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Objective: Retrospectively analyze several histopathologic variables that may predict neck recurrence after neck dissection. Design: From 1970 through 1980, 284 patients with pathologically confirmed metastatic squamous cell carcinoma underwent neck dissection and received no adjuvant therapy. Kaplan-Meier evaluation estimated a 74% 2-year neck recurrence–free rate. After adjusting for the standard covariates of age, gender, neck stage, and tumor grade, we also controlled for the time-dependent co-variates of primary recurrence, occurrence in the side of the neck not operated on, or development of new head and neck primary disease. Setting: A large referral-based practice. Results: The number of lymph nodes involved, invasion of vascular/lymphatic space, invasion of soft tissue, and desmoplastic lymph node pattern adversely affect neck recurrence. A desmoplastic stromal pattern was associated with almost a sevenfold increased risk of neck recurrence. To our knowledge, this finding has not been reported previously. Conclusion: Histopathologic evaluation of metastatically involved cervical nodes can identify patients with head and neck cancer who are at high risk for recurrence. (Arch Otolaryngol Head Neck Surg. 1994;120:1370-1374)

This work studies the possibility of using three new sequencing rules in a simple hybrid assembly shop with two bottleneck machines in order to study the conjecture that a job shop may be characterized by its bottleneck structure. A simulation model for a nine-machine job shop is developed and used to compare these rules. The total makespan is the performance measure. The study is made under a combination of three different factors. The effect of the bottleneck machines location is also studied. The results show that some job shops can be managed by simply managing the bottleneck machines, that the three new rules can be used to manage a job shop with two bottlenecks, and that the location of the bottleneck machines is of importance. The results indicate new management rules may be inferred for job shops by studying the application of single and multiple machine flow shop scheduling theory.

A fast heuristic for the facilities layout problem including aisle location is developed. The procedure utilizes the scatter diagram of Drezner to obtain a relative location between departments. A simple modification of the new algorithm produces a powerful technique for pure and near-pure flowshops.

Background. The authors determined the patterns of treatment failure in patients treated with surgery alone or surgery combined with postoperative radiation therapy for squamous cell carcinoma of the tonsil. Methods. Seventy-two patients underwent surgery alone (56) or surgery and postoperative adjuvant radiation therapy (16). All patients were followed up until death (40 patients) or for a minimum of 3.5 years. For patients treated with surgery alone, clinic notes, operative notes, and pathology reports and slides were reviewed to identify clinical or pathologic predictors of recurrence above the clavicles, cause-specific survival, and overall survival

The effects of reversible enhancement or suppression of locus coeruleus (LC) neuronal discharge activity on forebrain electroencephalographic (EEG) activity have been previously examined in two series of experiments in halothane-anesthetized rats. Unilateral enhancement of LC activity increased EEG measures of arousal in frontal cortex and hippocampus. The EEG effects of LC activation were blocked by intracerebroventricular pretreatment with the noradrenergic β-antagonist, propranolol. Bilateral, but not unilateral, suppression of LC activity substantially increased EEG measures of sedation/anesthesia in cortex and hippocampus. In all experiments: a) EEG responses were only observed following changes in LC activity levels; b) onset of EEG responses closely followed changes in LC neuronal activity; c) recovery of EEG responses closely followed the recovery of LC neuronal activity. The present report integrates these previous results and considers their implications for the hypothesis that the LC may be an important modulator of behavioral state and/or state-dependent processes. Together, the two series of experiments yield complementary observations that have implications for LC function that are not apparent when considering each series in isolation.

γ knife surgery (GKS) for vestibular schwannoma (VS) is an accepted treatment for small- to medium-sized tumors, generally smaller than 2.5 cm in the maximum posterior fossa dimension. The purpose of this study was to evaluate the efficacy and toxicity of GKS for larger tumors.Prospectively collected data were analyzed for 22 patients who had undergone GKS for VSs larger than 2.5 cm in the posterior fossa diameter between 1997 and 2006. No patient had symptomatic brainstem compression at the time of GKS. The median treated tumor volume was 9.4 cm(3) (range 5.3-19.1 cm(3)). The median maximum posterior fossa diameter was 2.8 cm (range 2.5-3.8 cm). The median tumor margin dose was 12 Gy (range 12-14 Gy). Serial imaging, audiometry (10 patients with serviceable hearing pre-GKS), and clinical follow-up were available for a median of 66 months (range 26-121 months). Tumor control failure was defined as either a progressive increase in tumor diameter of at least 2 mm in any dimension or a later resection.Four patients met the criteria for GKS failure, including 1 patient who demonstrated sarcomatous degeneration more than 7 years after GKS and died 3 months after microsurgical debulking. An enlarging cystic component was the surgical indication in 1 of the 2 patients who required resection, although 27% of tumors (6 lesions) were cystic before GKS. The 3-year actuarial rate of tumor control, freedom from new facial neuropathy, and preservation of functional hearing were 86%, 92%, and 47%, respectively. At 5 years post-GKS, these rates decreased to 82%, 85%, and 28%, respectively. At the most recent follow-up, 91% of tumors were smaller than at the time of GKS and the median maximum posterior fossa diameter reduction was 26%. On multivariate analysis, none of the following factors was associated with GKS failure, new facial weakness, new trigeminal neuropathy, or loss of serviceable hearing: patient age, tumor volume, tumor margin dose, and preoperative cranial nerve dysfunction.Single-session radiosurgery is a successful treatment for the majority of patients with larger VSs. Although tumor control rates are lower than those for smaller VSs managed with GKS, the cranial nerve morbidity of GKS is significantly lower than that typically achieved via resection of larger VSs.

