Rt Estimates Research Articles

A pitfall in estimating the e ective reproductive number Rt for COVID-19.

The effective reproductive number Rt of COVID-19 is determined indirectly from data that are only incompletely known (fig. 1). Approaches based on reconstructing these data by sampling time lags from suitable distributions introduce noise effects that can result in distorted estimates of Rt . This, in turn, may lead to misleading interpretations of the efficacy of the various measures taken to limit COVID-19 transmission. We discuss in some detail a study used for real time monitoring of the reproductive number in Switzerland [2].

Early dynamics of transmission and control of COVID-19: a mathematical modelling study

SummaryBackgroundAn outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to 95 333 confirmed cases as of March 5, 2020. Understanding the early transmission dynamics of the infection and evaluating the effectiveness of control measures is crucial for assessing the potential for sustained transmission to occur in new areas. Combining a mathematical model of severe SARS-CoV-2 transmission with four datasets from within and outside Wuhan, we estimated how transmission in Wuhan varied between December, 2019, and February, 2020. We used these estimates to assess the potential for sustained human-to-human transmission to occur in locations outside Wuhan if cases were introduced.MethodsWe combined a stochastic transmission model with data on cases of coronavirus disease 2019 (COVID-19) in Wuhan and international cases that originated in Wuhan to estimate how transmission had varied over time during January, 2020, and February, 2020. Based on these estimates, we then calculated the probability that newly introduced cases might generate outbreaks in other areas. To estimate the early dynamics of transmission in Wuhan, we fitted a stochastic transmission dynamic model to multiple publicly available datasets on cases in Wuhan and internationally exported cases from Wuhan. The four datasets we fitted to were: daily number of new internationally exported cases (or lack thereof), by date of onset, as of Jan 26, 2020; daily number of new cases in Wuhan with no market exposure, by date of onset, between Dec 1, 2019, and Jan 1, 2020; daily number of new cases in China, by date of onset, between Dec 29, 2019, and Jan 23, 2020; and proportion of infected passengers on evacuation flights between Jan 29, 2020, and Feb 4, 2020. We used an additional two datasets for comparison with model outputs: daily number of new exported cases from Wuhan (or lack thereof) in countries with high connectivity to Wuhan (ie, top 20 most at-risk countries), by date of confirmation, as of Feb 10, 2020; and data on new confirmed cases reported in Wuhan between Jan 16, 2020, and Feb 11, 2020.FindingsWe estimated that the median daily reproduction number (Rt) in Wuhan declined from 2·35 (95% CI 1·15–4·77) 1 week before travel restrictions were introduced on Jan 23, 2020, to 1·05 (0·41–2·39) 1 week after. Based on our estimates of Rt, assuming SARS-like variation, we calculated that in locations with similar transmission potential to Wuhan in early January, once there are at least four independently introduced cases, there is a more than 50% chance the infection will establish within that population.InterpretationOur results show that COVID-19 transmission probably declined in Wuhan during late January, 2020, coinciding with the introduction of travel control measures. As more cases arrive in international locations with similar transmission potential to Wuhan before these control measures, it is likely many chains of transmission will fail to establish initially, but might lead to new outbreaks eventually.FundingWellcome Trust, Health Data Research UK, Bill & Melinda Gates Foundation, and National Institute for Health Research.

Impact of mass vaccination campaigns on measles transmission during an outbreak in Guinea, 2017

ObjectiveTo estimate the time-dependent measles effective reproduction number (Rt) as an indicator of the impact of three outbreak response vaccination (ORV) campaigns on measles transmission during a nationwide outbreak in Guinea. MethodsRt represents the average number of secondary cases generated by a single primary case in a partially immune population during a given time period. Measles Rt was estimated using daily incidence data for 3952 outbreak-associated measles cases in Guinea in 2017 for the time periods prior to, between, and following each of three ORV campaigns using a simple and extensible mathematical model. ResultsRt was estimated to be above the threshold value of 1 during the initial growth period of the outbreak until the first ORV campaign began on March 13 (Rt = 1.60, 95% CI: 1.55–1.67). It subsequently dropped below 1 and remained <1 through the end of the year (range: 0.71–0.91), although low levels of transmission persisted. ConclusionsReduction in Rt coincided with implementation of the ORV campaigns, indicating success of the campaigns at maintaining measles transmission intensity below epidemic growth levels. However, persistent measles transmission remains an issue in Guinea due to insufficient levels of herd immunity. Estimation of Rt should be further leveraged to help decision makers and field staff understand outbreak progress and the timing and type of vaccination efforts needed to halt transmission.

