Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants.

We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. A total of 286 adults (with or without HIV) were enrolled >4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Overall, in the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: The study has been registered to the South African National Clinical Trial Registry (SANCTR): DOH-27-012022-7841. The approval letter from SANCTR has been provided in the up-loaded documents.

Measuring the radiation of sound sources with the radiation mode method: Towards realistic problems.

The measurement of the pressure field radiated by a sound source has many applications in the fields of noise control and loudspeaker system design. In this paper, the radiation mode method is used to measure the field radiated by a complex acoustic source whose surface impedance is arbitrary and does not correspond to the Neumann boundary condition used for the calculation of radiation modes. The most effective radiation modes are used as test functions to calculate a pressure expansion around the source under test, an expansion that matches the measured pressure at a limited number of points close to the source. This expansion is then used to calculate the radiated pressure at a greater distance at unmeasured locations. In a first step, numerical simulations are performed to evaluate the method's most influential parameters. Then, measurements are performed in a semi-anechoic room on two real sources of increasing complexity. Obtained results show that the radiation mode method allows an accurate evaluation of the pressure field radiated by the test object over a fairly wide frequency band (between 100 Hz and 2 kHz) even for complex sources.

More Frequent HIV Viral Load Testing With Point-Of-Care Tests Detects Elevated Viral Load Earlier in Postpartum HIV-Positive Women in a Randomized Controlled Trial in Two Clinics in Johannesburg, South Africa.

BACKGROUND: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure. METHODS: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit. Women were randomized 1:1 to arm 1 or 2. Trained staff performed point-of-care VL testing using the Cepheid's Xpert HIV-1 VL assay. We fitted a generalized linear mixed model with VL suppression (<50 copies/mL (cps/mL) and <1000 cps/mL) at enrollment and 6, 12, and 18 months postpartum as the outcome and indicator variables for time, study site, study arm, and interaction variables. The final model tested for a difference by study arm, pooling across time points. RESULTS: Of 405 women enrolled (204 arm 1 and 201 arm 2), 249 (61%) remained in follow-up through 18 months. There was no difference in VL suppression between arms at 6, 12, or 18 months. VL suppression rate (<50 cps/mL) at 18 months was 64.8% in arm 1 and 63.0% in arm 2 (P = 0.27). On bivariate analysis, there was an association with late antenatal booking and being in arm 2 for nonsuppressed VL, but no significant association with breastfeeding. HIV drug resistance was found in 12 of 23 participants (52.2%). CONCLUSION: We found no significant difference in VL suppression with more frequent VL testing in postpartum women living with HIV receiving first-line efavirenz-based antiretroviral treatment.

High prevalence of SARS-CoV-2 antibodies in pregnant women after the second wave of infections in the inner-city of Johannesburg, Gauteng Province, South Africa.

OBJECTIVES: After South Africa's second wave of COVID-19, this study estimated the SARS-CoV-2 seroprevalence among pregnant women in inner-city Johannesburg, South Africa. METHODS: In this cross-sectional survey, 500 pregnant women who were non-COVID-19-vaccinated (aged ≥12 years) were enrolled, and demographic and clinical data were collected. Serum samples were tested using the Wantai SARS-CoV-2 spike antibody enzyme-linked immunosorbent assay and Roche Elecsys® anti-SARS-CoV-2 nucleocapsid antibody assays. Seropositivity was defined as SARS-CoV-2 antibodies on either (primary) or both (secondary) assays. Univariate Poisson regression assessed risk factors associated with seropositivity. RESULTS: The median age was 27.4 years, and HIV prevalence was 26.7%. SARS-CoV-2 seroprevalence was 64.0% (95% confidence interval [CI]: 59.6-68.2%) on the primary and 54% (95% CI: 49.5-58.4%) on the secondary measure. Most (96.6%) women who were SARS-CoV-2-seropositive reported no symptoms. On the Roche assay, we detected lower seroprevalence among women living with HIV than women without HIV (48.9% vs 61.7%, P-value = 0.018), and especially low levels among women living with HIV with a clusters of differentiation 4 <350 cells/ml compared with women without immune suppression (22.2% vs 56.4%, prevalence rate ratio = 0.4; 95% CI: 0.2-0.9; P-value = 0.046). CONCLUSION: Pregnant women attending routine antenatal care had a high SARS-CoV-2 seroprevalence after the second wave in South Africa, and most had asymptomatic infections. Seroprevalence surveys in pregnant women present a feasible method of monitoring the course of the pandemic over time.