Purpose To define the rate of tumor control and factors associated with radiation-related complications after single-fraction radiosurgery (SRS) for patients with imaging defined intracranial meningiomas. Materials and Methods Retrospective review of 251 patients (192 women, 59 men) having SRS for imaging-defined intracranial meningiomas between 1990 and 2008. Excluded were patients with radiation-induced tumors, meningiomatosis, or neurofibromatosis. The mean patient age was 58.6 ± 13.4 years. The majority of tumors involved the skull base/tentorium ( n = 210, 83.7%). The mean treatment volume was 7.7 ± 6.2 cm 3 ; the mean tumor margin dose was 15.8 ± 2.0 Gy. Follow-up (mean, 62.9 ± 43.9 months) was censored at last evaluation ( n = 224), death ( n = 22), or tumor resection ( n = 5). Results No patient died from tumor progression or radiation-related complications. Tumor size decreased in 181 patients (72.1%) and was unchanged in 67 patients (26.7%). Three patients (1.2%) had in-field tumor progression noted at 28, 145, and 150 months, respectively. No patient had a marginal tumor progression. The 3- and 10-year local control rate was 99.4%. One patient had distant tumor progression at 105 months and underwent repeat SRS. Thirty-one patients (12.4%) had either temporary ( n = 8, 3.2%) or permanent ( n = 23, 9.2%) symptomatic radiation-related complications including cranial nerve deficits ( n = 14), headaches ( n = 5), hemiparesis ( n = 5), new/worsened seizure ( n = 4), cyst-formation ( n = 1), hemifacial spasm ( n = 1), and stroke ( n = 1). The 1- and 5-year complication rates were 8.3% and 11.5%, respectively. Radiation-related complications were associated with convexity/falx tumors (HR = 2.8, 95% CI 1.3–6.1, p = 0.009) and increasing tumor volume (HR = 1.05, 95% CI 1.0–1.1, p = 0.04) on multivariate analysis. No patient developed a radiation-induced tumor. Conclusions Single-fraction SRS at the used dose range provides a high rate of tumor control for patients with imaging defined intracranial meningiomas. However, treatment failures were noted after 10 years emphasizing the need for long-term imaging follow-up after meningioma SRS.

Putative metacognition data in animals may be explained by non-metacognition models (e.g., stimulus generalization). The primary objective of the present study was to develop a new method for testing metacognition in animals that may yield data that can be explained by meta-cognition but not by non-metacognition models. Next, we used the new method with rats. Rats were first presented with a brief noise duration which they would subsequently classify as short or long. Rats were sometimes forced to take an immediate duration test, forced to repeat the same duration, or had the choice to take the test or repeat the duration. Metacognition, but not an alternative non-meta-cognition model, predicts that accuracy on difficult durations is higher when subjects are forced to repeat the stimulus compared to trials in which the subject chose to repeat the stimulus, a pattern observed in our data. Simulation of a non-metacognition model suggests that this part of the data from rats is consistent with metacognition, but other aspects of the data are not consistent with metacognition. The current results call into question previous findings suggesting that rats have metacognitive abilities. Although a mixed pattern of data does not support metacognition in rats, we believe the introduction of the method may be valuable for testing with other species to help evaluate the comparative case for metacognition.

Analysis of oil-price movements is once again an important feature of economic policy discussions. To provide some background for this analysis, this paper summarizes a conference on the oil market held at the Federal Reserve Bank of Boston in June 2010. Four cross-cutting themes emerged from this symposium, which included scientific experts, market participants, business leaders, academics, and policymakers. First, the decline in real oil prices that followed the 1970s' oil shocks is unlikely to be repeated today, because there are fewer ways in which oil-importing countries can reduce oil demand or expand domestic supplies in response to higher prices. The second lesson of the conference, however, is that any prediction about oil markets is highly uncertain, a fact illustrated by the wide confidence intervals that result when futures-market data are used to quantify forecast uncertainty. Third, there is little consensus on whether new financial investment in commodity index funds has increased the volatility of oil prices. Finally, changes in oil prices still have large effects on the economy. Some research suggests that the rapid run-up in oil prices in 2007–08 may have significantly weakened the U.S. economy in the early stages of the Great Recession.

Metacognition has been divided into information monitoring and control processes. Monitoring involves knowing that you know or do not know some information without taking corrective action. Control involves taking corrective action based on the knowledge that you know or do not know some information. In comparative metacognition, considerable attention has been paid toward critically assessing putative evidence for information monitoring in non-human animals. However, less attention has been paid toward critically evaluating evidence for control processes in animals. We briefly review a critique of information-monitoring in animals. Next, we apply these concepts to a number of studies that focus on information seeking in animals. The main type of evidence for control processes in animals come from tube tipping experiments. Before having the opportunity to search for the bait in these experiments, the subject sometimes observes opaque tubes being baited but is sometimes prevented from seeing the baiting. The observations that the subjects look more if baiting was not seen and are more accurate if baiting was seen have been taken as evidence for metacognition in information-seeking experiments. We propose simple alternative hypotheses that are sufficient to explain putative evidence for information seeking in animals without positing metacognition. The alternative explanation focuses on two relatively simple principles: First, an animal has a default “look before you go” response which supersedes random searches in space. Second, spatially guided behavior follows a default rule of “go where something good is.” These principles can explain the results of tube tipping experiments without proposing metacognition.

Purpose : The efficacy and toxicity of radiation therapy used for preventing re-formation of heterotopic bone involving the temporomandibular joint are assessed. Methods and Materials : Ten patients (15 TMJs) with bony ankylosis of the TMJ were referred after reconstruction with costochondral graft, gap arthroplasty, or debridement of heterotopic bone. Treatment consisting of 10 Gy was delivered early postoperatively to a field encompassing the TMJ with adequate margin. Response to therapy was assessed by comparison of routine roentgenograms obtained preoperatively, immediately postoperatively, and at last follow-up; the Turlington-burr grading system was used. Median duration of postoperative follow-up was 19 months. Results : Radiation therapy prevented ectopic bone re-formation in 10 (69%) of 15 TMJs with prior bony ankylosis. Of the 15 TMJs, 13 (87%) had improvement in their Turlington-Durr scores compared with the preoperative scores. Development of ectopic bone formation was prevented in 9 (90%) of 10 TMJs rendered Turlington-burr grade 0 postoperatively. Eight of the 10 patients have remained asymptomatic. Treatment was well tolerated. The only complication experienced was parotitis in three patients. Conclusion : Radiation therapy is useful for prevention of heterotopic bone redevelopment after TMJ operation. We recommend 10 Gy in 5 fractions beginning early postoperatively for high-risk patients. This strategy appears beneficial in this young patient population, who suffer significant pain and functional impairment in the TMJ articulation.

