Time Course Of Mortality Research Articles

Cardiac events among a cohort of 17,389 patients receiving cancer chemotherapy: short and long term implications

BackgroundThe association between cardiovascular disease and carcinogenesis is bidirectional and well-established. Furthermore, cancer treatment improves overall patient survival, potentially at the cost of incremental and fatal cardiovascular disease (CVD).AimTo evaluate (a) In a real-world cohort, the proportion of patients offered cancer chemotherapy who have antecedent CVD (CVDA); (b) The rates of patient admission with subsequent development of CVD (CVDS) requiring hospital admission post assignment to chemotherapy; (c) The impact of CVDA and CVDS on mortality rates relative to those seen in patients without overt CVD (CVD−) and (d) The time course of mortality in CVD− versus CVDS patients.MethodsRetrospective analysis was performed in deidentified linked health data sets. Correlates of mortality were evaluated by Cox proportional hazards evaluation. Relative and absolute time-variability of CVD as a primary cause of death were determined.ResultsOf the total 17,389 patients, there were 2,159 with CVDA. Over a median follow-up time of 4.6 years, CVDS admissions (n = 8,529) occurred more commonly in the presence of CVDA (70.0% vs. 46.1%, p < 0.001), and more than 50% of CVDS cases occurred in the first 12 months of follow-up. The 5-year mortality rates were 71.5% for CVDA, 64.7% for CVDS, and 40.8% for CVD− (p < 0.001). Development of CVDS was associated with a substantially increased risk of mortality in the next 12 months. The development of CVDs was also associated with an increased risk of cardiovascular, as against non-cardiovascular, mortality (7.1% vs. 1.6%, p < 0.001).ConclusionsApproximately 50% of patients assigned to cancer chemotherapy developed CVDS, heralding a particularly high risk of mortality over the next 12 months. Both CVDA and CVDS are associated with substantial increases in mortality rates relative to those in CVD− patients. This increased risk merits close individual monitoring.

Potential use of pinenes to improve localized insecticide injections targeting the western drywood termite (Blattodea: Kalotermitidae).

The western drywood termite, Incisitermes minor (Hagen), causes significant economic damage to wood structures in the United States of America, especially California. When infestation is not widespread, localized insecticide injections may be useful for remedial control. However, the extensive gallery structure of drywood termites and their tendency to aggregate at specific parts of the galleries can impact the efficacy of localized insecticide injection. Chemicals that attract termites from a distance may improve the localized insecticide injection by increasing the number of termites contacting the insecticide residues. Two volatile terpenes, α-pinene and β-pinene, commonly found in many coniferous timber trees, were applied to artificial termite galleries to determine if termites were attracted from their original aggregation site. Furthermore, we examined if adding these pinenes would improve the overall efficacy of some insecticide products for drywood termite control. Behavioral assay results showed that the treatment with pinenes increased the likelihood that drywood termites would leave their original aggregation site and contact the treated part of the gallery. When tested with the pesticide products applied in a small area away from the termite aggregation, β-pinene significantly accelerated the time course of mortality for the aqueous fipronil. The efficacy of disodium octaborate tetrahydrate dust was not influenced by the addition of pinenes. Implications for drywood termite management and future research directions are discussed.

The Natural History of Acute Radiation-induced H-ARS and Concomitant Multi-organ Injury in the Non-human Primate: The MCART Experience.

