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Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity

The Capuchin Catacombs in Palermo, Sicily, have been home to non-adult mummified remains since the seventeenth century CE. Despite the increasing numbers of scientific studies conducted at this site, very little research has focused specifically on the youngest members of late modern (1787–1880 CE) society. This research aims to redress the balance by examining 43 individuals to gain insight into the demographic profile of mummified non-adults, to characterize their health status and possible cause of death, and to better understand the funerary treatment offered to the youngest members of society. A portable X-ray unit was used to capture anteroposterior and lateral images of each mummy; this facilitated age estimation, the identification of pathological and/traumatic lesions, and evidence of conservation and the mummification process more generally. This study revealed that regardless of age and health status at the time of death, the mortuary rite performed was primarily influenced by the wealth and social standing of the deceased’s kin. No demographic trends were observed in the data and the lack of evidence of metabolic, neoplastic, and traumatic bone lesions suggest these non-adults died from short-term, acute illnesses. Even when individuals did display evidence of chronic health conditions that would have impacted their day-to-day lives (e.g., B035), they were not excluded from this mortuary tradition on the basis of their long-term health and care requirements in life. Artifacts were found with all individuals examined and were associated with the mummification process, conservation of mummies, and/or their display. This research has ultimately demonstrated that non-invasive imaging can be used to gain a more comprehensive understanding of the lives and deaths of non-adults inhabiting late modern Palermo.

Abstract Background No single marker of bladder cancer (BC) exists in urine samples with sufficient accuracy for disease diagnosis and treatment monitoring. The multiplex Oncuria BC assay noninvasively quantifies the concentration of 10 protein analytes in voided urine samples to quickly generate a unique molecular profile with proven BC diagnostic and treatment-tracking utility. Test adoption by diagnostic and research laboratories mandates reliably reproducible assay performance across a variety of instrumentation platforms used in different laboratories. Methods We compared the performance of the clinically validated Oncuria BC multiplex immunoassay when data output was generated on three different analyzer systems. Voided urine samples from 36 subjects (18 with BC and 18 Controls) were reacted with Oncuria test reagents in three 96-well microtiter plates on Day 1, and consecutively evaluated on the LED/image-based MagPix, and laser/flow-based Luminex 200 and FlexMap 3D (all xMAP instruments from Luminex Corp., Austin, TX) on Day 2. The BC assay uses magnetic bead-based fluorescence technology (xMAP, Multi-analyte profiling; Luminex) to simultaneously quantify 10 protein analytes in urine specimens [i.e., angiogenin (ANG), apolipoprotein E (ApoE), carbonic anhydrase IX (CA9), CXCL8/interleukin-8 (IL-8), matrix metalloproteinase-9 (MMP-9), matrix metalloproteinase-10 (MMP-10), serpin A1/alpha-1 anti-trypsin (A1AT), serpin E1/plasminogen activator inhibitor-1 (PAI-1), CD138/syndecan-1 (SDC1), and vascular endothelial growth factor-A (VEGF-A)]. All three analyzers quantify fluorescence signals generated by the Oncuria assay. Results All three platforms categorized all 10 analytes in identical samples at nearly identical concentrations, with variance across systems typically

IntroductionDiffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy of B-cells frequently encountered among people living with HIV. Immunological abnormalities are common in immunocompetent individuals with DLBCL, and are often associated with poorer outcomes. Currently, data on derangements of immunological proteins, such as cytokines and acute phase reactants, and their impact on outcomes in HIV-associated DLBCL (HIV-DLBCL) is lacking. This study assessed the levels and prognostic relevance of interleukin (IL)-6, IL-10 and Transforming Growth Factor Beta (TGFβ), the acute phase proteins C-reactive protein (CRP) and ferritin; serum free light chains (SFLC) (elevation of which reflects a prolonged pro-inflammatory state); and the activity of the immunosuppressive enzyme Indoleamine 2,3-dioxygenase (IDO)in South African patients with DLBCL.MethodsSeventy-six patients with incident DLBCL were enrolled, and peripheral blood IL-6, IL-10, TGFβ, SFLC and IDO-activity measured in selected patients. Additional clinical and laboratory findings (including ferritin and CRP) were recorded from the hospital records.ResultsSixty-one (80.3%) of the included patients were people living with HIV (median CD4-count = 148 cells/ul), and survival rates were poor (12-month survival rate 30.0%). The majority of the immunological proteins, except for TGFβ and ferritin, were significantly higher among the people living with HIV. Elevation of IL-6, SFLC and IDO-activity were not associated with survival in HIV-DLBCL, while raised IL-10, CRP, ferritin and TGFβ were. On multivariate analysis, immunological proteins associated with survival independently from the International Prognostic Index (IPI) included TGFβ, ferritin and IL-10.ConclusionDerangements of immunological proteins are common in HIV-DLBCL, and have a differential association with survival compared to that reported elsewhere. Elevation of TGFβ, IL-10 and ferritin were associated with survival independently from the IPI. In view of the poor survival rates in this cohort, investigation of the directed targeting of these cytokines would be of interest in our setting.

