Environmental chambers are a commonly used tool for
studying the production and processing of aerosols in the atmosphere. Most
are located indoors and most are filled with air having prescribed
...concentrations of a small number of reactive gas species. Here we describe
portable chambers that are used outdoors and filled with mostly ambient air.
Each all-Teflon® 1 m3 Captive Aerosol Growth and
Evolution (CAGE) chamber has a cylindrical shape that rotates along its
horizontal axis. A gas-permeable membrane allows exchange of gas-phase
species between the chamber and surrounding ambient air with an exchange
time constant of approximately 0.5 h. The membrane is non-permeable to
particles, and those that are injected into or nucleate in the chamber are
exposed to the ambient-mirroring environment until being sampled or lost to
the walls. The chamber and surrounding enclosure are made of materials that
are highly transmitting across the solar ultraviolet and visible wavelength
spectrum. Steps taken in the design and operation of the chambers to
maximize particle lifetime resulted in averages of 6.0, 8.2, and 3.9 h
for ∼ 0.06, ∼ 0.3, and
∼ 2.5 µm diameter particles, respectively. Two of the
newly developed CAGE chamber systems were characterized using data acquired
during a 2-month field study in 2016 in a forested area north of Houston,
TX, USA. Estimations of measured and unmeasured gas-phase species and of
secondary aerosol production in the chambers were made using a
zero-dimensional model that treats chemical reactions in the chamber and the
continuous exchange of gases with the surrounding air. Concentrations of NO,
NO2, NOy, O3, and several organic compounds measured in the
chamber were found to be in close agreement with those calculated from the
model, with all having near 1.0 best fit slopes and high r2 values. The
growth rates of particles in the chambers were quantified by tracking the
narrow modes that resulted from injection of monodisperse particles and from
occasional new particle formation bursts. Size distributions in the two
chambers were measured intermittently 24 h d−1. A bimodal diel
particle growth rate pattern was observed, with maxima of about
6 nm h−1 in the late morning and early evening and minima of less than 1 nm h−1 shortly before sunrise and sunset. A pattern change was observed
for hourly averaged growth rates between late summer and early fall.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bruton tyrosine kinase (BTK), a clinically validated target for various B-cell malignancies, plays a critical role in regulating cell growth, adhesion and homing to key lymphoid tissues that provide ...a microenvironment favorable to cancer cells. Despite the success of approved covalent BTK inhibitors in diseases such as CLL, most patients do not achieve complete response with monotherapy and eventually relapse, often via the emergence of the BTK-C481S mutation. Additionally, covalent BTK inhibitors have not shown sufficient differentiation from standard-of-care (SoC) in B-cell malignancies such as diffuse large B cell lymphoma (DLBCL) to warrant approval to date. To address these unmet needs, a next-generation orally bioavailable BTK degrader ABBV-101 has been developed. Unlike BTK inhibitors that solely bind to and impede the catalytic domain of BTK, ABBV-101 eliminates the protein in a highly selective fashion. This degradation mechanism targets both the catalytic and scaffolding functions of BTK, and thus may enable deeper and more durable responses in patients with B-cell malignancies. In preclinical studies, the BTK degrader ABBV-101 has shown potent in vitro and in vivo efficacy in BCR pathway-dependent leukemia/lymphoma models, including covalent BTK inhibitor resistant BTK-C481S systemic mouse CLL and human DLBCL models. ABBV-101 degrades BTK-WT and BTK-C481S with similar sub-nanomolar potency in the human DLBCL cell line TMD8 which translates to potent cellular growth inhibition. In addition to the BTK-C481S mutation, ABBV-101 demonstrates similar potent activity against novel BTK mutations associated with resistance to reversible BTK inhibitors in the clinic, an emerging unmet need. ABBV-101 induces complete tumor regression in the BTK-C481S TMD8 DLBCL xenograft model. A spontaneous mouse CLL model carrying BTK-C481S mutation was developed through crossing BTK-C481S knock-in mice with the Emu-TCL1 transgenic mice in the C57BL/6 background. ABBV-101 completely inhibits BTK-C481S Emu-TCL1 CLL burden increase in the blood compartment and reduces CLL burden in the spleen and lymph nodes, whereas covalent BTK inhibitors show no activity. Further, ABBV-101 induces complete tumor regressions in multiple non-GCB DLBCL PDX models, demonstrating deeper and more durable response than covalent and reversible inhibitors. Combination with a BCL-2 inhibitor enhances the efficacy of ABBV-101 in CLL and DLBCL models. Kinome and global proteomics profiling showed ABBV-101 to be highly selective, a designed feature that may enable favorable tolerability in patients. ABBV-101 is currently in phase 1 clinical trial for a variety of B-cell malignancies. ClinicalTrials.gov identifier: NCT05753501
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IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZRSKP
