Search

Background: The administration of 5-fluorouracil (5FU) in the treatment of gastrointestinal (GI) malignancies is associated with common side effects such as mucositis, diarrhoea, and myelosuppression, which are easily managed with supportive measures and dose adjustments. Cardiotoxicity and neurotoxicity are rare but reversible side effects of 5-FU and are treated with withdrawal of the drug and conservative measures. The presenting symptoms of 5-FU-induced leukoencephalopathy are often confusing and pose a diagnostic dilemma in routine clinical practice. Methods: We report a series of five patients with GI malignancies who developed 5-FU-induced leukoencephalopathy. Results: All (n = 5) had Naranjo scores of 6–7, predictive of 5-FU-related adverse effects, with clinical and radiological findings suggestive of 5-FU-induced encephalopathy as described in prior literature. The median time to onset of symptoms from initiation of 5FU was 3 days (range: 2–4 days). All patients improved after conservative management with complete neurological recovery. Conclusion: Prompt recognition of this rare yet severe adverse effect of 5-FU-based chemotherapy aids early withdrawal of the offending agent (5-FU) and timely initiation of supportive measures and helps plan alternative oncological interventions. [ABSTRACT FROM AUTHOR]

The ketogenic diet (KD) is a type of diet in which the intake of fats significantly increases at the cost of carbohydrates while maintaining an adequate amount of proteins. This kind of diet has been successfully used in clinical therapies of drug-resistant epilepsy, but there is still insufficient evidence on its safety when used in pregnancy. To assess KD effects on the course of gestation and fetal development, pregnant females were fed with: (i) KD during pregnancy and lactation periods (KD group), (ii) KD during pregnancy replaced with ND from the day 2 postpartum (KDND group) and (iii) normal diet alone (ND group). The body mass, ketone and glucose blood levels, and food intake were monitored. In brains of KD-fed females, FTIR biochemical analyses revealed increased concentrations of lipids and ketone groups containing molecules. In offspring of these females, significant reduction of the body mass and delays in neurological development were detected. However, replacement of KD with ND in these females at the beginning of lactation period led to regainment of the body mass in their pups as early as on the postnatal day 14. Moreover, the vast majority of our neurological tests detected functional recovery up to the normal level. It could be concluded that the ketogenic diet undoubtedly affects the brain of pregnant females and impairs the somatic and neurological development of their offspring. However, early postnatal withdrawal of this diet may initiate compensatory processes and considerable functional restitution of the nervous system based on still unrecognized mechanisms. [ABSTRACT FROM AUTHOR]

Purpose: Paclitaxel plus ramucirumab is a standard second-line regimen for patients with advanced gastric adenocarcinoma, but clinical benefit remains modest. One potential resistance mechanism to VEGFR2 inhibition is activation of the PDGF/PDGFR pathway, which can be blocked by the selective inhibitor crenolanib. Therefore, we performed a phase I/Ib study of crenolanib in combination with paclitaxel/ramucirumab. Methods: Patients with metastatic esophagogastric adenocarcinoma refractory to first-line therapy received escalating doses of crenolanib [60 mg twice daily (BID) to 100 mg three times daily (TID)] in combination with paclitaxel 80 mg/m2 intravenously on days 1, 8 and 15 and ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary objective was to determine the maximally tolerated dose (MTD) of crenolanib. Additional patients were enrolled in the dose expansion cohort to assess 6-month progression-free survival (PFS) at the MTD. Results: We enrolled 19 patients in the dose escalation phase and 8 patients in the dose expansion phase at the MTD of crenolanib 100 mg BID. Common grade 3/4 treatment-emergent adverse events included leukopenia (19%), anemia (11%) and neutropenia (11%). In the 14 patients treated at the MTD, 6-month PFS was 43% [95% confidence interval (CI) 23–78%] and the objective response rate (ORR) was 42% (95% CI 15–72%). The trial was terminated early due to withdrawal of crenolanib by the sponsor. Conclusions: The addition of crenolanib to paclitaxel/ramucirumab is safe and well-tolerated at a dose level up to 100 mg BID. Clinical trial registration: NCT03193918. June 19, 2017. [ABSTRACT FROM AUTHOR]

Model simulations are highly sensitive to the formulation of the atmospheric mixing process or entrainment in the deep convective parameterizations used in their atmospheric component. In this paper, we have implemented stochastic entrainment in the deep convection scheme of NCAR CAM5 and analyzed the improvements in model simulation, focusing on the South Asian Summer Monsoon (SASM), as compared to the deterministic entrainment formulation in the default version of the model. Simulations using stochastic entrainment (StochCAM5) outperformed default model simulations (DefCAM5), as inferred from multiple metrics associated with the SASM. StochCAM5 significantly alleviated some of the longstanding SASM biases seen in DefCAM5, such as precipitation pattern and magnitude over the Arabian Sea and western Equatorial Indian ocean, early monsoon withdrawal, and the overestimation in the frequency of light precipitation and the underestimation in the frequency of large-to-extreme precipitation. Related SASM dynamical and thermodynamical features, such as Somali Jet, low-level westerly winds, and meridional tropospheric temperature gradient (MTTG), are improved in StochCAM5. Further, the simulation of monsoon intra-seasonal oscillation (MISO), Madden Julian Oscillation (MJO), and equatorial Kelvin waves are improved in StochCAM5. Many essential climate variables, such as shortwave and longwave cloud forcing, cloud cover, relative and specific humidity, and precipitable water, show significant improvement in StochCAM5. [ABSTRACT FROM AUTHOR]

In recent years, there has been an increasing concern about non-governmental development organisations' (NGDOs) sustainability especially in countries including Ghana that have transitioned into lower-middle-income status. The effect has been donor withdrawal and funding cuts for NGDOs. This presents opportunities and challenges for NGDOs in their attempt to mobilise alternative funding routes in ensuring their sustainability. Drawing on secondary literature and semi-structured interviews with fifty-seven respondents from national NGDOs, government, donors and corporate organisations, this article documents and expands our understanding of the different typologies of philanthropic institutions in Ghana as potential alternative funding routes for NGDOs. It finds that a weak enabling environment including the absence of a regulatory framework and fiscal incentives for domestic resource mobilisation stands to affect the potential of philanthropic institutions as alternative funding routes for NGDOs' sustainability. [ABSTRACT FROM AUTHOR]

This paper provides evidence on the wealth effect in the event of the withdrawal of a merger or acquisition, and the impact of termination fee provisions on acquirer withdrawal returns. I report a significant negative correlation between acquirer withdrawal returns and announcement returns, consistent with the theory of managerial learning in M&As. Target firms reap net gains in deal withdrawals, showing evidence of a permanent revaluation of targets even if the deals fail. I also find that acquirer termination fee provisions are positively associated with acquirer withdrawal returns, suggesting that such provisions may play a disciplinary role in the withdrawal decision-making and protect acquirer shareholders' interests in deal withdrawals. Furthermore, my results also show that target termination fee provisions are negatively associated with acquirer withdrawal returns, which supports the efficiency hypothesis. [ABSTRACT FROM AUTHOR]

We examine the volatility of overall withdrawal demands in banking using a model allowing for correlation between individual withdrawal demands. We derive various volatility and elasticity results which show the effects of correlated withdrawals in setting precautionary reserves. We discuss the implications of this analysis for fractional reserve banking. [ABSTRACT FROM AUTHOR]