Polymeric nanoparticles produced by electrohydrodynamic atomisation for the passive delivery of imatinib.

Imatinib is a chemotherapeutic agent known to cause severe side effects when administrated systemically. Encapsulating imatinib in co-polymer poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) offers a targeted drug delivery. In this work, PLGA 50:50 and PLGA 75:25 NPs encapsulated imatinib using the electrohydrodynamic atomisation technique. All particles generated were spherical with a smooth surface with a size distribution of 455±115 nm (PLGA 50:50) and 363±147 nm (PLGA 75:25). Encapsulation of imatinib was shown to be higher than 75 % and was shown to increase the zeta potential of the loaded NPs. The release of imatinib showed an initial burst in the first 12 h, and different sustained releases were up to 70 %. Both types of imatinib-loaded NPs' effect on cell viability and their cellular uptake were also studied on A549 cells, and the antiproliferative effect was comparable to that of cells treated with free drugs. Finally, Rhodamine-B-loaded NP-treated cells demonstrated the cellular uptake of NPs.

Private management costs of Popillia japonica: a study of viticulture in Italy.

The Japanese beetle (Popillia japonica) is classified as a high-priority pest in the European Union and is reported to have caused extensive damage to grapevine leaves in Italy. As there are few studies, which measure the beetle's socio-economic impact, we conduct a first descriptive assessment of grapevine farmers' perception of the beetle's impact and assess the pest's effect on private management costs using a partial budgeting approach. Our sample includes data from 65 producers and 118 vineyard plots. In terms of farmers' perception, we find that farmers anticipate increased management costs and believe a further spread of the beetle will lead to at least moderate yield and quality damages for the majority of plots (58-91%). While farmers do not expect to stop grapevine cultivation for the majority of vineyard plots, affected farmers they believe it is likely to very likely for 29% of plots. We also find that affected farmers rate their vines' resilience higher than unaffected farmers do. Using a partial budgeting approach, we find that a Japanese beetle infestation leads on average to a net income decrease of around €2727 per hectare. This decrease is due to an average increase in labor costs of around €1715. Additionally, an average yield reduction that results in a revenue loss of around €966 and additional control costs of around €47 per infested hectare, further contribute to the net income decrease. Even though the small number of observations does not allow us to make conclusions about the beetle's impact on the Italian viticulture sector as a whole, our findings provide first insights and demonstrate the need for environmentally friendly and effective control products that can replace labor-intensive manual control measures, which are currently applied in Japanese beetle infested vineyards.

Intravenous prostanoids in systemic sclerosis-associated pulmonary arterial hypertension: a single-centre experience.

OBJECTIVES: The current study evaluates survival rates among SSc-associated pulmonary arterial hypertension (SSc-PAH) patients on i.v. prostanoids, and short-term impact of i.v. prostanoids on clinical and haemodynamic parameters. METHODS: Baseline demographics, invasive and non-invasive data, European Society of Cardiology (ESC) score and REVEAL score of 81 SSc-PAH patients (median age 61 years, interquartile range 54-67 years, 84% females) were prospectively recorded, from November 2006 till November 2020, before initiation of i.v. prostanoids, and at first formal reassessment. Survival data were retrieved from National Health Service Spine and hospital databases. RESULTS: Significant improvements in clinical and haemodynamic parameters in response to i.v. prostanoid therapy were documented. Functional class (FC) (16.6% improved by 1FC, P =0.041), mean pulmonary arterial pressure (-6.5 mmHg, P =0.036), pulmonary vascular resistance (-2.6 WU, P =0.012), cardiac index (Q/m2) (+0.7 l/min/m2, P =0.003) and mixed venous oxygen saturation (SvO2) (+3%, P =0.036) improved. Estimated survival for CTD-PAH patients on i.v. prostanoids was 64%, 31% and 18%, at 1 year, 3 years and 5 years, respectively. Independent baseline predictors of mortality were older age (HR: 1.043, 95% CI: 1.011-1.075, P =0.007), higher N-terminal pro-brain natriuretic peptide levels (HR: 2.191, 95% CI: 1.131-4.243, P =0.020), and lower SvO2 levels (HR: 0.962, 95% CI: 0.926-0.998, P =0.039). High ESC risk or high and very high REVEAL score was associated with significantly worse survival compared with patients with lower risk scores, both at baseline and when reassessed after a median of 6.5 months. CONCLUSIONS: Survival among SSc-PAH patients on i.v. prostanoids remains poor, risk scoring at baseline and after 6.5 months of therapy improves prognostication.

Real-world challenges for patients with breast cancer in sub-Saharan Africa: a retrospective observational study of access to care in Ghana, Kenya and Nigeria.

