Hospital work load produced by breast-cancer screening programme run by trained non-medical staff.

In a feasibility study of mass population screening for breast cancer by annual clinical examination and mammography the findings of non-medical staff (nurses and radiographers) were used to estimate the hospital work load generated by such a programme. Among 2490 women who attended for the first time by invitation the rate of referral for a surgical opinion based on the findings of the non-medical staff was 7.9% and the biopsy rate 2.5%. In the second and third years referral rates fell to 4.3% and 2.7% respectively and the biopsy rates to 1.1% and 1.4%. The rates of referral and biopsy among 1203 women who referred themselves for screening were higher, but many self-referred women were symptomatic; those without symptoms had rates of referral and biopsy similar to those of the invited women. Extrapolation of these findings to a population of 200,000 in a typical health district showed that the hospital work load would be high in the first year of screening with 44 outpatient referrals per week and 14 biopsies. By the third year, however, only seven referrals and four biopsies a week could be expected. The work load would be reduced by a third if screening were confined to women over the age of 50.     

Screening for breast cancer.

The feasibility of mass population screening for breast cancer by clinical examination and x-ray mammography was studied. The results indicate that such a programme could be conducted effectively by non-medical staff and be safe from the dangers of irradiation. The response rate of women invited for screening suggests that such a service is acceptable to the general public. The additional work load produced by screening would not overburden the existing surgical services.     

Aldosterone dynamics during graded exercise at sea level and high altitude.

Hormonal responses to graded exercise of eight low altitude residents were examined at sea level (SL) and after 1 (acute) and 11 (chronic) days at 4,300 m (HA). Caloric, water, and electrolyte intakes were controlled, as were temperature and humidity. Blood was sampled at rest and during light and moderate upright bicycle exercise (20 min at 40% and 75% of maximal O2 uptake, respectively). Mean VO2 max at HA was 27% lower than at SL. Resting plasma levels of aldosterone (Aldo), renin, and angiotensin II (A II) were significantly lower (P smaller than 0.05) on day 1 at HA compared to SL, but returned to SL values by day 11. Plasma cortisol values at rest were similar at SL and HA and were not significantly altered by light or moderate exercise. Renin, A II, and Aldo rose progressively with increasing workload in each environment. With acute HA, renin and Aldo were lower than at either SL or chronic HA. The chronic HA levels tended to approximate SL findings, implying adaptation. The data suggest that aldosterone is predominantly under the control of the renin-angiotensin system during graded exercise at sea level and that the response of this system is altered on acute high-altitude exposure.     

Data-Driven Modeling to Assess Receptivity for Rift Valley Fever Virus

Rift Valley Fever virus (RVFV) is an enzootic virus that causes extensive morbidity and mortality in domestic ruminants in Africa, and it has shown the potential to invade other areas such as the Arabian Peninsula. Here, we develop methods for linking mathematical models to real-world data that could be used for continent-scale risk assessment given adequate data on local host and vector populations. We have applied the methods to a well-studied agricultural region of California with 1 million dairy cattle, abundant and competent mosquito vectors, and a permissive climate that has enabled consistent transmission of West Nile virus and historically other arboviruses. Our results suggest that RVFV outbreaks could occur from February–November, but would progress slowly during winter–early spring or early fall and be limited spatially to areas with early increases in vector abundance. Risk was greatest in summer, when the areas at risk broadened to include most of the dairy farms in the study region, indicating the potential for considerable economic losses if an introduction were to occur. To assess the threat that RVFV poses to North America, including what-if scenarios for introduction and control strategies, models such as this one should be an integral part of the process; however, modeling must be paralleled by efforts to address the numerous remaining gaps in data and knowledge for this system.     

