Aerosol science and technology: History and reviews

Aerosol Science and Technology: History and Reviews captures an exciting slice of history in the evolution of aerosol science. It presents in-depth biographies of four leading international aerosol researchers and highlights pivotal research institutions in New York, Minnesota, and Austria. One collection of chapters reflects on the legacy of the Pasadena smog experiment, while another presents a fascinating overview of military applications and nuclear aerosols. Finally, prominent researchers offer detailed reviews of aerosol measurement, processes, experiments, and technology that changed the face of aerosol science. This volume is the third in a series and is supported by the American Association for Aerosol Research (AAAR) History Working Group, whose goal is to produce archival books from its symposiums on the history of aerosol science to ensure a lasting record. It is based on papers presented at the Third Aerosol History Symposium on September 8 and 9, 2006, in St. Paul, Minnesota, USA

Brn-3b enhances the pro-apoptotic effects of p53 but not its induction of cell cycle arrest by cooperating in trans-activation of bax expression

The Brn-3a and Brn-3b transcription factor have opposite and antagonistic effects in neuroblastoma cells since Brn-3a is associated with differentiation whilst Brn-3b enhances proliferation in these cells. In this study, we demonstrate that like Brn-3a, Brn-3b physically interacts with p53. However, whereas Brn-3a repressed p53 mediated Bax expression but cooperated with p53 to increase p21(cip1/waf1), this study demonstrated that co-expression of Brn-3b with p53 increases trans-activation of Bax promoter but not p21(cip1/waf1). Consequently co-expression of Brn-3b with p53 resulted in enhanced apoptosis, which is in contrast to the increased survival and differentiation, when Brn-3a is co-expressed with p53. For Brn-3b to cooperate with p53 on the Bax promoter, it requires binding sites that flank p53 sites on this promoter. Furthermore, neurons from Brn-3b knock-out (KO) mice were resistant to apoptosis and this correlated with reduced Bax expression upon induction of p53 in neurons lacking Brn-3b compared with controls. Thus, the ability of Brn-3b to interact with p53 and modulate Bax expression may demonstrate an important mechanism that helps to determine the fate of cells when p53 is induced

Increasing access to institutional deliveries using demand and supply side incentives: early results from a quasi-experimental study

<p>Abstract</p> <p>Background</p> <p>Geographical inaccessibility, lack of transport, and financial burdens are some of the demand side constraints to maternal health services in Uganda, while supply side problems include poor quality services related to unmotivated health workers and inadequate supplies. Most public health interventions in Uganda have addressed only selected supply side issues, and universities have focused their efforts on providing maternal services at tertiary hospitals. To demonstrate how reforms at Makerere University College of Health Sciences (MakCHS) can lead to making systemic changes that can improve maternal health services, a demand and supply side strategy was developed by working with local communities and national stakeholders.</p> <p>Methods</p> <p>This quasi-experimental trial is conducted in two districts in Eastern Uganda. The supply side component includes health worker refresher training and additions of minimal drugs and supplies, whereas the demand side component involves vouchers given to pregnant women for motorcycle transport and the payment to service providers for antenatal, delivery, and postnatal care. The trial is ongoing, but early analysis from routine health information systems on the number of services used is presented.</p> <p>Results</p> <p>Motorcyclists in the community organized themselves to accept vouchers in exchange for transport for antenatal care, deliveries and postnatal care, and have become actively involved in ensuring that women obtain care. Increases in antenatal, delivery, and postnatal care were demonstrated, with the number of safe deliveries in the intervention area immediately jumping from <200 deliveries/month to over 500 deliveries/month in the intervention arm. Voucher revenues have been used to obtain needed supplies to improve quality and to pay health workers, ensuring their availability at a time when workloads are increasing.</p> <p>Conclusions</p> <p>Transport and service vouchers appear to be a viable strategy for rapidly increasing maternal care. MakCHS can design strategies together with stakeholders using a learning-by-doing approach to take advantage of community resources.</p

High-Affinity Inhibitors of Human NAD+-Dependent 15-Hydroxyprostaglandin Dehydrogenase: Mechanisms of Inhibition and Structure-Activity Relationships