OBJECTIVE: To evaluate medical resource utilisation and timeliness of access to specific aspects of a standard care pathway for breast cancer at tertiary centres in sub-Saharan Africa. DESIGN: Data were retrospectively abstracted from records of patients with breast cancer treated within a prespecified 2-year period between 2014 and 2017. The study protocol was approved by local institutional review boards. SETTING: Six tertiary care institutions in Ghana, Kenya and Nigeria were included. PARTICIPANTS: Health records of 862 patients with breast cancer were analysed: 299 in Ghana; 314 in Kenya; and 249 in Nigeria. INTERVENTIONS: As directed by the treating physician. OUTCOME MEASURES: Parameters selected for evaluation included healthcare resource and use, medical procedure turnaround times and out-of-pocket (OOP) payment patterns. RESULTS: Use of mammography or breast ultrasonography was <45% in all three countries. Across the three countries, 78%-88% of patients completed tests for hormone receptors and human epidermal growth factor receptor 2 (HER2). Most patients underwent mastectomy (64%-67%) or breast-conserving surgery (15%-26%). Turnaround times for key procedures, such as pathology, surgery and systemic therapy, ranged from 1 to 5 months. In Ghana and Nigeria, most patients (87%-93%) paid for diagnostic tests entirely OOP versus 30%-32% in Kenya. Similarly, proportions of patients paying OOP only for treatments were high: 45%-79% in Ghana, 8%-20% in Kenya and 72%-89% in Nigeria. Among patients receiving HER2-targeted therapy, the average number of cycles was five for those paying OOP only versus 14 for those with some insurance coverage. CONCLUSIONS: Patients with breast cancer treated in tertiary facilities in sub-Saharan Africa lack access to timely diagnosis and modern systemic therapies. Most patients in Ghana and Nigeria bore the full cost of their healthcare and were more likely to be employed and have secondary or postsecondary education. Access to screening/diagnosis and appropriate care is likely to be substantively lower for the general population.

Simultaneous feedback control for joint field and motion correction in brain MRI.

T2*-weighted gradient-echo sequences count among the most widely used techniques in neuroimaging and offer rich magnitude and phase contrast. The susceptibility effects underlying this contrast scale with B0, making T2*-weighted imaging particularly interesting at high field. High field also benefits baseline sensitivity and thus facilitates high-resolution studies. However, enhanced susceptibility effects and high target resolution come with inherent challenges. Relying on long echo times, T2*-weighted imaging not only benefits from enhanced local susceptibility effects but also suffers from increased field fluctuations due to moving body parts and breathing. High resolution, in turn, renders neuroimaging particularly vulnerable to motion of the head. This work reports the implementation and characterization of a system that aims to jointly address these issues. It is based on the simultaneous operation of two control loops, one for field stabilization and one for motion correction. The key challenge with this approach is that the two loops both operate on the magnetic field in the imaging volume and are thus prone to mutual interference and potential instability. This issue is addressed at the levels of sensing, timing, and control parameters. Performance assessment shows the resulting system to be stable and exhibit adequate loop decoupling, precision, and bandwidth. Simultaneous field and motion control is then demonstrated in examples of T2*-weighted in vivo imaging at 7T.

Feedback field control improves the precision of T2 * quantification at 7 T.

T2 * mapping offers access to a number of important structural and physiological tissue parameters. It is robust against RF field variations and overall signal scaling. However, T2 * measurement is highly sensitive to magnetic field errors, including perturbations caused by breathing motion at high baseline field. The goal of this work is to assess this issue in T2 * mapping of the brain and to study the benefit of field stabilization by feedback field control. T2 * quantification in the brain was investigated by phantom and in vivo measurements at 7 T. Repeated measurements were made with and without feedback field control using NMR field sensing and dynamic third-order shim actuation. The precision and reliability of T2 * quantification was assessed by studying variation across repeated measurements as well as fitting errors. Breathing effects were found to introduce significant error in T2 * mapping results. Field control mitigates this problem substantially. In a phantom it virtually eliminates the effects of emulated breathing fluctuations in the head. In vivo it enhances the structural fidelity of T2 * maps and reduces fitting residuals along with standard deviation. In conclusion, feedback field control improves the fidelity of T2 * mapping in the presence of field perturbations. It is an effective means of countering bulk susceptibility effects of breathing and hence holds particular promise for efforts to leverage high field for T2 * studies in vivo.

Clinical characteristics, haemodynamics and treatment of pulmonary hypertension in sarcoidosis in a single centre, and meta-analysis of the published data.

Pulmonary hypertension (PH) in sarcoidosis is associated with bad outcomes. Although there is interest in using pulmonary vasodilators (PVs) for PH in sarcoidosis, there are few data to support their use. In this study, a retrospective review of a cohort of patients with PH and sarcoidosis was conducted, focusing on those treated with PVs, and a meta-analysis of published reports indexed in MEDLINE was performed. Twenty-four patients were found. The rate of mortality or transplantation rate was 41.2%. Median survival without transplantation was 5.3 years. More patients who died or underwent transplantation during follow-up had moderate or severe lung fibrosis (66.7% vs 15.4%), had right ventricular dysfunction (80% vs 7.7%), and were in World Health Organization class IV (66.7% vs 30.8%). Body surface areas were lower in patients with events, as was cardiac output. Mortality was not different between patients treated with PVs and those not treated (54.5% vs 38.5%, p = 0.44) despite the treated patients' having more right ventricular dysfunction and worse hemodynamics. In a Cox regression survival model, lower body surface area, right ventricular dysfunction, and the presence of moderate or severe lung fibrosis were predictors of worse outcomes, but not treatment with PVs. PV-treated patients (n = 11) showed improved 6-minute walk distances and decreased N-terminal pro-B-type natriuretic peptide levels during follow-up. There was a trend toward improvement in hemodynamic profile. Four studies plus the data from this study were included in the meta-analysis. Six-minute walk distance improved by 30.64 m after treatment. Hemodynamics improved, with a reduction in mean pulmonary arterial pressure of 8.03 mm Hg and a decrease in pulmonary vascular resistance of 4.23 Wood units. In conclusion, PH in sarcoidosis is associated with adverse outcomes, particularly when accompanied by right ventricular dysfunction and/or moderate or severe lung fibrosis. Treating selected patients can improve hemodynamics and functional parameters.