Transmission potential of the novel coronavirus (COVID-19) onboard the diamond Princess Cruises Ship, 2020.

An outbreak of COVID-19 developed aboard the Princess Cruises Ship during January–February 2020. Using mathematical modeling and time-series incidence data describing the trajectory of the outbreak among passengers and crew members, we characterize how the transmission potential varied over the course of the outbreak. Our estimate of the mean reproduction number in the confined setting reached values as high as ~11, which is higher than mean estimates reported from community-level transmission dynamics in China and Singapore (approximate range: 1.1–7). Our findings suggest that Rt decreased substantially compared to values during the early phase after the Japanese government implemented an enhanced quarantine control. Most recent estimates of Rt reached values largely below the epidemic threshold, indicating that a secondary outbreak of the novel coronavirus was unlikely to occur aboard the Diamond Princess Ship.

Prostate Cancer Anxiety in Survivors, Results from a Population-Based Cohort

Anxiety in cancer survivors can be harmful because it is associated with depression, poorer adherence to medical treatment, poorer treatment outcomes, and higher rates of mortality. However, anxiety in prostate cancer survivors has not been well-studied and is not well understood. In the only modern, fully-prospective, population-based cohort, 951 men diagnosed from 2011-13 with localized prostate cancer were enrolled throughout the state in collaboration with the North Carolina state cancer registry. All patients were prospectively followed, and anxiety assessed using the validated Memorial Anxiety Scale for Prostate Cancer (MAX-PC); 11 items assess prostate cancer anxiety with total score range from 0 (none) to 33 (most anxiety). Multivariable analysis using generalized estimating equations assessed patient and diagnostic factors associated with anxiety. Diversity of the cohort reflects population-based recruitment: 26% non-white, 30% high school education or less, 23% rural. Median age 65. Mean anxiety score for the entire cohort was 6.1 (out of maximum 33) at 12 months, 5.1 at 24 months, 4.8 at 36 months, and 5.0 at 48 months. Mean score at 48 months by subgroup is summarized in Table. Multivariable analysis showed that longer follow-up (48 vs 12 months, estimate -1.1, p<.01), lower risk cancer (low vs high, estimate -1.5, p<.05; intermediate vs high, estimate -1.5, p=.04), and older age (estimate -0.1 per year, p<.01) were associated with less anxiety. Conversely, non-white men (vs white, estimate 2.4, p<.01) and lower education (vs college, estimate 2.1, p<.01) were associated with higher anxiety. Active surveillance patients had borderline higher anxiety compared to RT (estimate 1.0, p=.068). Anxiety in prostate cancer survivors decreases over time, but certain subgroups—especially minority patients and those with lower educational attainment—experience higher anxiety than other subgroups at 48 months follow-up. While disparities in prostate cancer treatment and survival are well-described, to our knowledge this is the first study demonstrating disparity by race and education in mental well-being in prostate cancer survivors.Abstract 198; Table 1Mean Prostate Cancer Anxiety score at 48 months by subgroup (range 0–33)Treatment ModalityActive surveillance5.6Radical prostatectomy4.9RT4.6RaceWhite4.2Non-white7.4NCCN Risk CategoryLow5.1Intermediate4.6High5.3EducationHigh school or less6.4College or higher4.3 Open table in a new tab

Estimating the effective reproduction number of dengue considering temperature-dependent generation intervals

The effective reproduction number, Rt, is a measure of transmission that can be calculated from standard incidence data to timely detect the beginning of epidemics. It has being increasingly used for surveillance of directly transmitted diseases. However, current methods for Rt estimation do not apply for vector borne diseases, whose transmission cycle depends on temperature. Here we propose a method that provides dengue's Rt estimates in the presence of temperature-mediated seasonality and apply this method to simulated and real data from two cities in Brazil where dengue is endemic. The method shows good precision in the simulated data. When applied to the real data, it shows differences in the transmission profile of the two cities and identifies periods of higher transmission.

