predicting their mixing capacity (near field dilution). Predictive methods for far field transport processes are then discussed. The application of simple models that are readily applied for approximate analysis is stressed. -from Authors
Published: 1994

38. Waste disposal in the ocean

Author: Jirka, Gerhard H., Lee, Joseph H W, Jirka, Gerhard H., and Lee, Joseph H W
Abstract: This review is structured into four main sections. First, the three major types of discharge into coastal receiving water are discussed: by means of a single submerged pipe outfall; a multiple port (multiport) submerged diffuser outfall; and surface discharge by means of a canal at the shoreline. All of these discharges produce jet-like motions that are modified in various ways by buoyancy, ambient geometry, and ambient currents. The emphasis in these three sections is to provide a classification of the behaviour of these discharges and to present simple methods for predicting their mixing capacity (near field dilution). Predictive methods for far field transport processes are then discussed. The application of simple models that are readily applied for approximate analysis is stressed. -from Authors
Published: 1994

39. Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: A cross-sectional study

Author: <p>National Institute on Aging Eunice Kennedy Shriver National Institute of Child Health and Human Development German Center for Neurodegenerative Diseases Japan Agency for Medical Research and Development</p>, Fagan, Anne M., Henson, Rachel L., Li, Yan, Boerwinkle, Anna H., Xiong, Chengjie, Bateman, Randall J., Goate, Alison, Ances, Beau M., Doran, Eric, Christian, Bradley T., Lai, Florence, Rosas, H. Diana, Schupf, Nicole, Krinsky-McHale, Sharon, Silverman, Wayne, Lee, Joseph H., Klunk, William E., Handen, Benjamin L., Allegri, Ricardo F., Chhatwal, Jasmeer P., Day, Gregory S., Graff-Radford, Neill R., Jucker, Mathias, Levin, Johannes, Martins, Ralph N., Masters, Colin L., Mori, Hiroshi, Mummery, Catherine J., Niimi, Yoshiki, Ringman, John M., Salloway, Stephen, Schofield, Peter R., Shoji, Mikio, Lott, Ira T., Alzheimer's Biomarker Consortium-Down Syndrome, Dominantly Inherited Alzheimer Network, <p>National Institute on Aging Eunice Kennedy Shriver National Institute of Child Health and Human Development German Center for Neurodegenerative Diseases Japan Agency for Medical Research and Development</p>, Fagan, Anne M., Henson, Rachel L., Li, Yan, Boerwinkle, Anna H., Xiong, Chengjie, Bateman, Randall J., Goate, Alison, Ances, Beau M., Doran, Eric, Christian, Bradley T., Lai, Florence, Rosas, H. Diana, Schupf, Nicole, Krinsky-McHale, Sharon, Silverman, Wayne, Lee, Joseph H., Klunk, William E., Handen, Benjamin L., Allegri, Ricardo F., Chhatwal, Jasmeer P., Day, Gregory S., Graff-Radford, Neill R., Jucker, Mathias, Levin, Johannes, Martins, Ralph N., Masters, Colin L., Mori, Hiroshi, Mummery, Catherine J., Niimi, Yoshiki, Ringman, John M., Salloway, Stephen, Schofield, Peter R., Shoji, Mikio, Lott, Ira T., Alzheimer's Biomarker Consortium-Down Syndrome, and Dominantly Inherited Alzheimer Network
Abstract: Fagan, A. M., Henson, R. L., Li, Y., Boerwinkle, A. H., Xiong, C., Bateman, R. J., . . . Lott, I. T. (2021). Comparison of CSF biomarkers in Down syndrome and autosomal dominant Alzheimer's disease: A cross-sectional study. The Lancet Neurology, 20(8), 615-626. https://doi.org/10.1016/S1474-4422(21)00139-3

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