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Albanian (endonym: Shqip; Glotto: alba1268) is an Indo-European language which has been suggested to form an independent branch of the Indo-European family since the middle of the nineteenth century (Bopp 1855, Pedersen 1897, Çabej 1976). Though the origin of the language has been debated, the prevailing opinion in the literature is that it is a descendant of Illyrian (Hetzer 1995). Albanian is currently spoken by around 6–7 million people (Rusakov 2017: 552; Curtis 2018: 1800), the majority of whom live in Albania and Kosovo, with others in Italy, Greece, North Macedonia and Montenegro. Figure 1 shows a map of the main Albanian-speaking areas of Europe, with major linguistic subdivisions according to Gjinari (1988) and Elsie & Gross (2009) marked by different colours and shades.

Supplementary Data from Antiglioma Immunological Memory in Response to Conditional Cytotoxic/Immune-Stimulatory Gene Therapy: Humoral and Cellular Immunity Lead to Tumor Regression

Retraction of /s/ to a more [ʃ]-like sound is a well-known sound change attested across many varieties of English for /stɹ/ words, e.g. street and strong. Despite recent sociophonetic interest in the variable, there remains disagreement over whether it represents a case of long-distance assimilation to /ɹ/ in these clusters or a two-step process involving local assimilation to an affricate derived from the sequence /tɹ/. In this paper, we investigate Manchester English and apply similar quantitative analysis to two contexts that are comparatively under-researched, but which allow us to tease apart the presence of an affricate and a rhotic: /stj/ as in student, which exhibits similar affrication of the /tj/ cluster in many varieties of British English, and /stʃ/ as in mischief. In an acoustic analysis conducted on a demographically-stratified corpus of over 115 sociolinguistic interviews, we track these three environments of /s/-retraction in apparent time and find that they change in parallel and behave in tandem with respect to the other factors conditioning variation in /s/-retraction. Based on these results, we argue that the triggering mechanisms of retraction are best modelled with direct reference to /t/-affrication and with /ɹ/ playing only an indirect, and not unique, role. Analysis of the whole sibilant space also reveals apparent-time change in the magnitude of the /s/–/ʃ/ contrast itself, highlighting the importance of contextualising this change with respect to the realisation of English sibilants more generally as these may be undergoing independent change.

What are the basic building blocks of verb meanings, how are they composed into more complex meanings, and how does this explain the grammatical properties of verbs and their relationships to other words with related meanings? These questions are fundamental to the study of verb meaning, and some of the most fruitful attempts to answer them have come from event-structural theories, wherein verb meanings are assumed to be decomposed into an event template, which captures the verb's broad temporal and causal contours, and an idiosyncratic root shared across templates, which describes specific actions and states for a given verb. An open question is what the division of labor is between the template and the root in a given verb's event template, and whether their meanings are bifurcated: are broad eventive lexical entailments introduced only by the templates, never the idiosyncratic roots? Since event templates and not roots are the primary semantic correlates of a verb's grammatical properties, bifurcation would make strong predictions about the correlation of a verb's broad temporal and causal semantics and its syntax and morphology. We argue against this bifurcation by comparing translation equivalents of Levin's (1993) non-deadjectival vs. deadjectival change-of-state verb roots in English (e.g. result vs. property concept roots) across languages. A broad-scale typological study reveals that property concept roots tend to have unmarked stative forms and marked verbal forms, while result roots have the opposite pattern. Semantic studies of several languages confirm that terms built on result roots always entail change, while terms based on property concept roots do not. This supports a theory wherein result roots entail change independent of the template, contra bifurcation. This supports a more complex, albeit still principled, theory of possible event-structural meaning and its grammatical correlates, one that takes subclasses of roots into account, while showing the value of this type of crosslinguistic methodology for testing the predictions of event-structural approaches.*

We provide data-driven machine learning methods that are capable of making real-time influenza forecasts that integrate the impacts of climatic factors and geographical proximity to achieve better forecasting performance. The key contributions of our approach are both applying deep learning methods and incorporation of environmental and spatio-temporal factors to improve the performance of the influenza forecasting models. We evaluate the method on Influenza Like Illness (ILI) counts and climatic data, both publicly available data sets. Our proposed method outperforms existing known influenza forecasting methods in terms of their Mean Absolute Percentage Error and Root Mean Square Error. The key advantages of the proposed data-driven methods are as following: (1) The deep-learning model was able to effectively capture the temporal dynamics of flu spread in different geographical regions, (2) The extensions to the deep-learning model capture the influence of external variables that include the geographical proximity and climatic variables such as humidity, temperature, precipitation and sun exposure in future stages, (3) The model consistently performs well for both the city scale and the regional scale on the Google Flu Trends (GFT) and Center for Disease Control (CDC) flu counts. The results offer a promising direction in terms of both data-driven forecasting methods and capturing the influence of spatio-temporal and environmental factors for influenza forecasting methods.

