tbuckley/cabot-search huggingface dataset:
Epithelial cell responses to rhinovirus identify an early-life-onset asthma phenotype in adults
Authors: Eugene Chang, Nima Pouladi, Stefano Guerra, Jana Jandova, Alexander Kim, Haiquan Li, Jianrong Li, Wayne Morgan, Debra Stern, Amanda Willis, Yves Lussier, Fernando Martinez
Journal: Journal of Allergy and Clinical Immunology (2022)
Vasopressin and Methylprednisolone vs Placebo and Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest—Reply
Authors: Lars W. Andersen, Asger Granfeldt
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
ASSOCIATION NEWS.
Authors: H. A. Hare
Journal: JAMA (1897)

<h3>The Meeting of the American Medical Association.</h3><h3>To the Editor:</h3> — May I call the attention of those of your readers who are thinking of coming to Philadelphia to attend the semi-centennial meeting of theAmerican Medical Associationto be held June 1, 2, 3, and 4, 1897, that there will be in addition to the meeting of theAssociationat the same time a large mercantile convention which will to a certain extent utilize a considerable number of the rooms in the various hotels. For this reason it is advisable that physicians who intend to be present at the meeting should write at once to one of the following hotels engaging such rooms as they desire at the rates named: Hotel Walton—Broad and Locust Streets: $1.50 and upward per day, European plan; $4 and upward per day, American The Colonnade—15th and Chestnut Streets: $1 and upward per day, European
Alpha-gal as the newest member of the glycan epitopes recognized in allergen nomenclature for cross-reactive carbohydrates
Authors: Thomas Platts-Mills, Uta Jappe, Christiane Hilger, Marianne van Hage, Gabriele Gadermaier, Edzard Spillner, Jonas Lidholm, Behnam Keshavarz, Rob Aalberse, Ronald Van Ree, Richard Goodman, Anna Pomes
Journal: Journal of Allergy and Clinical Immunology (2022)
Effect of Dupilumab on Eosinophilic Esophagitis when used for other approved indications
Authors: Benjamin Spergel, Bridget Godwin, Chris Liacouras, Antonella Cianferoni, Laura Gober, David Hill, Jonathan Spergel, Melanie Ruffner, Terri Brown-Whitehorn, Amanda Muir
Journal: Journal of Allergy and Clinical Immunology (2022)
INTERNATIONAL ABSTRACTS
Journal: JAMA (1983)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Organ Donor Recruitment
Journal: JAMA (1981)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effects Of The COVID-19 Pandemic On A Group Of Patients With Pathogenic Variant of Cytotoxic T-Lymphocyte Associated Protein 4 (CTLA-4) in a Tertiary Center in Florida
Authors: Priyanka Timothy, Peter Illes, Boglarka Ujhazi, Sumai Gordon, Bence Nagy, Eugenia Alas, Shannon Sullivan, Mary Ann Miranda, Carla Duff, Jocelyn Farmer, Panida Sriaroon, Ann Marie Szymanski, Krisztian Csomos, Emma Westermann-Clark, Joseph Dasso, Jolan Walter
Journal: Journal of Allergy and Clinical Immunology (2022)
New Approaches to the Treatment of Dense Deposit Disease
Authors: Richard J.H. Smith, Jessy Alexander, Paul N. Barlow, Marina Botto, Thomas L. Cassavant, H. Terence Cook, Santiago Rodriguez de[Combining Acute Accent]rdoba, Gregory S. Hageman, T. Sakari Jokiranta, William J. Kimberling, John D. Lambris, Lynne D. Lanning, Vicki Levidiotis, Christoph Licht, Hans U. Lutz, Seppo Meri, Matthew C. Pickering, Richard J. Quigg, Angelique L. Rops, David J. Salant, Sanjeev Sethi, Joshua M. Thurman, Hope F. Tully, Sean P. Tully, Johan van der Vlag, Patrick D. Walker, Reinhard Wu[Combining Diaeresis]rzner, Peter F. Zipfel
Journal: Journal of the American Society of Nephrology (2007)

