Internal Delensing of Cosmic Microwave Background Polarization B-Modes with the POLARBEAR Experiment.

Using only cosmic microwave background polarization data from the polarbear experiment, we measure B-mode polarization delensing on subdegree scales at more than 5σ significance. We achieve a 14% B-mode power variance reduction, the highest to date for internal delensing, and improve this result to 22% by applying for the first time an iterative maximum a posteriori delensing method. Our analysis demonstrates the capability of internal delensing as a means of improving constraints on inflationary models, paving the way for the optimal analysis of next-generation primordial B-mode experiments.

The POLARBEAR Fourier transform spectrometer calibrator and spectroscopic characterization of the POLARBEAR instrument.

We describe the Fourier Transform Spectrometer (FTS) used for in-field testing of the POLARBEAR receiver, an experiment located in the Atacama Desert of Chile which measures the cosmic microwave background (CMB) polarization. The POLARBEAR-FTS (PB-FTS) is a Martin-Puplett interferometer designed to couple to the Huan Tran Telescope (HTT) on which the POLARBEAR receiver is installed. The PB-FTS measured the spectral response of the POLARBEAR receiver with signal-to-noise ratio >20 for ∼69% of the focal plane detectors due to three features: a high throughput of 15.1 sr cm2, optimized optical coupling to the POLARBEAR optics using a custom designed output parabolic mirror, and a continuously modulated output polarizer. The PB-FTS parabolic mirror is designed to mimic the shape of the 2.5 m-diameter HTT primary reflector, which allows for optimum optical coupling to the POLARBEAR receiver, reducing aberrations and systematics. One polarizing grid is placed at the output of the PB-FTS and modulated via continuous rotation. This modulation allows for decomposition of the signal into different harmonics that can be used to probe potentially pernicious sources of systematic error in a polarization-sensitive instrument. The high throughput and continuous output polarizer modulation features are unique compared to other FTS calibrators used in the CMB field. In-field characterization of the POLARBEAR receiver was accomplished using the PB-FTS in April 2014. We discuss the design, construction, and operation of the PB-FTS and present the spectral characterization of the POLARBEAR receiver. We introduce future applications for the PB-FTS in the next-generation CMB experiment, the Simons Array.

Biological monitoring screening of patients provided antineoplastic drugs including adriamycin, cyclophosphamide, 5-fluorouracil, methotrexate, and vincristine.

The aim of the present study was to establish screening biomarkers of exposure to antineoplastic drugs administered to 11 patients undergoing cancer chemotherapy. Among the anticancer drugs administered were cyclophosphamide (all), Adriamycin (5 of 11), methotrexate (3 of 11), 5-fluorouracil (4 of 11), vincristine (3 of 11), megestrol acetate (1 of 11), and procarbazine (1 of 11). The noninvasive urinary parameters investigated were thioethers, D-glucaric acid, elements, and forward and reverse mutagenesis using bacterial bioassays. The data were analyzed in terms of the observed concentrations and those corrected for personal baseline. Personal baseline correction for parameters with significant nonexposure baseline levels was essential. While glucaric acid and thioethers were increased by the drug treatments, the correlations with baseline-uncorrected data showing an inverse relationship proved spurious, because saturation of the detoxification systems occurred at the high doses administered. Glucaric acid was also influenced by methotrexate and vincristine. Thioether content was affected by cyclophosphamide only. The forward mutagenesis assay was directly correlated to cyclophosphamide dose but the reverse assay was not, in the presence or absence of rat S9 fraction. The forward assay was not sensitive to the effects of smoking. Relative to controls, the elements changed by cyclophosphamide were K, S, and P. Those affected by Adriamycin were Ca, Mg, and Na; 5-fluorouracil affected Ca, Mg, Na, and C; methotrexate changed P and S. The forward mutagenesis assay and D-glucaric acid concentrations were the screening biomarkers best suited to monitoring for extent of exposure to these antineoplastic drugs.

Dietary evaluation of patients with smell and/or taste disorders.

