High-resolution acoustic ejection mass spectrometry for high-throughput library screening.

An approach is described for high-throughput quality assessment of drug candidate libraries using high-resolution acoustic ejection mass spectrometry (AEMS). Sample introduction from 1536-well plates is demonstrated for this application using 2.5 nL acoustically dispensed sample droplets into an Open Port Interface (OPI) with pneumatically assisted electrospray ionization at a rate of one second per sample.

Development of a high-throughput dual-stream liquid chromatography-tandem mass spectrometry method to screen for inhibitors of glutamate carboxypeptidase II.

Rationale: Glutamate carboxypeptidase II (GCPII) catalyzes the hydrolysis of N-acetylaspartylglutamate (NAAG) to yield glutamate (Glu) and N-acetylaspartate (NAA). Inhibition of GCPII has been shown to remediate the neurotoxicity of excess Glu in a variety of cell and animal disease models. A robust high-throughput liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was needed to quantify GCPII enzymatic activity in a biochemical high-throughput screening assay.

Target Class Profiling of Small-Molecule Methyltransferases.

Target class profiling (TCP) is a chemical biology approach to investigate understudied biological target classes. TCP is achieved by developing a generalizable assay platform and screening curated compound libraries to interrogate the chemical biological space of members of an enzyme family. In this work, we took a TCP approach to investigate inhibitory activity across a set of small-molecule methyltransferases (SMMTases), a subclass of methyltransferase enzymes, with the goal of creating a launchpad to explore this largely understudied target class.

Parent-Researcher Perspectives on Role Intersectionality Related to Autism Research.

Although parents of children with autism who are also experts in a related profession have been instrumental in shaping current practices, there is little known about parent-researchers and the benefits and obstacles to including individuals with these intersectional identities on autism focused research teams. The following study used collaborative autoethnographies from three parent-researchers hired for a large scale, federally funded project. The parent-researchers, and co-authors, collaborated on all phases of the reported study.

Reinspection of a Clinical Proteomics Tumor Analysis Consortium (CPTAC) Dataset with Cloud Computing Reveals Abundant Post-Translational Modifications and Protein Sequence Variants.

The Clinical Proteomic Tumor Analysis Consortium (CPTAC) has provided some of the most in-depth analyses of the phenotypes of human tumors ever constructed. Today, the majority of proteomic data analysis is still performed using software housed on desktop computers which limits the number of sequence variants and post-translational modifications that can be considered. The original CPTAC studies limited the search for PTMs to only samples that were chemically enriched for those modified peptides.

Prenatal HIV testing in Wisconsin: results of a survey among women who gave birth in 2003.

Since 1995 the United States Public Health Service has recommended voluntary prenatal human immunodeficiency virus (HIV) testing for all pregnant women in the United States. To better understand how well this goal is being met in Wisconsin, the Wisconsin Division of Public Health facilitated a review of hospital medical records for a random sample of women who gave birth in Wisconsin in 2003. Of the 968 maternal medical records reviewed, 68% (95% CI: 65%-71%) showed evidence that the mother had a completed HIV antibody test during pregnancy.

Wisconsin trends in pneumonia and influenza mortality, 1980-2003.

Introduction: Mortality due to pneumonia and influenza continues to be a serious public health threat, especially among those aged > or = 65. Continued monitoring of these high-risk populations is necessary for evaluating the impact of public health prevention activities, determining vaccine distribution policies, and ensuring that existing guidelines reflect the populations at risk.

Objectives: We characterized pneumonia and influenza mortality in Wisconsin from 1980 to 2003, including trend analysis, identification of high risk populations, and assessment of Wisconsin's progress toward state and national goals for vaccination.

Epidemiologic trends in infection, mortality, and transplants related to hepatitis C in Wisconsin.

Hepatitis C virus (HCV) infection is the most common chronic bloodborne infection in the United States. An estimated 3.9 million persons nationally and 85,000 persons in Wisconsin are currently infected.

Reductions in transmission risk behaviors in HIV-positive clients receiving prevention case management services: findings from a community demonstration project.

Prevention case management (PCM) for HIV-infected persons is an HIV risk reduction intervention designed to assist clients who are aware of their HIV infection and who continue to engage in risk transmission behaviors. PCM combines individual risk reduction counseling with case management to address the psychosocial factors affecting HIV transmission. More than 350 HIV-positive clients participated in PCM in Wisconsin between 2000 and 2003, and 109 completed both baseline and follow-up risk assessments.

Modification of Subdural Catheters for Long-Term Intracranial Pressure Monitoring of Conscious Rabbits.

Intracranial pressure monitoring of conscious rabbits poses major technical problems. Although surgical implantation of epidural, subdural, or parenchymal catheters is usually straightforward, the maintenance of such systems after surgery can be difficult. A simple and effective method of subdural intracranial pressure monitoring that used a modified catheter is described.

HIV infection in Wisconsin: an overview of epidemiologic trends, 1983-1999.

A review of HIV case surveillance data shows that the number of persons reported with HIV infection in Wisconsin steadily increased during the 1980s, leveled in the early 1990s and since 1993 has tended to decline. Cases reported in 1999 represented a 44% decrease compared to the 1990-1993 average. The number of deaths among persons with HIV infection declined 64% from 1993 to 1999; as a result, the number of persons living with HIV infection nearly doubled during the 1990s.

HIV seropositivity rates in outreach-based counseling and testing services: program evaluation.