BACKGROUND Accuracy of emergency department (ED) diagnosis affects care management including tests, discharges, and readmissions. PURPOSE This retrospective study compared nurse practitioners/physician assistants (NPs/PAs) with physicians (MDs/DOs) on accuracy of diagnosing Emergency Severity Index (ESI) level 3 pediatric abdominal pain (AP) in the ED. Abdominal pain unrelated to trauma is a common ED pediatric visit. METHODOLOGY Data acquired from four hospital sites of a multistate emergency group examined patients younger than 18 years who were initially admitted for AP ESI level 3. RESULTS The accuracy of AP ESI level 3 diagnoses was 94.9%, 90.9%, and 96.5% by physicians, NPs/PAs, and a collaboration of NP/PA/physician, respectively (χ2 = 13.187, p < .001). Accuracy of AP ESI level 3 diagnoses was greater with general admissions, intensive care unit admissions, transfers, or left against medical advice (100%) than with those who were discharged (χ2 = 11.058, p = .001). Abdominal pain complaints were segmented into five areas (i.e., AP, back pain, chest pain, epigastric pain, and pelvic pain). Irrespective of provider, those with a final diagnosis of AP or epigastric pain were correctly triaged and those with a final diagnosis of chest or back pain were incorrectly triaged as AP ESI level 3. CONCLUSIONS When comparing providers in this subset (n = 43), there was no significant difference in the accuracy of assigning AP ESI level 3 (χ2 = 0.467, p = .495). IMPLICATIONS Only cases with a final diagnosis of pelvic/genitourinary pain saw disparity in the accuracy (27 correct, 16 incorrect, χ2 = 1,681.80, p < .001).

This retrospective study compared nurse practitioners and physician assistants (NPs/PAs) with physicians on their assignment of Emergency Severity Index level 3 (ESI level 3) acute abdominal pain (AAP) in the emergency department (ED).Data obtained from a large ED group staffing four hospitals yielded 12,440 de-identified, adult patients diagnosed on ED admission with AAP ESI level 3 for descriptive analysis with logistic regression.Results revealed that the comparison of ESI level 3 AAP diagnoses was consistent between admission and discharge 95.3% for physicians, 92.9% for NPs/PAs, and 97.1% for NP/PA and physician collaboration (χ = 46.01, p.001). Logistic regression suggested that NP/PA had significantly reduced odds (31%) of consistent admitting/discharge diagnoses, whereas collaboration of NP/PA with physicians had significantly increased odds of consistent diagnosis (41%) compared with physicians alone. Two hospitals with similar distributions of NPs/PAs and physicians exhibited greater odds of consistent diagnoses over hospitals with disproportionate distributions; a secondary finding worth exploring. Consistent AAP ESI level 3 diagnoses by outcomes were admissions (99%), discharges (94%), and left against medical advice/transferred (98%; χ = 102.94, p.001).The highest percentage of consistent AAP ESI level 3 diagnoses between ED admission and discharge was when NPs/PAs and physicians collaborated.

The current guidelines provided by the 3rd AIAA CFD High Lift Prediction Workshop for building unstructured meshes representing high-lift wing configurations are demonstrated and discussed. Specifically, Pointwise grid generation software is used to generate general multi-element unstructured grids about the NASA High Lift Common Research Model and the Japanese Aerospace Exploration Agency Standard Model with and without nacelles and pylons. Several modifications to the guidelines that enhance grid quality are presented. Additionally, the user-defined parameters within Pointwise that govern the mesh generation process are reviewed in detail.

Accurately predicting the performance of high-lift wing configurations with Computational Fluid Dynamics is an active area of research for academia and industry alike. The compressible Navier–Stokes equations are usually used in these studies to predict the complex flow field generated by high lift wing configurations. However, since these configurations are applied in low-speed conditions where \(Mach \le 0.2\), the compressible equations can exhibit some numerical stiffness caused by the quasi-incompressible nature of air under these conditions. Instead of using preconditioned compressible equations to alleviate these numerical issues, this work proposes the use of the incompressible Navier–Stokes equations to predict these flow fields. Specifically, the incompressible solutions about the Japanese Aerospace Exploration Agency Standard Model configuration with and without nacelles and pylons are compared with experiment at multiple angles of attack to demonstrate the effectiveness of this approach.