Anatomic and electrophysiologic studies have provided evidence that CRF meets some of the criteria as a neurotransmitter in the noradrenergic nucleus, the locus coeruleus (LC), although some of the criteria have yet to be satisfied. Thus, immunohistochemical findings suggest that CRF innervates the LC, but this must be confirmed at the ultrastructural level. CRF alters discharge activity of LC neurons and these effects are mimicked by some stressors. Moreover, the effects of hemodynamic stress on LC activity are prevented by a CRF antagonist. However, it has not been demonstrated that stimulation of CRF neurons that project to the LC activates the LC or that the effects of such stimulation are prevented by a CRF antagonist. The role of CRF in LC activation by stressors other than hemodynamic stress needs to be determined. It could be predicted that the effects of CRF neurotransmission in the LC during stress would enhance information processing concerning the stressor or stimuli related to the stressor by LC target neurons. One consequence of this appears to be increased arousal. Although this may be adaptive in the response to an acute challenge, it could be predicted that chronic CRF release in the LC would result in persistently elevated LC discharge and norepinephrine release in targets. This could be associated with hyperarousal and loss of selective attention as occurs in certain psychiatric diseases. Manipulation of endogenous CRF systems may be a novel way in which to treat psychiatric diseases characterized by these maladaptive effects.

Background. Patients with esophageal cancer and a malignant tracheoesophageal fistula (TEF) have an extremely poor prognosis. Additionally, these patients often are denied treatment with radiation therapy because there is concern that these treatments may increase the size and associated problems of the TEF. Methods. To determine the appropriate treatment (use of radiation therapy) for patients with esophageal cancer and malignant TEF, a review was performed of all such cases seen at the Mayo Clinic between 1971 and 1991. Results. Between 1971 and 1991,41 patients with malignant TEF arising as a result of esophageal cancer were seen at the Mayo Clinic in Rochester. Twenty-eight of these cancers were locally recurrent, and this group of patients had a uniformly poor outcome (median survival time, 1.4 months). Thirteen patients had a malignant TEF and had not received previous treatment for their esophageal cancer. The median survival length was 4 months for this group of patients. Of the 41 patients in this study, 10 received radiation therapy for their malignant TEF (30–66 Gy). The median survival length of this group of patients was 4.8 months. Six of these 10 patients died of metastatic disease (median survival length, 9 months), and there was no evidence of progression of the local tumor. Four of these 10 patients died of local progression of the malignancy (median survival length, 3 months). Conclusions. Radiation therapy did not increase the severity of the TEF. The authors conclude that radiation therapy can be administered safely in patients with TEF resulting from esophageal cancer. In some patients, radiation treatment may contribute to stabilization of the local tumor process (60% of patients treated with radiation therapy died of metastatic disease without local progression of tumor); however, all patients in this study eventually died of esophageal cancer.

Social deprivation during early postnatal life has profound and long-lasting effects on the behavior of primates, including prolonged and exaggerated responses to stress as well as impaired performance on a variety of learning tasks. Although the cellular changes that underlie such alterations in behavior are unknown, environmentally induced psychopathology may involve morphologic or biochemical changes in select neuronal populations. The hippocampal formation of both socially deprived and socially reared prepubescent rhesus monkeys was selected for immunocytochemical investigation because of its association with the behavioral stress response and learning. Immunocytochemical analysis using antibodies specific for the neurofilament protein triplet was performed since these proteins are modified within degenerating neurons in a variety of neurodegenerative disorders. Results from optical density measurements indicate an increase in the intensity of non-phosphorylated neurofilament protein immunoreactivity in the dentate gyrus granule cell layer of socially deprived monkeys in comparison with that of socially reared animals, suggesting that early social deprivation may result in an increase in the amount of non-phosphorylated neurofilament protein in these cells. This phenotypic difference in dentate granule cells between differentially reared monkeys supports the notion that specific subpopulations of neurons in brain regions that subserve complex behaviors may undergo long-term modifications induced by environmental conditions. Furthermore, the data suggest that constitutive chemical components related to structural integrity may be as susceptible to early environmental manipulations as the more traditionally viewed measures of cellular perturbations, such as neurotransmitter dynamics, cell density and the establishment of connectivity. The observed modifications may serve as an anatomical substrate for behavioral abnormalities that persist in later life.

Most patients who have lung cancer will receive radiation therapy at some point during the course of their disease. For patients with non-small-cell lung cancer, radiation therapy is sometimes used after complete resection, particularly in patients with lymph node involvement. In addition, irradiation is commonly used after incomplete resection. In patients with unresectable non-small-cell lung cancer, radiation therapy alone is typically used, although recent studies of a combination of chemotherapy and radiation therapy, or radiation therapy given in twice-daily fractions, have yielded promising results. For patients with small-cell lung cancer who have limited (that is, nonmetastatic) disease, the addition of thoracic radiation therapy to chemotherapy has improved survival over that with chemotherapy only. The role of prophylactic cranial irradiation in small-cell lung cancer remains controversial. Radiation therapy has a major role in the management of locally recurrent and metastatic lung cancer. Both the bones and the brain are common metastatic sites in patients with lung cancer. Radiation therapy provides effective palliation of symptoms from these and other metastatic lesions.