Sharing genomic variant interpretations across laboratories promotes consistency in variant assertions. A landscape analysis of Australian clinical genetic-testing laboratories in 2017 identified ...that, despite the national-accreditation-body recommendations encouraging laboratories to submit genotypic data to clinical databases, fewer than 300 variants had been shared to the ClinVar public database. Consultations with Australian laboratories identified resource constraints limiting routine application of manual processes, consent issues, and differences in interpretation systems as barriers to sharing. This information was used to define key needs and solutions required to enable national sharing of variant interpretations. The Shariant platform, using both the GRCh37 and GRCh38 genome builds, was developed to enable ongoing sharing of variant interpretations and associated evidence between Australian clinical genetic-testing laboratories. Where possible, two-way automated sharing was implemented so that disruption to laboratory workflows would be minimized. Terms of use were developed through consultation and currently restrict access to Australian clinical genetic-testing laboratories. Shariant was designed to store and compare structured evidence, to promote and record resolution of inter-laboratory classification discrepancies, and to streamline the submission of variant assertions to ClinVar. As of December 2021, more than 14,000 largely prospectively curated variant records from 11 participating laboratories have been shared. Discrepant classifications have been identified for 11% (28/260) of variants submitted by more than one laboratory. We have demonstrated that co-design with clinical laboratories is vital to developing and implementing a national variant-interpretation sharing effort. This approach has improved inter-laboratory concordance and enabled opportunities to standardize interpretation practices.
Sharing genomic variant interpretations across laboratories promotes consistency. The Shariant platform was developed to enable ongoing sharing of variant interpretations and associated evidence, resolution of inter-laboratory discrepancies, and streamlined submission of variant assertions to ClinVar. This approach has improved concordance and enabled opportunities for standardization of practices between Australian laboratories.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The recruitment of asymptomatic volunteers has been identified as a critical factor that is delaying the development and validation of preventive therapies for Alzheimer disease (AD). Typical ...recruitment strategies involve the use of convenience samples or soliciting participation of older adults with a family history of AD from clinics and outreach efforts. However, high-risk groups, such as ethnic/racial minorities, are traditionally less likely to be recruited for AD prevention studies, thus limiting the ability to generalize findings for a significant proportion of the aging population. A community-engagement approach was used to create a registry of 2311 research-ready, healthy adult volunteers who reflect the ethnically diverse local community. Furthermore, the registry’s actual commitment to research was examined, through demonstrated participation rates in a clinical study. The approach had varying levels of success in establishing a large, diverse pool of individuals who are interested in participating in pharmacological prevention trials and meet the criteria for primary prevention research trials designed to delay the onset of AD. Our efforts suggest that entry criteria for the clinical trials need to be carefully considered to be inclusive of African Americans, and that sustained effort is needed to engage African Americans in pharmacological prevention approaches.
Folate fortification of food aims to reduce the number of babies born with neural tube defects, but has been associated with cognitive impairment when vitamin B12 levels are deficient. Given the ...prevalence of low vitamin B12 levels among the elderly, and the global deployment of food fortification programs, investigation of the associations between cognitive impairment, vitamin B12, and folate are needed.
To investigate the associations of serum vitamin B12, red cell folate, and cognitive impairment.
Data were collected on 1,354 subjects in two studies investigating cognitive impairment, and from patients attending for assessment or management of memory problems in the Barwon region of south eastern Australia between 2001 and 2011. Eligible subjects who had blood measurements of vitamin B12 and red cell folate taken within six months of cognitive testing were included. Subjects with stroke or neurodegenerative diseases other than Alzheimer's disease were excluded. A Mini-Mental State Examination score of <24 was used to define impaired cognitive function.
Participants with low serum vitamin B12 (<250 pmol/L) and high red cell folate (>1,594 nmol/L) levels were more likely to have impaired cognitive performance (adjusted odds ratio (AOR) 3.45, 95% confidence interval (CI): 1.60-7.43, p = 0.002) when compared to participants with biochemical measurements that were within the normal ranges. Participants with high folate levels, but normal serum vitamin B12, were also more likely to have impaired cognitive performance (AOR 1.74, 95% CI: 1.03-2.95, p = 0.04).
High folate or folic acid supplements may be detrimental to cognition in older people with low vitamin B12 levels. This topic is of global significance due to the wide distribution of food fortification programs, so prospective studies should be a high priority.
Reviews of teaching/learning resources Book, Cassandra L.; Phelps, Lynn A.; Sprague, Jo ...
