Unrestricted Population Research Articles

Application of information from external data to correct for collider bias in a Covid-19 hospitalised cohort

BackgroundThroughout the Covid-19 pandemic, researchers have made use of electronic health records to research this disease in a rapidly evolving environment of questions and discoveries. These studies are prone to collider bias as they restrict the population of Covid-19 patients to only those with severe disease. Inverse probability weighting is typically used to correct for this bias but requires information from the unrestricted population. Using electronic health records from a South London NHS trust, this work demonstrates a method to correct for collider bias using externally sourced data while examining the relationship between minority ethnicities and poor Covid-19 outcomes.MethodsThe probability of inclusion within the observed hospitalised cohort was modelled based on estimates from published national data. The model described the relationship between patient ethnicity, hospitalisation, and death due to Covid-19 – a relationship suggested to be susceptible to collider bias. The obtained probabilities (as applied to the observed patient cohort) were used as inverse probability weights in survival analysis examining ethnicity (and covariates) as a risk factor for death due to Covid-19.ResultsWithin the observed cohort, unweighted analysis of survival suggested a reduced risk of death in those of Black ethnicity – differing from the published literature. Applying inverse probability weights to this analysis amended this aberrant result to one more compatible with the literature. This effect was consistent when the analysis was applied to patients within only the first wave of Covid-19 and across two waves of Covid-19 and was robust against adjustments to the modelled relationship between hospitalisation, patient ethnicity, and death due to Covid-19 made as part of a sensitivity analysis.ConclusionsIn conclusion, this analysis demonstrates the feasibility of using external publications to correct for collider bias (or other forms of selection bias) induced by the restriction of a population to a hospitalised cohort using an example from the recent Covid-19 pandemic.

Diverse e-cigarette regulations in the Asia Pacific: A health economic perspective.

Diverse e-cigarette regulations in the Asia Pacific: A health economic perspective.

Characteristics of sudden death by clinical criteria.

Sudden death is a leading cause of deaths nationally. Definitions of sudden death vary greatly, resulting in imprecise estimates of its frequency and incomplete knowledge of its risk factors. The degree to which time-based and coronary artery disease (CAD) criteria impacts estimates of sudden death frequency and risk factors is unknown. Here, we apply these criteria to a registry of all-cause sudden death to assess its impact on sudden death frequency and risk factors. The sudden unexpected death in North Carolina (SUDDEN) project is a registry of out of-hospital, adjudicated, sudden unexpected deaths attended by Emergency Medical Services. Deaths were not excluded by time since last seen or alive or by prior symptoms or diagnosis of CAD. Common criteria for sudden death based on time since last seen alive (both 24 hours and 1 hour) and prior diagnosis of CAD were applied to the SUDDEN case registry. The proportion of cases satisfying each of the 4 criteria was calculated. Characteristics of victims within each restrictive set of criteria were measured and compared to the SUDDEN registry. There were 296 qualifying sudden deaths. Application of 24 hour and 1 hour timing criteria compared to no timing criteria reduced cases by 25.0% and 69.6%, respectively. Addition of CAD criteria to each timing criterion further reduced qualifying cases, for a total reduction of 81.8% and 90.5%, respectively. However, characteristics among victims meeting restrictive criteria remained similar to the unrestricted population. Timing and CAD criteria dramatically reduces estimates of the number of sudden deaths without significantly impacting victim characteristics.

Hypoxic conditions promote a proliferative, poorly differentiated phenotype in COPD lung tissue progenitor cells in vitro