Abstract Effective antiviral treatments for coronavirus disease 2019 (COVID‐19) are needed to reduce the morbidity and mortality associated with severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2) infection, particularly in patients with risk factors for severe disease. Molnupiravir (MK‐4482, EIDD‐2801) is an orally administered, ribonucleoside prodrug of β‐D‐N4‐hydroxycytidine (NHC) with submicromolar potency against SARS‐CoV‐2. A population pharmacokinetic (PopPK) analysis for molnupiravir exposure was conducted using 4202 NHC plasma concentrations collected in 1207 individuals from a phase I trial in healthy participants, a phase IIa trial in non‐hospitalized participants with COVID‐19, a phase II trial in hospitalized participants with COVID‐19, and a phase II/III trial in non‐hospitalized participants with COVID‐19. Molnupiravir pharmacokinetics (PK) was best described by a two‐compartment model with a transit‐compartment absorption model and linear elimination. Molnupiravir apparent elimination clearance increased with body weight less‐than‐proportionally (power 0.412) and was estimated as 70.6 L/h in 80‐kg individuals with a moderate interindividual variability (43.4% coefficient of variation). Additionally, effects of sex and body mass index on apparent central volume and food status and formulation on the absorption mean transit time were identified as statistically significant descriptors of variability in these PK parameters. However, none of the identified covariate effects caused clinically relevant changes in the area under the NHC concentration versus time curve between doses, the exposure metric most closely related to clinical response. Overall, the PopPK model indicates that molnupiravir can be administered in adults without dose adjustment based on age, sex, body size, food, and mild‐to‐moderate renal or mild hepatic impairment.

Abstract As global SARS-CoV-2 burden and testing frequency have decreased, wastewater surveillance has emerged as a key tool to support clinical surveillance efforts. The aims of this study were to identify and characterize SARS-CoV-2 variants in wastewater samples collected from urban centers across South Africa. Here we show that wastewater sequencing analyses are temporally concordant with clinical genomic surveillance and reveal the presence of multiple lineages not detected by clinical surveillance. We show that wastewater genomics can support SARS-CoV-2 epidemiological investigations by reliably recovering the prevalence of local circulating variants, even when clinical samples are not available. Further, we find that analysis of mutations observed in wastewater can provide a signal of upcoming lineage transitions. Our study demonstrates the utility of wastewater genomics to monitor evolution and spread of endemic viruses.

This article presents the results of the development and implementation of a mentorship program, now in its sixth year, designed to support the professional development of teaching skills for faculty and contract instructors. The program is unique in that it is a combination of a variety of other approaches such as formal and informal mentoring as well as intra-departmental and interdepartmental mentoring. This model incorporates the effective elements of a mentor program as identified in the literature, while eschewing the traditional model of one-to-one mentoring between senior and junior colleagues. The findings to date, which include more support for teaching after participating in the project as well as an increase in the amount of faculty accessing a mentor, indicate that the program is achieving its intended goals and should continue. The authors provide recommendations and suggestions for the inclusion of a teaching mentorship program at other institutions within (or outside of) Canada.

Objectives: Neoadjuvant therapy has been theorized to increase complexity of non–small cell lung cancer resections; however, specific factors that contribute to intraoperative challenges after induction therapy have not been well described. We aimed to characterize the effect of nodal involvement and nodal treatment response on surgical complexity after neoadjuvant therapy. Methods: We identified patients treated with neoadjuvant therapy followed by anatomic lung resection for cN + non–small cell lung cancer between 2010 and 2020. Patients were categorized according to clinical N1 versus N2 disease. To evaluate the effect of nodal response to therapy, thoracic radiologists measured clinically suspected and pathologically involved lymph nodes before and after induction therapy. Operative reports were reviewed to identify technical challenges specifically related to nodal disease. Categorical outcomes were compared using Fisher exact test. Results: One hundred twenty-four patients met inclusion criteria, among whom 107 (86.3%) were treated with neoadjuvant chemotherapy, whereas chemoradiation (n = 8) and targeted therapy (n = 9) were less common. In cases with N1 disease, 8/38 (21.0%) required proximal pulmonary arterial control, whereas this was necessary in only 2/88 (2.3%) of N2 cases (P = .001). Likewise, sleeve resection and arterioplasty were needed more frequently during resection of N1 disease (7/38, 18.4%) versus N2 disease (0/88, P

