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Background The shift to more transmissible but less virulent strains of SARS-CoV-2 has altered the risk calculation for infection. Particularly among young adults, the economic burden of lost work due to isolation exceeds the economic burden of morbidity due to infection. Testing strategies must adapt to these changing circumstances. Methods We modeled six testing strategies to estimate total societal costs for symptomatic people 18-49 years old: isolation of all individuals with no testing, rapid antigen test (RAg), RAg followed by a second RAg 48h later if first negative, RAg followed by a polymerase chain reaction (PCR) if negative, RAg followed by a PCR if positive, and PCR alone. We calculated costs for hypothetical cohorts of 100 symptomatic healthcare workers tested with each strategy; we included testing costs, lost wages, and hospitalization costs for the index, secondary, and tertiary cases. Key assumptions were 5% prevalence of infection, sensitivity of first/second RAg 40/80% with 97% specificity, PCR sensitivity/specificity 95/99%, all individuals isolate at symptom onset, are tested the same day, and isolate for 5 days if positive. RAg results were available the same day, PCR results were available the next day (Figure 1). One-way sensitivity analyses were performed for RAg sensitivity (20-80%) and positivity rate (1-80%). Results The least expensive strategy was RAg alone (Figure 2). This was primarily driven by its low sensitivity, which reduced lost wages at the expense of missing cases. At a threshold for RAg sensitivity lower than 29%, PCR testing alone became the cheapest strategy. When the positivity rate was > 6% confirming a negative RAg with a PCR became the cheapest strategy, closely followed by PCR alone. At a positivity rate of > 29%, isolation without testing was cheapest followed by confirming a negative RAg with a PCR and by the serial RAg test strategies (Figure 3). Conclusion In relatively young, healthy populations, a single rapid test was the least expensive strategy when the positivity rate was < 6%, testing that included PCR became cheapest at intermediate positivity, and empiric isolation was cheapest at positivity > 29%. Calibrating SARS-CoV-2 test strategies based on epidemiology may save societal costs. Disclosures Nicholas A. Turner, MD, MHSc, Aperio: Advisor/Consultant.

Rationale: More information on risk factors for death from tuberculosis in the United States could help reduce the tuberculosis mortality rate, which has remained steady for more than a decade.Objective: To identify risk factors for tuberculosis-related death in adults.Methods: We performed a retrospective study of 1,304 adults with tuberculosis who died before treatment completion and 1,039 frequency-matched control subjects who completed tuberculosis treatment in 2005 to 2006 in 13 states reporting 65% of U.S. tuberculosis cases. We used in-depth record abstractions and a standard algorithm to classify deaths in persons with tuberculosis as tuberculosis-related or not. We then compared these classifications to causes of death as coded in death certificates. We used multivariable logistic regression to calculate adjusted odds ratios for predictors of tuberculosis-related death among adults compared with those who completed tuberculosis treatment.Results: Of 1,304 adult deaths, 942 (72%) were tuberculosis related, 272 (21%) were not, and 90 (7%) could not be classified. Of 847 tuberculosis-related deaths with death certificates available, 378 (45%) did not list tuberculosis as a cause of death. Adjusting for known risks, we identified new risks for tuberculosis-related death during treatment: absence of pyrazinamide in the initial regimen (adjusted odds ratio, 3.4; 95% confidence interval, 1.9-6.0); immunosuppressive medications (adjusted odds ratio, 2.5; 95% confidence interval, 1.1-5.6); incomplete tuberculosis diagnostic evaluation (adjusted odds ratio, 2.2; 95% confidence interval, 1.5-3.3), and an alternative nontuberculosis diagnosis before tuberculosis diagnosis (adjusted odds ratio, 1.6; 95% confidence interval, 1.2-2.2).Conclusions: Most persons who died with tuberculosis had a tuberculosis-related death. Intensive record review revealed tuberculosis as a cause of death more often than did death certificate diagnoses. New tools, such as a tuberculosis mortality risk score based on our study findings, may identify patients with tuberculosis for in-hospital interventions to prevent death.

