Estimating the costs of induced abortion in Uganda: A model-based analysis

<p>Abstract</p> <p>Background</p> <p>The demand for induced abortions in Uganda is high despite legal and moral proscriptions. Abortion seekers usually go to illegal, hidden clinics where procedures are performed in unhygienic environments by under-trained practitioners. These abortions, which are usually unsafe, lead to a high rate of severe complications and use of substantial, scarce healthcare resources. This study was performed to estimate the costs associated with induced abortions in Uganda.</p> <p>Methods</p> <p>A decision tree was developed to represent the consequences of induced abortion and estimate the costs of an average case. Data were obtained from a primary chart abstraction study, an on-going prospective study, and the published literature. Societal costs, direct medical costs, direct non-medical costs, indirect (productivity) costs, costs to patients, and costs to the government were estimated. Monte Carlo simulation was used to account for uncertainty.</p> <p>Results</p> <p>The average societal cost per induced abortion (95% credibility range) was $177 ($140-$223). This is equivalent to$64 million in annual national costs. Of this, the average direct medical cost was $65 ($49-86) and the average direct non-medical cost was $19 ($16-$23). The average indirect cost was$92 ($57-$139). Patients incurred $62 ($46-$83) on average while government incurred$14 ($10-$20) on average.</p> <p>Conclusion</p> <p>Induced abortions are associated with substantial costs in Uganda and patients incur the bulk of the healthcare costs. This reinforces the case made by other researchers--that efforts by the government to reduce unsafe abortions by increasing contraceptive coverage or providing safe, legal abortions are critical.</p

FACS-based purification of Arabidopsis microspores, sperm cells and vegetative nuclei

Background: The male germline in flowering plants differentiates by asymmetric division of haploid uninucleated microspores, giving rise to a vegetative cell enclosing a smaller generative cell, which eventually undergoes a second mitosis to originate two sperm cells. The vegetative cell and the sperm cells activate distinct genetic and epigenetic mechanisms to control pollen tube growth and germ cell specification, respectively. Therefore, a comprehensive characterization of these processes relies on efficient methods to isolate each of the different cell types throughout male gametogenesis. Results: We developed stable transgenic Arabidopsis lines and reliable purification tools based on Fluorescence-Activated Cell Sorting (FACS) in order to isolate highly pure and viable fractions of each cell/nuclei type before and after pollen mitosis. In the case of mature pollen, this was accomplished by expressing GFP and RFP in the sperm and vegetative nuclei, respectively, resulting in 99% pure sorted populations. Microspores were also purified by FACS taking advantage of their characteristic small size and autofluorescent properties, and were confirmed to be 98% pure. Conclusions: We provide simple and efficient FACS-based purification protocols for Arabidopsis microspores, vegetative nuclei and sperm cells. This paves the way for subsequent molecular analysis such as transcriptomics, DNA methylation analysis and chromatin immunoprecipitation, in the developmental context of microgametogenesis in Arabidopsis.NSERC graduate student fellowship; Fred C. Gloeckner Foundation grant

Torsion and vibration-torsion levels of the S1 and ground cation electronic states of para-fluorotoluene

We investigate the low-energy transitions (0–570 cm-1) of the S1 state of para-fluorotoluene (pFT) using a combination of resonance-enhanced multiphoton ionization (REMPI) and zero-kinetic-energy (ZEKE) spectroscopy and quantum chemical calculations. By using various S1 states as intermediate levels, we obtain zero-kinetic-energy (ZEKE) spectra. The differing activity observed allows detailed assignments to be made of both the cation and S1 low-energy levels. The assignments are in line with the recently-published work on toluene from the Lawrance group [J. Chem. Phys. 143, 044313 (2015)], which considered vibration-torsion coupling in depth for the S1 state of toluene. In addition, we investigate whether two bands that occur in the range 390–420 cm-1 are the result of a Fermi resonance; we present evidence for weak coupling between various vibrations and torsions that contribute to this region. This work has led to the identification of a number of misassignments in the literature, and these are corrected

Impact of Genetic Ancestry on Outcomes in ECOG-ACRIN-E5103

Purpose: Racial disparity in breast cancer outcomes exists between African American and Caucasian women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for breast cancer patients in the context of a randomized, phase III adjuvant trial. Patients and Methods: This study compared outcomes between 386 patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary efficacy endpoint, invasive disease free survival (DFS) and clinically significant toxicities were compared including: anthracycline-induced congestive heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results: Overall, AAs had significantly inferior DFS (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (p=0.03); with a similar, non-significant trend for those who had triple negative breast cancer (TNBC; p=0.12). AAs also had significantly more grade 3-4 TIPN (OR=2.9; p=2.4 ×10-11) and grade 3-4 bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel (p=6.6 ×10-6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome (p=0.35). Conclusion: AAs had inferior DFS with more clinically important toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus centered on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions for paclitaxel, especially due to TIPN, are warranted for this population