The development of clinical treatment protocols usually relies on evidence-based guidelines that focus on randomized, controlled trials. For rare renal diseases, such stringent requirements can represent a significant challenge. Dense deposit disease (DDD; also known as membranoproliferative glomerulonephritis type II) is a prototypical rare disease. It affects only two to three people per million and leads to renal failure within 10 yr in 50% of affected children. On the basis of pathophysiology, this article presents a diagnostic and treatment algorithm for patients with DDD. Diagnostic tests should assess the alternative pathway of complement for abnormalities. Treatment options include aggressive BP control and reduction of proteinuria, and on the basis of pathophysiology, animal data, and human studies, plasma infusion or exchange, rituximab, sulodexide, and eculizumab are additional options. Criteria for treatment success should be prevention of progression as determined by maintenance or improvement in renal function. A secondary criterion should be normalization of activity levels of the alternative complement pathway as measured by C3/C3d ratios and C3NeF levels. Outcomes should be reported to a central repository that is now accessible to all clinicians. As the understanding of DDD increases, novel therapies should be integrated into existing protocols for DDD and evaluated using an open-label Bayesian study design.
Abortion Surveillance: Preliminary Data—United States, 1990
Journal: JAMA (1993)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
KIAA1199 drives immune suppression to promote colorectal cancer liver metastasis by modulating neutrophil infiltration
Authors: Haihong Wang, Biying Zhang, Ruiqi Li, Jiayuan Chen, Guojie Xu, Ying Zhu, Jiao Li, Qing Liang, Qingling Hua, Lanqing Wang, Lu Wen, Min Jin, Jun Fan, Dejun Zhang, Lei Zhao, Dandan Yu, Zhenyu Lin, Jinghua Ren, Tao Zhang
Journal: Hepatology (2022)

Abstract Background and Aims Metastasis is the primary cause of cancer mortality, and colorectal cancer (CRC) frequently metastasizes to the liver. Our previous studies demonstrated the critical role of KIAA1199 in tumor invasion and metastasis in CRC. In the present study, we described an immune regulatory effect of KIAA1199 that creates a permissive environment for metastasis. Approach and Results Flow cytometry was used to examine the effects of KIAA1199 on the infiltration of tumor immune cells. Neutrophils and T cells were isolated, stimulated, and/or cultured for in vitro function assays. In the patients with CRC, high expression levels of KIAA1199 were associated with an increased neutrophil infiltration into the liver. This result was further validated in mouse metastasis models. The increased influx of neutrophils contributed to the KIAA1199‐driven CRC liver metastasis. Mechanistically, KIAA1199 activated the TGFβ signaling pathway by interacting with the TGFBR1/2 to stimulate CXCL1 and CXCL3 production, thereby driving the aggregation of immunosuppressive neutrophils. Genetic blockade or pharmacologic inhibition of KIAA1199 restored tumor immune infiltration, impeded tumor progression, and potentiated response to immune checkpoint blockade (ICB). Conclusions These findings indicated that KIAA1199 could facilitate the liver infiltration of immunosuppressive neutrophils via the TGFβ–chemokine (C‐X‐C motif) ligand (CXCL)3/1–CXCR2 axis, which might be clinically targeted for the treatment of hepatic metastasis.
Hepatic injury associated with tromethamine
Authors: V. E. Goldenberg
Journal: JAMA (1968)

Hemorrhagic liver necrosis of varying degrees of severity was observed in 22 (32.8%) of 67 newborn infants with idiopathic respiratory distress syndrome (IRDS) given tromethamine (Tris) and sodium bicarbonate buffers via the umbilical vein for treatment of respiratory acidosis. Identical solutions, if injected via the umbilical artery, were not associated with liver injury. Nor was liver damage observed if bicarbonate alone was injected via the umbilical vein. It is doubtful whether liver injury was a crucial factor leading to death in these seriously ill infants. However, it is felt the long-term consequences of such extensive liver damage may be serious for the survivors.
Protests erupt in Poland as woman dies after hospital refuses to remove dead fetus
Authors: Owen Dyer
Journal: BMJ (2022)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Protests erupt in Poland as woman dies after hospital refuses to remove dead fetus Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Primary Prevention of Cardiovascular and Heart Failure Events With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Their Combination in Type 2 Diabetes
Authors: Alison K. Wright, Matthew J. Carr, Evangelos Kontopantelis, Lalantha Leelarathna, Hood Thabit, Richard Emsley, Iain Buchan, Mamas A. Mamas, Tjeerd P. van Staa, Naveed Sattar, Darren M. Ashcroft, Martin K. Rutter
Journal: Diabetes Care (2022)

