Building operational research capacity in the Pacific

Operational research (OR) in public health aims to investigate strategies, interventions, tools or knowledge that can enhance the quality, coverage, effectiveness or performance of health systems. Attention has recently been drawn to the lack of OR capacity in public health programmes throughout the Pacific Islands, despite considerable investment in implementation. This lack of ongoing and critical reflection may prevent health programme staff from understanding why programme objectives are not being fully achieved, and hinder long-term gains in public health. The International Union Against Tuberculosis and Lung Disease (The Union) has been collaborating with Pacific agencies to conduct OR courses based on the training model developed by The Union and Médecins Sans Frontières Brussels-Luxembourg in 2009. The first of these commenced in 2011 in collaboration with the Fiji National University, the Fiji Ministry of Health, the World Health Organization and other partners. The Union and the Secretariat of the Pacific Community organised a second course for participants from other Pacific Island countries and territories in 2012, and an additional course for Fijian participants commenced in 2013. Twelve participants enrolled in each of the three courses. Of the two courses completed by end 2013, 18 of 24 participants completed their OR and submitted papers by the course deadline, and 17 papers have been published to date. This article describes the context, process and outputs of the Pacific courses, as well as innovations, adaptations and challenges

Noise reduction in gravitational wave interferometers using feedback

We show that the quantum locking scheme recently proposed by Courty {\it et al.} [Phys. Rev. Lett. {\bf 90}, 083601 (2003)] for the reduction of back action noise is able to significantly improve the sensitivity of the next generation of gravitational wave interferometers.Comment: 12 pages, 2 figures, in print in the Special Issue of J. Opt. B on Fluctuations and Noise in Photonics and Quantum Optic

Investigating the Contribution of Mature Collagen Crosslinks to Cooked Meat Toughness Using a Stewed Beef Shank Model

Objective: The objective of this study was to investigate mature collagen crosslink densities and their relationship to connective tissue texture using a stewed beef shank model. Study Description: Connective tissue texture, Warner-Bratzler shear force, and collagen content and characteristics were measured for six different beef shank cuts from eight U.S. Department of Agriculture Low Choice beef carcasses (n = 48). Results: Deep digital flexor from the foreshank had the toughest connective tissue texture, greatest Warner-Bratzler shear force value, most cooked collagen content, one of the greatest insoluble collagen percentages, as well as greatest raw and cooked pyridinoline densities among all the beef shank cuts (P \u3c 0.05). Correlation analysis showed that cooked collagen content, percent insoluble collagen, as well as raw pyridinoline densities had positive correlations with connective tissue texture (r = 0.550, 0.498, and 0.560, respectively; P \u3c 0.01) and Warner-Bratzler shear force (r = 0.615, 0.392 and 0.730, respectively; P \u3c 0.05). The Bottom Line: Pyridinoline is a heat stable collagen crosslink that is difficult to degrade even with extensive heat treatment. As a result, raw pyridinoline density is a good indicator for heat insoluble collagen content, cooked beef connective tissue texture, and ultimately, tenderness in beef cuts with high concentration of connective tissue prepared with moist heat cookery

A Preliminary Investigation of the Contribution of Different Tenderness Factors to Beef Loin, Tri-tip, and Heel Tenderness

Objective: The objective is to better understand the contribution of each tenderness factor to the perception of tenderness of three specific beef muscles with similar tenderness ratings. Study Description: Longissimus lumborum (loin), tensor fascia latae (tri-tip), and gastrocnemius (heel) were collected from 10 U.S. Department of Agriculture low Choice beef carcasses and assigned to a 5- or 21-day aging period (n = 60). Steaks from each aging period from each subprimal were assigned to one of three assays: 1) trained sensory analysis; 2) objective tenderness evaluation (Warner-Bratzler shear force); or 3) physiochemical analysis (sarcomere length, proteolysis, intramuscular fat content, collagen crosslink, and content). Results: Sarcomere length, troponin-T degradation, collagen content, mature collagen crosslink density, intramuscular lipid content, and trained panel analysis were measured. Correlation analysis indicated each muscle has a specific tenderness factor that contributed to the overall tenderness evaluated by trained panelists. The equations indicated Longissimus lumborum tenderness was driven by lipid content (P \u3c 0.05) and that Tensor fascia latae tenderness was driven by collagen content (P \u3c 0.05). Gastrocnemius tenderness was driven by proteolysis (P \u3c 0.01), and only collagen content can be casually used as an overall tenderness predictor for all three cuts. The Bottom Line: Each muscle showed a unique tenderness factor profile. Loin is inherently tender, and tri-tip has the makings for a tender cut as seen by our biochemical analysis, yet panelists rated tri-tip to have similar overall tenderness as heel, an inherently tough muscle

