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Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses., Highlights • In vitro expression of PRRSV nsp2TF/nsp2N affects cellular innate immune response. • Nsp2TF/nsp2N suppressed immune genes expression in PRRSV-infected cells. • Nsp2TF/nsp2N-deficient mutants showed attenuated growth in vivo. • Nsp2TF/nsp2N-deficient mutants induced augmented immune responses in infected pigs.

Objective This paper tests the validity of a simple and easy to use scale, the Modified Mini Screen (MMS) to identify people with mental health problems in the treatment ecology for chemical dependency, including specialty sector substance abuse treatment settings, and shelters, jails and street community outreach programs.

In the usual design and analysis of a phase II trial, there is no differentiation between complete response and partial response. Since complete response is considered more desirable this paper proposes a weighted score method which extends Simon's (1989) two-stage design to the situation where the complete and partial responses are differentiated. The weight assigned to the complete response is suggested by examining the likelihood ratio (LR) statistic for testing a simple hypothesis of a trinomial distribution. Both optimal and minimax designs are tabulated for a wide range of design parameters. The weighted score approach is shown to give more efficient designs, especially when the response probability is moderate to large.

Some parametric tests for comparing several treatments to a control are examined. Those tests developed earlier tend to rest on a single principle: Simplicity or power; those developed later attempt to fill the gap. We propose a new test that represents another such attempt. The basic idea is to find a simple statistic that is a good approximation to the likelihood ratio statistic. This leads to a power function similar to that of the likelihood ratio test, which is optimal among the available competitors. Like the orthogonal contrast test, the new test is built on an orthogonal relationship, resulting in a relatively simple null distribution that depends on the sample sizes only through their total. Thus critical values can be easily computed and a detailed listing results in only a moderately large table. Computing the statistic is elementary when the sample sizes of the new treatments are equal; otherwise, some matrix operations are needed. A simple procedure is given to estimate the sample si...

We consider the problem of optimally quantifying the categories of an ordered response variable under a linear model. The mathematical formulation leads to the maximization of a ratio of quadratic forms subject to linear inequality constraints. The solution is given by a hierarchical active constraints search algorithm. We prove that the algorithm converges to the global optimum.

The great impact of diabetes mellitus (DM) on the development of China economically and sociomedically was firstly recognized by knowing the overall prevalence of the disease being 0.67% in the whole country from a nationwide cooperative survey in 1980. Shortly after the cooperative survey an epidemiological study carried out in Chengdu yielded a prevalence in DM of 1.12%, which was almost double the overall prevalence and slightly higher than that of Beijing (1.10%)--the highest one among the 14 places in the cooperative study. Increasing prevalence of DM is a general trend. Over the past decade the incidence of diabetes in hospitalized patients at the First University Hospital, WCUMS, increased from 5.7 to 13.54 per thousand. Factors that fluence the increment of prevalence of DM include increase of total calorie intake (2680 kcal/day in 1990--close to the average world level), inappropriate high carbohydrate diet habit, change of life style, e.g. urbanization, mental stress, and ageing of the population. Primary and secondary care conducted in recent decades involve nutritional intervention, education via news media and workshop, foundation of prevention networks and providing better clinical and laboratory services, etc. Future improvement of diabetes care in this region is determined by activation of the public, motivation of the policy makers, more effective education and propagation by an influenced organization, fund support, man power and resources development, and domestic and international communications and collaborations.

A most vital edge of a graph (w.r.t. the spanning trees) is an edge whose deletion most drastically decreases the number of spanning trees. We present an algorithm for determining the most vital edges based on Kirchoff's matrix-tree theorem whose asymptotic time-complexity can be reduced to that of the fastest matrix multiplication routine, currently O(n/sup 2.376/). The foundation for this approach is a more general algorithm for directed graphs for counting the rooted spanning arborescences containing each of the arcs of a digraph. A network can be modeled as a probabilistic graph. Under one such model proposed by Kel'mans, the all-terminal network reliability, maximizing the number of spanning trees is critical to maximizing reliability when edges are very unreliable. For this model, the most vital edges characterize the locations where an improvement of the reliability of the link most improves the reliability of the network. >

The pool-adjacent-violators algorithm (PAVA) is an efficient algorithm which converges in a finite number of steps. However, it has been applicable so far only in isotonic regression with the simple order. This report extends its applicability to other quadratic programming problems, including certain one-sided multivariate testing problems and concave regression problems.