To assess associations between current use of sodium-glucose cotransporter 2 inhibitors (SGLT2is), glucagon-like peptide 1 receptor agonists (GLP-1RAs), and their combination and risk for major adverse cardiac and cerebrovascular events (MACCE) and heart failure (HF) in people with type 2 diabetes.In three nested case-control studies involving patients with type 2 diabetes in England and Wales (primary care data from the Clinical Practice Research Datalink and Secure Anonymised Information Linkage Databank with linkage to hospital and mortality records), we matched each patient experiencing an event with up to 20 control subjects. Adjusted odds ratios (ORs) for MACCE and HF among patients receiving SGLT2i or GLP-1RA regimens versus other combinations were estimated using conditional logistic regression and pooled using random-effects meta-analysis.Among 336,334 people with type 2 diabetes and without cardiovascular disease, 18,531 (5.5%) experienced a MACCE. In a cohort of 411,206 with type 2 diabetes and without HF, 17,451 (4.2%) experienced an HF event. Compared with other combination regimens, the adjusted pooled OR and 95% CI for MACCE associated with SGLT2i regimens was 0.82 (0.73, 0.92), with GLP-1RA regimens 0.93 (0.81, 1.06), and with the SGLT2i/GLP-1RA combination 0.70 (0.50, 0.98). Corresponding data for HF were SGLT2i 0.49 (0.42, 0.58), GLP-1RA 0.82 (0.71, 0.95), and SGLT2i/GLP-1RA combination 0.43 (0.28, 0.64).SGLT2i and SGLT2i/GLP-1RA combination regimens may be beneficial in primary prevention of MACCE and HF and GLP-1RA for HF. These data call for primary prevention trials using these agents and their combination.
Manuscripts Approved for JNCI, June 15 to July 15, 1960
Journal: JNCI Journal of the National Cancer Institute (1960)

Manuscripts Approved for JNCI, June 15 to July 15, 1960 Get access JNCI: Journal of the National Cancer Institute, Volume 25, Issue 2, August 1960, Page 439, https://doi.org/10.1093/jnci/25.2.439 Published: 01 August 1960
"WARM" HEART AND "COLD" HEART
Journal: JAMA (1963)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Human pluripotent stem-cell-derived islets ameliorate diabetes in non-human primates
Authors: Yuanyuan Du, Zhen Liang, Shusen Wang, Dong Sun, Xiaofeng Wang, Soon Yi Liew, Shuaiyao Lu, Shuangshuang Wu, Yong Jiang, Yaqi Wang, Boya Zhang, Wenhai Yu, Zhi Lu, Yue Pu, Yun Zhang, Haiting Long, Shanshan Xiao, Rui Liang, Zhengyuan Zhang, Jingyang Guan, Jinlin Wang, Huixia Ren, Yanling Wei, Jiaxu Zhao, Shicheng Sun, Tengli Liu, Gaofan Meng, Le Wang, Jiabin Gu, Tao Wang, Yinan Liu, Cheng Li, Chao Tang, Zhongyang Shen, Xiaozhong Peng, Hongkui Deng
Journal: Nature Medicine (2022)
Alopecia areata: findings from a study of <scp>UK</scp> general practice records
Journal: British Journal of Dermatology (2022)

Journal Article Alopecia areata: findings from a study of UK general practice records Get access British Journal of Dermatology, Volume 186, Issue 2, 1 February 2022, Page e94, https://doi.org/10.1111/bjd.20922 Published: 01 February 2022
Covid-19: UK approves Novavax’s protein based vaccine
Authors: Jacqui Wise
Journal: BMJ (2022)

Covid-19: UK approves Novavax's protein based vaccine Jacqui WiseThe UK's regulator has approved Novavax's covid-19 vaccine that uses an established technology and so may prove attractive to people who are reluctant to be vaccinated.Nuvaxovid is the fifth covid vaccine authorised by the Medicines and Healthcare Products Regulatory Agency and the first protein based vaccine for the UK.
Biological Studies on the Rous Sarcoma Virus. IV. Interpretation of Tumor-Response Data Involving One Inoculation Site per Chicken
Authors: W. Ray Bryan
Journal: JNCI Journal of the National Cancer Institute (1956)

Biological Studies on the Rous Sarcoma Virus. IV. Interpretation of Tumor-Response Data Involving One Inoculation Site per Chicken W. Ray Bryan W. Ray Bryan National Cancer Institute,2Bethesda, Md. Search for other works by this author on: Oxford Academic PubMed Google Scholar 2National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare. Author Notes JNCI: Journal of the National Cancer Institute, Volume 16, Issue 4, February 1956, Pages 843–863, https://doi.org/10.1093/jnci/16.4.843 Published: 01 February 1956 Article history Received: 05 July 1955 Published: 01 February 1956
Prevalence, Incidence, and Progression of Radiographic and Symptomatic Hand Osteoarthritis: The Osteoarthritis Initiative
Authors: Charles B. Eaton, Lena F. Schaefer, Jeff Duryea, Jeff B. Driban, Grace H. Lo, Mary B. Roberts, Ida K. Haugen, Bing Lu, Michael C. Nevitt, Marc C. Hochberg, Rebecca D. Jackson, C. K. Kwoh, Timothy McAlindon
Journal: Arthritis & Rheumatology (2022)

