Understanding Polarizing Community Perspectives on Harm Reduction Strategies: Challenges to Addressing the Opioid Crisis in Appalachian Pennsylvania

Introduction: Rural communities face barriers to opioid treatment and overdose prevention including concerns about stigma and lack of harm reduction services. Purpose: The aim of this study was to explore community perspectives and understanding of harm reduction approaches to opioid use and overdose in a high-risk Northern Appalachian case community in Pennsylvania. Methods: A small town approximately 10 miles from Pittsburgh was identified as the community with the greatest predicted probabilities of epidemic outbreak using posteriors from spatial models of hospitalizations for opioid use disorders. We interviewed 20 key stakeholders in the case community in using a semi-structured interview guide and analyzed the qualitative data using an inductive grounded theory approach. Results: Our findings illustrate how conflicting perspectives about opioid dependence lay the foundation for the polarizing community perspectives on addressing opioid use and overdose and general disagreement regarding the legitimacy of harm reduction approaches versus abstinence-based recovery plans. Community members shared varying perspectives on multiple aspects of the opioid epidemic, including appropriate strategies, treatment, and overdose prevention methods and how community leaders and organizations should respond. Implications: Opinions, coupled with a general lack of education regarding opioid use and harm reduction options, make it challenging for small communities with limited resources to create comprehensive plans to address the opioid crisis

Gynecologic Oncologist Views Influencing Referral to Outpatient Specialty Palliative Care

Early specialty palliative care is underutilized for patients with advanced gynecologic malignancies. We sought to understand how gynecologic oncologists’ views influence outpatient specialty palliative care referral to help inform strategies for improvement

A multimodal cell census and atlas of the mammalian primary motor cortex

ABSTRACT We report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex (MOp or M1) as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties, and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Together, our results advance the collective knowledge and understanding of brain cell type organization: First, our study reveals a unified molecular genetic landscape of cortical cell types that congruently integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a unified taxonomy of transcriptomic types and their hierarchical organization that are conserved from mouse to marmoset and human. Third, cross-modal analysis provides compelling evidence for the epigenomic, transcriptomic, and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types and subtypes. Fourth, in situ single-cell transcriptomics provides a spatially-resolved cell type atlas of the motor cortex. Fifth, integrated transcriptomic, epigenomic and anatomical analyses reveal the correspondence between neural circuits and transcriptomic cell types. We further present an extensive genetic toolset for targeting and fate mapping glutamatergic projection neuron types toward linking their developmental trajectory to their circuit function. Together, our results establish a unified and mechanistic framework of neuronal cell type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties

Gynecologic Oncologist Views Influencing Referral to Outpatient Specialty Palliative Care

OBJECTIVE: Early specialty palliative care is underutilized for patients with advanced gynecologic malignancies. We sought to understand how gynecologic oncologists’ views influence outpatient specialty palliative care referral to help inform strategies for improvement. METHODS/MATERIALS: We conducted a qualitative interview study at six National Cancer Institute-designated cancer centers with well-established outpatient palliative care services. Between September 2015 and March 2016, 34 gynecologic oncologists participated in semi-structured telephone interviews focused on attitudes, experiences, and preferences related to outpatient specialty palliative care. A multidisciplinary team analyzed transcripts using constant comparative methods to inductively develop a coding framework. Through an iterative, analytic process codes were classified, grouped, and refined into themes. RESULTS: Mean participant age was 47 (SD 10) years. Mean interview length was 25 (SD 7) minutes. Three main themes emerged regarding how gynecologic oncologists view outpatient specialty palliative care: (1) long-term relationships with patients is a unique and defining aspect of gynecologic oncology that influences referral, (2) gynecologic oncologists value palliative care clinicians’ communication skills and third-party perspective to increase prognostic awareness and help negotiate differences between patient preferences and physician recommendation, and (3) gynecologic oncologists prefer specialty palliative care services embedded within gynecologic oncology clinics. CONCLUSIONS: Gynecologic oncologists value longitudinal relationships with patients and utilize specialty palliative care to negotiate conflict surrounding prognostic awareness or the treatment plan. Embedding specialty palliative care within gynecologic oncology clinics may promote communication between clinicians and facilitate gynecologic oncologist involvement throughout the illness course

