Adjusting a cancer mortality-prediction model for disease status-related eligibility criteria

<p>Abstract</p> <p>Background</p> <p>Volunteering participants in disease studies tend to be healthier than the general population partially due to specific enrollment criteria. Using modeling to accurately predict outcomes of cohort studies enrolling volunteers requires adjusting for the bias introduced in this way. Here we propose a new method to account for the effect of a specific form of healthy volunteer bias resulting from imposing disease status-related eligibility criteria, on disease-specific mortality, by explicitly modeling the length of the time interval between the moment when the subject becomes ineligible for the study, and the outcome.</p> <p>Methods</p> <p>Using survival time data from 1190 newly diagnosed lung cancer patients at MD Anderson Cancer Center, we model the time from clinical lung cancer diagnosis to death using an exponential distribution to approximate the length of this interval for a study where lung cancer death serves as the outcome. Incorporating this interval into our previously developed lung cancer risk model, we adjust for the effect of disease status-related eligibility criteria in predicting the number of lung cancer deaths in the control arm of CARET. The effect of the adjustment using the MD Anderson-derived approximation is compared to that based on SEER data.</p> <p>Results</p> <p>Using the adjustment developed in conjunction with our existing lung cancer model, we are able to accurately predict the number of lung cancer deaths observed in the control arm of CARET.</p> <p>Conclusions</p> <p>The resulting adjustment was accurate in predicting the lower rates of disease observed in the early years while still maintaining reasonable prediction ability in the later years of the trial. This method could be used to adjust for, or predict the duration and relative effect of any possible biases related to disease-specific eligibility criteria in modeling studies of volunteer-based cohorts.</p

PAUSED for thought? Using verbal protocol analysis to understand the situational and temporal cues in the decision-making of residential burglars

Using verbal protocol analysis (VPA) alongside semi-structured interviews, this research aimed to explicate the situational dynamics that inform the decision-making and target selection of residential burglars. Focusing on the VPA method, novel to criminological research, the paper considers the contribution of this empirical approach for studying the decision-making of offenders in situ. The findings reveal a series of cues, encapsulated in the ‘PAUSED’ model, that are drawn upon by residential burglars to assess the suitability of a target; determining whether it is profitable, accessible, uninterruptible, surveillable, escapable and/or dishonourable. The PAUSED model is unpacked to articulate a collection of visual stimuli that serve to disrupt and suspend the otherwise rapid flow of target appraisal. Discussion of the strengths and limitations of the VPA method, and how it can compliment other approaches to understanding the decision-making of residential burglars, is provided

Surface pretreatment for prolonged survival of cemented tibial prosthesis components: full- vs. surface-cementation technique

BACKGROUND: One of few persisting problems of cemented total knee arthroplasty (TKA) is aseptic loosening of tibial component due to degradation of the interface between bone cement and metallic tibial shaft component, particularly for surface cemented tibial components. Surface cementation technique has important clinical meaning in case of revision and for avoidance of stress shielding. Degradation of the interface between bone cement and bone may be a secondary effect due to excessive crack formation in bone cement starting at the opposite metallic surface. METHODS: This study was done to prove crack formation in the bone cement near the metallic surface when this is not coated. We propose a newly developed coating process by PVD layering with SiO(x )to avoid that crack formation in the bone cement. A biomechanical model for vibration fatigue test was done to simulate the physiological and biomechanical conditions of the human knee joint and to prove excessive crack formation. RESULTS: It was found that coated tibial components showed a highly significant reduction of cement cracking near the interface metal/bone cement (p < 0.01) and a significant reduction of gap formation in the interface metal-to-bone cement (p < 0.05). CONCLUSION: Coating dramatically reduces hydrolytic- and stress-related crack formation at the prosthesis interface metal/bone cement. This leads to a more homogenous load transfer into the cement mantle which should reduce the frequency of loosening in the interfaces metal/bone cement/bone. With surface coating of the tibial component it should become possible that surface cemented TKAs reveal similar loosening rates as TKAs both surface and stem cemented. This would be an important clinical advantage since it is believed that surface cementing reduces metaphyseal bone loss in case of revision and stress shielding for better bone health

