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On March 10, 2021, the FDA granted regular approval to tivozanib for treatment of patients with relapsed or refractory (R/R) advanced renal cell carcinoma (RCC) following two or more prior systemic therapies. Approval was based on the TIVO-3 study, a randomized trial of tivozanib versus sorafenib in patients with R/R advanced RCC. In TIVO-3, patients were randomized to receive either tivozanib 1.34 mg orally once daily for 21 consecutive days of every 28-day cycle or sorafenib 400 mg orally twice daily continuously. The primary endpoint was progression-free survival (PFS) per RECIST v1.1. Tivozanib demonstrated efficacy compared with sorafenib with an improvement in PFS [HR, 0.73; 95% confidence interval (CI), 0.56–0.95; P = 0.016]. The estimated median PFS was 5.6 months and 3.9 months in the tivozanib and sorafenib arms, respectively. There was no evidence of a detrimental effect on overall survival: HR, 0.97 (95% CI, 0.75–1.24). The most common grade 3 to 4 adverse reaction on the tivozanib arm was hypertension (24%). Compared with sorafenib, tivozanib was associated with lower rates of grade 3 to 4 diarrhea, rash, and palmar-plantar erythrodysesthesia. Patients receiving tivozanib in TIVO-3 had lower rates of dose reduction, interruption, or permanent discontinuation than those receiving sorafenib.

The FDA approved capmatinib and tepotinib on May 6, 2020, and February 3, 2021, respectively. Capmatinib is indicated for patients with metastatic non–small cell lung cancer (mNSCLC) whose tumors have a mutation leading to mesenchymal–epithelial transition (MET) exon 14 skipping as detected by an FDA-approved test. Tepotinib is indicated for mNSCLC harboring MET exon 14 skipping alterations. The approvals were based on trials GEOMETRY mono-1 (capmatinib) and VISION (tepotinib). In GEOMETRY mono-1, overall response rate (ORR) per Blinded Independent Review Committee (BIRC) was 68% [95% confidence interval (CI), 48–84] with median duration of response (DoR) 12.6 months (95% CI, 5.5–25.3) in 28 treatment-naïve patients and 41% (95% CI: 29, 53) with median DoR 9.7 months (95% CI, 5.5–13) in 69 previously treated patients with NSCLC with mutations leading to MET exon 14 skipping. In VISION, ORR per BIRC was 43% (95% CI: 32, 56) with median DoR 10.8 months (95% CI, 6.9–not estimable) in 69 treatment-naïve patients and 43% (95% CI, 33–55) with median DoR 11.1 months (95% CI, 9.5–18.5) in 83 previously-treated patients with NSCLC harboring MET exon 14 alterations. These are the first two therapies to be FDA approved specifically for patients with metastatic NSCLC with MET exon 14 skipping.

Objective: The aim was to describe the anthropometry, bone mineral content (BMC), bone mineral density (BMD), dietary calcium intake and 25(OH)D3 levels in 11- and 12-year-old children in a peri-urban area. Design: A cross-sectional, descriptive study in the quantitative domain was undertaken. Setting: Bronkhorstspruit, Gauteng, South Africa. Subjects: Children, conveniently selected, were assessed in two groups. The first group comprised 70 children. From the 70 children, 20 children were conveniently selected to form a sub-sample (n = 20). Outcome measures: Anthropometric data (weight, height) and dietary data (three quantified /multi-pass 24-hour recalls). Children in the sub-sample additionally underwent body composition assessment (dual-energy X-ray absorptiometry; DXA scan) and a finger prick for 25(OH)D3. Results: BMI and body composition data (body fat mass and lean fat mass) showed that the girls exceeded the boys in all measurements. The girls had a non-significantly higher BMD and BMC than the boys. The mean and median values for 25(OH)D3 were lower than the reference range values. Dietary intake results showed that the children had a sufficient macronutrient intake, but a deficient intake of calcium, phosphate and vitamin D. The sub-sample had a mean vitamin D intake of 3.2 mcg. Conclusion: The girls exceeded the boys in all the anthropometric and body composition measurements. The calcium and vitamin D intake of the children were of concern. There were no significant differences or relationships in the bone measurements and vitamin D status between the boys and girls.

On December 18, 2020, the FDA approved osimertinib as adjuvant therapy in patients with non–small cell lung cancer (NSCLC) whose tumors have EGFR exon 19 deletions or exon 21 (L858R) mutations, as detected by an FDA-approved test. The approval was based on the ADAURA study, in which 682 patients with NSCLC were randomized to receive osimertinib (n = 339) or placebo (n = 343). Disease-free survival (DFS) in the overall population (stage IB–IIIA) was improved for patients who received osimertinib, with an HR of 0.20; 95% confidence interval (CI), 0.15–0.27; P < 0.0001. Median DFS was not reached for the osimertinib arm compared with 27.5 months (95% CI, 22.0–35.0) for patients receiving placebo. Overall survival data were not mature at the time of the approval. This application was reviewed under FDA's Project Orbis, in collaboration with Australia Therapeutic Goods Administration, Brazil ANVISA, Health Canada, Singapore Health Sciences Authority, Switzerland Swissmedic, and the United Kingdom Medicines and Healthcare products Regulatory Agency. This is the first targeted therapy adjuvant approval for NSCLC and has practice-changing implications.

In robotics and mapping, prior knowledge of an environment can be included as virtual assets to a simultaneous localization and mapping (SLAM) solution. Borrowing the concept of affordances from robotic manipulation (i.e. virtual/interactive object models/primitives), this work addresses the fundamental duality in discrepancies between virtual and physical structures for localization and mapping. We propose a multimodal/non-Gaussian solution as a fundamental mechanism to leverage navigation-affordance assets during the localization and mapping process while simultaneously identifying any mismatches from the physical object. This allows the localization and mapping state-estimate more robust access to non-conventional and imperfect prior information about the environment, while computationally identifying assumed model discrepancies from imperfect sensor data. We use non-Gaussian factor graphs as modeling language to incorporate navigation-affordances with multi-sensor data similar to SLAM methods. We illustrate the approach with synthesized and real-world data from the construction industry where digital assets (such as drawings or models) are good proxies for how navigation-affordances can be generated and used in general.

Objectives Globally, tuberculosis (TB) incidence and mortality are declining; however, low detection of drug-resistant disease threatens to reverse current progress toward global TB control. Multiple, rapid molecular diagnostic tests have recently been developed to detect genetic mutations in Mycobacterium tuberculosis (Mtb) known to confer anti-TB drug resistance. Their utility, though, depends on the frequency and distribution of the resistance-associated mutations in the pathogen population. Therefore, this review aimed to assess the prevalence of the gene mutations associated with rifampicin (RIF) and isoniazid (INH) resistant Mtb in Ethiopia. Methods Using PRISMA guidelines, we searched the literature on PubMed/MEDLINE, Web of Science, Scopus, and Cochrane library databases. Data analysis was conducted in STATA 11. Results In total, 909 (95.8%) of 949 INH resistant Mtb isolates had detectable gene mutations: 95.8% in katG315 and 5.9% in the inhA-promoter region. The meta-analysis resulting an estimated prevalence of katGMUT1(S315T1) was 89.2% (95%CI:81.94-96.43%), while a pooled prevalence of inhAMUT1 (C15T) was 77.5% (95%CI:57.84-97.13%). Besides, 769 (90.8%) of 847 RIF resistant strains had detectable rpoB gene mutations, and the meta-analysis resulting in a pooled prevalence of rpoBMUT3 (S531L) was 74.2% (95%CI: 66.39-82.00%). Conclusions RIF-resistant Mtb isolates were spread widely, particularly those harboring S531L mutations. Similarly, INH-resistant Mtb strains with S315T1 and C15T mutations were common. Tracking S531L, S315T1, and C15T mutations among RIF and INH resistant isolates, respectively, would be diagnostically and epidemiologically valuable. Rapid diagnosis of RIF and INH-resistant Mtb in TB patients would expedite alteration of treatment regimens, and proper timely infection control interventions could reduce the risk of progression and transmission of multidrug-resistant TB (MDR-TB).