Increasingly, Artificial Intelligence (AI) is having an impact on distance-based higher education, where it is revealing multiple ethical issues. However, to date, there has been limited research addressing the perspectives of key stakeholders about these developments. The study presented in this paper sought to address this gap by investigating the perspectives of three key groups of stakeholders in distance-based higher education: students, teachers, and institutions. Empirical data collected in two workshops and a survey helped identify what concerns these stakeholders had about the ethics of AI in distance-based higher education. A theoretical framework for the ethics of AI in education was used to analyse that data and helped identify what was missing. In this exploratory study, there was no attempt to prioritise issues as more, or less, important. Instead, the value of the study reported in this paper derives from (a) the breadth and detail of the issues that have been identified, and (b) their categorisation in a unifying framework. Together these provide a foundation for future research and may also usefully inform future institutional implementation and practice.

The datafication of learning has created vast amounts of digital data which may contribute to enhancing teaching and learning. While researchers have successfully used learning analytics, for instance, to improve student retention and learning design, the topic of privacy in learning analytics from students' perspectives requires further investigation. Specifically, there are mixed results in the literature as to whether students are concerned about privacy in learning analytics. Understanding students' privacy concern, or lack of privacy concern, can contribute to successful implementation of learning analytics applications in higher education institutions. This paper reports on a study carried out to understand whether students are concerned about the collection, use and sharing of their data for learning analytics, and what contributes to their perspectives. Students in a laboratory session (n = 111) were shown vignettes describing data use in a university and an e-commerce company. The aim was to determine students' concern about their data being collected, used and shared with third parties, and whether their concern differed between the two contexts. Students' general privacy concerns and behaviours were also examined and compared to their privacy concern specific to learning analytics. We found that students in the study were more comfortable with the collection, use and sharing of their data in the university context than in the e-commerce context. Furthermore, these students were more concerned about their data being shared with third parties in the e-commerce context than in the university context. Thus, the study findings contribute to deepening our understanding about what raises students’ privacy concern in the collection, use and sharing of their data for learning analytics. We discuss the implications of these findings for research on and the practice of ethical learning analytics.

Abstract Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous population of neoplasms that arise from hormone-secreting islet cells of the pancreas and have increased markedly in incidence over the past four decades. Non-functional PanNETs, which occur more frequently than hormone-secreting tumors, are often not diagnosed until later stages of tumor development and have poorer prognoses. Development of successful therapeutics for PanNETs has been slow, partially due to a lack of diverse animal models for pre-clinical testing. Here, we report development of an inducible, conditional mouse model of PanNETs by using a bi-transgenic system for regulated expression of the aberrant activator of Cdk5, p25, specifically in β-islet cells. This model produces a heterogeneous population of PanNETs that includes a subgroup of well-differentiated, non-functional tumors. Production of these tumors demonstrates the causative potential of aberrantly active Cdk5 for generation of PanNETs. Further, we show that human PanNETs express Cdk5 pathway components, are dependent on Cdk5 for growth, and share genetic and transcriptional overlap with the INS-p25OE model. The utility of this model is enhanced by the ability to form tumor-derived allografts. This new model of PanNETs will facilitate molecular delineation of Cdk5-dependent PanNETs and the development of new targeted therapeutics.

Abstract A recently published article described the safety, tolerability, and pharmacokinetic profile of molnupiravir (Painter et al. 2021), a novel antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19). Here, we report an unprecedented collaboration between sponsor, contract research organization (CRO), and regulatory authorities that enabled accelerated generation of these phase I data, including administration of the first-in-human (FIH) dose of molnupiravir within 5 days of receiving regulatory approval in the United Kingdom (UK). Single and multiple ascending dose (SAD and MAD, respectively) cohorts were dosed in randomized, double-blind, and placebo-controlled fashion, with a 6:2 active-to-placebo ratio in each cohort. A food-effect (FE) cohort included 10 subjects who were randomized to receive drug in the fasted or fed state followed by the fed or fasted state to complete a fed and fasted sequence for each subject. Dose escalation decisions were accelerated and MAD cohorts were initiated prior to completion of all SAD cohorts with the provision that the total daily dose in a MAD cohort would not exceed a dose proven to be safe and well-tolerated in a SAD cohort. Dosing in healthy volunteers was completed for eight single ascending dose (SAD) cohorts, seven multiple ascending dose (MAD) cohorts, and one food-effect (FE) cohort within approximately 16 weeks of initial protocol submission to the Research Ethics Committee (REC) and Medicines and Healthcare products Regulatory Agency (MHRA). Working to standard industry timelines, the FIH study would have taken approximately 46 weeks to complete and 33 weeks to enable phase 2 dosing. Data from this study supported submission of a phase 2/3 clinical trial protocol to the US Food and Drug Administration (FDA) within 8 weeks of initial protocol submission, with FDA comments permitting phase 2 study initiation within two additional weeks. In the setting of a global pandemic, this model of collaboration allows for accelerated generation of clinical data compared to standard processes, without compromising safety.