Statistical Catch‐Free Age‐Structured Assessment to Estimate Year‐Class Strength for Inland Recreational Fisheries: A Largemouth Bass Example

AbstractStatistical catch‐at‐age analysis (SCAA) is commonly used to estimate recruitment and mortality for large‐scale, economically important fish stocks, but fishery‐dependent catch‐at‐age data are often unavailable for smaller‐scale inland fisheries, thus limiting the use of SCAA. In these systems, a catch‐free approach to age‐structure modeling may be useful for estimating recruitment and mortality rates solely from a time series of survey age composition and catch rate data by estimating recruitment as a relative index of year‐class strength (Rt). Here, we demonstrate a statistical catch‐free age‐structured assessment (SCFASA) model for small‐scale inland fish stocks as an alternative to traditional catch curve approaches by using Largemouth Bass Micropterus salmoides as an example. We fitted the SCFASA to fishery‐independent survey age composition and catch‐per‐effort data from Largemouth Bass stocks in three Alabama reservoirs to estimate Rt, annual fishing mortality rates, and age‐specific electrofishing survey vulnerability; we compared Rt to catch curve residual estimates and performed a sensitivity analysis under a variety of model assumptions. Model estimates of Rt and temporal trends in fishing mortality were robust to changes in assumptions about the effective sample size of multinomial age samples, natural mortality rate, and temporal variability in fishing mortality. However, the magnitude of instantaneous fishing mortality rates at two of the three reservoirs was somewhat higher than empirical estimates for similar stocks and was sensitive to model assumptions. Our application of the SCFASA to survey data sets routinely collected by management agencies for Largemouth Bass potentially provides a comprehensive approach to estimating Rt, mortality, and sampling vulnerability for these stocks without increasing sampling effort. Future investigations of SCFASA's utility for small‐scale inland stocks should address the potential for bias in the magnitude of fishing mortality estimates due to incorrectly specified vulnerability schedules.Received October 5, 2015; accepted September 19, 2016 Published online December 21, 2016

Multiscale Hydrologic Applications of the Latest Satellite Precipitation Products in the Yangtze River Basin using a Distributed Hydrologic Model

Abstract The present study aims to evaluate three global satellite precipitation products [TMPA 3B42, version 7 (3B42 V7); TMPA 3B42 real time (3B42 RT); and Climate Prediction Center morphing technique (CMORPH)] during 2003–12 for multiscale hydrologic applications—including annual water budgeting, monthly and daily streamflow simulation, and extreme flood modeling—via a distributed hydrological model in the Yangtze River basin. The comparison shows that the 3B42 V7 data generally have a better performance in annual water budgeting and monthly streamflow simulation, but this superiority is not guaranteed for daily simulation, especially for flood monitoring. It is also found that, for annual water budgeting, the positive (negative) bias of the 3B42 RT (CMORPH) estimate is mainly propagated into the simulated runoff, and simulated evapotranspiration tends to be more sensitive to negative bias. Regarding streamflow simulation, both near-real-time products show a region-dependent bias: 3B42 RT tends to overestimate streamflow in the upper Yangtze River, and, in contrast, CMORPH shows serious underestimation in those downstream subbasins while it is able to effectively monitor streamflow into the Three Gorges Reservoir. Using 394 selected flood events, the results indicate that 3B42 RT and CMORPH have competitive performances for near-real-time flood monitoring in the upper Yangtze, but for those downstream subbasins, 3B42 RT seems to perform better than CMORPH. Furthermore, the inability of all satellite products to capture some key features of the July 2012 extreme floods reveals the deficiencies associated with them, which will limit their hydrologic utility in local flood monitoring.