PurposeChronic obstructive pulmonary disease (COPD) patients experience hypoxemia and lung tissue hypoxia, causing vasoconstriction, and at its most severe Cor pulmonale. However, minimal attention has been given to the effects of hypoxia at the cellular level. We hypothesize that a persistent progenitor cell population undergoes an aberrant differentiation process, influenced by changes in oxygen.MethodsDistal lung progenitor cells from two emphysematous donors were cultured in 21% and 2% oxygen. Proliferation was determined on collagen-coated plastic and in 3T3-J2 co-culture. Epithelial (E-cadherin, pan-cytokeratin) and progenitor (TP63, cytokeratin 5) marker expressions were examined. Cells were differentiated at air–liquid interface, and ciliated, mucus-producing, and club cell populations identified by immunofluorescence. MUC5AC, MUC5B, CC10, and TP63 expression were determined using qRT-PCR, mucin5AC, and mucin5B protein levels by ELISA, and secreted mucin by periodic acid biotin hydrazide assay.ResultsCells were positive for epithelial and progenitor markers at isolation and passage 5. Passage 5 cells in hypoxia increased the proportion of TP63 by 10% from 51.6 ± 1.2% to 62.6 ± 2.3% (p ≤ 0.01). Proliferative capacity was greater on 3T3J2 cells and in 2% oxygen, supporting the emergence of a proliferation unrestricted population with limited differentiation capacity. Differentiation resulted in βIV tubulin positive-ciliated cells, mucin5AC, mucin5B, and CC10 positive secretory cells. Epithelial barrier formation was reduced (p ≤ 0.0001) in hypoxia-expanded cells. qRT-PCR showed higher mucin expression in 2% cells, significantly so with MUC5B (p ≤ 0.05). Although overall mucin5AC and mucin5B content was greater in 21% cells, normalization of secreted mucin to DNA showed a trend for increased mucin by low oxygen cells.ConclusionsThese results demonstrate that hypoxia promotes a proliferative phenotype while affecting subsequent progenitor cell differentiation capacity. Furthermore, the retained differentiation potential becomes skewed to a more secretory phenotype, demonstrating that hypoxia may be contributing to disease symptoms and severity in COPD patients.

The biasing effects of selection and attrition on estimating the mean.

Organizational and validation researchers often work with data that has been subjected to selection on the predictor and attrition on the criterion. These researchers often use the data observed under these conditions to estimate either the predictor or criterion's restricted population means. We show that the restricted means due to direct or indirect selection are a function of the population means plus the selection ratios. Thus, any difference between selected mean groups reflects the population difference plus the selection ratio difference. When there is also attrition on the criterion, the estimation of group differences becomes even more complicated. The effect of selection and attrition induces measurement bias when estimating the restricted population mean of either the predictor or criterion. A sample mean observed under selection and attrition does not estimate either the population mean or the restricted population mean. We propose several procedures under normality that yield unbiased estimates of the mean. The procedures focus on correcting the effects of selection and attrition. Each procedure was evaluated with a Monte Carlo simulation to ascertain its strengths and weaknesses. Given appropriate sample size and conditions, we show that these procedures yield unbiased estimators of the restricted and unrestricted population means for both predictor and criterion. We also show how our findings have implications for replicating selected group differences.

Global prevalence of occult hepatitis C virus: A systematic review and meta-analysis.

BACKGROUNDOccult hepatitis C infection (OCI) is characterized by the presence of hepatitis C virus (HCV) RNA in the liver, peripheral blood mononuclear cells (PBMC) and/or ultracentrifuged serum in the absence of detectable HCV-RNA in serum. OCI has been described in several categories of populations including hemodialysis patients, patients with a sustained virological response, immunocompromised individuals, patients with abnormal hepatic function, and apparently healthy subjects.AIMTo highlight the global prevalence of OCI.METHODSWe performed a systematic and comprehensive literature search in the following 4 electronic databases PubMed, EMBASE, Global Index Medicus, and Web of Science up to 6th May 2021 to retrieve relevant studies published in the field. Included studies were unrestricted population categories with known RNA status in serum, PBMC, liver tissue and/or ultracentrifuged serum. Data were extracted independently by each author and the Hoy et al tool was used to assess the quality of the included studies. We used the random-effect meta-analysis model to estimate the proportions of OCI and their 95% confidence intervals (95%CI). The Cochran's Q-test and the I2 test statistics were used to assess heterogeneity between studies. Funnel plot and Egger test were used to examine publication bias. R software version 4.1.0 was used for all analyses.RESULTSThe electronic search resulted in 3950 articles. We obtained 102 prevalence data from 85 included studies. The pooled prevalence of seronegative OCI was estimated to be 9.61% (95%CI: 6.84-12.73) with substantial heterogeneity [I² = 94.7% (95%CI: 93.8%-95.4%), P < 0.0001]. Seropositive OCI prevalence was estimated to be 13.39% (95%CI: 7.85-19.99) with substantial heterogeneity [I2 = 93.0% (90.8%-94.7%)]. Higher seronegative OCI prevalence was found in Southern Europe and Northern Africa, and in patients with abnormal liver function, hematological disorders, and kidney diseases. Higher seropositive OCI prevalence was found in Southern Europe, Northern America, and Northern Africa.CONCLUSIONIn conclusion, in the present study, it appears that the burden of OCI is high and variable across the different regions and population categories. Further studies on OCI are needed to assess the transmissibility, clinical significance, long-term outcome, and need for treatment.