The dose response relationship and corresponding values for mid-lethal dose and slope are used to define the dose- and time-dependent parameters of the hematopoietic acute radiation syndrome. The characteristic time course of mortality, morbidity, and secondary endpoints are well defined. The concomitant comorbidities, potential mortality, and other multi-organ injuries that are similarly dose- and time-dependent are less defined. Determination of the natural history or pathophysiology associated with the lethal hematopoietic acute radiation syndrome is a significant gap in knowledge, especially when considered in the context of a nuclear weapon scenario. In this regard, the exposure is likely ill-defined, heterogenous, and nonuniform. These conditions forecast sparing of bone marrow and increased survival from the acute radiation syndrome consequent to threshold doses for the delayed effects of acute radiation exposure due to marrow sparing, medical management, and use of approved medical countermeasures. The intent herein is to provide a composite natural history of the pathophysiology concomitant with the evolution of the potentially lethal hematopoietic acute radiation syndrome derived from studies that focused on total body irradiation and partial body irradiation with bone marrow sparing. The marked differential in estimated LD50/60 from 7.5 Gy to 10.88 Gy for the total body irradiation and partial body irradiation with 5% bone marrow sparing models, respectively, provided a clear distinction between the attendant multiple organ injury and natural history of the two models that included medical management. Total body irradiation was focused on equivalent LD50/60 exposures. The 10 Gy and 11 Gy partial body with 5% bone marrow sparing exposures bracketed the LD50/60 (10.88 Gy). The incidence, progression, and duration of multiple organ injury was described for each exposure protocol within the hematopoietic acute radiation syndrome. The higher threshold doses for the partial body irradiation with bone marrow sparing protocol induced a marked degree of multiple organ injury to include lethal gastrointestinal acute radiation syndrome, prolonged crypt loss and mucosal damage, immune suppression, acute kidney injury, body weight loss, and added clinical comorbidities that defined a complex timeline of organ injury through the acute hematopoietic acute radiation syndrome. The natural history of the acute radiation syndrome presents a 60-d time segment of multi-organ sequelae that is concomitant with the latent period or time to onset of the evolving multi-organ injury of the delayed effects of acute radiation exposure.

The impact of supportive care on survival in large animal models of total body irradiation

Purpose Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are necessary in order to assess the efficacy of candidate medical countermeasures under the criteria of the U.S. Food and Drug Administration ‘Animal Rule’. Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity under scenarios likely to be present in the human population during mass casualty situations. These scenarios include understanding the impact of medical management on survival of the hematopoietic acute radiation syndrome (H-ARS). Little information is available to compare the impact of medical management under identical study conditions. The work presented here provides a comparison of the impact of different levels of medical management (supportive care) on the survival outcome in two large animal models: the male Gottingen minipig and the male rhesus macaque (NHP). Materials and Methods In the context of this comparison, limited supportive care consisted of administration of analgesics only, standard supportive care consisted of prophylactic administration of analgesics, antibiotics and fluids (minipigs) or analgesics, antibiotics, antidiarrheals, nutritional and fluid support (NHP) on a set schedule regardless of indication, and full supportive care (NHP only) consisted of analgesics, antibiotics, antidiarrheals, nutritional and fluid support, antiemetics and blood transfusions on an individual animal, trigger-to-treat regimen. Regardless of level of supportive care, minipigs were exposed to total body irradiation using a Co60 source and NHPs were exposed to total body irradiation using 6 MV photon energy. Results Based on estimated LD50 values, the inclusion of antimicrobial or broad-spectrum antibiotics provided a dose modifying factor (DMF) of 1.09 in the minipig, and by 1.15 in the NHP (standard supportive care to limited supportive care ratio. For the NHP, the administration of supportive care based on symptomology rather than a set schedule, and inclusion of blood transfusions yielded a DMF of 1.05 (full supportive care to standard supportive care ratio). Conversely, comparison of the estimated LD50 values between full supportive care and limited supportive care in the NHP provided a DMF of 1.21. Conclusion The study reported here provides a comparison of the impact of antibiotic administration on radiation-induced lethality.

The Gastrointestinal Subsyndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose-response Relationship With and Without Medical Management.

Well-characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the US Food and Drug Administration's Animal Rule. Development of a model for the gastrointestinal acute radiation syndrome requires knowledge of the radiation dose-response relationship and time course of mortality and morbidity across the acute and prolonged gastrointestinal radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that has been used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality relative to the hematopoietic acute radiation syndrome, gastrointestinal acute radiation syndrome, and lung injury. It can be used to assess the natural history of gastrointestinal damage, concurrent multiple organ injury, and aspects of the mechanism of action for acute radiation exposure and treatment. A systematic review of relevant studies that determined the dose-response relationship for the gastrointestinal acute and prolonged radiation syndrome in the rhesus macaque relative to radiation dose, quality, dose rate, exposure uniformity, and use of medical management has never been performed.