The impact of smell and taste disorders on dietary habits and nutritional status has received limited research attention. This paper reports findings obtained from questionnaires and diet records completed by 40 healthy subjects and 118 patients with chemosensory dysfunction. Chemosensory disorders were frequently associated with decreases in food acceptability. Although dietary responses to these dysfunctions varied greatly, patients with distorted or phantom smell and/or taste sensations tended to report weight loss whereas those with simple sensory loss were more likely to report weight gain. Indices derived from diet records did not indicate that either group of patients was at substantial nutritional risk, but food frequency responses and estimates of body mass index were consistent with patient reports of changes in dietary patterns and weight. In addition, marked weight change and aberrant dietary practices were noted in individual patients. Thus, there were indications that chemosensory dysfunction may be associated with nutritionally important dietary alterations.

Randomized study of preoperative versus postoperative radiation therapy in advanced head and neck carcinoma: long-term follow-up of RTOG study 73-03.

This is a report of a 10-year median follow-up of a randomized, prospective study investigating the optimal sequencing of radiation therapy (RT) in relation to surgery for operable advanced head and neck cancer. In May 1973, the Radiation Therapy Oncology Group (RTOG) began a Phase III study of preoperative radiation therapy (50.0 Gy) versus postoperative radiation therapy (60.0 Gy) for supraglottic larynx and hypopharynx primaries. Of 277 evaluable patients, duration of follow-up is 9-15 years, with 7.6% patients lost to follow-up before 7 years. Loco-regional control was significantly better for 141 postoperative radiation therapy patients than for 136 preoperative radiation therapy patients (p = 0.04), but absolute survival was not affected (p = 0.15). When the analysis was restricted to supraglottic larynx primaries (60 postoperative radiation therapy patients versus 58 preoperative radiation therapy patients), the difference for loco-regional control was highly significant (p = .007), but not for survival (p = 0.18). In considering only supraglottic larynx, 78% of loco-regional failures occurred in the first 2 years. Thirty-one percent (18/58) of preoperative patients failed locally within 2 years versus 18% (11/60) of postoperative patients. After 2 years, distant metastases and second primaries became the predominant failure pattern, especially in postoperative radiation therapy patients. This shift in the late failure pattern along with the increased number of unrelated deaths negated any advantage in absolute survival for postoperative radiation therapy patients. The rates of severe surgical and radiation therapy complications were similar between the two arms. Because of an increased incidence of late distant metastases and secondary primaries, additional therapeutic intervention is required beyond surgery and postoperative irradiation to impact significantly upon survival.

Does malignant hibernoma exist?

The authors present a case of a highly atypical, possibly malignant, hibernoma. It presented as a deep-seated tumor in the retropharynx of a 57-year-old male. A review of possible similar cases is presented. The patient is without recurrence 4 years after complete excision and radiation therapy. The tumor must be differentiated from liposarcoma. The clinical potential must await the accumulation and observation of additional cases.

Modulation of odor-induced increases in [Ca(2+)](i) by inhibitors of protein kinases A and C in rat and human olfactory receptor neurons.

Protein kinases A and C have been postulated to exert multiple effects on different elements of signal transduction pathways in olfactory receptor neurons. However, little is known about the modulation of olfactory responses by protein kinases in intact olfactory receptor neurons. To further elucidate the details of the modulation of odorant responsiveness by these protein kinases, we investigated the action of two protein kinase inhibitors: H89, an inhibitor of protein kinase A, and N-myristoylated EGF receptor, an inhibitor of protein kinase C, on odorant responsiveness in intact olfactory neurons. We isolated individual olfactory neurons from the adult human and rat olfactory epithelium and measured responses of the isolated cells to odorants or biochemical activators that have been shown to initiate cyclic AMP or inositol 1,4,5-trisphospate production in biochemical preparations. We employed calcium imaging techniques to measure odor-elicited changes in intracellular calcium that occur over several seconds. In human olfactory receptor neurons, the protein kinase A and C inhibitors affected the responses to different sets of odorants. In rats, however, the protein kinase C inhibitor affected responses to all odorants, while the protein kinase A inhibitor had no effect. In both species, the effect of inhibition of protein kinases was to enhance the elevation and block termination of intracellular calcium levels elicited by odorants. Our results show that protein kinases A and C may modulate odorant responses of olfactory neurons by regulating calcium fluxes that occur several seconds after odorant stimulation. The effects of protein kinase C inhibition are different in rat and human olfactory neurons, indicating that species differences are an important consideration when applying data from animal studies to apply to humans.

Induction of differentiation of human olfactory neuroblastoma cells into odorant-responsive cells.