Ambient temperature during pregnancy and risk of maternal hypertensive disorders: A time-to-event study in Johannesburg, South Africa.

Hypertensive disorders in pregnancy are a leading cause of maternal and perinatal mortality and morbidity. We evaluate the effects of ambient temperature on risk of maternal hypertensive disorders throughout pregnancy. We used birth register data for all singleton births (22-43 weeks' gestation) recorded at a tertiary-level hospital in Johannesburg, South Africa, between July 2017-June 2018. Time-to-event analysis was combined with distributed lag non-linear models to examine the effects of mean weekly temperature, from conception to birth, on risk of (i) high blood pressure, hypertension, or gestational hypertension, and (ii) pre-eclampsia, eclampsia, or HELLP (hemolysis, elevated liver enzymes, low platelets). Low and high temperatures were defined as the 5th and 95th percentiles of daily mean temperature, respectively. Of 7986 women included, 844 (10.6%) had a hypertensive disorder of which 432 (51.2%) had high blood pressure/hypertension/gestational hypertension and 412 (48.8%) had pre-eclampsia/eclampsia/HELLP. High temperature in early pregnancy was associated with an increased risk of pre-eclampsia/eclampsia/HELLP. High temperature (23 °C vs 18 °C) in the third and fourth weeks of pregnancy posed the greatest risk, with hazard ratios of 1.76 (95% CI 1.12-2.78) and 1.79 (95% CI 1.19-2.71), respectively. Whereas, high temperatures in mid-late pregnancy tended to protect against pre-eclampsia/eclampsia/HELLP. Low temperature (11°) during the third trimester (from 29 weeks' gestation) was associated with an increased risk of high blood pressure/hypertension/gestational hypertension, however the strength and statistical significance of low temperature effects were reduced with model adjustments. Our findings support the hypothesis that high temperatures in early pregnancy increase risk of severe hypertensive disorders, likely through an effect on placental development. This highlights the need for greater awareness around the impacts of moderately high temperatures in early pregnancy through targeted advice, and for increased monitoring of pregnant women who conceive during periods of hot weather.

Physiological mechanisms of the impact of heat during pregnancy and the clinical implications: review of the evidence from an expert group meeting.

Many populations experience high seasonal temperatures. Pregnant women are considered vulnerable to extreme heat because ambient heat exposure has been linked to pregnancy complications including preterm birth and low birthweight. The physiological mechanisms that underpin these associations are poorly understood. We reviewed the existing research evidence to clarify the mechanisms that lead to adverse pregnancy outcomes in order to inform public health actions. A multi-disciplinary expert group met to review the existing evidence base and formulate a consensus regarding the physiological mechanisms that mediate the effect of high ambient temperature on pregnancy. A literature search was conducted in advance of the meeting to identify existing hypotheses and develop a series of questions and themes for discussion. Numerous hypotheses have been generated based on animal models and limited observational studies. There is growing evidence that pregnant women are able to appropriately thermoregulate; however, when exposed to extreme heat, there are a number of processes that may occur which could harm the mother or fetus including a reduction in placental blood flow, dehydration, and an inflammatory response that may trigger preterm birth. There is a lack of substantial evidence regarding the processes that cause heat exposure to harm pregnant women. Research is urgently needed to identify what causes the adverse outcomes in pregnancy related to high ambient temperatures so that the impact of climate change on pregnant women can be mitigated.

The clinical and demographic profile of women living with HIV admitted to the acute unit at Stikland Psychiatric Hospital.

