This is a summary of a publication about Black participants of the GRIFFIN clinical study that was published in
in April 2022. The GRIFFIN clinical study looked at the treatment combination of ...daratumumab plus a standard therapy for multiple myeloma (called RVd therapy, which stands for lenalidomide, bortezomib, and dexamethasone) in adult patients who had not been treated before for multiple myeloma and so were considered to have newly diagnosed multiply myeloma. Multiple myeloma is a blood cancer of plasma cells. Based on the participants' age, medical history, and indicators of good general health, the participants in the GRIFFIN study were also eligible to receive autologous stem cell transplant as part of their therapy. This summary describes results for the Black participants of the GRIFFIN clinical study who received daratumumab plus RVd therapy (called D-RVd) to see if D-RVd therapy is better than RVd therapy at reducing the amount of multiple myeloma cancer cells in a patient's body.
Due to racial disparities leading to historically low representation of minority groups in clinical studies, optimal treatments are not defined for Black patients with newly diagnosed multiple myeloma. Since previously published results from the overall population in the GRIFFIN study indicated that D-RVd therapy was better than RVd therapy, the researchers wanted to determine if this was also the case among Black participants.
Out of 207 participants in the GRIFFIN study, 15% (32 participants) were Black and 78% (161 participants) were White. In both Black and White participants, D-RVd therapy reduced the amount of myeloma cancer cells more than RVd therapy. Additionally, D-RVd and RVd therapy had similar safety results for Black and White participants.
This analysis of GRIFFIN by race shows that Black people benefit from the daratumumab-containing D-RVd therapy as much as White people. Additionally, D-RVd therapy had similar safety results to RVd therapy for both Black and White people.
: NCT02874742 (ClinicalTrials.gov).
A series of studies were conducted to explore the mechanism of the pharmacokinetic interaction between simvastatin (SV) and gemfibrozil (GFZ) reported recently in human subjects. After administration ...of a single dose of SV (4 mg/kg p.o.) to dogs pretreated with GFZ (75 mg/kg p.o., twice daily for 5 days), there was an increase (approximately 4-fold) in systemic exposure to simvastatin hydroxy acid (SVA), but not to SV, similar to the observation in humans. GFZ pretreatment did not increase the ex vivo hydrolysis of SV to SVA in dog plasma. In dog and human liver microsomes, GFZ exerted a minimal inhibitory effect on CYP3A-mediated SVA oxidation, but did inhibit SVA glucuronidation. After i.v. administration of (14)CSVA to dogs, GFZ treatment significantly reduced (2-3-fold) the plasma clearance of SVA and the biliary excretion of SVA glucuronide (together with its cyclization product SV), but not the excretion of a major oxidative metabolite of SVA, consistent with the in vitro findings in dogs. Among six human UGT isozymes tested, UGT1A1 and 1A3 were capable of catalyzing the glucuronidation of both GFZ and SVA. Further studies conducted in human liver microsomes with atorvastatin (AVA) showed that, as with SVA, GFZ was a less potent inhibitor of the CYP3A4-mediated oxidation of this drug than its glucuronidation. However, with cerivastatin (CVA), the glucuronidation as well as the CYP2C8- and CYP3A4-mediated oxidation pathways were much more susceptible to inhibition by GFZ than was observed with SVA or AVA. Collectively, the results of these studies provide metabolic insight into the nature of drug-drug interaction between GFZ and statins, and a possible explanation for the enhanced susceptibility of CVA to interactions with GFZ.
Although differences in the rate of virus fusion and budding from the host cell membrane have been correlated with pathogenicity, no systematic study of the contribution of differences in viral ...envelope composition has previously been attempted. Using rigorous virus purification, marked differences between virions and host were observed. Over 125 phospholipid species have been quantitated for three strains of influenza (HKx31-H3N2, PR8-H1N1, and VN1203-H5N1) grown in eggs. The glycerophospholipid composition of purified virions differs from that of the host or that of typical mammalian cells. Phosphatidylcholine is the major component in most mammalian cell membranes, whereas in purified virions phosphatidylethanolamine dominates. Due to its effects on membrane curvature, it is likely that the variations in its content are important to viral processing during infection. This integrated method of virion isolation with systematic analysis of glycerophospholipids provides a tool for the assessment of species-specific biomarkers of viral pathogenicity.
In this article we describe the architecture, algorithms and real-world benchmarks performed by
Johnny Jackanapes
, an autonomous service robot for domestic environments.
Johnny
serves as a research ...and development platform to explore, develop and integrate capabilities required for real-world domestic service applications. We present a control architecture which allows to cope with various and changing domestic service robot tasks. A software architecture supporting the rapid integration of functionality into a complete system is as well presented. Further, we describe novel and robust algorithms centered around multi-modal human robot interaction, semantic scene understanding and SLAM. Evaluation of the complete system has been performed during the last years in the RoboCup@Home competition where
Johnnys
outstanding performance led to successful participation. The results and lessons learned of these benchmarks are explained in more detail.
