Extraneous Causes Research Articles

Interstitial Lung Disease: A Focused Review for the Emergency Clinician

BackgroundInterstitial lung disease (ILD) is a group of restrictive pulmonary diseases associated with diffuse interstitial and parenchymal inflammation. Patients can present to the emergency department with severe exacerbation. ObjectiveThis narrative review provides emergency clinicians with the most recent evidence concerning acute exacerbation of ILD (AE-ILD). DiscussionAE-ILD can present as acute respiratory distress in a patient with a pre-existing ILD diagnosis or as a de novo presentation of ILD, and is associated with significant morbidity and mortality. A variety of underlying triggers may result in AE-ILD. Emergency clinicians must first assess for extraneous causes of respiratory decompensation prior to diagnosing AE-ILD. For a de novo presentation of ILD, emergency physicians should also assess for possible reversible causes. AE-ILD is managed with systemic steroids, immunosuppressants, intravenous antibiotics, supplemental oxygen, and extracorporeal membrane oxygenation in severe cases. Given the high mortality rates in the absence of lung transplantation, early referral to transplant centers is essential to increase chances of survival. ConclusionsEmergency clinician knowledge of AE-ILD can improve the evaluation and management of these patients.

Sharp Reductions in COVID-19 Case Fatalities and Excess Deaths in Peru in Close Time Conjunction, State-By-State, with Ivermectin Treatments

On May 8, 2020, Peru’s Ministry of Health approved ivermectin (IVM) for the treatment of COVID-19. A drug of Nobel Prize-honored distinction, IVM has been safely distributed in 3.7 billion doses worldwide since 1987. It has exhibited major, statistically significant reductions in case mortality and severity in 11 clinical trials for COVID-19, three with randomized controls. The indicated biological mechanism of IVM is the same as that of antiviral antibodies generated by vaccines—binding to SARS-CoV-2 viral spike protein, blocking viral attachment to host cells.Mass distributions of IVM for COVID-19 treatments, inpatient and outpatient, were conducted in different timeframes with local autonomy in the 25 states (departamentos) of Peru. These treatments were conducted early in the pandemic’s first wave in 24 states, in some cases beginning even a few weeks before the May 8 national authorization, but delayed four months in Lima. Analysis was performed using Peruvian public health data for all-cause deaths and for COVID-19 case fatalities, as independently tracked for ages 60 and above. These daily figures were retrieved and analyzed by state. Case incidence data were not analyzed due to variations in testing methods and other confounding factors. These clinical data associated with IVM treatments beginning in different time periods, April through August 2020, in each of 25 Peruvian states, spanning an area equivalent to that from Denmark to Italy and Greece in Europe or from north to south along the US, with a total population of 33 million, provided a rich source for analysis.For the 24 states with early IVM treatment (and Lima), excess deaths dropped 59% (25%) at +30 days and 75% (25%) at +45 days after day of peak deaths. Case fatalities likewise dropped sharply in all states but Lima, yet six indices of Google-tracked community mobility rose over the same period. For nine states having mass distributions of IVM in a short timeframe through a national program, Mega-Operación Tayta (MOT), excess deaths at +30 days dropped by a population-weighted mean of 74%, each drop beginning within 11 day after MOT start. Extraneous causes of mortality reductions were ruled out. These sharp major reductions in COVID-19 mortality following IVM treatment thus occurred in each of Peru’s states, with such especially sharp reductions in close time conjunction with IVM treatments in each of the nine states of operation MOT. Its safety well established even at high doses, IVM is a compelling option for immediate, large scale national deployments as an interim measure and complement to pandemic control through vaccinations.

Лучевая терапия остеохондродисплазии у шотландских вислоухих кошек

Osteochondrodysplasia in the Scottish Fold cats is the genetic disease, inherited according to the autosomal-dominant type; it is manifested by the deformation of bones and cartilages of the skeleton in the form of unhealthy bone growths in the region of the wrist, metacarpal, fetlock, mesopodial and phalanx joints of breast and pelvic extremities, and also tailed vertebrae.
 
 Purpose of research. To assess the effectiveness of radiation therapy in the treatment of Scottish fold cats with osteochondrodysplasia.
 