Zimbabwe requires USD2 billion annually until 2032 for financing economic infrastructure. However, the Government of Zimbabwe currently affords about 20% of this financing requirement leaving an 80% gap. The aim of the study was to establish the main sources of finance for economic public infrastructure and recommend alternative financing sources to supplement the current sources. The qualitative descriptive study collected primary data through 23 interviews conducted with officials from ministries of the Government of Zimbabwe, government departments and parastatal enterprises. Secondary data was obtained from documentary analysis. The study revealed bilateral loans from the China Exim Bank as the main source of finance for economic infrastructure, contributing USD2.1 billion whilst budget appropriations from the Government of Zimbabwe contributed USD1 billion during the 10-year period under study. Infrastructure finance was also obtained from development partners (USD200 million) and commercial and multilateral lenders (USD400 million). The study recommends developing a framework that promotes and protects private sector and/or innovative financiers of infrastructure through policy stability.

Summary Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. Methods In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. Findings Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27–1·43), past tuberculosis (1·26, 1·15–1·38), current tuberculosis (1·42, 1·22–1·64), and both past and current tuberculosis (1·48, 1·32–1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22–1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. Interpretation Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. Funding South African National Government.

Background The first wave of COVID-19 in South Africa peaked in July, 2020, and a larger second wave peaked in January, 2021, in which the SARS-CoV-2 501Y.V2 (Beta) lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves. Methods In this prospective cohort study, we analysed data from the DATCOV national active surveillance system for COVID-19 admissions to hospital from March 5, 2020, to March 27, 2021. The system contained data from all hospitals in South Africa that have admitted a patient with COVID-19. We used incidence risk for admission to hospital and determined cutoff dates to define five wave periods: pre-wave 1, wave 1, post-wave 1, wave 2, and post-wave 2. We compared the characteristics of patients with COVID-19 who were admitted to hospital in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using random-effect multivariable logistic regression. Findings Peak rates of COVID-19 cases, admissions, and in-hospital deaths in the second wave exceeded rates in the first wave: COVID-19 cases, 240·4 cases per 100 000 people vs 136·0 cases per 100 000 people; admissions, 27·9 admissions per 100 000 people vs 16·1 admissions per 100 000 people; deaths, 8·3 deaths per 100 000 people vs 3·6 deaths per 100 000 people. The weekly average growth rate in hospital admissions was 20% in wave 1 and 43% in wave 2 (ratio of growth rate in wave 2 compared with wave 1 was 1·19, 95% CI 1·18–1·20). Compared with the first wave, individuals admitted to hospital in the second wave were more likely to be age 40–64 years (adjusted odds ratio [aOR] 1·22, 95% CI 1·14–1·31), and older than 65 years (aOR 1·38, 1·25–1·52), compared with younger than 40 years; of Mixed race (aOR 1·21, 1·06–1·38) compared with White race; and admitted in the public sector (aOR 1·65, 1·41–1·92); and less likely to be Black (aOR 0·53, 0·47–0·60) and Indian (aOR 0·77, 0·66–0·91), compared with White; and have a comorbid condition (aOR 0·60, 0·55–0·67). For multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 31% increased risk of in-hospital mortality in the second wave (aOR 1·31, 95% CI 1·28–1·35). In-hospital case-fatality risk increased from 17·7% in weeks of low admission (8000 admissions; aOR 1·24, 1·17–1·32). Interpretation In South Africa, the second wave was associated with higher incidence of COVID-19, more rapid increase in admissions to hospital, and increased in-hospital mortality. Although some of the increased mortality can be explained by admissions in the second wave being more likely in older individuals, in the public sector, and by the increased health system pressure, a residual increase in mortality of patients admitted to hospital could be related to the new Beta lineage. Funding DATCOV as a national surveillance system is funded by the National Institute for Communicable Diseases and the South African National Government.

Background. The benefit of deep learning compared with surface learning is the ability to retrieve, apply and integrate previously learnt knowledge rather than simply memorising course content most likely to be evaluated during assessments. Team-based learning (TBL) is an educational strategy that echoes the purpose of deeper learning. Objectives. To identify whether TBL as a teaching strategy increases pharmacy students’ understanding of theoretical work. Method. Fourth-year pharmacy students completed a questionnaire consisting of biographical data (gender, age and ethnicity) and 16 questions on their understanding of course content. A total of 183 students (91.5%) participated after giving informed consent that their data may be included in the study. Results. The results indicated that, due to the implementation of TBL in the course, students perceived that they learnt more and made more effort, experienced increased understanding of content, perceived higher knowledge retention, performed better during assessments in the module where TBL was implemented and felt that course outcomes were achieved more easily. Conclusion. TBL as a teaching strategy could potentially promote deeper learning of course content.

Background and aims The L-arginine derivatives asymmetric (ADMA) and symmetric dimethylarginine (SDMA), as well as L-homoarginine may have opposing effects in the pathogenesis of atherosclerosis. We aimed to investigate (i) 5-year changes in arginine derivatives, and (ii) the association between baseline arginine derivatives and follow-up measures of carotid wall thickness in South Africans. Methods and results This study included men (n = 187) and women (n = 396) who took part in the 2010 and 2015 data collections of the South African arm of the Prospective Urban and Rural Epidemiology (PURE) study. Arginine derivatives were determined in plasma with liquid chromatography-tandem mass spectrometry. Carotid intima-media thickness (cIMT) and cross-sectional wall area (CSWA) were determined with B-mode ultrasonography. Results Mean values of arginine derivatives did not change over time. In the study group, follow-up cIMT (β = − 0.10 p = 0.018) and CSWA (β = − 0.12; p = 0.004) inversely associated with baseline L-homoarginine, and cIMT inversely associated with ADMA (β = − 0.09; p = 0.033). In women, CSWA inversely associated with both ADMA (β = − 0.11; p = 0.034) and L-homoarginine (β = − 0.11; p = 0.024). No such associations were found in men. Conclusion These results suggest that higher levels of L-homoarginine may play a protective role against vascular injury and delay progression of carotid wall thickening in this cohort. The role of ADMA in atherosclerosis deserves further investigation in this population

