STalign: Alignment of spatial transcriptomics data using diffeomorphic metric mapping.

Spatial transcriptomics (ST) technologies enable high throughput gene expression characterization within thin tissue sections. However, comparing spatial observations across sections, samples, and technologies remains challenging. To address this challenge, we develop STalign to align ST datasets in a manner that accounts for partially matched tissue sections and other local non-linear distortions using diffeomorphic metric mapping. We apply STalign to align ST datasets within and across technologies as well as to align ST datasets to a 3D common coordinate framework. We show that STalign achieves high gene expression and cell-type correspondence across matched spatial locations that is significantly improved over landmark-based affine alignments. Applying STalign to align ST datasets of the mouse brain to the 3D common coordinate framework from the Allen Brain Atlas, we highlight how STalign can be used to lift over brain region annotations and enable the interrogation of compositional heterogeneity across anatomical structures. STalign is available as an open-source Python toolkit at https://github.com/JEFworks-Lab/STalign and as Supplementary Software with additional documentation and tutorials available at https://jef.works/STalign .

Alignment of spatial transcriptomics data using diffeomorphic metric mapping.

Spatial transcriptomics (ST) technologies enable high throughput gene expression characterization within thin tissue sections. However, comparing spatial observations across sections, samples, and technologies remains challenging. To address this challenge, we developed STalign to align ST datasets in a manner that accounts for partially matched tissue sections and other local non-linear distortions using diffeomorphic metric mapping. We apply STalign to align ST datasets within and across technologies as well as to align ST datasets to a 3D common coordinate framework. We show that STalign achieves high gene expression and cell-type correspondence across matched spatial locations that is significantly improved over landmark-based affine alignments. Applying STalign to align ST datasets of the mouse brain to the 3D common coordinate framework from the Allen Brain Atlas, we highlight how STalign can be used to lift over brain region annotations and enable the interrogation of compositional heterogeneity across anatomical structures. STalign is available as an open-source Python toolkit at https://github.com/JEFworks-Lab/STalign and as supplementary software with additional documentation and tutorials available at https://jef.works/STalign.

Geneva Statement on Heritable Human Genome Editing: The Need for Course Correction.

As public interest advocates, policy experts, bioethicists, and scientists, we call for a course correction in public discussions about heritable human genome editing. Clarifying misrepresentations, centering societal consequences and concerns, and fostering public empowerment will support robust, global public engagement and meaningful deliberation about altering the genes of future generations.

Do blind people see race? Social, legal, and theoretical considerations.

Although the meaning, significance, and definition of race have been debated for centuries, one thread of thought unifies almost all of the many diverging perspectives: a largely unquestioned belief that race is self-evident and visually obvious, defined largely by skin color, facial features, and other visual cues. This suggests that "seeing race" is an experience largely unmediated by broader social forces; we simply know it when we see it. It also suggests that those who cannot see are likely to have a diminished understanding of race. But is this empirically accurate?I examine these questions by interviewing people who have been totally blind since birth about race and compare their responses to sighted individuals. I not only find that blind people have as significant an understanding of race as anyone else and that they understand race visually, but that this visual understanding of race stems from interpersonal and institutional socializations that profoundly shape their racial perceptions. These findings highlight how race and racial thinking are encoded into individuals through iterative social practices that train people to think a certain way about the world around them. In short, these practices are so strong that even blind people, in a conceptual sense, "see" race. Rather than being self-evident, these interviews draw attention to how race becomes visually salient through constitutive social practices that give rise to visual understandings of racial difference for blind and sighted people alike. This article concludes with a discussion of these findings' significance for understanding the role of race in law and society.

Beyond best practices: strict scrutiny as a regulatory model for race-specific medicines.

A resounding debate has ensued over the utility of race in biomedical research, particularly as new drugs claiming to serve particular racial populations attempt to enter the marketplace. This creates a number of challenges for the Food and Drug Administration over how best to regulate new drugs seeking race specific indications. This article suggests that it may be beneficial for the FDA to turn to an area with experience negotiating such dilemmas--Constitutional Law--and its approach--strict scrutiny--to help guide when and under what circumstances Government should give effect to racial categories in biomedicine.

Multidrug-resistant tuberculosis at the National Hospital, Abuja, Nigeria

Five hundred (500) cases of pulmonary tuberculosis (TB) were seen at the Chest Clinic of the National Hospital; Abuja; Nigeria over a 2-year period (2004-2005). The diagnosis and management of multidrug-resistant (MDR) TB were studied as part of DOTS-Plus: Directly Observed Treatment Short-course (DOTS) programmes that add components for MDR-TB diagnosis; management; and treatment. The cases of pulmonary TB that showed mycobacterium resistance to rifampicin and isoniazid (MDR-TB) using the Lowenstein Jensen (solid medium) slope at the National Hospital and later using BACTEC 460 available at Zankli Medical Center at Abuja; were treated with the standard WHO recommended regimen for MDR-TB and the outcomes were studied. Twenty cases (4) of MDRTB were recorded; all 20 were also HIV-positive. One (8) died and 19 (95) were apparently cured at the end of therapy. This is the first report of MDR-TB and DOTS-Plus in Nigeria. There is an urgent need to study the MDR-TB pattern in Nigeria as extensive resistant TB (XDR-TB) has now been reported which is even worse prognostically than MDR-TB

Hospital admissions for acute painful crisis in Trinidad and Tobago. Are the British Committee for Standards in Haematology (BCSH) guidelines applicable?

We observed consecutive hospital admissions for acute painful crisis (APC) among adults with Sickle Cell Disease (SCD) over a 6-month period in Trinidad and Tobago. Episodes (111) of APC resulted in 82 admissions of 59 patients. The most common site for pain was the trunk. Patients ranged in age from 17 to 53 years (median: 25). Median length of hospital stay was 4 days. Total dose of Pethidine given per admission ranged from 100 to 1650 mg (median: 525). The mean dose of morphine was 70 mg. Six (7%) of patients were readmitted within 10 days of discharge. Twenty-five (30%) of patients had chest pain at presentation of whom 10 (12%) had consolidation on chest X-ray, defining the acute chest syndrome (ACS). There was one death caused by biliary sepsis. The study revealed seemingly low opiate usage for in-hospital treatment of APC with acceptable rates of readmission. The BCSH 2003 guidelines seemed applicable apart for the choice and route of fluid for rehydration and opiate analgesia.

Hospital admissions for acute painful crisis in Trinidad and Tobago. Are the British Committee for Standards in Haematology (BCSH) guidelines applicable?

We observed consecutive hospital admissions for acute painful crisis (APC) among adults with Sickle Cell Disease (SCD) over a 6-month period in Trinidad and Tobago. Episodes (111) of APC resulted in 82 admissions of 59 patients. The most common site for pain was the trunk. Patients ranged in age from 17 to 53 years (median: 25). Median length of hospital stay was 4 days. Total dose of Pethidine given per admission ranged from 100 to 1650 mg (median: 525). The mean dose of morphine was 70 mg. Six (7%) of patients were readmitted within 10 days of discharge. Twenty-five (30%) of patients had chest pain at presentation of whom 10 (12%) had consolidation on chest X-ray, defining the acute chest syndrome (ACS). There was one death caused by biliary sepsis. The study revealed seemingly low opiate usage for in-hospital treatment of APC with acceptable rates of readmission. The BCSH 2003 guidelines seemed applicable apart for the choice and route of fluid for rehydration and opiate analgesia.