Early mortality after liver transplantation: Defining the course and the cause

The objective of the current study was to define the incidence, as well as time course of mortality within the first year after liver transplantation. Data on adult, first-time liver transplant recipients transplanted between February 2002 and June 2016 were obtained from the United Network for Organ Sharing. Among 64,977 who underwent liver transplantation, the incidence of 90-day and 1-year mortality was 5% and 10%, respectively. Although death associated with cardiovascular/cerebrovascular/pulmonary/hemorrhage was the most cause of death within the first 21 days (7-day: 53%), only 20% of liver transplantation patients died from these causes after 180 days. Infections were the most frequent cause of death during 30-180 days after liver transplantation. In contrast, after roughly 200 days from the time of liver transplantation, other causes of death were the most frequent cause of death. Although patients with autoimmune hepatitis, nonalcoholic steatohepatitis, and alcoholic cirrhosis had a similar risk of 1-year mortality, patients undergoing liver transplantation for viral hepatitis and hepatocellular carcinoma had an increased risk of 1-year mortality (viral: OR 1.56; hepatocellular carcinoma: OR 1.57; P < .001). Roughly, 1 in 10 patients died within the first year after liver transplantation. The cause of death had a notable, time-specific variation over the first year after liver transplantation.

High Summer Temperatures and Mortality in Estonia.

BackgroundOn-going climate change is predicted to result in a growing number of extreme weather events—such as heat waves—throughout Europe. The effect of high temperatures and heat waves are already having an important impact on public health in terms of increased mortality, but studies from an Estonian setting are almost entirely missing. We investigated mortality in relation to high summer temperatures and the time course of mortality in a coastal and inland region of Estonia.MethodsWe collected daily mortality data and daily maximum temperature for a coastal and an inland region of Estonia. We applied a distributed lag non-linear model to investigate heat related mortality and the time course of mortality in Estonia.ResultsWe found an immediate increase in mortality associated with temperatures exceeding the 75th percentile of summer maximum temperatures, corresponding to approximately 23°C. This increase lasted for a couple of days in both regions. The total effect of elevated temperatures was not lessened by significant mortality displacement.DiscussionWe observed significantly increased mortality in Estonia, both on a country level as well as for a coastal region and an inland region with a more continental climate. Heat related mortality was higher in the inland region as compared to the coastal region, however, no statistically significant differences were observed. The lower risks in coastal areas could be due to lower maximum temperatures and cooling effects of the sea, but also better socioeconomic condition. Our results suggest that region specific estimates of the impacts of temperature extremes on mortality are needed.

The Hematopoietic Syndrome of the Acute Radiation Syndrome in Rhesus Macaques: A Systematic Review of the Lethal Dose Response Relationship.

Well characterized animal models that mimic the human response to potentially lethal doses of radiation are required to assess the efficacy of medical countermeasures under the criteria of the U.S. Food and Drug Administration "animal rule." Development of a model requires the determination of the radiation dose response relationship and time course of mortality and morbidity across the hematopoietic acute radiation syndrome. The nonhuman primate, rhesus macaque, is a relevant animal model that may be used to determine the efficacy of medical countermeasures to mitigate major signs of morbidity and mortality at selected lethal doses of total body irradiation. A systematic review of relevant studies that determined the dose response relationship for the hematopoietic acute radiation syndrome in the rhesus macaque relative to radiation quality, dose rate, and exposure uniformity has never been performed. The selection of data cohorts was made from the following sources: Ovid Medline (1957-present), PubMed (1954-present), AGRICOLA (1976-present), Web of Science (1954-present), and U.S. HHS REPORT (2002 to present). The following terms were used: Rhesus, total body-irradiation, total body x irradiation, TBI, irradiation, gamma radiation, hematopoiesis, LD50/60, Macaca mulatta, whole-body irradiation, nonhuman primate, NHP, monkey, primates, hematopoietic radiation syndrome, mortality, and nuclear radiation. The reference lists of all studies, published and unpublished, were reviewed for additional studies. The total number of hits across all search sites was 3,001. There were a number of referenced, unpublished, non-peer reviewed government reports that were unavailable for review. Fifteen studies, 11 primary (n = 863) and four secondary (n = 153) studies [n = 1,016 total nonhuman primates (NHP), rhesus Macaca mulatta] were evaluated to provide an informative and consistent review. The dose response relationships (DRRs) were determined for uniform or non-uniform total body irradiation (TBI) with 250 kVp or 2 MeV x radiation, Co gamma radiation and reactor- and nuclear weapon-derived mixed gamma: neutron-radiation, delivered at various dose rates from a total body, bilateral, rotational, or unilateral exposure aspect. The DRRs established by a probit analysis vs. linear dose relationship were characterized by two main parameters or dependent variables: a slope and LD50/30. Respective LD50/30 values for studies that used 250 kVp x radiation (five primary studies combined, n = 338), 2 MeV x radiation, Co gamma radiation, and steady-state reactor-derived mixed gamma:neutron radiation for total body uniform exposures were 521 rad [498, 542], 671 rad [632, 715], 644 rad [613, 678], and 385 rad [357, 413]. The respective slopes were steep and ranged from 0.738 to 1.316. The DRR, LD50/30 values and slopes were also determined for total body, non-uniform, unilateral, pulse-rate exposures of mixed gamma:neutron radiation derived at reactor and nuclear weapon detonations. The LD50/30 values were, respectively, 395 rad [337, 432] and 412 rad [359, 460]. Secondary data sets of limited studies that did not describe a DRR were used to support the mid-to-high lethal dose range for the H-ARS and the threshold dose range for the concurrent acute GI ARS. The available evidence provided a reliable and extensive database that characterized the DRR for the H-ARS in young rhesus macaques exposed to 250 kVp uniform total body x radiation without the benefit of medical management. A less substantial but consistent database demonstrated the DRR for total body exposure of differing radiation quality, dose rate and non-uniform exposure. The DRR for the H-ARS is characterized by steep slopes and relative LD50/30 values that reflect the radiation quality, exposure aspect, and dose rate over a range in time from 1954-2012.

