Accelerating COVID-19 Treatment Interventions and Vaccines (ACTIV) was initiated by the US government to rapidly develop and test vaccines and therapeutics against COVID-19 in 2020. The ACTIV Therapeutics-Clinical Working Group selected ACTIV trial teams and clinical networks to expeditiously develop and launch master protocols based on therapeutic targets and patient populations. The suite of clinical trials was designed to collectively inform therapeutic care for COVID-19 outpatient, inpatient, and intensive care populations globally. In this report, we highlight challenges, strategies, and solutions around clinical protocol development and regulatory approval to document our experience and propose plans for future similar healthcare emergencies.

In March 2018, the US Food and Drug Administration (FDA), US Centers for Disease Control and Prevention, California Department of Public Health, Los Angeles County Department of Public Health and Pennsylvania Department of Health initiated an investigation of an outbreak of Burkholderia cepacia complex (Bcc) infections. Sixty infections were identified in California, New Jersey, Pennsylvania, Maine, Nevada and Ohio. The infections were linked to a no-rinse cleansing foam product (NRCFP), produced by Manufacturer A, used for skin care of patients in healthcare settings. FDA inspected Manufacturer A's production facility (manufacturing site of over-the-counter drugs and cosmetics), reviewed production records and collected product and environmental samples for analysis. FDA's inspection found poor manufacturing practices. Analysis by pulsed-field gel electrophoresis confirmed a match between NRCFP samples and clinical isolates. Manufacturer A conducted extensive recalls, FDA issued a warning letter citing the manufacturer's inadequate manufacturing practices, and federal, state and local partners issued public communications to advise patients, pharmacies, other healthcare providers and healthcare facilities to stop using the recalled NRCFP. This investigation highlighted the importance of following appropriate manufacturing practices to minimize microbial contamination of cosmetic products, especially if intended for use in healthcare settings.

Early in the COVID-19 pandemic, the World Health Organization stressed the importance of daily clinical assessments of infected patients, yet current approaches frequently consider cross-sectional timepoints, cumulative summary measures, or time-to-event analyses. Statistical methods are available that make use of the rich information content of longitudinal assessments. We demonstrate the use of a multistate transition model to assess the dynamic nature of COVID-19-associated critical illness using daily evaluations of COVID-19 patients from 9 academic hospitals. We describe the accessibility and utility of methods that consider the clinical trajectory of critically ill COVID-19 patients.

The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.7 times as many males as females. The disease became more common over the study period. Most cases (86%) were seen between March and July. Cerebrospinal fluid (CSF) was obtained from the cisterna magna in 77 dogs, the lumbar cistern in f5, and both sites in 3. Nucleated cell counts for 84 specimens ranged from 1 to 146 150 cells μL−1 (median 4500). Percentage eosinophils varied from 0 to 98% (median 83%). When both cisternal and lumbar CSF were collected, inflammation was more severe caudally. Seventy-three CSF specimens were subjected to enzyme-linked immunosorbent assay (ELISA) testing for antibodies against A. cantonensis; 61 (84%) tested positive, titres ranging from <100 to ⩾12 800 (median 1600). Sixty-one CSF specimens were subjected to real-time quantitative polymerase chain reaction (qPCR) testing using a new protocol targeting a bioinformatically-informed repetitive genetic target; 53/61 samples (87%) tested positive, CT values ranging from 23.4 to 39.5 (median 30.0). For 57 dogs, it was possible to compare CSF ELISA serology and qPCR. ELISA and qPCR were both positive in 40 dogs, in 5 dogs the ELISA was positive while the qPCR was negative, in 9 dogs the qPCR was positive but the ELISA was negative, while in 3 dogs both the ELISA and qPCR were negative. NA is an emerging infectious disease of dogs in Sydney, Australia.

Three complementary points to Jaswal & Akhtar are raised: (1) As a person with autism, I desire sociality despite vulnerability to others’ antisocial behaviour; (2) Asperger's conflation of autism with psychopathy (Czech 2018) likely caused clinicians to disregard social motivation among those with autism; and (3) adverse experiences cause social-engagement diversity to develop in all people, not just those on the spectrum.

We support Pepper and Nettle's (P&N's) hypothesised adaptive responses to deprivation. However, we argue that adaptive responses to stress shift with age. Specifically, present-oriented behaviours are adaptive for young people (e.g., in terms of mating and reproduction) but costly for older people in deprived communities who would benefit from investing in grandchildren. Epigenetic mechanisms may be responsible for age-related tactical shifts.

Field studies were conducted at three sites in Missouri in 1986 and 1987 to evaluate the performance of below-label rates of bentazon, acifluorfen, and chlorimuron tank mixed with sethoxydim and applied to soybeans 7 and 14 days after planting to evaluate broadleaf and grass weed control and weed seed production. Sequential applications of 0.25X-labeled rates of all three broadleaf herbicides tank mixed with 0.5X sethoxydim rates controlled giant foxtail, velvetleaf, and common cocklebur equivalent to one application of standard-labeled rates of the same tank mixes. Single applications of below-labeled rates of the postemergence herbicides did not control weeds, and soybean yields were not equal to sequential 0.25X or single full-rate treatments. A preemergence treatment of clomazone plus imazaquin applied at labeled rates controlled weeds, and soybean yields were equal to a handweeded check in both years at all test locations. Weeds survived and produced seed to reinfest the plots the following year unless nearly 100% control was achieved.

Since the turn of the century, a Pliocene-Pleistocene connection between the Death Valley-Owens River pluvial system and the Colorado River drainage basin has been frequently postulated. The two most commonly proposed routes involve (1) a southward overflow from the Death Valley Lake system or (2) southward migration of the Mojave River between its present course and a more southerly route. Under the present topographic regime, a Death Valley Lake capable of overflowing the bedrock saddle at Ludlow, California and discharging southward into the Bristol, Cadiz, and Danby Lake basins (and eventually the Colorado River) would be over 12,000 km2 in size. Few surface and subsurface indicators exist to support either a fluvial or lacustrine connection. Evidence from deep cores and boreholes drilled in Soda, Bristol, Cadiz, and Danby dry lake basins indicate that a hydrologic connection has not occurred during the past 4 myr. No well-documented paleoshoreline features have been located at elevations corresponding to the above hydrologic systems in Death Valley, Silver-Soda, Bristol, or Danby Lake basins. In the Cadiz, Silurian, and Broadwell basins these features have not been found at all. Therefore, we conclude that a hydrologic connection between the Death Valley-Owens River system and the Colorado River has not occurred along either of these routes since the middle Pliocene.

Direct stimulation of 23 median, 13 ulnar and 2 peroneal nerves at the time of surgical exploration has been used to locate, and characterize the conduction abnormalities in thenerves. The most frequent location of the major conduction abnormalities in the median nerve was in the first 1-2 cm distal to the origin of the carpal tunnel. In the ulnar nerve the important conduction abnormalities were located most frequently in the segments 1 cm proximal and distal to the medial epicondyle. In the peroneal nerve the major conduction abnormalities occurred proximal or distal to the entry point of the common peroneal nerve into the peroneus longusmuscle.