On the importance of integrating comparative anatomy and One Health perspectives in anatomy education.

As a result of many factors, including climate change, unrestricted population growth, widespread deforestation and intensive agriculture, a new pattern of diseases in humans is emerging. With increasing encroachment by human societies into wild domains, the interfaces between human and animal ecosystems are gradually eroding. Such changes have led to zoonoses, vector‐borne diseases, infectious diseases and, most importantly, the emergence of antimicrobial‐resistant microbial strains as challenges for human health. Now would seem to be an opportune time to revisit old concepts of health and redefine some of these in the light of emerging challenges. The One Health concept addresses some of the demands of modern medical education by providing a holistic approach to explaining diseases that result from a complex set of interactions between humans, environment and animals, rather than just an amalgamation of isolated signs and symptoms. An added advantage is that the scope of One Health concepts has now expanded to include genetic diseases due to advancements in omics technology. Inspired by such ideas, a symposium was organised as part of the 19th International Federation of Associations of Anatomists (IFAA) Congress (August 2019) to investigate the scope of One Health concepts and comparative anatomy in contemporary medical education. Speakers with expertise in both human and veterinary anatomy participated in the symposium and provided examples where these two disciplines, which have so far evolved largely independent of each other, can collaborate for mutual benefit. Finally, the speakers identified some key concepts of One Health that should be prioritised and discussed the diverse opportunities available to integrate these priorities into a broader perspective that would attempt to explain and manage diseases within the scopes of human and veterinary medicine.

Ecological and behavioral mechanisms of density‐dependent habitat expansion in a recovering African ungulate population

AbstractMajor disturbances can temporarily remove factors that otherwise constrain population abundance and distribution. During such windows of relaxed top‐down and/or bottom‐up control, ungulate populations can grow rapidly, eventually leading to resource depletion and density‐dependent expansion into less‐preferred habitats. Although many studies have explored the demographic outcomes and ecological impacts of these processes, fewer have examined the individual‐level mechanisms by which they occur. We investigated these mechanisms in Gorongosa National Park, where the Mozambican Civil War devastated large‐mammal populations between 1977 and 1992. Gorongosa’s recovery has been marked by proliferation of waterbuck (Kobus ellipsiprymnus), an historically marginal 200‐kg antelope species, which is now roughly 20‐fold more abundant than before the war. We show that after years of unrestricted population growth, waterbuck have depleted food availability in their historically preferred floodplain habitat and have increasingly expanded into historically avoided savanna habitat. This expansion was demographically skewed: mixed‐sex groups of prime‐age individuals remained more common in the floodplain, while bachelors, loners, and subadults populated the savanna. By coupling DNA metabarcoding and forage analysis, we show that waterbuck in these two habitats ate radically different diets, which were more digestible and protein‐rich in the floodplain than in savanna; thus, although individuals in both habitats achieved positive net energy balance, energetic performance was higher in the floodplain. Analysis of daily activity patterns from high‐resolution GPS‐telemetry, accelerometry, and animal‐borne video revealed that savanna waterbuck spent less time eating, perhaps to accommodate their tougher, lower‐quality diets. Waterbuck in savanna also had more ectoparasites than those in the floodplain. Thus, plasticity in foraging behavior and diet selection enabled savanna waterbuck to tolerate the costs of density‐dependent spillover, at least in the short term; however, the already poorer energetic performance of these individuals implies that savanna occupancy may become prohibitively costly as heterospecific competitors and predators continue to recover in Gorongosa. Our results suggest that behavior can provide a leading indicator of the onset of density‐dependent limitation and the likelihood of subsequent population decline, but that reliable inference hinges on understanding the mechanistic basis of observed behavioral shifts.