Olfactory neuroblastoma is a rare malignancy of the olfactory mucosa that may be derived from the olfactory epithelium. To characterize this tumor, we cultured olfactory neuroblastoma cells in the presence or absence of growth factors (transforming growth factor alpha and basic fibroblast growth factor) known to affect olfactory tissue and assessed their responsiveness to known odorants by measuring changes in intracellular calcium. Untreated cells did not respond to odorants. Basic fibroblast growth factor treatment had cytotoxic effects, and treated cells did not respond to odorants. Transforming growth factor alpha treatment resulted in the induction of odor responsiveness in these cells. Cells responded to odorants at 100 nM to 100 microM concentrations and responded with both increases and decreases in intracellular calcium. Increases in intracellular calcium were mediated by a calcium influx and were reversibly blocked by compounds known to inhibit second messenger pathways in olfactory receptor neurons. The calcium responses of the olfactory neuroblastoma cells were thus specific to the odorants and similar to those found in olfactory receptor neurons. The results support the notion that olfactory neuroblastoma cells may be of olfactory origin and thus they can be used as a model cell line to study human olfaction.

Analyses of ethylene glycol monoalkyl ethers and their proposed metabolites in blood and urine.

Glycol ethers are known to produce embryotoxic and teratogenic effects in a variety of animal species. In addition, testicular edema and tubular atrophy have been reported. The health effects of this class of compounds are not known in humans, despite the fact that these solvents are widely used in industry. In order to evaluate potential effects in humans, it is first necessary to estimate exposure in the workplace (environmental monitoring). However, in the case of glycol ethers traditional air monitoring may be ineffective because of the low volatility of these solvents and the possible significant exposure via the skin. Biological monitoring can be used to estimate glycol ether uptake by all routes of exposure. The compounds can be measured in blood or their metabolites quantitated in urine. These procedures are suggested for measuring 2-methoxyethanol, 2-ethoxyethanol and 2-butoxyethanol in blood. In addition, tentative procedures have been developed to measure the oxidized acidic metabolites, methoxyacetic acid and ethoxyacetic acid in urine as possible indices of exposure. All procedures have detection limits of less than 11 parts per million. These procedures are ready to be validated in workers exposed to these solvents.

The maturation of frequency selectivity in C57BL/6J mice studied with auditory evoked response tuning curves.

The present study was designed to examine the ontogeny of frequency selectivity in the neonatal auditory system. Mice were tested between 12 and 65 days of age. At each age two measures of auditory sensitivity were made from cochlear nucleus evoked responses. Tone-burst evoked-response thresholds in the quiet were determined for frequencies between 1.0 and 39.0 kHz. A two-tone simultaneous masking procedure was then used to obtain evoked response tuning curves. The frequency selectivity of the tuning curves was quantified by calculating a Q ratio. The results show that tuning is poor in neonates but rapidly improves to adult-like levels within 5-16 days after the inception of auditory function. The data also indicate that the development of frequency selectivity varies directly with the maturation of threshold sensitivity.

Functionally mature olfactory neurons from two anosmic patients with Kallmann syndrome.

Patients with Kallmann syndrome (KS) exhibit hypogonadotropic hypogonadism and anosmia [Kallmann et al., Am. J. Mental Def., 48 (1944) 203-236] secondary to failure of gonadotropin-releasing hormone (GnRH)-producing neurons to migrate from the olfactory placode to the brain, and to agenesis of the olfactory bulbs. It has been hypothesized that olfactory neurons (ON) from individuals with KS are immature partly on the basis of studies in animals showing that lack of synaptic connection of ON with the olfactory bulb results in expression of immature ON [Schwob et al., J. Neurosci., 12 (1979) 880-883]. To test this assumption, we obtained olfactory tissue samples from two males diagnosed with KS on the basis of medical history and MRI studies. Both patients were anosmic. The functioning of cells isolated from biopsies taken from the upper middle turbinate and septum was studied by measuring changes in intracellular Ca2+ concentration ([Cai]) using dual excitation fluorescence microscopy. Biopsies from both patients yielded cells that morphologically appeared to be ON. Seven of 16 cells that morphologically resembled ON responded with a change in [Cai] upon stimulation with an odorant mixture. These studies show that at least some ON in KS individuals are functionally mature and suggest that complete development of the olfactory bulbs is not required for differentiation of mature human ON.

