This paper identifies instruments and measures that may be appropriate for randomized clinical trials in participants with autism spectrum disorders (ASDs HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author Manuscript scale was recommended for all randomized clinical trials. At this point, however, there is no "perfect" choice of outcome measure for core features of autism, although we will discuss five measures of potential utility. Several communication instruments are recommended, based in part on suitability across the age range. In trials where the intention is to alter core features of ASDs, adaptive behavior scales are also worthy of consideration. Several "behavior complexes" common to ASDs are identified, and instruments are recommended for assessment of these. Given the prevalence of cognitive impairment in ASDs, it is important to assess any cognitive effects, although cognitive data from ASD randomized clinical trials, thus far, are minimal. Guidance from trials in related pharmacologic areas and behavioral pharmacology may be helpful. We recommend routine elicitation of side effects, height and weight, vital signs, and (in the case of antipsychotics) extrapyramidal side-effects assessment. It is often appropriate to include laboratory tests and assessments for continence and sleep pattern.

On 5 March 2020, South Africa recorded its first case of imported COVID-19. Since then, cases in South Africa have increased exponentially with significant community transmission. A multisectoral approach to containing and mitigating the spread of SARS-CoV-2 was instituted, led by the South African National Department of Health. A National COVID-19 Command Council was established to take government-wide decisions. An adapted World Health Organiszion (WHO) COVID-19 strategy for containing and mitigating the spread of the virus was implemented by the National Department of Health. The strategy included the creation of national and provincial incident management teams (IMTs), which comprised of a variety of work streams, namely, governance and leadership; medical supplies; port and environmental health; epidemiology and response; facility readiness and case management; emergency medical services; information systems; risk communication and community engagement; occupational health and safety and human resources. The following were the most salient lessons learnt between March and September 2020: strengthened command and control were achieved through both centralised and decentralised IMTs; swift evidenced-based decision-making from the highest political levels for instituting lockdowns to buy time to prepare the health system; the stringent lockdown enabled the health sector to increase its healthcare capacity. Despite these successes, the stringent lockdown measures resulted in economic hardship particularly for the most vulnerable sections of the population.

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Objective Recent sequencing studies of head and neck squamous cell carcinomas (HNSCCs) have identified the phosphatidylinositol 3-kinase (PI3K) pathway as the most frequently mutated, oncogenic pathway in this cancer type. Despite the frequency of activating genomic alterations in PIK3CA (the gene encoding the catalytic subunit of PI3K, targeted inhibitors of PI3K have not shown clinical efficacy as monotherapies. We hypothesized that co-dependent pathways, including the Ras-MEK-ERK pathway, may still be functional in the presence of PI3K inhibitors and might serve as mediators of this resistance. Methods We assessed the hypothesis using resazurin cell viability and trypan blue exclusion assays. We also used Western blot to characterize Ras-MEK-ERK pathway activity. Study Design We evaluated this hypothesis in six PIK3CA-amplified, PI3K inhibitor-resistant HNSCC cell lines following treatment with pan and alpha-isoform selective PI3K inhibitors (BKM120 and HS-173 respectively). We also tested the effect of combination treatment with PI3K inhibitor HS-173 and MEK inhibitor trametinib or EGFR inhibitor gefitinib. Results Our results displayed maintenance of Ras-MEK-ERK pathway activity in 4 of 6 HNSCC cell lines after PI3K inhibitor treatment. We also found that UM-SCC-69 and UM-SCC-108 cells display synergistic responses to dual therapy. Conclusion This study suggests that inhibition of the PI3K and Ras-MEK-ERK pathways might be effective in some HNSCC patients; however, it also prompts the study of additional resistance mechanisms to identify synergistic combination therapies for tumors resistant to these di-therapies.

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