Transient-grating single-shot supercontinuum spectral interferometry (TG-SSSI): publisher's note.

This publisher's note contains corrections to Opt. Lett.46, 1013 (2021)OPLEDP0146-959210.1364/OL.417803.

Transient-grating single-shot supercontinuum spectral interferometry (TG-SSSI).

We present a technique for the single-shot measurement of the spatiotemporal (1D space+time) amplitude and phase of an ultrashort laser pulse. The method, transient grating single-shot supercontinuum spectral interferometry (TG-SSSI), is demonstrated by the space-time imaging of short pulses carrying spatiotemporal optical vortices. TG-SSSI is well suited for characterizing ultrashort laser pulses that contain singularities associated with spin/orbital angular momentum or polarization.

Mode Structure and Orbital Angular Momentum of Spatiotemporal Optical Vortex Pulses.

We identify a class of modal solutions for spatiotemporal optical vortex (STOV) electromagnetic pulses propagating in dispersive media with orbital angular momentum (OAM) orthogonal to propagation. We find that symmetric STOVs in vacuum can carry half-integer intrinsic OAM; for general asymmetric STOVs in a dispersive medium, the OAM is quantized in integer multiples of a parameter that depends on the STOV symmetry and the group velocity dispersion. Our results suggest that STOVs propagating in dispersive media are accompanied by a polaritonlike quasiparticle. The modal theory is in excellent agreement with measurements of free space propagation of STOVs.

Clinical experience across the fetal-fraction spectrum of a non-invasive prenatal screening approach with low test-failure rate.

OBJECTIVE: To describe our clinical experience across the entire range of fetal-fraction (FF) measurements of a non-invasive prenatal screen (NIPS) that uses whole- genome sequencing (WGS). METHODS: We analyzed retrospectively results from 58 105 singleton pregnancies that underwent NIPS on a customized WGS platform during an 8-month period and assessed clinical test performance for trisomy 21, trisomy 18 and trisomy 13. Pregnancy outcomes were sought for all screen-positive patients and for 18% of screen-negative patients. As differences in outcome-collection response rates could artificially impact test-performance calculations, we computed inferred sensitivity, specificity, positive predictive values (PPV) and negative predictive values adjusted for ascertainment bias. RESULTS: The screening test yielded a result for 99.9% (n = 58 048) of patients, meaning that approximately 1 in 1000 patients received a test failure (i.e. test failure rate = 0.1%). Of pregnancies with a test result, 572 (1%) screened positive for one of the common aneuploidies (362 for trisomy 21, 142 for trisomy 18 and 68 for trisomy 13). Informative outcomes were received for 237 (41.4%) patients with a screen-positive result and 3258 (5.7%) of those with a screen-negative result. In the full cohort, inferred sensitivities for trisomy 21, trisomy 18 and trisomy 13 were 99.7%, 96.8% and 94.3%, respectively, and PPVs were 93.1%, 85.2% and 48.4%, respectively. If a FF threshold of 4% had been employed to guard against false negatives, calculated sensitivities for the three aneuploidies would not have changed significantly, yet, importantly, the overall test-failure rate would have increased to 6.6% (n = 3829), impacting 1 in 15 women. CONCLUSIONS: Our clinical experience demonstrates that a customized WGS-based NIPS without a FF threshold achieves high accuracy while maintaining a low test-failure rate of 0.1%. As such, alternative strategies to ensure high accuracy of detection of common aneuploidies in samples with low FF (such as redraw after test failure, redrawing at a later gestational age, risk scoring based on FF) are not necessary for this screening approach. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Ultrashort infrared 2.5-11 µm pulses: spatiotemporal profiles and absolute nonlinear response of air constituents.

We measure the detailed spatiotemporal profiles of femtosecond laser pulses in the infrared wavelength range of λ=2.5-11 µm and the absolute nonlinear response of major air constituents (N2, O2, and Ar) over this range. The spatiotemporal measurements reveal wavelength-dependent pulse front tilt and temporal stretching in the infrared pulses.

Histologic subtypes of breast cancer following radiotherapy for Hodgkin lymphoma.