Environmental issues in the coverage of the elections are usually framed in relation to voters’ attitudes towards the specific problems, for instance, water quality or land use. The environment is not given standing in these discussions, rather, it is an instrument or resource for voters. In this article we investigate the relationship between news and politics by looking at media coverage of the 2019 local body elections in New Zealand. We follow a call to put place at the centre of journalism research and to investigate the emerging forms of environmental citizenship. We focus on a media market at each end of New Zealand’s two main islands and relate analysis of the coverage of local body elections coverage to related social groups engaged in environmental issues. The objective of our article is to consider the extent to which age plays a role in media representation of environmental issues in the context of local body elections.

While recent research has provided increasing insight into ocean ecosystem functions and rapidly improving predictive ability, it has become clear that for some key processes, including grazing by zooplankton, there simply is no currently available instrumentation to quantify relevant stocks and rates, remotely or in situ. When measurement capacity is lacking, collaborative research between instrument manufacturers and researchers can bring us closer to addressing key knowledge gaps. By necessity, this high risk, high rewards research will require iterative steps from best case scenarios under highly controlled and often artificial laboratory conditions to empirical verification in complex in situ conditions with diverse biota. To illustrate our point, we highlight the example of zooplankton grazing in marine planktonic food webs. Grazing by single-celled zooplankton accounts for the majority of organic carbon loss from marine primary production but is still measured with logistically demanding, point-sample incubation methods that result in reproducible results but at insufficient resolution to adequately describe temporal and spatial dynamics of grazer induced impacts on primary production, export production and the annual cycle of marine plankton. We advance a collaborative research and development agenda to eliminate this knowledge gap. Resolving primary production losses through grazing is fundamental to a predictive understanding of the transfer of matter and energy through marine ecosystems, major reservoirs of the global carbon cycle.

Abstract Results from the first VHF profiler research radar in Costa Rica, operating at a central radar frequency of 46.6 MHz, are presented. Emphasis has been on studies of scattering layers detected in the altitude range 1–6 km, with the main goal being to identify regions with radar echoes and observe the temporal evolution of the echoes. Data were obtained over the course of a full year using a vertical resolution of better than 100 m. Layers of strong scatter were observed regularly, often with simultaneous broad spectra, which may indicate enhanced turbulence. Similar layers have been observed over equatorial Indonesia, and these have been associated with the planetary boundary layer. The presence of echo layers was more common during the dry-season months (December–April); in fact during March, two layers were observed in the lower troposphere for more than 35% of the time. Stable pattern structures often occurred for extended periods, but at times the layers could also vary drastically in behavior from 1 day to the next. After sunset, strong echo layers could persist for several hours. Some examples of regularly observed layer behavior are given.

Pachodynerus erynnis (Lepeletier) is a predatory wasp that specializes in preying upon caterpillars, the larvae of moths and butterflies (Lepidoptera). This insect does not yet have an officially accepted common name and has been referred to as the red and black mason wasp, red-marked Pachodynerus, and a mason wasp. As with other closely related wasps, Pachodynerus erynnis does not form a communal hive, but builds solitary nests in holes or crevices of trees or man-made structures, as well as abandoned nests created by other cavity-nesting bees and wasps. The red and black mason wasp frequently visits flowering plants and can be found entering nesting cavities nearby. This insect is considered highly beneficial because it feeds on several key caterpillar pests, including armyworms (Spodoptera spp.), cutworms (Agrotis spp.), and loopers (Noctuoidea), and has been associated with increased pest control in managed landscapes. Although fairly common, this wasp often goes unnoticed due to its solitary nature and quick flight. Also published on the Featured Creatures website at http://entnemdept.ufl.edu/creatures/MISC/WASPS/Pachodynerus_erynnis.html

