Modeling the impact of climate change on the hydrology of Andasa watershed

This paper was aimed to study the impact of climate change on the hydrology of Andasa watershed for the period 2013–2099. The soil and water assessment tool (SWAT) was calibrated and validated, and thereby used to study the impact of climate change on the water balance. The future climate change scenarios were developed using future climate outputs from the Hadley Center Climate Model version 3 (HadCM3) A2 (high) and B2 (low) emission scenarios and Canadian Earth System Model version 2 (CanESM2) Representative concentration pathways (RCP) 4.5 and 8.5 scenarios. The large-scale maximum/minimum temperature and rainfall data were downscaled to fine-scale resolution using the Statistical Downscaling Model (SDSM). The mean monthly temperature projection of the four scenarios indicated an increase by a range of 0.4–8.5 °C while the mean monthly rainfall showed both a decrease of up to 97% and an increase of up to 109%. The long-term mean of all the scenarios indicated an increasing temperature and decreasing rainfall trends. Simulations showed that climate change may cause substantial impacts in the hydrology of the watershed by increasing the potential evapotranspiration (PET) by 4.4–17.3% and decreasing streamflow and soil water by 48.8–95.6% and 12.7–76.8%, respectively. The findings suggested that climate change may cause moisture-constrained environments in the watershed, which may impact agricultural activities in the watershed. Appropriate agricultural water management interventions should be implemented to mitigate and adapt to the plausible impacts of climate change by conserving soil moisture and reducing evapotranspiration

Mechanism for deep crustal seismicity: Insight from modeling of deformation process at the Main Ethiopian Rift

We combine numerical modeling of lithospheric extension with analysis of seismic moment release and earthquake b-value in order to elucidate the mechanism for deep crustal seismicity and seismic swarms in the Main Ethiopian Rift (MER). We run 2-D numerical simulations of lithospheric deformation calibrated by appropriate rheology and extensional history of the MER to simulate migration of deformation from mid-Miocene border faults to ∼30 km wide zone of Pliocene to recent rift floor faults. While currently the highest strain rate is localized in a narrow zone within the rift axis, brittle strain has been accumulated in a wide region of the rift. The magnitude of deviatoric stress shows strong variation with depth. The uppermost crust deforms with maximum stress of 80 MPa, at 8–14 km depth stress sharply decreases to 10 MPa and then increases to a maximum of 160 MPa at ∼18 km depth. These two peaks at which the crust deforms with maximum stress of 80 MPa or above correspond to peaks in the seismic moment release. Correspondingly, the drop in stress at 8–14 km correlates to a low in seismic moment release. At this depth range, the crust is weaker and deformation is mainly accommodated in a ductile manner. We therefore see a good correlation between depths at which the crust is strong and elevated seismic deformation, while regions where the crust is weaker deform more aseismically. Overall, the bimodal depth distribution of seismic moment release is best explained by the rheology of the deforming crust

Pharmaceutical assistance programs for cancer patients in the era of orally administered chemotherapeutics

Introduction: The rising cost of cancer drugs may make treatment unaffordable for some patients. Patients often rely on drug manufacturer-administered Pharmaceutical Assistance Programs (PAPs) to obtain drugs and reduced or no cost. The overall usage of PAPs within cancer care delivery is unknown. Methods: We included all cancer patients across an academically affiliated, integrated health system in North Carolina during 2014 (N = 8591). We identified the subset of patients receiving PAP assistance to afford one or more cancer drugs, in order to calculate the proportion of patients receiving PAP assistance, and the retail value of the assistance. Results: Among 8591 cancer patients, 215 unique patients submitted a total of 478 successful PAP requests for cancer drugs. 40% of PAP-utilizing patients were uninsured, 23% had Medicaid coverage, 20% had Medicare coverage, 2% were dual Medicare/Medicaid eligible, and 14% were commercially insured. Among all cancer patients who received medical treatment, 6.0% required PAP assistance, whereas 10.6% receiving an oral agent required PAP assistance. The proportion receiving PAP assistance varied substantially by drug, ranging from <1% of patients (e.g. carboplatin, methotrexate) to 50% of patients (e.g. ponatinib, temsirolimus). The majority of the retail value obtained was for oral agents, including $1,556,575 of imatinib and$1,449,633 of dasatinib, which were the two drugs with the highest aggregate retail value. Conclusions: A substantial proportion of cancer patients receive private charitable assistance to obtain standard-of-care treatments. This includes patients with federal and private insurance, suggesting an inability of patients to meet cost-sharing requirements