A multimodal cell census and atlas of the mammalian primary motor cortex

none258Here we report the generation of a multimodal cell census and atlas of the mammalian primary motor cortex as the initial product of the BRAIN Initiative Cell Census Network (BICCN). This was achieved by coordinated large-scale analyses of single-cell transcriptomes, chromatin accessibility, DNA methylomes, spatially resolved single-cell transcriptomes, morphological and electrophysiological properties and cellular resolution input-output mapping, integrated through cross-modal computational analysis. Our results advance the collective knowledge and understanding of brain cell-type organization1-5. First, our study reveals a unified molecular genetic landscape of cortical cell types that integrates their transcriptome, open chromatin and DNA methylation maps. Second, cross-species analysis achieves a consensus taxonomy of transcriptomic types and their hierarchical organization that is conserved from mouse to marmoset and human. Third, in situ single-cell transcriptomics provides a spatially resolved cell-type atlas of the motor cortex. Fourth, cross-modal analysis provides compelling evidence for the transcriptomic, epigenomic and gene regulatory basis of neuronal phenotypes such as their physiological and anatomical properties, demonstrating the biological validity and genomic underpinning of neuron types. We further present an extensive genetic toolset for targeting glutamatergic neuron types towards linking their molecular and developmental identity to their circuit function. Together, our results establish a unifying and mechanistic framework of neuronal cell-type organization that integrates multi-layered molecular genetic and spatial information with multi-faceted phenotypic properties.openCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; McCarroll, Steven A.; McMillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; McCracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, SusanCallaway, Edward M.; Dong, Hong-Wei; Ecker, Joseph R.; Hawrylycz, Michael J.; Huang, Z. Josh; Lein, Ed S.; Ngai, John; Osten, Pavel; Ren, Bing; Tolias, Andreas Savas; White, Owen; Zeng, Hongkui; Zhuang, Xiaowei; Ascoli, Giorgio A.; Behrens, M. Margarita; Chun, Jerold; Feng, Guoping; Gee, James C.; Ghosh, Satrajit S.; Halchenko, Yaroslav O.; Hertzano, Ronna; Lim, Byung Kook; Martone, Maryann E.; Ng, Lydia; Pachter, Lior; Ropelewski, Alexander J.; Tickle, Timothy L.; Yang, X. William; Zhang, Kun; Bakken, Trygve E.; Berens, Philipp; Daigle, Tanya L.; Harris, Julie A.; Jorstad, Nikolas L.; Kalmbach, Brian E.; Kobak, Dmitry; Li, Yang Eric; Liu, Hanqing; Matho, Katherine S.; Mukamel, Eran A.; Naeemi, Maitham; Scala, Federico; Tan, Pengcheng; Ting, Jonathan T.; Xie, Fangming; Zhang, Meng; Zhang, Zhuzhu; Zhou, Jingtian; Zingg, Brian; Armand, Ethan; Yao, Zizhen; Bertagnolli, Darren; Casper, Tamara; Crichton, Kirsten; Dee, Nick; Diep, Dinh; Ding, Song-Lin; Dong, Weixiu; Dougherty, Elizabeth L.; Fong, Olivia; Goldman, Melissa; Goldy, Jeff; Hodge, Rebecca D.; Hu, Lijuan; Keene, C. Dirk; Krienen, Fenna M.; Kroll, Matthew; Lake, Blue B.; Lathia, Kanan; Linnarsson, Sten; Liu, Christine