Margo D Lauterbach,1 Paula L Notarangelo,1 Stephen J Nichols,2 Kristy S Lane,1 Vassilis E Koliatsos11The Neuropsychiatry Program at Sheppard Pratt, Sheppard Pratt Health System, Baltimore, MD, 2Department of Emergency Medicine, The University of Tennessee College of Medicine Chattanooga, Chattanooga, TN, USAAbstract: Traumatic brain injury (TBI) causes a variety of neuropsychiatric problems that pose diagnostic and treatment challenges for providers. In this report, we share our experience as a referral neuropsychiatry program to assist the general psychiatrist when adult TBI patients with psychiatric symptoms present for evaluation and treatment. We completed a retrospective study of patients with moderate-to-severe TBI and severe neuropsychiatric impairments. We collected information on demographics, nature of injury, symptomatology, diagnoses, and treatments. Data analysis indicates that mood stabilization was a key concern, often requiring aggressive pharmacological management. Cognitive dysfunction was a problem for the majority of patients, but was only medicated in a third, due to poor efficacy or behavioral side effects. The co-occurrence of multiple TBI-related symptoms and diagnoses in this patient cohort emphasizes the need for individualized psychopharmacological approaches and interventions.Keywords: traumatic brain injury, neurobehavioral, treatment

Cultural heritage management (CHM) of Indigenous places is the dominant area of professional practice in Australian archaeology, yet relatively few Indigenous Australians take up a career in the sector. The internet is providing new and effective avenues for Indigenous outreach programmes. This paper describes a self-contained, web-enabled, free-to-user cultural heritage training programme designed in consultation with, and for the use of, Indigenous Australians. It includes a consideration of the potential and design requirements of web-delivered courses for more effectively introducing Indigenous communities to the professional CHM sector and thus achieving the long-term goal of increasing the participation of those communities in professional work.

Results from comprehensive surveys of Australian professional archaeologists undertaken in 2005 and 2010 are considered in the context of disciplinary trends, focusing on changes in access and participation, archaeological workplaces, qualifications and skill gaps. Strong growth is demonstrated in the professional archaeology sector between 2005 and 2010, showing substantial restructuring in the last five years, with an increase in Indigenous archaeology and a corresponding decrease in other subfields, especially historical archaeology. An analysis of self-assessed skill sets and skill gaps shows that the training of many professionals continues to leave significant gaps in core skill and knowledge areas which are consistent across industry subfields.

Introduction: High-intensity statin therapy (HIST) reduces cardiovascular events, however sex-related differences in treatment effects are not well characterized, possibly contributing to gender disparities in HIST use. Hypothesis: Sex-related differences in coronary atheroma regression exist following HIST. Methods: We undertook a patient-level post-hoc pooled analysis of 3 randomized trials utilizing serial coronary IVUS to test the anti-atherosclerotic effects of HIST in patients with coronary disease. Sex-related differences in changes (Δ) in coronary percent atheroma volume (PAV) were ascertained following 18-24 months of either atorvastatin 80 mg or rosuvastatin 40 mg. Results: In women (n=451) compared with men (n=1190), levels of on-treatment LDL-C (68±24 vs. 68±22mg/dl, p=0.62) were similar, however HDL-C (53±12 vs. 47±11 mg/dl, p Conclusion: Women systematically demonstrate greater degrees of coronary plaque regression compared with men following long-term HIST, especially in the setting of lower achieved LDL-C levels. Further research is required for elucidating mechanisms underpinning sex-related variations in plaque progression-regression.

Numerical solutions of the unsteady Reynolds-averaged Navier–Stokes equations using a parallel implicit flow solver are given to investigate unsteady aerodynamic flows affecting the fuel economy of Class 8 trucks. Both compressible and incompressible forms of the equations are solved using a finite-volume discretization for unstructured grids and using Riemann-based interfacial fluxes and characteristic-variable numerical boundary conditions. A preconditioned primitive-variable formulation is used for compressible solutions, and the incompressible solutions employ artificial compressibility. Detached eddy simulation (DES) versions of the one-equation Menter SAS and the two-equation k − ϵ / k − ω hybrid turbulence models are used. A fully nonlinear implicit backward-time approximation is solved using a parallel Newton-iterative algorithm with numerically computed flux Jacobians. Unsteady three-dimensional aerodynamic simulations with grids of 18–20 million points and 50,000 time steps are given for the Generic Conventional Model (GCM), a 1:8 scale tractor–trailer model that was tested in the NASA Ames 7 × 10 tunnel. Computed pressure coefficients and drag force are in good agreement with measurements for a zero-incidence case. Similar computations for a case with 10° yaw gave reasonable agreement for drag force, while the pressure distributions suggested the need for tighter grid resolution or possibly improved turbulence models. Unsteady incompressible flow simulations were performed for a modified full scale version of the GCM geometry to evaluate drag reduction devices. All of these simulations were performed with a moving ground plane and rotating rear wheels. A simulation with trailer base flaps is compared with drag reduction data from wind tunnels and track and road tests. A front spoiler and three mud-flap designs with modest drag reduction potential are also evaluated.

