Responding to Crisis: Evaluation of the Australian Aid Program's Contribution to the National HIV Response in Papua New Guinea, 2006-2010

The Australian aid program has played a prominent role in responding to HIV in Papua New Guinea (PNG) since 1995. The evaluation focused on AusAID’s contribution to the response and its HIV program activities from 2006, led by the PNG-Australia HIV and AIDS Program, in the broader historical context. The evaluation found that AusAID was a major driver of the national HIV response in PNG. However, the relevance and effectiveness of Australia’s interventions was mixed. For this reason, the evaluation recommended that AusAID move to an integrated health approach to HIV in PNG; step back from a dominant role in shaping and implementing the response and intensify support for PNG champions of the HIV response; and retain the leadership of the in-house senior technical expert but contract out grant management and capacity building functionsThis report was commisioned by Australian Agency for International Development (AusAID

Pelagic Functional Group Modeling: Progress, Challenges and Prospects

In this paper, we review the state of the art and major challenges in current efforts to incorporate biogeochemical functional groups into models that can be applied on basin-wide and global scales, with an emphasis on models that might ultimately be used to predict how biogeochernical cycles in the ocean will respond to global warming. We define the term biogeochemical functional group to refer to groups of organisms that mediate specific chemical reactions in the ocean. Thus, according to this definition, functional groups have no phylogenetic meaning-these are composed of many different species with common biogeochemical functions. Substantial progress has been made in the last decade toward quantifying the rates of these various functions and understanding the factors that control them. For some of these groups, we have developed fairly sophisticated models that incorporate this understanding, e.g. for diazotrophs (e.g. Trichodesmium), silica producers (diatoms) and calcifiers (e.g. coccolithophorids and specifically Emiliania huxleyi). However, current representations of nitrogen fixation and calcification are incomplete, i.e., based primarily upon models of Trichodesmium and E huxleyi, respectively, and many important functional groups have not yet been considered in open-ocean biogeochemical models. Progress has been made over the last decade in efforts to simulate dimethylsulfide (DMS) production and cycling (i.e., by dinoflagellates and prymnesiophytes) and denitrification, but these efforts are still in their infancy, and many significant problems remain. One obvious gap is that virtually all functional group modeling efforts have focused on autotrophic microbes, while higher trophic levels have been completely ignored. It appears that in some cases (e.g., calcification), incorporating higher trophic levels may be essential not only for representing a particular biogeochemical reaction, but also for modeling export. Another serious problem is our tendency to model the organisms for which we have the most validation data (e.g., E huxleyi and Trichodesmium) even when they may represent only a fraction of the biogeochemical functional group we are trying to represent. When we step back and look at the paleo-oceanographic record, it suggests that oxygen concentrations have played a central role in the evolution and emergence of many of the key functional groups that influence biogeochemical cycles in the present-day ocean. However, more subtle effects are likely to be important over the next century like changes in silicate supply or turbulence that can influence the relative success of diatoms versus dinoflagellates, coccolithophorids and diazotrophs. In general, inferences drawn from the paleo-oceanographic record and theoretical work suggest that global warming will tend to favor the latter because it will give rise to increased stratification. However, decreases in pH and Fe supply could adversely impact coccolithophorids and diazotrophs in the future. It may be necessary to include explicit dynamic representations of nitrogen fixation, denitrification, silicification and calcification in our models if our goal is predicting the oceanic carbon cycle in the future, because these processes appear to play a very significant role in the carbon cycle of the present-day ocean and they are sensitive to climate change. Observations and models suggest that it may also be necessary to include the DMS cycle to predict future climate, though the effects are still highly uncertain. We have learned a tremendous amount about the distributions and biogeochemical impact of bacteria in the ocean in recent years, yet this improved understanding has not yet been incorporated into many of our models. All of these considerations lead us toward the development of increasingly complex models. However, recent quantitative model intercomparison studies suggest that continuing to add complexity and more functional groups to our ecosystem models may lead to decreases in predictive ability if the models are not properly constrained with available data. We also caution that capturing the present-day variability tells us little about how well a particular model can predict the future. If our goal is to develop models that can be used to predict how the oceans will respond to global warming, then we need to make more rigorous assessments of predictive skill using the available data

In-situ Temperature Stations Elucidate Species’ Phenological Responses to Climate in the Alps, but Meteorological and Snow Reanalysis Facilitates Broad Scale and Long-Term Studies

Linking climate variability and change to the phenological response of species is particularly challenging in the context of mountainous terrain. In these environments, elevation and topography lead to a diversity of bioclimatic conditions at fine scales affecting species distribution and phenology. In order to quantify in situ climate conditions for mountain plants, the CREA (Research Center for Alpine Ecosystems) installed 82 temperature stations throughout the southwestern Alps, at different elevations and aspects. Dataloggers at each station provide local measurements of temperature at four heights (5 cm below the soil surface, at the soil surface, 30 cm above the soil surface, and 2 m above ground). Given the significant amount of effort required for station installation and maintenance, we tested whether meteorological data based on the S2M reanalysis could be used instead of station data. Comparison of the two datasets showed that some climate indices, including snow melt-out date and a heat wave index, can vary significantly according to data origin. More general indices such as daily temperature averages were more consistent across datasets, while threshold-based temperature indices showed somewhat lower agreement. Over a 12 year period, the phenological responses of four mountain tree species (ash (Fraxinus excelsior), spruce (Picea abies), hazel (Corylus avellana), birch (Betula pendula)), coal tits (Periparus ater) and common frogs (Rana temporaria) to climate variability were better explained, from both a statistical and ecological standpoint, by indices derived from field stations. Reanalysis data out-performed station data, however, for predicting larch (Larix decidua) budburst date. Overall, our study indicates that the choice of dataset for phenological monitoring ultimately depends on target bioclimatic variables and species, and also on the spatial and temporal scale of the study