BACKGROUND: The purpose of the study was to determine whether breast cancers (BCs) that develop in women previously irradiated for Hodgkin lymphoma (HL) are biologically similar to sporadic BC. MATERIALS AND METHODS: We retrospectively reviewed the charts of patients who developed BC after radiotherapy (RT) for HL. Tumors were classified as ductal carcinoma in situ (DCIS) or invasive carcinoma. Invasive carcinomas were further characterized according to the subtype: hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)-, HR+/HER2+, HR-/HER2+, and HR-/HER2-. BCs after HL were compared with four age-matched sporadic, non-breast cancer (BRCA) I or II mutated BCs. RESULTS: One hundred forty-seven HL patients who were treated with RT between 1966 and 1999 and subsequently developed BCs were identified. Of these, 65 patients with 71 BCs had complete pathologic information. The median age at HL diagnosis was 23 (range, 10-48). The median age at BC diagnosis was 44 (range, 28-66). The median time to developing BC was 20 years. Twenty cancers (28%) were DCIS and 51 (72%) were invasive. Of the 51 invasive cancers, 24 (47%) were HR+/HER2-, 2 (4%) were HR+/HER2+, 5 (10%) were HR-/HER2+, and 20 (39%) were HR-/HER2-. There were no differences in BC histologic subtype according to the age at which patients were exposed to RT, the use of chemotherapy for HL treatment, or the time from RT exposure to the development of BC. In a 4 : 1 age-matched comparison to sporadic BCs, BCs after HL were more likely to be HR-/HER2- (39% versus 14%) and less likely to be HR+/HER2- (47% versus 61%) or HR+/HER2+ (4% versus 14%) (P = 0.0003). CONCLUSION(S): BCs arising in previously irradiated breast tissue were more likely to be triple negative compared with age-matched sporadic invasive cancers and less likely to be HR positive. Further studies will be important to determine the molecular pathways of carcinogenesis in breast tissue that is exposed to RT.

Size at birth and adult fat mass in twin sheep are determined in early gestation.

Size at birth is related to adult health outcomes. Twins are born smaller than singletons; this has been assumed to be secondary to limited nutrient supply in late gestation.We hypothesised that growth trajectory in twins, and the adult consequences of being conceived a twin, are determined in early gestation. Twin pregnancies in sheep were randomised to reduction of one twin on day 42 of a 148 day pregnancy by intra-thoracic KCl (Reductions, n =46) or a sham procedure (Twins, n =22). Singleton-bearing ewes also underwent a sham procedure (n =27). Ewes lambed spontaneously. Linear measures of size at birth were similar in Twins and Reductions, and significantly less than in Singletons. Birthweight was lower in Twins and Reductions than in Singletons, and less in Twins than in Reductions (means (SEM): Singletons, liveborn n =23: 6.59 (0.17) kg; Twins, liveborn n =36: 5.23 (0.16) kg; Reductions, liveborn n =27: 5.76 (0.15) kg; all comparisons P <0.05). Reductions grew most rapidly between birth and weaning (Singletons, 20.0 (0.4) g kg⁻¹ day⁻¹; Twins, 20.0 (0.3) g kg⁻¹ day⁻¹; Reductions, 21.0 (0.3) g kg⁻¹ day⁻¹, P <0.05) and were of similar weight as Singletons by weaning; Twins remained smaller by weaning but grew most rapidly thereafter (Singletons, 1.6 (0.1) g kg⁻¹ day⁻¹; Twins, 2.1 (0.1) g kg⁻¹ day⁻¹; Reductions, 1.6 (0.1) g kg⁻¹ day⁻¹, P <0.01), so that all groups had similar weight at 2 years. However, Twins and Reductions had greater percentage fat mass than Singletons at 2 years (Singletons, 11.1 (1.1)%; Twins, 14.8 (1.2)%; Reductions, 15.5 (1.1)%, P <0.05). Thus, in twins, fetal growth trajectory, linear size at birth and adult fat mass are largely determined in early gestation. If this is also true in humans, there are important implications for interventions aimed at optimising fetal growth and pregnancy outcome.