Information about the non-target effects of glyphosate, a broad-spectrum systemic herbicide on soil-borne nematodes is scarce and not well documented for South African agricultural fields. In the present study, the abundance and identity of plant-parasitic nematodes in roots and rhizosphere soil of commercial glyphosate- tolerant (genetically modified; GM) and conventional (non-glyphosate-tolerant) soybean cultivars from cultivated fields were obtained for two consecutive growing seasons. Grass and soil from adjacent natural vegetation were sampled, representing the reference system. Thirty plant-parasitic nematode species, belonging to 13 genera were identified in the roots and rhizosphere soil of soybean cultivars and natural vegetation. In rhizosphere soil, Meloidogyne (for glyphosate-tolerant and conventional soybean), followed by Helicotylenchus (for glyphosate-tolerant soybean) and Scutellonema (for conventional soybean), were the predominant genera. Seven species, namely Pratylenchus flakkensis, Pratylenchus scribneri, Pratylenchus vulnus, Rotylenchus brevicaudatus, Telotylenchus avaricus, Tylenchorhynchus brevicaudatus and Quinisulcius capitatus are first reports for soybean in South Africa. Although it was not possible to define the impact of each ecosystem on the plant-parasitic nematode assemblages, this study suggested that glyphosate had no deleterious effects on plant-parasitic nematodes

Superconductor electronics is gaining traction as the increasing density of integration of recent and future digital circuits pushes the limits of available simulation models. Designers often make assumptions in the behavioral models of circuit elements when simulating circuits. For instance high-frequency effects have been neglected so far in the design of superconductor digital circuits, while much has been done in the past to model them. Indeed these effects had little influence on the accuracy of digital circuits simulations until recently. The increase in clock frequency, combined with longer paths between cells and higher yield requirements for large scale circuits fabrication, has led to the need of more accurate models, including in particular high frequency effects such as quasi-particle losses. To do so, this work uses a state-space model that describes the circuit under study with internal state variables and a set of first-order differential equations. We extract the state-space model while analytically enforcing the DC requirements of superconductors that are required to account for flux-trapping. The model accurately traps flux at DC, and given the model is fitted with enough poles, the high-frequency effects are also accurate relative to the reference model. The high-frequency effects have been investigated on a practical circuit: a long-distance Passive Transmission Line (PTL) designed for the high-density MIT Lincoln Labs SFQ5ee process. Results obtained in the time domain allow to observe the effects of dispersion of pulses traveling on long paths of PTLs. Indeed the energy of voltage pulses is sufficient to break Cooper pairs for the highest clock frequencies.

Funding: This paper presents independent research supported by the National Funding: Institute for Health Research (NIHR) Clinical Research Facility and the NIHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust. AA is supported by an NIHR Clinician Scientist award (CS‐2018‐18‐ST2‐002). MAM is funded by the Tommy’s National Centre for Miscarriage Research. MP is supported by an NIHR Academic Clinical Lectureship. CI-E is supported by an Imperial College-BRC IPPRF Fellowship. SAC is supported by an NIHR Academic Clinical Lectureship. EGM is supported by an MRC clinical training fellowship (MR/T006242/1). LY is supported by an MRC clinical training fellowship (MR/R000484/1). ANC is supported by the NHS and BRC. TB is supported by the NIHR Biomedical Research Centre based at Imperial College Healthcare NHS Trust. WSD is supported by an NIHR Research Professorship (RP-2014-05-001). Context: Antenatal complications such as hypertensive disorders of pregnancy (HDP), fetal growth restriction (FGR), gestational diabetes (GDM), and preterm birth (PTB) are associated with placental dysfunction. Kisspeptin has emerged as a putative marker of placental function, but limited data exist describing circulating kisspeptin levels across all three trimesters in women with antenatal complications. Objective: To assess whether kisspeptin levels are altered in women with antenatal complications. Methods: Women with antenatal complications (n = 105) and those with uncomplicated pregnancies (n = 265) underwent serial ultrasound scans and blood sampling at the Early Pregnancy Assessment Unit at Hammersmith Hospital, UK, at least once during each trimester (March 2014 to March 2017). The women with antenatal complications (HDP [n = 32], FGR [n = 17], GDM [n = 35], PTB [n = 11], and multiple complications [n=10]) provided 373 blood samples and the controls provided 930 samples. Differences in circulating kisspeptin levels were assessed. Participants: Women with antenatal complications: HDP (n=32), FGR (n=17), GDM (n=35) and PTB (n=11), and 10 women with multiple complications, provided 373 blood samples, and a further 265 controls provided 930 samples. Results: Third-trimester kisspeptin levels were higher than controls in HDP but lower in FGR. The odds of HDP adjusted for gestational age, maternal age, ethnicity, BMI, smoking, and parity were increased by 30% (95% CI, 16%-47%; P

Background Moxifloxacin is a recommended drug for rifampin-resistant tuberculosis (RR-TB) treatment, but there is limited pediatric pharmacokinetic and safety data, especially in young children. We characterize moxifloxacin population pharmacokinetics and QT interval prolongation and evaluate optimal dosing in children with RR-TB. Methods Pharmacokinetic data were pooled from 2 observational studies in South African children with RR-TB routinely treated with oral moxifloxacin once daily. The population pharmacokinetics and Fridericia-corrected QT (QTcF)-interval prolongation were characterized in NONMEM. Pharmacokinetic simulations were performed to predict expected exposure and optimal weight-banded dosing. Results Eighty-five children contributed pharmacokinetic data (median [range] age of 4.6 [0.8–15] years); 16 (19%) were aged Conclusions Moxifloxacin doses above 10–15 mg/kg are likely required in young children to match adult exposures but require further safety assessment, especially when coadministered with other QT-prolonging agents.

In the following systematic review and meta-analyses, we report several conclusions about resistance to carbapenem and polymyxin last-resort antibiotics for treating multidrug-resistant bacterial infections among pregnant women and infants. Resistance to carbapenems and polymyxins is increasing, even in otherwise vulnerable groups such as pregnant women, toddlers, and infants, for whom therapeutic options are limited. In almost all countries, carbapenem-/polymyxin-resistant Klebsiella pneumoniae, Escherichia coli, and Acinetobacter baumannii infect and/or colonize neonates and pregnant women, causing periodic outbreaks with very high infant mortalities. Downregulation of plasmid-borne blaNDM , blaKPC , blaOXA-48 , blaIMP, blaVIM , blaGES-5 , and ompK35/36 in clonal strains accelerates the horizontal and vertical transmissions of carbapenem resistance among these pathogens. New Delhi metallo-β-lactamase (NDM)-positive isolates in infants/neonates have been mainly detected in China and India, while OXA-48-positive isolates in infants/neonates have been mainly detected in Africa. NDM-positive isolates in pregnant women have been found only in Madagascar. Antibiotic therapy, prolonged hospitalization, invasive procedures, mechanical ventilation, low birth weight, and preterm delivery have been common risk factors associated with carbapenem/polymyxin resistance. The use of polymyxins to treat carbapenem-resistant infections may be selecting for resistance to both agents, restricting therapeutic options for infected infants and pregnant women. Currently, low- and middle-income countries have the highest burden of these pathogens. Antibiotic stewardship, periodic rectal and vaginal screening, and strict infection control practices in neonatal ICUs are necessary to forestall future outbreaks and deaths.

