USING A MULTIPLE PRODUCT AND MULTIPLE INPUT APPROACH TO DAIRY PROFIT MAXIMIZATION: A SIMULATION USING OPERATIONS RESEARCH METHODS

Dairy producers generally take a single output/multiple input approach when making production decisions. Under component pricing, with large variance in individual component prices, a multiple output/multiple input approach maximizes profits. This paper applied our approach to the individual farm milk production decision.Livestock Production/Industries, Productivity Analysis,

The New Agent: A Qualitative Study to Strategically Adapt New Agent Professional Development

The qualitative study reported here assessed the needs of agents related to new agent professional development to improve the current model. Agents who participated in new agent professional development within the last 5 years were selected to participate in focus groups to determine concerns and continued needs. Agents enjoyed networking and struggled with the time away from their home counties. Recommendations for improvement include integrating the idea of pre-entry competencies, developing online new agent professional development sessions, introducing new agents to existing communities of practice, developing new communities of practice, and developing more resources for new agents

Dehiscence of detached internal limiting membrane in eyes with myopic traction maculopathy with spontaneous resolution

Background: Idjwi, an island of approximately 220,000 people, is located in eastern DRC and functions semi-autonomously under the governance of two kings (mwamis). At more than 8 live births per woman, Idjwi has one of the highest total fertility rates (TFRs) in the world. Rapid population growth has led to widespread environmental degradation and food insecurity. Meanwhile family planning services are largely unavailable.Methods: At the invitation of local leaders, we conducted a representative survey of 2,078 households in accordance with MEASURE DHS protocols, and performed ethnographic interviews and focus groups with key informants and vulnerable subpopulations. Modelling proximate determinates of fertility, we evaluated how the introduction of contraceptives and/or extended periods of breastfeeding could reduce the TFR.Results: Over half of all women reported an unmet need for spacing or limiting births, and nearly 70% named a specific modern method of contraception they would prefer to use; pills (25.4%) and injectables (26.5%) were most desired. We predicted that an increased length of breastfeeding (from 10 to 21 months) or an increase in contraceptive prevalence (from 1% to 30%), or a combination of both could reduce TFR on Idjwi to 6, the average desired number of children. Increasing contraceptive prevalence to 15% could reduce unmet need for contraception by 8%.Conclusions: To meet women’s need and desire for fertility control, we recommend adding family planning services at health centers with NGO support, pursuing a community health worker program, promoting extended breastfeeding, and implementing programs to end sexual- and gender-based violence toward women

Murine Renal Transplantation Procedure

Renal orthotopic transplantation in mice is a technically challenging procedure. Although the first kidney transplants in mice were performed by Russell et al over 30 years ago (1) and refined by Zhang et al years later (2), few people in the world have mastered this procedure. In our laboratory we have successfully performed 1200 orthotopic kidney transplantations with > 90% survival rate. The key points for success include stringent control of reperfusion injury, bleeding and thrombosis, both during the procedure and post-transplantation, and use of 10-0 instead of 11-0 suture for anastomoses

CD103 Expression Is Required for Destruction of Pancreatic Islet Allografts by CD8+ T Cells

The mechanisms by which CD8 effector populations interact with epithelial layers is a poorly defined aspect of adaptive immunity. Recognition that CD8 effectors have the capacity to express CD103, an integrin directed to the epithelial cell-specific ligand E-cadherin, potentially provides insight into such interactions. To assess the role of CD103 in promoting CD8-mediated destruction of epithelial layers, we herein examined the capacity of mice with targeted disruption of CD103 to reject pancreatic islet allografts. Wild-type hosts uniformly rejected islet allografts, concomitant with the appearance of CD8+CD103+ effectors at the graft site. In contrast, the majority of islet allografts transplanted into CD103−/− hosts survived indefinitely. Transfer of wild-type CD8 cells into CD103−/− hosts elicited prompt rejection of long-surviving islet allografts, whereas CD103−/− CD8 cells were completely ineffectual, demonstrating that the defect resides at the level of the CD8 cell. CD8 cells in CD103−/− hosts exhibited normal effector responses to donor alloantigens in vitro and trafficked normally to the graft site, but strikingly failed to infiltrate the islet allograft itself. These data establish a causal relationship between CD8+CD103+ effectors and destruction of graft epithelial elements and suggest that CD103 critically functions to promote intragraft migration of CD8 effectors into epithelial compartments

TGF-β–dependent CD103 expression by CD8+ T cells promotes selective destruction of the host intestinal epithelium during graft-versus-host disease

Destruction of the host intestinal epithelium by donor effector T cell populations is a hallmark of graft-versus-host disease (GVHD), but the underlying mechanisms remain obscure. We demonstrate that CD8+ T cells expressing CD103, an integrin conferring specificity for the epithelial ligand E-cadherin, play a critical role in this process. A TCR transgenic GVHD model was used to demonstrate that CD103 is selectively expressed by host-specific CD8+ T cell effector populations (CD8 effectors) that accumulate in the host intestinal epithelium during GVHD. Although host-specific CD8 effectors infiltrated a wide range of host compartments, only those infiltrating the intestinal epithelium expressed CD103. Host-specific CD8 effectors expressing a TGF-β dominant negative type II receptor were defective in CD103 expression on entry into the intestinal epithelium, which indicates local TGF-β activity as a critical regulating factor. Host-specific CD8 effectors deficient in CD103 expression successfully migrated into the host intestinal epithelium but were retained at this site much less efficiently than wild-type host-specific CD8 effectors. The relevance of these events to GVHD pathogenesis is supported by the finding that CD103-deficient CD8+ T cells were strikingly defective in transferring intestinal GVHD pathology and mortality. Collectively, these data document a pivotal role for TGF-β–dependent CD103 expression in dictating the gut tropism, and hence the destructive potential, of CD8+ T cells during GVHD pathogenesis