S.; Macosko, Evan Z.; Mccarroll, Steven A.; Mcmillen, Delissa; Nadaf, Naeem M.; Nguyen, Thuc Nghi; Palmer, Carter R.; Pham, Thanh; Plongthongkum, Nongluk; Reed, Nora M.; Regev, Aviv; Rimorin, Christine; Romanow, William J.; Savoia, Steven; Siletti, Kimberly; Smith, Kimberly; Sulc, Josef; Tasic, Bosiljka; Tieu, Michael; Torkelson, Amy; Tung, Herman; van Velthoven, Cindy T. J.; Vanderburg, Charles R.; Yanny, Anna Marie; Fang, Rongxin; Hou, Xiaomeng; Lucero, Jacinta D.; Osteen, Julia K.; Pinto-Duarte, Antonio; Poirion, Olivier; Preissl, Sebastian; Wang, Xinxin; Aldridge, Andrew I.; Bartlett, Anna; Boggeman, Lara; O’Connor, Carolyn; Castanon, Rosa G.; Chen, Huaming; Fitzpatrick, Conor; Luo, Chongyuan; Nery, Joseph R.; Nunn, Michael; Rivkin, Angeline C.; Tian, Wei; Dominguez, Bertha; Ito-Cole, Tony; Jacobs, Matthew; Jin, Xin; Lee, Cheng-Ta; Lee, Kuo-Fen; Miyazaki, Paula Assakura; Pang, Yan; Rashid, Mohammad; Smith, Jared B.; Vu, Minh; Williams, Elora; Biancalani, Tommaso; Booeshaghi, A. Sina; Crow, Megan; Dudoit, Sandrine; Fischer, Stephan; Gillis, Jesse; Hu, Qiwen; Kharchenko, Peter V.; Niu, Sheng-Yong; Ntranos, Vasilis; Purdom, Elizabeth; Risso, Davide; de Bézieux, Hector Roux; Somasundaram, Saroja; Street, Kelly; Svensson, Valentine; Vaishnav, Eeshit Dhaval; Van den Berge, Koen; Welch, Joshua D.; An, Xu; Bateup, Helen S.; Bowman, Ian; Chance, Rebecca K.; Foster, Nicholas N.; Galbavy, William; Gong, Hui; Gou, Lin; Hatfield, Joshua T.; Hintiryan, Houri; Hirokawa, Karla E.; Kim, Gukhan; Kramer, Daniel J.; Li, Anan; Li, Xiangning; Luo, Qingming; Muñoz-Castañeda, Rodrigo; Stafford, David A.; Feng, Zhao; Jia, Xueyan; Jiang, Shengdian; Jiang, Tao; Kuang, Xiuli; Larsen, Rachael; Lesnar, Phil; Li, Yaoyao; Li, Yuanyuan; Liu, Lijuan; Peng, Hanchuan; Qu, Lei; Ren, Miao; Ruan, Zongcai; Shen, Elise; Song, Yuanyuan; Wakeman, Wayne; Wang, Peng; Wang, Yimin; Wang, Yun; Yin, Lulu; Yuan, Jing; Zhao, Sujun; Zhao, Xuan; Narasimhan, Arun; Palaniswamy, Ramesh; Banerjee, Samik; Ding, Liya; Huilgol, Dhananjay; Huo, Bingxing; Kuo, Hsien-Chi; Laturnus, Sophie; Li, Xu; Mitra, Partha P.; Mizrachi, Judith; Wang, Quanxin; Xie, Peng; Xiong, Feng; Yu, Yang; Eichhorn, Stephen W.; Berg, Jim; Bernabucci, Matteo; Bernaerts, Yves; Cadwell, Cathryn René; Castro, Jesus Ramon; Dalley, Rachel; Hartmanis, Leonard; Horwitz, Gregory D.; Jiang, Xiaolong; Ko, Andrew L.; Miranda, Elanine; Mulherkar, Shalaka; Nicovich, Philip R.; Owen, Scott F.; Sandberg, Rickard; Sorensen, Staci A.; Tan, Zheng Huan; Allen, Shona; Hockemeyer, Dirk; Lee, Angus Y.; Veldman, Matthew B.; Adkins, Ricky S.; Ament, Seth A.; Bravo, Héctor Corrada; Carter, Robert; Chatterjee, Apaala; Colantuoni, Carlo; Crabtree, Jonathan; Creasy, Heather; Felix, Victor; Giglio, Michelle; Herb, Brian R.; Kancherla, Jayaram; Mahurkar, Anup; Mccracken, Carrie; Nickel, Lance; Olley, Dustin; Orvis, Joshua; Schor, Michael; Hood, Greg; Dichter, Benjamin; Grauer, Michael; Helba, Brian; Bandrowski, Anita; Barkas, Nikolaos; Carlin, Benjamin; D’Orazi, Florence D.; Degatano, Kylee; Gillespie, Thomas H.; Khajouei, Farzaneh; Konwar, Kishori; Thompson, Carol; Kelly, Kathleen; Mok, Stephanie; Sunkin, Susa