Before the Pandemic Ends: Making Sure This Never Happens Again

Introduction On 30 January 2020, the World Health Organization (WHO) declared a Global Health Emergency of international concern attendant to the emergence and spread of SARS-CoV-2, nearly two months after the first reported emergence of human cases in Wuhan, China. In the subsequent two months, global, national and local health personnel and infrastructures have been overwhelmed, leading to suffering and death for infected people, and the threat of socio-economic instability and potential collapse for humanity as a whole. This shows that our current and traditional mode of coping, anchored in responses after the fact, is not capable of dealing with the crisis of emerging infectious disease. Given all of our technological expertise, why is there an emerging disease crisis, and why are we losing the battle to contain and diminish emerging diseases? Part of the reason is that the prevailing paradigm explaining the biology of pathogen-host associations (coevolution, evolutionary arms races) has assumed that pathogens must evolve new capacities - special mutations – in order to colonize new hosts and produce emergent disease (e.g. Parrish and Kawaoka, 2005). In this erroneous but broadly prevalent view, the evolution of new capacities creates new opportunities for pathogens. Further, given that mutations are both rare and undirected, the highly specialized nature of pathogen-host relationships should produce an evolutionary firewall limiting dissemination; by those definitions, emergences should be rare (for a historical review see Brooks et al., 2019). Pathogens, however, have become far better at finding us than our traditional understanding predicts. We face considerable risk space for pathogens and disease that directly threaten us, our crops and livestock – through expanding interfaces bringing pathogens and hosts into increasing proximity, exacerbated by environmental disruption and urban density, fueled by globalized trade and travel. We need a new paradigm that explains what we are seeing. Additional section headers: The Stockholm Paradigm The DAMA Protocol A Sense of Urgency and Long-Term Commitment Reference

Charcot-Marie-Tooth gene, SBF2, associated with taxaneinduced peripheral neuropathy in African Americans

PURPOSE: Taxane-induced peripheral neuropathy (TIPN) is one of the most important survivorship issues for cancer patients. African Americans (AA) have previously been shown to have an increased risk for this toxicity. Germline predictive biomarkers were evaluated to help identify a priori which patients might be at extraordinarily high risk for this toxicity. EXPERIMENTAL DESIGN: Whole exome sequencing was performed using germline DNA from 213 AA patients who received a standard dose and schedule of paclitaxel in the adjuvant, randomized phase III breast cancer trial, E5103. Cases were defined as those with either grade 3-4 (n=64) or grade 2-4 (n=151) TIPN and were compared to controls (n=62) that were not reported to have experienced TIPN. We retained for analysis rare variants with a minor allele frequency <3% and which were predicted to be deleterious by protein prediction programs. A gene-based, case-control analysis using SKAT was performed to identify genes that harbored an imbalance of deleterious variants associated with increased risk of TIPN. RESULTS: Five genes had a p-value < 10-4 for grade 3-4 TIPN analysis and three genes had a p-value < 10-4 for the grade 2-4 TIPN analysis. For the grade 3-4 TIPN analysis, SET binding factor 2 (SBF2) was significantly associated with TIPN (p-value=4.35 x10-6). Five variants were predicted to be deleterious in SBF2. Inherited mutations in SBF2 have previously been associated with autosomal recessive, Type 4B2 Charcot-Marie-Tooth (CMT) disease. CONCLUSION: Rare variants in SBF2, a CMT gene, predict an increased risk of TIPN in AA patients receiving paclitaxel

Breakthrough Capability for the NASA Astrophysics Explorer Program: Reaching the Darkest Sky

We describe a mission architecture designed to substantially increase the science capability of the NASA Science Mission Directorate (SMD) Astrophysics Explorer Program for all AO proposers working within the near-UV to far-infrared spectrum. We have demonstrated that augmentation of Falcon 9 Explorer launch services with a 13 kW Solar Electric Propulsion (SEP) stage can deliver a 700 kg science observatory payload to extra-Zodiacal orbit. This new capability enables up to ~13X increased photometric sensitivity and ~160X increased observing speed relative to a Sun- Earth L2, Earth-trailing, or Earth orbit with no increase in telescope aperture. All enabling SEP stage technologies for this launch service augmentation have reached sufficient readiness (TRL-6) for Explorer Program application in conjunction with the Falcon 9. We demonstrate that enabling Astrophysics Explorers to reach extra-zodiacal orbit will allow this small payload program to rival the science performance of much larger long development time systems; thus, providing a means to realize major science objectives while increasing the SMD Astrophysics portfolio diversity and resiliency to external budget pressure. The SEP technology employed in this study has strong applicability to SMD Planetary Science community-proposed missions. SEP is a stated flight demonstration priority for NASA's Office of the Chief Technologist (OCT). This new mission architecture for astrophysics Explorers enables an attractive realization of joint goals for OCT and SMD with wide applicability across SMD science disciplines