The relationship between parental genetic or phenotypic divergence and progeny variation in the maize nested association mapping population.

Appropriate selection of parents for the development of mapping populations is pivotal to maximizing the power of quantitative trait loci detection. Trait genotypic variation within a family is indicative of the family's informativeness for genetic studies. Accurate prediction of the most useful parental combinations within a species would help guide quantitative genetics studies. We tested the reliability of genotypic and phenotypic distance estimators between pairs of maize inbred lines to predict genotypic variation for quantitative traits within families derived from biparental crosses. We developed 25 families composed of ~200 random recombinant inbred lines each from crosses between a common reference parent inbred, B73, and 25 diverse maize inbreds. Parents and families were evaluated for 19 quantitative traits across up to 11 environments. Genetic distances (GDs) among parents were estimated with 44 simple sequence repeat and 2303 single-nucleotide polymorphism markers. GDs among parents had no predictive value for progeny variation, which is most likely due to the choice of neutral markers. In contrast, we observed for about half of the traits measured a positive correlation between phenotypic parental distances and within-family genetic variance estimates. Consequently, the choice of promising segregating populations can be based on selecting phenotypically diverse parents. These results are congruent with models of genetic architecture that posit numerous genes affecting quantitative traits, each segregating for allelic series, with dispersal of allelic effects across diverse genetic material. This architecture, common to many quantitative traits in maize, limits the predictive value of parental genotypic or phenotypic values on progeny variance.

Esophageal tolerance to high-dose stereotactic ablative radiotherapy.

Dose-volume parameters are needed to guide the safe administration of stereotactic ablative radiotherapy (SABR). We report on esophageal tolerance to high-dose hypofractionated radiation in patients treated with SABR. Thirty-one patients with spine or lung tumors received single- or multiple-fraction SABR to targets less than 1 cm from the esophagus. End points evaluated include D(5cc) (minimum dose in Gy to 5 cm(3) of the esophagus receiving the highest dose), D(2cc) , D(1cc) , and D(max) (maximum dose to 0.01 cm(3) ). Multiple-fraction treatments were correlated using the linear quadratic and linear quadratic-linear/universal survival models. Three esophageal toxicity events occurred, including esophagitis (grade 2), tracheoesophageal fistula (grade 4-5), and esophageal perforation (grade 4-5). Chemotherapy was a cofactor in the high-grade events. The median time to development of esophageal toxicity was 4.1 months (range 0.6-6.1 months). Two of the three events occurred below a published D(5cc) threshold, all three were below a D(2cc) threshold, and one was below a D(max) threshold. We report a dosimetric analysis of incidental dose to the esophagus from SABR. High-dose hypofractionated radiotherapy led to a number of high-grade esophageal adverse events, suggesting that conservative parameters to protect the esophagus are necessary when SABR is used, especially in the setting of chemotherapy or prior radiotherapy.

Seropositivity to Campylobacter and association with abortion and lamb mortality in maiden ewes from Western Australia, South Australia and Victoria.

This case-control study investigated associations between Campylobacter fetus or Campylobacter jejuni titre and reproductive outcomes in 22 flocks of Merino and non-Merino maiden ewes aged 1-2 years old. Campylobacter titres were also determined for multiparous ewes aged 3 years or older on the same farms. C. fetus 'positivity' (titre ≥1:80) was detected for 12% (57/462; 95% confidence interval [95% CI] 9.6 to 15.6) of maiden ewes and 31% (65/210; 95% CI 25.0 to 37.4) of mature ewes. The odds for failing to rear a lamb in C. fetus-'exposed' maiden ewes (titre ≥1:10) was 2.01 times that of seronegative ewes (95% CI 1.09 to 3.77; P = 0.027), but there was no association between C. fetus-'positivity' (titre ≥1:80) and failure to rise (OR 1.69; 95% CI 0.77 to 3.76; P = 0.191). C. fetus abortions were confirmed with microbial culture in one maiden ewe flock. In this flock, C. fetus titres fluctuated and often waned by lamb marking, highlighting the value of necropsies during abortion investigations. C. jejuni-'positivity' (titre ≥1:80) was detected for 44% (204/462; 95% CI 39.7 to 48.7) maiden ewes, but odds of failing to rear were decreased for C. jejuni-'positive' ewes (OR 0.52; 95% CI 0.32 to 0.83; P = 0.007). The association between Campylobacter serology and the reproductive outcome was inconsistent in these flocks. Serology should be considered in the context of other risk factors and used in conjunction with other strategies to investigate the impact of Campylobacter exposure on ewe reproductive performance such as monitoring for abortions and lamb necropsies to determine aetiological diagnosis, and vaccination trials.

