Generalized high-order iterative methods for solutions of nonlinear systems and their applications

In this paper, we have constructed a family of three-step methods with sixth-order convergence and a novel approach to enhance the convergence order $p$ of iterative methods for systems of nonlinear equations. Additionally, we propose a three-step scheme with convergence order $p+3$ (for $p\geq3$) and have extended it to a generalized $(m+2)$-step scheme by merely incorporating one additional function evaluation, thus achieving convergence orders up to $p+3m$, $m\in\mathbb{N}$. We also provide a thorough local convergence analysis in Banach spaces, including the convergence radius and uniqueness results, under the assumption of a Lipschitz-continuous Fréchet derivative. Theoretical findings have been validated through numerical experiments. Lastly, the performance of these methods is showcased through the analysis of their basins of attraction and their application to systems of nonlinear equations

An overview of airborne measurement in Nepal – Part 1: Vertical profile of aerosol size, number, spectral absorption, and meteorology

The paper provides an overview of an airborne measurement campaign with a microlight aircraft over the Pokhara Valley region, Nepal, a metropolitan region in the central Himalayan foothills. This is the first aerial measurement in the central Himalayan foothill region, one of the polluted but relatively poorly sampled regions of the world. Conducted in two phases (in May 2016 and December 2016–January 2017), the goal of the overall campaign was to quantify the vertical distribution of aerosols over a polluted mountain valley in the Himalayan foothills, as well as to investigate the extent of regional transport of emissions into the Himalayas. This paper summarizes results from the first phase where test flights were conducted in May 2016 (pre-monsoon), with the objective of demonstrating the potential of airborne measurements in the region using a portable instrument package (size with housing case: 0.45 m × 0.25 m × 0.25 m, 15 kg) onboard an ultralight aircraft (IKARUS-C42). A total of five sampling test flights were conducted (each lasting for 1–1.5 h) in the Pokhara Valley to characterize vertical profiles of aerosol properties such as aerosol number and size distribution (0.3–2 µm), total particle concentration (>14 nm), aerosol absorption (370–950 nm), black carbon (BC), and meteorological variables. Although some interesting observations were made during the test flight, the study is limited to a few days (and only a few hours of flight in total) and thus the analysis presented may not represent the entire pollution–meteorology interaction found in the Pokhara Valley. The vertical profiles of aerosol species showed decreasing concentrations with altitude (815 to 4500 m a.s.l.); a steep concentration gradient below 2000 m a.s.l. in the morning; and mixed profiles (up to ca. 4000 m a.s.l.) in the afternoon. The near-surface (<1000 m a.s.l.) BC concentrations observed in the Pokhara Valley were much lower than pre-monsoon BC concentrations in the Kathmandu Valley, and similar in range to Indo-Gangetic Plain (IGP) sites such as Kanpur in India. The sampling test flight also detected an elevated polluted aerosol layer (around 3000 m a.s.l.) over the Pokhara Valley, which could be associated with the regional transport. The total aerosol and black carbon concentration in the polluted layer was comparable with the near-surface values. The elevated polluted layer was also characterized by a high aerosol extinction coefficient (at 550 nm) and was identified as smoke and a polluted dust layer. The observed shift in the westerlies (at 20–30∘ N) entering Nepal during the test flight period could be an important factor for the presence of elevated polluted layers in the Pokhara Valle

Changes to the World Health Organization guideline on hormonal contraceptive eligibility for women at high risk of HIV: South African perspective and response

The World Health Organization (WHO) published guidelines for hormonal contraceptive eligibility for women at high risk of HIV in March 2017. This guidance followed from a technical consultative meeting convened by the WHO in December 2016, where all the available evidence on hormonal contraceptives and risk of HIV acquisition was reviewed. This was an expert meeting with representation from global experts in family planning and HIV management, including clinicians, epidemiologists, researchers and civil society. The guideline development group, through a consensus, made recommendations to change the medical eligibility criteria for contraceptive use from category 1 to category 2 for progestogen-only injectable contraceptives among women at high risk of HIV. There was no change in the recommendation for all other methods of hormonal contraception. The data that informed this decision are from observational studies, which have limitations; therefore, causality or association of hormonal contraception and risk of HIV acquisition have not been proven. This guidance will have an impact on countries that have a high HIV disease burden and where progestogen-only injectable contraceptives are the highest used, as in South Africa (SA). The information has to be communicated in line with the WHO’s sexual and reproductive health rights principles of ensuring that all women should receive evidence-based recommendations. This will empower them to make informed choices about their reproductive needs. This article seeks to clarify the decision-making process of the WHO and how the new recommendations were formulated. It also gives SA’s response to the guidance and a perspective of what informed the National Department of Health’s position, taking into account the effect this will have on SA’s contraceptive guidelines