Antibiotic resistance is increasing resulting in a decreasing number of fully active antimicrobial agents available to treat infections with multi-drug resistant (MDR) bacteria. Herbal medicines may offer alternative treatment options. A direct inoculation method simulating the standard disc diffusion assay was developed to determine in vitro antimicrobial activity of sixty herbal extracts against MDR-Acinetobacter baumannii (A. baumannii). Eighteen herbal extracts inhibited MDR-A. baumannii on agar plates, although the magnitude and quality of bacterial inhibition differed considerably among the antibacterial herbal extracts. Next, minimal inhibitory concentration (MIC) of these antibacterial herbal extracts was calculated using a broth microdilution assay. For most herbal extracts, the larger the zone of inhibition on agar plates, the lower the MIC. In general, hetero-resistance on agar plates correlated with higher MIC. The skip well phenomenon was seen with two herbal extracts. In conclusion, 30% of the screened herbal extracts demonstrated in vitro antibacterial activity against MDR-A. baumannii using similar rigorous testing methods as those commonly employed for assessing antimicrobial activity of synthetic antibacterial agents. Characterization of a specific compound conferring this antibacterial activity of the herbal extracts may help to identify novel antimicrobial agents active against highly resistant bacteria.

BACKGROUND: High-risk (HR) human papillomavirus (HPV) testing is standard practice for triaging women who have Papanicolaou (Pap) smears with atypical squamous cells of undetermined significance (ASC-US), however, only 5% to 17% of these women have underlying cervical intraepithelial neoplasia 2 (CIN-2)/CIN-3. Recent reports have demonstrated that the presence of either HPV type 16 (HPV-16) or HPV-18 confers an elevated risk for CIN-2/CIN-3. The current study was designed to determine the prevalence of HPV-16 and HPV-18 in ASC-US Pap smears and to determine whether further typing would enhance the risk stratification of patients for CIN-2/CIN-3. METHODS: One hundred seventy-eight Pap smears with ASC-US were screened retrospectively for HR HPV by using the proprietary Invader screening assay followed by typing for HPV-16 and HPV-18 by using Invader type-specific probes on 100 of the samples. Clinical follow-up results were correlated with HPV types. RESULTS: Fifty-one percent of the ASC-US samples were positive for HR HPV, the majority of which (70%) harbored non-HPV-16/HPV-18 HR HPV types; 27% were associated with HPV-16, whereas only 3% contained HPV-18. The screening assay indicated that 46% of women who had Pap smears with ASC-US were in need of further HPV-16/HPV-18 typing. Testing for HPV-16 stratified women with ASC-US into 3 groups: 1) 14% of women were positive for HPV-16 and had a high risk (54%) of CIN-2/CIN-3 on follow-up biopsy, 2) 35% of women were positive for non-HPV-16 HPV types and had an intermediate risk (9%), and 3) 51% of women were negative for HPV and had a negligible risk for CIN-2/CIN-3. CONCLUSIONS: The combined application of a proprietary screening assay and a type-specific HPV-16 assay demonstrated global potential for the development of tailored management protocols for women who have Pap smears with ASC-US. Cancer 2009. © 2009 American Cancer Society.

In surveillance for cervical neoplasia, a diagnosis of cytologically atypical squamous cells of undetermined significance (ASCUS) presents a significant clinical issue, often dependent on testing for high-risk (HR) human papillomavirus (HPV) for the triage of patients. HPV type 16 now appears to be a critical concern in the follow-up of patients with ASCUS. The Invader HPV (Inv2) test, by Third Wave Technologies, Inc., is a recently developed analyte-specific reagent assay that uses probe sets for the detection of 14 HR HPV subtypes. These probe sets are A5/A6 (HPV types 51, 56, and 66), A7 (HPV types 18, 39, 45, 59, and 68), and A9 (HPV types 16, 31, 33, 35, 52, and 58). This report describes the performance characteristics of the Inv2 test in the screening of ASCUS cervical cytology specimens and correlates the results of the Inv2 test with those of the Hybrid Capture II HPV (HC2) test by Digene. The linear array HPV genotyping test (Roche Molecular Systems) was used as a reference method for the testing of samples with discordant results. Ninety-four Pap smear samples with a cytological diagnosis of ASCUS and 39 samples with a negative diagnosis were tested. The results of the Inv2 test demonstrated a good (86.6%) concordance with those of the HC2 test, with an overall sensitivity and specificity of 96% for the Inv2 test. Additionally, the Inv2 assay, which offers high-throughput, semiautomated DNA extraction, allows the subgrouping of HPV types by differential probe sets, could provide a useful test for screening for HPV, and has the potential to provide an improved means of risk stratification and the selection of patients for further HPV subtyping.

A Parabolized Navier-Stokes (PNS) approximation for the incompressible equations is developed to simulate flows through a wind turbine embedded in an atmospheric boundary layer (ABL). The PNS formulation differs from commonly used parabolic formulations in that the pressure field is calculated as a dependent variable without any approximation for the streamwise pressure gradient. The turbine influence is modeled by incorporating timeaveraged aerodynamic forces predicted by an actuator-line model (FAST developed at NREL). Using this coupled time-averaged spatial-marching method, the calculation can begin well upstream of the turbine and continue through the turbine to predict the entire wake region. In this study, the original model is extended to simulate neutral atmospheric boundary layers (ABL) and study the wake development of a single wind turbine. The PNS model has been validated for laminar and turbulent flat-plate boundary-layer cases and verified for a wind turbine (uniform inflow conditions) by comparing the computed solutions with the blade-resolved Navier-Stokes solutions for the NREL offshore 5-MW baseline wind turbine.