Breast cancer is the most frequently diagnosed cancer in women globally. Although there have been many significant advances made in the diagnosis and treatment of breast cancer, numerous unresolved challenges remain, which include prevention, early diagnosis, metastasis and recurrence. The role of inflammation in cancer development is well established and is believed to be one of the leading hallmarks of cancer progression. Recently, the role of the inflammasome, a cytosolic multiprotein complex, has received attention in different cancers. By contributing to the activation of inflammatory cytokines the inflammasome intensifies the inflammatory cascade. The inflammasome can be activated through several pathways, which include the binding of pattern associated molecular patterns (PAMPs) and damage associated molecular patterns (DAMPs) to toll-like receptors (TLRs). Serum amyloid A (SAA), a non-specific acute-phase protein, can function as an endogenous DAMP by binding to pattern recognition receptors like TLRs on both breast cancer cells and cancer associated fibroblasts (CAFs). SAA can thus stimulate the production of IL-1β, thereby creating a favourable inflammatory environment to support tumour growth. The aim of this review is to highlight the possible role of SAA as an endogenous DAMP in the tumour microenvironment (TME) thereby promoting breast cancer growth through the activation of the NLRP3 inflammasome.

Nitric oxide plays a major role in the regulation of blood pressure, and impaired nitric oxide bioavailability contributes to the development of hypertension (HT). Various factors may contribute to nitric oxide bioavailability-including availability of the substrate for nitric oxide synthesis, L-arginine and its homolog L-homoarginine. We investigated whether blood pressure after 10 years associates with baseline L-homoarginine in participants who remained normotensive (NT) or developed HT, respectively. Data from the South African leg of the Prospective Urban and Rural Epidemiology study, performed in the North-West Province, were used. We investigated participants who either remained NT (N = 166) or who developed HT (N = 166) over 10 years. Blood pressure was measured with validated OMRON devices and serum L-homoarginine was analyzed with liquid chromatography-tandem mass spectrometry. L-homoarginine levels were similar at baseline (p = 0.39) and follow-up (p = 0.93) between NT and hypertensive groups. In the group that remained NT after 10 years, baseline L-homoarginine correlated positively with follow-up brachial systolic blood pressure (adj.R2 = 0.13; β = 0.33; p = 0.001), brachial pulse pressure (adj.R2 = 0.15 β = 0.40; p = 0.001), and central pulse pressure (adj.R2 = 0.20; β = 0.30; p = 0.003). No significant associations were found in the group that developed HT after 10 years. We found a positive, independent association between blood pressure and L-homoarginine in a group that remained NT, but not in a group that developed HT after 10 years. This may suggest a protective role for L-homoarginine to maintain normal blood pressure, but only to a certain level. Once HT develops other factors may overshadow the protective effects of L-homoarginine.

The potential for human adipose-derived stromal cells (hASCs) to be used as a therapeutic product is being assessed in multiple clinical trials. However, much is still to be learned about these cells before they can be used with confidence in the clinical setting. An inherent characteristic of hASCs that is not well understood is their heterogeneity. The aim of this exploratory study was to characterize the heterogeneity of freshly isolated hASCs after two population doublings (P2) using single-cell transcriptome analysis. A minimum of two subpopulations were identified at P2. A major subpopulation was identified as contractile cells which, based on gene expression patterns, are likely to be pericytes and/or vascular smooth muscle cells (vSMCs).

In light of the various advantages the e-learning experience could have for students, a blended teaching approach, where instructors make use of e-learning, has become increasingly prominent in higher education institutions. This study, which was conducted at a South African institute of higher education with a diverse and multilingual student population, focusses on student perceptions of theefficacy and accessibility of a multimodal tool called WIReD to supplement the existing academic literacy module. The review of student perceptions was structured around the outcomes for the module unit with which WIReD is intended to blend. In order to determine student perception, a questionnaire using a Likert-scale to measure responses along with open-ended questions, were used. As such, this study firstly examined students’ impressions of the design (overall appearance) and accessibility of WIReD. Secondly, it investigated the appropriateness of content, especially with regard to the envisaged blend between WIReD and the module contentas taught during lectures and in the workbook. Despite being a pilot study with results based exclusively on student perception, it seems that WIReD can be utilized as a supplementary multimodal tool and that the outcomes thereof blends effectively with the outcomes of the academic literacy module. Keywords: academic literacy; blended learning; e-learning; multimodal teaching tool; student perception; WIReD

The responsibility for building community resilience cannot and should not rest with the public sector alone. It requires all sectors to collaborate for the benefit of the entire community. Specifically, it is important for private sector organisations to participate in building community resilience because they have vested interest in the area because of their physical assets, suppliers, customers and corporate value of social responsibility. This article explores collaboration between private companies and community of Diepsloot, Johannesburg, South Africa, to build disaster resilience in the community. The study applied qualitative research methods. Data were collected through focus group interviews with the community of Diepsloot and semi-structured individual interviews with representatives of private companies operating in the vicinity of Diepsloot. A total of 55 respondents participated in the study. Respondents included five corporate social responsibility (CSR) managers from private companies and 50 community members. The findings of the study showed that private companies are involved in addressing socio-economic challenges in Diepsloot. Addressing such challenges contributes a great deal to reducing exposure to hazards and the vulnerability factors to disasters, thereby contributing to building resilience. Whereas some respondents preferred the private companies to work with the communities directly, the study recommends the use of community structures such as Community Based Organisations (CBOs) when private companies engage in community initiatives. The article contributes to better understanding of the private sector’s contribution to build community resilience.

Depression continues to carry a major disease burden worldwide, with limitations on the success of traditional pharmacological or psychological treatments. Recent approaches have therefore focused upon the neurobiological underpinnings of depression, and on the “individualization” of depression symptom profiles. One such model of depression has divided the standard diagnostic criteria into four “depression subtypes”, with neurological and behavioral pathways. At the same time, attention has been focused upon the region of the brain known as the “default mode network” (DMN) and its role in attention and problem-solving. However, to date, no review has been published of the links between the DMN and the four subtypes of depression. By searching the literature studies from the last 20 years, 62 relevant papers were identified, and their findings are described for the association they demonstrate between aspects of the DMN and the four depression subtypes. It is apparent from this review that there are potential positive clinical and therapeutic outcomes from focusing upon DMN activation and connectivity, via psychological therapies, transcranial magnetic stimulation, and some emerging pharmacological models.

In this article, I consider two fairly recent English poems by Marlene van Niekerk: “Mud school” (2013) and “Fallist art (in memory of Bongani Mayosi)” (2018). Specifically, I explore the context s...

Robotics and related technologies are central to the ongoing digitization and advancement of manufacturing. In recent years, a variety of strategic initiatives around the world including "Industry 4.0", introduced in Germany in 2011 have aimed to improve and connect manufacturing technologies in order to optimize production processes. In this work, we study the changing technological landscape of robotics and "internet-of-things" (IoT)-based connective technologies over the last 7-10 years in the wake of Industry 4.0. We interviewed key players within the European robotics ecosystem, including robotics manufacturers and integrators, original equipment manufacturers (OEMs), and applied industrial research institutions and synthesize our findings in this paper. We first detail the state-of-the-art robotics and IoT technologies we observed and that the companies discussed during our interviews. We then describe the processes the companies follow when deciding whether and how to integrate new technologies, the challenges they face when integrating these technologies, and some immediate future technological avenues they are exploring in robotics and IoT. Finally, based on our findings, we highlight key research directions for the robotics community that can enable improved capabilities in the context of manufacturing.