Sural nerve grafting for patients undergoing prostatectomy has been previously reported using open and minimally invasive methods. We report our experience with sural nerve grafting during robot-assisted laparoscopic radical prostatectomy (RLRP).Patients with preoperative potency and a minimum of 6 months follow-up were included in this prospective review. A total of 333 patients were identified between February 2003 and January 2006 who met these criteria including 22 of the 25 patients who underwent sural nerve grafting. Patients were divided into 5 groups to compare unilateral and bilateral sural nerve cohorts with non-nerve-sparing and unilateral and bilateral nerve-sparing groups. Patients were followed prospectively using health-related quality-of-life questionnaires.Twenty-two patients underwent sural nerve grafting that included three bilateral grafts. Mean follow-up was 14 months. There was no statistical difference in patients' ages, body mass index, preoperative prostate-specific antigen level, blood loss, complications, and positive margin rate. Operative time was statistically longer for both sural graft cohorts when compared with unilateral (without graft) and bilateral nerve sparing cohorts. No significant differences in subjective or objective sexual function, sexual bother, or urinary function were seen with 6 and 12 months follow-up, possibly related to smaller sural cohorts. Graft-related complications include leg pain in one patient.Sural nerve grafting during RLRP is technically feasible and safe and offers improved dexterity and visualization deep within the pelvis. However, a larger randomized cohort of patients will be required to validate any improved benefits afforded by the robot system.

We tested the hypothesis that first-trimester exposure to acute food deprivation is a risk factor for schizophrenia. A sharp and time-limited decline in the food intake of the Dutch population following a Nazi blockade in 1944 to 1945 created a unique if tragic natural experiment to test this hypothesis in three regions of Holland (west, north, and south). In the west, or famine region, birth cohorts exposed to severe food deprivation (an average daily ration under 4200 kJ) during the first trimester showed a substantial increase in hospitalized schizophrenia for women but not for men. Relative risks for women were 2.17 for "broad" and 2.56 for "restricted" schizophrenia. Moderate food deprivation during the first trimester (average daily ration under 6300 kJ) was not associated with increased risk of schizophrenia in the famine region. In the north and south regions, numbers were smaller and there was no exposure to severe famine. Birth cohorts exposed to moderate food deprivation during the first trimester showed a trend toward increased risk of schizophrenia for women. These findings give plausibility to the proposition that early prenatal nutrition can have a gender-specific effect on the risk of schizophrenia.

The authors compared the rates of treated mental illness among ethnically advantaged Ashkenazic Jews and ethnically disadvantaged Sephardic Jews in four areas of Jerusalem defined by socioeconomic status. They found that the rates of illness were higher in areas of lower socioeconomic status, that the Ashkenazim had higher rates of illness than the Sephardim in the areas of lower status, and that there was a comparatively high rate of illness among the Ashkenazim in the very religious Jewish neighborhoods. They interpret these findings on the basis of the theories of social causation and social selection, including genetic transmission.

This study relates inpatient-treated prevalence of the three mental illnesses most often requiring inpatient treatment--schizophrenia, alcoholism, and affective disorders--to social class in a suburban area. Rates were developed for the total population, including those living in domiciliary care, for those living in households only, and for first-admission patients living in households. Log-linear models supported the finding that low socioeconomic status was related to a high prevalence of alcoholism and affective disorders. In contrast, socioeconomic status was not related to the prevalence of schizophrenia among those living in households or among first-admission patients living in households.

A study of a cohort of 223 schizophrenic patients from a single catchment area followed up for two years after discharge from inpatient status revealed a significant association between the presence of two of 38 clinical problem categories (social withdrawal and drug abuse) and subsequent readmission. In addition, patients without social withdrawal who were readmitted showed a significantly greater use of aftercare services than those not readmitted, while, among those with social withdrawal, male patients were significantly more likely to be readmitted than female patients. Neither prior hospitalization nor the presence of affective symptoms were significantly associated with readmission. Clinical and research implications of these findings are discussed.

The relationship between mental illness and neoplastic disease has been the subject of controversy for decades. 1–3 Early studies using proportionate mortality rates (i.e., the proportion of cancer deaths to total deaths in a given population) were interpreted as evidence that psychotic patients have a significantly lower rate of cancer than the general population. 3–5 These studies have been extensively criticized on the grounds that since psychiatric patients tend to have increased mortality from a variety of causes (e.g., pneumonia) relative to the general population, if cancer mortality were more equal in incidence between patient and general population groups, the proportionate mortality data would spuriously suggest reduced cancer risk among patients. 4–6 Other reports using age specific or age adjusted mortality data, with three exceptions, 7–9 have indicated an equal or slightly increased incidence of cancer mortality among psychiatric patients as compared to the general population. 4–6,10–15 However, several of these studies have suggested that the relative risk of cancer is greater among female patients than among male patients, with male patients having relative risk equal to or less than the male general population. 11–13,15 In addition, a number of reports have commented that paranoid schizophrenics have an increased risk for cancer while other categories of schizophrenia are associated with reduced risk. 1,4,5 To our knowledge, this hypothesis has not been further replicated. To complicate the picture, recent reports have raised the question of whether neuroleptic treatment might predispose to breast cancer through its dopamine blocking effect of raising serum prolactin. 16,17 Virtually none of the studies examines cancer rates by age, sex, and diagnosis, however; thus there is little opportunity to identify more subtle trends. The present study, part of a larger study of mortality among psychiatric inpatients, provided the opportunity to investigate these issues in a relatively large sample.