 Materials and methods. 10 Scottish Fold cats (3 males, 7 females; age ― from 5 months to 10 years) with osteochondrodysplasia were treated from 2013 to 2017. All patients had clinical signs of disease in the form of skeletal growths in the wrist, metacarpus, finger bones, lumbar, sacral or tail spine. Most of them (9 of 10) were lame. All patients were examined clinically and radiologically before the treatment. Radiation therapy was carried out on gamma therapy unit «AGAT-R» with inclusion of the affected limbs to the middle of the shoulder or thigh. Immobilization was achieved either by general anesthesia or by means of physical restraint. Fraction doses used were 1.5 Gy up to total doses of 15.0 Gy, 2 to 3 fractions per week.
 
 Results. In 9 of 10 cases (90 %) there is a subjective improvement in mobility and regression of lameness after 6 months and furthermore after treatment. Two patients in the group died within 8 and 12 months from extraneous causes, others are alive and well for the time being with no need for pain relief. In three cases a radiological control of skeletal growths was performed, with no signs of progression 6.15 and 71 months after treatment. The maximum observation period is 2196 days, the observation median is 705 days.
 
 We used a questionnaire to improve the objectiveness of cat’s mobility and pain assessment before and after treatment. Based on animal owners’ answers the score for each symptom was assigned from 0 (severe dysfunction) to 2 (function not impaired). Scores from individual cases were summed, and the averaged total results were compared. Generally, after radiation therapy, animals’ mobility improved significantly (the averaged mobility score in the group imcreased from 3.0 to 6.5).
 
 Conclusion. The radiation therapy is an effective pathogenetic and symptomatic method of treatment of Scottish fold cats with osteochondrodysplasia: in most cases it leads to pain relief and increased mobility of the animal. According to clinical and radiological (in three cases) criteria, it can also be assumed that radiation therapy leads to suppression of the skeletal growths enlargement. The effect of treatment develops within 6 months after its completion and is persistent (lasts for many months and years). The technique involves the use of small total doses, so it does not cause complications and is practically safe for the patient.

Mixture Modeling on Related Samples by ψ-Stick Breaking and Kernel Perturbation

There has been great interest recently in applying nonparametric kernel mixtures in a hierarchical manner to model multiple related data samples jointly. In such settings several data features are commonly present: (i) the related samples often share some, if not all, of the mixture components but with differing weights, (ii) only some, not all, of the mixture components vary across the samples, and (iii) often the shared mixture components across samples are not aligned perfectly in terms of their kernel parameters such as the location and spread in Gaussian kernels, but rather display small misalignments either due to systematic cross-sample difference or more often due to uncontrolled, extraneous causes. Properly incorporating these features in mixture modeling will enhance the efficiency of inference, whereas ignoring them not only reduces efficiency but can jeopardize the validity of the inference due to issues such as confounding. We propose to use two techniques for incorporating these features in modeling related data samples using kernel mixtures. The first technique, called ψ-stick breaking, is a joint generative process for the mixing weights through the breaking of both a stick shared by all the samples for the components that do not vary in size across samples and an idiosyncratic stick for each sample for those components that do vary in size. The second technique is to imbue random perturbation into the kernels, thereby accounting for cross-sample misalignment. These techniques can be used either separately or together in both parametric and nonparametric kernel mixtures. We derive efficient Bayesian inference recipes based on Markov Chain Monte Carlo (MCMC) sampling for models featuring these techniques, and illustrate their work through both simulated data and a real flow cytometry data set in prediction/estimation and testing multi-sample differences.

Analysis of Distributional Variation Through Graphical Multi-Scale Beta-Binomial Models

ABSTRACTMany scientific studies involve comparing multiple datasets collected under different conditions to identify the difference in the underlying distributions. A common challenge in these multi-sample comparison problems is the presence of overdispersion, or extraneous causes other than the conditions of interest that also contribute to the cross-sample difference, which frequently results in false findings—identified “differences” not replicable in follow-up studies. When proper replicate samples are available under the conditions, one can in principle identify the interesting distributional variation from overdispersion through what we call the “analysis of distributional variation” (ANDOVA). We introduce a fully probabilistic framework for ANDOVA that achieves high computational efficiency. We take a divide-and-conquer multi-scale inference strategy: (i) first transform a general nonparametric ANDOVA task into a collection of ANDOVA tasks on Binomial experiments—each characterizing variations in the distributions at a particular location and scale, (ii) address each Binomial ANDOVA using a Beta-Binomial (BB) model, and (iii) use hierarchical graphical modeling to combine the inference from the BB models. We derive efficient MCMC-free Bayesian inference recipe under this framework through a combination of Laplace approximation-based numerical integration and message passing, and evaluate the performance of our method through extensive simulation. We apply the framework to analyzing DNase-seq data for identifying differences in transcriptional factor binding. Supplementary material for this article is available online.

