"Call a Teenager… That's What I Do!" - Grandchildren Help Older Adults Use New Technologies: Qualitative Study.

BackgroundAlthough family technical support seems intuitive, there is very little research exploring this topic.ObjectiveThe objective of this study was to conduct a subanalysis of data collected from a large-scale qualitative project regarding older adults' experiences in using health information technology. Specifically, the subanalysis explored older adults' experiences with technology support from family members to inform strategies for promoting older adults' engagement with new health technologies. Although the primary analysis of the original study was theoretically driven, this paper reports results from an inductive, open-coding analysis.MethodsThis is a subanalysis of a major code identified unexpectedly from a qualitative study investigating older adults' use experience of a widespread health technology, the patient portal. A total of 24 older patients (≥65 years) with multiple chronic conditions (Charlson Comorbidity Index >2) participated in focus groups conducted at the patients' primary clinic. While conducting the primary theoretically driven analysis, coders utilized an open-coding approach to ensure important ideas not reflected in the theoretical code book were captured. Open coding resulted in 1 code: family support. This subanalysis further categorized family support by who provided tech support, how tech support was offered, and the opinions of older participants about receiving family tech support.ResultsThe participants were not specifically asked about family support, yet themes around family assistance and encouragement for technology emerged from every focus group. Participants repeatedly mentioned that they called their grandchildren and adult children if they needed help with technology. Participants also reported that family members experienced difficulty when teaching technology use. Family members struggled to explain simple technology tasks and were frustrated by the slow teaching process.ConclusionsThe results suggest that older adults ask their family members, particularly grandchildren, to support them in the use of new technologies. However, family may experience difficulties in providing this support. Older adults will be increasingly expected to use health technologies, and family members may help with tech support. Providers and health systems should consider potential family support and engagement strategies to foster adoption and use among older patients

Rapid geographical source attribution of Salmonella enterica serovar Enteritidis genomes using hierarchical machine learning.

Salmonella enterica serovar Enteritidis is one of the most frequent causes of Salmonellosis globally and is commonly transmitted from animals to humans by the consumption of contaminated foodstuffs. In the UK and many other countries in the Global North, a significant proportion of cases are caused by consumption of imported food products or contracted during foreign travel, therefore making the rapid identification of the geographical source of new infections a requirement for robust public health outbreak investigations. Herein, we detail the development and application of a hierarchical machine learning model to rapidly identify and trace the geographical source of S. Enteritidis infections from whole genome sequencing data. 2,313 S. Enteritidis genomes, collected by the UKHSA between 2014-2019, were used to train a 'local classifier per node' hierarchical classifier to attribute isolates to 4 continents, 11 sub-regions and 38 countries (53 classes). The highest classification accuracy was achieved at the continental level followed by the sub-regional and country levels (macro F1: 0.954, 0.718, 0.661 respectively). A number of countries commonly visited by UK travellers were predicted with high accuracy (hF1: >0.9). Longitudinal analysis and validation with publicly accessible international samples indicated that predictions were robust to prospective external datasets. The hierarchical machine learning framework provided granular geographical source prediction directly from sequencing reads in <4 minutes per sample, facilitating rapid outbreak resolution and real-time genomic epidemiology. The results suggest additional application to a broader range of pathogens and other geographically structured problems, such as antimicrobial resistance prediction, is warranted

Gβ Association and Effector Interaction Selectivities of the Divergent Gγ Subunit Gγ 13

