Examining the Challenges and Opportunities of Managing Public Services in a Complex and Interconnected World

This research looks into the difficulties and potentials of public service management in today's increasingly complicated and interconnected world. Through a review of the literature and an examination of the available data, the authors of this study highlight the obstacles that public administration must overcome in order to advance social, economic, and environmental sustainability. Multilateral cooperation, stakeholder engagement, strategic planning, public-private partnerships, innovation and entrepreneurship, sustainable development, community engagement, inclusive policies, social safety nets, renewable energy, sustainable land use, disaster risk reduction, digitalization of services, smart infrastructure, and cybersecurity are all identified as opportunities and potential solutions in the study. Managing public services in today's fast-paced world is fraught with complex challenges, and this analysis emphasizes the need for holistic approaches that involve cooperation and innovation across sectors. Policymakers and researchers working to promote social, economic, and environmental sustainability in the public sector can benefit from this study's suggestions and consequences

Effect of tillage and fertiliser treatments on yield of maize (Zea mays L.) hybrids

This research was conducted in a spilt-plot design at the University of Debrecen Látókép Research Station, site (N 47°33’ E 21°27’) in 2015 and repeated in 2016. There were three main plots, each 1.0 ha in size which represents the tillage treatments: moldboard plowing (MT), strip tillage (ST) and ripper tillage (RT). Maize hybrids, Loupiac (FAO 380) and Armagnac(FAO 490) were sown at 80,000 plants ha−1 with a row spacing of 76 cm in the main plots which were subdivided to accommodate three fertiliser treatments (N0 kg ha−1 (control); N80 kg ha−1; N160 kg ha−1) with four replications. The hybrids were harvested at the end of the growing cycle with a Sampo 2010 plot harvester and the grain moisture content was computed at 15% moisture to arrive at the final yield. The findings revealed RT produced the highest yield of 10.37 t ha−1, followed by MT and ST with 10.22 and 9.60 t ha−1 respectively. There was no significant difference(p>0.05) in yield between the RT and MT treatments. However, both the RT and MT were found to be statistically significant (p<0.05) when compared to ST treatment. In 2015, a relatively dry year, yield of ST plots were not significantly different compared to MT and RT plots. A positive interaction between tillage and fertilisation was evident, with higher yield variation (CV=40.07) in the non-fertilised (N0) tillage plots, compared to those which received the N80 and N160 kg ha−1 treatments (CV=22.42). Fertilizer application greatly increased the yield of maize and accounted for 43% of yield variances. The highest yield (11.88 t ha−1) was obtained with N160 kg ha−1 treatment, followed by N80 kg ha−1 ( 10.83 t ha−1), while the lowest yield (7.48 t ha−1) was recorded in the nonfertilised plots(N0 kg ha−1). Year effect was highly significant with vast variation in yield between the two years, ranging from 8.36 t ha−1 in 2015 to 12.43 t ha−1 in 2016 for the same set of agrotechnical inputs. In 2016, higher yield was obtained with increase fertiliser dosage due to favourable growing condition which allowed for better fertiliser utilisation. However, with 2015 being a relatively dry year there was no yield increasing effect with higher fertiliser dosage ( N160 kg ha−1 ). Loupiac (FAO 380) was the better performing hybrid, with a yield of 11.09 t ha−1 compared Armagnac (FAO 490) with 10.60 t ha−1 . The adaptability traits of the two hybrids appears very similar, since the yield differential between the two hybrids was almost constant (0.48 vs 0.49) in both years , despite the vast variation in weather condition

Modulation of Signaling and Intracellular Trafficking Pathways by Surface-Engineered Hydrogel Nanoparticles in Tumor Cells.