Population Based Survey of Chronic Non-Communicable Diseases at Gilgel Gibe Field Research Center, Southwest Ethiopia

BACKGROUND: Chronic Non-communicable Diseases are increasingly becoming more prevalent and burden to the health care system in developing countries including Ethiopia. However, evidences showing the magnitude of the problem in those countries are scarce particularly in a community setting.The objective of this study was to determine the magnitude of chronic non communicable diseases in a community.METHODS: A population-based cross-sectional study was conducted in Gilgel Gibe Field Research Center from late September 2008 to end of January 2009. A random sample of 4,469 individuals aged 15-64 years was studied. Data on characteristics and chronic symptom inventories were collected by interviewing study participants. Blood pressure was taken three times from each individual and blood sugar and lipid levels were determined after an overnight fasting. Data were analyzed using SPSS for Windows version 16.0 and STATA 11.RESULTS: The overall prevalence of CNCD was 8.9% (7.8% men and 9.8% women). The specific observed prevalence were 0.5% for diabetes mellitus (DM), 2.6% for hypertension, 3.0% for cardiovascular diseases, 1.5% for asthma and 2.7% for mental illness. In addition 3.1% and 9.3% of the study population had been informed to have DM and hypertension respectively.CONCLUSION: There is a high prevalence of CNCD among the study population indicating an immediate need for preventive action and also warrant further nationally representative study.Keywords: CNCD, Non-communicable, Prevalence, Southwest Ethiopi

Aborted propagation of the Ethiopian rift caused by linkage with the Kenyan rift

International audienceContinental rift systems form by propagation of isolated rift segments that interact, and eventually evolve into continuous zones of deformation. This process impacts many aspects of rifting including rift morphology at breakup, and eventual ocean-ridge segmentation. Yet, rift segment growth and interaction remain enigmatic. Here we present geological data from the poorly documented Ririba rift (South Ethiopia) that reveals how two major sectors of the East African rift, the Kenyan and Ethiopian rifts, interact. We show that the Ririba rift formed from the southward propagation of the Ethiopian rift during the Pliocene but this propagation was short-lived and aborted close to the Pliocene-Pleistocene boundary. Seismicity data support the abandonment of laterally offset, overlapping tips of the Ethiopian and Kenyan rifts. Integration with new numerical models indicates that rift abandonment resulted from progressive focusing of the tectonic and magmatic activity into an oblique, throughgoing rift zone of near pure extension directly connecting the rift sectors

Impact of pregnancy related hormones on drug metabolizing enzyme and transport protein concentrations in human hepatocytes

Pregnancy alters the disposition and exposure to multiple drugs indicated for pregnancy-related complications. Previous in vitro studies have shown that pregnancy-related hormones (PRHs) alter the expression and function of certain cytochrome P450s (CYPs) in human hepatocytes. However, the impact of PRHs on hepatic concentrations of non-CYP drug-metabolizing enzymes (DMEs) and transport proteins remain largely unknown. In this study, sandwich-cultured human hepatocytes (SCHH) from five female donors were exposed to vehicle or PRHs (estrone, estradiol, estriol, progesterone, cortisol, and placental growth hormone), administered individually or in combination, across a range of physiologically relevant PRH concentrations for 72 h. Absolute concentrations of 33 hepatic non-CYP DMEs and transport proteins were quantified in SCHH membrane fractions using a quantitative targeted absolute proteomics (QTAP) isotope dilution nanoLC-MS/MS method. The data revealed that PRHs altered the absolute protein concentration of various DMEs and transporters in a concentration-, isoform-, and hepatocyte donor-dependent manner. Overall, eight of 33 (24%) proteins exhibited a significant PRH-evoked net change in absolute protein concentration relative to vehicle control (ANOVA p < 0.05) across hepatocyte donors: 1/11 UGTs (9%; UGT1A4), 4/6 other DMEs (67%; CES1, CES2, FMO5, POR), and 3/16 transport proteins (19%; OAT2, OCT3, P-GP). An additional 8 (24%) proteins (UGT1A1, UGT2B4, UGT2B10, FMO3, OCT1, MRP2, MRP3, ENT1) exhibited significant PRH alterations in absolute protein concentration within at least two individual hepatocyte donors. In contrast, 17 (52%) proteins exhibited no discernable impact by PRHs either within or across hepatocyte donors. Collectively, these results provide the first comprehensive quantitative proteomic evaluation of PRH effects on non-CYP DMEs and transport proteins in SCHH and offer mechanistic insight into the altered disposition of drug substrates cleared by these pathways during pregnancy