Group A Streptococcus (GAS) is a major human pathogen responsible for superficial infections through to life-threatening invasive disease and the autoimmune sequelae acute rheumatic fever (ARF). ...Despite a significant global economic and health burden, there is no licensed vaccine available to prevent GAS disease. Several pre-clinical vaccines that target conserved GAS antigens are in development. Assays that measure antigen-specific antibodies are essential for vaccine research. The aim of this study was to develop a multiplex beadbased immunoassay that can detect and quantify antibody responses to multiple GAS antigen targets in small volume blood samples. This builds on our existing triplex assay comprised of antigens used in clinical serology for the diagnosis of ARF (SLO, DNase B and SpnA). Five additional conserved putative GAS vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD and the Group A carbohydrate), were coupled to spectrally unique beads to form an 8-plex antigen panel. After optimisation of the assay protocol, standard curves were generated, and assessments of assay specificity, precision and reproducibility were conducted. A broad range of antibody (IgG) titres were able to be quickly and accurately quantified from a single serum dilution. Assay utility was assessed using a panel of 62 clinical samples including serum from adults with GAS bacteraemia and children with ARF. Circulating IgG to all eight antigens was elevated in patients with GAS disease (n = 23) compared to age-matched controls (n = 39) (P < 0.05). The feasibility of using dried blood samples to quantify antigen-specific IgG was also demonstrated. In summary, a robust and reproducible 8-plex assay has been developed that simultaneously quantifies IgG antibodies to GAS vaccine and diagnostic antigens.
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•An 8-plex assay, that measures IgG responses to Group A Streptococcus (GAS) antigens, was developed, optimised and evaluated.•Vaccine antigens (Spy0843, SCPA, SpyCEP, SpyAD, GAC), and antigens from a previous triplex (SLO, DNaseB, SpnA) were included.•The assay will be a useful tool for profiling responses to diagnostic and vaccine antigens to support GAS vaccine research.
BACKGROUND
Non-verbal communication is an important aspect of the diagnostic and therapeutic process, especially with older patients. It is unknown how non-verbal communication varies with physician ...and patient race.
OBJECTIVE
To examine the joint influence of physician race and patient race on non-verbal communication displayed by primary care physicians during medical interviews with patients 65 years or older.
DESIGN, SETTING, AND PARTICIPANTS
Video-recordings of visits of 209 patients 65 years old or older to 30 primary care physicians at three clinics located in the Midwest and Southwest.
MAIN MEASURES
Duration of physicians’ open body position, eye contact, smile, and non-task touch, coded using an adaption of the Nonverbal Communication in Doctor–Elderly Patient Transactions form.
KEY RESULTS
African American physicians with African American patients used more open body position, smile, and touch, compared to the average across other dyads (adjusted mean difference for open body position = 16.55, p < 0.001; smile = 2.35, p = 0.048; touch = 1.33, p < 0.001). African American physicians with white patients spent less time in open body position compared to the average across other dyads, but they also used more smile and eye gaze (adjusted mean difference for open body position = 27.25, p < 0.001; smile = 3.16, p = 0.005; eye gaze = 17.05, p < 0.001). There were no differences between white physicians’ behavior toward African American vs. white patients.
CONCLUSION
Race plays a role in physicians’ non-verbal communication with older patients. Its influence is best understood when physician race and patient race are considered jointly.
The cingulum bundle (CB) connects gray matter structures of the limbic system and as such has been implicated in the etiology of schizophrenia. There is growing evidence to suggest that the CB is ...actually comprised of a conglomeration of discrete sub-connections. The present study aimed to use Diffusion Tensor tractography to subdivide the CB into its constituent sub-connections, and to investigate the structural integrity of these sub-connections in patients with schizophrenia and matched healthy controls. Diffusion Tensor Imaging scans were acquired from 24 patients diagnosed with chronic schizophrenia and 26 matched healthy controls. Deterministic tractography was used in conjunction with FreeSurfer-based regions-of-interest to subdivide the CB into 5 sub-connections (I1 to I5). The patients with schizophrenia exhibited subnormal levels of FA in two cingulum sub-connections, specifically the fibers connecting the rostral and caudal anterior cingulate gyrus (I1) and the fibers connecting the isthmus of the cingulate with the parahippocampal cortex (I4). Furthermore, while FA in the I1 sub-connection was correlated with the severity of patients' positive symptoms (specifically hallucinations and delusions), FA in the I4 sub-connection was correlated with the severity of patients' negative symptoms (specifically affective flattening and anhedonia/asociality). These results support the notion that the CB is a conglomeration of structurally interconnected yet functionally distinct sub-connections, of which only a subset are abnormal in patients with schizophrenia. Furthermore, while acknowledging the fact that the present study only investigated the CB, these results suggest that the positive and negative symptoms of schizophrenia may have distinct neurobiological underpinnings.
Background
New Zealand's (NZ) complete absence of community transmission of influenza and respiratory syncytial virus (RSV) after May 2020, likely due to COVID‐19 elimination measures, provided a ...rare opportunity to assess the impact of border restrictions on common respiratory viral infections over the ensuing 2 years.
Methods
We collected the data from multiple surveillance systems, including hospital‐based severe acute respiratory infection surveillance, SHIVERS‐II, ‐III and ‐IV community cohorts for acute respiratory infection (ARI) surveillance, HealthStat sentinel general practice (GP) based influenza‐like illness surveillance and SHIVERS‐V sentinel GP‐based ARI surveillance, SHIVERS‐V traveller ARI surveillance and laboratory‐based surveillance. We described the data on influenza, RSV and other respiratory viral infections in NZ before, during and after various stages of the COVID related border restrictions.
Results
We observed that border closure to most people, and mandatory government‐managed isolation and quarantine on arrival for those allowed to enter, appeared to be effective in keeping influenza and RSV infections out of the NZ community. Border restrictions did not affect community transmission of other respiratory viruses such as rhinovirus and parainfluenza virus type‐1. Partial border relaxations through quarantine‐free travel with Australia and other countries were quickly followed by importation of RSV in 2021 and influenza in 2022.
Conclusion
Our findings inform future pandemic preparedness and strategies to model and manage the impact of influenza and other respiratory viral threats.
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