Chronic use of renin-angiotensin-aldosterone system blockers and mortality in COVID-19: A multicenter prospective cohort and literature review.

AimsThe role of renin‐angiotensin‐aldosterone system (RAAS) blockers on the course of coronavirus disease 2019 (COVID‐19) is debated. We assessed the association between chronic use of RAAS blockers and mortality among inpatients with COVID‐19 and explored reasons for discrepancies in the literature.Methods and resultsWe included adult hypertensive patients from a prospective nationwide cohort of 3512 inpatients with COVID‐19 up to June 30, 2020. Cox proportional hazard models with various adjustment or propensity weighting methods were used to estimate the hazard ratios (HR) of 30‐day mortality for chronic users versus non‐users of RAAS blockers. We analyzed data of 1160 hypertensive patients: 719 (62%) were male and 777 (67%) were older than 65 years. The main comorbidities were diabetes (n = 416, 36%), chronic cardiac disease (n = 401, 35%), and obesity (n = 340, 29%); 705 (61%) received oxygen therapy. We recorded 135 (11.6%) deaths within 30 days of diagnosis. We found no association between chronic use of RAAS blockers and mortality (unadjusted HR = 1.13, 95% CI [0.8–1.6]; propensity inverse probability treatment weighted HR = 1.09 [0.86‐1.39]; propensity standardized mortality ratio weighted HR = 1.08 [0.79–1.47]). Our comprehensive review of previous studies highlighted that significant associations were mostly found in unrestricted populations with inappropriate adjustment, or with biased in‐hospital exposure measurement.ConclusionOur results do not support previous concerns regarding these drugs, nor a potential protective effect as reported in previous poorly designed studies and meta‐analyses. RAAS blockers should not be discontinued during the pandemic, while in‐hospital management of these drugs will be clarified by randomized trials. NCT04262921.

Incidence of myelodysplastic syndrome and acute myeloid leukemia in patients receiving poly-ADP ribose polymerase inhibitors for the treatment of solid tumors: A meta-analysis of randomized trials

BackgroundClinical trials demonstrated that PARPi (poly [adenosine diphosphate–ribose]-ADP polymerase inhibitor) therapy is effective in solid tumors. However, long term effects such as therapy-related myelodysplastic syndrome or acute myeloid leukemia (MDS/AML) are poorly described. We sought to quantify whether PARPi therapy is associated with the development of MDS/AML. MethodsMedline, Embase, and Cochrane databases were searched (inception to January 6, 2020) and phase 2 and 3 clinical trials that randomized patients with solid tumors to a PARPi or control therapy were included. The PRISMA guidelines were used to extract data independently by multiple authors. We extracted person-time and number of cases of MDS/AML in the PARPi and control arms of each study and pooled results with a random-effects Poisson regression model. The pooled incidence rate ratio (IRR) for MDS/AML among patients randomized to PARPi therapy was compared to those randomized to a control. ResultsWe identified 14 studies that included 5739 patients. Accounting for intra-study clustering, the risk of MDS/AML was similar in patients who were randomly assigned to receive PARPi compared to controls (IRR 1.32, 95% confidence interval [CI] 0.78–2.26). In the front-line setting, PARPi therapy was associated with developing MDS/AML (IRR 5.43, 95% CI 1.51–19.60). Among patients treated for recurrence, however, the risk of MDS/AML appeared to be similar among patients randomized to PARPi or control treatment. Among studies that included only patients with a BRCA mutation, the risk of MDS/AML was similar in both treatment groups (IRR 0.83, 95% CI 0.45–1.53), but PARPi therapy was associated with MDS/AML in studies with an unrestricted population (IRR 2.43, 95% CI 1.17–5.06). ConclusionThe pooled overall effect was not statistically significant. However, treatment with PARPi was associated with a statistically significant increase in the incidence of MDS/AML among patients receiving front-line cancer therapy and those with limited prior exposure to chemotherapy.