Evaluation of Real-Time Satellite Precipitation Data for Global Drought Monitoring

Abstract The Tropical Rainfall Measuring Mission (TRMM) Multi-satellite Precipitation Analysis (TMPA) near-real-time (RT) data are considered less accurate than the TMPA research quality (RP) data because of the simplified data processing algorithm and the lack of gauge adjustments. However, for near-real-time hydrological applications, such as drought nowcasting, the RT data must play a key role given latency considerations and consistency is essential with products like RP, which have a long-term climatology. The authors used a bivariate test to examine the consistency between the monthly RT and RP precipitation estimates for 12 yr (2000–12) and found that, for over 75% of land cells globally, RT and RP were statistically consistent at 0.05 significance level. The inconsistent grid cells are spatially clustered in western North America, northern South America, central Africa, and most of Australia. The authors also show that RT generally increases with time relative to RP in northern South America and western Australia, while in western North America and eastern Australia, RT decreases relative to RP. In other areas such as the eastern part of North America, Eurasia, and southern part of the South America, the RT data are statistically consistent with the RP data and are appropriate for global- or macroscale hydrological applications.

Transmission dynamics of the 2009 influenza A (H1N1) pandemic in India: The impact of holiday-related school closure

The role of social-distancing measures, such as school closures, is a controversial aspect of pandemic mitigation planning. However, the timing of 2009 pandemic provides a natural experiment for evaluating the impact of school closure during holidays on influenza transmission.To quantify the transmission intensity of the influenza A (H1N1) pdm’09 in India, by estimating the time varying reproduction number (Rt) and correlating the temporal changes in the estimates of Rt for different regions of India with the timing of school holidays. We used daily lab-confirmed case reports of influenza A (H1N1) pdm’09 in India (during 17 May’09 to 17 May’10), stratified by regions. We estimated the transmissibility of the pandemic for different regions from these time-series, using Bayesian methods applied to a branching process model of disease spread and correlated the resulting estimates with the timing of school holidays in each region.The North-west region experienced two notable waves, with the peak of the first wave coinciding with the start of a 4 week school holiday (September–October’09). In the southern region the two waves were less clear cut, though again the first peak of the first wave coincided with the start of school holidays – albeit of less than 2 weeks duration (August’09). Our analysis suggests that the school holidays had a significant influence on the epidemiology of the 2009 pandemic in India. We estimate that school holidays reduced the reproduction number by 14–27% in different regions of India, relative to levels seen outside holiday periods. The estimates of the reproduction number obtained (with peak R values below 1.5) are compatible with those reported from other regions of the world. This work reinforces past studies showing the significant impact of school holidays on spread of 2009 pandemic virus, and by inference the role of contact patterns in children on transmission.

Modeling renewal times in Amvrakikos Gulf, Greece

The Amvrakikos Gulf, located in the northwest Greece, is one of the largest semi-enclosed embayments being about 40 km long and 15 km wide. Water renewal is made via a narrow channel which connects the Gulf with the Ionian Sea having a 3.0 km length, width ranging from 0.8 to 2.0 km and depth from 2.0 to 13.0 m. The most common terms being used to indicate how fast the water of semi-enclosed coastal embayments is renewed are hydraulic retention time (HRT) and residence time (RT). A preliminary estimation of HRT and RT is performed via a 3-D integrated model consisting of the hydrodynamic sub-model FLOW-3DL and the water quality sub-model QUAL-3DL. The models involve the 3-D non-steady state continuity, momentum and convection-diffusion equations expressed in layer formulation. A space-staggered computational grid was used and the following conclusions were drawn: (1) The HRT ranges from 1.86 to 2.42 years. (2) The flow rates of Louros and Arachthos rivers, which gush into the Gulf, reduce the HRT by 0.56 years. (3) The effect of the wind on HRT is minor due to the small size of the entrance to the Gulf. (4) The theoretical RT is equal to 3.85 years.