Combined radiation therapy and surgery in the management of advanced head and neck cancer: final report of study 73-03 of the Radiation Therapy Oncology Group.

Between March 1973 and June 1979, patients with advanced operable squamous cell carcinoma of the supraglottic larynx or hypopharynx were randomly allocated to receive either preoperative radiation therapy (5,000 rad) or postoperative radiation therapy (6,000 rad). Patients with oral cavity or oropharynx lesions were randomly assigned either preoperative radiation, postoperative radiation, or definitive radiation therapy (6,500-7,000 rad), with surgery reserved for salvage if residual disease was present 6 weeks after completion of irradiation. Three hundred twenty patients were evaluable with a median follow-up of 60 months. Based on results in 277 patients across all four regions combined, locoregional control was significantly better for patients assigned to receive postoperative radiation therapy (65%) compared with those assigned to receive preoperative radiation therapy (48%, P = 0.04). This was due to a higher rate of both persistent and recurrent local and regional disease in the preoperative group. Survival also showed a trend to be better in the postoperative group (38%) compared with the preoperative group (33%, P = 0.10). Rates of severe surgical and radiation therapy complications were similar overall. Forty-three patients were evaluable for each of the three treatment regimens assigned to patients with oral cavity or oropharynx lesions. Due to the small number of patients available for this portion of the trial, the observed differences for overall survival (4-year percentage 33% overall; 30% preoperative, 36% postoperative, 33% definitive radiation therapy) and for locoregional control (45% overall; 43% preoperative, 52% postoperative, 38% definitive radiation therapy) were not statistically significant. The use of definitive radiation therapy with surgical rescue as an ethically justified alternative treatment for these tumors remains a question for further research.

The biological exposure index: its use in assessing chemical exposures in the workplace.

Human exposure to chemicals in the workplace has traditionally been assessed by determining the concentration of an airborne chemical in the workroom air. More recently, biological monitoring has been used to assess worker uptake of chemicals by all routes of exposure. Both approaches for the assessment of exposure and uptake are complementary. This relationship is examined, along with the advantages and limitations of using biological monitoring. The concept of the biological exposure index (BEI), developed by the American Conference of Governmental Industrial Hygienists (ACGIH), and information on the intended use and interpretation of BEIs are described. Examples are presented on the use of biological monitoring in NIOSH Health Hazard Evaluations (e.g., carboxyhemoglobin in blood to assess exposure to carbon monoxide, urinary metabolites of trichloroethylene to assess exposure to trichloroethanol, and 2-ethoxyacetic acid in urine to assess exposure to 2-ethoxyethanol). The progress of current research studies on the biological monitoring of volunteers exposed to paint spray solvents is presented, along with speculation on the future directions of biological monitoring research.

Role of biomarkers of exposure in the assessment of health risks.

Biomarkers of exposure can be used as part of an exposure assessment to assess potential health risks when exposure measurements and health effects occur during the same period of time. Exposure assessment is the determination of the concentration of a chemical in an environmental medium coupled with the presence of the human in that environment. A biomarker of exposure gives an assessment of absorbed dose in the worker. A biomarker of effect, often referred to as a biomarker, is used in the assessment of health risk. A biomarker of effect gives an assessment of the effect of a chemical on a physiological process and is an indicator of a possible adverse health effect. For example, biomarkers of exposure give an assessment of a worker's current exposure to solvents and some metals. Biomarkers of exposure for chronic health effects with long latent periods, such as carcinogens, are more problematical. These exposure indicators, however, can be used to help reconstruct past exposures. Selected biomarkers of exposure can also be predictors of adverse health effects. Examples include the use of 2,5-hexanedione and 2-ethoxyacetic acid in urine as indicators of exposure to n-hexane and 2-ethoxyethanol, respectively. These two urinary metabolites are 'active' metabolites responsible for observed neurotoxic and reproductive effects. Biomarkers of exposure are particularly useful for the objective assessment of current systemic exposure to chemicals that are readily absorbed through the skin. Exposure assessments, including the use of biomarkers of exposure, are necessary to postulate a cause of observed adverse health effects seen in epidemiological investigations and to determine the bioavailability of the chemicals present in the workplace.

Chemical monitoring of urine from workers potentially exposed to benzidine-derived azo dyes.