Communication Education,
19/5/1/, Volume:
29, Issue:
2
Book Review, Journal Article
Peer reviewed
Basic books
The Challenge Of Effective Speaking. 4th ed. By Rudolph F. Verderber. Belmont, Calif.: Wadsworth, 1979; pp. x+319. $7.95. Paper.
Communication: Personal And Public. By William I. Gorden. ...Sherman Oaks, Calif.: Alfred Publ., 1978; pp. viii+377. $12.95. Hardcover.
Creative Speech Communication. By James W. Gibson and Clifton Cornwell. New York: Macmillan, 1979; pp. x+175. $6.95. Paper.
Fundamentals Of Human Communication. By Robert G. King. New York: Macmillan, 1979; pp. xiii+372. $9.95. Paper.
Idea To Delivery: A HANDBOOK OF ORAL COMMUNICATION. 3rd ed. By Dwight L. Gamer. Belmont, Calif.: Wadsworth, 1979; pp. x+163. $5.95. Paper.
A Brief Introduction To Speech. By Donovan J. Ochs and Anthony C. Winkler. New York: Harcourt Brace Jovanovich, 1979; pp. xv+231. $7.95. Paper.
Listening: A PROGRAMMED APPROACH. 2nd ed. By Ella A. Erway. New York: McGraw-Hill, 1979; pp. vii+117. 58.50. Paper.
People To People: Essentials Of Personal And Public Communication. By Jack G. McAulay. Belmont, Calif.: Wadsworth, 1979; pp. xi+268. $8.95. Paper.
Public Speaking. By Wayne C. Minnick, Boston: Houghton Mifflin, 1979; pp. x+244. $8.25. Paper.
Speak, Listen, Communicate! By Merritt B. Jones. New York: D. Van Nostrand, 1978; pp. xiii+321. $8.25. Paper.
Speech Communication. 2nd ed. By Saundra Hybels and Richard L. Weaver, II. New York: D. Van Nostrand, 1979; pp. x+240. $8.95. Paper.
TEchniques FOR EFFECTIVE COMMUNICATION. By R. Wayne Pace, Brent D. Peterson, and M. Dallas Burnett. Reading, Mass.: Addison-Wesley, 1979; pp. xv+329. $8.95. Paper.
Thinking And Speaking: A GUIDE TO INTELLIGENT ORAL COMMUNICATION. 4th ed. By Otis M. Walter and Robert L. Scott. New York: Macmillan, 1979; pp. viii+264. $7.95. Paper.
COMMUNICATION AND INSTRUCTION By Ronald E. Bassett and Mary-Jeanette Smythe. New York: Harper and Row, Publishers, 1979; pp. xii+276. $10.95.
AN INTRODUCTION TO REASONING By Stephen Toulmin, Richard Rieke, and Allan Janik. New York: Macmillan, 1979; pp. v-vi+ 343. With Teaching Guide, pp. 52. $12.95.
COMMUNICATION FOR MANAGERS By Paul Preston. Englewood Cliffs, New Jersey: Prentice-Hall, Inc., 1979; pp. xi+307. $14.95.
MASS COMMUNICATION: PRINCIPLES AND PRACTICES By Mary B. Cassata and Molefi K. Asante. New York: Macmillan Publishing Co., Inc. 1979; pp. xvii+360. $7.95.
COMMUNICATION THROUGH ORAL READING By Donald H. Ecroyd and Hilda Stahl Wagner. Manchester, Mo.: McGraw-Hill, 1979; pp. viii+219. $9.95.
The objective of this study was to document pulse oximeter saturation levels achieved in the first 4 weeks of life in infants who were born at < 28 weeks' gestation, compared with the levels that ...were targeted by local policy, and examine factors that are associated with compliance with the target range.
Infants who were < 28 weeks' gestation and < or = 96 hours of age were enrolled in a prospective, multicenter cohort study. Oximetry data were collected with masked signal-extraction oximeters for a 72-hour period in each of the first 4 weeks of life. Data were compared with the pulse oximeter saturation target range prescribed by local institutional policy. Factors that were associated with intended range compliance were identified with hierarchical modeling.
Fourteen centers from 3 countries enrolled 84 infants with mean +/- SD birth weight of 863 +/- 208 g and gestational age of 26 +/- 1.4 weeks. Oxygen saturation policy limits ranged between 83% and 92% for lower limits and 92% and 98% for upper limits. For infants who received respiratory support, median pulse oximeter saturation level achieved was 95%. Center-specific medial levels were within the intended range at 12 centers. Centers maintained infants within their intended range 16% to 64% of the time but were above range 20% to 73% of the time. In hierarchical modeling, wider target ranges, higher target range upper limits, presence of a policy of setting oximeter alarms close to the target range limits, and lower gestational age were associated with improved target range compliance.
