Whole blood-based measurement of SARS-CoV-2-specific T cells reveals asymptomatic infection and vaccine immunogenicity in healthy subjects and patients with solid-organ cancers.

Accurate assessment of SARS-CoV-2 immunity is critical in evaluating vaccine efficacy and devising public health policies. Whilst the exact nature of effective immunity remains incompletely defined, SARS-CoV-2-specific T-cell responses are a critical feature that will likely form a key correlate of protection against COVID-19. Here, we developed and optimized a high-throughput whole blood-based assay to determine the T-cell response associated with prior SARS-CoV-2 infection and/or vaccination amongst 231 healthy donors and 68 cancer patients. Following overnight in vitro stimulation with SARS-CoV-2-specific peptides, blood plasma samples were analysed for TH 1-type cytokines. Highly significant differential IFN-γ+ /IL-2+ SARS-CoV-2-specific T-cell responses were seen amongst previously infected COVID-19-positive healthy donors in comparison with unknown / naïve individuals (p < 0·0001). IFN-γ production was more effective at identifying asymptomatic donors, demonstrating higher sensitivity (96·0% vs. 83·3%) but lower specificity (84·4% vs. 92·5%) than measurement of IL-2. A single COVID-19 vaccine dose induced IFN-γ and/or IL-2 SARS-CoV-2-specific T-cell responses in 116 of 128 (90·6%) healthy donors, reducing significantly to 27 of 56 (48·2%) when measured in cancer patients (p < 0·0001). A second dose was sufficient to boost T-cell responses in the majority (90·6%) of cancer patients, albeit IFN-γ+ responses were still significantly lower overall than those induced in healthy donors (p = 0·034). Three-month post-vaccination T-cell responses also declined at a faster rate in cancer patients. Overall, this cost-effective standardizable test ensures accurate and comparable assessments of SARS-CoV-2-specific T-cell responses amenable to widespread population immunity testing, and identifies individuals at greater need of booster vaccinations.

Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery.

A novel production process flow is presented here for the manufacture of hollow silicon microneedles using deep reactive-ion etching (DRIE) technology. The patent-pending three-step process flow has been developed to produce multiple arrays of sharp-tipped, hollow microneedles, which facilitate easy insertion and controlled fluid injection into excised skin samples. A bevelled tip and vertical sidewalls for the microneedle have been achieved with good uniformity, despite >45% open etch area. Processing steps and etch challenges are discussed, and preliminary skin testing results are presented, showing effective needle insertion and delivery of fluorescent dye into ex vivo skin from human breast tissue.

Advanced deep reactive-ion etching technology for hollow microneedles for transdermal blood sampling and drug delivery.

Using an SPTS Technologies Ltd. Pegasus deep reactive-ion etching (DRIE) system, an advanced two-step etching process has been developed for hollow microneedles in applications of transdermal blood sampling and drug delivery. Because of the different etching requirements of both narrow deep hollow and large open cavity, hollow etch and cavity etch steps have been achieved separately. This novel two-step etching process is assisted with a bi-layer etching mask. Results show that the etch rate of silicon during this hollow etch step was about 7.5 microm/min and the etch rate of silicon during this cavity etch step was about 8-10 microm/min, using the coil plasma etching power between 2.0 and 2.8 kW. Especially for the microneedle bores etch, the deeper it etched, the slower the etch rate was. The microneedle bores have successfully been obtained 75-150 microm in inner diametre and 700-1000 microm long with high aspect ratio DRIE, meanwhile, the vertical sidewall structures have been achieved with the high etch load exposed area over 70% for the cavity etch step.

Homicide-suicide in Durban, South Africa.

This study investigated homicide-suicide in Durban, South Africa, for the years 2000 to 2001. The incidence was 0.89 per 100,000, higher than the international average. A majority of perpetrators (91%) and victims (87%) were Black African, proportional to their representation in the population. Perpetrators were typically men (in 95% of cases), older than, and intimate partners (in 75% of cases) of the female victims (in 100% of cases). Average ages of perpetrators and victims were 32 and 27, respectively. The security sector was overrepresented as an employment category for perpetrators. A firearm was used in 87% of the homicides and 80% of the suicides. The individuals involved in homicide-suicides in Durban are similar to homicide-suicide perpetrators and victims in industrialized countries. The fact that homicide-suicides in South Africa, as in most countries, involve almost exclusively men killing female intimates confirms the importance of examining and challenging social norms enabling male violence against women.