Local, district, and metropolitan municipalities as spheres of government should deploy a highly competent and professional management corps to address complex integrated development planning demands, local service delivery issues, and various governance-related dynamics (Polo & Kantola, 2019). However, official oversight, performance reports, and media scrutiny regularly reveal that the current South African situation fails to meet these requirements. Corruption, maladministration, political factionalism, and managerial incompetence have led to violent public protests (SACN, 2016). This paper assesses the current competency profile of senior managers in the South African local government sector, focusing on their integrated development planning responsibilities. The methodology followed a qualitative design involving an intensive literature review on international management competency models, document analyses to assess official statutory and regulatory prescriptions for senior managers, and semi-structured interviews with senior managers in sampled municipalities. The study established that most challenges faced by municipalities stem from a lack of senior management competency. Recommendations are made to address the current competency deficit.

Background Silicone adhesive multilayer foam dressings are used as adjuvant therapy to prevent hospital-acquired pressure ulcers (PUs). Objectives To determine whether silicone foam dressings in addition to standard prevention reduce the incidence of PUs of category 2 or worse compared with standard prevention alone. Methods This was a multicentre, randomized controlled medical device trial conducted in eight Belgian hospitals. At-risk adult patients were centrally randomized (n = 1633) to study groups based on a 1 : 1 : 1 allocation: experimental groups 1 (n = 542) and 2 (n = 545) - pooled as the treatment group - and the control group (n = 546). The experimental groups received PU prevention according to hospital protocol, and a silicone foam dressing on the relevant body sites. The control group received standard of care. The primary endpoint was the incidence of a new PU of category 2 or worse at the studied body sites. Results In the intention-to-treat population (n = 1605), PUs of category 2 or worse occurred in 4·0% of patients in the treatment group and 6·3% in the control group [relative risk (RR) 0·64, 95% confidence interval (CI) 0·41-0·99, P = 0·04]. Sacral PUs were observed in 2·8% and 4·8% of the patients in the treatment group and the control group, respectively (RR 0·59, 95% CI 0·35-0·98, P = 0·04). Heel PUs occurred in 1·4% and 1·9% of patients in the treatment and control groups, respectively (RR 0·76, 95% CI 0·34-1·68, P = 0·49). Conclusions Silicone foam dressings reduce the incidence of PUs of category 2 or worse in hospitalized at-risk patients when used in addition to standard of care. The results show a decrease for the sacrum, but no statistical difference for the heel and trochanter areas.

Background People living with the Human Immunodeficiency Virus (PLHIV) have an increased susceptibility to develop non-communicable diseases such as cardiovascular disease (CVD). Infection with HIV contributes to the development of CVD independent of traditional risk factors, with endothelial dysfunction being the central physiological mechanism. While HIV-related mortality is declining due to antiretroviral treatment (ART), the number of deaths due to CVD is rising in South Africa - the country with the highest number of PLHIV and the world's largest ART programme. The EndoAfrica study was developed to determine whether HIV infection and ART are associated with cardiovascular risk markers and changes in vascular structure and function over 18 months in adults from different provinces of South Africa. This paper describes the rationale, methodology and baseline cohort profile of the EndoAfrica study conducted in the North West Province, South Africa. Methods In this case-control study, conducted between August 2017 and June 2018, 382 volunteers of African descent (276 women; 106 men), comprising of 278 HIV infected and 104 HIV free individuals were included. We measured health behaviours, a detailed cardiovascular profile, and performed biomarker analyses. We compared baseline characteristics, blood pressure, vascular function and biochemical markers between those infected and HIV free. Results At baseline, the HIV infected participants were older (43 vs 39 years), less were employed (21% vs 40%), less had a tertiary education (7% vs 16%) and their body mass index was lower (26 vs 29 kg/m(2)) than that of the HIV free participants. While the cardiovascular profile, flow-mediated dilation and pulse wave velocity did not differ, glycated haemoglobin was lower (p = 0.017) and total cholesterol, high density lipoprotein cholesterol, triglycerides, gamma-glutamyltransferase and tobacco use were higher (allp < 0.047) in PLHIV. Conclusion Despite PLHIV being older, preliminary cross-sectional analysis suggests that PLHIV being treated with ART do not have poorer endothelial or vascular function compared to the HIV free participants. More detailed analyses on the baseline and follow-up data will provide further clarity regarding the cardiovascular profile of South Africans living with HIV. The EndoAfrica-NWU study formed part of a broader consortium under the ERAfrica program of the European Union 7th Framework Program. Funding is disbursed via the Department of Science and Innovation in South Africa (contract number DST/CON 0077/2014). AES is funded by the South African National Research Foundation (SARChI GUN 86895) and South African Medical Research Council. PDB and NG received funding from the Belgian Science Policy in Belgium (Grant number BL/67/eranet03), and the Osterreichische Agentur fur internationale Mobilitat und Kooperation in Bildung, Wissenschaft und Forschung, OeAD GmbH (OAD) in Austria (Grant number: KEF-Projekt P202). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Fourie, CMT (corresponding author), North West Univ, Hypertens Africa Res Team HART, Private Bag X1290, Potchefstroom, South Africa; North West Univ, Fac Hlth Sci, South African Med Res Council, Unit Hypertens & Cardiovasc Dis, Potchefstroom, South Africa. carla.fourie@nwu.ac.za

On May 8, 2020, the FDA granted accelerated approval to selpercatinib for (i) adult patients with metastatic RET fusion–positive non–small cell lung cancer (NSCLC), (ii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET-mutant medullary thyroid cancer who require systemic therapy, and (iii) adult and pediatric patients ≥12 years of age with advanced or metastatic RET fusion–positive thyroid cancer who require systemic therapy and who are radioactive iodine refractory (if radioactive iodine is appropriate). Approval was granted on the basis of the clinically important effects on the overall response rate (ORR) with prolonged duration of responses observed in a multicenter, open-label, multicohort clinical trial (LIBRETTO-001, NCT03157128) in patients whose tumors had RET alterations. ORRs within the approved patient populations ranged from 64% [95% confidence interval (CI), 54–73] in prior platinum-treated RET fusion–positive NSCLC to 100% (95% CI, 63–100) in systemic therapy–naïve RET fusion–positive thyroid cancer, with the majority of responders across indications demonstrating responses of at least 6 months. The product label includes warnings and precautions for hepatotoxicity, hypertension, QT interval prolongation, hemorrhagic events, hypersensitivity, risk of impaired wound healing, and embryo-fetal toxicity. This is the first approval of a drug specifically for patients with RET alterations globally.

Clinical specimens unfit for laboratory processing represent missed opportunities for diagnosing tuberculosis. Poor-quality cough specimens (n=61) from presumptive tuberculosis cases were cultured and GeneXpert MTB/RIF (Xpert) successfully performed on samples transferred by flocked swab into PrimeStore molecular transport medium (PS-MTM). Mycobacterium tuberculosis was grown in culture from 13 (21.3 %) and Xpert reported 15 (24.2 %) positive, of which 10 concordant. RT-PCR of PS-MTM samples showed enhanced sensitivity; three positives were missed by Xpert, five by culture and three more detected for a total of 21 positives (34.4 %).