Popular representations of archaeology are investigated through a content analysis study of documentary programmes screened on Australian free-to-air television. Although public opinion survey research suggests that mass media, particularly television, are one of the major ways in which the Australian public encounters archaeology, no systematic investigation of the archaeological content appearing on Australian television has previously been undertaken. The results of the study show that the archaeo-historical documentary genre reinforces and perpetuates many familiar archaeological stereotypes and that Australian archaeology rarely, if ever, features in these programmes. The implications for Australian archaeology are discussed and potential strategies for engaging mass media in a public archaeology context are considered.

Event structural theories decompose verb meanings into an event template and idiosyncratic root. Many mainstream theories assume a bifurcation in the kinds of entailments contributed by roots and templates, in particular that lexical entailments of change of an individual in change-of-state verbs are only introduced by templates, not roots. We argue against such theories by comparing Levin's(1993) non-deadjectival vs. deadjectival change-of-state verb roots (e.g. crack vs. red roots). A broad-scale typological study reveals that red-type roots tend to have simple (e.g. non-deverbal) stative forms, but crack-type roots do not. Semantic studies of Kakataibo and English show that terms built on crack-type roots always entail change, while terms based on red-type roots may not. We thus suggest that crack-type roots entail change-of-state, contra Bifurcation.

Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)--positive (anti-HBc(+)) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc(+) allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc(+) allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc(+) donors. Six patients were hepatitis B surface antigen (HBsAg)(+) (group 1), and 9 patients were HBsAg negative (HBsAg(-); group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg(+) before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg(-) at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs(+) and HBsAg(-). Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc(+) allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc(+) liver allografts to susceptible recipients.

To evaluate whether the immune system of systemic lupus erythematosus (SLE) patients shows features of premature aging, we compared telomere length and proliferative potential of SLE peripheral blood mononuclear cells (PBMC) ( N = 90) to those of controls ( N = 64). SLE samples showed accelerated loss of telomeric DNA ( P = 0.00008) and higher levels of senescent (≤5 kb) telomeric DNA ( P = 0.00003). Viability cell counts and CFSE tracking in 6-week-old cell cultures indicated that SLE PBMC (CD8 + and CD4 + T cells) underwent fewer mitotic cycles and had shorter telomeres than controls ( P = 0.04). However, a CD8 + CD28 lo T cell subset expanded preferentially in SLE-derived bulk cultures ( P = 0.0009), preserved telomeric DNA ( P = 0.01 vs entire CD8 + ), and displayed telomerase activity [2.1 telomerase arbitrary units (TAU) vs 0.5 TAU in CD8 + CD28 hi cells and 0.3 TAU in bulk PBMC; P = 0.05]. These T cell anomalies could be due to chronic in vivo stimulation of the immune system and may contribute to the immune dysregulation found in SLE.

Previously, we developed a model for high incidence, endogenously generated hepatocellular carcinoma (HCC), the human alpha-1-antitrypsin (alpha1AT) Z gene transgenic mouse (Z#2). We now examine the potential utility of a model for endogenous carcinogenesis utilizing the Z#2 mouse also transgenic for the lacI gene, a convenient target for in vivo mutagenesis studies. We crossed the Z#2 line and mice transgenic for lambda/lacI shuttle vector (Big Blue), for determination of lacI mutant frequency during initiation of endogenous carcinogenesis. Five month old double transgenic mice (Z#2+/lacI+) successfully displayed: (1) the expected post-inflammatory stage of Z#2 carcinogenesis; and (2) hepatic lacI mutants measured at frequencies (10(-5)-10(-4)) useful to mutagenesis studies. In this study, hepatic lacI mutation frequencies in Z#2 transgenic mice appeared to be only slightly increased (2x) when compared to age matched negative controls. In the future, it may be important to reconcile possibly limited lacI mutagenesis at the time of initiation and demonstrated high incidence of hepatocarcinogenesis.

Results from the most comprehensive survey of professional Australian archaeologists ever undertaken are considered in the context of teaching and learning issues. The survey focused on the composition of the archaeological workforce, professional activities of archaeologists, skills and qualifications needed to work in archaeology, and opinions on archaeology teaching, learning and professional training. Data about the discipline are a basic requirement for informed decision making on archaeology teaching and learning, but few useful datasets are available. While results generally confirm anecdotal evidence and findings of previous surveys, the large sample size (n = 301) enables more detailed characterisation of important aspects of the contemporary archaeological workplace. An analysis of self-assessed skill sets and skill gaps indicates that the training of many professionals left significant gaps in several core skill and knowledge areas which are remarkably consistent across industry sectors. These findings can be used to inform curriculum development and the exploration of new archaeology teaching and learning models that are more attuned to the contemporary Australian archaeological workplace.