Changes to the World Health Organization guideline on hormonal contraceptive eligibility for women at high risk of HIV: South African perspective and response

The World Health Organization (WHO) published guidelines for hormonal contraceptive eligibility for women at high risk of HIV in March 2017. This guidance followed from a technical consultative meeting convened by the WHO in December 2016, where all the available evidence on hormonal contraceptives and risk of HIV acquisition was reviewed. This was an expert meeting with representation from global experts in family planning and HIV management, including clinicians, epidemiologists, researchers and civil society. The guideline development group, through a consensus, made recommendations to change the medical eligibility criteria for contraceptive use from category 1 to category 2 for progestogen-only injectable contraceptives among women at high risk of HIV. There was no change in the recommendation for all other methods of hormonal contraception. The data that informed this decision are from observational studies, which have limitations; therefore, causality or association of hormonal contraception and risk of HIV acquisition have not been proven. This guidance will have an impact on countries that have a high HIV disease burden and where progestogen-only injectable contraceptives are the highest used, as in South Africa (SA). The information has to be communicated in line with the WHO’s sexual and reproductive health rights principles of ensuring that all women should receive evidence-based recommendations. This will empower them to make informed choices about their reproductive needs. This article seeks to clarify the decision-making process of the WHO and how the new recommendations were formulated. It also gives SA’s response to the guidance and a perspective of what informed the National Department of Health’s position, taking into account the effect this will have on SA’s contraceptive guidelines

Observation and analysis of spatiotemporal characteristics of surface ozone and carbon monoxide at multiple sites in the Kathmandu Valley, Nepal

Residents of the Kathmandu Valley experience severe particulate and gaseous air pollution throughout most of the year, even during much of the rainy season. The knowledge base for understanding the air pollution in the Kathmandu Valley was previously very limited but is improving rapidly due to several field measurement studies conducted in the last few years. Thus far, most analyses of observations in the Kathmandu Valley have been limited to short periods of time at single locations. This study extends the past studies by examining the spatial and temporal characteristics of two important gaseous air pollutants (CO and O3) based on simultaneous observations over a longer period at five locations within the valley and on its rim, including a supersite (at Bode in the valley center, 1345&thinsp;m above sea level) and four satellite sites: Paknajol (1380&thinsp;m&thinsp;a.s.l.) in the Kathmandu city center; Bhimdhunga (1522&thinsp;m&thinsp;a.s.l.), a mountain pass on the valley's western rim; Nagarkot (1901&thinsp;m&thinsp;a.s.l.), another mountain pass on the eastern rim; and Naikhandi (1233&thinsp;m&thinsp;a.s.l.), near the valley's only river outlet. CO and O3 mixing ratios were monitored from January to July 2013, along with other gases and aerosol particles by instruments deployed at the Bode supersite during the international air pollution measurement campaign SusKat-ABC (Sustainable Atmosphere for the Kathmandu Valley – endorsed by the Atmospheric Brown Clouds program of UNEP). The monitoring of O3 at Bode, Paknajol and Nagarkot as well as the CO monitoring at Bode were extended until March 2014 to investigate their variability over a complete annual cycle. Higher CO mixing ratios were found at Bode than at the outskirt sites (Bhimdhunga, Naikhandi and Nagarkot), and all sites except Nagarkot showed distinct diurnal cycles of CO mixing ratio, with morning peaks and daytime lows. Seasonally, CO was higher during premonsoon (March–May) season and winter (December–February) season than during monsoon season (June–September) and postmonsoon (October–November) season. This is primarily due to the emissions from brick industries, which are only operational during this period (January–April), as well as increased domestic heating during winter, and regional forest fires and agro-residue burning during the premonsoon season. It was lower during the monsoon due to rainfall, which reduces open burning activities within the valley and in the surrounding regions and thus reduces sources of CO. The meteorology of the valley also played a key role in determining the CO mixing ratios. The wind is calm and easterly in the shallow mixing layer, with a mixing layer height (MLH) of about 250&thinsp;m, during the night and early morning. The MLH slowly increases after sunrise and decreases in the afternoon. As a result, the westerly wind becomes active and reduces the mixing ratio during the daytime. Furthermore, there was evidence of an increase in the O3 mixing ratios in the Kathmandu Valley as a result of emissions in the Indo-Gangetic Plain (IGP) region, particularly from biomass burning including agro-residue burning. A top-down estimate of the CO emission flux was made by using the CO mixing ratio and mixing layer height measured at Bode. The estimated annual CO flux at Bode was 4.9&thinsp;µg&thinsp;m−2&thinsp;s−1, which is 2–14 times higher than that in widely used emission inventory databases (EDGAR HTAP, REAS and INTEX-B). This difference in CO flux between Bode and other emission databases likely arises from large uncertainties in both the top-down and bottom-up approaches to estimating the emission flux. The O3 mixing ratio was found to be highest during the premonsoon season at all sites, while the timing of the seasonal minimum varied across the sites. The daily maximum 8&thinsp;h average O3 exceeded the WHO recommended guideline of 50&thinsp;ppb on more days at the hilltop station of Nagarkot (159 out of 357 days) than at the urban valley bottom sites of Paknajol (132 out of 354 days) and Bode (102 out of 353 days), presumably due to the influence of free-tropospheric air at the high-altitude site (as also indicated by Putero et al., 2015, for the Paknajol site in the Kathmandu Valley) as well as to titration of O3 by fresh NOx emissions near the urban sites. More than 78&thinsp;% of the exceedance days were during the premonsoon period at all sites. The high O3 mixing ratio observed during the premonsoon period  is of a concern for human health and ecosystems, including agroecosystems in the Kathmandu Valley and surrounding regions.</p