Cause-specific mortality time series analysis: a general method to detect and correct for abrupt data production changes

BackgroundMonitoring the time course of mortality by cause is a key public health issue. However, several mortality data production changes may affect cause-specific time trends, thus altering the interpretation. This paper proposes a statistical method that detects abrupt changes ("jumps") and estimates correction factors that may be used for further analysis.MethodsThe method was applied to a subset of the AMIEHS (Avoidable Mortality in the European Union, toward better Indicators for the Effectiveness of Health Systems) project mortality database and considered for six European countries and 13 selected causes of deaths. For each country and cause of death, an automated jump detection method called Polydect was applied to the log mortality rate time series. The plausibility of a data production change associated with each detected jump was evaluated through literature search or feedback obtained from the national data producers.For each plausible jump position, the statistical significance of the between-age and between-gender jump amplitude heterogeneity was evaluated by means of a generalized additive regression model, and correction factors were deduced from the results.ResultsForty-nine jumps were detected by the Polydect method from 1970 to 2005. Most of the detected jumps were found to be plausible. The age- and gender-specific amplitudes of the jumps were estimated when they were statistically heterogeneous, and they showed greater by-age heterogeneity than by-gender heterogeneity.ConclusionThe method presented in this paper was successfully applied to a large set of causes of death and countries. The method appears to be an alternative to bridge coding methods when the latter are not systematically implemented because they are time- and resource-consuming.

Larvicidal constituents of Zingiber officinale (ginger) against Anisakis simplex.

In this study, we investigated the anthelmintic activity of [10]-shogaol, [6]-shogaol, [10]-gingerol and [6]-gingerol, compounds isolated from the roots of Zingiber officinale L., Zingiberaceae (ginger), against Anisakis simplex. The above compounds kill or reduce spontaneous movement in A. simplex larvae. The maximum lethal efficacy of [10]-shogaol and [10]-gingerol was approximately 80% and 100%, respectively. We further examined the time course of compound-induced loss of mobility in A. simplex. The results showed that various concentrations of [10]-shogaol, [6]-shogaol, [10]-gingerol and [6]-gingerol have maximum effects on loss of spontaneous movement from 24 to 72 h. In addition, the time course of mortality and the percentage of loss of spontaneous movements were ascertained to determine the minimum effective doses of [10]-gingerol and [10]-shogaol. [10]-Gingerol exhibited a larger maximum larvicidal effect and greater loss of spontaneous movement than [10]-shogaol and albendazole. In addition, these constituents of Zingiber officinale showed effects against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and peroxyl radicals. These constituents of Zingiber officinale are responsible for its larvicidal activity against A. simplex.