A Comparative Study of Recent Multi-objective Metaheuristics for Solving Constrained Truss Optimisation Problems

Multi-objective truss optimisation is a research topic that has been less investigated in the literature compared to the single-objective cases. This paper investigates the comparative performance of fourteen new and established multi-objective metaheuristics when solving truss optimisation problems. The optimisers include multi-objective ant lion optimiser, multi-objective dragonfly algorithm, multi-objective grasshopper optimisation algorithm, multi-objective grey wolf optimiser, multi-objective multi-verse optimisation, multi-objective water cycle algorithm, multi-objective Salp swarm algorithm, success history-based adaptive multi-objective differential evolution, success history–based adaptive multi-objective differential evolution with whale optimisation, non-dominated sorting genetic algorithm II, hybridisation of real-code population-based incremental learning and differential evolution, differential evolution for multi-objective optimisation, multi-objective evolutionary algorithm based on decomposition, and unrestricted population size evolutionary multi-objective optimisation algorithm. The design problem is assigned to minimise structural mass and compliance subject to stress constraints. Eight classical trusses found in the literature are used for setting up the design test problems. Various optimisers are then implemented to tackle the problems. A comprehensive comparative study is given to critically analyse the performance of all algorithms in this problem area. The results provide new insights to the pros and cons of evolutionary multi-objective optimisation algorithms when addressing multiple, often conflicting objective in truss optimisation. The results and findings of this work assist with not only solving truss optimisation problem better but also designing customised algorithms for such problems.

Sensitivity, specificity, positive and negative predictive values of identifying atrial fibrillation using administrative data: a systematic review and meta-analysis.

IntroductionAtrial fibrillation (AF) is the commonest arrhythmia and a major cause of stroke and health care utilization. Researchers and administrators use electronic health data to assess disease burden, quality and variance in care, value of interventions and prognosis. We performed a systematic review and meta-analysis to assess the validity of AF case definitions in administrative databases.MethodsMedline was searched from 2000 to 2018. Extracted information included sensitivity, specificity, positive and negative predictive values (PPV and NPV) for various AF case definitions. Estimates were pooled using random-effects models due to significant heterogeneity between studies.ResultsWe identified 24 studies, including 21 from North America or Scandinavia. Hospital, ambulatory and mixed data sources were assessed in 10, 4 and 10 studies, respectively. Nine different AF case definitions were evaluated, most based on ICD-9 or 10 codes. Twenty-two studies assessed case definitions in patients diagnosed with AF and thus could generate PPV alone. Half the studies sampled unrestricted populations including a mix of those with and without AF to assess sensitivity. Only 13 studies included ECG confirmation as a gold standard. The pooled random effects estimates were: sensitivity 80% (95% CI 72–86%); specificity 98% (96–99%); PPV 88% (82–94%); NPV 97% (94–99%). Only 3 studies reported all accuracy parameters and included rhythm monitoring in the gold standard definition.ConclusionRelatively few studies examined sensitivity, and fewer still included rhythm monitoring in the gold standard comparison. Administrative data may fail to identify a significant proportion of patients with AF. This, in turn, may bias estimates of quality of care and prognosis.

