Prediction of CHO cell line stability using expression of DNA repair genes.

Chinese hamster ovary (CHO) cells are essential to biopharmaceutical manufacturing and production instability, the loss of productivity over time, is a long-standing challenge in the industry. Accurate prediction of cell line stability could enable efficient screening to identify clones suitable for manufacturing saving significant time and costs. DNA repair genes may offer biomarkers to address this need. In this study, over 40 cell lines representing various host lineages from three companies/organizations were evaluated for expression of five DNA repair genes (Fam35a, Lig4, Palb2, Pari, and Xrcc6). Expression measured in cells with less than 30 population doubling levels (PDLs) was correlated to stability profiles at 60+ PDL. Principal component analysis identified markers which separate stable and unstable CHO-DG44 cell lines. Notably, two genes, Lig4 and Xrcc6, showed higher expression in unstable CHO-DG44 cell lines with copy number loss identified as the mechanism of production instability. Expression levels across all cell ages showed lower DNA repair gene expression was associated with increased cell age. Collectively, DNA repair genes provide critical insight into long-term behavior of CHO cells and their expression levels have potential to predict cell line stability in certain cases.

A Qualitative Study of Nurses' Perceptions of Narcotic Administration after Subarachnoid Hemorrhage.

BACKGROUND: Nearly every patient admitted to a neuroscience intensive care unit (ICU) will experience pain and nurses are tasked with analgesic administration. Within the setting of the ongoing opioid epidemic it is not well understood how nurses meet the need to alleviate pain while individualizing analgesic administration. AIMS: This qualitative study used a phenomenological approach to determine nurses' perceptions in pain management of patientswith subarachnoid hemorrhage (SAH). DESIGN: Prospective qualitative inquiry using phenomenology SETTING: The study was conducted in a neuroscience intensive care unit at a university hospital. PARTICIPANTS: Nine neuroscience intensive care unit nurses were enrolled using snowball sampling. METHODS: Saturation was reached after nine individual nurse interviews. Hermeneutic cycling analysis was used throughout interviews and codes and themes were developed throughout the interview process. Rigor was established using triangulation, rich and thick descriptions, and member checks. RESULTS: Emerging themes included discernment and hesitation. Discernment is supported by codes such as: "nursing judgement" and "follow the orders." Hesitation is supported by codes such as "clouded exam" and "over sedation." Eight nurses made references to hesitation of administering opioids due to the perception that it would cause a poorer neurological exam. All nurses described a reliance on education, experience, or intuition to guide their decision to administer opioids along with using approved pain scales. Themes were confirmed by member checks, which prompted slight modifications to coding. CONCLUSIONS: Results of this study support that nurses do express apprehension in administering opioids to patients with (SAH). This apprehension leads to hesitation to administer the medication and a thought out discernment process.

Common values in assessing health outcomes from disease and injury: disability weights measurement study for the Global Burden of Disease Study 2010.

BACKGROUND: Measurement of the global burden of disease with disability-adjusted life-years (DALYs) requires disability weights that quantify health losses for all non-fatal consequences of disease and injury. There has been extensive debate about a range of conceptual and methodological issues concerning the definition and measurement of these weights. Our primary objective was a comprehensive re-estimation of disability weights for the Global Burden of Disease Study 2010 through a large-scale empirical investigation in which judgments about health losses associated with many causes of disease and injury were elicited from the general public in diverse communities through a new, standardised approach. METHODS: We surveyed respondents in two ways: household surveys of adults aged 18 years or older (face-to-face interviews in Bangladesh, Indonesia, Peru, and Tanzania; telephone interviews in the USA) between Oct 28, 2009, and June 23, 2010; and an open-access web-based survey between July 26, 2010, and May 16, 2011. The surveys used paired comparison questions, in which respondents considered two hypothetical individuals with different, randomly selected health states and indicated which person they regarded as healthier. The web survey added questions about population health equivalence, which compared the overall health benefits of different life-saving or disease-prevention programmes. We analysed paired comparison responses with probit regression analysis on all 220 unique states in the study. We used results from the population health equivalence responses to anchor the results from the paired comparisons on the disability weight scale from 0 (implying no loss of health) to 1 (implying a health loss equivalent to death). Additionally, we compared new disability weights with those used in WHO's most recent update of the Global Burden of Disease Study for 2004. FINDINGS: 13,902 individuals participated in household surveys and 16,328 in the web survey. Analysis of paired comparison responses indicated a high degree of consistency across surveys: correlations between individual survey results and results from analysis of the pooled dataset were 0·9 or higher in all surveys except in Bangladesh (r=0·75). Most of the 220 disability weights were located on the mild end of the severity scale, with 58 (26%) having weights below 0·05. Five (11%) states had weights below 0·01, such as mild anaemia, mild hearing or vision loss, and secondary infertility. The health states with the highest disability weights were acute schizophrenia (0·76) and severe multiple sclerosis (0·71). We identified a broad pattern of agreement between the old and new weights (r=0·70), particularly in the moderate-to-severe range. However, in the mild range below 0·2, many states had significantly lower weights in our study than previously. INTERPRETATION: This study represents the most extensive empirical effort as yet to measure disability weights. By contrast with the popular hypothesis that disability assessments vary widely across samples with different cultural environments, we have reported strong evidence of highly consistent results. FUNDING: Bill & Melinda Gates Foundation.

Financing of global health: tracking development assistance for health from 1990 to 2007.

BACKGROUND: The need for timely and reliable information about global health resource flows to low-income and middle-income countries is widely recognised. We aimed to provide a comprehensive assessment of development assistance for health (DAH) from 1990 to 2007. METHODS: We defined DAH as all flows for health from public and private institutions whose primary purpose is to provide development assistance to low-income and middle-income countries. We used several data sources to measure the yearly volume of DAH in 2007 US$, and created an integrated project database to examine the composition of this assistance by recipient country. FINDINGS: DAH grew from $5.6 billion in 1990 to $21.8 billion in 2007. The proportion of DAH channelled via UN agencies and development banks decreased from 1990 to 2007, whereas the Global Fund to Fight AIDS, Tuberculosis and Malaria, the Global Alliance for Vaccines and Immunization (GAVI), and non-governmental organisations became the conduit for an increasing share of DAH. DAH has risen sharply since 2002 because of increases in public funding, especially from the USA, and on the private side, from increased philanthropic donations and in-kind contributions from corporate donors. Of the $13.8 [corrected] billion DAH in 2007 for which project-level information was available, $4.9 [corrected] billion was for HIV/AIDS, compared with $0.6 [corrected] billion for tuberculosis, $0.7 [corrected] billion for malaria, and $0.9 billion for health-sector support. Total DAH received by low-income and middle-income countries was positively correlated with burden of disease, whereas per head DAH was negatively correlated with per head gross domestic product. INTERPRETATION: This study documents the substantial rise of resources for global health in recent years. Although the rise in DAH has resulted in increased funds for HIV/AIDS, other areas of global health have also expanded. The influx of funds has been accompanied by major changes in the institutional landscape of global health, with global health initiatives such as the Global Fund and GAVI having a central role in mobilising and channelling global health funds. FUNDING: Bill & Melinda Gates Foundation.