Accuracy of chronic aquatic toxicity estimates determined from acute toxicity data and two time–response models

Traditionally, chronic toxicity in aquatic organisms and wildlife has been determined from either toxicity test data, acute to chronic ratios, or application of safety factors. A more recent alternative approach has been to estimate chronic toxicity by modeling the time course of mortality as determined in standard acute toxicity tests, but these approaches have received limited validation. The accuracy of chronic toxicity estimates from two time-response models, linear regression analysis (LRA) and accelerated life testing (ALT), was investigated using a dataset of more than 150 matched species pairs of standard acute toxicity test data and measured chronic no-observed-effect concentrations (NOECs). Chronic survival was more accurately modeled by both ALT (accuracy, 69%) and LRA (accuracy, 76%) than was reproduction, growth, or the most sensitive endpoint (accuracy, 50-60%). In general, LRA estimates of chronic toxicity were less conservative than ALT estimates, with 66 to 79% of LRA estimates being greater than the measured NOEC. Acute datasets with early mortality produced estimates of chronic survival that were more accurate (ALT, 92%; LRA, 89%) compared to all datasets but were less conservative (84% of ALT estimates were overestimated vs 93% of LRA estimates). Acute datasets with late mortality resulted in poor ALT and LRA estimates of chronic toxicity for all endpoints. Additional survival time measurements did not improve the accuracy of ALT or LRA estimates of chronic toxicity over the standard four acute measurement times (24, 48, 72, and 96 h). The time course of mortality should be considered when applying time-response models to estimate chronic aquatic toxicity, with greater accuracy likely for chronic survival than for growth or reproduction.

Detecting critical periods in larval flatfish populations

We evaluate the time-course of deaths and evidence of periods of increased mortality (i.e., critical periods) in laboratory populations of larval flatfish. First, we make the distinction between age-at-death and abundance-at-time data for fish larvae, the latter being typical in studies of natural populations. Next, we describe an experimental investigation of age- and temperature-dependent mortality in larval winter flounder, Pseudopleuronectes americanus. The survivorship curves of these populations differed significantly in both the magnitude and time-course of mortality among the four water temperatures evaluated (7, 10, 13, and 16°C). Mortality was highest in the cooler temperatures and concentrated in the third quarter of larval life, largely concurrent with settlement of surviving members of the cohort. Among the statistical methods for analysing survival data, the proportional-hazards model with time-varying covariates proved best at capturing the patterns of age-specific mortalities. We conclude that fair appraisals of recruitment hypotheses which are predicated on periods of high, age-specific mortality that vary with environmental conditions (e.g., Hjort's critical period hypothesis) will require: (1) data that are based on age, not time; (2) data that are of higher temporal resolution than commonly available at present and (3) analytical methods that are sensitive to irregularities in survivorship curves. We suggest four research approaches for evaluating critical periods in nature.

Birth Weight-specific Mortality for Extremely Low Birth Weight Infants Vanishes by Four Days of Life: Epidemiology and Ethics in the Neonatal Intensive Care Unit

