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Most emerging infectious diseases of humans are transmitted to humans from other animals. The transmission of these "zoonotic" pathogens is affected by the abundance and behavior of their wildlife hosts. However, the effects of infection with zoonotic pathogens on behavior of wildlife hosts, particularly those that might propagate through ecological communities, are not well understood. Borrelia burgdorferi is a bacterium that causes Lyme disease, the most common vector-borne disease in the USA and Europe. In its North American range, the pathogen is most frequently transmitted among hosts through the bite of infected blacklegged ticks (Ixodes scapularis). Using sham and true vaccines, we experimentally manipulated infection load with this zoonotic pathogen in its most competent wildlife reservoir host, the white-footed mouse, Peromyscus leucopus, and quantified the effects of infection on mouse foraging behavior, as well as levels of mouse infestation with ticks. Mice treated with the true vaccine had 20% fewer larval blacklegged ticks infesting them compared to mice treated with the sham vaccine, a significant difference. We observed a nonsignificant trend for mice treated with the true vaccine to be more likely to visit experimental foraging trays (20%-30% effect size) and to prey on gypsy moth pupae (5%-20% effect size) compared to mice treated with the sham vaccine. We observed no difference between mice on true- versus sham-vaccinated grids in risk-averse foraging. Infection with this zoonotic pathogen appears to elicit behavioral changes that might reduce self-grooming, but other behaviors were affected subtly or not at all. High titers of B. burgdorferi in mice could elicit a self-reinforcing feedback loop in which reduced grooming increases tick burdens and hence exposure to tick-borne pathogens.

Biological invasions reshape environments and affect the ecological and economic welfare of states and communities. Such invasions advance on multiple spatial scales, complicating their control. When modeling stochastic dispersal processes, intractable likelihoods and autocorrelated data complicate parameter estimation. As with other approaches, the recent synthetic likelihood framework for stochastic models uses summary statistics to reduce this complexity; however, it additionally provides usable likelihoods, facilitating the use of existing likelihood-based machinery. Here, we extend this framework to parameterize multi-scale spatio-temporal dispersal models and compare existing and newly developed spatial summary statistics to characterize dispersal patterns. We provide general methods to evaluate potential summary statistics and present a fitting procedure that accurately estimates dispersal parameters on simulated data. Finally, we apply our methods to quantify the short and long range dispersal of Chagas disease vectors in urban Arequipa, Peru, and assess the feasibility of a purely reactive strategy to contain the invasion.

Migration is a primary force of biological evolution that alters allele frequencies and introduces novel genetic variants into populations. Recent migration has been proposed as the cause of the emergence of many infectious diseases, including those carried by blacklegged ticks in North America. Populations of blacklegged ticks have established and flourished in areas of North America previously thought to be devoid of this species. The recent discovery of these populations of blacklegged ticks may have resulted from either in situ growth of long-established populations that were maintained at very low densities or by migration and colonization from established populations. These alternative evolutionary hypotheses were investigated using Bayesian phylogeographic approaches to infer the origin and migratory history of recently detected blacklegged tick populations in the Northeastern United States. The data and results indicate that newly detected tick populations are not the product of in situ population growth from a previously established population but from recent colonization resulting in a geographic range expansion. This expansion in the geographic range proceeded primarily through progressive and local migration events from southern populations to proximate northern locations although long-distance migration events were also detected.

Urban transmission of arthropod-vectored disease has increased in recent decades. Understanding and managing transmission potential in urban landscapes requires integration of sociological and ecological processes that regulate vector population dynamics, feeding behavior, and vector-pathogen interactions in these unique ecosystems. Vectorial capacity is a key metric for generating predictive understanding about transmission potential in systems with obligate vector transmission. This review evaluates how urban conditions, specifically habitat suitability and local temperature regimes, and the heterogeneity of urban landscapes can influence the biologically-relevant parameters that define vectorial capacity: vector density, survivorship, biting rate, extrinsic incubation period, and vector competence.Urban landscapes represent unique mosaics of habitat. Incidence of vector-borne disease in urban host populations is rarely, if ever, evenly distributed across an urban area. The persistence and quality of vector habitat can vary significantly across socio-economic boundaries to influence vector species composition and abundance, often generating socio-economically distinct gradients of transmission potential across neighborhoods.Urban regions often experience unique temperature regimes, broadly termed urban heat islands (UHI). Arthropod vectors are ectothermic organisms and their growth, survival, and behavior are highly sensitive to environmental temperatures. Vector response to UHI conditions is dependent on regional temperature profiles relative to the vector’s thermal performance range. In temperate climates UHI can facilitate increased vector development rates while having countervailing influence on survival and feeding behavior. Understanding how urban heat island (UHI) conditions alter thermal and moisture constraints across the vector life cycle to influence transmission processes is an important direction for both empirical and modeling research.There remain persistent gaps in understanding of vital rates and drivers in mosquito-vectored disease systems, and vast holes in understanding for other arthropod vectored diseases. Empirical studies are needed to better understand the physiological constraints and socio-ecological processes that generate heterogeneity in critical transmission parameters, including vector survival and fitness. Likewise, laboratory experiments and transmission models must evaluate vector response to realistic field conditions, including variability in sociological and environmental conditions.