G gamma(13) is a divergent member of the G gamma subunit family considered to be a component of the gustducin G-protein heterotrimer involved in bitter and sweet taste reception in taste bud cells. G gamma(13) contains a C-terminal asparagine-proline-tryptophan (NPW) tripeptide, a hallmark of RGS protein G gamma-like (GGL) domains which dimerize exclusively with G beta(5) subunits. In this study, we investigated the functional range of G gamma(13) assembly with G beta subunits using multiple assays of G beta association and G beta gamma effector modulation. G gamma(13) was observed to associate with all five G beta subunits (G beta(1-5)) upon co-translation in vitro, as well as function with all five G beta subunits in the modulation of Kir3.1/3.4 (GIRK1/4) potassium and N-type (alpha(1B)) calcium channels. Multiple G beta/G gamma(13) pairings were also functional in cellular assays of phospholipase C (PLC) beta 2 activation and inhibition of G alpha(q)-stimulated PLC beta 1 activity. However, upon cellular co-expression of G gamma(13) with different G beta subunits, only G beta(1)/G gamma(13), G beta(3)/G gamma(13), and G beta(4)/G gamma(13) pairings were found to form stable dimers detectable by co-immunoprecipitation under high-detergent cell lysis conditions. Collectively, these data indicate that G gamma(13) forms functional G beta gamma dimers with a range of G beta subunits. Coupled with our detection of G gamma(13) mRNA in mouse and human brain and retina, these results imply that this divergent G gamma subunit can act in signal transduction pathways other than that dedicated to taste reception in sensory lingual tissue

Dendritic cells promote the spread of human T-cell leukemia virus type 1 via bidirectional interactions with CD4+ T cells

Human T-cell leukemia virus type-1 (HTLV-1) propagates within and between individuals via cell-to-cell transmission, and primary infection typically occurs across juxtaposed mucosal surfaces during breastfeeding and sexual intercourse. It is therefore likely that dendritic cells (DCs) are among the first potential targets for HTLV-1. However, it remains unclear how DCs contribute to virus transmission and dissemination in the early stages of infection. We show that an HTLV-1-infected cell line (MT-2) and naturally-infected CD4+ T-cells transfer p19+ viral particles to the surface of allogeneic DCs via cell-to-cell contacts. Similarly organized cell-to-cell contacts facilitate DC-mediated transfer of HTLV-1 to autologous CD4+ T-cells. These findings shed light on the cellular structures involved in anterograde and retrograde transmission, and suggest a key role for DCs in the natural history and pathogenesis of HTLV-1 infection

“Beads-on-a-string” star formation tied to one of the most powerful active galactic nucleus outbursts observed in a cool-core galaxy cluster

With two central galaxies engaged in a major merger and a remarkable chain of 19 young stellar superclusters wound around them in projection, the galaxy cluster SDSS J1531+3414 (z = 0.335) offers an excellent laboratory to study the interplay between mergers, active galactic nucleus (AGN) feedback, and star formation. New Chandra X-ray imaging reveals rapidly cooling hot (T ∼ 106 K) intracluster gas, with two “wings” forming a concave density discontinuity near the edge of the cool core. LOFAR 144 MHz observations uncover diffuse radio emission strikingly aligned with the “wings,” suggesting that the “wings” are actually the opening to a giant X-ray supercavity. The steep radio emission is likely an ancient relic of one of the most energetic AGN outbursts observed, with 4pV > 1061 erg. To the north of the supercavity, GMOS detects warm (T ∼ 104 K) ionized gas that enshrouds the stellar superclusters but is redshifted up to +800 km s−1 with respect to the southern central galaxy. The Atacama Large Millimeter/submillimeter Array detects a similarly redshifted ∼1010 M ⊙ reservoir of cold (T ∼ 102 K) molecular gas, but it is offset from the young stars by ∼1–3 kpc. We propose that the multiphase gas originated from low-entropy gas entrained by the X-ray supercavity, attribute the offset between the young stars and the molecular gas to turbulent intracluster gas motions, and suggest that tidal interactions stimulated the “beads-on-a-string” star formation morphology

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Protocol for the ROSE sustainment (ROSES) study, a sequential multiple assignment randomized trial to determine the minimum necessary intervention to maintain a postpartum depression prevention program in prenatal clinics serving low-income women