Forty-nine patients with esthesioneuroblastoma were treated at the Mayo Clinic between 1951 and 1990. Their clinical manifestations and treatment results were reviewed to identify possible prognostic factors. The 5-year survival rate for all patients was 69%. Tumor progression occurred in 25 patients (51%; no local control in 6 and local recurrence in 19). Metastasis was found in 15 patients (31%; regional in 10 and distant in 9). Nineteen patients died directly from metastatic or intracranial tumor extension. The pathological grade of the tumor was the most significant prognostic factor identified. The 5-year survival rate was 80% for the low-grade tumors and 40% for the high-grade tumors (P = 0.0001). Surgical treatment alone is effective for low-grade tumors if tumor-free margins can be obtained. Radiation is used for low-grade tumors when margins are close, for residual or recurrent disease, and for all high-grade cancers. The poor prognosis associated with high-grade tumors may also mandate the addition of chemotherapy. Recurrent tumor and regional metastasis should be treated aggressively because this approach has been shown to be worthwhile. A craniofacial resection is now the surgical procedure performed in all cases. Because recurrence can occur after 5 or even 10 years, long-term follow-up is mandatory.

A retrospective review of 493 patients treated during a single month in a general hospital in mid-Michigan revealed that a majority (84.2%) of them received prescriptions for sedative-hypnotic drugs. These were p.r.n. in 66% of cases and routine prescriptions in the remainder. Prescriptions were equally distributed across the specialties: internal medicine 15%, surgery 23%, family practice 19%, psychiatry 22%, and OB/GYN 20%. Flurazepam was the most frequently prescribed drug (48.4%), followed by triazolam (24.6%) and temazepam (12.2%). Actual utilization rates were highest among psychiatric patients (85%) and lowest in obstetrics (33%). The therapeutic rationale for prescribing sedative hypnotic agents to hospitalized patients is discussed.

This retrospective study analyzed the outcome of lung cancer patients who were treated with either 4-MV or 10-MV photons. From October 1979 through December 1982, 126 patients with locally advanced, unresectable or medically inoperable, nonmetastatic non-small cell lung cancer were treated in a prospective trial in which they were randomly assigned to one of three chemotherapy combinations and thoracic radiotherapy. The patients were stratified by cell type, extent of operation, age, sex, and status of supraclavicular lymph nodes. All patients were followed until death or for a minimum of 4.8 years. Of the 102 evaluable patients, 98 were treated with either 4-MV or 10-MV photons (49 patients in each group). Outcomes examined included best primary tumor response, time to first local (in-field) recurrence, disease-free survival, and overall survival. No significant differences were detected between the patients treated with 4-MV or 10-MV photons for several important prognostic and treatment factors or for any of the study outcomes, including first local (in-field) recurrence, disease-free survival, and overall survival. For the group of 98 patients treated with either 4-MV or 10-MV photons, the estimated 2-year freedom from first local (in-field) recurrence was 47.7%. The estimated 2-year disease-free and overall survivals were 21.6% and 28.6%, respectively.

Historical outcomes in anaplastic thyroid carcinoma (ATC) are poor, with a median survival of only 5 months and20% of patients surviving 1 year from diagnosis. We hypothesized that survival in newly diagnosed patients with stages IVA and IVB locoregionally confined ATC might be improved by utilizing an aggressive therapeutic approach, prioritizing both the eradication of disease in the neck and preemptive treatment of occult metastatic disease.Between January 1, 2003, and December 31, 2007, 25 new ATC patients were evaluated at our institution. Of these 25 patients, 10 (40%) had metastatic disease at diagnosis and therefore underwent palliative treatment, whereas 5 (20%) had regionally confined disease and desired treatment at their local medical facilities. The remaining 10 consecutive patients (40%) had regionally confined ATC and elected aggressive therapy combining individualized surgery (where feasible), intensity-modulated radiation therapy (IMRT), and radiosensitizing + adjuvant chemotherapy intending four cycles of docetaxel + doxorubicin. Outcomes were assessed on an intention to treat basis.There were no deaths from therapy, but hospitalization was required in two patients (20%) because of treatment-related adverse events. Five patients (50%) are alive and cancer-free, all having been followed32 months (range: 32-89 months; median: 44 months) with a median overall Kaplan-Meier survival of 60 months. Overall survival at 1 and 2 years was 70% and 60%, respectively, compared to20% historical survival at 1 year in analogous patients previously treated with surgery and conventional postoperative radiation at our and other institutions.Although based upon a small series of consecutively treated patients, an aggressive approach combining IMRT and radiosensitizing plus adjuvant chemotherapy appears to improve outcomes, including survival in stages IVA and IVB regionally confined ATC, but remains of uncertain benefit in patients with stage IVC (metastatic) disease. Also uncertain is the optimal chemotherapy regimen to use in conjunction with IMRT. Further multicenter randomized trials are required to define optimal therapy in this rare but deadly cancer.

Understanding the evolution of real-time beliefs about house price appreciation is central to understanding the U.S. housing crisis. At the peak of the recent housing cycle, both borrowers and lenders appealed to optimistic house price forecasts to justify undertaking increasingly risky loans. Many observers have argued that these rosy forecasts ignored basic theoretical and empirical evidence that pointed to a massive overvaluation of housing and thus to an inevitable and severe price decline. We revisit the boom years and show that the economics profession provided little such countervailing evidence at the time. Many economists, skeptical that a bubble existed, attempted to justify the historic run-up in housing prices based on housing fundamentals. Other economists were more uncertain, pointing to some evidence of bubble-like behavior in certain regional housing markets. Even these more skeptical economists, however, refused to take a conclusive position on whether a bubble existed. The small number of economists who argued forcefully for a bubble often did so years before the housing market peak, and thus lost a fair amount of credibility, or they make arguments fundamentally at odds with the data even ex post. For example, some economists suggested that cities where new construction was limited by zoning regulations or geography were particularly "bubble-prone," yet the data shows that the cities with the biggest gyrations in house prices were often those at the epicenter of the new construction boom. We conclude by arguing that economic theory provides little guidance as to what should be the "correct" level of asset prices -- including housing prices. Thus, while optimistic forecasts held by many market participants in 2005 turned out to be inaccurate, they were not ex ante unreasonable.