Synthesis of multiple cross-section pin fin heat sinks using multiobjective evolutionary algorithms

This paper demonstrates multiobjective optimization of a multi cross-section pin fin heat sink (MCSPFHS) for use in electronic devices. The design problem is assigned to optimize junction temperature and fan pumping power of the heat sink. Design variables are encoded to shape the fin geometry with several pin fin cross-sections. The heat sink is set to be side-inlet-side-outlet (SISO) while several multiobjective evolutionary algorithms (MOEAs) including hybrid real code population-based incremental learning and differential evolution (PBIL-DE), second version of strength Pareto evolutionary algorithm (SPEA2), and unrestricted population size evolutionary multiobjective optimization algorithm (UPSEMOA) are applied to solve the bi-objective optimization problem. The results obtained are superior to those conventional pin fin heat sinks.

Clinical Significance of Incidentally Detected Torus Tubarius Calcification.

Calcification of the torus tubarius has been rarely reported in the literature. Histopathologic studies have previously described cases of Eustachian tube calcification and cite an association with increasing patient age. The purpose of this study was to examine the prevalence of torus tubarius calcification and potential clinical significance on an unrestricted patient population using thin-section computed tomography (CT), which has not been previously reported. After the institutional review board approval, 1571 consecutive patients who underwent noncontrast head CT between January 2011 and July 2011 were retrospectively reviewed for torus tubarius calcification. Images were acquired at 1.25-mm slice thickness using a 64-detector row CT. Medical records were reviewed for chronic medical conditions including chronic kidney disease, alcoholism, autoimmune conditions, endocrine disorders, elevated alkaline phosphatase levels, history of otitis media, purified protein derivative positivity, history of head and neck surgery and radiation, and human immunodeficiency virus infection. Motion-limited studies and patients with limited clinical data were excluded. Statistical analyses were performed using the independent sample t test and Fisher exact test. Ten (0.6%) of 1571 patients had torus tubarius calcification, of which 7 (70%) were unilateral, and 3 (30%) were bilateral calcification. There was no significant association between torus tubarius calcification and common medical disorders including endocrine disorders, human immunodeficiency virus, chronic kidney disease, alcoholism, purified protein derivative positivity, history of head and neck surgery or radiation, and autoimmune diseases. Based on the largest series to date on an unrestricted population using thin-section CT imaging, calcification of the torus tubarius is a rare entity with an overall prevalence of 0.6%. Although the clinical significance remains uncertain, there is no significant association between torus tubarius calcification and common medical conditions.

Population trends and live birth rates associated with common ART treatment strategies.