Speech-Model Based Accurate Blind Reverberation Time Estimation Using an LPC Filter

In this paper, we propose a speech-model based method using the linear predictive (LP) residual of the speech signal and the maximum-likelihood (ML) estimator proposed in “Blind estimation of reverberation time,” (R. Ratnam , J. Acoust. Soc. Amer., 2004) to blindly estimate the reverberation time (RT <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">60</sub> ). The input speech is passed through a low order linear predictive coding (LPC) filter to obtain the LP residual signal. It is proven that the unbiased autocorrelation function of this LP residual has the required properties to be used as an input to the ML estimator. It is shown that this method can successfully estimate the reverberation time with less data than existing blind methods. Experiments show that the proposed method can produce better estimates of RT <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">60</sub> , even in highly reverberant rooms. This is because the entire input speech data is used in the estimation process. The proposed method is not sensitive to the type of input data (voiced, unvoiced), number of gaps, or window length. In addition, evaluation using white Gaussian noise and recorded babble noise shows that it can estimate RT <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">60</sub> in the presence of (moderate) background noise.

Prognostic factors in a series of 504 breast cancer patients with metastatic spinal cord compression

This study was performed to identify new significant prognostic factors in breast cancer patients irradiated for metastatic spinal cord compression (MSCC). The data of 504 patients with breast cancer patients with MSCC were retrospectively analyzed with respect to posttreatment motor function, local control of MSCC, and survival. The investigated potential prognostic factors included age, Eastern Cooperative Oncology Group (ECOG) performance score, number of involved vertebrae, other bone metastases, visceral metastases, pretreatment ambulatory status, interval from cancer diagnosis to radiotherapy of MSCC, time developing motor deficits before radiotherapy, and the radiation schedule. On multivariate analysis, better functional outcome was associated with ambulatory status prior to RT (estimate - 1.29, p < 0.001), no visceral metastases (estimate - 0.52, p = 0.020), and slower development of motor deficits (estimate + 2.47, p < 0.001). Improved local control was significantly associated with no other bone metastases (risk ratio (RR) 4.33, 95% confidence interval (CI) 1.36-14.02, p = 0.013) and no visceral metastases (RR 3.02, 95%CI 1.42-6.40, p = 0.005). Improved survival was significantly associated with involvement of only 1-2 vertebrae (RR 1.27, 95%CI 1.01-1.60, p = 0.044), ambulatory status before radiotherapy (RR 1.75, 95%CI 1.23-2.50, p = 0.002), no other bone metastases (RR 1.93, 95%CI 1.18-3.13, p = 0.009), no visceral metastases (RR 7.60, 95%CI 5.39-10.84, p < 0.001), and time developing motor deficits before radiotherapy (RR 1.55, 95%CI 1.30-1.86, p < 0.001). Several new independent prognostic factors were identified for treatment outcomes. These prognostic factors should be considered in future trials and may be used to develop prognostic scores for breast cancer patients with MSCC.

The Effective Reproduction Number of Pandemic Influenza

Timely estimation of the transmissibility of a novel pandemic influenza virus was a public health priority in 2009. We extended methods for prospective estimation of the effective reproduction number (Rt) over time in an emerging epidemic to allow for reporting delays and repeated importations. We estimated Rt based on case notifications and hospitalizations associated with laboratory-confirmed pandemic (H1N1) 2009 virus infections in Hong Kong from June through October 2009. Rt declined from around 1.4-1.5 at the start of the local epidemic to around 1.1-1.2 later in the summer, suggesting changes in transmissibility perhaps related to school vacations or seasonality. Estimates of Rt based on hospitalizations of confirmed H1N1 cases closely matched estimates based on case notifications. Real-time monitoring of the effective reproduction number is feasible and can provide useful information to public health authorities for situational awareness and calibration of mitigation strategies.

Transmission potential of the new influenza A(H1N1) virus and its age-specificity in Japan

On 16 May 2009, Japan confirmed its first three cases of new influenza A(H1N1) virus infection without a history of overseas travel, and by 1 June, 361 cases, owing to indigenous secondary transmission, have been confirmed. Of these, 287 cases (79.5%) were teenagers (i.e. between 10 and 19 years of age). The reproduction number is estimated at 2.3 (95% confidence interval: 2.0, 2.6). The average number of secondary transmissions involving minors (those under 20 years of age) traced back to infected minors is estimated at 2.8. That is, minors can sustain transmission even in the absence of adults. Estimates of the effective reproduction number Rt moved below 1 by 17 May. Active surveillance and public health interventions, including school closures most likely have contributed to keeping Rt below one.

