Natural ventilation reduces high TB transmission risk in traditional homes in rural KwaZulu-Natal, South Africa

Background: Transmission of drug susceptible and drug resistant TB occurs in health care facilities, and community and households settings, particularly in highly prevalent TB and HIV areas. There is a paucity of data regarding factors that may affect TB transmission risk in household settings. We evaluated air exchange and the impact of natural ventilation on estimated TB transmission risk in traditional Zulu homes in rural South Africa. Methods: We utilized a carbon dioxide decay technique to measure ventilation in air changes per hour (ACH). We evaluated predominant home types to determine factors affecting ACH and used the Wells-Riley equation to estimate TB transmission risk. Results: Two hundred eighteen ventilation measurements were taken in 24 traditional homes. All had low ventilation at baseline when windows were closed (mean ACH = 3, SD = 3.0), with estimated TB transmission risk of 55.4% over a ten hour period of exposure to an infectious TB patient. There was significant improvement with opening windows and door, reaching a mean ACH of 20 (SD = 13.1, p < 0.0001) resulting in significant decrease in estimated TB transmission risk to 9.6% (p < 0.0001). Multivariate analysis identified factors predicting ACH, including ventilation conditions (windows/doors open) and window to volume ratio. Expanding ventilation increased the odds of achieving ≥12 ACH by 60-fold. Conclusions: There is high estimated risk of TB transmission in traditional homes of infectious TB patients in rural South Africa. Improving natural ventilation may decrease household TB transmission risk and, combined with other strategies, may enhance TB control efforts

Atomic layering at the liquid silicon surface: a first- principles simulation

We simulate the liquid silicon surface with first-principles molecular dynamics in a slab geometry. We find that the atom-density profile presents a pronounced layering, similar to those observed in low-temperature liquid metals like Ga and Hg. The depth-dependent pair correlation function shows that the effect originates from directional bonding of Si atoms at the surface, and propagates into the bulk. The layering has no major effects in the electronic and dynamical properties of the system, that are very similar to those of bulk liquid Si. To our knowledge, this is the first study of a liquid surface by first-principles molecular dynamics.Comment: 4 pages, 4 figures, submitted to PR

Deploying a Top-100 Supercomputer for Large Parallel Workloads: the Niagara Supercomputer

Niagara is currently the fastest supercomputer accessible to academics in Canada. It was deployed at the beginning of 2018 and has been serving the research community ever since. This homogeneous 60,000-core cluster, owned by the University of Toronto and operated by SciNet, was intended to enable large parallel jobs and has a measured performance of 3.02 petaflops, debuting at #53 in the June 2018 TOP500 list. It was designed to optimize throughput of a range of scientific codes running at scale, energy efficiency, and network and storage performance and capacity. It replaced two systems that SciNet operated for over 8 years, the Tightly Coupled System (TCS) and the General Purpose Cluster (GPC). In this paper we describe the transition process from these two systems, the procurement and deployment processes, as well as the unique features that make Niagara a one-of-a-kind machine in Canada.Comment: PEARC'19: "Practice and Experience in Advanced Research Computing", July 28-August 1, 2019, Chicago, IL, US

Squeezed by a Habitat Split: Warm Ocean Conditions and Old‐forest Loss Interact to Reduce Long‐term Occupancy of a Threatened Seabird

Theory predicts that species requiring multiple habitat types simultaneously should have heightened sensitivity to anthropogenic pressures, yet tests of this prediction are especially rare. We tested whether breeding site occupancy of the threatened marbled murrelet (Brachyramphus marmoratus) was driven by the synergistic effects of nesting habitat loss in forests, and changing ocean condi- tions. We paired 70,700 murrelet surveys at 19,837 sites across 20 years from the Oregon Coast Range with annual data on the extent of old forest and biophysical ocean conditions. Dynamic occupancy models indicated that local murrelet col- onization rates were strongly reduced during warm ocean conditions with low prey availability. Landscapes that contained more old forest and were closer to the ocean showed reduced rates of local extinction. Given predictions of accel- erated ocean warming and increased global timber demand, our results suggest murrelets may continue to be imperiled by deterioration of the two habitats upon which they depend

Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations

Background Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disease affecting multiple body systems with wide variability in presentation. In 2013, Pediatric Neurology published articles outlining updated diagnostic criteria and recommendations for surveillance and management of disease manifestations. Advances in knowledge and approvals of new therapies necessitated a revision of those criteria and recommendations. Methods Chairs and working group cochairs from the 2012 International TSC Consensus Group were invited to meet face-to-face over two days at the 2018 World TSC Conference on July 25 and 26 in Dallas, TX, USA. Before the meeting, working group cochairs worked with group members via e-mail and telephone to (1) review TSC literature since the 2013 publication, (2) confirm or amend prior recommendations, and (3) provide new recommendations as required. Results Only two changes were made to clinical diagnostic criteria reported in 2013: “multiple cortical tubers and/or radial migration lines” replaced the more general term “cortical dysplasias,” and sclerotic bone lesions were reinstated as a minor criterion. Genetic diagnostic criteria were reaffirmed, including highlighting recent findings that some individuals with TSC are genetically mosaic for variants in TSC1 or TSC2. Changes to surveillance and management criteria largely reflected increased emphasis on early screening for electroencephalographic abnormalities, enhanced surveillance and management of TSC-associated neuropsychiatric disorders, and new medication approvals. Conclusions Updated TSC diagnostic criteria and surveillance and management recommendations presented here should provide an improved framework for optimal care of those living with TSC and their families

The transcription factor EBF directs B lineage commitment

B cell development proceeds through a defined set of cellular intermediates that give rise to mature cells. Current understanding of B cell development places EBF downstream of the transcription factors E2A and Pu.1 and signaling through the interleukin 7 receptor. EBF acts upstream of Pax5 which is considered to be the master regulator of B cell development. Contrary to this prevailing belief, Pax5 is incapable of rescuing the B cell deficiencies imposed by loss of E2A, Pu.1, IL-7R or EBF. However, ectopic expression of EBF partially restores the B cell defects imposed by loss of each of these factors. In this thesis we evaluated the role of EBF in B cell development. Loss of EBF function in B cell progenitors increases their ability to develop into non-B lineages. When expression of EBF is forced, it instructs multipotent and myeloid progenitors into the B lineage at the expense of myeloid and T development. We suggest that EBF effects this lineage decision by reducing the expression of C/EBPα and PU.1 to limit myeloid development and by lowering expression of GATA3 to limit T cell development. In order to address the cellular context where EBF can operate, we expressed EBF in E2A deficient myeloid progenitors. We demonstrated that EBF can redirect myeloid progenitors to the B lineage in the absence of E2A. Because EBF induces Pax5, we expressed EBF in Pax5-/- progenitors to determine the Pax5 independent roles of EBF. Strikingly, EBF blocked the generation of both myeloid and T lineage cells in the absence of Pax5. Because EBF is a Pax5 target, we hypothesize that a central role of Pax5 in the B lineage is to sustain EBF expression. The stable loop consisting of these two factors constitutes the core regulation of B lineage commitment. Although EBF promoted the development of B lineage cells in the absence of Pax5, they were incapable of maturation. Without EBF, Pax5 is capable of inducing the expression of CD19 and Ig-α, known Pax5 targets previously thought to depend on EBF. These results show that the principal regulators of the B lineage have both shared and separate roles

The transcription factor EBF directs B lineage commitment

B cell development proceeds through a defined set of cellular intermediates that give rise to mature cells. Current understanding of B cell development places EBF downstream of the transcription factors E2A and Pu.1 and signaling through the interleukin 7 receptor. EBF acts upstream of Pax5 which is considered to be the master regulator of B cell development. Contrary to this prevailing belief, Pax5 is incapable of rescuing the B cell deficiencies imposed by loss of E2A, Pu.1, IL-7R or EBF. However, ectopic expression of EBF partially restores the B cell defects imposed by loss of each of these factors. In this thesis we evaluated the role of EBF in B cell development. Loss of EBF function in B cell progenitors increases their ability to develop into non-B lineages. When expression of EBF is forced, it instructs multipotent and myeloid progenitors into the B lineage at the expense of myeloid and T development. We suggest that EBF effects this lineage decision by reducing the expression of C/EBPα and PU.1 to limit myeloid development and by lowering expression of GATA3 to limit T cell development. In order to address the cellular context where EBF can operate, we expressed EBF in E2A deficient myeloid progenitors. We demonstrated that EBF can redirect myeloid progenitors to the B lineage in the absence of E2A. Because EBF induces Pax5, we expressed EBF in Pax5-/- progenitors to determine the Pax5 independent roles of EBF. Strikingly, EBF blocked the generation of both myeloid and T lineage cells in the absence of Pax5. Because EBF is a Pax5 target, we hypothesize that a central role of Pax5 in the B lineage is to sustain EBF expression. The stable loop consisting of these two factors constitutes the core regulation of B lineage commitment. Although EBF promoted the development of B lineage cells in the absence of Pax5, they were incapable of maturation. Without EBF, Pax5 is capable of inducing the expression of CD19 and Ig-α, known Pax5 targets previously thought to depend on EBF. These results show that the principal regulators of the B lineage have both shared and separate roles