Surface engineering of a polyacrylamide (PAA) hydrogel nanoparticle (NP) with the tumor-targeting ligand, F3 peptide (KDEPQRRSARLSAKPAPPKPEPKPKKAPAKKC), confers binding specificity toward Nucleolin overexpressing tumor cells (9L rat gliosarcoma, and MDA-MB-435 human breast adenocarcinoma). In this study, the endocytic internalization, and intracellular trafficking of the non-targeted PAA-NPs (NTNPs), and F3-targeted PAA-NPs (F3NPs) in the above-mentioned cell lines, was investigated. Caveolae-mediated internalization of both types of PAA-NPs peaked at 2 hours post-delivery, although internalization of the NTNPs was ~2-fold greater than for the F3NPs. In contrast, clathrin-mediated internalization of both types of PAA-NPs was markedly faster; the NTNPs and F3NPs both reached similar peak colocalization levels with early endosome antigen-1 (EEA1, ~32%) at 30 minutes post-delivery. However, at 60 minutes post-delivery, the NTNPs exhibited faster egress from the early endosomes than the F3NPs, with a concomitant, sharp increase in trafficking to the lysosomes (acidic, degradative vesicles), whereas the F3NPs largely evaded trafficking to the lysosomes. Furthermore, the F3 peptides alone exhibited significantly higher accumulation within the lysosomes than both the NTNPs, and the F3NPs. The p38 Mitogen-Activated Protein Kinases (MAPKs), upon activation, promote (i) internalization of caveolae from the cell membrane, and (ii) rapid trafficking of early endosomes to the lysosomes by directly phosphorylating Caveolin1 and EEA1, respectively. Phospho-proteomic analyses, in MDA-MB-435 cells, revealed that the peak levels of activated p38β and p38δ MAPKs (at 2 hours post-delivery) elicited by the F3 peptides alone, and the NTNPs was ~2-fold greater than by the F3NPs. These data therefore provide compelling evidence that the intracellular trafficking behavior of the F3 peptides, NTNPs and F3NPs are attributable to their differential activation of the p38 MAPKs. Further analysis of the ERK MAPK, JNK MAPK, and Akt pathways revealed that the NTNPs elicit a pro-apoptotic signaling profile, whereas the F3 peptides, and F3NPs elicit proliferative profiles. The findings of this thesis suggest that the design of tumor-targeting nanoparticles also need to consider the MAPK signaling profiles that they elicit on the intended target cell type, due to the influence of the p38 MAPKs, in particular, on endocytic trafficking, and the survival status of the target tumor cell.PHDChemical BiologyUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/110348/1/leshernk_1.pd

Morbidity from antiretroviral metabolic effects in Africa: The Mama Study

Introduction: Combination antiretroviral therapy (ART) has considerably reduced both the morbidity and mortality of Human Immunodeficiency Virus (HIV) infection and its associated complications, thus effectively transforming a fatal disease into a manageable chronic condition. However, the chronic use of ART has been accompanied by the emergence of adverse metabolic abnormalities in HIV-infected patients, including dysglycaemia. There is, however, a paucity of data from sub-Saharan Africa on the incidence and risk factors associated with new onset diabetes mellitus in the HIV-infected population. Furthermore, efavirenz is the preferred nonnucleoside reverse transcriptase inhibitor (NNRTI) in first-line antiretroviral therapy (ART) regimens in low- and middle-income countries, where the prevalence of diabetes is increasing. Randomized control trials have shown mild increases in plasma glucose in participants in the efavirenz arms, but no association has been reported with overt diabetes. This study explores the risk factors and incidence of diabetes, and in particular the association between efavirenz exposure and diabetes, in a large Southern African cohort commencing NNRTI-based first-line ART. Subjects and Methods: The study cohort included HIV-infected adults commencing NNRTI-based ART in a private sector HIV disease management programme from January 2002 to December 2011. Incident diabetes was identified by the initiation of diabetes treatment. Patients with prevalent diabetes were excluded. The incidence of diabetes in patients receiving efavirenz versus nevirapine containing regimens was compared with a Kaplan-Meier plot and a log-rank test. The association of efavirenz exposure with the hazard of developing diabetes was modelled using a multivariate Cox-proportional hazards model. The following variables were adjusted for in the regression model: age, sex, baseline BMI, baseline CD4, baseline viral load, exposure to diabetogenic drugs, and nucleoside reverse transcriptase inhibitor (NRTI) exposure. Results: Between January 2002 and June 2011, 62,467 patients commenced ART in the AfA program, of whom 56,298 patients met the inclusion and exclusion criteria and were included in the analysis. Median follow-up was 1.56 years (interquartile range (IQR): 0.71- 2.79 years), 21.7% of patients were followed up for 3 or more years. New onset diabetes was identified in 1500 (2.66%) patients over 113,297 patient-years of follow-up (PYFU), giving a crude incidence of 13.24 cases per 1000 PYFU. In the multivariate analysis treatment with efavirenz rather than nevirapine was associated with increased risk of developing diabetes (hazard ratio 1.27 (95% confidence interval: 1.10 - 1.46). Zidovudine and stavudine exposure, older baseline age, elevated baseline BMI, and exposure to diabetogenic medication were also associated with increased risk of diabetes. No association was found between baseline CD4 and an increased risk of diabetes. There was an association between the lowest stratum of baseline viral load and an increased relative risk for developing diabetes, but no association with higher viral load strata. Conclusion: Treatment with efavirenz, as well as stavudine and zidovudine, increased the risk of incident diabetes. Interventions to detect and prevent diabetes should be implemented in ART programmes, and use of antiretrovirals with lower risk of metabolic complications should be encouraged