BACKGROUND: There is a paucity of research on the clinical profile of women living with human immunodeficiency virus (HIV) (WLWH) admitted with acute mental health illness. Existing studies are small and did not look at factors that could have an impact on medication adherence. As a first step to inform service delivery for this vulnerable population, a thorough understanding of the composition and needs of these patients should be identified. OBJECTIVES: To describe the socio-demographic and clinical profile that could have an influence on the antiretroviral therapy (ART) adherence of WLWH at an inpatient psychiatric unit. METHODS: In this retrospective audit, the medical records of all WLWH (18-59 years of age), discharged from the acute unit at Stikland Psychiatric Hospital, were reviewed over a 12-month period. RESULTS: Of the 347 female patients discharged, 55 patients were positive for HIV (15.9%). The majority of them were unmarried (78.2%), unemployed (92.7%), had a secondary level of education (Grade 8-10) (58.2%), lived with a family member (83.6%) and had children (61.8%). The most common psychiatric diagnosis on discharge was substance use disorder with 78.2% of patients being categorised as substance users. Interpersonal violence was only reported by 5.5% of patients. Although most patients performed poorly on the Montreal Cognitive Assessment (MoCA) and International HIV Dementia Scale (IHDS), only 12% of patients received a diagnosis of HIV-associated neurocognitive disorder (HAND) upon discharge. Antiretroviral therapy (ART) was initiated in 21.8% of patients. Only eight patients had a viral load of < 200 copies/mL, indicating viral suppression. CONCLUSION: Our findings may inform service planning and emphasise the need for targeted intervention strategies to improve treatment outcomes in this vulnerable group.

Forward propagation of time evolving acoustic pressure: formulation and investigation of the impulse response in time-wavenumber domain.

The aim of this work is to continuously provide the acoustic pressure field radiated from nonstationary sources. From the acquisition in the nearfield of the sources of a planar acoustic field which fluctuates in time, the method gives instantaneous sound field with respect to time by convolving wavenumber spectra with impulse response and then inverse Fourier transforming into space for each time step. The quality of reconstruction depends on the impulse response which is composed of investigated parameters as transition frequency and propagation distance. Sampling frequency also affects errors of the practically discrete impulse response used for calculation. To avoid aliasing, the impulse response is low-pass filtered with Chebyshev or Kaiser-Bessel filter. Another approach to implement the impulse response consists of applying an inverse Fourier transform to the theoretical transfer function for propagation. To estimate the performance of each processing method, a simulation test involving several source monopoles driven by nonstationary signals is executed. Some indicators are proposed to assess the accuracy of the temporal signals predicted in a forward plane. The results show that the use of a Kaiser-Bessel filter numerically implemented or that of the inverse Fourier transform can provide the most accurate instantaneous acoustic signals.

When to walk away from a deal.

Deal making is glamorous; due diligence is not. That simple statement goes a long way toward explaining why so many companies have made so many acquisitions that have produced so little value. The momentum of a transaction is hard to resist once senior management has the target in its sights. Companies contract "deal fever," and due diligence all too often becomes an exercise in verifying the target's financial statements rather than conducting a fair analysis of the deal's strategic logic and the acquirer's ability to realize value from it. Seldom does the process lead managers to kill potential acquisitions, even when the deals are deeply flawed. In a recent Bain & Company survey of 250 international executives with M&A responsibilities, only 30% of them were satisfied with the rigor of their due diligence. And fully a third admitted they hadn't walked away from deals they had nagging doubts about. In this article, the authors, all Bain consultants, emphasize the importance of comprehensive due diligence practices and suggest ways companies can improve their capabilities in this area. They provide rich real-world examples of companies that have had varying levels of success with their due diligence processes, including Safeway, Odeon, American Sea-foods, and Kellogg's. Effective due diligence requires answering four basic questions: What are we really buying? What is the target's stand-alone value? Where are the synergies--and the skeletons? And what's our walk-away price? Each of these questions will prompt an even deeper level of querying that puts the broader, strategic rationale for acquisitions under a microscope. Successful acquirers pay close heed to the results of such in-depth investigations and analyses--to the extent that they are prepared to walk away from a deal, even in the very late stages of negotiations.