Using intervention time series analyses to assess the effects of imperfectly identifiable natural events: a general method and example

Background  

Intervention time series analysis (ITSA) is an important method for analysing the effect of sudden events on time series data. ITSA methods are quasi-experimental in nature and the validity of modelling with these methods depends upon assumptions about the timing of the intervention and the response of the process to it.     

West Nile virus infection rates in Culex nigripalpus (Diptera: Culicidae) do not reflect transmission rates in Florida

We describe the first documented field transmission of West Nile (WN) virus by a North American mosquito. WN was first detected in northern Florida in 2001. An intensive mosquito trapping and surveillance program was conducted in this region for four nights to assess mosquito transmission of WN. Four mosquito traps, each with a single sentinel chicken, were placed at five different locations on each of four nights. A total of 11,948 mosquitoes was collected, and 14 mosquito pools were found to contain WN, giving a minimum infection rate between 1.08 and 7.54 per 1,000. Only one of the 80 sentinel chickens seroconverted to WN, demonstrating a single mosquito transmission event during the study and a mosquito transmission rate of between 0.8 and 1 per 1,000. Culex nigripalpus Theobald was responsible for WN transmission to the sentinel chicken, although both Cx. nigripalpus and Culex quinquefasciatus Say were found infected with WN. Mosquito transmission rates are reported in this study for the first time for a WN outbreak. This information is essential to determine risk of human and animal infection.     

Use of multiepitope polyproteins in serodiagnosis of active tuberculosis

Screening of genomic expression libraries from Mycobacterium tuberculosis with sera from tuberculosis (TB) patients or rabbit antiserum to M. tuberculosis led to the identification of novel antigens capable of detecting specific antibodies to M. tuberculosis. Three antigens, Mtb11 (also known as CFP-10), Mtb8, and Mtb48, were tested together with the previously reported 38-kDa protein, in an enzyme-linked immunosorbent assay (ELISA) to detect antibodies in TB patients. These four proteins were also produced as a genetically fused polyprotein, which was tested with two additional antigens, DPEP (also known as MPT32) and Mtb81. Sera from individuals with pulmonary and extrapulmonary TB, human immunodeficiency virus (HIV)-TB coinfections, and purified protein derivative (PPD)-positive and PPD-negative status with no evidence of disease were tested. In samples from HIV-negative individuals, the ELISA detected antibodies in >80% of smear-positive individuals and >60% smear-negative individuals, with a specificity of approximately 98%. For this group, smears detected 81.6% but a combination of smear and ELISA had a sensitivity of approximately 93%. The antigen combination detected a significant number of HIV-TB coinfections as well as antibodies in patients with extrapulmonary infections. Improved reactivity in the HIV-TB group was observed by including the antigen Mtb81 that was identified by proteomics. The data indicate that the use of multiple antigens, some of which are in a single polyprotein, can be used to facilitate the development of a highly sensitive test for M. tuberculosis antibody detection.     

The hippocampus is not necessary for a place response but may be necessary for pliancy

Rats with kainate-colchicine hippocampal lesions (HL) and controls (C) were initially trained in the Morris water maze with procedures that deterred their prepotent thigmotaxic response. Training began with an escape platform that occupied nearly the entire pool. The area to which the rats could escape was made smaller by substituting smaller platforms as training progressed. In contrast to standard procedures, HL rats and C rats showed comparable performance during acquisition and preferentially searched the goal quadrant on probe trials during which the platform was removed. In a follow-up experiment, the platform was moved to a random position along the wall, which required a switch to a thigmotaxic response for most effective escape. HL rats that were thigmotaxic before place training did not switch to a thigmotaxic response as readily as did controls, behavior consistent with the view that hippocampal damage reduces pliancy.     