Functional and biochemical parameters of peptide antigen presentation

To understand the mechanism by which peptide antigens are processed and presented to T cells, we examined the T-cell response to the 13-amino-acid peptide [alpha]-melanocyte-stimulating hormone ([alpha]-MSH). To determine the fine specificity of T-cell recognition, T cells specific for [alpha]-MSH, and genetically restricted by I-Ab/d, were challenged with different [alpha]-MSH analogs and homologs. It was found that intact [alpha]-MSH, including the blocked amino and carboxy termini of the native molecule, was required for T-cell responsiveness. Antigen-presenting cells (APC) could be briefly pulsed with [alpha]-MSH and then present the [alpha]-MSH antigenic determinant to T cells, indicating that the relevant antigen was retained by the APC. APC stimulatory capacity was dramatically reduced by aldehyde treatment of the APC, or by pulsing the APC with [alpha]-MSH at low temperature. Efficient [alpha]-MSH pulsing was also impaired by treatment of the APC with the carboxylic ionophore, monensin, but not by the lysosomotropic agents chloroquine and methylamine. In addition, isolated APC plasma membranes added to the T cells in the presence of soluble [alpha]-MSH were not stimulatory. However, plasma membranes isolated from APC that had been previously pulsed with [alpha]-MSH retained stimulatory activity for T-cell responses. The only detectable [alpha]-MSH contained in these pulsed APC membranes was in an acid-stable complex of higher molecular weight than native peptide. The amount of [alpha]-MSH detected in the cellular membrane fraction isolated by density gradient sedimentation was also reduced by treatments that reduced the APC stimulatory capacity, such as pulsing at low temperature or in the presence of monensin. Taken together, these results suggest that processing of [alpha]-MSH is unlike that heretofore described for other peptide antigens and seems to involve APC handling to form the stimulatory moiety presented on the APC surface.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/27319/1/0000341.pd

CD103 Deficiency Prevents Graft-versus-Host Disease but Spares Graft-versus-Tumor Effects Mediated by Alloreactive CD8 T Cells

Graft-versus-host disease (GVHD) remains the main barrier to broader application of allogeneic hematopoietic stem cell transplantation (alloSCT) as a curative therapy for host malignancy. GVHD is mediated by allogeneic T cells directed against histocompatibility antigens expressed by host tissues. Based on previous studies, we postulated that the integrin CD103 is required for CD8-mediated GVHD, but not for graft-versus-tumor effects (GVT).We herein provide evidence in support of this hypothesis. To circumvent the potentially confounding influence of donor CD4 T cells, we developed an alloSCT model in which GVHD mortality is mediated by purified CD8 T cells. In this model, host-reactive CD8 T cells receive CD4 T cell help at the time of initial activation but not in the effector phase in which mature CD8 T effectors migrate into host tissues. We show that donor CD8 T cells from wild-type BALB/c mice primed to host alloantigens induce GVHD pathology and eliminate tumors of host origin in the absence of host CD4 T cells. Importantly, CD103 deficiency dramatically attenuated GVHD mortality, but had no detectable impact on the capacity to eliminate a tumor line of host origin. We provide evidence that CD103 is required for accumulation of donor CD8 T cells in the host intestinal epithelium but not in the tumor or host lymphoid compartments. Consistent with these data, CD103 was preferentially expressed by CD8 T cells infiltrating the host intestinal epithelium but not by those infiltrating the tumor, lamina propria, or lymphoid compartments. We further demonstrate that CD103 expression is not required for classic CD8 effector activities including cytokine production and cytotoxicity.These data indicate that CD103 deficiency inhibits GVHD pathology while sparing anti-tumor effects mediated by CD8 T cells, identifying CD103 blockade as an improved strategy for GVHD prophylaxis

Fractional solubility of aerosol iron : synthesis of a global-scale data set

Aerosol deposition provides a major input of the essential micronutrient iron to the open ocean. A critical parameter with respect to bioavailability is the proportion of aerosol iron that enters the oceanic dissolved iron pool – the so-called fractional solubility of aerosol iron (%FeS). Here we present a global-scale compilation of total aerosol iron loading (FeT) and %FeS values for ~1100 samples collected over the open ocean, the coastal ocean, and some continental sites, including new data from the Atlantic Ocean. The global-scale compilation reveals a remarkably consistent trend in the fractional solubility of aerosol iron as a function of total aerosol iron loading, with the great bulk of the data falling along an inverse hyperbolic trend. The large dynamic range in %FeS (0-95%) varies with FeT in a manner similar to that identified for aerosols collected in the Sargasso Sea by Sedwick et al. (2007), who posit that the trend reflects near-conservative mixing between air masses that carry lithogenic mineral dust (with high FeT and low %FeS) and non-soil-dust aerosols such as anthropogenic combustion emissions (with low FeT and high %FeS), respectively. An increasing body of empirical evidence points to the importance of aerosol source and composition in determining the fractional solubility of aerosol iron, such that anthropogenic combustion emissions appear to play a critical role in determining this parameter in the bulk marine aerosol. The robust global-scale relationship between %FeS and FeT may provide a simple heuristic method for estimating aerosol iron solubility at the regional to global scale