Understanding the evolution of real-time beliefs about house price appreciation is central to understanding the U.S. housing crisis. At the peak of the recent housing cycle, both borrowers and lenders appealed to optimistic house price forecasts to justify undertaking increasingly risky loans. Many observers have argued that these rosy forecasts ignored basic theoretical and empirical evidence that pointed to a massive overvaluation of housing and thus to an inevitable and severe price decline. We revisit the boom years and show that the economics profession provided little such countervailing evidence at the time. Many economists, skeptical that a bubble existed, attempted to justify the historic run-up in housing prices based on housing fundamentals. Other economists were more uncertain, pointing to some evidence of bubble-like behavior in certain regional housing markets. Even these more skeptical economists, however, refused to take a conclusive position on whether a bubble existed. The small number of economists who argued forcefully for a bubble often did so years before the housing market peak, and thus lost a fair amount of credibility, or they make arguments fundamentally at odds with the data even ex post. For example, some economists suggested that cities where new construction was limited by zoning regulations or geography were particularly bubble-prone, yet the data shows that the cities with the biggest gyrations in house prices were often those at the epicenter of the new construction boom. We conclude by arguing that economic theory provides little guidance as to what should be the correct level of asset prices - including housing prices. Thus, while optimistic forecasts held by many market participants in 2005 turned out to be inaccurate, they were not ex ante unreasonable.

Between Jan. 1, 1976, and Dec. 31, 1985, at our institution, 37 patients who had undergone prior complete surgical resection of non-small-cell lung cancer received definitive thoracic radiation therapy (TRT) for locally recurrent disease. Of the 37 recurrences, 33 were in the pulmonary parenchyma or the hilar, mediastinal, or supraclavicular lymph nodes; the other 4 were in the chest wall. The initial stage of disease was I in 43%, II in 35%, and IIIA in 19%, whereas at the time of local recurrence, the stage was I in 8%, II in 11%, IIIA in 57%, IIIB in 22%, and IV in 3% (this patient had multiple pulmonary nodules encompassible within a single TRT field). The locally recurrent lesions were squamous cell carcinoma in 30%, adenocarcinoma or large-cell carcinoma in 46%, mixed types in 5%, and unknown type in 19%. All patients received megavoltage TRT, most often 4,000 cGy in 10 fractions administered in a split-course schedule. In addition, 15 patients received multiagent chemotherapy, usually a combination of cyclophosphamide, doxorubicin hydrochloride, and cisplatin or a regimen that included these drugs. The 2-year and 5-year survivals were 30% and 4%, respectively, and the median duration of survival was 13.7 months. Survival was not improved by the addition of chemotherapy. Approximately half of the patients had radiographic and symptomatic responses after TRT. Of 33 patients assessable for post-TRT patterns of failure, 46% had local failure only, 18% had local plus systemic failure, and 32% had systemic failure only. Two-thirds of the patients died as a direct consequence of progressive chest disease, despite receiving TRT. Thus, these patients have a poor long-term survival. More aggressive local treatment might improve local control and survival.

Previous anatomical studies of corticotropin-releasing factor (CRF)-like immunoreactivity in rat brain have reported prominent clustering of neuronal elements containing this peptide within the amygdala. The highest concentrations of both CRF-positive cells and fibers were evident in the central nucleus, an observation consistent with the putative role of this peptide in autonomic and endocrine regulation. In addition, lower densities of CRF-positive somata and processes have boon noted in other amygdaloid nuclei. However, the distribution of CRF-like immunoreactivity in the amygdala has not been described for any primate species. Such a description would be of interest since substantial differences in the distribution of CRF in rodent and primate have been reported for other brain regions. The present study uses immunohistochemical methods, with a polyclonal antiserum directed against the human form of CRF, to determine the distribution of this peptide in non-colchicine-treated monkeys (Saimiri sciureus). Within the amygdaloid complex, the most numerous and concentrated collections of CRF-positive neurons were seen in the basal and lateral nuclei. The highest densities of CRF-positive fibers and terminals were seen in the lateral and central amygdaloid nuclei. Moderately dense plexuses of CRF-positive fibers also were seen in layer Ia of the periamygdaloid cortex, nucleus of the lateral olfactory tract, anterior and posterior cortical nuclei, and the medial nucleus. Thus, the distribution of CRF-like immunoreactivity differs substantially in monkey and rat amygdala. Since CRF-positive perikarya in monkey are most prominent in nuclei with pronounced interconnections with neocortex, these differences may be an integral component of the increased cortical development that characterizes the primate brain. © 1992 Wiley-Liss, Inc.

Between January 1975 and December 1985, 45 patients with carcinoma in situ or invasive squamous cell carcinoma of the glottic larynx received radiation therapy at the Mayo Clinic. Local control in the entire group of 45 patients was 84% (in 6 of 6 with carcinoma in situ and in 32 of 39 with invasive cancers). Three of seven patients (43%) with local recurrences underwent successful larynx-preserving surgical procedures; thus, the rate of laryngeal preservation was 91%. In our study of several treatment factors, including the duration of treatment, type of treatment (continuous course versus split course), photon energy ( 60 Co versus 4-MV photons versus 6-MV photons), total dose, and dose per fraction, we found that only total dose of 6,300 cGy or more was associated with significantly improved local control (in 35 of 38 patients [92%]). Two patients (4%) died of uncontrolled delayed nodal metastases, one of which was preceded by a local recurrence. Severe laryngeal edema developed in two patients, associated with recurrent glottic carcinoma in one of them. No larynx was lost because of complications. In our current treatment recommendations, patients receive a total dose of 6,300 cGy in 28 fractions of 225 cGy each, administered in a continuous course with use of 6-MV photons

The rates and patterns of discharge activity exhibited by 16 spontaneously active substantia nigra pars compacta dopamine neurons were studied in halothane-anesthetized rats using three types of quantitative measures: 1) mean discharge rates, 2) population characteristics of interspike interval samples, and 3) interspike interval time-series measures which were used to examine patterns in the ordering of interspike intervals. The mean discharge rate of these 16 cells was 2.9 +/- 0.3 spikes/sec, and each cell was classified as bursting (25% of the cells) or non-bursting (75%). The distribution of interspike intervals of non-bursting neurons were more normally distributed. Time-series analyses (raw time-series plots, return maps, and phase portraits) revealed a substantial oscillatory tendency in the magnitudes of consecutive interspike intervals in these neurons under baseline conditions: Successive interspike intervals tended to alternate between short and long durations, although short bursts often occurred. Under baseline conditions, these cells exhibited both multispike bursts and consecutive long intervals less frequently than would have been predicted by chance ordering of the interspike intervals. These results imply that there are mechanisms acting to reduce the probability of these types of events. Locally infused nicotine enhanced discharge rates in these neurons. Burst firing increased in four neurons, while five neurons did not show any change in burst firing. LY 163502 induced significant decreases in both discharge rate and bursting activity in all cells tested. The variation coefficient, skew, and kurtosis of the interspike interval distributions were not consistently altered by either drug. The local infusion of either nicotine or LY 163502 decreased the oscillatory phenomenon seen in the baseline condition. Neither the nicotine or LY 163502 time-series data exhibited a larger proportion of long-short and short-long pairs (relative to the median interval) than would be expected by chance. It is hypothesized that these neurons have intrinsic mechanisms, made manifest under anesthesia, which induce oscillations in interspike interval length. The oscillatory effect of these mechanisms can be overridden by tonic increases in either excitatory or inhibitory tone.

Between 1974 and 1988, 10 Mayo Clinic patients had unresectable, locally recurrent, or partially resected chemodectomas. Of these 10 tumors, 9 were confirmed pathologically, and 1 was diagnosed clinically. The chemodectoma was located in the jugular bulb in five patients, the middle ear in three, and the carotid body in two. The following symptoms were noted: tinnitus (in eight patients), loss of hearing (in six), hoarseness (in six), dysphagia (in four), pain (in three), and alteration of mental status (in one). Many patients had more than one symptom. Treatment was delivered with megavoltage photons and electrons; total doses ranged from 16.2 to 52 Gy (median, 46 Gy), and the daily doses ranged from 1.6 to 2.4 Gy. Follow-up among the nine survivors ranged from 3 1/2 to 16 years (median, 7 1/2 years). In one patient, the response could not be assessed because the patient died of renal failure 4 months after treatment. All nine assessable patients had decreased symptoms and objective control of the tumor (no evidence of progression of disease). Of the nine assessable patients, four had complete responses, one had a partial response, and four had stable disease. No patient experienced progression of disease after radiotherapy. We conclude that radiotherapy for chemodectomas yields successful results--namely, decreased symptoms and objective control of the tumor.

Electrophysiological and anatomical observations suggest that terminals of olfactory bulb mitral cells ending in rat primary olfactory cortex exert certain postsynaptic effects via an excitatory amino acid neurotransmitter. Recent anatomical studies have shown that several peptides, most notably corticotropin-releasing factor (CRF) (Imaki et al., '89) Brain Res., 496: 35-44), are also localized within rat olfactory bulb projection neurons, thus raising the possibility that there is a peptide cotransmitter in this system. In contrast to the availability of data for rodents, very little is known about the distribution of peptides and other putative transmitters in the olfactory systems of primate species. In the present study, sections through the olfactory bulb and its target areas were obtained from two monkey species (Saimiri sciureus and Macaca fascicularis) and processed for immunohistochemistry with a well-characterized polyclonal antiserum directed against the human form of CRF. Virtually identical results were obtained in the two species. Within the olfactory bulb, nearly all mitral and many tufted cells contained CRF-like immunoreactivity. CRF-positive fibers were seen within the olfactory tract and olfactory stria, which contain the axons of mitral and tufted cells. Within the anterior olfactory nucleus and layer Ia of the olfactory tubercle and piriform cortex, immunoreactivity was seen within fine processes, as well as in coarse, varicose fibers and isolated puncta. CRF-positive cells were seen within layer III of the olfactory tubercle and piriform cortex. Immunoreactive fibers and varicosities were also seen within olfactory-recipient regions of the amygdala and entorhinal cortex. These observations suggest that CRF may act as a transmitter and/or neuromodulator in primate olfactory system.

The impact of social support on successful smoking cessation has been well documented. However, little is known about whether personal experience with cancer may motivate cancer survivors to support smoking cessation among their family members and friends. As a first step in this line of research, we sought to explore interest in playing a supportive role for smoking cessation as well as correlates of such interest among cancer survivors.Cancer survivors undergoing radiation therapy (N=211) completed a 77-item pencil-paper questionnaire. A section of the survey assessed interest in helping a smoker quit and characteristics of the smoking social network member. Respondents provided information on their smoking status, medical status, and psychosocial and behavioral factors related to cigarette smoking.Over half of the respondents 114 (54%) reported having someone close to them (family member or friend) smoking cigarettes who they thought should quit. Of these respondents (44 females, 70 males) 78% (89/114) reported they were definitely or probably interested in helping a smoker quit. Nearly all respondents wanted to help a family member (typically an adult child).Results suggest the potential feasibility of engaging cancer survivors to help family members quit smoking. Research is needed to determine the optimal methods and timing for engaging the cancer patient to maximize positive effects and minimize potential harms.

Radiation therapy (RT) is an integral component of the multidisciplinary management of a variety of endocrine neoplasia. Typical indications include unresectable or recurrent, benign or malignant tumors of the pituitary, thyroid and parathyroid glands. Typical doses administered over 5–7 weeks for benign tumors and malignant tumors are 45–50 Gy and 60–70 Gy, respectively. RT techniques employed in these treatments include 3D conformal, intensity modulated, stereotactic, and proton radiotherapy. RT is also beneficial in palliating bone metastases and preventing recurrence after complete resection of high-risk thyroid or parathyroid cancers, with adjacent organ invasion, nodal metastases and/or positive resection margins.