The basis for folinic acid treatment in neuro-psychiatric disorders

Multiple factors such as genetic and extraneous causes (drugs, toxins, adverse psychological events) contribute to neuro-psychiatric conditions. In a subgroup of these disorders, systemic folate deficiency has been associated with macrocytic anemia and neuropsychiatric phenotypes. In some of these, despite normal systemic levels, folate transport to the brain is impaired in the so-called cerebral folate deficiency (CFD) syndromes presenting as developmental and psychiatric disorders. These include infantile-onset CFD syndrome, infantile autism with or without neurologic deficits, a spastic-ataxic syndrome and intractable epilepsy in young children expanding to refractory schizophrenia in adolescents, and finally treatment-resistant major depression in adults. Folate receptor alpha (FRα) autoimmunity with low CSF N(5)-methyl-tetrahydrofolate (MTHF) underlies most CFD syndromes, whereas FRα gene abnormalities and mitochondrial gene defects are rarely found. The age at which FRα antibodies of the blocking type emerge, determines the clinical phenotype. Infantile CFD syndrome and autism with neurological deficits tend to be characterized by elevated FRα antibody titers and low CSF MTHF. In contrast, in infantile autism and intractable schizophrenia, abnormal behavioral signs and symptoms may wax and wane with fluctuating FRα antibody titers over time accompanied by cycling changes in CSF folate, tetrahydrobiopterin (BH4) and neurotransmitter metabolites ranging between low and normal levels. We propose a hypothetical model explaining the pathogenesis of schizophrenia. Based on findings from clinical, genetic, spinal fluid and MRI spectroscopic studies, we discuss the neurochemical changes associated with these disorders, metabolic and regulatory pathways, synthesis and catabolism of neurotransmitters, and the impact of oxidative stress on the pathogenesis of these conditions. A diagnostic algorithm and therapeutic regimens using high dose folinic acid, corticosteroids and milk-free diet is presented which has proven to be beneficial in providing adequate folate to the brain and decreasing the FRα autoantibody titer in those positive for the antibody.

Competing risks a statistical approach

Survival analyses are commonly applied to study death or other events of interest. In such analyses, so-called competing risks may form an important problem. Competing risk are said to be present when a patient is at risk of more than one mutually exclusive event, such as death from different cause which will prevent any other from happening. when competing events are not independent treating subjects dying from extraneous causes as censored and then computing the ordinary Kaplan-Meir estimate results in biased survival estimates, in such cases,the cumulative incidence and cause-specific hazard may lead to valid results, but the resulting model does not allow one to estimate risks conditional on removal of one or more causes of the event.

Shewhart Control Chart in Microbiological Quality Control of Purified Water and its Use in Quantitative Risk Evaluation

Water in pharmaceutical industry is a key ingredient in many industrial processes, including machine washing and preparation of most medicinal products. The process of regular monitoring for the microbiological quality of water at the points of use is a critical aspect in ensuring the compliance to the limit. However, the full value of the microbiological control could be accomplished by the use of control charts and statistical quality control to show the trend and behavior of bioburden. In addition, Shewhart charts provide insight for prediction of the future of the water quality. In the current study, purified water samples were analyzed microbiologically during a two-year period. The generated data were continuously interpreted using statistical software packages. The trend indicated that two regions in Shewhart chart were in the out-of-control state at these periods generating either out-of-trend (OOT) and/or out-of-specification (OOS). Investigations showed that these deteriorations in the performance were chronologically coincided with unusual rise in the microbial count of city water, although there was no direct correlation between the input and output water microbiologically. The rate of failure of product purified water was determined to be 7.69x10-4 and Ppk was 1.06 which were unsatisfactory performance. However, by removing the excursion periods due to the expected extraneous causes from the I-MR chart, a 337 times increase in the process performance was estimated with Ppk index of 1.53 and quantitative performance failure risk (QPR) equals 2.28x10-6. This finding highlighted the criticality of the quality of the feed city water and its impact on the final purified water. Thus, the processing stages in the water purification plant are not absolute barriers against microbial creeping into the distribution system, and the purification system of water has a certain tolerance limit after which an outbreak of microbial population occurs and hence compromising the system efficacy and performance. From the present study, it is recommended to design protective pretreatment system that buffers severe fluctuations in raw water quality so that water station possesses the ability to work optimally in an attempt of delivering safe water for medicinal and pharmaceutical manufacturing purposes.