In a previous study we showed that prenatal neuroleptic drug exposure has postnatal effects on children's growth (Platt et al., 1988). In the present study the effect of prenatal exposure to neuroleptic drugs on motor performance at birth, 8 months, 4 years and 7 years of age was examined in children of psychiatrically normal parents, and of parents with a history of psychiatric treatment, using-data from the Collaborative Perinatal Project of the National Institute of Neurological Diseases, Communicative Disorders and Stroke. The majority of the analyses were done using multiple logistic regression to control for possible confounding factors and to derive risk ratios. Some negative effects on motor behaviour were present in all groups at birth, most noticeably in the group of children who had been exposed to dopamine (DA)-depleting drugs. Negative effects were less prevalent at later ages, but were still present. The results are discussed in terms of possible mechanisms and methodological limitations.

Study of the sex ratio of mortality rates among three categories of long-term psychiatric inpatients suggests a trend toward equalization of death rates between the sexes by specific cause of death, given the constant inpatient environment. The most dramatic example of this equalization was the virtual parity of death rates for ischemic heart disease among younger schizophrenic patients of both sexes in contrast to a three- to fourfold male excess in the general population. An exception to this equalization was seen for neoplasm deaths, which showed a female excess in all three patient groups in contrast to the male excess seen in the general population. Further study of chronically hospitalized psychiatric patients seems indicated to delineate patterns of death associated with biologic variation in a relatively constant environment.

A logistic regression analysis of the association among specific causes of mortality and indices of psychotropic medication use was carried out among 722 psychiatric inpatient deaths and age, sex, diagnosis, and length of stay matched controls. Overall findings revealed remarkably few significant associations between death and drug use. Of the significant findings, an increased proportion of dead patients in three categories were using piperidine phenothiazines at death while young male patients dying of heart disease tended to be receiving significantly higher average daily doses of medications with strong anticholinergic effects than controls, often in combination. On the positive side, elderly living patients tended to be receiving tricyclic antidepressants for longer durations than controls for several death categories, suggesting a possible beneficial effect of medication use.

Analysis of cause-specific death rates among 750 elderly psychiatric inpatients revealed a markedly increased risk of death from pneumonia and a lesser but still substantial risk of death from cardiovascular disorders during the first year of hospitalization. Although the risks of cardiovascular death are considerably less among longer-stay patients, the pneumonia risks remain high. This suggests differing preventive strategies. To help prevent cardiovascular deaths, more attention should be paid to avoiding transfer trauma and its attendant stress. To help prevent pneumonia deaths, high priority should be given to an aggressive program of immunization, adequate nutrition, reduction of hospital overcrowding, and recognition of early pneumonia symptoms.

Recently, we identified a unique -2/-1 ribosomal frameshift mechanism in PRRSV, which yields two truncated forms of nonstructural protein (nsp) 2 variants, nsp2TF and nsp2N. Here, in vitro expression of individual PRRSV nsp2TF and nsp2N demonstrated their ability to suppress cellular innate immune responses in transfected cells. Two recombinant viruses were further analyzed, in which either nsp2TF was C-terminally truncated (vKO1) or expression of both nsp2TF and nsp2N was knocked out (vKO2). Host cellular mRNA profiling showed that a panel of cellular immune genes, in particular those involved in innate immunity, was upregulated in cells infected with vKO1 and vKO2. Compared to the wild-type virus, vKO1 and vKO2 expedited the IFN-α response and increased NK cell cytotoxicity, and subsequently enhanced T cell immune responses in infected pigs. Our data strongly implicate nsp2TF/nsp2N in arteriviral immune evasion and demonstrate that nsp2TF/nsp2N-deficient PRRSV is less capable of counteracting host innate immune responses.

• Comparison of age-adjusted death rates for inpatient and general populations from three pre-drug era and one post-drug era samples revealed a progressive decline in mortality that was most marked among elderly men. When length of stay was considered, the post-drug era sample showed a 30% reduction in mortality among patients hospitalized less than one year and a 50% reduction among longer-stay patients. The findings fail to support an increased mortality risk associated with the use of psychotropic drugs but dramatize the increased need for psychiatric services resulting from the increased survival of patients, especially those with long-term hospital stays.