Benzidine (Bzd) and monoacetylbenzidine (MoAcBzd) were found in the urine of workers exposed to benzidine-based azo dyes. A colorimetric screening method, based on the reaction of extracted free aromatic amines with 2,4,6-trinitrobenzene-sulfonic acid (TNBS), was used with a specific electron-capture gas chromatographic (EC-GC) method. Alkaline hydrolyzable conjugates of Bzd and 2,4-diaminoazobenzene (DiAmAzBz) were found together with free DiAmAzBz and traces of 3,3'-dimethylbenzidine (DiMeBzd) and 3,3'-dimethoxybenzidine (DiMxBzd). The presence of a known human bladder carcinogen (Bzd) and its metabolites in the urine of workers exposed to benzidine-based azo dyes is a cause for concern.

Safe use of epinephrine with halothane anesthesia.

A review of the anesthesia literature outlines safe limits for use of epinephrine with halothane anesthesia and adequate ventilation. Excluded from the safe category are patients with previous cardiac disease, hypertension, patients taking monoamine oxidase inhibitors and reserpine. Considered as safe is 10 milliliters of 1:100,000 epinephrine in 10 minutes and not more than 30 milliliters of 1:100,000 epinephrine per hour.

Lipoinjection for unilateral vocal cord paralysis.

Injection of Teflon paste is a commonly accepted procedure to improve the caliber of voice in unilateral vocal cord paralysis. There are several drawbacks to Teflon injection, among them respiratory obstruction (from overinjected Teflon) and unsatisfactory voice quality (Teflon causes stiffness of the vocal folds). This paper is a preliminary report on lipoinjection instead of Teflon injection into a paralyzed vocal fold. Fat appears to impart a soft bulkiness to the injected cord, while allowing it to retain its vibratory qualities. It is autologous material and can be retrieved if excessively overinjected. The fate of autologous fat injected into a paralyzed vocal cord remains unknown. Most of the literature on lipoinjection concerns repairs of depressed scars or breast augmentation. Our longest follow-up has been 12 months. Three patients have had this procedure, and the results appear to be very encouraging.

Motion-induced sickness following bilateral ablation of area postrema in squirrel monkeys.

Using squirrel monkeys as experimental subjects, we reexamined the disputed role of the area postrema (AP) in motion-induced vomiting. After anesthetization, the obex and rhomboid fossa were exposed surgically, and the AP was ablated by thermal coagulation using either a battery cautery or a CO2 microsurgical laser. Sham operations were performed on another sample of monkeys. Two or more weeks after surgery, all animals were given 10 daily 2-hour horizontal rotations at 30 rpm. Every monkey in both the lesions and sham samples vomited on two or more test days. While the vomiting characteristics were modified following ablation of AP, its function is not indispensible for the development of motion sickness in horizontally-rotated squirrel monkeys.

Horizontal nystagmus in methylmercury poisoned squirrel monkeys.

Chronic states of methylmercurialism were induced in squirrel monkey subjects. Principal neurological signs included ataxia, abnormal gait, incoordination and amaurosis. Although slight to moderate vacuolization occurred in supporting cell layers of the cristae and maculae, receptor cell function was essentially normal. Except for a lowered cold threshold, bithermal caloric-induced nystagmus was not significantly different from control values. Pre and postrotatory (Barany chair) tests revealed a reduction only in frequency related variables. The development of spontaneous and positional nystagmus (sometimes with eyes open) coupled with the behavioral signs and the evidence of normal receptor response suggested cerebellar dysfunction. Severe pathologic changes were present in the cerebral cortex, but no lesions were found in the cerebellar cortex. Substantial neuronal degeneration and gliosis, however, were observed in several subcortical nuclei, including cerebellar and vestibular nuclei.

Randomized preoperative and postoperative radiation therapy for patients with carcinoma of the head and neck: preliminary report.

Two hundred and ninety-eight patients with squamous cell carcinoma of the oral cavity, oropharynx, supraglottic larynx, hypopharynx or maxillary sinus have been randomized for preoperative radiation therapy and surgery vs. surgery and postoperative radiation therapy plus, in the case of patients with lesions of the oral cavity and oropharynx, radical radiation therapy. Data have been analyzed on 243 patients in this interim report. The differences between the three groups with respect to local control and survival are not statistically significant at this time. Additional accrual and continued follow-up are necessary to make definite treatment comparisons.