Z mutant–associated α1-antitrypsin deficiency in human beings leads to hepatitis and, in some cases, hepatocellular carcinoma. To begin to delineate the molecular basis for the development of hepatocellular carcinoma in α1-antitrypsin deficiency, we previously developed transgenic mice using human α1-antitrypsin M and Z genomic clones. High-copy Z lineage mice (12 gene copies/haploid mouse genome; “Z#2”) had hepatocytes distended with human α1-antitrypsin deficiency globules. Hepatitis was present, and the morphological changes mimicked those observed in human α1-antitrypsin deficiency-related liver disease. The numbers of hepatocytes containing α1-antitrypsin globules decreased with age, and α1-antitrypsin-negative nodular aggregates of hepatocytes increased in number and size. Hepatocytic dysplasia occurred as early as 6 wk and was almost universally present at 1 yr. Nodules of dysplastic cells demonstrating aneuploidy were seen as early as 10 wks. These became persistent, proliferative lesions. Dysplasia and aneuploidy distinctly increased with time and advancing microscopic stage as lesions progressed to malignancy. Tumors were seen after 1 yr as adenomas, which are aneuploid and most likely well-differentiated hepatocellular carcinoma, and borderline malignant lesions; and, in 82 of Z#2 mice 16 to 20 mo old, as invasive hepatocellular carcinoma. These observations suggest but do not conclusively prove that hepatocellular carcinoma in α1-antitrypsin deficiency and other hepatic disorders arises as a result of a common, endogenously stimulated pathway for hepatocellular carcinogenesis. (Hepatology 1994;19:389–397).

High-grade cervical intraepithelial lesions (HGCINs) are easily diagnosed by established histologic criteria. However, we encountered problematic cases that are difficult to diagnose because features intermediate between dysplasia and metaplasia are present. p16 and Ki-67 immunostains proved HGCIN in these difficult and unusual cases. Because these are unusual cases of cervical dysplasia, we decided to type the human papillomavirus (HPV) using the Invader HPV test with analyte-specific reagents developed by Third Wave Technologies (Madison, WI, USA) (a new HPV screening assay applicable to tissue and amenable to rapid, sensitive, and specific detection of 14 high- to intermediate-risk HPV types) and a panel of immunostains. Results of these difficult cases are compared with classic HGCIN cases. We searched our pathology files over a period of 16 months for high-grade squamous intraepithelial lesion, cervical intraepithelial neoplasia II, cervical intraepithelial neoplasia III, and p16. To identify cases of difficult HGCIN with features intermediate between dysplasia and metaplasia, we reviewed all surgical cases of HGCIN that required p16 and Ki-67 diagnosis confirmation. Cases of interest were also stained with ProExC. Human papillomavirus screening and HPV 16/18 typing were performed by the Invader assays as described previously. Ten cases of classic HGCIN were easily diagnosed by hypercellularity, significant atypia, mitotic figures, and diffuse staining by p16, Ki67 and ProExC. The Invader assay identified HPV 16 (A9 positive/HPV16 positive) in 7 of 10 cases; the 3 others were A7 positive/not HPV18 (1) and A9 positive/not HPV16 (2). Eight cases of difficult HGCIN were identified. These showed only mild-to-moderate cellularity, a lack of significant atypia, absent-to-rare mitotic figures, and diffuse staining by p16, Ki-67, and ProExC. Human papillomavirus DNA was detected in 5 of 8 cases: only 1 was A9 positive/HPV16 positive, 1 was A5/A6 positive, 1 was A7 positive/not HPV18, and 2 were A9 positive/not HPV16. Three remaining cases demonstrated sufficient DNA to be analyzed by the Invader assay, but results were negative. This is a poorly recognized unusual group of cervical HGCIN with features intermediate between dysplasia and metaplasia that is easily confused by histologic examination. Immunostains prove the high-grade nature of these lesions, and Invader assay demonstrates association with HPV types other than 16/18 (ie, other HPV types detected by Invader assay). In this study, we present an unusual group of cases of high-grade dysplasia, not recognized by hematoxylin and eosin but identified by Ki67 and P16. It is very important to emphasize that this unusual group of high-grade dysplasias is associated with high-risk HPV but with types other than 16/18.