1. Land use intensification and climate change are two prominent drivers of variation in biological communities. However, we know very little about how these two potential environmental stressors interact. Here, we use a stable isotope approach to quantify how animal communities respond to urban and agriculture land use, and to latitudinal variation in climate (rainfall and temperature), in 29 streams across South Africa. 2. Community structure was shaped by both land use and climatic factors. The taxonomic diversity of invertebrates was best explained by an independent negative effect of urbanisation, while abundance declined in summer. However, we could not use our variables to predict fish diversity (suggesting that other factors may be more important). 3. Both trophic functional diversity (quantifed using isotopic richness ) and food chain length declined with increasing temperature. Functional redundancy (quantifed using isotopic uniqueness ) in the invertebrate community was high in wet areas, and a synergistic interaction with urbanisation caused the lowest values in dry urban regions. There was an additive effect of agriculture and rainfall on abundance‐weighted vertebrate functional diversity (quantified using isotopic dispersion ), with the former causing a decline in dispersion, with this partially compensated for by high rainfall. 4. In most cases, we found that a single dominant driver (either climate or land use) explained variation between streams. We only found two incidences of combined effects improving the model, one of which was amplified (i.e., the drivers combined to cause an effect larger than the sum of their independent effects), indicating that management should first focus on mitigating the dominant stressor in stream ecosystems for successful restoration efforts. 5. Overall, our study indicates subtle food web responses to multiple drivers of change, only identified by using functional isotope metrics – these are a useful tool for a whole‐systems biology understanding of global change.

Machine learning has become an immensely important technique for automatically extracting information from large data sets. By doing so, it has become a valuable tool in various industries. In this investigation, the use of machine learning techniques for the production of railway wheel prognostics was investigated. Metrorail’s railway wheel wear data was used as a case study for this investigation. The goal was to demonstrate how machine learning can used on the data generated by Metrorail’s routine operations. Three machine learning models were implemented: logistic regression, artificial neural networks, and random forest. The investigation showed that all three models provided prognoses with an accuracy of over 90 per cent, and had an area under curve (AUC) measurement exceeding 0.8. Random forest was the best performing model, with an AUC measurement of 0.897 and an accuracy of 93.5 per cent.

We present the development of a low-noise, fundamental-mode, orthogonal fluxgate magnetometer with four amorphous, annealed ferromagnetic wires. The 1-Hz noise obtained in the open and closed loop is as low as 0.75 and 1.5 pTrms/ $\surd $ Hz, respectively, with the white noise level about 0.6 pTrms/ $\surd $ Hz. This is to the best of our knowledge the lowest figure published for a fluxgate magnetometer so far. By using the annealed sensor cores, we also found the offset drift to decrease approximately six times to 2.5 nT/K. We compared the instrument performance to a low-noise observatory magnetometer when doing geomagnetic measurements and show that it is fully suitable for measurements at mHz frequencies, e.g., magnetotellurics. The magnetometer performance enables room-temperature, unshielded magnetocardiography. With a gradiometric arrangement of two sensors, we were able to perform an MCG measurement in ambient field, and even without averaging, the signal could be clearly resolved.

OBJECTIVES: Our primary aim was to report the incidence of enhanced myometrial vascularity (EMV) in consecutive women attending our early pregnancy assessment unit, following first-trimester miscarriage. We aimed further to evaluate the clinical presentation and complications associated with expectant and surgical management of EMV in these women. METHODS: This was a prospective cohort study conducted in a London teaching hospital between June 2015 and June 2018, including consecutive patients with an observation of EMV on transvaginal ultrasonography following first-trimester miscarriage. The diagnosis was made following the subjective identification of EMV using color Doppler ultrasonography and a peak systolic velocity (PSV) ≥ 20 cm/s within the collection of vessels. Women were followed up with repeat scans every 14 days. Management was expectant unless intervention was indicated because of excessive or prolonged bleeding, persistent presence of retained tissue in the endometrial cavity or patient choice. The final clinical outcome was recorded. Time to resolution of EMV was defined as the interval from detection of EMV until resolution. RESULTS: During the study period, there were 2627 first-trimester fetal losses in the department and, of these, 40 patients were diagnosed with EMV, hence the incidence of EMV following miscarriage was 1.52%. All cases were associated with ultrasound evidence of retained products of conception (RPOC) at presentation (mean dimensions, 22 × 20 × 20 mm). Thirty-one patients opted initially for expectant management, of which 18 had successful resolution without intervention, five were lost to follow-up and eight subsequently had surgical evacuation due to patient choice. No expectantly managed case required emergency intervention. Nine patients chose surgical evacuation as primary treatment. No significant correlation was seen between PSV within the EMV at presentation and blood loss at surgery. Median PSV was 47 (range, 20-148) cm/s. The estimated blood loss in all cases managed surgically ranged from 20-300 mL. Presence of RPOC was confirmed in all specimens that were sent for analysis following surgery. For cases successfully managed expectantly, the mean time to resolution was 48 (range, 21-84) days. In the nine cases managed surgically from the beginning, the mean time to resolution of EMV was 10.6 (range, 3-29) days. CONCLUSIONS: This study suggests that EMV is an uncommon finding following miscarriage and is associated with the presence of RPOC. Expectant management was a safe option in our cohort, with minimal bleeding, although it was associated with protracted time to resolution. In patients who opted for surgery, the maximum blood loss was 300 mL and no patient required blood transfusion or embolization. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:55 issue:5 pages:676-682 ispartof: location:England status: published

OBJECTIVE: To assess whether sonographic diagnosis of intrauterine hematoma (IUH) in the first trimester of pregnancy is associated with first-trimester miscarriage and antenatal, delivery and neonatal complications. METHODS: This was a prospective observational cohort study of women with an intrauterine singleton pregnancy between 5 and 14 weeks' gestation recruited at Queen Charlotte's and Chelsea Hospital, London, UK, between March 2014 and March 2016. Participants underwent serial ultrasound examinations in the first trimester, and the presence, location, size and persistence of any IUH was evaluated. First-trimester miscarriage was defined as pregnancy loss before 14 weeks' gestation. Clinical symptoms, including pelvic pain and vaginal bleeding, were recorded at each visit using validated symptom scores. Antenatal, delivery and neonatal outcomes were obtained from hospital records. Logistic regression analysis and the chi-square test were used to assess the association between the presence and features of IUH and the incidence of adverse pregnancy outcome. Odds ratios (OR) were first adjusted for maternal age (aOR) and then further adjusted for the presence of vaginal bleeding or pelvic pain in the first trimester. RESULTS: Of 1003 women recruited to the study, 946 were included in the final analysis and of these, 268 (28.3%) were diagnosed with an IUH in the first trimester. The presence of IUH was associated with the incidence of preterm birth (aOR, 1.94 (95% CI, 1.07-3.52)), but no other individual or overall antenatal, delivery or neonatal complications. No association was found between the presence of IUH in the first trimester and first-trimester miscarriage (aOR, 0.81 (95% CI, 0.44-1.50)). These findings were independent of the absolute size of the hematoma and the presence of vaginal bleeding or pelvic pain in the first trimester. When IUH was present in the first trimester, there was no association between its size, content or position in relation to the gestational sac and overall antenatal, delivery and neonatal complications. Diagnosis of a retroplacental IUH was associated with an increased risk of overall antenatal complications (P = 0.04). CONCLUSIONS: Our findings demonstrate that there is no association between the presence of IUH in the first trimester and first-trimester miscarriage. However, an association with preterm birth, independently of the presence of symptoms of pelvic pain and/or vaginal bleeding, is evident. Women diagnosed with IUH in the first trimester should be counseled about their increased risk of preterm birth and possibly be offered increased surveillance during the course of their pregnancy. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:55 issue:4 pages:536-545 ispartof: location:England status: published