To describe the prevalence, incidence, and progression of radiographic and symptomatic hand osteoarthritis (OA), and to evaluate differences according to age, sex, race, and other risk factors. Participants were assessed for radiographic and symptomatic hand OA at baseline and year 4 to determine incident disease. A modified Poisson regression with a robust variance estimator was used to account for clustering of joints within fingers within persons to estimate the prevalence ratios and relative risk estimates associated with participant characteristics. Among 3,588 participants, the prevalence of radiographic hand OA was 41.4%, and the prevalence of symptomatic hand OA was 12.4%. The incidence over 48 months was 5.6% for radiographic hand OA and 16.9% for symptomatic hand OA. Over 48 months, 27.3% of the participants exhibited OA progression. We found complex differences by age, sex, and race, with increasing rates of prevalent hand OA with older age in both men and women, but with rates of incident disease peaking at ages 55-64 years in women. Women had higher rates of symptomatic hand OA, but only nonsignificantly higher rates of incident radiographic hand OA, than men. Women more frequently had distal interphalangeal joint disease, while men more frequently had metacarpophalangeal joint OA. Black men and women had lower rates of hand OA than White participants, but Black men had higher rates of prevalent hand OA than Black women at younger ages. Hand OA is a heterogeneous disease with complex differences by age, sex, race, hand symptoms, and patterns of specific joints affected. Further research investigating the mechanisms behind these differences, whether mechanical, metabolic, hormonal, or constitutional, is warranted.
S113: COST OF ILLNESS, EPIDEMIOLOGY AND HEALTHCARE RESOURCE UTILIZATION FOR SICKLE CELL DISEASE IN GULF COUNTRIES (CESCGU)
Authors: S Alkindi, J Altooq, H Dewedar, D Soliman, S Elsawy, A Ibrahim
Journal: HemaSphere (2022)

Background: Sickle cell disease (SCD) is one of the most predominant form of haemoglobinopathy worldwide. In the Middle East, SCD is prevalent, with high impact on health care systems. Currently, there are insufficient information published on the economic burden of SCD in the Gulf Countries (GC). Aim: Estimate the economic burden incurred by payors in Oman (OMN), Bahrain (BHR) and United-Arab-Emirates (UAE). Methodology: A prevalence-based probabilistic model was used to estimate the direct medical costs (DMC) associated with SCD within different treatment sites across 3 countries in the gulf region. Data from three treatment sites across GC has been collected through meetings with one principle investigator from each site. Aggregate patients' data input was gathered from hospital record databases of adult SCD patients managed in year 2019. Additionally, 50 Case Report Forms (CRFs) were filled from UAE site. Results: Aggregate data for 2,600 SCD patients in BHR, 2,000 in OMN and 350 in UAE were collected. The total DMC per patient per year was estimated at $15,300, $10,000 and $15,800 in BHR, OMN and UAE, respectively. The costs incurred by payors for "VOCs management" were identified as major cost driver. Conclusion: As far as our knowledge, this is the first COI study in SCD done in the GC. The economic burden of individuals affected by SCD in Gulf countries is rising. Severe SCD patients with ≥5 VOCs represent a significant burden on payors.
Physician, nurse relief workers killed in Rwanda
Authors: R. Voelker
Journal: JAMA (1997)

A 3-MONTH project to shore up the beleaguered medical care system in Ruhengeri, Rwanda, has been suspended following the deaths of a Spanish physician and 2 other relief workers in an apparently deliberate attack on their compound in war-torn central Africa. The physician, Manuel Madrazo Osuna, 42, of Seville, Spain, was shot to death last month inside a house serving as the compound for Medicos del Mundo, the Spanish affiliate of the French medical relief group Médecins du Monde (MDM). "He came from a family of doctors and was committed to social causes since medical school," said Elizabeth Wagley, spokesperson for MDM's US affiliate, Doctors of the World (DOW). Also killed in the attack were nurse Maria Flors Sirera Fortuny, 35, of Lérida, Spain, and Luis Valtuena Gallego, 30, originally from Madrid, a photographer and logistician at the compound. Nitin Madhav, 28, of Pittsburgh, Pa, was wounded in the attack.