Facial action units, activity and time spent with dam are effective measures of pain in response to mulesing of Merino lambs.

Repeatable measures of pain in ruminants following husbandry procedures are required to validate responses to pain relief. This study tested the hypotheses that facial action units, activity and time spent with dam can be used to assess the efficacy of pain relief in lambs following mulesing. Merino lambs (n = 120) were allocated to one of six treatments implemented at mulesing: (1) lambs that were not mulesed or lambs that were mulesed and administered (2) no pain relief, (3) meloxicam 15 min before mulesing, (4) Tri-Solfen®, (5) a combination of meloxicam 15 min before mulesing and Tri-Solfen after mulesing and (6) meloxicam at mulesing. Facial action units detected a difference in pain between mulesed and non-mulesed lambs at 1 and 5 h post-mulesing (P = 0.005 and <0.001) but not at 26 h post-mulesing. Lambs that were not mulesed were more active and spent more time with their dams than mulesed lambs (P < 0.001). No differences were observed between lambs that were mulesed with or without pain relief. Therefore, facial action units, activity of the lamb and time spent with dam can detect pain in response to mulesing in Merino lambs but cannot detect any changes associated with pain relief.

Vacuolation of sensory ganglion neuron cytoplasm in rats with long-term exposure to organophosphates.

Cytoplasmic vacuolation of sensory neurons has been reported to occur within the dorsal root ganglia in studies investigating various neuropathic conditions including the effects of neurotoxic chemicals. In this study, we investigated this lesion in adult (98-119 days old) male Long-Evans rats, after multiple exposures to two organophosphates (tri-ortho-tolyl phosphate [TOTP] and chlorpyrifos) and the modifying effects of concurrent corticosterone. Tri-ortho-tolyl phosphate was administered by gavage (75, 150, or 300 mg/kg) every other day between days 14 and 28 and between days 49 and 63, chlorpyrifos (60 mg/kg) was administered subcutaneously on days 7 and 42, and corticosterone was provided in the drinking water throughout the study at a concentration of 400 microg/mL. Although relatively uncommon, there was an increase in frequency of cytoplasmic vacuoles seen in treatment groups having multiple exposures to TOTP. They were characterized as peripherally located, single-limiting membrane-bound structures in the neuronal perikarya. There was no associated cell death, even when vacuoles were large. This is the initial report of an association of this change following exposure to neurotoxic organophosphates.

Behavioural measures reflect pain-mitigating effects of meloxicam in combination with Tri-Solfen® in mulesed Merino lambs.