Apoptosis in peripheral blood mononuclear cells of human immunodeficiency virus (HIV) infected patients undergoing highly active antiretroviral therapy.

Thesis (M.Med.Sci.)--University of KwaZulu-Natal, 2008.Highly active antiretroviral therapy (HAART) is currently the only treatment that effectively reduces the morbidity and mortality of individuals infected with Human Immunodeficiency Virus-1 (HIV-1). Standard HAART regimens typically comprise 2 nucleoside reverse transcriptase inhibitors and either one non-nucleoside reverse transcriptase inhibitor or a protease inhibitor. These drugs bind to and inhibit the HIV-1 Reverse Transcriptase and Protease enzymes respectively, thereby suppressing viral replication. The nucleoside reverse transcriptase inhibitors promote mitochondrial (mt) dysfunction by strongly inhibiting mt polymerase gamma (Pol-y) and subsequently, mtDNA replication. In contrast, the non-nucleoside reverse transcriptase inhibitors, efavirenz (EFV) and nevirapine (NVP) do not inhibit Pol-y although EFV has been shown to induce mt depolarisation ( mlow) in vitro at supra-therapeutic concentrations. However, the capacity of non-nucleoside reverse transcriptase inhibitor drugs to induce mt toxicity in vivo previously remained undetermined. The objective of this study was to determine the influence of EFV and NVP on peripheral lymphocyte mt transmembrane potential (Avj/m) and apoptosis in HIV-1-infected patients treated with these non-nucleoside reverse transcriptase inhibitors. Thirty-two HIV-1-infected patients on HAART between 4 and 24 months (12 on EFV, 20 on NVP) and 16 HAART-naive HIV-1-infected patients were enrolled into this study. All participants were black South African patients. Spontaneous peripheral lymphocyte apoptosis and mlow were measured ex vivo by flow cytometry for all patients. CD4 T-helper apoptosis for the EFV and NVP cohorts was 19.38% ± 2.62% and 23.35% ± 1.51% (mean ± SEM), respectively, whereas total lymphocyte mlow was 27.25% ± 5.05% and 17.04% ± 2.98%, respectively. Both parameters for each cohort were significantly lower (P < 0.05) than that of the HAART-naive patients. The NVP cohort exhibited both a significant time dependent increase in peripheral lymphocyte ö¿mlow (P = 0.038) and correlation between Thelper apoptosis and low (P = 0.0005). These trends were not observed in the EFV cohort. This study provides evidence that both EFV and NVP induce peripheral lymphocyte ö¿ m low in HIV-1-infected patients on non-nucleoside reverse transcriptase inhibitor-based HAART, which in the case of NVP is sufficient to induce the apoptosis cascade

The socio-ethical aspects of scientific theory with particular reference to biology.