The persistent differences between those who question the appropriateness of aggressive resuscitative measures for many extremely low birth weight (ELBW) infants (birth weight < 1001 g) and those who generally initiate such treatment has been a source of ongoing tension for physicians, parents, judges, and policymakers. We believe that much of this tension may be a result of the way the issue is framed. We began this study with the intuition that although many ELBW infants die, most succumb quickly. Were this true, discussions that considered only survival rates might miss the point. A more relevant statistic might be the degree to which interventions prolong dying, extend suffering, or use resources for infants who will eventually die. We determined the survival and nonsurvival for 429 ELBW infants admitted to our neonatal intensive care unit (NICU) for 3 years. We noted particularly the relationship between birth weight, illness severity (fraction of inspired oxygen [Fio2] requirement for infants requiring mechanical ventilation), and the time course of mortality for nonsurvivors. We next calculated a resource utilization index (NICU bed days occupied by survivors and nonsurvivors) for each patient and for the population as a whole. Finally, we determined how NICU resources were distributed among infants who eventually died and those who survived. Of the 429 ELBW infants alive on day of life (DOL) 1,202 (47%) survived to be discharged. on DOL 1, both birth weight and illness severity independently predicted likelihood of survival. Approximately 80% of ELBW deaths occurred in the first 3 days of life-- consequently, once an infant had survived to DOL 4, the likelihood of survival was dramatically enhanced (81% for the 249 patients alive on DOL 4). In addition, although survival for DOL 4 infants continued to depend on illness severity, survival no longer depended on birth weight. These observations on DOL 4 were confirmed in the subpopulation of 212 infants whose birth weight was < 750 g. Overall, although 53% of ELBW babies admitted died, only approximately 13% of all NICU bed-days (a proxy for resource allocation) were devoted to infants who did not survive. This figure did not vary as a function of birth weight. Generally, when we talk of survival rates to parents, ethics committees, or policy makers, we base our predictions largely on birth weight. The data presented here suggest that predictions should be corrected by including DOL and that, when this is done, the prognostic value of birth weight rapidly diminishes. In addition, birth weight-specific mortality and day of death for nonsurvivors correlated inversely; that is more of the smaller infants died, but the doomed ones died more quickly. Consequently, medical resources allocated to nonsurvivors remained low, and independent of birth weight. This formulation lends weight both to the reasonableness of physicians in offering NICU care to ELBW infants, with unlikely prospects for survival, and of parents and surrogate decision-makers in requesting/ assenting to it.

2,3,7,8-Tetrachlorodibenzo-p-dioxin toxicity in yellow perch (Perca flavescens).

Growth, mortality and morphologic lesions in juvenile, hatchery-reared yellow perch, Perca flavescens, were studied after treatment with graded single doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD, 1-125 micrograms/kg, intraperitoneally). TCDD doses of 25 and 125 micrograms/kg caused 95% mortality by 28 d after treatment, without decreasing body weight. A TCDD dose of 5 micrograms/kg resulted in progressive loss of body weight with cumulative mortality of 80% by 80 d posttreatment. Periodic handling stress did not affect the time course of mortality or cumulative percent lethality in TCDD-treated perch. Fin necrosis, petechial cutaneous hemorrhage, and ascites occurred in perch treated with 5 micrograms/kg or more of TCDD. Thymic atrophy, decreased hematopoiesis in the head kidney, fibrinous pericarditis, focal myocardial necrosis, submucosal gastric edema, and hyperplasia of the epithelium of gill filaments and lamellae occurred in perch dosed with 25 or 125 micrograms/kg. Dose-related splenic lymphoid depletion occurred in perch receiving 5 micrograms/kg or more TCDD, and hepatocyte lipidosis occurred in groups treated with doses of 1 microgram/kg or more TCDD. Thus yellow perch are as responsive to the acute toxic effects of TCDD as some of the more sensitive mammalian species, and neither loss of body weight nor histologic lesions in TCDD-treated perch are sufficient to explain mortality.

EFFECT OF TEMPERATURE ON MORTALITY AND RECOVERY OF SPRUCE BUDWORM (LEPIDOPTERA: TORTRICIDAE) EXPOSED TO BACILLUS THURINGIENSIS BERLINER

AbstractSpruce budworm larvae were bioassayed against Bacillus thuringiensis Berliner to study the effect of temperature on the expression of toxicity. Temperatures between 16 and 28°C did not affect the ultimate level of toxicity (LC50). However, LT50’s increased from 2–8 days at 28°C to 11–20 days at 16°C, depending on concentration of the pathogen. When larvae were force-fed with a single dose, temperature had a similar effect on the time course of mortality without affecting the level of mortality. Feeding inhibition of force-fed larvae commenced immediately after dosing. Larvae that did not recover died without further feeding, even at lower temperatures when death occurred 2–3 weeks after dosing. Recovering larvae resumed feeding after 2 (28°C) to 6 (13°C) days. Recovered larvae took longer to develop and produced lighter pupae than untreated larvae. Our data suggest that temperature-dependent feeding and recovery did not contribute to quicker death at higher temperatures. Expression of the toxin itself appears to depend on temperature, possibly through the influence of temperature on metabolic rate of affected gut cells. Implications of these findings for the efficacy of spruce budworm control operations are discussed.