Local population dynamics are important to the conservation of metapopulations in highly fragmented landscapes

Summary 1. Population viability analyses (PVA) are extremely useful tools for the management of endangered species at the landscape scale. Two main families of spatially explicit models are available to perform PVA: (i) presence–absence models, in which local populations are either existing or extinct at each generation, and (ii) structured population models, in which the dynamics of each local population are modelled. In this study we compared the usefulness of both approaches for the prediction of the persistence of a species living in a highly fragmented landscape. 2. The cranberry fritillary Boloria aquilonaris is an arctic–alpine relict species in western Europe. It lives in landscapes where altitude or the proximity of oceans provide the high humidity conditions required for the formation of peat bogs, the only habitat of the butterfly. In such landscapes, the distribution of the butterfly is fragmented, following the natural distribution of peat bogs; this fragmentation is increased by human‐induced peat bog destruction. 3. The study of the dynamics of a highly fragmented metapopulation of the cranberry fritillary in a network of 14 habitat patches totalling 26·23 ha revealed that: (i) the density at the equilibrium was c. 700 butterflies ha−1; (ii) local population dynamics in small populations were negative; and (iii) six estimates of the growth rate Rt showed large variations even in a large population. Both local extinctions and recolonization events are likely to occur, and two sites (one of 7 ha) unoccupied during two generations were recolonized in the third year. 4. We conclude that the future of this metapopulation is not guaranteed, given its large spatial scale and unbalanced, erratic local population dynamics. We hypothesize that global warming could explain the instability of local population dynamics detected here in addition to the decline of this arctic–alpine relict species, which is currently reported in all its refuge localities in the Netherlands. 5. Presence–absence models based on metapopulation structure and habitat characteristics should provide relatively safe predictions, as the population network (14 patches) is just below the minimum amount of suitable habitat (MASH) for the long‐term persistence of a viable metapopulation. However, careful investigation of local population dynamics showed a high instability in the network, which is confirmed by population extinction at a large site. 6. Synthesis and applications. We urge conservation biologists to consider the local population dynamics of endangered species for the management of metapopulations in fragmented landscapes. In the case of the cranberry fritillary, continuing site protection is essential.

Normal human subjects with slow reaction times and larger time estimations after waking have diminished delta sleep

A sample of 42 healthy young male human subjects was submitted to whole night polysomnography and attention performance tests upon awakening (simple visuomotor reaction time, RT, and time estimation, TE). In order to test whether performance is related to specific sleep parameters, the 15 fastest subjects (mean = 210 msec) and 15 slowest subjects (mean = 357 msec) in RT were compared in their TE and sleep parameters. Fast subjects were more precise in the estimation of 10 sec intervals (9.89; S.E. = 0.23 sec) than slow subjects (10.73; S.E. = 0.32). Slow subjects had significantly less delta sleep (mean = 73 min) than fast subjects (100 min, P < 0.01) and otherwise similar sleep parameters. It can be suggested that attention after awakening is related to the amount of delta sleep in the night.

Inverse modeling of dog airway and respiratory system impedances.

Mechanical parameters of the respiratory system are often estimated from respiratory impedances using lumped-element inverse models. One such six-element model is composed of an airway branch [with a resistance (Raw) and inertance (Iaw)] separated from a tissue branch [with a resistance (Rt), inertance (It), and compliance (Ct)] by a shunt compliance representing alveolar gas compression (Cg). Even though the airways are known to have frequency-dependent resistance and inertance, these inverse models have been composed of linear frequency-independent elements. In this study we investigated the use of inverse models where the airway branch was represented by a frequency-independent Raw and Iaw, a Raw that is linearly related to frequency and an Iaw that is independent of frequency, and a system of identical parallel tubes the impedance of which was computed from the tube radius and length. These inverse models were used to analyze airway and respiratory impedances between 2 and 1,024 Hz that were predicted from an anatomically detailed forward model. The forward model represented the airways by an asymmetrically branched network with a terminal impedance representative of known Cg, Rt, It, and Ct. For respiratory impedances between 2 and 128 Hz, all models fit the data reasonably well, and reasonably accurate estimates of Cg, Rt, It, and Ct were extracted from these data. For data above 200 Hz, however, only the multiple-tube model accurately fitted respiratory impedances (Zrs). This model fitted the Zrs data best when composed of 27 tubes, each having a radius of 0.148 cm and a length of 16.5 cm.