Thesis (M.A.)-University of Durban-Westville, 1987.In this dissertation scientific theory is investigated in order to show its socio-ethical aspects. An historical approach shows that prevailing historical conditions influence the development of scientific theory. These conditions are also created by the theories that they influence. Thus there is a continual interaction between theory and practice, pointinig to the socio-ethical aspects of theory. An investigation of scientific theory including biological theory also shows this continual interaction. Efforts to derive moral precepts from biological theory, e.g., Darwinism, sociobiology and genetic theory reveal the influences and prejudices of the particular historical periods in which the theories are developed. These aspects of scientific theory show that the scientific enterprise is not characterised by objectivity and disinteredness. The community aspect of scientific practice also shows that scientists are dependent on one another and that theories are interrelated. These spects of scientific theory show the transcultural and transnational nature of theory and lays a foundation for the basis of ethics and for scientific responsibility

Association of -308 TNF-alpha promoter polymorphism with viral load and CD4 T-helper cell apoptosis in HIV-1 infected black South Africans

Objective. To determine whether the -308 TNF-α promoter polymorphism is associated with markers of HIV progression in the South African population. Methods. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the -308 TNF-α polymorphism in 75 patients and 76 healthy controls. Serum TNF-α concentrations were measured using ELISA in each cohort. CD4+ T cell apoptosis and HIV-1 RNA viral load were determined using Annexin-V-FITC assay and Nuclisens Easy Q HIV-1 assay respectively. CD4 + T cell counts were measured flow cytometrically. Results. The frequency of -308 G allele was similar in the HIV-1 and control cohorts. The -308GG genotype was associated with lower TNF-α concentrations and markers of increased HIV progression indicated by higher TH lymphocyte apoptosis, lower TH lymphocyte count and higher plasma viral load, irrespective of treatment. Conclusion. The presence of the TNF-α -308 G allele in HIV-1 patients may be associated with increased risk of HIV-1 progression. Further research is required to investigate the nature of this association. S Afr J HIV Med 2012;13(2):72-77

HIV and SARS-CoV-2 co-infection: The diagnostic challenges of dual pandemics

The first critically ill patient admitted to our hospital in Cape Town, South Africa, during the COVID-19 pandemic was co-infected with HIV and SARS-CoV-2. Pneumocystis jirovecii pneumonia (PCP) and other respiratory opportunistic infections share many clinical features with severe COVID-19. Our understanding of the nuances of co-management of HIV and COVID-19 is evolving. We describe the diagnostic and therapeutic challenges presented by this case

Leadership and early strategic response to the SARS-CoV-2 pandemic at a COVID-19 designated hospital in South Africa

While many countries are preparing to face the COVID-19 pandemic, the reported cases in Africa remain low. With a high burden of both communicable and non-communicable disease and a resource-constrained public healthcare system, sub-Saharan Africa is preparing for the coming crisis as best it can. We describe our early response as a designated COVID-19 provincial hospital in Cape Town, South Africa (SA).While the first cases reported were related to international travel, at the time of writing there was evidence of early community spread. The SAgovernment announced a countrywide lockdown from midnight 26 March 2020 to midnight 30 April 2020 to stem the pandemic and save lives. However, many questions remain on how the COVID-19 threat will unfold in SA, given the significant informal sector overcrowding and poverty in our communities. There is no doubt that leadership and teamwork at all levels is critical in influencing outcomes

Beyond the water column: aquatic hyphomycetes outside their preferred habitat

Aquatic hyphomycetes have adapted to running waters by their uncommon conidial shape, which facilitates dispersal as well as adherence to plant substrata. However, they have been early and regularly reported to occur in a variety of environments other than their preferred habitat (e.g., in lentic freshwaters, brackish and marine environments, in terrestrial niches such as stream banks, dew, canopy waters and tree holes). In addition, several aquatic hyphomycetes have adapted to a mutualistic lifestyle which may involve plant defence, as endophytes in leaves, gymnosperm needles, orchids and terrestrial roots. There are several lines of evidence suggesting that aquatic hyphomycetes survive under terrestrial conditions due to their sexual states. Although exhibiting higher diversity in pristine streams, aquatic hyphomycetes can survive environmental stress, e.g., pollution or river intermittency. They also inhabit ground and hyporheic waters, where they appear to be subjected to both physical and physiological selection. Appropriate methods including molecular ones should provide a more comprehensive view of the occurrence and ecological roles of aquatic hyphomycetes outside their preferred habitat