Flystrike costs the Australian industry $173 to 280 M per annum and 70% to 80% of Merino lambs are currently mulesed to reduce the risk of flystrike. To alleviate welfare concerns there has been widespread adoption of analgesics to mitigate the pain associated with mulesing. The objective of this experiment was to determine the effectiveness of Tri-Solfen® and meloxicam (Metacam® 20) at reducing pain-related behavioural responses to mulesing in Merino lambs. One hundred and forty Merino lambs were allocated to one of seven treatment groups: (1) non-mulesed (Control); (2) mulesed with no pain relief; (3) subcutaneous (s.c.) meloxicam administered 15 min before mulesing; (4) Tri-Solfen® administered at time of mulesing; (5) Tri-Solfen® and saline injection (s.c.) 15 min before mulesing; (6) Tri-Solfen® and meloxicam (s.c.) 15 min before mulesing; and (7) meloxicam (s.c.) at time the of mulesing. Behavioural responses such as standing, walking and lying were measured every 15 min for 6 h on the day of marking and for up to 2 h for 4 days thereafter. Standing (hunched v. normal) and walking (stiff v. normal) behaviours were then categorised into pain- and normal-related behaviours while lying remained in its own category. Mulesed lambs with no pain relief displayed significantly more pain-related behaviours than Control lambs during the 6 h post-mulesing (1.22 v. 0.22 out of a total score of 3; RSD=1.15). Lambs that received a combination of pain relief displayed significantly less pain-related behaviour than mulesed lambs with no pain relief on the day of mulesing (0.85 v. 1.22 out of a total score of 3; RSD=1.15). Administration of meloxicam or Tri-Solfen® on their own had minimal if any significant effect on pain-related behaviours on the day of mulesing. The results of this experiment support the use of pain-related behaviours to measure the efficacy of analgesics and the use of multimodal analgesia during mulesing of lambs.

Mob size of single-bearing or twin-bearing Merino ewes at lambing may not influence lamb survival when feed-on-offer is high.

Limited research has suggested that higher lambing densities increase interference from foreign ewes at lambing which disrupts the ewe-lamb bond and compromises lamb survival. This may be particularly evident in mobs of twin-bearing ewes compared to single-bearing ewes because a greater number of lambs are born per day. Therefore, we hypothesised that; (i) decreasing the mob size of ewes at lambing has a greater impact on the survival of twin-born lambs than single-born lambs; (ii) the relationship between mob size and lamb survival can be explained by differences in the rate of interaction with foreign ewes and lambs at lambing; and (iii) ewes will utilise a limited area of the paddock at lambing and thus lambing density will be defined by the distribution of ewes in the paddock rather than the paddock area. Merino ewes were allocated into a 2×2 factorial combination of ewe pregnancy status (single- or twin-bearing) and mob size (high (n=130 ewes) or low (n=50 ewes)) on day 140 from the start of joining. Each treatment had two replicates excepting the low mob size for twins which had a third replicate. Ewes lambed at a stocking rate of 11 ewes/ha. Feed-on-offer during lambing exceeded 2400 kg dry matter (DM)/ha. Ewe-lamb behaviour was observed and dead lambs were autopsied over 11 days during the peak of lambing. The distribution of ewes in each paddock was recorded every 2 h during daylight hours by counting the number of ewes occupying 2500 m2 grids. The proportion of ewes and their newborn progeny which interacted with foreign ewes at lambing did not differ between the high and low mob sizes for single- (24.9% v. 20.8%) or twin-bearing ewes (14.3% v. 19.6%; P=0.74). Similarly, interaction with foreign lambs did not differ between the high and low mob sizes for single- (14.5% v. 25.2%) and twin-bearing ewes (34.5% v. 26.4%; P=0.44). The distribution of ewes within the paddock did not differ between treatments (P=0.95). On average, single-bearing ewes which lambed at the high and low mob sizes occupied 34% and 36% of the paddock during daylight hours, and the corresponding values for twin-bearing ewes were 40% and 43%. Survival of twin-born lambs was lower than single-born lambs (75.3% v. 87.9%; P<0.01), however, lamb survival was not influenced by mob size regardless of birth type. These results suggest that higher mob sizes may not compromise lamb survival when feed-on-offer during lambing exceeds 2400 kg DM/ha.

Regression method-derived energy value of dried egg albumen for broiler chickens.

The energy value of dried egg albumen (DEA) for broiler chickens was determined with male Ross 708 broilers. Birds were fed a common broiler starter diet from day 0 to 17 and experimental diets from day 17 to 22 post hatching. A total of 192 birds was allotted to 3 diets in a randomized complete block design with 8 replicate cages per diet and 8 birds per cage. The experiment used a corn-soybean meal reference diet and 2 test diets which the DEA was added at 50 or 100 g/kg to partially replace the energy source in the reference diet. The analyzed DM of DEA was 934 g/kg, and the respective analyzed gross energy and CP were 5,310 kcal and 894 g/kg DM. Addition of DEA to the reference diet linearly increased (P < 0.01) ileal DM digestibility, ileal energy digestibility, and ileal digestible energy (IDE), metabolizable energy (ME), and nitrogen-corrected metabolizable energy (MEn), whereas the effect on N retention was quadratic (P < 0.05). The IDE, ME, MEn of DEA values determined by the regression method were 4,777, 4,966, and 4,750 kcal/kg DM, respectively. In conclusion, the current study demonstrated that between 89 and 94% of the gross energy in dried egg albumen is utilized by broiler chickens.