Acute hemorrhage related to gastric varices (GV) is more severe and often more difficult to immediately treat upon detection, leading to a poorer patient prognosis, as compared to esophageal variceal bleeding. Currently, the recommended treatment of bleeding GV is endoscopic cyanoacrylate injection and transjugular intrahepatic portosystemic shunt placement for endoscopic failures. Newer endoscopic (e.g. hemospray) and endosonographic (e.g. coil injection, glue obliteration, or combined coil and glue injection) techniques have been developed to offer an alternative treatment and improve patient outcome. The present article serves to review the endoscopic, endosonographic, and interventional radiological techniques used to treat GV and their clinical applications.

BACKGROUND Multigene molecular testing to guide personalized therapy for oncology patients is of increasing clinical relevance. Molecular testing of fine-needle aspiration samples is underused, but when acquired with minimally invasive techniques could become the standard of care to obtain theranostic specimens. The aims of the current study were to identify key cytology specimen selection criteria suitable for next-generation sequencing (NGS) and to determine the prevalence and spectrum of pathogenic alterations in a cohort of patients with AJCC stage IV lung cancer. METHODS A total of 70 adrenal gland cytology specimens with direct smears were screened to identify 56 patients with a single slide containing at least 300 total cells and 20% tumor nuclei. After DNA extraction, the NGS protocols were used to simultaneously detect mutations in >2800 exonic regions in 50 key cancer genes. RESULTS A total of 28 specimens produced acceptable NGS results. Specimens with a combined critical cell mass (>5000 viable cells) and a DNA concentration >5 ng/µL resulted in a 95% chance of successful sequencing. A total of 37 pathogenic alterations were identified in 10 genes and in 25 patients (85%). A pathogenic alteration (≥1) linked to available or developing targeted therapies was revealed in 50% of cases. CONCLUSIONS The data from the current study demonstrate that theranostic NGS can be applied to adrenal gland metastasis using routine cytologic smear specimens. The characteristics of such smears could be evaluated during onsite adequacy assessment by cytopathology professionals. This model greatly augments the opportunity for customized genotype-directed therapy from minimally invasive techniques. Cancer (Cancer Cytopathol) 2014;122:822–832. © 2014 American Cancer Society.

Background Dobutamine stress echocardiography (DSE) is commonly used to risk stratify patients in the cardiac evaluation prior to orthotopic liver transplantation (OLT). Data remain limited regarding the accuracy to predict obstructive coronary artery disease (CAD) using this approach. Hypothesis We hypothesize that DSE may have limitations in the investigation of underlying CAD in patients with end-stage liver disease. Methods A retrospective chart review of all patients who underwent OLT at Mayo Clinic in Florida between 1998 and 2010 was performed. Sixty-six underwent invasive coronary angiography (ICA) within 1 year of DSE and were included in our study. Based on DSE results, patients were stratified into 1 of 3 groups: nonischemic, ischemic, and indeterminate. The relationship between DSE, ICA, and death from all cause and cardiac-related cause with a minimum 3-year follow-up period were analyzed. Results A total of 66 patients were included in our cohort. There was no difference in age, gender, severity of liver disease, and echocardiographic findings among the groups. Forty-three percent of patients (n = 12) with an abnormal result on DSE were found to have moderate or severe obstructive CAD on cardiac catheterization, whereas 49% of patients (n = 17) with a normal finding on DSE had moderate or severe CAD. Of 5 patients who died from a documented cardiac etiology, 3 had normal stress test results, 1 had abnormal findings, and 1 had an indeterminate DSE result. When compared with ICA, our study demonstrated that DSE has a sensitivity of 41.4% (95% confidence interval [CI]: 0.24-0.61), specificity of 47.1% (95% CI: 0.30-0.65), positive predictive value of 40.0% (95% CI: 0.23-0.59), and negative predictive value of 48.0% (95% CI: 0.31-0.66) in identification of underlying CAD. Conclusions Although widely used, DSE may not always accurately reflect the severity of obstructive CAD in patients undergoing OLT.