Background: Human enteroviruses (EV) consist of 106 serotypes and four species: EV-A, EV-B, EV-C and EV-D. Enteroviruses cause clinical symptoms varying from severe to mild. Knowledge of EV burden in South Africa is limited, and as non-polio EV are important causes of acute flaccid paralysis (AFP) and meningitis, information on the circulating serotypes is vital. Methods: Between 2010 and 2012, a total of 832 stool and viral isolate specimens were obtained from two national surveillance programmes at the National Institute for Communicable Diseases: the Rotavirus Sentinel Surveillance Programme (RSSP) and the AFP surveillance programme. Real-time polymerase chain reaction and Sanger sequencing were performed to detect and serotype EV. Results: Non-polio EV were detected in 446 specimens, of which 308 were sequenced. Stool specimens yielded a greater variety of serotypes than viral cultures. EV-B viruses were predominant (58.44%), whilst EV-C viruses were detected in 31% of the specimens tested. South African prevalence for these viruses was higher than other countries, such as France with less than 2%, and Spain and the United States with less than 10%. The most common serotype detected was Enterovirus 99 (EV-C, 8.63%), which has not been reported in other regions. Conclusion: Direct sequencing from stool specimens yields a broader, more comprehensive description of EV infections compared to sequencing from viral cultures. Disease-associated serotypes were detected, but only in small numbers. This study provides a baseline for EV strain circulation; however, surveillance needs to be expanded to improve EV knowledge in South Africa.

What type of capitalism do we live in today? My answer to this question draws upon two interrelated lines of argument. Firstly, I will argue that we inhabit an epoch of global capitalism. The precursors of this kind of capitalism originated from the late nineteenth century when the development of telegraph networks, modern transport systems and world time zones provided a global template for industrialisation and Western imperialism. From about 1980 a confluence of global events and processes bought a fully-fledged global capitalism into being. These included the collapse of Fordist Keynesianism, national Keynesianism and Soviet Communism along with First, Second and Third World demarcations; the international proliferation of neo-liberal policy regimes; the growth of transnational corporations in all economic sectors; the predominance of financialisation and the reconstitution of global workforces. Secondly, I will argue that the shift from organic surface energy to underground fossil energy intertwined the time of the earth with the time of human history as nature was being instrumentalised as a resource for humanity. Understanding the capitalist relations of power involved here requires that we rethink the emergence of industrial capitalism in the historical context of a world system built upon unequal socio-ecological exchange between core and periphery. Today, global capitalism has intensified the anthropogenic feedback loops associated with CO2 emissions and climate change and universalised the organisational frameworks of profit extraction and socio-ecological destruction. I refer here to the transnational systems of fossil fuel capitalism along with their interlinkages with financialisation and advertising/commodity fetishism. From the preceding lines of argument I will briefly outline the intra-capitalist and planetary-ecological crises out of which transnational coalitions of opposition might emerge.

During the 2014–2015 outbreak of Ebola virus disease in Guinea, 13 type 2 circulating vaccine-derived polioviruses (cVDPVs) were isolated from 6 polio patients and 7 healthy contacts. To clarify the genetic properties of cVDPVs and their emergence, we combined epidemiologic and virologic data for polio cases in Guinea. Deviation of public health resources to the Ebola outbreak disrupted polio vaccination programs and surveillance activities, which fueled the spread of neurovirulent VDPVs in an area of low vaccination coverage and immunity. Genetic properties of cVDPVs were consistent with their capacity to cause paralytic disease in humans and capacity for sustained person-to-person transmission. Circulation ceased when coverage of oral polio vaccine increased. A polio outbreak in the context of the Ebola virus disease outbreak highlights the need to consider risks for polio emergence and spread during complex emergencies and urges awareness of the challenges in polio surveillance, vaccination, and diagnosis.

There is an increased recognition that learning design drives both student learning experience and quality enhancements of teaching and learning. The Open University UK (OU) has been one of few institutions that have explicitly and systematically captured the designs for learning at a large scale. By applying advanced analytical techniques on large and fine-grained datasets, the OU has been unpacking the complexity of instructional practices, as well as providing conceptual and empirical evidence of how learning design influences student behaviour, satisfaction, and performance. This study discusses the implementation of learning design at the OU in the last ten years, and critically reviews empirical evidence from eight recent large-scale studies that have linked learning design with learning analytics. Four future research themes are identified to support future adoptions of learning design approaches.