Various combinations of antibiotics are reported to show synergy to in treating nosocomial infections with multidrug resistant (MDR)-Acinetobacter baumannii (A. baumannii). Here we studied hospital-acquired outbreak strains of MDR-A. baumannii to evaluate optimal combinations of antibiotics. One hundred twenty-one strains were grouped into one major and one minor clonal group based on repetitive-polymerase chain reaction amplification. Twenty representative strains were tested for antibiotic synergy using Etest®. Five strains were further analyzed by analytical isoelectric focusing and PCR to identify β-lactamase resistance genes or other antibiotic resistance determinants. Our investigation showed that the outbreak strains of MDR-A. baumannii belonged to two dominant clones. A combination of colistin and doxycycline showed the best result, being additive or synergistic against 70% of tested strains. Antibiotic additivity was observed more frequently than synergy. Strains possessing the same clonality did not necessarily demonstrate the same response to antibiotic combinations in vitro. We conclude that the effect of antibiotic combinations on our outbreak strains of MDR-A. baumannii seemed strain-specific. The bacterial response to antibiotic combinations is probably a result of complex interactions between multiple concomitant antibiotic resistance determinants in each strain.

Antibiotic resistance is increasing resulting in a decreasing number of fully active antimicrobial agents available to treat infections with multi-drug resistant (MDR) bacteria. Herbal medicines may offer alternative treatment options. A direct inoculation method simulating the standard disc diffusion assay was developed to determine in vitro antimicrobial activity of sixty herbal extracts against MDR-Acinetobacter baumannii (A. baumannii). Eighteen herbal extracts inhibited MDR-A. baumannii on agar plates, although the magnitude and quality of bacterial inhibition differed considerably among the antibacterial herbal extracts. Next, minimal inhibitory concentration (MIC) of these antibacterial herbal extracts was calculated using a broth microdilution assay. For most herbal extracts, the larger the zone of inhibition on agar plates, the lower the MIC. In general, hetero-resistance on agar plates correlated with higher MIC. The skip well phenomenon was seen with two herbal extracts. In conclusion, 30% of the screened herbal extracts demonstrated in vitro antibacterial activity against MDR-A. baumannii using similar rigorous testing methods as those commonly employed for assessing antimicrobial activity of synthetic antibacterial agents. Characterization of a specific compound conferring this antibacterial activity of the herbal extracts may help to identify novel antimicrobial agents active against highly resistant bacteria.

Human papillomavirus (HPV) infection strongly correlates with the development of anal intraepithelial neoplasias and carcinomas; however, few studies have characterized the distribution of the specific subtypes of the virus in the varying grades of dysplasia. This report characterizes the distribution of HPV 16/18 in surgical specimens with anal intraepithelial neoplasia (AIN) I-III and histological variants of anal carcinoma. A total of 111 anal surgical specimens with no dysplasia (10), AIN I-III (53), and anal carcinomas (48) were evaluated for the presence of high-risk HPV infection and subtyped by nested PCR or the Invader Assay. High-risk virus types were detected in progressively greater number of anal intraepithelial lesions from 56% in low grade to 88% in high grade. Type 16 was the prevalent subtype and was noted in 28% of low grade and 68% of high-grade lesions. Moderate dysplasias showed type 16 in 20%, a prevalence similar to that in low-grade lesions. The non-16/18 subtypes of the virus predominated and were present in 50% of the cases. Most (89%) squamous carcinomas were associated with high-risk viruses, 68% with type 16, a prevalence similar to that noted in high-grade dysplasia. Non-16/18 subtypes were encountered more frequently in squamous carcinomas from immunodeficient individuals (57% cases) as compared with immunocompetent individuals (18% cases). The similarity in the prevalence of type 16 in high-grade dysplasia and squamous carcinomas suggests that anal intraepithelial lesion III is the true precursor of squamous carcinoma and warrants aggressive management. Anal intraepithelial lesions II showed a virus distribution that was similar to low-grade dysplasia. In addition, a subset of these that were associated with type 16 or 18 showed progression, whereas those associated with non-16/18 subtypes regressed, thereby raising the possibility of conservative management for these lesions.

Purpose: Glioblastoma multiforme is a deadly primary brain cancer. Because the tumor kills due to recurrences, we tested the hypothesis that a new treatment would lead to immunological memory in a rat model of recurrent glioblastoma multiforme. Experimental Design: We developed a combined treatment using an adenovirus (Ad) expressing fms-like tyrosine kinase-3 ligand (Flt3L), which induces the infiltration of immune cells into the tumor microenvironment, and an Ad expressing herpes simplex virus-1–thymidine kinase (TK), which kills proliferating tumor cells in the presence of ganciclovir. Results: This treatment induced immunological memory that led to rejection of a second glioblastoma multiforme implanted in the contralateral hemisphere and of an extracranial glioblastoma multiforme implanted intradermally. Rechallenged long-term survivors exhibited anti-glioblastoma multiforme–specific T cells and displayed specific delayed-type hypersensitivity. Using depleting antibodies, we showed that rejection of the second tumor was dependent on CD8+ T cells. Circulating anti-glioma antibodies were observed when glioblastoma multiforme cells were implanted intradermally in naïve rats or in long-term survivors. However, rats bearing intracranial glioblastoma multiforme only exhibited circulating antitumoral antibodies upon treatment with Ad-Flt3L + Ad-TK. This combined treatment induced tumor regression and release of the chromatin-binding protein high mobility group box 1 in two further intracranial glioblastoma multiforme models, that is, Fisher rats bearing intracranial 9L and F98 glioblastoma multiforme cells. Conclusions: Treatment with Ad-Flt3L + Ad-TK triggered systemic anti–glioblastoma multiforme cellular and humoral immune responses, and anti–glioblastoma multiforme immunological memory. Release of the chromatin-binding protein high mobility group box 1 could be used as a noninvasive biomarker of therapeutic efficacy for glioblastoma multiforme. The robust treatment efficacy lends further support to its implementation in a phase I clinical trial. (Clin Cancer Res 2009;15(19):6113–27)