Interactive effects of salinity, temperature and polycyclic aromatic hydrocarbons on the survival and development rate of larvae of the mud crabRhithropanopeus harrisii

Zoeae of the mud crabRhithropanopeus harrisii (Gould) were exposed continuously throughout larval development to factorial combinations of salinity, temperature and specific aromatic hydrocarbon concentrations. Salinities and temperatures were 5, 15, or 25‰ and 20°, 25°, or 30°C, respectively. Either phenanthrene or naphthalene was tested separately at respective concentrations of 0, 100, 150 or 200 ppb and 0, 125, 250 or 500 ppb. Phenanthrene was much more toxic than naphthalene. Naphthalene was not acutely toxic at any physical factor combination-naphthalene concentration tested. Both compounds caused the highest mortality at low salinities. The time course of mortality due to phenanthrene exposure showed that ecdysis between the first and second zoeal stage was the most sensitive period for the larvae exposed to aqueous hydrocarbons. Phenanthrene-exposed larvae had a decreased development rate, but the naphthalene-exposed larvae developed faster than the controls.

Acute Lethality after Fast-Neutron and X-Irradiation of Tribolium confusum

The acute lethal effects of fast neutrons and of X-rays on adults and larvae of T. confusum are compared. The time course of mortality of adults of the Oklahoma strain was the same after midlethal doses of neutrons and X-rays, although the neutrons were about twice as effective as X-rays in producing lethality, based on ${\rm LD}_{50(35)}$. The neutron RBE for adults of the Ebony mutant strain was also about 2, but that for Oklahoma larvae was about 3.85. Larvae surviving midlethal doses of neutrons showed a tendency toward wing abnormalities and delayed pupation. Dose-fractionation recovery with neutron doses in the midlethal range was not detectable in the adults or in the larvae. A considerable sparing effect of dose fractionation was found in X-irradiated adults. Also presented are techniques for using a beam port of a Triga research reactor for fast-neutron irradiation and a method of neutron and gamma dosimetry.

Effects of ethanol on serum electrolytes and respiration in euthyroid and hyperthyroid rats

A single large peroral dose of ethanol (3 g/kg) caused death within 12 hr after administration to rats pretreated with triiodothyronine (0.15 mg/kg/day on 6 successive days). Compared with the slight combined metabolic and respiratory acidosis observed in euthyroid controls 3 hr after ethanol administration, the triiodothyronine-pretreated rats developed only a milder acidosis of respiratory origin. Concentrations of serum Na +, Cl −, K +, Ca 2+, and Mg 2+ as well as red cell K + content were within normal limits in both hyper- and euthyroid rats 3 hr after ethanol administration. Pretreatment with 4-methylpyrazole or pyrithioxin did not affect the mortality rate or the time course of mortality after ethanol administration in the triiodothyronine-intoxicated rats. It is concluded that respiratory depression induced by ethanol does not play any significant role in the increased toxicity of ethanol in the hyperthyroid state. Nor are blood glucose or ion disturbances great enough to afford the primary cause of death. The results suggest that tissue sensitivity in the central nervous system to high ethanol concentrations per se is increased in the hyperthyroid state, but the actual mechanisms which contribute to this phenomenon are still unresolved.

Acute lethality in irradiated flour beetles: Evidence against a role of bacterial infection

The time course of mortality and the mean survival time of flour beetles dying after X-irradiation varied slightly in different strains and species. Within a given strain, however, both minimum and mean survival time were independent of dose over a wide range of exposures and independent of percent mortality. These findings suggest the operation of a single mode of death in irradiated beetles, in contrast to the “hierarchy of modes of death” recognized in irradiated mammals. Invasion of blood and tissues by enteric bacteria which gain entrance through the damaged intestinal lining, and subsequent spread of such infection, have been implicated in the lethal syndrome of irradiated mammals. The present investigation indicates that bacterial invasion does not contribute to the death of irradiated beetles. This conclusion is based on the lack of influence on survival of (1) administration of neomycin at levels which eliminated virtually all bacteria from the insects, (2) crowding or isolation, or (3) maintenance of irradiated beetles on medium in which other beetles previously had been raised. In addition, analysis of the distribution of deaths among a large number of vials each containing a small number of beetles disclosed no deviation from expectation based on random distribution; thus it seems unlikely that there is any “spread” of contagion within vials.