Protecting residential care facilities from pandemic influenza.

It is widely believed that protecting health care facilities against outbreaks of pandemic influenza requires pharmaceutical resources such as antivirals and vaccines. However, early in a pandemic, vaccines will not likely be available and antivirals will probably be of limited supply. The containment of pandemic influenza within acute-care hospitals anywhere is problematic because of open connections with communities. However, other health care institutions, especially those providing care for the disabled, can potentially control community access. We modeled a residential care facility by using a stochastic compartmental model to address the question of whether conditions exist under which nonpharmaceutical interventions (NPIs) alone might prevent the introduction of a pandemic virus. The model projected that with currently recommended staff-visitor interactions and social distancing practices, virus introductions are inevitable in all pandemics, accompanied by rapid internal propagation. The model identified staff reentry as the critical pathway of contagion, and provided estimates of the reduction in risk required to minimize the probability of a virus introduction. By using information on latency for historical and candidate pandemic viruses, we developed NPIs that simulated notions of protective isolation for staff away from the facility that reduced the probability of bringing the pandemic infection back to the facility to levels providing protection over a large range of projected pandemic severities. The proposed form of protective isolation was evaluated for social plausibility by collaborators who operate residential facilities. It appears unavoidable that NPI combinations effective against pandemics more severe than mild imply social disruption that increases with severity.

The Japanese experience with vaccinating schoolchildren against influenza.

BACKGROUND: Influenza epidemics lead to increased mortality, principally among elderly persons and others at high risk, and in most developed countries, influenza-control efforts focus on the vaccination of this group. Japan, however, once based its policy for the control of influenza on the vaccination of schoolchildren. From 1962 to 1987, most Japanese schoolchildren were vaccinated against influenza. For more than a decade, vaccination was mandatory, but the laws were relaxed in 1987 and repealed in 1994; subsequently, vaccination rates dropped to low levels. When most schoolchildren were vaccinated, it is possible that herd immunity against influenza was achieved in Japan. If this was the case, both the incidence of influenza and mortality attributed to influenza should have been reduced among older persons. METHODS: We analyzed the monthly rates of death from all causes and death attributed to pneumonia and influenza, as well as census data and statistics on the rates of vaccination for both Japan and the United States from 1949 through 1998. For each winter, we estimated the number of deaths per month in excess of a base-line level, defined as the average death rate in November. RESULTS: The excess mortality from pneumonia and influenza and that from all causes were highly correlated in each country. In the United States, these rates were nearly constant over time. With the initiation of the vaccination program for schoolchildren in Japan, excess mortality rates dropped from values three to four times those in the United States to values similar to those in the United States. The vaccination of Japanese children prevented about 37,000 to 49,000 deaths per year, or about 1 death for every 420 children vaccinated. As the vaccination of schoolchildren was discontinued, the excess mortality rates in Japan increased. CONCLUSIONS: The effect of influenza on mortality is much greater in Japan than in the United States and can be measured about equally well in terms of deaths from all causes and deaths attributed to pneumonia or influenza. Vaccinating schoolchildren against influenza provides protection and reduces mortality from influenza among older persons.

Fc-receptor for mouse IgG1 (Fc gamma RII) and antibody-mediated cell clearance in patients treated with Leu2a antibody.

A pilot study was performed to explore the clinical potential of Leu2a antibody in reversing acute renal allograft rejection. Anti-Leu2a, a murine IgG1 monoclonal antibody (mIgG1 mAb), is specific for the CD8 molecule that is expressed in high density on class I reactive T cells. Of the 6 recipients treated with anti-Leu2a, two responded with a complete reversal of rejection with long-term allograft function maintained for over a year. In two other recipients, acute rejection was initially reversed, but later rejection episodes resulted in allograft failure at 2-3 months posttreatment. Rejection in the two other recipients showed no response to Leu2a mAb treatment. Specific depletion of peripheral blood CD8+ cells occurred in four of the six recipients. Even in this small series, it was evident that cell clearance was neither necessary nor sufficient for reversal of rejection. However, a complete correspondence between cell clearance and the ability of the recipients' mononuclear cells to undergo mitogenic response to the mIgG1 anti-CD3 (Leu4) mAb in vitro was noted. Binding of IgG1 mAb to the Fc-receptor (Fc gamma RII/CD32) expressed on blood monocytes is known to be essential for the T cell mitogenic response to soluble mIgG1 CD3 mAb in vitro. Our data suggest that binding to Fc gamma RII may be an essential step in the process of mIgG1 Leu2a mAb-mediated cell clearance in vivo.