Platelet gel in cutaneous radiation dermatitis

Radiotherapy, alone or in combination with chemotherapy and/or surgery, is a fundamental and irreplaceable method of treating tumours. Nonetheless, although the technological advances made during recent years and the associated improvements in this type of treatment have reduced the incidence of complications, 5-15 % of patients still experience damage to the healthy tissues exposed to radiation. Cutaneous and mucosal lesions are severe collateral effects of radiotherapy that have an enormous impact on a patient's quality of life. Unfortunately, however, the efficacy of conventional treatments, while demonstrably useful in acute lesions, remains disputed in chronic cases. Nevertheless, numerous studies and clinical findings have demonstrated that topical, non-transfusional plasma-rich platelet gel is able to accelerate the regeneration and repair of tissues through the action of the various growth factors contained within the alpha granules of platelets. We therefore set out to evaluate the efficacy of autologous platelet gel, chosen for its limited cost and ease of preparation, in chronic cutaneous radiation dermatitis. "Home-made" platelet gel was produced by treating platelets with autologous thrombin. The safety of the product was ensured by microbiological tests. The autologous platelet gel was applied topically once a week, for a mean duration of 35 days, to chronic third- and fourth-degree (European Pressure Ulcer Advisory Panel classification and Common Terminology Criteria for Adverse Events score) cutaneous radiation dermatitis in a group of ten patients previously treated for moderate-to-high grade (histology G2-G3) limb sarcoma by tumour excision and post-surgical radiotherapy (dose 50-64 Gy). The radiation dermatitis had appeared at different intervals after treatment and had all proved resistant to conventional treatments. The autologous platelet gel was found to be successful in seven out of the ten patients treated. The various phases of the healing process were observed in all cases. Platelet gel application was suspended in three patients: in one patient after one application due to tumour progression, in another patient after two applications due to development of distant metastases and in the third after six applications with only partial tissue response. At 5-year follow-up, six of the seven successfully treated patients remained free of both disease and lesion, while the remaining patient, the eldest, had passed away in the interim due to extraneous causes. Platelet gel treatment could therefore be used to bring about healing in chronic cutaneous radiation dermatitis, lending itself to better patient compliance and a favourable cost/benefit ratio, due to a reduction in the number of medications and hospital visits required.

Analysis of the cases of trauma and suicide attempts serviced by University General Hospital ‘Tsaritsa Yoanna—ISUL’, Sofia over 1 year period

AimTo estimate the rate of hospital admissions for trauma and burns due to external causes (ICD-10) for a 1 year period in comparison with the overall number of admissions in...

Direct calibration of a reference standard against the air kerma strength primary standard, at 192Ir HDR energy

The primary standard of low air kerma rate sources or beams, maintained at the Radiological Standards Laboratory (RSL) of the Bhabha Atomic Research Centre (BARC), is a 60 cm3 spherical graphite ionization chamber. A 192Ir HDR source was standardized at the hospital site in units of air kerma strength (AKS) using this primary standard.A 400 cm3 bakelite chamber, functioning as a reference standard at the RSL for a long period, at low air kerma rates (compared to external beam dose rates), was calibrated against the primary standard. It was seen that the primary standard and the reference standard, both being of low Z, showed roughly the same scatter response and yielded the same calibration factor for the 400 cm3 reference chamber, with or without room scatter.However, any likelihood of change in the reference chamber calibration factor would necessitate the re-transport of the primary standard to the hospital site for re-calibration. Frequent transport of the primary standard can affect the long-term stability of the primary standard, due to its movement or other extraneous causes. The calibration of the reference standard against the primary standard at the RSL, for an industrial type 192Ir source maintained at the laboratory, showed excellent agreement with the hospital calibration, making it possible to check the reference chamber calibration at RSL itself.Further calibration procedures have been developed to offer traceable calibration of the hospital well ionization chambers.

