Thermally Induced Nano-Structural and Optical Changes of nc-Si:H Deposited by Hot-Wire CVD

We report on the thermally induced changes of the nano-structural and optical properties of hydrogenated nanocrystalline silicon in the temperature range 200–700 °C. The as-deposited sample has a high crystalline volume fraction of 53% with an average crystallite size of ~3.9 nm, where 66% of the total hydrogen is bonded as ≡Si–H monohydrides on the nano-crystallite surface. A growth in the native crystallite size and crystalline volume fraction occurs at annealing temperatures ≥400 °C, where hydrogen is initially removed from the crystallite grain boundaries followed by its removal from the amorphous network. The nucleation of smaller nano-crystallites at higher temperatures accounts for the enhanced porous structure and the increase in the optical band gap and average gap

Undiagnosed comorbidities among individuals hospitalised with COVID-19 in South African public hospitals

Background. Previous studies have reported comorbid disease, including hypertension, diabetes mellitus, chronic cardiac and renal disease, malignancy, HIV, tuberculosis (TB) and obesity, to be associated with COVID‑19 mortality. National demographic surveys have reported a high proportion of undiagnosed and untreated comorbid disease in South Africa (SA). Objectives. To determine the number of individuals with previously undiagnosed HIV, TB and non-communicable diseases (NCDs) among patients hospitalised with COVID‑19, and the level of medical control of these chronic diseases. Methods. We conducted a sentinel surveillance study to collect enhanced data on HIV, TB and NCDs among individuals with COVID‑19 admitted to 16 secondary-level public hospitals in six of the nine provinces of SA. Trained surveillance officers approached all patients who met the surveillance case definition for inclusion in the study, and consenting patients were enrolled. The data collection instrument included questions on past medical history to determine the self-reported presence of comorbidities. The results of clinical and laboratory testing introduced as part of routine clinical care for hospitalised COVID‑19 patients were collected for the study, to objectively determine the presence of hypertension, diabetes, HIV and TB and the levels of control of diabetes and HIV. Results. On self-reported history, the most prevalent comorbidities were hypertension (n=1 658; 51.5%), diabetes (n=855; 26.6%) and HIV (n=603; 18.7%). The prevalence of self-reported active TB was 3.1%, and that of previous TB 5.5%. There were 1 254 patients admitted with COVID‑19 (39.0%) who met the body mass index criteria for obesity. On clinical and laboratory testing, 87 patients were newly diagnosed with HIV, 29 with TB, 215 with diabetes and 40 with hypertension during their COVID‑19 admission. There were 151/521 patients living with HIV (29.0%) with a viral load >1 000 copies/mL and 309/570 (54.2%) with a CD4 count <200 cells/μL. Among 901 patients classified as having diabetes, 777 (86.2%) had a glycated haemoglobin (HbA1c) level ≥6.5%. Conclusion. The study revealed a high prevalence of comorbid conditions among individuals with COVID‑19 admitted to public hospitals in SA. In addition, a significant number of patients had previously undiagnosed hypertension, diabetes, HIV and active TB, and many and poorly controlled chronic disease, as evidenced by high HbA1c levels in patients with diabetes, and high viral loads and low CD4 levels in patients with HIV. The findings highlight the importance of strengthening health systems and care cascades for chronic disease management, which include prevention, screening for and effectively treating comorbidities, and ensuring secure and innovative supplies of medicines in primary healthcare during the COVID‑19 pandemic

Improving a Mother to Child HIV Transmission Programme through Health System Redesign: Quality Improvement, Protocol Adjustment and Resource Addition

Health systems that deliver prevention of mother to child transmission (PMTCT) services in low and middle income countries continue to underperform, resulting in thousands of unnecessary HIV infections of newborns each year. We used a combination of approaches to health systems strengthening to reduce transmission of HIV from mother to infant in a multi-facility public health system in South Africa.All primary care sites and specialized birthing centers in a resource constrained sub-district of Cape Metro District, South Africa, were enrolled in a quality improvement (QI) programme. All pregnant women receiving antenatal, intrapartum and postnatal infant care in the sub-district between January 2006 and March 2009 were included in the intervention that had a prototype-innovation phase and a rapid spread phase. System changes were introduced to help frontline healthcare workers to identify and improve performance gaps at each step of the PMTCT pathway. Improvement was facilitated and spread through the use of a Breakthrough Series Collaborative that accelerated learning and the spread of successful changes. Protocol changes and additional resources were introduced by provincial and municipal government. The proportion of HIV-exposed infants testing positive declined from 7.6% to 5%. Key intermediate PMTCT processes improved (antenatal AZT increased from 74% to 86%, PMTCT clients on HAART at the time of labour increased from 10% to 25%, intrapartum AZT increased from 43% to 84%, and postnatal HIV testing from 79% to 95%) compared to baseline.System improvement methods, protocol changes and addition/reallocation of resources contributed to improved PMTCT processes and outcomes in a resource constrained setting. The intervention requires a clear design, leadership buy-in, building local capacity to use systems improvement methods, and a reliable data system. A systems improvement approach offers a much needed approach to rapidly improve under-performing PMTCT implementation programmes at scale in sub-Saharan Africa

Inhibition of resistance-refractory P. falciparum kinase PKG delivers prophylactic, blood stage, and transmission-blocking antiplasmodial activity

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation. Metabolomic, phosphoproteomic, and chemoproteomic studies, validated with conditional knockdown parasites, molecular docking, and recombinant kinase assays, identified cGMP-dependent protein kinase (PKG) as the primary target of MMV030084. PKG is known to play essential roles in Plasmodium invasion of and egress from host cells, matching MMV030084's activity profile. Resistance selections and gene editing identified tyrosine kinase-like protein 3 as a low-level resistance mediator for PKG inhibitors, while PKG itself never mutated under pressure. These studies highlight PKG as a resistance-refractory antimalarial target throughout the Plasmodium life cycle and promote MMV030084 as a promising Plasmodium PKG-targeting chemotype