Response to Tyrosine Kinase Inhibitors in Real-World Patients With Chronic Myeloid Leukemia

Background: Tyrosine kinase inhibitors (TKIs) are the front-line therapy for chronic myeloid leukemia (CML), where phase 3 clinical trials have demonstrated their safety and efficacy. However, trial patients may not be representative of real-world patients (RWPs). Objective: To evaluate RWP clinical factors associated with effectiveness and safety in CML patients treated with TKIs. Methods: Patients with CML treated with at least 30 days of imatinib, dasatinib, nilotinib, or bosutinib between 2014 and 2018 were included. Patients were stratified into categories based on the number of factors that would have precluded enrollment into pivotal TKI phase 3 trials (0, 1, ≥2). End points included complete hematologic response (CHR), early molecular response (EMR), major molecular response (MMR), adverse event (AE)-induced dose decreases, treatment interruptions, and treatment discontinuations. Results: Final analyses included 174 patients. Patients with ≥2 factors had a higher risk of dose decreases (relative risk = 1.54; 95% CI = 1.02-2.34; P = 0.02) and a shorter time to dose decrease (hazard ratio = 2.43; 95% CI = 1.23-4.97; P = 0.006) compared with patients with 0 factors. Significant differences were observed in CHR at 1 month and MMR at 3 months between patients with 0 and ≥2 factors (P = 0.03 and P = 0.04, respectively). Conclusion and Relevance: Approximately 60% of our RWPs would have been excluded from the pivotal phase 3 TKI trials. These data suggest that RWPs require more precise dosing to achieve CML clinical milestones and to mitigate AEs, but findings should be validated prospectively

Structural Analysis of the Western Afar Margin, East Africa: Evidence for Multiphase Rotational Rifting

The Afar region in East Africa represents a key location to study continental breakup. We present an integrated structural analysis of the Western Afar Margin (WAM) aiming to better understand rifted margin development and the role of plate rotation during rifting. New structural information from remote sensing, fieldwork, and earthquake data sets reveals that the N-S striking WAM is still actively deforming and is characterized by NNW-SSE normal faulting as well as a series of marginal grabens. Seismicity distribution analysis and the first-ever borehole-calibrated sections of this developing passive margin show recent slip concentrated along antithetic faults. Tectonic stress parameters derived from earthquake focal mechanisms reveal different extension directions along the WAM (82°N), in Afar (66°N) and in the Main Ethiopian Rift (108°N). Fault slip analysis along the WAM yields the same extension direction. Combined with GPS data, this shows that current tectonics in Afar is dominated by the local rotation of the Danakil Block, considered to have occurred since 11 Ma. Earlier stages of Afar development (since 31–25 Ma) were most likely related to the large-scale rotation of the Arabian plate. Various authors have proposed scenarios for the evolution of the WAM. Any complete model should consider, among other factors, the multiphase tectonic history and antithetic fault activity of the margin. The findings of this study are not only relevant for a better understanding of the WAM but also provide insights into the role of multiphase rotational extension during rifting and passive margin formation in general.</p

Barriers and facilitators associated with implementing interventions to support oral anticancer agent adherence in academic and community cancer center settings

Purpose The goal of this study is to determine barriers and facilitators to the implementation of medication adherence interventions to support cancer patients taking novel, targeted oral anticancer agents (OAAs). Methods We conducted qualitative interviews using a semi-structured guide from the Consolidated Framework for Implementation Research (CFIR). We used purposive sampling to identify clinicians (physicians, pharmacists, nurse practitioners, nurses) and administrators (leadership from medicine, pharmacy, and nursing) who delivered care and/or oversee care delivery for patients with chronic leukemia prescribed an OAA. Results A total of 19 individuals participated in an interview (12 clinicians and 7 administrators), with 10 primarily employed by an academic cancer center; 5 employed by the community cancer center; and 4 employed by the integrated health-system specialty pharmacy. Barriers identified included low awareness of adherence interventions, difficulty in adherence measurement, complexity of designing and implementing a structured adherence intervention, and competing priorities. Facilitators identified included support of hospital administrators, value for pharmacists, and willingness to embrace change. Participants also made recommendations moving forward including standardizing workflow, designating champions, iterating implementation strategies, and improving communication between clinicians and with patients. Conclusion Individual and system level factors were identified as determinants of implementation effectiveness of medication adherence interventions. A multidisciplinary advisory panel will be assembled to design comprehensive and actionable strategies to refine and implement a structured intervention to improve medication adherence in cancer patients