Interannual variability of primary production and dissolved organic nitrogen storage in the North Pacific Subtropical Gyre

Author Posting. © American Geophysical Union, 2012. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 117 (2012): G03019, doi:10.1029/2011JG001830.The upper ocean primary production measurements from the Hawaii Ocean Time series (HOT) at Station ALOHA in the North Pacific Subtropical Gyre showed substantial variability over the last two decades. The annual average primary production varied within a limited range over 1991–1998, significantly increased in 1999–2000 and then gradually decreased afterwards. This variability was investigated using a one-dimensional ecosystem model. The long-term HOT observations were used to constrain the model by prescribing physical forcings and lower boundary conditions and optimizing the model parameters against data using data assimilation. The model reproduced the general interannual pattern in the observed primary production, and mesoscale variability in vertical velocity was identified as a major contributing factor to the interannual variability in the simulation. Several strong upwelling events occurred in 1999, which brought up nitrate at rates several times higher than other years and elevated the model primary production. Our model results suggested a hypothesis for the observed interannual variability pattern of primary production at Station ALOHA: Part of the upwelled nitrate input in 1999 was converted to and accumulated as semilabile dissolved organic nitrogen (DON), and subsequent recycling of this semilabile DON supported enhanced primary productivity for the next several years as the semilabile DON perturbation was gradually removed via export.This work was supported in part by the Center for Microbial Oceanography, Research and Education (C-MORE) (NSF EF-0424599), Hawaii Ocean Time series program (NSF OCE09–26766), the Gordon and Betty Moore Foundation, and the Marine Biological Laboratory.2013-03-1

Stromal architecture directs early dissemination in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDA) is an extremely metastatic and lethal disease. Here, in both murine and human PDA, we demonstrate that extracellular matrix architecture regulates cell extrusion and subsequent invasion from intact ductal structures through tumor-associated collagen signatures (TACS). This results in early dissemination from histologically premalignant lesions and continual invasion from well-differentiated disease, and it suggests TACS as a biomarker to aid in the pathologic assessment of early disease. Furthermore, we show that pancreatitis results in invasion-conducive architectures, thus priming the stroma prior to malignant disease. Analysis in potentially novel microfluidic-derived microtissues and in vivo demonstrates decreased extrusion and invasion following focal adhesion kinase (FAK) inhibition, consistent with decreased metastasis. Thus, data suggest that targeting FAK or strategies to reengineer and normalize tumor microenvironments may have roles not only in very early disease, but also for limiting continued dissemination from unresectable disease. Likewise, it may be beneficial to employ stroma-targeting strategies to resolve precursor diseases such as pancreatitis in order to remove stromal architectures that increase risk for early dissemination

Undoing gender through performing the other

Following the perspective of gender as a socially constructed performance, consumer research has given light to how individuals take on, negotiate, and express a variety of gender roles. Yet the focus of research has remained on gender roles themselves, largely overlooking the underlying process of gender performativity and consumers’ engagement with it in the context of their everyday lives. Set within a performance methodology and the context of crossplay in live action role-playing games, this paper explores how individuals undo gender on a subjective level, thus becoming conscious and reflexive of gender performativity. The study suggests that individuals become active in undoing gender through engaging in direct, bodily performance of the gender other. Such performance does not challenge or ridicule norms, but pushes individuals to actively figure out for themselves how gender is performed. As a result, individuals become aware of gender performativity and become capable of actively recombining everyday performance

Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation.Wesuggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency

Roles of the 15-kDa Selenoprotein (Sep15) in Redox Homeostasis and Cataract Development Revealed by the Analysis of Sep 15 Knockout Mice

The 15-kDa selenoprotein (Sep15) is a thioredoxin-like, endoplasmic reticulum-resident protein involved in the quality control of glycoprotein folding through its interaction with UDP-glucose:glycoprotein glucosyltransferase. Expression of Sep15 is regulated by dietary selenium and the unfolded protein response, but its specific function is not known. In this study, we developed and characterized Sep15 KO mice by targeted removal of exon 2 of the Sep15 gene coding for the cysteinerich UDP-glucose:glycoprotein glucosyltransferase-binding domain. These KO mice synthesized a mutant mRNA, but the shortened protein product could be detected neither in tissues nor in Sep15 KO embryonic fibroblasts. Sep15 KO mice were viable and fertile, showed normal brain morphology, and did not activate endoplasmic reticulum stress pathways. However, parameters of oxidative stress were elevated in the livers of these mice. We found that Sep15 mRNA was enriched during lens development. Further phenotypic characterization of Sep15KO mice revealed a prominent nuclear cataract that developed at an early age. These cataracts did not appear to be associated with severe oxidative stress or glucose dysregulation.Wesuggest that the cataracts resulted from an improper folding status of lens proteins caused by Sep15 deficiency

Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial

In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4(+) BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy-even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements