National Data and the Applicability to Understanding Rural and Remote Substance Use.

Responding to increases in overdose, addiction, and substance misuse, local public health experts need accurate data to plan and implement evidence-based prevention and treatment programs. In many countries, national data are the tool most readily available for these efforts. In the United States, the National Study on Drug Use and Health and the Treatment Episode Data Set are data sources used by states to determine the extent of addiction. This project sought to determine if these national data sources are applicable for local use in addiction prevention and program planning. NSDUH prevalence estimates from 2015 to 2019 were applied to the state population to determine the number of persons estimated to be substance users. The prevalence estimates were compared over time with the population data and substance use treatment admissions to assess the covariance and population change as an indicator of efficacy. The primary drivers of fatal overdose in Alaska are fentanyl, heroin, and methamphetamine. Fentanyl use was not assessed in either dataset. When applying the estimated use prevalence to the population, heroin users varied annually by 1777 persons and methamphetamine varied up to 2143 persons. These observed variances did not correspond with state population changes nor any trend in the persons seeking treatment for these substances. Our analyses do not support the use of NSDUH data for planning in rural and remote areas. The methods used in NSDUH data collection exclude ~ 20% of the state population, mostly Native persons, based on location and language. The annual prevalence estimates applied to the population did not correspond with changes in population nor changes in treatment. Fentanyl, which causes the most overdoses in Alaska and is of primary concern locally, was not assessed.

Biologically based artificial navigation systems: review and prospects.

Diverse theories of animal navigation aim at explaining how to determine and maintain a course from one place to another in the environment, although each presents a particular perspective with its own terminologies. These vocabularies sometimes overlap, but unfortunately with different meanings. This paper attempts to define precisely the existing concepts and terminologies, so as to describe comprehensively the different theories and models within the same unifying framework. We present navigation strategies within a four-level hierarchical framework based upon levels of complexity of required processing (Guidance, Place recognition-triggered Response, Topological navigation, Metric navigation). This classification is based upon what information is perceived, represented and processed. It contrasts with common distinctions based upon the availability of certain sensors or cues and rather stresses the information structure and content of central processors. We then review computational models of animal navigation, i.e. of animats. These are introduced along with the underlying conceptual basis in biological data drawn from behavioral and physiological experiments, with emphasis on theories of "spatial cognitive maps". The goal is to aid in deriving algorithms based upon insights into these processes, algorithms that can be useful both for psychobiologists and roboticists. The main observation is, however, that despite the fact that all reviewed models claim to have biological inspiration and that some of them explicitly use "Cognitive Map"-like mechanisms, they correspond to different levels of our proposed hierarchy and that none of them exhibits the main capabilities of real "Cognitive Maps"--in Tolman's sense--that is, a robust capacity for detour and shortcut behaviors.

Prevention by splenectomy of thymus weight depletion in the presence of progressively growing tumor in rats: Brief communication.

Groups of inbred rats were inoculated with the Walker 256 carcinosarcoma. The weights of their spleens and thymuses were determined on days 16 and 23 after the tumor inoculation. Spleen weights increased progressively as the tumors grew (P less than 0.001 on day 16 as compared to controls, much less on day 23). Thymus weights decreased at the same intervals (P less than 0.05 on day 16 as compared to controls; P less than 0.001 on day 23). In other groups of inbred rats, splenectomy was performed 5 days prior to tumor inoculation. If splenectomized animals were not inoculated with tumor, thymus weight did not change. Previously splenectomized, tumor-bearing animals also showed no decrease in thymus weight on day 16 or 23. Thymus weight remained greater in splenectomized, tumor-bearing animals than in intact, tumor-bearing animals on day 16 (P less than 0.05) and on day 23 (P less than 0.001). Microscopic examination of thymuses on day 23 revealed some depletion of cortical lymphocytes in splenectomized, tumor-bearing animals and profound depletion of these lymphocytes in intact, tumor-bearing animals. Tumor weights and measurements did not differ between splenectomized, tumor-bearing and intact, tumor-bearing animals. Equal rates of tumor growth provided for a roughly equal tumor burden at termination of the experiment.

Universal access to health care. A comprehensive tax-based approach.

More than 30 million Americans lack health insurance, and millions more are "underinsured." Meanwhile, the cost of health care in the United States is escalating, and some of our care is of questionable value. This article presents a health care reform strategy that addresses these three fundamental problems in the US health care system. The strategy, designed to empower consumers to make cost-conscious health care choices, combines a universal tax credit that enables all Americans to purchase basic health coverage; insurance reforms including pooling and reinsurance mechanisms; requirements that all employers make insurance available to their employees and that all consumers purchase coverage; and efforts to measure and improve the quality and efficiency of health care services. This strategy would help us to achieve universal health insurance coverage, while creating the proper incentives for cost control. In addition, it can be largely internally financed through savings automatically triggered by its implementation.

Dosimetric evaluation of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction.

The accuracy of a pencil-beam algorithm for electrons employing a two-dimensional heterogeneity correction is demonstrated by comparing calculation with measurement. Ionization measurements have been made in a water phantom for a variety of non-standard geometries. Geometries to demonstrate the effect of an extended treatment distance, a sloping skin surface, and an irregular skin surface have been selected. Additionally, thermoluminescent dosimeters have been used to measure distributions in tissue-substitute phantoms, which were designed from individual patient computerized tomographic scans. Three patient scans have been selected: (1) diffuse hystiocytic lymphoma of the left buccal mucosa and retromolar trigone; (2) squamous cell carcinoma of the nose at the columnella ; and (3) carcinoma of the maxillary antrum. Results demonstrate the algorithm's ability to simultaneously account for the isodose shifting as a result of internal heterogeneities and for sidescatter non-equilibrium caused by lateral discontinuities of the skin surface and internal anatomy. The algorithm is shown to generally be accurate to within +/- 4% in the treatment volume or +/- 4 mm in regions of sharp dose gradients as found in the penumbra and distal edge of the beam. Examples of greater disagreement are shown and their physical interpretation discussed.

Solubilized HLA class I antigen enzyme-linked immunoassay to identify HLA-typing reagents.

The objective of this study was to evaluate the use of sHLA in a solid-phase EIA as a rapid and sensitive way to identify potential IgG HLA class-I-typing reagents. To evaluate the efficacy of the sHLA EIA, we used the assay to screen 259 HLA-A, -B, and -C antisera that our laboratory had procured using the standard NIH LCA. A positive result obtained by the sHLA EIA, which was defined as an EIA ratio of 3 SD above the mean of 91 anti-HLA-negative sera, revealed that 91% (79 of 87) of the A-locus-typing reagents were positive, 96% (150 of 156) of the B-locus antisera were positive, and only 75% (12 of 16) of the C-locus reagents were positive. The typing reagents that were negative by EIA (n = 18) fell into two categories. First, 38% (7 of 18) were negative by sHLA EIA, as they were IgM-typing reagents (NIH LCA reactivity ameliorated by DTT). The second group of the 11 remaining typing reagents had a mean EIA ratio of 1.0 +/- 0.246 (mean +/- 1 SD), which was significantly (P < 0.001) higher than the mean of the 91 negative controls that were used to establish the negative cutoff. The overall sensitivity of the sHLA EIA to detect HLA class-I-directed IgG was 97.2%.

Primary solitary lymphoma of the trachea.

A case history is reported of an 81-year-old woman with progressively increasing airway obstruction and progressive stenosis of the intrathoracic trachea. Repeated endoscopic biopsies failed to establish a diagnosis. At thoracotomy, an isolated tumor mass was found originating in the trachea without grossly apparent mediastinal nodes. Biopsy of the tumor mass revealed lymphoma. Radiotherapy resulted in complete remission, which continues at 22 months.

Random versus predictable risks of mortality after thoracotomy for lung cancer.

Over a period of 12 1/2 years, 476 patients underwent thoracotomy for lung cancer at two affiliated hospitals. Hospital mortality for all patients was 5.25% and for those undergoing pulmonary resection, 5.67%. Hospital mortality is more indicative of true risk than is the 30 day mortality figure, which we regard as arbitrary and misleadingly low. Thirty-seven preoperative risk factors were analyzed for their effects on both morbidity and mortality, and 12 classes of postoperative complications were analyzed for their effect on mortality. All preoperative risk factors together accounted only for 12% of the risk of mortality (R2 by multiple regression analysis). Only three of these factors bore a significant association with mortality: patient age 60 years or over (p less than 0.05), need for pneumonectomy (p less than 0.005), and premature ventricular contractions on the admission electrocardiogram (p less than 0.05). All the listed postoperative complications together accounted for only 28% of the risk of mortality. Of these complications, four showed a significant association with postoperative death: infectious complications (pneumonia and empyema) and cardiovascular accidents (pulmonary embolism and myocardial infarction). In both analyses, the remainder of the risk of death must be attributed either to factors not considered or to purely random factors. It follows that much the greater part of the risk of death from surgical treatment of lung cancer could not be predicted from the preoperative status of the patients.

Selective surgical resection in small cell carcinoma of the lung.

Surgical resection has failed notably as definitive treatment for small cell carcinoma of the lung. Newer treatment programs combining intensive chemotherapy with radiation therapy achieve a significant response in about 85 percent of cases, with about 50 percent of patients showing clinically complete remission. Long-term survival without recurrence has been the outcome in a small minority of cases. A frequent mode of failure after treatment of limited disease is recurrence within the chest. The course of one patient treated early in this series suggests that exclusion of initial surgical resection from programs of combined treatment may be a serious omission. Since that time, four patients have undergone initial resection, apparently with uniformly favorable courses to date. Selection criteria based on staging factors are proposed. Admittedly, only a minority of patients will be suitable for this treatment at the time of first diagnosis. Much opportunity exists for improvement in survival rates of patients, even those with limited disease.

Histologic alterations in small cell carcinoma of the lung after two cycles of intensive chemotherapy.

In patients treated nonsurgically for "limited" small cell carcinoma of the lung, the most frequent site of relapse is within the chest. We have treated patients with clinical Stage III M0 disease (T3 and/or N2, M0) by two cycles of chemotherapy, surgical resection of the primary site and mediastinal nodes, and continued chemotherapy thereafter. Since May, 1979, the regimen has consisted of cyclophosphamide, doxorubicin, vincristine, and etoposide on a 3 week cycle. The first 12 patients so treated had partial or complete remission after two cycles. Resection was technically not possible in two. Residual small cell carcinoma was not identifiable in the specimens from two of the 10 patients undergoing resection. Microscopic tumor extended to a resection line in two of the eight with residual tumor. Malignant tissue appearing to have the structure of papillary adenocarcinoma was found in hilar and paratracheal nodes in one patient, but nowhere in the resected lung; some residual small cell carcinoma remained in the lung. Nuclear ballooning and eosinophilic inclusions were noted in cells still identifiable as small cell carcinoma in one case. Marked fibrotic scarring was noted in eight cases, acute and organizing bronchopneumonia in three, and multiple small parenchymal abscesses in one case. Long disease-free survival occurred in one patient, in whom residual tumor could not be found in the specimen; in at least one more in whom residual tumor was present; and even in one patient in whom tumor was present at the bronchial resection line.

Adverse prognostic effect of N2 disease in treated small cell carcinoma of the lung.

We reviewed survival of patients with clinically localized small cell carcinoma of the lung treated by surgical resection, combination chemotherapy, and prophylactic cranial irradiation. Long-term survival was defined as continuing complete remission 30 months after the start of treatment. Initial TNM staging determined the course of treatment. Ten patients with disease in Stages I and II were treated over 30 months ago by initial resection followed by the full course of chemotherapy. Only one has had a relapse, whereas 80% remained disease-free at 30 months. Five of these patients have passed 5 years. Four patients with T3 N1 disease were treated by two cycles of chemotherapy, surgical resection, and cranial irradiation plus resumption of chemotherapy thereafter; two remained in remission at 30 months. Sixteen patients initially with N2 disease were treated according to the same schedule; 10 of the 16 underwent successful resection. All 16 patients have had a relapse, but the relapse occurred very late in three--at 27, 30, and 37 months. The reasons for the apparently poor prognosis of N2 disease are not clear. Considerations of tumor response kinetics and somatic mutation suggest that these biologic factors are fundamentally responsible. Other studies may find disease control achieved in a very few patients with N2 disease.

Phase II trial of extended indications for resection is small cell carcinoma of the lung.

Surgical resection offers distinct theoretical advantages as the "local" modality in treatment of Stage I and II small cell carcinoma of the lung. We have treated 10 such patients by initial resection since 1975; all survivors but one received adjuvant chemotherapy for the full course thereafter. One patient died of a pulmonary embolus; the other nine remain without evidence of disease from 7 to 69 months after resection. A trial was undertaken of extended indications for resection in selected patients with Stage III-M0 disease. Criteria for patient selection have been developed gradually; these exclude patients for reasons of refusal, physiological inadequacy, disease unsuited to gross total eradication, or lack of adequate initial response to chemotherapy. Of six patients who survived the exclusion criteria and underwent resection, one has had a relapse at 26 months. All others remain without evidence of disease, 5 to 25 months after the start of treatment. We believe that systematic patient selection on the basis of defined criteria will identify a subset of patients having markedly improved chances for disease control. This group may represent as many as half of the patients first presenting with localized or MO disease. Patients excluded as candidates for resection have continued to receive standard nonsurgical combined-modality therapy.

Friedrich Trendelenburg and the surgical approach to massive pulmonary embolism.

A surgical approach to embolectomy from the pulmonary artery had been worked out in laboratory animals prior to 1908 by Friedrich Trendelenburg, professor of surgery and director of the University Surgical Clinic at Leipzig, Germany. His technique was based on limited opening of the left side of the chest directly over the common or undivided pulmonary artery and encircling the proximal aorta and pulmonary artery together through the transverse sinus of the pericardium. Both vessels were to be occluded by traction on the encircling band. Emboli were to be extracted through a small pulmonary arteriotomy, which then was to be controlled by a tangentially applied clamp, while occlusion of the great blood vessels was released. Unfortunately, during the first clinical trial of the technique, the patient died because of technical difficulties. Not until 1924 was a surviving patient described, by Trendelenburg's former trainee, Martin Kirschner.

Splenectomy and the thymic involution of increasing age.

Forty young female rats, aged about 3 months, were weighed on entry into the study; half were subjected to initial splenectomy. Animals were weighed at monthly intervals therafter. Ten animals from each group were killed at four months, and ten from each group at one year. Thymuses and spleens were dissected out and weighted. Because of progressive weight gain, all groups showed declining thymic index. Absolute thymus weight did not change signficiantly in splenectomized animals. Intact animals showed significantly reduced thymus weight at 4 months (P less than .001) and at 12 months (P less than .005). We conclude that the spleen may be a causative factor in the thymic involution of increasing age. The process is gradual and indolent compared to the rapid thymic weight depletion that occurs in the presence of growing tumor.

Hugh Morriston Davies and lobectomy for cancer, 1912.

The report of a lobectomy for bronchogenic carcinoma in 1912, by Hugh Morriston Davies of London, and without precedent, describes a surgical technique strikingly similar to that of today. Unfortunately, Davies' patient died because postoperative management of the pleural space was not yet well understood. The tumor had been identified by radiographic examination and the diagnosis confirmed by cytological examination of the sputum. The operative technique included individual ligation of hilar vessels and suture closure of the bronchus, neither of which was to be reported again for more than 20 years. More effective management of the pleural space was described, without special emphasis, by Harold Brunn of San Francisco 17 years later.

Claude Beck and cardiac resuscitation.

The problem of sudden death due to derangement of the cardiac mechanism remained poorly defined into the 20th century. The physiologist Carl J. Wiggers proposed maintenance of the circulation by manual massage of the heart, followed by electrical defibrillation at a suitable time. His surgical colleague Claude S. Beck, with several associates, defined a precise sequence of steps for management of cardiac arrest in the operating room and was able to apply them clinically with complete success. Subsequently, patients were resuscitated outside the operating room as well; and finally, massage and defibrillation across the intact chest have made cardiac resuscitation available at any place or time.

Werner Forssmann and catheterization of the heart, 1929.

Invasive study of cardiac anatomy and function traces its origin to the work of a 25-year-old surgical trainee in a provincial German town in the pre-Depression years of 1929 and 1930. Only 1 year out of medical school and undeterred by the medical profession's fear of tampering with the heart, Dr Werner Forssmann explored methods for a more direct access to the cardiac chambers, finding it necessary to make the observations on himself. Later he was able to show that the right-sided cardiac chambers could be visualized radiographically after injection of iodinated contrast materials through a catheter into the right atrium, and again he tried the method on himself.

A practical mechanical respirator, 1929: the "iron lung".

No satisfactory mechanical respirator existed before 1929, when Philip Drinker and Louis Shaw described an apparatus of their own design. This machine was in the form of a cylindrical tank enclosing the patient's body and chest, leaving the head outside the chamber under atmospheric pressure. Air pumps, later a bellows, raised and lowered pressure within the tank to assume the entire work of breathing. Popularly named the iron lung, the Drinker respirator supported thousands of patients afflicted with respiratory paralysis during the polio era. It was being superseded by positive-pressure airway ventilators just as the polio era came to a close. Today the Drinker respirator has disappeared virtually without a trace. Although its disadvantage was its cumbersome size, we must concede that it supported patients over the long term with fewer complications than do the respirators of today.

Tuberculosis, the Adirondacks, and coming of age for thoracic surgery.

"The Captain of all these men of death," wrote John Bunyan in 1680, "that came against him to take him away, was the Consumption, for it was that that brought him down to the grave." Until the twentieth century tuberculosis, or the Consumption, was the foremost cause of death among adults. It had not been recognized as a specific infectious process until 1882. The sanatorium movement for segregation and treatment of tuberculous patients originated in the late nineteenth century. Locations in the mountains were thought to be especially favorable, for the sake of fresh air, sunshine, and the aromas of pine and spruce. Long before the epidemic of lung cancer, or the possibilities of correction for cardiac disease, development of thoracic surgery was closely intertwined with the history of the sanatoriums. All of them had disappeared, however, soon after the middle of the twentieth century.