Summary Background There is no consensus on the standard treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma for Helicobacter pylori-negative patients and for patients with persistent disease despite H. pylori eradication. Aim To evaluate the comparative efficacy and safety of alkylating agents and rituximab alone or in combination. Methods In this monocentric retrospective study, which included 106 patients who had not been previously treated with anti-cancer agents, we evaluated the efficacy and safety of oral alkylating agents monotherapy (n = 48), rituximab monotherapy (n = 28) and the therapy combining both drugs (n = 30). Evaluations were performed at weeks 6 (W6), 25 (W25), and 52 (W52) and after 2 years (W104). Results After a median follow-up period of 4.9 years (range 0.4–17.2 years), complete remission and overall response were significantly higher in patients in the combination therapy group at W104 (92% and 100% respectively) compared with patients treated with alkylating agents alone (66% and 68%) and rituximab alone (64% and 73%). The 5-year progression-free survival probabilities were 68%, 70% and 89% in patients treated with alkylating agents alone, rituximab alone and combination therapy respectively. Haematological adverse events were reported in 32 (30%) patients (mostly grade 1) and were more frequent in the two groups receiving alkylating agents (P = 0.05 and P

Background and Objective Photodynamic therapy (PDT) is a potential treatment for pancreatic cancer. A second-generation photosensitizer, 2-[1-hexyloxyethyl]-2-devinyl pyropheophorbide (HPPH) has a long wavelength absorption, high-tumor selectivity, and shorter duration of skin photosensitivity. We investigated the efficacy of PDT with HPPH and gemcitabine in inducing cell death in multiple pancreatic cancer cell lines. Methods We used three pancreatic cancer cell lines (PANC-1, MIA PaCa-2, and BXPC-3) incubated with HPPH concentration of 0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, and 0.5 µg/ml for 6 hours, followed by photoradiation at a light dose of 60 J/cm2. Afterwards, each cell line was treated with gemcitabine at concentrations of 0, 1, 10, and 100 µM and incubated for another 96 hours. Cell death was detected with SYTOX green staining. We also assessed the difference in cytotoxicity in adding gemcitabine before and after PDT. Results HPPH-PDT can effectively induce cell death in all cell lines in a dose-dependent manner, with a 100% of cell death at the 0.5 µg/ml HPPH concentration. In contrast, monotherapy with gemcitabine alone (100 µM) only achieved

Summary A recent paper published by Lowe and Romney in Emerging Infectious Diseases titled, Bed bugs as Vectors for Drug-Resistant Bacteria has sparked a renewed interest in bed bug vector potential. We followed a pyrethroid resistant strain of the human bed bug (Cimex lectularius, L.) fed either human blood or human blood with added methicillin resistant Staphylococcus aureus (MRSA) for 9 days post-feeding. Results indicated that while the bed bug midgut is a hospitable environment for MRSA, the bacteria does not survive longer than 9 days within the midgut. Additionally, MRSA is not amplified within the midgut of the bug as the infection was cleared within 9 days. Due to the weekly feeding behaviours of bed bugs, these results suggest that bed bug transmission of MRSA is highly unlikely.

Background and Aims: Aberrant right subclavian artery (ARSA) is the most common congenital anomaly of the aortic arch occurring in 0.4–2.0% of the general population. Instead of arising from the brachiocephalic artery, the ARSA arises as the last branch from the aortic arch. The aim of this study was to determine the prevalence of ARSA in patients undergoing upper endoscopic ultrasound (EUS) and to describe the EUS characteristics of ARSA. Methods: A retrospective review was conducted of 7513 upper EUS exams performed from 1 July 2000 to 1 February 2005. Results: In total, 27 (0.36%, 95% CI 0.22–0.50%) of 7513 patients undergoing upper EUS were found to have an ARSA (10 male, 17 female; mean age 58 years, range 23–81 years). Of the 27 patients, 16 had only radial EUS, 10 had radial and linear EUS, and one had only linear EUS. In all 26 patients who underwent radial imaging, a well-defined, anechoic tubular structure was seen originating from the aortic arch and passing between the esophagus and spine. In all 11 patients undergoing linear imaging, the abnormal anatomy was detected and the vascular nature confirmed by Doppler. In one patient, both radial and linear imaging identified unsuspected aneurismal dilatation of the ARSA; a rare condition referred to as Kommerell’s diverticulum (KD). None of the other 26 patients had symptoms to suggest an ARSA. Of the 14 patients who had computed tomography (CT) prior to EUS, only four were initially reported to have ARSA. However, later review of the CT scans verified an ARSA in all 14 patients. Of the two patients who underwent a barium swallow, only one had findings suggestive of ARSA. Conclusions: This report highlights the utility of both radial and linear EUS imaging in identifying previously unsuspected ARSA and associated anomalies. This report also suggests the need for careful review of the CT in patients suspected of having ARSA due to the frequent failure of radiologists to identify, or report, this anomaly when particular focus is not given.