Supplementation of Merino ewes with vitamin E plus selenium increases α-tocopherol and selenium concentrations in plasma of the lamb but does not improve their immune function.

Vitamin E and selenium have been reported to improve immune function across a range of species. Ewes lambing on poor-quality dry pasture in autumn in Western Australia are at risk of being deficient in vitamin E and selenium at lambing thus predisposing their lambs to deficiencies and increasing the risk of infection and disease. This study tested the hypotheses that (i) supplementation of autumn-lambing ewes with vitamin E plus selenium in late gestation will increase the concentrations of vitamin E and selenium in plasma in the ewe and lamb and (ii) that the increased concentrations of vitamin E and selenium in plasma in the lambs will improve their innate and adaptive immune responses and thus survival. Pregnant Merino ewes were divided into a control group (n=58) which received no supplementation or a group supplemented with vitamin E plus selenium (n=55). On days 111, 125 and 140 of pregnancy ewes in the vitamin E plus selenium group were given 4 g all-rac-α-tocopherol acetate orally. On day 111 the ewes were also given 60 mg of selenium as barium selenate by subcutaneous injection. The concentrations of α-tocopherol and selenium were measured in ewes and/or lambs from day 111 of pregnancy to 14 weeks of age±10 days (weaning). Immune function of the lamb was assessed by analysing the numbers and phagocytic capacities of monocytes and polymorphonuclear leucocytes and plasma IgG and anti-tetanus toxoid antibody concentrations between birth and 14 weeks of age±10 days. Maternal supplementation with vitamin E plus selenium increased the concentration of α-tocopherol in plasma (1.13 v. 0.67 mg/l; P<0.001) and selenium in whole blood (0.12 v. 0.07 mg/l; P<0.01) of the ewes at lambing compared with controls. Supplementation also increased the concentration of α-tocopherol (0.14 v. 0.08 mg/l; P<0.001) and selenium (0.08 v. 0.05 mg/l; P<0.01) in lambs at birth compared with controls. There was no significant effect of supplementation on immune function or survival in the lambs.

Some dissociating factors in the analysis of structural and functional progressive damage in open-angle glaucoma.

AIM: To identify the presence, and origin, of any "dissociating factors" inherent to the techniques for evaluating progression that mask the relationship between structural and functional progression in open-angle glaucoma (OAG). METHODS: 23 patients (14 with OAG and 9 with ocular hypertension (OHT)) who had received serial Heidelberg Retina Tomograph (HRT II) and Humphrey Field Analyser (HFA) examinations for >or=5 years (mean 78.4 months (SD 9.5), range 60-101 months) were identified. Evidence of progressive disease was retrospectively evaluated in one eye of each patient using the Topographic Change Analysis (TCA) and Glaucoma Progression Analysis (GPA) for the HRT II and HFA, respectively. RESULTS: Six patients were stable by both techniques; four exhibited both structural and functional progression; seven exhibited structural progression, only, and six showed functional progression, only. Three types of dissociating factors were identified. TCA failed to identify progressive structural damage in the presence of advanced optic nerve head damage. GPA failed to identify progressive functional damage at stimulus locations, with sensitivities exhibiting test-retest variability beyond the maximum stimulus luminance of the perimeter, and where a perimetric learning effect was apparent. CONCLUSION: The three dissociating factors accounted for nine of the 13 patients who exhibited a lack of concordance between structural and functional progressive damage.

Neurological effects of acute uranium exposure with and without stress.