Success with maintaining the intended pulse oximeter saturation range varied substantially among centers, among patients within centers, and for individual patients over time. Most noncompliance was above the intended range. Methods for improving compliance and the effect of improved compliance on neonatal outcomes require additional research.
The Alzheimer's Association International Conference held its sixth Satellite Symposium in Sydney, Australia in 2019, highlighting the leadership of Australian researchers in advancing the ...understanding of and treatment developments for Alzheimer's disease (AD) and other dementias.
This leadership includes the Australian Imaging, Biomarker, and Lifestyle Flagship Study of Ageing (AIBL), which has fueled the identification and development of many biomarkers and novel therapeutics. Two multimodal lifestyle intervention studies have been launched in Australia; and Australian researchers have played leadership roles in other global studies in diverse populations.
Australian researchers have also played an instrumental role in efforts to understand mechanisms underlying vascular contributions to cognitive impairment and dementia; and through the Women's Healthy Aging Project have elucidated hormonal and other factors that contribute to the increased risk of AD in women. Alleviating the behavioral and psychological symptoms of dementia has also been a strong research and clinical focus in Australia.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract Bruton tyrosine kinase (BTK), a clinically validated target for various B-cell malignancies, plays a critical role in regulating cell growth, adhesion, and homing to lymphoid tissues that ...provide a microenvironment favorable to cancer cells. Despite the success of approved covalent BTK inhibitors in diseases such as CLL, most patients do not achieve complete response with monotherapy and eventually relapse, often via the emergence of the BTK-C481S mutation. Although second-generation reversible BTK inhibitors may temporarily overcome the C481S mutation, novel BTK mutations associated with resistance emerged in the clinic recently. Additionally, covalent BTK inhibitors have not shown sufficient differentiation from standard-of-care (SoC) in B-cell malignancies, such as diffuse large B cell lymphoma (DLBCL) to warrant approval to date. To address these unmet needs, a next-generation orally bioavailable BTK degrader ABBV-101 has been developed. Unlike BTK inhibitors that solely bind to and impede the catalytic domain of BTK, ABBV-101 eliminates the protein in a highly selective fashion. This degradation mechanism targets both the catalytic and scaffolding functions of BTK, and thus may enable deeper and more durable responses in patients with B-cell malignancies. Cellular activity of ABBV-101 was determined in a panel of DLBCL cell lines. We show that most non-germinal center B cell DLBCL (non-GCB-DLBCL) cell lines are sensitive to ABBV-101. To determine whether ABBV-101 could overcome BTK mutations-induced resistance, we engineered human DLBCL cell line TMD8 using CRISPR technology to express these BTK mutations and tested for sensitivity to ABBV-101 and BTK inhibitors. We show that ABBV-101 demonstrates similar potent activity against all BTK mutations associated with resistance to both covalent and reversible BTK inhibitors. The modulation of downstream pathway by ABBV-101 and how it differentiates from other BTK inhibitors will be presented. Further, ABBV-101 induces complete tumor regression in the BTK-C481S TMD8 DLBCL xenograft model. A spontaneous mouse CLL model carrying BTK-C481S mutation was developed through crossing BTK-C481S knock-in mice with the Emu-TCL1 transgenic mice in the C57BL/6 background. ABBV-101 completely inhibits BTK-C481S Emu-TCL1 CLL burden increase in the blood compartment and reduces CLL burden in the spleen and lymph nodes, whereas covalent BTK inhibitors show no activity. Finally, combination with a BCL-2 inhibitor enhances the efficacy of ABBV-101 in CLL and DLBCL models. Taken together, our results suggest that ABBV-101 has potent in vitro and in vivo efficacy. ABBV-101 is currently in phase 1 clinical trial for a variety of B-cell malignancies. ClinicalTrials.gov identifier: NCT05753501 Citation Format: Chin Pan, Jacob Riehm, Tarikere L. Gururaja, Haiyan Li, Henry Nguyen, Yongjiao Zhai, Xiaoping Xie, Rong-Xian Ding, Rebecca Matthew, Hana Y. Hoh, Zhaozhong J. Jia, Bo Liu, Cassandra P. Shu, Claudina A. Stevenson, Christine Will, Federico Innocenti, Wissam Assaily, Lloyd T. Lam, Alexey Rivkin. ABBV-101, a highly potent and selective clinical stage Bruton tyrosine kinase degrader, overcomes BTK mutation-induced resistance to BTK inhibitors abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 605.
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