Implementation of single-use technologies for antibody conjugation processes

Implementation of single use technologies offers significant advantages for antibody-drug conjugate (ADC) processes, including removal of cleaning validation requirements, reducing the volume of cleaning solutions which must be handled as hazardous waste, and eliminating the risk of product carryover. While these advantages afford numerous cost, resource, and timeline savings, there are several challenges that must also be addressed to support implementation of single use equipment for ADC processes. During conjugation process development, additional effort is required to understand the potential process/product quality impact, Material-of-Construction (MOC) compatibility, and potential leachables risk. A key focus area is to understand whether the MOC has any interaction with the reagents and/or process reactions that may influence the product quality attributes including the average drug-to-antibody ratio (DAR) and product aggregation. Additionally, the solvent background in ADC processes requires a detailed, risk assessment of the MOC compatibility and leachables risk prior to GMP implementation of single use technologies. Finally, increased at-scale process evaluation may be required prior to GMP implementation to ensure that the process performs as expected and delivers consistent product quality in the single use equipment upon scale-up. This presentation will provide current strategies that have been utilized during development and GMP implementation of ADC processes to assess single use technologies. Case studies from multiple programs will be shared describing how these various challenges can be addressed to ensure successful implementation of robust processes in GMP

Controlling Organization and Forces in Active Matter Through Optically-Defined Boundaries

Living systems are capable of locomotion, reconfiguration, and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, "active" molecules that create and manipulate non-equilibrium structures and force fields that span up to millimeter length scales [1-3]. Experimental active matter systems of biological or synthetic molecules are capable of spontaneously organizing into structures [4,5] and generating global flows [6-9]. However, these experimental systems lack the spatiotemporal control found in cells, limiting their utility for studying non-equilibrium phenomena and bioinspired engineering. Here, we uncover non-equilibrium phenomena and principles by optically controlling structures and fluid flow in an engineered system of active biomolecules. Our engineered system consists of purified microtubules and light-activatable motor proteins that crosslink and organize microtubules into distinct structures upon illumination. We develop basic operations, defined as sets of light patterns, to create, move, and merge microtubule structures. By composing these basic operations, we are able to create microtubule networks that span several hundred microns in length and contract at speeds up to an order of magnitude faster than the speed of an individual motor. We manipulate these contractile networks to generate and sculpt persistent fluid flows. The principles of boundary-mediated control we uncover may be used to study emergent cellular structures and forces and to develop programmable active matter devices

Evaluation of Distillers Grains Components Singly or in Combination in a Calf Fed Feedlot Study

A finishing study was conducted to determine the value of the fiber, protein, fat, and solubles components from wet distillers grains plus solubles (WDGS) alone or in combination for feedlot cattle in comparison to WDGS diets. The fiber portion alone did not improve F:G. When protein was included in the composite with fiber, F:G improved. With fat and solubles both added separately, F:G continued to improve. None of the components alone could make up the feeding value of WDGS, however the composite diet of fiber, protein, fat, and solubles combined matched the performance observed when WDGS is fed

Radio Astronomy in LSST Era

A community meeting on the topic of "Radio Astronomy in the LSST Era" was hosted by the National Radio Astronomy Observatory in Charlottesville, VA (2013 May 6--8). The focus of the workshop was on time domain radio astronomy and sky surveys. For the time domain, the extent to which radio and visible wavelength observations are required to understand several classes of transients was stressed, but there are also classes of radio transients for which no visible wavelength counterpart is yet known, providing an opportunity for discovery. From the LSST perspective, the LSST is expected to generate as many as 1 million alerts nightly, which will require even more selective specification and identification of the classes and characteristics of transients that can warrant follow up, at radio or any wavelength. The LSST will also conduct a deep survey of the sky, producing a catalog expected to contain over 38 billion objects in it. Deep radio wavelength sky surveys will also be conducted on a comparable time scale, and radio and visible wavelength observations are part of the multi-wavelength approach needed to classify and understand these objects. Radio wavelengths are valuable because they are unaffected by dust obscuration and, for galaxies, contain contributions both from star formation and from active galactic nuclei. The workshop touched on several other topics, on which there was consensus including the placement of other LSST "Deep Drilling Fields," inter-operability of software tools, and the challenge of filtering and exploiting the LSST data stream. There were also topics for which there was insufficient time for full discussion or for which no consensus was reached, which included the procedures for following up on LSST observations and the nature for future support of researchers desiring to use LSST data products.Comment: Conference summary, 29 pages, 1 figure; to be published in the Publ. Astron. Soc. Pacific; full science program and presentations available at http://science.nrao.edu/science/event/RALSST201

“I fear those things”: non-uptake of contraceptives, and barriers to use among adolescent girls and young women at high risk of HIV infection in Kampala, Uganda

BackgroundAdolescent girls and young women involved in risky behaviors are vulnerable to multiple health problems, yet sexual and reproductive health services remain underutilized. We evaluated factors associated with non-uptake of contraceptives and barriers to use among adolescent girls and young women (14–24 years old) at high risk of HIV infection in an environment where contraceptives were provided at no cost.MethodsWe conducted a mixed methods study, utilizing data from a baseline cross sectional survey and qualitative in-depth interviews. Survey participants tested negative for pregnancy and reported willingness to use contraception. Non-uptake of contraceptives was defined as not taking contraception at any study visit (baseline and throughout the study). Logistic regression model was used to assess factors associated with non-uptake of contraceptives. We purposively selected participants for interviews to discuss their knowledge and experiences with contraceptives and make suggestions to improve uptake. Qualitative data were analyzed thematically.ResultsAll 285 participants were included in the analysis. Out of the 285 participants 127 were not using contraceptives and of the 127, 44 (34.6%) did not take up any method throughout the study while 43 of the 83 remaining participants (who took up a method) chose male condoms only. Non-uptake of contraceptives was less likely among older women (20–24 years) (aOR = 0.32, 95% CI 0.16–0.89) compared to younger women (less than 20 years). Qualitative data showed that concerns about future fertility, fear of associated side effects and influence from close relations contributed to non-uptake of contraception.ConclusionNon-uptake of contraceptives was common despite the promotion and provision of contraceptives in the context of a research study mainly because adolescents lack autonomy while making contraceptive decisions. Identifying and addressing their concerns and continued counselling on contraceptive use alongside condom promotion may improve uptake and utilization of contraceptives

Controlling Organization and Forces in Active Matter Through Optically-Defined Boundaries

Living systems are capable of locomotion, reconfiguration and replication. To perform these tasks, cells spatiotemporally coordinate the interactions of force-generating, ‘active’ molecules that create and manipulate non-equilibrium structures and force fields of up to millimetre length scales. Experimental active-matter systems of biological or synthetic molecules are capable of spontaneously organizing into structures and generating global flows. However, these experimental systems lack the spatiotemporal control found in cells, limiting their utility for studying non-equilibrium phenomena and bioinspired engineering. Here we uncover non-equilibrium phenomena and principles of boundary-mediated control by optically modulating structures and fluid flow in an engineered system of active biomolecules. Our system consists of purified microtubules and light-activatable motor proteins that crosslink and organize the microtubules into distinct structures upon illumination. We develop basic operations—defined as sets of light patterns—to create, move and merge the microtubule structures. By combining these operations, we create microtubule networks that span several hundred micrometres in length and contract at speeds up to an order of magnitude higher than the speed of an individual motor protein. We manipulate these contractile networks to generate and sculpt persistent fluid flows. The principles of boundary-mediated control that we uncover may be used to study emergent cellular structures and forces and to develop programmable active-matter devices

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): a qualitative study of experiences of COVID-19 among people who inject drugs

BACKGROUND: : People who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour. METHODS: : Telephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis. RESULTS: : Concern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to ‘stay home’ led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources. CONCLUSION: : This study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services

A novel blood proteomic signature for prostate cancer

International audienceSimple Summary Despite intensive research, effective tools for detection and monitoring of prostate cancer remain to be found. Prostate-specific antigen (PSA), commonly used in prostate cancer assessments, can lead to overdiagnosis and overtreatment of indolent disease. This highlights the need for supporting non-invasive diagnostic, prognostic, and disease stratification biomarkers that could complement PSA in clinical decision-taking via increased sensitivity and specificity. In order to address this need, we uncover novel prostate cancer protein signatures by leveraging a cutting-edge analytical technique to measure proteins in patient samples. This strategy was used as a discovery tool to identify changes in protein levels in the serum of newly diagnosed patients as compared with healthy controls; the feature set was then further validated by reference to a second cohort of patients, achieving a high discriminatory ability. The proteomic maps generated also identified relevant changes in biological functions, notably the complement cascade. Prostate cancer is the most common malignant tumour in men. Improved testing for diagnosis, risk prediction, and response to treatment would improve care. Here, we identified a proteomic signature of prostate cancer in peripheral blood using data-independent acquisition mass spectrometry combined with machine learning. A highly predictive signature was derived, which was associated with relevant pathways, including the coagulation, complement, and clotting cascades, as well as plasma lipoprotein particle remodeling. We further validated the identified biomarkers against a second cohort, identifying a panel of five key markers (GP5, SERPINA5, ECM1, IGHG1, and THBS1) which retained most of the diagnostic power of the overall dataset, achieving an AUC of 0.91. Taken together, this study provides a proteomic signature complementary to PSA for the diagnosis of patients with localised prostate cancer, with the further potential for assessing risk of future development of prostate cancer. Data are available via ProteomeXchange with identifier PXD025484