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Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

In a 250 patient cohort from the US and Canada in the current era (2010–2018), we show that over 90% of patients with severe combined immunodeficiency (SCID) can be genetically-characterized.

White Mountain is centrally located in the bedding-plane portion of the Eocene Heart Mountain detachment and contains the only upper plate Mississippian Madison Group rocks that have been metamorphosed into marble. The marble rests upon the thickest (1 m) part of a carbonate ultracataclasite that marks the detachment. Thermodynamic and mechanical calculations based on possible frictional melting of calcite and other minerals, geochemical data, the characteristics of the carbonate ultracataclasite, and the geometrical characteristics of White Mountain suggest a possible initial upper plate emplacement rate of 126-340 m/sec and that the duration of the emplacement event was less than 4 min, too brief a time to develop an emplacement-related calcite twinning strain overprint in upper or lower plate carbonates. While the detachment-related carbonate ultracataclasite did not form by melting, it does preserve a magnetic fabric where [K.sub.max] is parallel to the detachment slip direction and records a westward and down paleopole (287[degrees] and 27[degrees]), where magnetite is the carrier mineral. The Eocene (49.6 Ma) paleopole for this latitude in North America was southerly and upward (0[degrees] and 45[degrees]). This brief and catastrophic detachment event produced a significant amount of C[O.sub.2] by flash heating. This report is the first to quantify the emplacement rate of the upper plate of the Heart Mountain detachment based on physical and geochemical parameters. Keywords: Heart Mountain detachment, calcite strains, paleomagnetism, thermodynamics, flash heating.

The onset of the Dead Sea transform has recently been reevaluated by U-Pb age-strain analyses of fault-related calcite taken from several fault strands along its main 500-km-long sector. The results suggest that the relative motion between Africa and Arabia north of the Red Sea was transferred northward to the Dead Sea transform as early as 20 Ma and along a ~10-km-wide deformation zone that formed the central rift with contemporaneous bounding sinistral motion. The Gishron fault is the western bounding fault with normal and sinistral fault offsets that placed Proterozoic crystalline rocks and a cover of Cambrian sandstones in fault contact with Cretaceous-Eocene carbonates. Fault-related calcite veins are common in the Gishron fault zone, and we report the results of a detailed study of one sample with nine calcite fillings. Low fluid inclusion entrapment temperatures <50 °C, stable isotopes values of-3.3-0‰ (δ13C; PDB) and 15.3‰ to 17.6‰ (δ18O; SMOW), and low rare earth element (REE) concentrations within the nine calcite fault fillings indicate that a local, meteoric fluid fed the Gishron fault zone over ca. 7 Ma at depths of <2 km. Laser ablation U-Pb ages within the thin section range from 20.37 Ma to 12.89 Ma and allow a detailed fault-filling chronology with the oldest calcite filling in the middle, younging outward with shearing between the oldest eight zones, all of which are finally crosscut by a perpendicular (E-W) vein. All nine calcite fillings have unique mechanical twinning strain results (n = 303 grains). Shortening strain magnitudes (-0.28% to-2.8%) and differential stresses (-339 bars to-415 bars) vary across the sample, as do the orientations of the shortening (ε1) and extension (ε3) axes with no evidence of any twinning strain overprint (low negative expected values). Overall, the tectonic compression and shortening is sub-horizontal and sub-parallel to the Gishron fault (~N-S) and Dead Sea transform plate boundary. Most strikingly, the 7 m.y. period of vein growth correlates exactly with the timing of fault activity as evident within the 10-km-wide deformation zone in this evolving plate boundary (between 20 Ma and 13 Ma). [ABSTRACT FROM AUTHOR]

Calcite veins and amygdule fillings within basalts (older than 0.7 Ma) are mechanically twinned and preserve a subhorizontal shortening strain that resulted from compression and shortening normal to the Mid-Atlantic Ridge on both sides of the plate boundary. Our sample suite includes 19 specimens, 7 from the North American plate (4 veins, 3 amygdule fillings) and 12 from the European plate (9 veins, 3 amygdule fillings), 18 of which record ridge-normal subhorizontal shortening. Five of the strain analyses, two from the North American plate and three from the European plate, have a high percentage of negative expected values, and these secondary strain results record a ridge-parallel shortening strain with plunges that vary parallel to the ridge axis. Averaged shortening strain magnitudes for the twinned calcite (-2.5%, European plate; -6.02%, North American plate) and inferred differential stresses (-48 MPa) that caused the twinning are modest and are thought to represent regional tectonic conditions (i.e., ridge push), not local (e.g., hotspot or glacial loading) phenomena. Keywords: divergent plate boundary, calcite twinning, stress-strain field, ridge push.