Both short photoperiod and communal social living conserve metabolic energy by deer mice held in thermal neutral ambient temperatures. Initial socialization was energetically more costly than solitary living, but huddling behaviors reduced thermal conductance and mass specific metabolic rate by 30% within 5 days. While short photoperiod reduced metabolic energy expenditure by decreasing thermoregulatory demand, huddling mediated behavioral conservation was achieved with hyperthermic core temperatures.

1. 1. Adrenal secretion and frequency and severity of renal pathology was positively correlated with animal densities of both species. 2. 2. Lemmings had a greater capacity for increased adrenal response than deer mice. 3. 3. Similar rates of increased pathology and of adrenal function in response to increased density were expressed by both species. 4. 4. Marked species differences in the expression of reproductive inhibition with density increase were apparent.

1. 1. Cycles in breeding and adaptive endocrine responses of Peromyscus maniculatus follow seasonal climatic changes. 2. 2. Randomly cropped and undisturbed populations followed parallel spring and autumn peaks in adrenal-pituitary, gonadal-pituitary, breeding and density. 3. 3. There was a midsummer reduction of breeding, recruitment and density followed by declines in adrenal response. 4. 4. Prevention of juvenile recruitment and emergence through selective cropping increased the productivity of resident adults and extended the autumn breeding cycle. 5. 5. Juvenile cropping also attenuated the adrenal secretory response to reduced day length and cold without impairing adrenal-pituitary responsiveness. 6. 6. Winter breeding occurred in the manipulated population even though most animals in the population showed a reduction in pituitary-gonadal activity in response to winter conditions.

1. Resting, daytime, thermal conductances and metabolic rates of mice conditioned to winter (10:14LD) and summer (14:10LD) photoperiods were reduced by social huddling; huddling resulted in group size related elevations in core temperature during summer, but not with winter light-dark cycle exposures. 2. Core temperatures of resting, solitary winter animals were lower than those of summer; both summer and winter animals' core temperatures were further reduced by increased thermal conductance resulting from (phentolamine) alpha receptor blockade. 3. Social huddling reduction of the heat loss from phentolamine treatment was more effective for winter (10:14LD) animals. 4. While phentolamine treatment resulted in increased thermal conductance and lower core temperatures of the mice, propranalol treatment resulted in lower core temperatures and resting metabolic rates, with a resulting decrease in thermal conductance. 5. Since adrenergic blockade was less dose-effective on winter animals, we reasoned that winter animals display higher levels of endogenous adrenergic capacity than summer animals and that lower winter thermoregulatory set points provide for energy conservation with enhanced capacity for meeting cold challenge.

1. 1. Seasonal changes in metabolic rate can be induced in mice held in thermal neutral (26–29°C) ambient temperatures. 2. 2. The metabolic effect of winter photoperiod is a lower metabolic rate without compromise to metabolic reserve. 3. 3. Manipulations of photoperiod or melatonin backgrounds adjust the thermoregulatory setting for core temperature level and affect thermal conductance.

1. 1. Randomly trapped samples of saturated (land-fill) and expanding (pen) Norway rat populations revealed variations in structure brought about by spring and summer recruitment and fall and winter depression of reproduction. 2. 2. Pituitary-adrenal hyperfunction occurred in the saturated population during the recruitment period; breeding and recruitment were curtailed in the saturated population when the population showed signs of stress. 3. 3. Recruitment in low-density, expanding pen populations did not elicit signs of stress or depress reproductive potential. 4. 4. Winter conditions elicited hyperadrenalism and reproductive depression in both saturated and expanding populations. The frequency of regressed gonads and sex accessory tissues was highest in January when no pregnancies or juvenile recruitment was apparent. 5. 5. A progression of pathological changes in the hearts, livers and kidneys of animals developed following the summer social stress which was maximal with the onset of winter. The decreasing frequency of severe metabolic disease as the winter turned to spring was attributed to probable deaths of weakened animals during the severe winter cold.