Genomic surveillance of Nevada patients revealed prevalence of unique SARS-CoV-2 variants bearing mutations in the RdRp gene

Patients with signs of COVID-19 were tested through diagnostic RT-PCR for SARS-CoV-2 using RNA extracted from the nasopharyngeal/nasal swabs.To determine the variants of SARS-CoV-2 circulating in the state of Nevada,specimens from 200 COVID-19 patients were sequenced through our robust sequencing platform,which enabled sequencing of SARS-CoV-2 from specimens with even very low viral loads,without the need of culture-based amplification.High genome coverage allowed the identification of single and multi-nucleotide variants in SARS-CoV-2 in the community and their phylogenetic relationships with other variants present during the same period of the outbreak.We report the occurrence of a novel mutation at 323aa (314aa of orf1b) of nsp12 (RNA-dependent RNA polymerase) changed to phenylalanine(F) from proline (P),in the first reported isolate of SARS-CoV-2,Wuhan-Hu-1.This 323F variant was present at a very high frequency in Northern Nevada.Structural modeling determined this mutation in the interface domain,which is important for the association of accessory proteins required for the polymerase.In conclusion,we report the introduction of specific SARS-CoV-2 variants at very high frequency in distinct geographic locations,which is important for understanding the evolution and circulation of SARS-CoV-2variants of public health importance,while it circulates in humans.     

Effects of seasonal snow on the growing season of temperate vegetation in China

Variations in seasonal snowfall regulate regional and global climatic systems and vegetation growth by changing energy budgets of the lower atmosphere and land surface. We investigated the effects of snow on the start of growing season (SGS) of temperate vegetation in China. Across the entire temperate region in China, the winter snow depth increased at a rate of 0.15 cm yr^?1 (P = 0.07) during the period 1982–1998, and decreased at a rate of 0.36 cm yr^?1 (P = 0.09) during the period 1998–2005. Correspondingly, the SGS advanced at a rate of 0.68 day yr^?1 (P < 0.01) during 1982–1998, and delayed at a rate of 2.13 day yr^?1 (P = 0.07) during 1998–2005, against a warming trend throughout the entire study period of 1982–2005. Spring air temperature strongly regulated the SGS of both deciduous broad‐leaf and coniferous forests, whereas the winter snow had a greater impact on the SGS of grassland and shrubs. Snow depth variation combined with air temperature contributed to the variability in the SGS of grassland and shrubs, as snow acted as an insulator and modulated the underground thermal conditions. In addition, differences were seen between the impacts of winter snow depth and spring snow depth on the SGS; as snow depths increased, the effect associated went from delaying SGS to advancing SGS. The observed thresholds for these effects were snow depths of 6.8 cm (winter) and 4.0 cm (spring). The results of this study suggest that the response of the vegetation's SGS to seasonal snow change may be attributed to the coupling effects of air temperature and snow depth associated with the underground thermal conditions.     

A trs20 Mutation That Mimics an SEDT‐Causing Mutation Blocks Selective and Non‐Selective Autophagy: A Model for TRAPP III Organization

TRAPP is a multisubunit complex that functions in membrane traffic. Mutations in the mammalian TRAPP protein C2 are linked to the skeletal disorder spondyloepiphyseal dysplasia tarda (SEDT) that is thought to arise from an inability to secrete procollagen from the endoplasmic reticulum. Here, we show that C2 binds to the SNARE protein Syntaxin 5 and this interaction is weakened by an SEDT‐causing missense mutation (D47Y). Interestingly, the equivalent mutation (D46Y) in the yeast C2 homolog Trs20p does not block anterograde traffic but did affect endocytosis. The trs20D46Y mutation interfered with the interaction between Trs20p and Trs85p (TRAPP III‐specific subunit), Trs120p and Trs130p (TRAPP II‐specific subunits). Size exclusion chromatography suggested that this yeast mutation destabilized the TRAPP III complex that is involved in autophagy. We further show that this mutation blocks both the selective cytosol‐to‐vacuole (cvt) pathway as well as non‐selective autophagy. We demonstrate that the apparent molecular size of the TRAPP III complex is dependent upon membranes, and that the presence of TRAPP III is dependent upon Atg9p. Finally, we demonstrate that lipidated Bet3p is enriched in TRAPP III and that lipidation increases the efficiency of autophagy. Our study suggests that Trs20p acts as an adaptor for Trs85p and Trs120p and reveals complexities in TRAPP III assembly and function. The implications of C2D47Y in SEDT are discussed .