A common assumption is that outreach-based HIV counseling and testing services reach a clientele with a higher HIV seroprevalence than clinic-based counseling and testing. To examine this assumption, we analyzed Wisconsin's anonymous counseling and testing client records for 62,299 contacts (testing episodes) from 1992 to 1995. Bivariate analysis of counseling and testing service setting (outreach-based or clinic-based) and HIV test results suggested that outreach contacts were 23% (odds ratio [OR], 1.

HIV seroprevalence among male prison inmates in the Wisconsin Correctional System.

Objective: To estimate HIV seroprevalence and the acceptance of voluntary HIV testing among male inmates entering the Wisconsin Correctional System during July 1, 1994-June 30, 1995, and compare these estimates with similar data obtained in 1987-1988.

Methods: A blinded HIV seroprevalence survey concurrent with a review of voluntary HIV antibody testing records.

Results: HIV test results were obtained for 3,681 (89%) male prison entrants during the study period; 26 (0.

Cryptosporidiosis-associated mortality following a massive waterborne outbreak in Milwaukee, Wisconsin.

Objectives: This study estimated the magnitude of cryptosporidiosis-associated mortality in the Milwaukee vicinity for 2 years following a massive waterborne outbreak.

Methods: Death certificates were reviewed.

Results: During approximately 2 years before the outbreak, cryptosporidiosis was listed as an underlying or contributing cause of death on the death certificates of four Milwaukee-vicinity residents.

Clinical and epidemiologic features of a massive waterborne outbreak of cryptosporidiosis in persons with HIV infection.

During March and April 1993, a massive outbreak of Cryptosporidium infection resulted from contamination of the public water supply in Milwaukee, Wisconsin. The health impact of this outbreak in HIV-infected persons was unknown but was perceived as severe. We surveyed HIV-infected persons who resided in the greater Milwaukee area to examine the acute health impact of cryptosporidiosis on this population.

Setting standards for the Wisconsin HIV Counseling and Testing Program: an application of threshold analysis.

Human immunodeficiency virus (HIV) counseling and testing (CT) services are an important component of any comprehensive HIV prevention program. Because resources are limited and must be used wisely, it is important to determine if the expenditures on CT services are sufficiently effective that they might be considered cost-saving or cost-effective to society. The policy analysis technique of "threshold analysis" was employed to determine how many HIV infections the publicly funded Wisconsin CT program would have to prevent in order to be considered cost-saving or cost-effective.

Massive outbreak of waterborne cryptosporidium infection in Milwaukee, Wisconsin: recurrence of illness and risk of secondary transmission.

Contamination of the public water supply in Milwaukee during March and April 1993 resulted in a massive outbreak of cryptosporidium infection. We investigated the clinical and epidemiological features of visitors to the Milwaukee area in whom cryptosporidiosis developed, and we conducted a telephone survey of Milwaukee County households to evaluate the risk of recurrent illness and secondary transmission. Cryptosporidium infection during this outbreak generally seemed more severe than cases described in previous reports of large case series.

A massive outbreak in Milwaukee of cryptosporidium infection transmitted through the public water supply.

Background: Early in the spring of 1993 there was a widespread outbreak of acute watery diarrhea among the residents of Milwaukee.

Methods: We investigated the two Milwaukee water-treatment plants, gathered data from clinical laboratories on the results of tests for enteric pathogens, and examined ice made during the time of the outbreak for cryptosporidium oocysts. We surveyed residents with confirmed cryptosporidium infection and a sample of those with acute watery diarrhea consistent with cryptosporidium infection.

HIV seroprevalence among patients attending a Milwaukee clinic for sexually transmitted diseases: findings from four annual surveys, 1988-1991.

Blinded HIV seroprevalence surveys were conducted annually from 1988 through 1991 among patients at a Milwaukee sexually transmitted disease (STD) clinic. Among 5,295 patients tested, 70 (1.3%) were HIV-1 Western blot positive.

Improving estimates of HIV-1 seroprevalence among childbearing women: use of smaller blood spots.

Objectives: Nationwide, human immunodeficiency virus type 1 (HIV-1) seroprevalence surveys using dried neonatal blood specimens are critical to estimating HIV-1 seroprevalence among childbearing women. However, the noninclusion of blood specimens deemed "quantity not sufficient" (QNS) for HIV-1 antibody testing potentially introduces bias. In Wisconsin beginning in 1990, we modified the survey protocol to reduce QNS rates and assess bias introduced by QNS specimens.

HIV-1 among childbearing women and newborns in Wisconsin.

To estimate the prevalence of antibody to human immunodeficiency virus-type 1 (HIV-1) among Wisconsin childbearing women (CBW), a continuous blinded HIV-1 seroprevalence survey is being conducted. This survey uses dried blood specimens obtained from infants as part of the Wisconsin Newborn Screening Program. From February 1989 through March 1990, 79,546 specimens from Wisconsin residents were tested for HIV-1 antibody, 21 (0.

HIV seroprevalence and the acceptance of voluntary HIV testing among newly incarcerated male prison inmates in Wisconsin.

In 1986-88, voluntary and blinded HIV testing was conducted among Wisconsin male prison entrants. The HIV seroprevalence was 0.30 percent in 1986, 0.

AIDS and HIV in Wisconsin: projections for the decade.

Based on a projection model developed by the Wisconsin AIDS/HIV Program, at the beginning of 1990 there were between 7,143 and 11,957 HIV-infected persons in Wisconsin. During the 1990s the cumulative number of HIV-infected persons in the state may more than double to between 16,471 and 25,932. We project that between 6,329 and 9,489 new cases of acquired immunodeficiency syndrome (AIDS), and between 3,577 and 5,365 AIDS deaths will occur in Wisconsin in next ten years.