BACKGROUND: 15-Hydroxyprostaglandin dehydrogenase (15-PGDH, EC 1.1.1.141) is the key enzyme for the inactivation of prostaglandins, regulating processes such as inflammation or proliferation. The anabolic pathways of prostaglandins, especially with respect to regulation of the cyclooxygenase (COX) enzymes have been studied in detail; however, little is known about downstream events including functional interaction of prostaglandin-processing and -metabolizing enzymes. High-affinity probes for 15-PGDH will, therefore, represent important tools for further studies. PRINCIPAL FINDINGS: To identify novel high-affinity inhibitors of 15-PGDH we performed a quantitative high-throughput screen (qHTS) by testing &gt;160 thousand compounds in a concentration-response format and identified compounds that act as noncompetitive inhibitors as well as a competitive inhibitor, with nanomolar affinity. Both types of inhibitors caused strong thermal stabilization of the enzyme, with cofactor dependencies correlating with their mechanism of action. We solved the structure of human 15-PGDH and explored the binding modes of the inhibitors to the enzyme in silico. We found binding modes that are consistent with the observed mechanisms of action. CONCLUSIONS: Low cross-reactivity in screens of over 320 targets, including three other human dehydrogenases/reductases, suggest selectivity of the present inhibitors for 15-PGDH. The high potencies and different mechanisms of action of these chemotypes make them a useful set of complementary chemical probes for functional studies of prostaglandin-signaling pathways. ENHANCED VERSION: This article can also be viewed as an enhanced version in which the text of the article is integrated with interactive 3D representations and animated transitions. Please note that a web plugin is required to access this enhanced functionality. Instructions for the installation and use of the web plugin are available in Text S2

Cluster-randomised controlled trial of community mobilisation in Mumbai slums to improve care during pregnancy, delivery, postpartum and for the newborn

Background: The United Nations Millennium Development Goals look to substantial improvements in child and maternal survival. Morbidity and mortality during pregnancy, delivery and the postnatal period are prime obstacles to achieving these goals. Given the increasing importance of urban health to global prospects, Mumbai's City Initiative for Newborn Health aims to improve maternal and neonatal health in vulnerable urban slum communities, through a combination of health service quality improvement and community participation. The protocol describes a trial of community intervention aimed at improving prevention, care seeking and outcomes.Objective: To test an intervention that supports local women as facilitators in mobilising communities for better health care. Community women's groups will build an understanding of their potential to improve maternal and infant health, and develop and implement strategies to do so.Design: Cluster-randomized controlled trial.Methods: The intervention will employ local community-based female facilitators to convene groups and help them to explore maternal and neonatal health issues. Groups will meet fortnightly through a seven-phase process of sharing experiences, discussion of the issues raised, discovery of potential community strengths, building of a vision for action, design and implementation of community strategies, and evaluation.The unit of allocation will be an urban slum cluster of 1000-1500 households. 48 clusters have been randomly selected after stratification by ward. 24 clusters have been randomly allocated to receive the community intervention. 24 clusters will act as control groups, but will benefit from health service quality improvement. Indicators of effect will be measured through a surveillance system implemented by the project. Key distal outcome indicators will be neonatal mortality and maternal and neonatal morbidity. Key proximate outcome indicators will be home care practices, uptake of antenatal, delivery and postnatal care, and care for maternal and neonatal illness.Data will be collected through a vital registration system for births and deaths in the 48 study clusters. Structured interviews with families will be conducted at about 6 weeks after index deliveries. We will also collect both quantitative and qualitative data to support a process evaluation.Trial registration: Current controlled trials ISRCTN9625679

Addressing the double-burden of diabetes and tuberculosis : Lessons from Kyrgyzstan

Background: The incidence of diabetes and tuberculosis co-morbidity is rising, yet little work has been done to understand potential implications for health systems, healthcare providers and individuals. Kyrgyzstan is a priority country for tuberculosis control and has a 5% prevalence of diabetes in adults, with many health system challenges for both conditions. Methods: Patient exit interviews collected data on demographic and socio-economic characteristics, health spending and care seeking for people with diabetes, tuberculosis and both diabetes and tuberculosis. Qualitative data were collected through semi-structured interviews with healthcare workers involved in diabetes and tuberculosis care, to understand delivery of care and how providers view effectiveness of care. Results: The experience of co-affected individuals within the health system is different than those just with tuberculosis or diabetes. Co-affected patients do not receive more care and also have different care for their tuberculosis than people with only tuberculosis. Very high levels of catastrophic spending are found among all groups despite these two conditions being included in the Kyrgyz state benefit package especially for medicines. Conclusions: This study highlights that different patterns of service provision by disease group are found. Although Kyrgyzstan has often been cited as an example in terms of health reforms and developing Primary Health Care, this study highlights the challenge of managing conditions that are viewed as "too complicated" for non-specialists and the impact this has on costs and management of individuals

Phase I Trial of Arginine Deprivation Therapy with ADI-PEG 20 Plus Docetaxel in Patients with Advanced Malignant Solid Tumors

