Structured Grading

This paper describes a compromise between the idealism of criterion based grading and the pragmatism of a norm based approach. The discussion is supported by a series of computer programs that are deliberately devoid of packaging clutter so that the users can clearly comprehend the processes and adapt the code to suit their particular purposes. The input data can be in numerical, alphabetical or categorical form and the primary output is a matrix of standardized marks. Additional analyses provide frequency distributions, rank order and alphabetic grade matrices, component correlations and categorical item analyses. The programs are designed to provide timely and appropriate information for final grade allocation.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

Background: We previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15–20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in ~ 80% of cases. Methods: We report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded. Results: No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5–528.7, P = 1.1 × 10−4) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR = 3.70[95%CI 1.3–8.2], P = 2.1 × 10−4). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR = 19.65[95%CI 2.1–2635.4], P = 3.4 × 10−3), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR = 4.40[9%CI 2.3–8.4], P = 7.7 × 10−8). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD] = 43.3 [20.3] years) than the other patients (56.0 [17.3] years; P = 1.68 × 10−5). Conclusions: Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

Inborn errors of OAS-RNase L in SARS-CoV-2-related multisystem inflammatory syndrome in children

Multisystem inflammatory syndrome in children (MIS-C) is a rare and severe condition that follows benign COVID-19. We report autosomal recessive deficiencies of OAS1, OAS2, or RNASEL in five unrelated children with MIS-C. The cytosolic double-stranded RNA (dsRNA)-sensing OAS1 and OAS2 generate 2'-5'-linked oligoadenylates (2-5A) that activate the single-stranded RNA-degrading ribonuclease L (RNase L). Monocytic cell lines and primary myeloid cells with OAS1, OAS2, or RNase L deficiencies produce excessive amounts of inflammatory cytokines upon dsRNA or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulation. Exogenous 2-5A suppresses cytokine production in OAS1-deficient but not RNase L-deficient cells. Cytokine production in RNase L-deficient cells is impaired by MDA5 or RIG-I deficiency and abolished by mitochondrial antiviral-signaling protein (MAVS) deficiency. Recessive OAS-RNase L deficiencies in these patients unleash the production of SARS-CoV-2-triggered, MAVS-mediated inflammatory cytokines by mononuclear phagocytes, thereby underlying MIS-C

Formation of colloidal alloy semiconductor CdTeSe magic-size clusters at room temperature

Alloy magic-size clusters (MSCs) are difficult to synthesize, in part because so little is known about how they form. Here, the authors produce single-ensemble alloy CdTeSe MSCs at room temperature by mixing prenucleation-stage solutions of CdTe and CdSe, uncovering a formation pathway that may extend to the synthesis of other alloy MSCs

Analysis of the environmental control technology for tar sand development

The environmental technology for control of air pollution, water pollution, and for the disposal, stabilization, and vegetation of the waste tar sand were thoroughly investigated. Although some difficulties may be encountered in any of these undertakings, it seems clear that the air and water pollution problems can be solved to meet any applicable standard. Currently there are two large-scale plants producing liquid fuels from tar sands in Alberta, Canada which use similar technology involving surface mining, hot water extraction, and surface disposal of waste sand. These projects all meet the Canadian environmental control regulations in force at the time they began. The largest US deposits of tar sands are much smaller than the Canadian; 95 percent are located in the state of Utah. Their economics do not appear as attractive as the Canadian deposits. The environmental control costs are not large enough to make an otherwise economic project uneconomic. The most serious environmental conflict likely to occur over the recovery of liquid fuels from the US deposits of tar sands is that caused by the proximity of the deposits to national parks, national monuments, and a national recreation area in Utah. These areas have very stringent air pollution requirements; and even if the air pollution control requirements can be met, there may still be adequate opposition to large-scale mining ventures in these areas to prevent their commercial exploitation. Another environmental constraint may be water rights availability.Essentially all of the water running in the Colorado river basin is now legally allocated. Barring new interpretations of the legality of water rights purchase, Utah tar sands developments should be able to obtain water by purchasing existing irrigation water rights

Analysis of the environmental control technology for oil shale development

The environmental control technology proposed in the various oil shale projects which are under development are examined. The technologies for control of air pollution, water pollution, and for the disposal, stabilization, and vegetation of the processed shale were thoroughly investigated. Although some difficulties may be encountered in any of these undertakings, it seems clear that the air and water pollution problems can be solved to meet any applicable standard. There are no published national standards against which to judge the stabilization and vegetation of the processed shale. However, based on the goal of producing an environmentally and aesthetically acceptable finished processed shale pile, it seems probable that this can be accomplished. It is concluded that the environmental control technology is available to meet all current legal requirements. This was not the case before Colorado changed their applicable Air Pollution regulations in August of 1977; the previous ones for the oil shale region were sufficiently stringent to have caused a problem for the current stage of oil shale development. Similarly, the federal air-quality, non-deterioration regulations could be interpreted in the future in ways which would be difficult for the oil shale industry to comply with. The Utah water-quality, non-deterioration regulations could also be a problem. Thus, the only specific regulations which may be a problem are the non-deterioration parts of air and water quality regulations. The unresolved areas of environmental concern with oil shale processing are mostly for the problems not covered by existing environmental law, e.g., trace metals, polynuclear organics, ground water-quality changes, etc. These may be problems, but no evidence is yet available that these problems will prevent the successful commercialization of oil shale production