Have ART live birth rates improved in Australia over the last 12 years? There were striking improvements in per-cycle live birth rates observed for frozen/thaw embryo transfers, blastocyst transfer and single embryo transfer (SET), while live birth rates following ICSI were lower than IVF for non-male factor infertility in most years. ART and associated techniques have become the predominant treatment of infertility over the past 30 years in most developed countries. However, there are differences in ART laboratory and clinical practices, and success rates worldwide. Australia has one of the highest ART utilization rates and lowest multiple birth rates in the world, thus providing a unique setting to investigate the contribution of common ART strategies in an unrestricted population of patients to ART success rates. A retrospective cohort study of 585 065 ART treatment cycles performed in Australia between 2002 and 2013 using the Australian and New Zealand Assisted Reproduction Database (ANZARD). An unrestricted population of all women who underwent autologous ART treatment between 2002 and 2013. Visual descriptive analysis was used to assess the trends in ART procedures by the calendar years. Adjusted odds ratios (aORs) of a live birth for four common ART techniques were calculated after controlling for important confounders including female age, infertility diagnosis, stage of the embryo (blastocyst versus cleavage stage), type of embryo (fresh versus thawed), fertilization method (IVF versus ICSI) and number of embryos transferred (SET versus multiple embryos). The overall live birth rate per embryo transfer increased from 19.2% in 2002 to 23.3% in 2013 (21.9-24.3% for fresh embryo transfers and 14.6-23.3% for frozen/thaw embryo transfers). This occurred concurrently with an increase in SET from 29.7% to 78.9%, and an increase in the average age of women undergoing treatment from 35.0 to 35.9 years. Individuals who had a frozen/thaw embryo transfer cycle in 2002 had 43% (aOR: 0.57, 95% CI: 0.53-0.61) reduced odds of a live birth compared with a fresh embryo transfer cycle. This contrasted with 16% (aOR: 0.84, 95% CI: 0.80-0.98) reduced odds of a live birth from frozen/thaw embryo transfer cycles in 2013. In 2013, the odds of blastocyst transfer resulting in a live birth were more than twice as great as for cleavage stage transfer (aOR 2.01, 95% CI: 1.92-2.11). The adjusted odds of live birth per SET compared with multiple embryo transfer increased significantly over the last 12 years, from a 38% reduced odds of a live birth follow SET in 2002 (aOR: 062, 95% CI: 0.57-0.67) compared to an 8% reduced odds in 2013 (aOR: 0.92, 95% CI: 0.87-0.98). The aOR of a live birth using ICSI compared to IVF in non-male factor patients was lower in most years bringing into question its widespread use. This is a retrospective cohort analysis and cannot confirm causality. High-level evidence on the effectiveness of particular ART techniques, particularly ICSI and blastocyst culture, requires prospective randomized controlled trials or detailed statistical analysis using large-scale data that counts for fertilization failure, embryo loss, prognostic factors and cycle characteristics. The most striking improvements in ART success rates in Australia have been observed for frozen/thaw embryo transfers, blastocyst transfer and SET. Further studies of the role of ICSI in non-male factor infertility and blastocyst transfer success rates that take into account embryo loss are needed. No funding was received to undertake this study. The authors declare that they do not have competing interests with this study. NA.

Natural and Synthetic Neurotoxins in Our Environment: From Alzheimer's Disease (AD) to Autism Spectrum Disorder (ASD).

Humankind has inadvertently designed a remarkably precarious combination of rapidly increasing and unchecked population growth with an increased liberation of novel and potentially pathogenic chemical compounds and neurotoxins into the biosphere. Parallel increases in the deleterious consequences of unrestricted population growth and diseasecausing toxic exposures in our environment are on the horizon. Globally this poses very significant socioeconomic and healthcare concerns that have been neglected for far too long. The perception of ‘human biochemical individuality’ indicates that certain individuals or human populations with specific genetic backgrounds may be predisposed to these toxic actions through either an acute or a more chronic type of life-long environmental exposure [11,33–36]. To cite one important example, since there is abundant evidence that neurotoxic compounds such as aluminum may play initiator or disease-propagating roles for AD, ASD and other progressive, age-related neurological diseases, then we should expect these kinds of exposure situations that can adversely affect human health and welfare to become even more common and widespread in the foreseeable future [7–27]. This may be particularly important socioeconomically and epidemiologically due in part to the excessive and additional burden it will place on our already strained healthcare system both here in the United States and in global situations where even basic healthcare systems remain underdeveloped or are simply unavailable to the local human population.

Intrauterine device use in an urban university clinic: safety of use in a population at high risk for sexually transmitted infections

ObjectiveThe objective was to describe infection rates after intrauterine device (IUD) placement at an urban teaching hospital that did not restrict IUD eligibility based on risk factors for sexually transmitted infections (STIs). MethodsWe reviewed charts of patients undergoing IUD placement at the University of Chicago obstetrics and gynecology resident clinic from July 2007 to June 2008 (n=283). The primary outcome was diagnosis of pelvic inflammatory disease (PID) within 12 months. ResultsAlmost half (49.5%) of patients reported a history of any STI. Two patients (0.7%) were diagnosed with PID. ConclusionPostplacement infection in this unrestricted population was infrequent and comparable to reported rates in previous studies.