Circulating uranium rapidly enters the brain and may cause adverse effects on the nervous system that are potentially modulated by stress. In this study, the neurological effects of a single intramuscular injection of 0, 0.1, 0.3, or 1 mg uranium/kg (as uranyl acetate, UA) in rats were examined in the presence and absence of stress. Treatment with UA produced time and dose-dependent increases in serum and regional brain uranium levels. While serum levels returned to control levels by day 30, brain levels remained elevated. Application of stress did not affect the distribution or retention of uranium. Exposure to 1 mg U/kg significantly decreased ambulatory activity, weight gain, forelimb grip strength and transiently impaired working memory. Effects on grip strength and memory were prevented by application of stress prior to uranium exposure. Striatal dopamine content was reduced by 30% 3 days after treatment with 1mg/kg (59+/-6 nmol/mg tissue versus 41+/-5 nmol/mg tissue), but levels returned to control 7 days after uranium exposure. The effect on dopamine was ameliorated by prior application of stress. Exposure to UA did not alter 3,4 dihydroxyphenylacetic acid (DOPAC) levels or numbers of D2 receptors in the striatum. No effect of uranium or stress was observed on levels of GABA, serotonin, norepinephrine, or glutathione (GSH) in the striatum, hippocampus, cerebellum, or cortex. These results indicate that single intramuscular exposures to uranium produce sustained elevation of brain uranium levels and at doses above 0.3 mg/kg can have adverse neurological effects. Application of stress prior to uranium administration modulates neurological effects, but the mechanism is not due to effects on uranium distribution. Uranium exposure also produced renal toxicity which must be considered to accurately assess the effects of uranium on neurological function.

Breast cancer after treatment of Hodgkin's disease.

BACKGROUND: Most studies of survivors of Hodgkin's disease have shown a low risk for subsequent breast cancer, even though much lower doses of radiation than those used for Hodgkin's disease have been shown to induce breast cancer in other settings. PURPOSE: This study quantifies the risk of breast cancer following Hodgkin's disease treatment according to age at treatment and type of treatment. METHODS: To evaluate the risk of breast cancer from irradiation, we reviewed records of 885 women treated for Hodgkin's disease between 1961 and 1990 (mean follow-up, 10 years). Risks for breast cancer incidence and mortality were calculated by comparison with expected rates for a general female population matched by age and race. RESULTS: Twenty-five patients have developed invasive breast cancer, yielding a relative risk (RR) of 4.1 (95% confidence interval [CI] = 2.5-5.7). An additional patient developed multifocal carcinoma in situ. Age at irradiation strongly influenced risk: RR was 136 for women treated before 15 years of age (95% CI = 34-371). RR declined with age at irradiation (P for trend < .0001), but the elevation remained statistically significant for subjects less than 30 years old at the time of irradiation (for those 15-24, RR = 19 [95% CI = 10.3-32]; for those 24-29, RR = 7 [95% CI = 3.2-14.4]). In women above 30 years of age, the risk was not elevated (RR = 0.7; 95% CI = 0.2-1.8). Risk of breast cancer increased significantly with time since treatment (P for trend < .0001). The RR was 2.0 (95% CI = 1.0-3.5) with follow-up under 15 years and 13.6 (95% CI = 7.9-18.2) with follow-up equal to or exceeding 15 years. The addition of mechlorethamine, vincristine, procarbazine, and prednisone chemotherapy to irradiation increased the risk within the first 15 years. Most breast cancers (22 of 26) arose within or at the margin of the radiation field and were infiltrating ductal carcinomas. Stage distribution and outcome suggest that the increased incidence was not solely attributable to vigilant screening. RR of death from breast cancer was 5.1 (95% CI = 2.2-10.0). CONCLUSIONS: Women treated for Hodgkin's disease with radiation before 30 years of age are at markedly increased risk for breast cancer, with risk increasing dramatically more than 15 years after therapy. IMPLICATIONS: The high RR for development of breast cancer in women exposed to therapeutic radiation under 30 years of age raises important issues about optimal treatment strategies for patients with Hodgkin's disease, breast cancer, and other cancers.