Florida is home to approximately 315 species of native wild bees. These bees rely on flowers for survival; their diets consist exclusively of pollen and nectar harvested from flowers. Recently reported declines in some bee species have heightened awareness of bee conservation across the United States and motivated efforts to increase floral resources for bees. This 7-page fact sheet written by Rachel E. Mallinger, Wayne Hobbs, Anne Yasalonis, and Gary Knox and published by the UF/IFAS Entomology and Nematology Department shows how gardeners and land managers can aid in conservation efforts by planting flowers for bees in home or community gardens. http://edis.ifas.ufl.edu/IN1255

Mouse models of gastroesophageal junction (GEJ) cancer strive to recapitulate the intratumoral heterogeneity and cellular crosstalk within patient tumors to improve clinical translation. GEJ cancers remain a therapeutic challenge due to the lack of a reliable mouse model for preclinical drug testing. In this study, a novel patient-derived orthotopic xenograft (PDOX) was established from GEJ cancer via transabdominal surgical implantation. Patient tumor was compared to subcutaneously implanted patient-derived tumor xenograft (PDX) and PDOX by Hematoxylin and Eosin staining, immunohistochemistry and next-generation sequencing. Treatment efficacy studies of radiotherapy were performed. We observed that mechanical abrasion of mouse GEJ prior to surgical implantation of a patient-derived tumor in situ promotes tumor engraftment (100%, n=6). Complete PDOX engraftment was observed with rapid intra- and extraluminal tumor growth, as evidenced by magnetic resonance imaging. PDOXs contain fibroblasts, tumor-associated macrophages, immune and inflammatory cells, vascular and lymphatic vessels. Stromal hallmarks of aggressive GEJ cancers are recapitulated in a GEJ PDOX mouse model. PDOXs demonstrate tumor invasion into vasculature and perineural space. Next-generation sequencing revealed loss of heterozygosity with very high allelic frequency in NOTCH3, TGFB1, EZH2 and KMT2C in the patient tumor, the subcutaneous PDX and the PDOX. Immunohistochemical analysis of Her2/neu (also known as ERBB2), p53 (also known as TP53) and p16 (also known as CDKN2A) in PDX and PDOX revealed maintenance of expression of proteins found in patient tumors, but membranous EGFR overexpression in patient tumor cells was absent in both xenografts. Targeted radiotherapy in this model suggested a decrease in size by 61% according to Response Evaluation Criteria in Solid Tumors (RECIST), indicating a partial response to radiation therapy. Our GEJ PDOX model exhibits remarkable fidelity to human disease and captures the precise tissue microenvironment present within the local GEJ architecture, providing a novel tool for translating findings from studies on human GEJ cancer. This model can be applied to study metastatic progression and to develop novel therapeutic approaches for the treatment of GEJ cancer. This article has an associated First Person interview with the first author of the paper.

University ranking systems are being implemented with the aim of assessing and comparing higher education institutions at a global level. Despite their being increasingly used, rankings are often strongly criticized for their social and economic implications, as well as for limitations in their technical implementation. One of these limitations is that they do not consider the specific characteristics of online education. This study used a participatory approach to define a set of criteria and indicators suitable to reflect the specific nature of distance education. This endeavour will help evaluate and rank online higher education institutions more appropriately than in current practice, where indicators are devised for traditional universities. To this end, several stakeholders and informants were involved in a Delphi study in an attempt to reach the broader higher education institutions (HEI) community. According to the study participants, apart from students’ achievements and general quantitative measures of HEI performance, which are quite common in traditional ranking systems, teaching and student learning experience turned out to be the most important criteria. Student support, teacher support, technological infrastructure, research and organization were deemed middle ground criteria, while sustainability and reputation were regarded as the least important criteria.

Many occupant activities can adversely affect indoor air quality which has been shown to be detrimental to human health. This research eliminated some of the variability of previous measured levels of indoor particulate matter (PM) by removing all human activity and providing baseline data on the contribution occurring from home furnishings. Further objectives included investigating the effects of airtightness and mechanical ventilation on internal PM concentrations with controlled simulated occupancy.With natural ventilation, PM concentrations were 15% greater in bedroom of the less airtight (Control) house than that of the (Test house), post-furnishing which indicates that there is a considerable amount of natural variation which may not be solely due to occupant activities.Simulated occupancy dramatically increased the concentration of PM found in both houses by just under 5-fold. With simulated occupancy, the majority of the PM was present as fine particles (≤PM1) for both houses (93–94%), whereas without simulated occupancy, the proportion of fine particles was lower (88–89%).After furnishing and without the use of mechanical ventilation, PM10 concentrations exceeded the WHO Guidelines for PM10 of 50 μg m−3 for 56% of the testing duration for the Control bedroom and 35% for the Test bedroom. The use of mechanical ventilation reduced the mean internal PM concentrations by approximately 90% for all PM sizes in both study bedrooms which highlights the importance of use and maintenance of effective ventilation systems especially after furnishing activities. Keywords: Particulate matter, Indoor air quality, Mechanical ventilation, Simulated occupancy, Infiltration factor, New Zealand