Purpose To assess the long-term efficacy and toxicity of radiation therapy (RT) for postoperative prophylaxis of recurrent heterotopic ossification (HO) in the temporomandibular joint (TMJ). Patients and Methods Twelve patients (18 joints) with bony ankylosis of the TMJ from HO were referred to undergo RT after arthrotomy with osseous recontouring, gap arthroplasty, or costochondral grafting. Treatment consisted of 10 Gy in 5 daily fractions to a field encompassing the TMJ with an adequate margin. RT was initiated 1 to 3 days postoperatively. Response to therapy was assessed by routine x-ray films obtained preoperatively, immediately postoperatively, and at follow-up by use of the Turlington-Durr grading system. Treatment efficacy was defined as freedom from HO re-formation requiring further surgical intervention. Efficacy and toxicity data were obtained from review of the medical records and were augmented by telephone interview of patients when possible (6 patients, all with follow-up >16 years). Efficacy rates by patient were estimated by the Kaplan-Meier method. Results The median follow-up after RT was 16.4 years (range, 2.5-19.2 years). Symptomatic re-formation of HO requiring further surgery occurred in 5 patients (7 joints). Treatment efficacy rates were 71% (95% confidence interval [CI], 44-99) at 5 years and 48% (95% CI, 15-80) at 10 years. Of the 6 patients contacted regarding late toxicity, 2 had clinical xerostomia (grade 1, CTCAE v3.0) attributable to RT; no other late RT-related toxicities were noted. None of the 12 patients had malignancy attributable to RT. Conclusions Postoperative RT prevented re-formation of TMJ HO in 50% of treated patients long term. Late toxicities from RT were mild and infrequent.

The decline in cranial nerve morbidity after radiosurgery for vestibular schwannoma (VS) correlates with dose reduction and other technical changes to this procedure. The effect these changes have had on tumor control has not been well documented.The authors performed a retrospective review of 293 patients with VSs who underwent radiosurgery between 1990 and 2004 and had a minimum of 24 months of imaging follow-up (90% of the entire series). The median radiation dose to the tumor margin was 13 Gy. Treatment failure was defined as progressive tumor enlargement noted on 2 or more imaging studies. The mean postradiosurgical follow-up was 60.9 +/- 32.5 months.Tumor growth was noted in 15 patients (5%) at a median of 32 months after radiosurgery. Radiographically demonstrated tumor control was 96% at 3 years and 94% at 7 years after radiosurgery. Univariate analysis revealed 2 factors that correlated with failed radiosurgery for VS: an increasing number of isocenters (p = 0.03) and tumor margin radiation dosesor= 13 Gy (p = 0.02). Multivariate analysis showed that only an increasing number of isocenters correlated with failed VS radiosurgery (hazard ratio 1.1, 95% CI 1.02-1.32, p0.05). The tumor margin radiation dose (p = 0.22) was not associated with tumor growth after radiosurgery.Distortion of stereotactic MR imaging coupled with increased radiosurgical conformality and progressive dose reduction likely caused some VSs to receive less than the prescribed radiation dose to the entire tumor volume.

Several characteristic times have been identified for describing force-ventilated enclosure fires. By using the initial properties of an enclosure and a prescribed fire heat release rate, a set of appropriate times for hazard evaluation can be calculated. Three times are proposed, defined, and tested. These times are characteristic of (1) the histories of the mass of gas in the room, (2) the energy in the room, and (3) the response of the enclosure walls. These parameters are independent indicators of steady state conditions in force-ventilated enclosure fires. 9 refs., 7 figs., 2 tabs.

There is widespread agreement that metacognition is not demonstrated if alternative explanations account for putative meta-cognition data. However, there is less agreement on which studies are protected from alternative explanations. We have argued that existing experiments on uncertainty monitoring can be explained by low-level explanations without assuming metacognition (Crystal & Foote, 2009). The field would benefit from the development of accepted standards for what is required to produce a convincing example of metacognition in animals.

This public policy brief presents a proposal, originally posted on the website of the Federal Reserve Bank of Boston in January of this year, designed to help homeowners who are unable to afford mortgage payments on their principal residence because they have suffered a significant income disruption and because the balance owed on their mortgage exceeds the value of their home. These homeowners represent a subset of the population of distressed homeowners, but according to our research they face an elevated risk of default and are unlikely to be helped by current foreclosure-reduction programs. The plan is a government payment-sharing arrangement that works with the homeowner's existing mortgage and provides a significant reduction in the homeowner's monthly mortgage payment. The plan does not involve principal reduction. Two options are presented; both are designed to help people with negative equity and a significant income disruption, such as job loss. In one version, the assistance comes in the form of a government loan, which must be repaid when the borrower returns to financial health. The second version features government grants that do not have to be repaid. In either case, the homeowner must provide evidence of negative equity in the home and of job loss or other significant income disruption. The costs of the plan are moderate, and the benefits should help not only the participating homeowners but also the housing industry, the financial markets, and the economy more broadly.

This public policy brief presents a proposal, originally posted on the website of the Federal Reserve Bank of Boston in January of this year, designed to help homeowners who are unable to afford mortgage payments on their principal residence because they have suffered a significant income disruption and because the balance owed on their mortgage exceeds the value of their home. These homeowners represent a subset of the population of distressed homeowners, but according to our research they face an elevated risk of default and are unlikely to be helped by current foreclosure-reduction programs. The plan is a government payment-sharing arrangement that works with the homeowner’s existing mortgage and provides a significant reduction in the homeowner’s monthly mortgage payment. The plan does not involve principal reduction. Two options are presented; both are designed to help people with negative equity and a significant income disruption, such as job loss. In one version, the assistance comes in the form of a government loan, which must be repaid when the borrower returns to financial health. The second version features government grants that do not have to be repaid. In either case, the homeowner must provide evidence of negative equity in the home and of job loss or other significant income disruption. The costs of the plan are moderate, and the benefits should help not only the participating homeowners but also the housing industry, the financial markets, and the economy more broadly. Chris Foote, Jeff Fuhrer, and Paul S. Willen are research economists at the Federal Reserve Bank of Boston. Eileen Mauskopf is a research economist at the Board of Governors of the Federal Reserve System.