A radioimmunoassay for measurement of 3,3',5'-triiodothyronine (reverse T3).

A highly specific antiserum to 3,3',5'-triiodothyronine (reverse T(3), rT(3)) was prepared by immunization of rabbits with D,L-rT(3)-human serum albumin conjugate. Of the various thyroid hormone derivatives tested, only 3,3'-diiodothyronine (3,3'-T(2)) cross-reacted significantly (10%) with rT(3)-binding sites on the antiserum, while thyroxine (T(4)) and triiodothyronine (T(3)) cross-reacted by less than 0.1%. The antiserum was used in a simple, sensitive, precise, and reproducible radioimmunoassay (RIA) for measurement of rT(3) in ethanolic extracts of serum. The dose-response curves of inhibition of the binding of [(125)I]rT(3) to antibody obtained by serial dilutions of serum extracts were essentially parallel to the standard assay curve. Recovery of nonradioactive rT(3) added to serum before extraction averaged 93%. Serum rT(3) concentrations were found to be (mean+/-SD) 41+/-10 ng/100 ml in 27 normal subjects, 103+/-49 ng/100 ml in 22 hyperthyroid patients, 19+/-9 ng/100 ml in 12 hypothyroid patients, and 54+/-7 ng/100 ml in five subjects with elevated serum thyroxine-binding globulin: the values in each of the latter three groups of individuals were significantly different from normal. Reverse T(3) was detected regularly in normal or supranormal concentrations in serum of 12 hypothyroid patients rendered euthyroid or mildly hyperthyroid by treatment with synthetic T(4). It is suggested that serum rT(3) values noted here should be taken to reflect the relative changes in serum rT(3) rather than its absolute values in health and thyroid disease. True serum rT(3) may be somewhat different because: (a) D.L-rT(3) employed in the standard curve and L-rT(3) present in human serum may react differently with anti-D,L-rT(2). (b) Even though 3,3'-T(2), which cross-reacted 10% in rT(3) RIA, has been considered unlikely to be present in human serum, it may circulate in low levels. (c) Cross-reaction of T(4) in rT(3) RIA of 0.06% although small, could contribute to RIA estimates of rT(2); the effect of T(4) would be particularly important in case of serum of hyperthyroid patients. Thus, serum rT(3) concentration in hyperthyroid patients averaged 89+/-48 mug/100 ml after correction for cross-reaction effects of T(4): this value was about 14% lower than that before correction (see above). Serum rT(3) concentration in cord sera of seven newborns averaged 136+/-19 ng/100 ml; it was clearly elevated and within the range of values seen in hyperthyroid patients. This was the case when the mean T(4) concentration in the newborn cord sera was moderately higher than normal and about one-half that in hyperthyroid patients, whereas serum T(3) was markedly below the normal adult level. A Pronase hydrolysate of thyroglobulin prepared from pooled normal thyroid glands contained 0.042, 3.0, and 0.16 mug/mg protein of rT(3), T(4), and T(3), respectively. The various data suggest that: (a) rT(3) is a normal component of human serum and thyroglobulin: (b) peripheral metabolism of T(4) is an important source of the rT(3) present in serum: (c) peripheral conversion of T(4) to T(3) and rT(3) may not necessarily be a random process.

PERFORMANCE, HEART RATE, AND RESPIRATION RATE ON THE DAY-NIGHT CONTINUUM.

Each of 15 female college students was tested at 4 P.M., 10 P.M., 4 A.M., and 10 A.M. Pulse rate and respiration rate were gauged directly before task performance. An RT task was followed by time estimation. Pulse and respiration rates were slowest at 4 A.M. and increased significantly by the 10 A.M. testing, followed by a gradual decline. Both RT and time estimation were poorest at 4 A.M., reached a peak at 10 A.M. and gradually declined. These findings agree with previous data which show that, as activation level increases up to a certain point, performance improves. No Ss showed over-activation previously observed to lead to disintegration of performance. A major criticism of the procedure was discussed.