Native Beef Collagenase MMP-9 May Contribute to Tenderness Improvement by Degrading Connective Tissues in Extended Aged Beef

Objective: Collagen is one of the main components in the connective tissue (CT) and contributes to background toughness in beef. It is known that in living animals, collagen can be degraded and remodeled by collagenase matrix metalloproteinases (MMP); however, it is unclear if collagenase MMP can impact CT texture during postmortem aging of beef. Therefore, this study aimed to understand how collagenase MMP activity may impact postmortem connective tissue degradation in beef in three different cuts and four different aging periods. Study Description: Beef boneless striploin, top sirloin butt, and heel were acquired from 10 U.S. Department of Agriculture high choice beef carcasses and assigned to be aged for 3, 21, 42, or 63 days (n = 120). Following each aging time, Warner-Bratzler shear force (WBSF), connective tissue shear force (CTSF), trained panel responses, collagen content, denaturation temperature of connective tissue, collagen crosslinks density, connective tissue degradation product, and native collagenase activity were measured, and collagenase identity was identified as MMP-9 through Western blot. Results: Striploin was considered the most tender muscle (P \u3c 0.01), and tenderness was improved (P \u3c 0.01) after 21 days of aging. In addition, CTSF data and trained panelists demonstrated softening (P \u3c 0.05) of CT after 21 days of aging. Heel and top sirloin butt did not differ (P \u3e 0.10) in collagen content and had greater (P \u3c 0.01) collagen content than striploin. However, no aging effect was found for collagen content (P \u3e 0.10). Denaturation temperature of CT decreased and collagen crosslinks density increased after 42 days of aging for all cuts evaluated in this study (P \u3c 0.01). The MMP-9 activity decreased (P \u3c 0.01) from 3 to 21 to 42 days, and it had the greatest (P \u3c 0.01) activity in heel compared to the other two cuts. Heel and striploin had greater (P \u3c 0.01) connective tissue degradation product than top sirloin butt. It was interesting to note that while striploin and heel showed a decrease (P \u3c 0.05) in the degradation product from 3 to 21 to 42 days, top sirloin butt did not show any changes (P \u3e 0.10) in degradation product during the entire 63 days of aging period. The Bottom Line: These results provide an explanation on CT softening during postmortem aging. Understanding the mechanism of tenderness improvement from the softening of CT may help the industry improve the eating quality of lower quality beef cuts

An Investigation on the Influence of Various Biochemical Tenderness Factors on Eight Different Bovine Muscles

Objective: Beef tenderness is a complex palatability trait with many tenderness-contributing components. The objective of this study is to understand the relative contribution of each tenderness component to eight different beef muscles. Study Description: Top sirloin butt, ribeye, brisket, flank, knuckle, eye of round, mock tender, and shoulder clod were collected from 10 U.S. Department of Agriculture high choice beef carcasses and assigned to a 2- or 21-day aging period (n = 160). Protein degradation, collagen content, mature collagen crosslink density, intramuscular lipid content, pH, shear force, and trained sensory panel analysis were determined. A Pearson correlation analysis was used to determine the relationship between each tenderness contributor measured in this study to the overall tenderness evaluated by the trained panelist. Results: Overall tenderness of ribeye, flank, eye of round, and shoulder clod were largely driven by the protein degradation of muscle fibers (effect of aging). On the other hand, overall tenderness for brisket was determined by collagen content and crosslink density (effect from connective tissue). Finally, overall tenderness of top sirloin butt was strongly correlated with lipid content. When all the cuts were combined together and analyzed as a whole (n = 160), all of the biochemical measurements conducted in this study played a small but important role as an overall tenderness contributor. The Bottom Line: Results from this study filled in some of the knowledge gap on the relative contribution of each tenderness component to the overall perception of tenderness from each cut. The industry can utilize this information to provide tenderness management strategies for each cut as well as improve the robustness of current tenderness predicting technology

Age-Related Pathology Associated with H1N1 A/California/07/2009 Influenza Virus Infection