Unexpected Postoperative Diagnosis of Parathyroid Carcinoma Abstract. Parathyroid carcinoma is a rare endocrine malignancy. It typically presents itself with similar clinical features as seen in patients with primary hyperparathyroidism caused by a parathyroid adenoma. Due to overlapping clinical manifestations, imaging findings and pathological characteristics, the differentiation between benign and malignant parathyroid disease poses a diagnostic challenge, especially prior to surgery. We report the case of a 67-year-old male who presented with symptomatic hypercalcemia and primary hyperparathyroidism. During resection of the enlarged parathyroid gland, suspicious macroscopic features were noticed and the histopathology finding confirmed the malignancy. Parathyroid carcinoma is rarely diagnosed preoperatively, which is mainly due to the lack of distinctive symptoms or morphological features suggesting a malignant disease. As parathyroid carcinoma often has a genetic background, knowledge of mutation status and family history is of high relevance. Surgery with complete resection of the parathyroid carcinoma is the mainstay for a successful treatment and a good prognosis.

Cough-associated headache (CAH) is the most distinctive symptom of patients with Chiari I malformation (CMI) and indicates clinically significant disease. We determined the clinical utility of simple 2D anatomic measurements performed on a PACS workstation by assessing their diagnostic accuracy in predicting CAH in CMI patients. Seventy-two consecutive CMI patients (cerebellar tonsillar herniation > 5 mm) with headache seen by neurosurgeons over 6 years were included. Sagittal T1 images were used by two readers to measure: extent of tonsillar herniation, lengths of the clivus and supra-occiput, McRae and pB-C2 lines, as well as clivus-canal, odontoid retroversion, and skull base angles. Neurosurgery notes were reviewed to determine presence of CAH. Mann-Whitney test was used to compare measurements between patients with and without CAH. Predictive accuracy was assessed by receiver operating characteristic (ROC) curve. 47/72 (65.3%) CMI patients reported CAH. Tonsillar herniation with CAH (10.2 mm, 7–14 mm; median, interquartile range) was significantly greater than those without CAH (7.9 mm, 6.3–10.9 mm; p = 0.02). Tonsillar herniation ≥ 10 mm showed sensitivity and specificity of 51% and 68%, and tonsillar herniation > 14 mm showed sensitivity and specificity of 30% and 100%, respectively, for predicting CAH. Other 2D measurements showed no statistically significant differences. Among the 2D measurements used, only the extent of tonsillar herniation is different between CMI patients with and without CAH. Although CMI is diagnosed with tonsillar herniation of only 5 mm, we found that a much higher extent of herniation is needed to be predictive of CAH.

Large-scale urban conflagrations in informal settlements are a frequent global event, however there is a lack of experimental research and knowledge within literature on how informal settlements fires spread to support local or national intervention strategies. This paper, therefore, presents results and analysis of a full-scale fire spread experiment of a mock 20 dwelling test settlement with a 4 by 5 layout aimed at understanding settlement-scale fire spread behaviour. A “fire line” scenario was created by imultaneously igniting four dwellings in a row, and then allowing the fire to propagate through the settlement to replicate fire disasters involving large numbers of homes. Results highlight the critical hazard posed by the close proximity of neighbouring dwellings (1-2 m), with wind playing a primary role in directing and driving the spread process. Even with a relatively mild wind speed of 15-25 km/h, the fire spread through the entire mock settlement within a mere 5 minutes. Following ignition of a given dwelling, flashover is reached very quickly, with the temperatures reaching more than 1000°C within one minute, and downwind neighbour structures igniting less than a minute thereafter. The results suggest that multi-dwelling effects are not dominant in these types of fires, but may become meaningful at a larger scale when branding and topography play a role. Findings show that on a global scale fire behaviour is analogous to a wildfire with a continuous fire front moving through an area, although individual dwellings still do follow the distinct phases of enclosure fires, except that collapse occurs more rapidly than in formal structures. This experiment represents one of the larger urban fire tests conducted to date, and the largest informal settlement fire experiment.

The sarcoid-lymphoma syndrome is a rare condition where both entities co-exist in the same patient. Overlapping clinical manifestations, imaging findings, and pathological characteristics pose both a diagnostic as well as therapeutic challenge, especially in the setting of life-threatening complications. The objective of this case report is to highlight rare complications caused by abdominal sarcoidosis as well as a subsequently diagnosed non-Hodgkin lymphoma. A 35-year-old man presented with massive upper gastrointestinal bleeding caused by a large retroperitoneal mass. Following several endoscopic and radiologic interventions, successful hemostasis could only be achieved by an emergency Whipple procedure. Biopsies of the mass showed an abdominal manifestation of sarcoidosis and corticosteroid therapy was started. The patient required several additional emergency surgeries due to a complicated bronchoperitoneal fistula, splenic abscess, perforation of the sigmoid colon, small bowel leakage, and repetitive intra-abdominal bleeding. Histopathological findings finally revealed a concurrent lymphoma, as clinically suspected earlier. Ultimately, polychemotherapy was administered. A concurrent lymphoma can lead to emergency surgery and should be considered when sarcoidosis treatment does not improve symptoms, lymphadenopathy occurs, or hematologic changes persist under therapy.

Institutions of higher education play a critical role in bridging academia and workforce, yet college students find it challenging to transfer their learning across and beyond instructional formats, including online, hybrid, and face-to-face. The goals of this exploratory, sequential, mixed-methods study were to (1) explore graduate students’ conceptualizations of transfer, and (2) examine online pedagogical practices for enhancing transfer. Participants included students enrolled in a full-time online graduate degree program in education at a private university in the Mid-Atlantic USA. Findings from the qualitative phase with seven semi-structured interviews were used to design a survey study with 68 graduate students to explore their perceptions of effective online pedagogical practices for enhancing transfer. This study is significant since its findings revealed a number of online practices that instructional designers and faculty can use to optimize learning and transfer in higher education.