Background: Endoscopic ultrasound (EUS) is an accurate imaging modality for local staging of esophageal cancer. We aimed to determine if depth of tumor invasion beyond muscularis propria (MP), as determined by preoperative EUS, is predictive of tumor recurrence or survival (a positive change in mortality) in patients with T3 esophageal cancer. Methods: Records and images of all patients with T3 N1 M0 esophageal cancer staged with EUS at our institution between January 1999 and October 2003 were reviewed. EUS images were independently reviewed by five blinded endosonographers and tumors were classified as minimally invasive (invasion

Background: Depth of invasion beyond the muscularis propria (MP) by T3 rectal cancer can vary. The purpose of the present paper was to determine if depth of invasion beyond MP, as assessed by preoperative endoscopic ultrasound (EUS), can predict tumor recurrence in patients with T3 rectal tumors. Methods: Patients with T3NxM0 rectal cancer, as determined by EUS, who underwent surgical resection (without preoperative neoadjuvant therapy) were reviewed by two blinded endosonographers. Tumors were classified as minimally invasive T3 (invasion ≤ 2 mm beyond MP by EUS) and advanced T3 disease (invasion > 2 mm). Results: Forty-two patients with T3 rectal tumors underwent surgical resection without receiving preoperative neoadjuvant therapy, of whom 14 had minimally invasive T3 and 28 had advanced T3 disease, as determined by preoperative EUS. Median follow up was 19 months. Tumor recurrence rates in minimally invasive and advanced T3 tumors were 14.3% and 39.3%, respectively, P = 0.02 (log–rank test). Adjusting for nodal status and postoperative adjuvant therapy administration, Cox proportional hazards model demonstrated advanced T3 disease (by EUS) to predict tumor recurrence, hazard ratio, 2.28 (95% confidence interval: 1.17–5.81), P = 0.01. Conclusions: All T3 rectal tumors are not equal, with minimally invasive disease carrying a more favorable prognosis. By discriminating minimally invasive from advanced T3 disease, preoperative EUS provides important prognostic information. Further subclassification of T3 tumors, based on preoperative EUS staging, should be considered to enhance selection of patients for neoadjuvant therapy. © 2004 Blackwell Publishing Asia Pty Ltd

We report the case of a 14-year-old male treated with arsenic trioxide for recurrent acute promyelocytic leukemia. He developed hyperleukocytosis (WBC 111.6 x 10(9)/L) which then resolved while continuing daily arsenic. Hyperleukocytosis without other complications may not be an indication for adding cytotoxic therapy or steroids, nor for discontinuing arsenic trioxide therapy in children.

The ability to image the gastrointestinal wall in addition to mediastinal, abdominal, retroperitoneal and pelvic organs with endosonography has permitted substantive advances in our diagnostic capabilities. Requisite to this evolution was the development of endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) and trucut biopsy (TCB). These techniques permit pathologic confirmation of abnormalities heretofore only possible by surgical means. The next generation in this evolution is just emerging in the form of EUS-guided fine needle injection (FNI) therapy. Standard EUS-guided techniques for injection therapy include celiac plexus block/neurolysis, treatment of achalasia, and variceal sclerotherapy. However, this review will focus on the limited information available on EUS-FNI of anti-neoplastic agents for pancreatic cancer as well as EUS-FNI of alcohol for cystic pancreatic tumors. We will also discuss potential technical hurdles that must be overcome to allow for the safe proliferation of these techniques.

The population densities of many organisms have changed dramatically in recent history. Increases in the population density of medically relevant organisms are of particular importance to public health as they are often correlated with the emergence of infectious diseases in human populations. Our aim is to delineate increases in density of a common disease vector in North America, the blacklegged tick, and to identify the environmental factors correlated with these population dynamics. Empirical data that capture the growth of a population are often necessary to identify environmental factors associated with these dynamics. We analyzed temporally- and spatially-structured field collected data in a geographical information systems framework to describe the population growth of blacklegged ticks (Ixodes scapularis) and to identify environmental and climatic factors correlated with these dynamics. The density of the ticks increased throughout the study’s temporal and spatial ranges. Tick density increases were positively correlated with mild temperatures, low precipitation, low forest cover, and high urbanization. Importantly, models that accounted for these environmental factors accurately forecast future tick densities across the region. Tick density increased annually along the south-to-north gradient. These trends parallel the increases in human incidences of diseases commonly vectored by I. scapularis. For example, I. scapularis densities are correlated with human Lyme disease incidence, albeit in a non-linear manner that disappears at low tick densities, potentially indicating that a threshold tick density is needed to support epidemiologically-relevant levels of the Lyme disease bacterium. Our results demonstrate a connection between the biogeography of this species and public health.