Influenza virus infection causes a spectrum of diseases, ranging from mild upper respiratory tract infection to severe lower respiratory tract infection, that can lead to diffuse alveolar damage, interstitial and airspace inflammation, or acute respiratory failure. Mechanisms instructing disease severity are not completely understood, but host, viral, and bacterial factors influence disease outcome. With age being one host factor associated with a higher risk of severe influenza, we investigated regional pulmonary distribution and severity of pneumonia after 2009 H1N1 influenza virus infection in newly weaned, adult, and aged ferrets to better understand age-dependent susceptibility and pathology. Aged ferrets exhibited greater weight loss and higher rates of mortality than adult ferrets, whereas most newly weaned ferrets did not lose weight but had a lack of weight gain. Newly weaned ferrets exhibited minimal pneumonia, whereas adult and aged ferrets had a spectrum of pneumonia severity. Influenza virus-induced pneumonia peaked earliest in adult ferrets, whereas aged ferrets had delayed presentation. Bronchial severity differed among groups, but bronchial pathology was comparable among all cohorts. Alveolar infection was strikingly different among groups. Newly weaned ferrets had little alveolar cell infection. Adult and aged ferrets had alveolar infection, but aged ferrets were unable to clear infection. These different age-related pneumonia and infection patterns suggest therapeutic strategies to treat influenza should be tailored contingent on age

Clonogenic growth of human breast cancer cells co-cultured in direct contact with serum-activated fibroblasts

INTRODUCTION: Accumulating evidence suggests that fibroblasts play a pivotal role in promoting the growth of breast cancer cells. The objective of the present study was to characterize and validate an in vitro model of the interaction between small numbers of human breast cancer cells and human fibroblasts. METHODS: We measured the clonogenic growth of small numbers of human breast cancer cells co-cultured in direct contact with serum-activated, normal human fibroblasts. Using DNA microarrays, we also characterized the gene expression profile of the serum-activated fibroblasts. In order to validate the in vivo relevance of our experiments, we then analyzed clinical samples of metastatic breast cancer for the presence of myofibroblasts expressing α-smooth muscle actin. RESULTS: Clonogenic growth of human breast cancer cells obtained directly from in situ and invasive tumors was dramatically and consistently enhanced when the tumor cells were co-cultured in direct contact with serum-activated fibroblasts. This effect was abolished when the cells were co-cultured in transwells separated by permeable inserts. The fibroblasts in our experimental model exhibited a gene expression signature characteristic of 'serum response' (i.e. myofibroblasts). Immunostaining of human samples of metastatic breast cancer tissue confirmed that myofibroblasts are in direct contact with breast cancer cells. CONCLUSION: Serum-activated fibroblasts promote the clonogenic growth of human breast cancer cells in vitro through a mechanism that involves direct physical contact between the cells. This model shares many important molecular and phenotypic similarities with the fibroblasts that are naturally found in breast cancers

Ibudilast, a Pharmacologic Phosphodiesterase Inhibitor, Prevents Human Immunodeficiency Virus-1 Tat-Mediated Activation of Microglial Cells

Human Immunodeficiency Virus-1 (HIV-1)-associated neurocognitive disorders (HAND) occur, in part, due to the inflammatory response to viral proteins, such as the HIV-1 transactivator of transcription (Tat), in the central nervous system (CNS). Given the need for novel adjunctive therapies for HAND, we hypothesized that ibudilast would inhibit Tat-induced excess production of pro-inflammatory cytokines, such as tumor necrosis factor-alpha (TNFα) in microglial cells. Ibudilast is a non-selective cyclic AMP phosphodiesterase inhibitor that has recently shown promise as a treatment for neuropathic pain via its ability to attenuate glial cell activation. Accordingly, here we demonstrate that pre-treatment of both human and mouse microglial cells with increasing doses of ibudilast inhibited Tat-induced synthesis of TNFα by microglial cells in a manner dependent on serine/threonine protein phosphatase activity. Ibudilast had no effect on Tat-induced p38 MAP kinase activation, and blockade of adenosine A2A receptor activation did not reverse ibudilast's inhibition of Tat-induced TNFα production. Interestingly, ibudilast reduced Tat-mediated transcription of TNFα, via modulation of nuclear factor-kappa B (NF-κB) signaling, as shown by transcriptional activity of NF-κB and analysis of inhibitor of kappa B alpha (IκBα) stability. Together, our findings shed light on the mechanism of ibudilast's inhibition of Tat-induced TNFα production in microglial cells and may implicate ibudilast as a potential novel adjunctive therapy for the management of HAND