Aerodynamic simulations were carried out for the Generic Conventional Model, a 1/8th scale tractor-trailer model, that was tested in the NASA Ames 7’x10’ tunnel. The computed forces are compared for the zero, ten and fourteen degree yaw cases while the pressure coefficients are compared to experimental data for the ten and fourteen degree cases. A DES version of the one-equation Menter SAS is used in these simulations. Overall forces as well as pressure distributions matched well for the fourteen degree case. For the ten degree case, the forces were in reasonable agreement while the pressure distributions indicated a need for tighter grid resolution as well as possibly advanced turbulence models.

The Launder-Shima 1 Reynolds stress model is implemented in an existing scalable parallel flow solver. The complexity of the dissipation equation for this model adds stiness and instability characteristics to the equation system, particularly when integrating to the wall with sub-layer resolution. In the present work, the dissipation equation from LaunderShima model was replaced by the well known k model dissipation equation in an eort to produce a more robust and stable Reynolds stress model. Computations for standard flat plate, square cylinder, backward facing step, surface mounted cube, and DARPA SUBOFF body are compared to experimental data for both models. The modified model showed a significant improvement in stability and robustness over the Launder-Shima model, while keeping the same flow prediction accuracy.

Transgenic mice were constructed using human alpha 1-antitrypsin M and Z genomic clones. Livers of the M lineage mice showed slight cellular pleomorphism and immunohistochemically demonstrable finely granular alpha 1-antitrypsin material in hepatocytes. Z lineage mice with five gene copies per haploid mouse genome (Z#1) demonstrated fine granular alpha 1-antitrypsin material and a few large globules. In contrast, Z lineage mice with 12 gene copies per haploid mouse genome (Z#2) demonstrated hepatocytes filled with homogeneous, eosinophilic globules that were strongly reactive with diastase and periodic acid-Schiff and antibody to alpha 1-antitrypsin. Scattered microscopic polymorphonuclear leukocyte accumulations were seen that contained extracellular alpha 1-antitrypsin material, but there was neither histological nor serological evidence of mouse infectious hepatitis. In young animals, small clusters of hepatocytes lacking alpha 1-antitrypsin material were seen. These cells were the dominant population in older animals and formed nodular arrangements. Fibrosis was not demonstrable in neonatal and young animals or in any of the controls, but perisinusoidal fibrosis was seen in older Z#2 mice. Groups of hepatocytes without alpha 1-antitrypsin material showed dysplastic changes. We conclude that the transgenic mouse is a reliable and useful model in which to study the effects of alpha 1-antitrypsin in the liver because it demonstrates changes similar to those in the human disease.

Although rodent glioblastoma (GBM) models have been used for over 30 years, the extent to which they recapitulate the characteristics encountered in human GBMs remains controversial. We studied the histopathological features of dog GBM and human xenograft GBM models in immune-deficient mice (U251 and U87 GBM in nude Balb/c), and syngeneic GBMs in immune-competent rodents (GL26 cells in C57BL/6 mice, CNS-1 cells in Lewis rats). All GBMs studied exhibited neovascularization, pleomorphism, vimentin immunoreactivity, and infiltration of T-cells and macrophages. All the tumors showed necrosis and hemorrhages, except the U87 human xenograft, in which the most salient feature was its profuse neovascularization. The tumors differed in the expression of astrocytic intermediate filaments: human and dog GBMs, as well as U251 xenografts expressed glial fibrillary acidic protein (GFAP) and vimentin, while the U87 xenograft and the syngeneic rodent GBMs were GFAP(-) and vimentin(+). Also, only dog GBMs exhibited endothelial proliferation, a key feature that was absent in the murine models. In all spontaneous and implanted GBMs we found histopathological features compatible with tumor invasion into the non-neoplastic brain parenchyma. Our data indicate that murine models of GBM appear to recapitulate several of the human GBM histopathological features and, considering their reproducibility and availability, they constitute a valuable in vivo system for preclinical studies. Importantly, our results indicate that dog GBM emerges as an attractive animal model for testing novel therapies in a spontaneous tumor in the context of a larger brain.