This paper takes a skeptical look at a leading argument about what is causing the foreclosure crisis and what should be done to stop it. We use an economic model to focus on two key decisions: the borrower's choice to default on a mortgage and the lender's subsequent choice whether to renegotiate or modify the loan. The theoretical model and econometric analysis illustrate that unaffordable loans, defined as those with high mortgage payments relative to income at origination, are unlikely to be the main reason that borrowers decide to default. In addition, this paper provides theoretical results and empirical evidence supporting the hypothesis that the efficiency of foreclosure for investors is a more plausible explanation for the low number of modifications to date than contract frictions related to securitization agreements between servicers and investors. While investors might be foreclosing when it would be socially efficient to modify, there is little evidence to suggest they are acting against their own interests when they do so. An important implication of our analysis is that policies designed to reduce foreclosures should focus on ameliorating the immediate effects of job loss and other adverse life events rather than modifying loans to make them more affordable on a long-term basis.

Metacognition is thinking about thinking. There is considerable interest in developing animal models of metacognition to provide insight about the evolution of mind and a basis for investigating neurobiological mechanisms of cognitive impairments in people. Formal modeling of low-level (i.e., alternative) mechanisms has recently demonstrated that prevailing standards for documenting metacognition are inadequate. Indeed, low-level mechanisms are sufficient to explain data from existing methods. Consequently, an assessment of what is 'lost' (in terms of existing methods and data) necessitates the development of new, innovative methods for metacognition. Development of new methods may prompt the establishment of new standards for documenting metacognition.

This paper takes a skeptical look at a leading argument about what is causing the foreclosure crisis and what should be done to stop it. We use an economic model to focus on two key decisions: the borrower’s choice to default on the mortgage and the lender’s choice on whether to renegotiate or “modify” the loan. The theoretical model and econometric analysis illustrate that “unaffordable” loans, defined as those with high mortgage payments relative to income at origination, are unlikely to be the main reason that borrowers decide to default. Rather, the typical problem appears to be a combination of household income shocks and an unprecedented fall in house prices. Regarding the small number of loan modifications to date, we show, both theoretically and empirically, that the efficiency of foreclosure for investors is a more plausible explanation for the low number of modifications than contract frictions related to securitization agreements between servicers and investors. While investors might be foreclosing when it would be socially efficient to modify, there is little evidence to suggest they are acting against their own interests when they do so. An important implication of our analysis is that policies designed to reduce foreclosures should focus on ameliorating the immediate effects of job loss and other adverse life events, rather than modifying loans to make them more “affordable” on a long-term basis.

The application of flow shop sequencing to a flow shop generated by organization of a repair shop into modular repair centres is investigated. Such an organization in the repair industry generates processing plans with many zero processing times. The Nawaz, Enscoreand Ham(NEH) heuristic is shown to give superior schedules according to C max, but the modified Petrov heuristic gives much better computation times. When a simulation experiment is run to compare the above heuristics in an implementation, the superiority of the NEH heuristic disappears due to the variation of the processing times from the times assumed to develop the schedule.

This paper presents a nonlinear mixed integer goal programming model of the deterministic, static two-machine closed flow shop (CFS) problem. The model incorporates two sets of goals that are of importance to the production manager: cost goals and production goals. The cost goals are setup costs, finished goods holding costs, machine idle costs, and work-in-process inventory costs. The production goals are makespan, mean tardiness, mean flow time, capacity between runs and end shop capacity.

In human, the amplitudes of specific event-related potential (ERP) components can increase or decrease in response to increasing stimulus intensity depending on the location of the recording site. Large increases characterize components presumably generated by modality-specific sites, while smaller increases or even decreases are associated with those originating in associational areas. Comparable data from non-human primates, which would permit invasive studies of the neural substrates underlying these intensity-amplitude differences, are limited. To more fully characterize these relationships, auditory ERPs were recorded from chronically implanted epidural electrodes in 5 squirrel monkeys (Saimiri sciureus) in response to tones (500 Hz, 300 msec duration) of varying intensities (50, 60, 70, 80 dB SPL). Squirrel monkey ERPs recorded at Fz exhibited 3 peaks during the 200 msec post-stimulus interval. These peaks included a positivity (P1), followed by a negativity (N1), and then another positivity (P2). At posterior sites, the frontal P1-N1 configuration was recorded as an N1-P1 complex. At these sites, a small negativity (N2) preceded the last positive peak (P2). Changes in polarity were independent of reference site and posterior N1-P1 peaks exhibited latencies similar to those of the frontal P1-N1 components. Amplitudes at Fz, Cz, and Pz increased substantially with increasing stimulus intensity ('augmenting'). In contrast, only small increases or even decreases in amplitude ('reducing') were evident at T3 and T4. On the other hand, peak latencies decreased with higher stimulus intensities at most sites. The site-specific amplitude responses exhibited considerable temporal stability. In one subject, for example, similar 'augmenting' profiles were recorded at Fz in 8 sessions over a 6-month period. The topography of monkey intensity-amplitude response profiles, their temporal stability, and peak latency shifts resemble observations made in humans. The data show that 'augmenting' characterizes monkey vertex potentials, which, like the analogous human potentials, may originate in primary auditory cortex. In contrast, potentials recorded over temporal cortex, which may originate in auditory association cortex, exhibit 'reducing.' Thus, the data support the hypothesis that differences in amplitude with increasing intensity may reflect differences in cortical origin.