Tu1130 Impact of Clinical and Endoscopic Features on BMI in Patients With Eosinophilic Esophagitis

G A A b st ra ct s standard grocery store for the SFED needed more items from a second store to complete his/her shopping when compared to a patient consuming an unrestricted diet (39% vs 4%; p=0.008; Table 2). The prices of the SFED and unrestricted diet just using a specialty supermarket were comparable ($104.86 vs 108.25; p=0.84), as was the percentage of items requiring a trip to a second store (5% vs 1%; p=0.25). Shopping at a specialty grocery store increased weekly grocery costs by $27.93 (p=0.008) for the SFED and $42.31 (p=0.008) for the unrestricted diet. Conclusions: For a patient shopping at a standard grocery store, the cost of an SFED is higher than the cost of an unrestricted diet (~$570/year), and an SFED requires visits to multiple grocery stores to complete a shopping trip. These differences disappear at a specialty grocery store, but the weekly grocery bill at a specialty store was significantly higher. The cost and logistical burden of maintaining an SFED can be communicated to patients when deciding between swallowed steroids and dietary therapy. We also note that our research team required considerable dietician assistance, and this may be a major challenge for patients with limited health literacy, financial means, or the time to carefully read labels. Future research should assess whether the difference in dietary cost is offset by the price of medication in the unrestricted diet population or other savings in the SFED community. Table 1. Weekly Menu Cost by City and Supermarket

Guidelines-based diagnostic process does increase hospital delay in a cohort of colorectal cancer patients: a population-based study.

This is an investigation of factors determining hospital delay until treatment in an unrestricted population of colorectal cancer patients in the western part of the Netherlands. All patients with newly diagnosed colon (n=2146) and rectal carcinoma (n=1036) in the period 2006-2008 were included in analyses of inhospital delay (first hospital visit until first treatment >35 days). One-third of all patients were also available for analyses of prehospital delay (enrollment until first hospital visit >7 days). Patient, tumour and process factors predicting delay were examined in logistic regression models. The median prehospital and inhospital time intervals were 2 days [(p25-p75) 0-16] and 32 days (17-49), respectively, for colon cancer patients and 7 days (1-21) and 43 days (33-60) for rectal cancer patients. After adjustment for patient and tumour factors, colon and rectal cancer patients with first hospital visit before histological confirmation of cancer, complete diagnostic assessment or discussed in a multidisciplinary meeting had a higher probability of increased inhospital delay. Furthermore, first hospital visit before histological confirmation of cancer was associated with decreased prehospital delay in colon and rectal cancer patients. A guidelines-based diagnostic process (considered high quality of care) and multidisciplinary collaboration were associated with increased hospital delay in colorectal cancer patients.

Patterns and dynamics of rapid local adaptation and sex in varying habitat types in rotifers

Local adaptation is an important principle in a world of environmental change and might be critical for species persistence. We tested the hypothesis that replicated populations can attain rapid local adaptation under two varying laboratory environments. Clonal subpopulations of the cyclically parthenogenetic rotifer Brachionus calyciflorus were allowed to adapt to two varying harsh and a benign environment: a high-salt, a food-limited environment and untreated culture medium (no salt addition, high food). In contrast to most previous studies, we re-adjusted rotifer density to a fixed value (two individuals per ml) every 3–4 days of unrestricted population growth, instead of exchanging a fixed proportion of the culture medium. Thus our dilution regime specifically selected for high population growth during the entire experiment and it allowed us to continuously track changes in fitness (i.e., maximum population growth under the prevailing conditions) in each population. After 56 days (43 asexual and eight sexual generations) of selection, the populations in the harsh environments showed a significant increase in fitness over time relative to the beginning compared to the population in untreated culture medium. Furthermore, the high-salt population exhibited a significantly elevated ratio of sexual offspring from the start of the experiment, which suggested that this environment either triggered higher rates of sex or that the untreated medium and the food-limited environment suppressed sex. In a following assay of local adaptation we measured population fitness under “local” versus “foreign” conditions (populations adapted to this environment compared to those of the other environment) for both harsh habitats. We found significantly higher fitness values for the local populations (on average, a 38% higher fitness) compared to the foreign populations. Overall, local adaptation was formed rapidly and it seemed to be more pronounced in the high-salt treatment.