Mapping oral health related quality of life to generic health state values

BACKGROUND: A summary utility index is useful for deriving quality-adjusted life years (QALY) for cost analyses or disability weights for burden of disease studies. However, many quality of life instruments provide descriptive profiles rather than a single utility index. Transforming quality of life instruments to a utility index could extend the use of quality of life instruments to costs analyses and burden of disease studies. The aims of the study were to map a specific oral health measure, the Oral Health Impact Profile to a generic health state measure, the EuroQol, in order to enable the estimation of health state values based on OHIP data. METHODS: Data were collected from patients treated by a random sample of South Australian dentists in 2001–02 using mailed self-complete questionnaires. Dentists recorded the diagnosis of dental conditions and provided patients with self-complete questionnaires to record the nature, severity and duration of symptoms using the EuroQol (EQ-5D) and 14-item version of the Oral Health Impact Profile (OHIP-14) instruments. Data were available from 375 patients (response rate = 72%). A random two-thirds sample of patients was used in tobit regressions of EQ-5D health state values estimated using OHIP-14 in a model with categories of OHIP responses as indicator variables and in a model with OHIP responses as continuous variables. Age and sex were included as covariates in both models. The remaining one-third sample of patients was used to test the models. RESULTS: The OHIP item 'painful aching in mouth' was significantly related to health state values in both models while 'life less satisfying' was also significant in the continuous model. Mean forecast errors relative to the mean observed health state value were higher when fitted to the categorical model (17.4%) compared to the continuous model (15.2%) (P < 0.05). CONCLUSION: The findings enable health state values to be derived from OHIP-14 scores for populations where utility has not or cannot be measured directly

Characterization of Cholinesterases in Plasma of Three Portuguese Native Bird Species: Application to Biomonitoring

Over the last decades the inhibition of plasma cholinesterase (ChE) activity has been widely used as a biomarker to diagnose organophosphate and carbamate exposure. Plasma ChE activity is a useful and non-invasive method to monitor bird exposure to anticholinesterase compounds; nonetheless several studies had shown that the ChE form(s) present in avian plasma may vary greatly among species. In order to support further biomonitoring studies and provide reference data for wildlife risk-assessment, plasma cholinesterase of the northern gannet (Morus bassanus), the white stork (Ciconia ciconia) and the grey heron (Ardea cinerea) were characterized using three substrates (acetylthiocholine iodide, propionylthiocholine iodide, and S-butyrylthiocholine iodide) and three ChE inhibitors (eserine sulphate, BW284C51, and iso-OMPA). Additionally, the range of ChE activity that may be considered as basal levels for non-exposed individuals was determined. The results suggest that in the plasma of the three species studied the main cholinesterase form present is butyrylcholinesterase (BChE). Plasma BChE activity in non-exposed individuals was 0.48±0.11 SD U/ml, 0.39±0.12 SD U/ml, 0.15±0.04 SD U/ml in the northern gannet, white stork and grey heron, respectively. These results are crucial for the further use of plasma BChE activity in these bird species as a contamination bioindicator of anti-cholinesterase agents in both wetland and marine environments. Our findings also underscore the importance of plasma ChE characterization before its use as a biomarker in biomonitoring studies with birds

Detection of Melanoma Nodal Metastases; Differences in Detection Between Elderly and Younger Patients Do Not Affect Survival

Background. Melanoma lymph nodes metastases may be detected by patients or by physicians. Understanding the outcomes of self-detection or physician detection is essential for the design of follow-up studies. We evaluated the role of the method of detection in nodal disease in the prognosis of melanoma patients who underwent therapeutic lymph node dissection (TLND). Materials and Methods. All melanoma patients with palpable lymph nodes were included in a prospective database (n = 98), and the method of detection was recorded. Detection of lymph node metastases compared with pathological findings in the TLND was assessed by multivariate logistic regression. Disease-free survival (DFS) and disease-specific survival (DSS) were assessed by univariate and multivariate Cox proportional hazard analysis. Results. Nodal metastases were detected by physicians in 45% and by patients in 55% (P <0.001). Age was significantly associated with method of detection. Patients 60 years (odds ratio [OR] 0.3; P = 0.007). However, this was not associated with prognostic findings in TLND, number of positive nodes, tumor size, or extranodal spread. Method of detection or age at the time of nodal metastases was not significantly associated with 2-year DFS or DSS. Conclusions. 45% of all lymph node metastases in stage I-II melanoma patients are physician detected. Younger patients detect their own lymph node metastases significantly more often than elderly patients. However, neither the method of detection nor age correlates with DSS. More frequent follow-up would not alter DFS and DSS significantly

An Epididymis-Specific Secretory Protein HongrES1 Critically Regulates Sperm Capacitation and Male Fertility

Mammalian sperm capacitation is an essential prerequisite to fertilizion. Although progress had been made in understanding the physiology and biochemistry of capacitation, little is known about the potential roles of epididymal proteins during this process. Here we report that HongrES1, a new member of the SERPIN (serine proteinase inhibitor) family exclusively expressed in the rat cauda epididymis and up-regulated by androgen, is secreted into the lumen and covers the sperm head. Co-culture of caudal sperms with HongrES1 antibody in vitro resulted in a significant increase in the percentage of capacitated spermatozoa. Furthermore, the percentage of capacitated spermatozoa clearly increased in rats when HongrES1 was down-regulated by RNAi in vivo. Remarkably, knockdown of HongrES1 in vivo led to reduced fertility accompanied with deformed appearance of fetuses and pups. These results identify HongrES1 as a novel and critical molecule in the regulation of sperm capacitation and male fertility