Made available in DSpace on 2022-05-01T10:19:00Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-12-01 Background: Arthropod-borne pathogens and their vectors are present throughout Africa. They have been well-studied in livestock of sub-Saharan Africa, but poorly in companion animals. Given the socio-economic importance of companion animals, the African Small Companion Animal Network (AFSCAN), as part of the WSAVA Foundation, initiated a standardized multi-country surveillance study. Methods: Macro-geographic variation in ectoparasite (ticks and fleas) and pathogen communities in dogs was assessed through molecular screening of approximately 100 infested dogs in each of six countries (Ghana, Kenya, Nigeria, Tanzania, Uganda and Namibia), both in rural and urban settings. The most important intrinsic and extrinsic risk factors within the subpopulation of infested dogs were evaluated. Results: Despite the large macro-geographic variation in the dogs screened, there was no consistent difference between East and West Africa in terms of the diversity and numbers of ticks. The highest and lowest numbers of ticks were found in Nigeria and Namibia, respectively. Most often, there was a higher diversity of ticks in rural habitats than in urban habitats, although the highest diversity was observed in an urban Uganda setting. With the exception of Namibia, more fleas were collected in rural areas. We identified tick species (including Haemaphysalis spinulosa) as well as zoonotic pathogens (Coxiella burnetti, Trypanosoma spp.) that are not classically associated with companion animals. Rhipicephalus sanguineus was the most abundant tick, with a preference for urban areas. Exophilic ticks, such as Haemaphysalis spp., were more often found in rural areas. Several multi-host ticks occurred in urban areas. For R. sanguineus, housing conditions and additional pets were relevant factors in terms of infestation, while for a rural tick species (Haemaphysalis elliptica), free-roaming dogs were more often infested. Tick occurrence was associated to the use of endoparasiticide, but not to the use of ectoparasiticide. The most prevalent tick-borne pathogen was Hepatozoon canis followed by Ehrlichia canis. High levels of co-parasitism were observed in all countries and habitats. Conclusions: As dogs share a common environment with people, they have the potential to extend the network of pathogen transmission to humans. Our study will help epidemiologists to provide recommendations for surveillance and prevention of pathogens in dogs and humans. Graphical abstract: [Figure not available: see fulltext.]. Eco-Epidemiology Group Department of Biomedical Sciences Institute of Tropical Medicine Interuniversity Institute for Biostatistics and Statistical Bioinformatics Hasselt University Department of Ecology and Evolutionary Biology Princeton University School of Veterinary and Life Sciences Murdoch University Bayer Animal Health Elanco Animal Health Inc. Clinvet LLC ClinVet International (Pty) Ltd. Clinomics School of Veterinary Medicine College of Basic and Applied Sciences (CBAS) University of Ghana Department of Veterinary Pathology Microbiology and Parasitology University of Nairobi Department of Veterinary Parasitology and Entomology College of Veterinary Medicine Federal University of Agriculture Sokoine University of Agriculture Research Center for Tropical Diseases and Vector Control College of Veterinary Medicine Animal Resources and Biosecurity Makerere University School of Veterinary Medicine University of Namibia, Neudamm São Paulo State University University of Pretoria Clinglobal São Paulo State University

Parasites threaten human and animal health globally. It is estimated that more than 60% of people on planet Earth carry at least one parasite, many of them several different species. Unfortunately, parasite studies suffer from duplications and inconsistencies between different investigator groups. Hence, groups need to collaborate in an integrated manner in areas including parasite control, improved therapy strategies, diagnostic and surveillance tools, and public awareness. Parasite studies will be better served if there is coordinated management of field data and samples across multidisciplinary approach plans, among academic and non-academic organizations worldwide. In this paper we report the first 'Living organism-World Molecular Network', with the cooperation of 167 parasitologists from 88 countries on all continents. This integrative approach, the 'Sarcoptes-World Molecular Network', seeks to harmonize Sarcoptes epidemiology, diagnosis, treatment, and molecular studies from all over the world, with the aim of decreasing mite infestations in humans and animals. © 2011 International Society for Infectious Diseases.

When considering sustainability from a socioeconomic and environmental point, the South African public transport industry was not an integral part of such planning until the last decade. Various well-intended and well-defined public procurement and environmental regulatory policies and instruments were put in place over the years, however, they appear to be failing in achieving the goals of local job creation and alleviation of unemployment. This exploratory literature review study of various public documents, regulatory instruments, and review reports aims to evaluate current knowledge pertaining to the current level of sustainable transport from a life-cycle approach, in support of overall sustainable goals in South Africa. The research set out to assess the status of public procurement in the revitalising of public rail freight transport towards identifying areas of excellence that could be used to address under-performance in other areas. The documentary analysis found various areas where the public procurement policies within South Africa, which aims to promote local participation, are facing difficulties due to lack of access to modern technology as well as inadequate skills levels to be able to partake in the ventures. In exploring South African challenges and current solutions, the article recommends a holistic and integrated approach to provide for a sustained manufacturing and service supply stream within the local railway transport environment.

Objectives: The PartneRships in cOngeniTal hEart disease (PROTEA) project aims to establish a densely phenotyped and genotyped Congenital Heart Disease (CHD) cohort for southern Africa. This will facilitate research into the epidemiology and genetic determinants of CHD in the region. This paper introduces the PROTEA project, characterizes its initial cohort, from the Western Cape Province of South Africa, and compares the proportion or “cohort-prevalences” of CHD-subtypes with international findings.Methods: PROTEA is a prospective multicenter CHD registry and biorepository. The initial cohort was recruited from seven hospitals in the Western Cape Province of South Africa from 1 April 2017 to 31 March 2019. All patients with structural CHD were eligible for inclusion. Descriptive data for the preliminary cohort are presented. In addition, cohort-prevalences (i.e., the proportion of patients within the cohort with a specific CHD-subtype) of 26 CHD-subtypes in PROTEA's pediatric cohort were compared with the cohort-prevalences of CHD-subtypes in two global birth-prevalence studies.Results: The study enrolled 1,473 participants over 2 years, median age was 1.9 (IQR 0.4–7.1) years. Predominant subtypes included ventricular septal defect (VSD) (339, 20%), atrial septal defect (ASD) (174, 11%), patent ductus arteriosus (185, 11%), atrioventricular septal defect (AVSD) (124, 7%), and tetralogy of Fallot (121, 7%). VSDs were 1.8 (95% CI, 1.6–2.0) times and ASDs 1.4 (95% CI, 1.2–1.6) times more common in global prevalence estimates than in PROTEA's pediatric cohort. AVSDs were 2.1 (95% CI, 1.7–2.5) times more common in PROTEA and pulmonary stenosis and double outlet right ventricle were also significantly more common compared to global estimates. Median maternal age at delivery was 28 (IQR 23–34) years. Eighty-two percent (347/425) of mothers used no pre-conception supplementation and 42% (105/250) used no first trimester supplements.Conclusions: The cohort-prevalence of certain mild CHD subtypes is lower than for international estimates and the cohort-prevalence of certain severe subtypes is higher. PROTEA is not a prevalence study, and these inconsistencies are unlikely the result of true differences in prevalence. However, these findings may indicate under-diagnosis of mild to moderate CHD and differences in CHD management and outcomes. This reemphasizes the need for robust CHD epidemiological research in the region.

The Industrial Internet of Things (IIoT) promises numerous benefits for smart cities and intelligent transport is not an exception. This work demonstrates one such benefit by designing and implementing an IoT bicycle sharing service for smart city transportation. The proposed system is also based on renewable energy further pushing the drive towards zero carbon emission. The proposed system is composed of two subsystems namely a smart docking rack and a bicycle subsystem. This is coupled with server communication based on a Low Power Wide Area Network (LPWAN) protocol and a mobile application for efficient bicycle tracking, obstacle monitoring and billing management. The proposed sharing service was deployed on a university campus with a vision to scale up to smart city applications.