This study investigated the in vitro toxic effects of Bitis arietans venom and the ability of antivenom produced by the South African Institute of Medical Research (SAIMR) to neutralize these effects. The venom (50 µg/mL) reduced nerve-mediated twitches of the chick biventer muscle to 19% ± 2% of initial magnitude (n = 4) within 2 h. This inhibitory effect of the venom was significantly attenuated by prior incubation of tissues with SAIMR antivenom (0.864 µg/µL; 67% ± 4%; P < 0.05; n = 3–5, unpaired t-test). Addition of antivenom at t50 failed to prevent further inhibition or reverse the inhibition of twitches and responses to agonists. The myotoxic action of the venom (50 µg/mL) was evidenced by a decrease in direct twitches (30% ± 6% of the initial twitch magnitude) and increase in baseline tension (by 0.7 ± 0.3 g within 3 h) of the chick biventer. Antivenom failed to block these effects. Antivenom however prevented the venom induced cytotoxic effects on L6 skeletal muscle cells. Venom induced a marginal but significant reduction in plasma clotting times at concentrations above 7.8 µg/100 µL of plasma, indicating poor procoagulant effects. In addition, the results of western immunoblotting indicate strong immunoreactivity with venom proteins, thus warranting further detailed studies on the neutralization of the effects of individual venom toxins by antivenom.

Introduction:Upper trunk brachial plexus palsy can result from high energy trauma and has never been reported following spinal manipulation.Background:The case is presented of a patient who developed an acute brachial plexus upper trunk palsy following spinal manipulative therapy. Discussion:Discussion is made on the incidence of complications following manipulation and recommendations to prospectively capture all serious complications.Concluding Remarks:Risks exist with spinal manipulative therapy. Neurological injury can occur. Risk assessment and re-examination should occur at every visit. Large rigorous prospective studies are required to identify the true incidence of serious complications resulting from manipulative therapy and the benefit:risk ratio.

In spite of the wealth of research on the Great Barrier Reef, few detailed biodiversity assessments of its inshore coral communities have been conducted. Effective conservation and management of marine ecosystems begins with fine-scale biophysical assessments focused on diversity and the architectural species that build the structural framework of the reef. In this study, we investigate key coral diversity and environmental attributes of an inshore reef system surrounding the Keppel Bay Islands near Rockhampton in Central Queensland, Australia, and assess their implications for conservation and management. The Keppels has much higher coral diversity than previously found. The average species richness for the 19 study sites was ~40 with representatives from 68% of the ~244 species previously described for the southern Great Barrier Reef. Using scleractinian coral species richness, taxonomic distinctiveness and coral cover as the main criteria, we found that five out of 19 sites had particularly high conservation value. A further site was also considered to be of relatively high value. Corals at this site were taxonomically distinct from the others (representatives of two families were found here but not at other sites) and a wide range of functionally diverse taxa were present. This site was associated with more stressful conditions such as high temperatures and turbidity. Highly diverse coral communities or biodiversity ‘hotspots’ and taxonomically distinct reefs may act as insurance policies for climatic disturbance, much like Noah’s Arks for reefs. While improving water quality and limiting anthropogenic impacts are clearly important management initiatives to improve the long-term outlook for inshore reefs, identifying, mapping and protecting these coastal ‘refugia’ may be the key for ensuring their regeneration against catastrophic climatic disturbance in the meantime.

To determine the incidence, clinical and laboratory characteristics, and utility of molecular diagnosis of human monocytotropic ehrlichiosis (HME) in the primary care setting, we conducted a prospective study in an outpatient primary care clinic in Cape Girardeau, Missouri. One hundred and two patients with a history of fever for 3 days (>37.7°C), tick bite or exposure, and no other infectious disease diagnosis were enrolled between March 1997 and December 1999. HME was diagnosed in 29 patients by indirect immunofluorescent antibody assay and polymerase chain reaction (PCR). Clinical and laboratory manifestations included fever (100%), headache (72%), myalgia or arthralgia (69%), chills (45%), weakness (38%), nausea (38%), leukopenia (60%), thrombocytopenia (56%), and elevated aspartate aminotransferase level (52%). Hospitalization occurred in 41% of case-patients. PCR sensitivity was 56%; specificity, 100%. HME is a prevalent, potentially severe disease in southeastern Missouri that often requires hospitalization. Because clinical presentation of HME is nonspecific, PCR is useful in the diagnosis of acute HME.