Analysis of risk factors for excess mortality after aortic valve replacement

This study sought to identify risk factors for both late observed and late "excess" mortality after aortic valve replacement and to examine the causes of late mortality. Because operative mortality after aortic valve replacement is very low, the timing of surgical intervention should focus on maximizing long-term survival. However, to judge the effect of valve replacement on long-term survival in an elderly population, it is important to separate mortality resulting from extraneous causes (background mortality) from disease-related mortality (excess mortality). Background mortality can be estimated by calculating expected mortality on the basis of age and gender. From 1966 to 1986, 643 patients (mean age 59.6 years, 138 [21%] > or = 70 years old) underwent aortic valve replacement, 129 of whom also underwent coronary bypass grafting; 594 patients survived > or = 30 days after the procedure. The overall operative mortality rate for isolated aortic valve replacement decreased over time from 25.5% (1966 to 1972) to 2.6% (1980 to 1986). Cumulative total follow-up after discharge was 3,603 patient-years. Multivariate analysis was performed for both observed and excess mortality. Risk factors for both observed and excess mortality were previous myocardial infarction, coronary artery disease, heart failure and atrial fibrillation. Although age > or = 70 years was a risk factor for observed mortality (hazard rate ratio [HRR] 2.4, 95% confidence interval [CI] 1.6 to 3.7), it was not a risk factor for excess mortality. In contrast, isolated aortic regurgitation was an important risk factor for excess mortality only (HRR 3.8, 95% CI 1.3 to 11.2). Late mortality was valve related in 22% of patients, including sudden death in 7% and cerebral vascular accidents in 7%. Congestive heart failure was an important cause of death (21%) irrespective of the time elapsed since aortic valve replacement. In patients with aortic regurgitation, congestive heart failure was the main cause of death (38%); in patients with aortic regurgitation and preoperative heart failure or severe left ventricular dysfunction, heart failure was the cause of death in 44% and 63%, respectively. Analysis of excess mortality revealed that older age in itself is not a risk factor for late mortality after aortic valve replacement. Aortic regurgitation carries a high risk, probably associated with left ventricular dysfunction at the time of operation. Earlier operation may be warranted in such patients.

Myocardial Ischemia

Isoflurane may precipitate ischemia in patients with coronary artery disease, presumably via “coronary steal.” We sought to examine whether myocardial ischemia is more common in patients with coronary artery disease receiving isoflurane (0.7%) than in a control group receiving enflurane (0.9%). Thirty-eight patients scheduled for coronary artery bypass surgery were randomly assigned one anesthetic and monitored for ischemia. All patients had ejection fractions of at least 45%. Extraneous causes of ischemia were controlled as much as possible: arterial blood pressure was maintained within 20% of baseline (primarily with phenylephrine), heart rate was maintained below 80 bpm, effects from endotracheal intubation were monitored, and measurements were made before incision. Electrocardiogram, transthoracic echocardiography, and coronary sinus lactate measurement were used to detect ischemia. Measurements were made after insertion of vascular catheters, after intubation, and after 20 min of breathing the inhaled anesthetic. During the awake period and after induction of anesthesia with fentanyl (25 μg/kg), there was no significant difference detected between the two groups in incidence of ischemia: 20% in the enflurane group and 22% in the isoflurane group (P = 0.38). After 20 min of receiving the inhaled anesthetic, the incidence of ischemia in the isoflurane group increased to 50%, whereas the incidence in the enflurane group was unchanged at 20% (P = 0.02). These results show that, even with strict control of hemodynamics, isoflurane is associated with more myocardial ischemia than is enflurane. (Anesth Analg 1993;77:221-6)

On the Use of Cause-Specific Failure and Conditional Failure Probabilities: Examples From Clinical Oncology Data