PURPOSE: This phase I study examined the toxicity and tolerability, of pegylated arginine deiminase (ADI-PEG 20) in combination with docetaxel in patients with advanced solid malignancies. EXPERIMENTAL DESIGN: Eligible patients had histologically proven advanced solid malignancies, with any number of prior therapies, zubrod performance status 0–2 and adequate organ function. Patients received ADI-PEG 20 weekly intramuscular injection ranging from 4.5–36 mg/m(2), and up to ten doses of docetaxel 75 mg/m(2) every three weeks. Primary endpoints were safety, toxicity and a recommended phase II dose. Circulating arginine levels were measured prior to each cycle. Tumor response was measured as a secondary endpoint every six weeks on study. RESULTS: Eighteen patients received a total of 116 cycles of therapy through four dose levels of ADI-PEG 20. A single dose-limiting toxicity (grade 3 urticarial rash) was observed at the 1(st) dose level, with no additional dose-limiting toxicities observed. Hematologic toxicities were common with 14 patients experiencing at least one grade 3–4 leukopenia. Fatigue was the most prevalent toxicity reported by 16 patients. Arginine was variably suppressed with ten patients achieving at least a 50% reduction in baseline values. In 14 patients with evaluable disease, four partial responses (including two patients with PSA response) were documented and seven patients had stable disease. CONCLUSIONS: ADI-PEG 20 demonstrated reasonable toxicity in combination with docetaxel. Promising clinical activity was noted and expansion cohorts are now accruing for both castrate resistant prostate cancer and non-small cell lung cancer at a recommended phase II dose of 36 mg/m(2)

Unlocking community capabilities for improving maternal and newborn health: participatory action research to improve birth preparedness, health facility access, and newborn care in rural Uganda

Background: Community capacities and resources must be harnessed to complement supply side initiatives addressing high maternal and neonatal mortality rates in Uganda. This paper reflects on gains, challenges and lessons learnt from working with communities to improve maternal and newborn health in rural Uganda. Methods: A participatory action research project was supported from 2012 to 2015 in three eastern districts. This project involved working with households, saving groups, sub county and district leaders, transporters and village health teams in diagnosing causes of maternal and neonatal mortality and morbidity, developing action plans to address these issues, taking action and learning from action in a cyclical manner. This paper draws from project experience and documentation, as well as thematic analysis of 20 interviews with community and district stakeholders and 12 focus group discussions with women who had recently delivered and men whose wives had recently delivered. Results: Women and men reported increased awareness about birth preparedness, improved newborn care practices and more male involvement in maternal and newborn health. However, additional direct communication strategies were required to reach more men beyond the minority who attended community dialogues and home visits. Saving groups and other saving modalities were strengthened, with money saved used to meet transport costs, purchase other items needed for birth and other routine household needs. However saving groups required significant support to improve income generation, management and trust among members. Linkages between savings groups and transport providers improved women’s access to health facilities at reduced cost. Although village health teams were a key resource for providing information, their efforts were constrained by low levels of education, inadequate financial compensation and transportation challenges. Ensuring that the village health teams and savings groups functioned required regular supervision, review meetings and payment for supervisors to visit. Conclusions: This participatory program, which focused on building the capacity of community stakeholders, was able to improve local awareness of maternal and newborn health practices and instigate local action to improve access to healthcare. Collaborative problem solving among diverse stakeholders, continuous support and a participatory approach that allowed flexibility were essential project characteristics that enabled overcoming of challenges faced

Tracking cryptococcal meningitis to monitor HIV program success during the Treat-All era: an analysis of national data in Botswana.

BACKGROUND: Cryptococcal meningitis causes substantial mortality in high-HIV prevalence African countries despite advances in disease management and increasing antiretroviral therapy coverage. Reliable diagnosis of cryptococcal meningitis is cheap and more accessible than other indicators of AHD burden such as CD4 testing or investigation for disseminated tuberculosis; therefore, monitoring cryptococcal meningitis incidence has the potential to serve as a valuable metric of HIV programmatic success. METHODS: Botswana national meningitis surveillance data from 2015 to 2022 were obtained from electronic health records. All electronic laboratory records from cerebrospinal fluid samples analysed within government healthcare facilities in Botswana were extracted from a central online repository. Adjustments for missing data were made through triangulation with prospective cohort study datasets. Cryptococcal meningitis case frequency was enumerated using a case definition and incidence calculated using national census data. RESULTS: A total of 1,744 episodes of cryptococcal meningitis were identified; incidence declined from 15.0 (95% CI 13.4-16.7) cases/100,000 person-years in 2015 to 7.4 (95% CI 6.4-8.6) cases/100,000 person-years in 2022. However, the rate of decline slowed following the introduction of universal treatment in 2016. The highest incidence was observed in men and individuals aged 40-44. The proportion of cases diagnosed through cryptococcal antigen testing increased from 35.5% to 86.3%. CONCLUSION: Cryptococcal meningitis incidence has decreased in Botswana following expansion of ART coverage but persists at a stubbornly high incidence. Most cases are now diagnosed through the cheap and easy-to-use cryptococcal antigen test highlighting the potential of using cryptococcal meningitis as key metric of programme success in the Treat All era