Background: More research on sustainment of interventions is needed, especially return on investment (ROI) studies to determine cost-benefit trade-offs for effort required to sustain and how much is gained when effective programs are sustained. The ROSE sustainment (ROSES) study uses a sequential multiple assignment randomized (SMART) design to evaluate the effectiveness and cost-effectiveness of a stepwise approach to sustainment of the ROSE postpartum depression prevention program in 90 outpatient clinics providing prenatal care to pregnant women on public assistance. Postpartum depression (PPD) is common and can have lasting consequences. Outpatient clinics offering prenatal care are an opportune place to provide PPD prevention because most women visit while pregnant. The ROSE (Reach Out, Stay Strong, Essentials for mothers of newborns) program is a group educational intervention to prevent PPD, delivered during pregnancy. ROSE has been found to reduce cases of PPD in community prenatal settings serving low-income pregnant women. Methods: All 90 prenatal clinics will receive enhanced implementation as usual (EIAU; initial training + tools for sustainment). At the first time at which a clinic is determined to be at risk for failure to sustain (i.e., at 3, 6, 9, 12, and 15 months), that clinic will be randomized to receive either (1) no additional implementation support (i.e., EIAU only), or (2) low-intensity coaching and feedback (LICF). If clinics receiving LICF are still at risk at subsequent assessments, they will be randomized to either (1) EIAU + LICF only, or (2) high-intensity coaching and feedback (HICF). Additional follow-up interviews will occur at 18, 24, and 30 months, but no implementation intervention will occur after 18 months. Outcomes include (1) percent sustainment of core program elements at each time point, (2) health impact (PPD rates over time at each clinic) and reach, and (3) ROI (costs and cost-effectiveness) of each sustainment step. Hypothesized mechanisms include sustainment of capacity to deliver core elements and engagement/ownership. Discussion: This study is the first randomized trial evaluating the ROI of a stepped approach to sustainment, a critical unanswered question in implementation science. It will also advance knowledge of implementation mechanisms and clinical care for an at-risk population

JWST reveals a possible z∼11z \sim 11 galaxy merger in triply-lensed MACS0647−-JD

MACS0647$-$JD is a triply-lensed $z\sim11$ galaxy originally discovered with the Hubble Space Telescope. Here we report new JWST imaging, which clearly resolves MACS0647$-$JD as having two components that are either merging galaxies or stellar complexes within a single galaxy. Both are very small, with stellar masses $\sim10^8\,M_\odot$ and radii $r<100\,\rm pc$. The brighter larger component "A" is intrinsically very blue ($\beta\sim-2.6$), likely due to very recent star formation and no dust, and is spatially extended with an effective radius $\sim70\,\rm pc$. The smaller component "B" appears redder ($\beta\sim-2$), likely because it is older ($100-200\,\rm Myr$) with mild dust extinction ($A_V\sim0.1\,\rm mag$), and a smaller radius $\sim20\,\rm pc$. We identify galaxies with similar colors in a high-redshift simulation, finding their star formation histories to be out of phase. With an estimated stellar mass ratio of roughly 2:1 and physical projected separation $\sim400\,\rm pc$, we may be witnessing a galaxy merger 400 million years after the Big Bang. We also identify a candidate companion galaxy C $\sim3\,{\rm kpc}$ away, likely destined to merge with galaxies A and B. The combined light from galaxies A+B is magnified by factors of $\sim$8, 5, and 2 in three lensed images JD1, 2, and 3 with F356W fluxes $\sim322$, $203$, $86\,\rm nJy$ (AB mag 25.1, 25.6, 26.6). MACS0647$-$JD is significantly brighter than other galaxies recently discovered at similar redshifts with JWST. Without magnification, it would have AB mag 27.3 ($M_{UV}=-20.4$). With a high confidence level, we obtain a photometric redshift of $z=10.6\pm0.3$ based on photometry measured in 6 NIRCam filters spanning $1-5\rm\mu m$, out to $4300\,\r{A}$ rest-frame. JWST NIRSpec observations planned for January 2023 will deliver a spectroscopic redshift and a more detailed study of the physical properties of MACS0647$-$JD.Comment: 27 pages, 14 figures, submitted to Natur