Intonational Impairment Following Naturally Occurring Callosal Disconnection

TB

Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma

The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterised. Current practice is guided by physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult LBCL patients in relation to outcomes following axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel). The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity/mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death following CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of Polatuzumab-containing chemotherapy regimens. Our data suggested that complete/partial response to BT may be more important for Tisa-cel than Axi-cel, as all Tisa-cel patients with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned towards optimal response and disease debulking, to improve CD19CAR-T patient outcomes. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete/partial response to BT pre-Tisa-cel may prompt consideration of further lines of BT where possible

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries.

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Metallicities and ages of stellar populations at a high Galactic latitude field

We present an analysis of $UBVRI$ data from the Selected Area SA 141. By applying recalibrated methods of measuring ultraviolet excess (UVX), we approximate abundances and absolute magnitudes for 368 stars over 1.3 square degrees out to distances over 10 kpc. With the density distribution constrained from our previous photometric parallax investigations and with sufficient accounting for the metallicity bias in the UVX method, we are able to compare the vertical abundance distribution to those measured in previous studies. We find that the abundance distribution has an underlying uniform component consistent with previous spectroscopic results that posit a monometallic thick disk and halo with abundances of $[Fe/H]$ = $-$0.8 and $-$1.4, respectively. However, there are a number of outlying data points that may indicate contamination by more metal-rich halo streams. The absence of vertical abundance gradients in the Galactic stellar populations and the possible presence of interloping halo streams would be consistent with expectations from merger models of Galaxy formation. We find that our UVX method has limited sensitivity in exploring the metallicity distribution of the distant Galactic halo, owing to the poor constraint on the $UBV$ properties of very metal-poor stars. The derivation of metallicities from broadband $UBV$ photometry remains fundamentally sound for the exploration of the halo but is in need of both improved calibration and superior data.Comment: 11 pages, 11 figures, accepted for publication in MNRAS Journa

Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma

The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterized. Current practice is guided through physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve both CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult patients with LBCL in relation to outcomes after axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel) administration. The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity or mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death after CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of polatuzumab-containing chemotherapy regimens. Our data suggested that complete or partial response to BT may be more important for Tisa-cel than for Axi-cel, because all patients receiving Tisa-cel with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned toward optimal response and disease debulking, to improve patient outcomes associated with CD19CAR-T. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete or partial response to BT before Tisa-cel administration may prompt consideration of further lines of BT where possible

Whole Genome Sequencing Reveals Local Transmission Patterns of Mycobacterium bovis in Sympatric Cattle and Badger Populations

Whole genome sequencing (WGS) technology holds great promise as a tool for the forensic epidemiology of bacterial pathogens. It is likely to be particularly useful for studying the transmission dynamics of an observed epidemic involving a largely unsampled ‘reservoir' host, as for bovine tuberculosis (bTB) in British and Irish cattle and badgers. BTB is caused by Mycobacterium bovis, a member of the M. tuberculosis complex that also includes the aetiological agent for human TB. In this study, we identified a spatio-temporally linked group of 26 cattle and 4 badgers infected with the same Variable Number Tandem Repeat (VNTR) type of M. bovis. Single-nucleotide polymorphisms (SNPs) between sequences identified differences that were consistent with bacterial lineages being persistent on or near farms for several years, despite multiple clear whole herd tests in the interim. Comparing WGS data to mathematical models showed good correlations between genetic divergence and spatial distance, but poor correspondence to the network of cattle movements or within-herd contacts. Badger isolates showed between zero and four SNP differences from the nearest cattle isolate, providing evidence for recent transmissions between the two hosts. This is the first direct genetic evidence of M. bovis persistence on farms over multiple outbreaks with a continued, ongoing interaction with local badgers. However, despite unprecedented resolution, directionality of transmission cannot be inferred at this stage. Despite the often notoriously long timescales between time of infection and time of sampling for TB, our results suggest that WGS data alone can provide insights into TB epidemiology even where detailed contact data are not available, and that more extensive sampling and analysis will allow for quantification of the extent and direction of transmission between cattle and badgers

The Zwicky Transient Facility Census of the Local Universe. I. Systematic Search for Calcium-rich Gap Transients Reveals Three Related Spectroscopic Subclasses

Using the Zwicky Transient Facility alert stream, we are conducting a large spectroscopic campaign to construct a complete, volume-limited sample of transients brighter than 20 mag, and coincident within 100" of galaxies in the Census of the Local Universe catalog. We describe the experiment design and spectroscopic completeness from the first 16 months of operations, which have classified 754 supernovae. We present results from a systematic search for calcium-rich gap transients in the sample of 22 low-luminosity (peak absolute magnitude M > −17), hydrogen-poor events found in the experiment. We report the detection of eight new events, and constrain their volumetric rate to ≳ 15% ± 5% of the SN Ia rate. Combining this sample with 10 previously known events, we find a likely continuum of spectroscopic properties ranging from events with SN Ia–like features (Ca-Ia objects) to those with SN Ib/c–like features (Ca-Ib/c objects) at peak light. Within the Ca-Ib/c events, we find two populations distinguished by their red (g − r ≈ 1.5 mag) or green (g - r ≈ 0.5 mag) colors at the r-band peak, wherein redder events show strong line blanketing features and slower light curves (similar to Ca-Ia objects), weaker He lines, and lower [Ca ii]/[O i] in the nebular phase. We find that all together the spectroscopic continuum, volumetric rates, and striking old environments are consistent with the explosive burning of He shells on low-mass white dwarfs. We suggest that Ca-Ia and red Ca-Ib/c objects arise from the double detonation of He shells, while green Ca-Ib/c objects are consistent with low-efficiency burning scenarios like detonations in low-density shells or deflagrations