Book review of: Inequality: A New Zealand Crisis, by Max Rushbrooke (ed), Wellington: Bridget Williams, 2013, 279pp. ISBN 9781927131510. This book follows international publications, such as Richard Wilkinson and Kate Pickets’ Spirit Level (2009) and Joseph Stiglitz’s The Price of Inequality (2012). After 30 plus years of neo-liberal ideology mainstream social scientists and non-doctrinaire economists had reached a consensus; increasing inequality had worsened social problems without improving economic growth or development. Some well-off people were even prepared to support progressive taxes and increased social provision for the purposes of social cohesion. It was thus hard to sustain an ethical defence of neo-liberal policy programmes. Max Rashbrooke’s introduction to this edited collection notes that New Zealand is a special case. From the mid-1980s to the mid-2000s the rich-poor gap widened faster than in any other developed country (p. 1). Various authors consider the nature, causes and consequences of this development over 15 chapters. Interspersed between them are 14 unique viewpoints on wealth and poverty in New Zealand. A range of graphs, figures and tables give empirical weight to the view that inequality is structurally entrenched and socially damaging

We recently showed that IGFBP2 is overexpressed in primary lung cancer tissues. This study aims to determine whether IGFBP2 is elevated in blood samples of lung cancer patients and whether its level is associated with clinical outcomes.Plasma IGFBP2 levels were determined blindly by enzyme-linked immunosorbent assay in 80 lung cancer patients and 80 case-matched healthy controls for comparison. We analyzed blood samples for IGFBP2 levels from an additional 84 patients with lung cancer and then tested for associations between blood IGFBP2 levels and clinical parameters in all 164 lung cancer patients. All statistical tests were two-sided and differences with p160.9 ng/ml is 15.1 months; whereas median survival time was 128.2 months for the patients whose blood IGFBP2 was ≤ 160.9 ng/ml (p =0.0002).Blood IGFBP2 is significantly increased in lung cancer patients. A high circulating level of IGFBP2 is significantly associated with poor survival, suggesting that blood IGFBP2 levels could be a prognostic biomarker for lung cancer.

Reviewed book edited by Stuart Allan Publication date: October, 2011 A number of articles deal with the social reception of new media content. Important themes here include citizenship and public knowledge, ethnographies of news consumption, news consumption and social memory. Another set of chapters looks at news and journalism against the backdrop of crisis and conflict. Relevant titles here include 'Journalists and war crimes', 'Peace journalism', 'News and foreign policy', 'Reporting the climate change crisis', 'Iconic Photojournalism and Absent Images: Democratisation and Memories of Terror'.

The editor describes this book as a first ever attempt to map the impact of the internet on key aspects of governance within Asia: democratisation, e-government, cybersecurity and terrorism, technical coordination, internet policy and regulation. The subtitle of the book also suggests that these matters will be critically evaluated.

"Over subsesquent chapters, Trotter explains how key phases of New Zealand hisotry were shaped by institutionalised power and political struggle. Along the way major villains are identified, paraded and held to account. During the colonisation phase we observe how Edward Wakefield's land speculation schemes overruled the customary rights of Maori and exploited the aspirations of lowly settlers..."

The arrival of this book last November (2006) was a landmark event for political journalism in New Zealand. There had been rumours about exposé of National Party links with the Exclusive Brethren sect and wealthy corporate donors. This kind of journalism is rarely attempted within New zealand's mainstream media organisations. Consequently, the public sphere is routinely shaped by the market researchers, public relations practitioners and micro-managing spin doctors. The reception accorded to Hager's book illustrates this process.

Review of The Three Waves of Globalisation: A History is a Developing Global Consciousness, by Robbie Robertson Robertson's all-embracing, long dureé conception of globalisation provides important anthropological isights. However, the universalist scale of his narrative leads to over-generalised accounts of structural power and political opposition.

ON 3 October 2004, APN News and Media, owners of the New Zealand Herald launched a Sunday paper. The Herald on Sunday arrived as a major competitor for the Fairfax-owned Sunday Star-Times and Sunday News. The first issue featured a group photo of eager-looking new staff. Missing from their news coverage, however, was a timely story about media ownership and democracy. Ten days earlier, journalists at the weekday New Zealand Herald had announced plans for court action against their employers. APN had refused to extend the New Zealand Herald collective agreement to workers on the Sunday edition. This story began on July 30 with APN’s decision to launch the new paper.

Review of Can we talk about the news? A discussion of media criticism in New Zealand, by Jane Dunbar. NZ Journalism Monographs, No3, Department of Mass Communication and Journalism, University of Canterbury. In this monograph, Jane Dunbar interviews news journalists and media commentators about the quality of media criticism in New Zealand. This is certainly a pertinent theme for research. Dunbar's interviewees point out that local scrutiny of the news media is difficult to sustain. Thus, journalists within coporate media are unlikely to comment upon ownership patterns, within all media organisations unbiquitous advertising contracts available news space.