Abstract Nonparametric maximum likelihood estimation of the probability of failing from a particular cause by time t in the presence of other acting causes (i.e., the cause-specific failure probability) is discussed. A commonly used incorrect approach is to take 1 minus the Kaplan-Meier (KM) estimator (1 – KM), whereby patients who fail of extraneous causes are treated as censored observations. Examples showing the extent of bias in using the 1-KM approach are presented using clinical oncology data. This bias can be quite large if the data are uncensored or if a large percentage of patients fail from extraneous causes prior to the occurrence of failures from the cause of interest. Each cause-specific failure probability is mathematically defined as a function of all of the cause-specific hazards. Therefore, nonparametric estimates of the cause-specific failure probabilities may not be able to identify categorized covariate effects on the cause-specific hazards. These effects would be correctly identified by cause-specific cumulative hazard or KM plots in which the extraneous causes of failure are treated as censored observations. Examples are provided. Finally, nonparametric graphical representation of the two distinct cause-specific failure components of the mixture model (i.e., the probability of ever failing from a particular cause and the time-to-failure distribution given that a patient will fail of that cause) are presented. The difficulty in extrapolating the nonparametric estimates beyond the range of observed failure times is highlighted. In addition, the mathematical relationship of a single covariate z and the two cause-specific failure components is shown for the case where z acts multiplicatively on the cause-specific hazards. Examples are considered using the important prognostic factors in adult soft tissue sarcoma (STS) of the extremity and adult acute lymphoblastic leukemia (ALL). In each of the mathematical and actual examples considered, the characteristic that was associated with a higher hazard rate of failure from the disease was also associated with a higher probability of ever failing from the disease as well as a shorter time-to-failure distribution given that failure due to the disease will occur. Thus it may be quite common in chronic disease situations to find prognosticators that are associated with both cause-specific failure components.

On the Use of Cause-Specific Failure and Conditional Failure Probabilities: Examples from Clinical Oncology Data

Abstract Nonparametric maximum likelihood estimation of the probability of failing from a particular cause by time t in the presence of other acting causes (i.e., the cause-specific failure probability) is discussed. A commonly used incorrect approach is to take 1 minus the Kaplan-Meier (KM) estimator (1 – KM), whereby patients who fail of extraneous causes are treated as censored observations. Examples showing the extent of bias in using the 1-KM approach are presented using clinical oncology data. This bias can be quite large if the data are uncensored or if a large percentage of patients fail from extraneous causes prior to the occurrence of failures from the cause of interest. Each cause-specific failure probability is mathematically defined as a function of all of the cause-specific hazards. Therefore, nonparametric estimates of the cause-specific failure probabilities may not be able to identify categorized covariate effects on the cause-specific hazards. These effects would be correctly identified ...

Background mortality in clinical survival studies

In long-term follow-up studies of survival after an initial event (eg, an operation) mortality from causes other than the one under study obscures the results, especially in elderly patients. In the traditional approach to the calculation of expected mortality a fictitious cohort is drawn from the general population, being matched for age, sex, and calendar time at the time of the initial event. The membership of this cohort is then kept constant from the intitial event until the closing date of the study. The survival and mortality of this static cohort is then compared with that of the dynamic patient cohort to throw light on mortality from extraneous causes. This method can lead to severe bias if there is a strong correlation between the duration of observation of the patients and their age. The analysis can be improved by applying rate adjustment when calculating the background component of mortality. In this approach mortality rates from the general population are adjusted (weighted) so that the age, sex, and calendar year are at all times identical with those of each of the patients still alive and under observation. This is illustrated by means of a simplified example and a real-life one from a study at survival after aortic valve replacement. Estimation of rate-adjusted background mortality provides a framework that may put long-term survival, especially of elderly patients, in proper perspective.