Alcohol use following liver transplantation: a comparison of follow-up methods

Alcoholic cirrhosis is one of the most common indications for liver transplantation. Previous researchers have studied rates of return to drinking following transplantation, however, few have employed prospective measures of alcohol use. The authors prospectively studied the alcohol use of patients transplanted for alcoholic liver disease. The authors improved the accuracy of monitoring alcohol use by using various methods for tracking patient's alcohol consumption, and we report on the time to first alcohol use after transplantation comparing these different methods. The authors found that alcohol use can occur very early after transplantation, even within the first 3 months posttransplant. Thirty-eight percent of the patients consumed any alcohol after transplantation. The clinical interviews by the psychiatrist were the most successful method for identifying posttransplant alcohol use. Posttransplant alcohol use was significantly associated with prior nonalcohol substance use (P < 0.025), family history of alcoholism in a first-degree relative (P < 0.025), and prior alcohol rehabilitation experience (P < 0.05) but not with a prior psychiatric history or less than 6 months of pretransplant sobriety. The authors indicate that prospective monitoring, using a combination of methods, is the most accurate approach to identify alcohol consumption. With this type of accuracy, risk factors can be identified and alcohol use can be compared with alcohol-related morbidity posttransplant.     

The Role of Telehealth in Sideline Management of Sports-Related Injuries

The COVID-19 pandemic has affected the ability of the sports medicine physician to be present to participate in in-person sideline evaluation of the injured athlete. The purpose of this review is to assess existing literature regarding the utilization of telehealth for sideline evaluation and management of the injured athlete, as well as to identify further areas of research. With the rapid incorporation of telehealth visits, the utilization and capabilities of telemedicine continue to expand. A number of evidence-based resources are available to support medical providers to develop and utilize video evaluation for the sideline evaluation of sports-related injuries. Future research, including the development of validated, modified examination techniques and technologies, will allow for improved interactive physical examinations, which may be better utilized for sideline evaluation.     

E-cadherin expression in prostate cancer: a broad survey using high-density tissue microarray technology

E-cadherin is a calcium 2+-dependent cell-adhesion molecule that determines epithelial development in the embryo and maintains adult differentiated epithelium and homeostasis. Aberrant or decreased expression has been reported to be associated with prostate carcinoma progression. The degree of E-cadherin expression in prostate cancer remains controversial. Some studies have reported decreased expression of E-cadherin as tumors advance and metastasize. Other studies have not demonstrated this relationship. To address these variations, we undertook a study to systematically evaluate E-cadherin expression in a broad range of prostate tissue. Benign prostate, clinically localized prostate cancer, and hormone-refractory metastatic prostate cancer were analyzed under uniform conditions using high-density tissue microarrays (TMA). Formalin-fixed, paraffin-embedded prostate carcinoma from men with clinically localized prostate carcinoma and autopsy material from men who died of widely metastatic, hormone-refractory prostate carcinoma were arrayed into 6 high-density TMA blocks. Benign and atrophic prostate tissue and high-grade prostatic intraepithelial neoplasia (PIN) were also included from the clinically localized cases. Immunohistochemistry was performed using the immunoglobulin G1 mouse monoclonal antibody (HECD-1; Zymed, San Francisco, CA). Membranous staining was recorded as low (aberrant) or high (normal). E-cadherin expression was considered aberrant if less than 70% of the cells had strong membranous staining. A total of 1,220 prostate TMA samples were analyzed. High (normal) E-cadherin expression was seen in 87% of 757 benign, 80% of 41 high-grade PIN, 82% of 325 prostate carcinoma and 90% of 97 hormone-refractory prostate carcinoma TMA samples. Mean E-cadherin expression was determined for each of the 128 clinically localized prostate cancer cases. Aberrant E-cadherin expression showed a statistical trend toward an association with positive surgical margins (P =.012), higher Gleason score (P =.18), and prostate-specific antigen (PSA) failure (Kaplan-Meier analysis, log-rank P =.09). There was a statistically significant association between aberrant E-cadherin expression and larger tumor size (P =.01). No significant associations were seen with extraprostatic extension and seminal vesicle invasion. The current study shows a broad-spectrum approach to evaluating E-cadherin protein expression in prostate carcinoma. Clinically localized prostate tumors, treated with surgery alone, show a high level of E-cadherin expression. Aberrant expression was identified in tumors with positive surgical margins, higher Gleason score, and a higher rate of PSA failure. However, these trends were not statistically significant. A statically significant association between aberrant E-cadherin expression and larger tumor size was identified. In the metastatic hormone-refractory prostate tumors, E-cadherin expression was vastly expressed, and only rare cases had aberrant expression. Therefore, the findings of this study are most consistent with a transient down-regulation of E-cadherin in localized prostate cancer. Metastatic prostate cancer shows strong E-cadherin expression as determined by anti-E-cadherin antibody HECD-1.