Differentiation between essential thrombocythemia and polycythemia vera with marked thrombocytosis.

Accurate distinction between essential thrombocythemia and thrombocytotic polycythemia vera requires determination of the red cell mass in the presence of adequate iron stores, but this is not always possible. We therefore compared the clinical and laboratory features at the time of presentation of 50 patients with unequivocal essential thrombocythemia and 27 patients with thrombocytotic polycythemia vera. Univariate analysis failed to identify any single parameter capable of reliably separating the groups. A logistic regression algorithm incorporating hematocrit, white cell count, and spleen size markedly increased the diagnostic accuracy (92%) compared with predictions based on the hematocrit alone (52%). The algorithm's usefulness for patients with intermediate hematocrits was confirmed by analysis of independent samples of essential thrombocythemia and thrombocytotic polycythemia vera patients, and also by analysis of patients with probable essential thrombocythemia in whom the diagnosis could not be confirmed because of inadequate exclusion of polycythemia vera. Furthermore, comparison of survival data suggests that differentiating these disorders is prognostically important. The algorithm is recommended as an alternate method for differentiating essential thrombocythemia from thrombocytotic polycythemia vera whenever the red cell mass is unavailable or iron deficiency cannot be excluded.

The phenotypic diversity of peripheral T-cell lymphomas: the Southeastern Cancer Study Group experience.

Four member institutions of the Southeastern Cancer Study Group (SECSG) investigated 27 cases of malignant lymphoma proved to be of T-cell origin by a frozen section immunoperoxidase technique. The specimens were sent to one central laboratory in Michel's transport medium, where phenotyping studies were performed with a large number of monoclonal antibodies. The phenotypes encountered differed as a group from that reported for lymphoblastic lymphoma, but there was significant diversity within the peripheral T-cell lymphomas. Most tumors were of a mature helper/inducer phenotype (Leu-3+, Leu-2-), but nine of the 27 lymphomas expressed Leu-3 and Leu-2 in other combinations. Half of the lymphomas expressed abnormal T-cell phenotypes in that one or more pan-T-cell markers usually present in nonneoplastic T-cell proliferations were absent. Antibody 3A1 was the pan-T marker that was most frequently lacking in the peripheral T-cell lymphomas. The tumors were also studied for their expression of three markers associated with T-cell activation--HLA-DR, transferrin receptor, and interleukin 2 receptor. The majority of the lymphomas expressed one or more activation markers. However, these three markers appear to be expressed independently. In general, there was no simple correlation between the phenotype of the tumor and the histologic appearance, although neoplasms of morphologically higher grades were somewhat more likely to express T-cell activation markers.

Regression models for prognostic prediction: advantages, problems, and suggested solutions.

Multiple regression models have wide applicability in predicting the outcome of patients with a variety of diseases. However, many researchers are using such models without validating the necessary assumptions. All too frequently, researchers also "overfit" the data by developing models using too many predictor variables and insufficient sample sizes. Models developed in this way are unlikely to stand the test of validation on a separate patient sample. Without attempting such a validation, the researcher remains unaware that overfitting has occurred. When the ratio of the number of patients suffering endpoints to the number of potential predictors is small (say less than 10), data reduction methods are available that can greatly improve the performance of regression models. Regression models can make more accurate predictions than other methods such as stratification and recursive partitioning, when model assumptions are thoroughly examined; steps are taken (ie, choosing another model or transforming the data) when assumptions are violated; and the method of model formulation does not result in overfitting the data.

Spatial summation effects on two-component grating thresholds.

Some experimental studies of subthreshold summation between sinusoidal grating components have been interpreted as showing very narrow channel bandwidths in human visions. This paper discusses an alternative interpretation of these experiments based on consideration of probability-summation effects among spatially distributed detectors. We conclude that frequency-selective channels must still be hypothesized in order to fit the data, but the channel bandwidth may be much wider than earlier interpretations suggest.

Molecular evolution as a process of message refinement.

Amino acid sequences are often said to code for proteins. Taking that statement literally, we propose a methodology in which protein sequences appear as messages and as such are amenable to the techniques of signal analysis. Not only does this view of amino acid sequences as messages appear to be tenable, but the clarity of expression of these sequences seems to increase, i.e., the noisiness decreases, consonant with notions of ascendancy in the hierarchy of morphological taxonomy.