A phenomenological study of the Fleischmann-Pons effect

This paper reports experiments similar to those in the initial work by Fleischmann and Pons, on electrochemically induced nuclear fusion of deuterium. The experiments have been concerned with measurements of heat evolution and of neutron radiation in and around a cell in which mixtures of deuterium oxide and tritium oxide have been electrolysed using cathodes of palladium. The heat measurements have been made by flow calorimetry. For comparison, analogous measurements have also been made of the heat evolution occuring in similar cells in which common water has been electrolysed under essentially the same conditions. LiOH has been used as electrolyte in all these experiments. The cathodes were made from the bulk metal in a hard-worked condition or after careful annealing to remove structural defects and occluded hydrogen. The data obtained from one experiment with a cathode made of 99.95 % palladium, 3.0 × 3.5 × 55 mm, annealed at 900° C are consistent with the generation of an excess enthalpy of about 1 W during a 30 h period of electrolysis of deuterium oxide at a current density of 84 mA/cm 2. Sporadic flares in the count rates indicated by the neutron detector were observed in this experiment. They correspond to the emission of neutrons from the cell, in brief pulses leading to counts in 15 min intervals from 2 to 8 times (5 to 40 σ) higher than background. Some of the pulses have been shown to have extraneous causes. In the congruent experiments on the electrolysis of common water a heat balance was found that is satisfactory in terms of current theory, i.e., with no excess enthalpy. Two further experiments were made, at current densities of 104 and 115 mA/cm 2 respectively, the first of them with a cathode made of cold-worked palladium and the other with one made of palladium annealed at 800°C. Upward thermal ramps were observed in both of them. They occurred when deuterium oxide was added to the cells to make up the electrolyte to its initial volume. Because of an error in the temperature measurements, these experiments must be taken to be inconclusive as regards the magnitude of the enthalpy excess. It is concluded that the data from these experiments in part support the views advanced by Fleischmann and Pons, regarding anomalies arising in the electrolysis of deuterium oxide at palladium cathodes. It has not been possible to establish any consistent and reproducible pattern in the observations of excess enthalpy and neutron emission. The thermal and the radiation phenomena observed in this work are at a level very close to the limits of resolution of the apparatus used.

Responsibilities of the pathology laboratory

Current estimates suggest that the lifespan of humans can be 110 to 120 years, if extraneous causes of death are eliminated. The fact that present-day survival in the Western world averages only seven or eight decades suggests that intercurrent disease and injury are a major significant limitation of our existence. 1 In the broades t sense, these rema tu re deaths are the result ofenvironmental diseases derived from our surroundings. Our past successes as pathologists in defining the alterations in health have been most rewarding. One need only review the history of diseases such as tuberculosis to be impressed. Pathology, pathologists , and clinical l abora tory workers can make equally important contributions to our unders tanding of environmental disease. Our challenges are now more difficult and perhaps re- quire a broader approach, since etiologic factors are more variable and more diverse. Furthermore, these agents may interact with one another, potentiating or modifying the responses to each. The resultant disease processes are equally complex. A brief review of the development o f analysis of disease provides a background for what we can do. Perhaps the results of our current attention to environmental disease will match our success with microbial disease. eases, and the subsequent selection o f antibiotic therapy directed to the causative bacteria or fungi, const i tuted a major t r iumph in medicine and directed therapeutics. The careful search of diseased tissue p roduced immediate reward-d iagnoses as well as background information to select therapy. These successes also have indirectly established a philosophical approach that permeates current medical thinking. Inherent in this sequence is the suggestion that a factor or an agent produces a disease. For many illnesses, especially microbial, this is correct. The simplicity of this notion has made it popular; the frequency of its success in bacterial, fungal, and viral illness is striking. However, the universality of this notion is not so apparent, especially when nonmicrobial disease is considered. Adherence to these concepts, a simple cause-and-effect relationship, currently may be limiting our ability to interpret more complex disease etiologies and mechanisms and to explore new and intricate disease patterns. Evidence for more indirect interacting modalities o f disease production has become apparent.

Adjusting proportional mortality ratios for the influence of extraneous causes of death.

Proportional mortality ratios (PMRs) are frequently used where denominators of the population at risk are not available or are known to be seriously biased. The interpretation of proportional measures requires care and can be complicated by the fact that a PMR of a cause of interest may be affected by disproportionate mortality from one or more other causes of death. This problem is examined using occupational mortality data for England and Wales. A method of allowing for the influence of other causes of death on a PMR of interest is proposed and it is argued that this approach is a useful aid to the general interpretation of PMRs.

Improved agile notch adaptive equaliser

A major source of ‘outage’ in high-capacity digital radio-relay systems operating in the lower microwave bands is multipath propagation. Adaptive equalisation of the channel and other remedial measures such as the use of space diversity are often necessary for adequate system performance. A common type of adaptive frequency-domain equaliser employs a variable single-pole filter controlled by three fixed spectrum-sampling detectors. The effectiveness of this type is limited by extraneous causes of spectrum distortion such as tilts. The letter describes a new form of equaliser which searches for and equalises according to minima in the distorted spectrum and is insensitive to extraneous spectrum tilts.