The COVID-19 pandemic in Nepal: Emerging evidence on the effectiveness of action by, and cooperation between, different levels of government in a federal system

A new coronavirus disease (COVID-19) caused by a novel pathogen (SARS-CoV-2) spread rapidly around the world in the early months of 2020, and was declared a pandemic by the World Health Organization (WHO) on 11 March. COVID-19 has, and continues to have, large implications for individuals, societies, and for national health systems across the globe. Due to its novelty and impact, it has challenged all health care systems where the virus has taken hold. The ways in which governments and health systems have responded have varied widely across the world. In the case of Nepal, the pandemic represented a major test for the newly decentralised health system, created as a result of the implementation of the 2015 federal constitution. This paper, which forms a part of our large on-going study of the decentralisation of the health system in the country, presents some of the early evidence on the effectiveness of the actions taken by Federal, Provincial and Local Governments and the levels of cooperation and coordination between them

Target attainment with continuous dosing of piperacillin/tazobactam in critical illness:A prospective observational study

Optimal dosing of β-lactam antibiotics in critically ill patients is a challenge given the unpredictable pharmacokinetic profile of this patient population. Several studies have shown intermittent dosing to often yield inadequate drug concentrations. Continuous dosing is an attractive alternative from a pharmacodynamic point of view. This study evaluated whether, during continuous dosing, piperacillin concentrations reached and maintained a pre-defined target in critically ill patients. Adult patients treated with piperacillin by continuous dosing in the intensive care unit of a university medical centre in The Netherlands were prospectively studied. Total and unbound piperacillin concentrations drawn at fixed time points throughout the entire treatment course were determined by liquid chromatography-tandem mass spectrometry. A pharmacokinetic combined target of a piperacillin concentration ≥80 mg/L, reached within 1 h of starting study treatment AND maintained throughout the treatment course, was set. Eighteen patients were analysed. The median duration of monitored piperacillin treatment was 60 h (interquartile range, 33-96 h). Of the 18 patients, 5 (27.8 %) reached the combined target; 15 (83.3%) reached and maintained a less strict target of >16 mg/L. In this patient cohort, this dosing schedule was insufficient to reach the pre-defined target. Depending on which target is to be met, a larger initial cumulative dose is desirable, combined with therapeutic drug monitoring

Impact of rituximab biosimilars on overall survival in diffuse large B-cell lymphoma:a Dutch population-based study

In 2017, the European Medicines Agency approved rituximab biosimilars (R-biosimilars) for treatment of diffuse large B-cell lymphoma (DLBCL). Thereafter, the Netherlands was one of the first countries to implement R-biosimilars, given lower costs compared with rituximab originator (R-originator). This study's objective was to investigate whether overall survival (OS) of patients with DLBCL receiving R-biosimilars is similar to patients treated with R-originator. DLBCL patients ≥18 years, diagnosed between 2014 and 2018, who received at least 1 cycle of rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) were identified in the Netherlands Cancer Registry. Patients were categorized into R-originator or R-biosimilars groups based on data from a central repository of the Dutch medicinal drug market. The primary end point was 3-year OS, defined as the time between diagnosis and all-cause death. By the end of 2018, 91% of purchased rituximab were biosimilars. In total, 4429 patients were identified with 876 in the R-biosimilars group and 3553 in the R-originator group. Patients in the R-biosimilars group less frequently received .6 cycles of R-CHOP compared with patients treated with R-originator (24% vs 30%, P 5 .003). The 3-year OS did not differ between patients treated with R-originator or R-biosimilars (73% vs 73%, P = .855). This was confirmed with a multivariable Cox regression analysis accounting for sex, age, International Prognostic Index score, and number of R-CHOP cycles. In conclusion, the 3-year OS is similar for patients treated with CHOP in combination with R-originator or R-biosimilars and, therefore, favors the use of R-biosimilars in DLBCL treatment management