Characterization and translational development of IOA-289, a novel autotaxin inhibitor for the treatment of solid tumors.

Background: Autotaxin-lysophosphatidic acid (ATX-LPA) signaling has a predominant role in immunological and fibrotic processes, including cancer. Several ATX inhibitors and LPA receptor antagonists have been clinically evaluated, but none in patients with solid tumors. Many cancers are burdened with a high degree of fibrosis and an immune desert phenotype (so-called 'cold' tumors). In these cold tumors, the fibrotic stroma provides an intrinsic cancer-supporting mechanism. Furthermore, the stroma prevents penetration and limits the effectiveness of existing therapies. IOA-289 is a novel ATX inhibitor with a unique chemical structure, excellent potency and an attractive safety profile. Materials and methods: In vitro and in vivo pharmacology studies have been carried out to elucidate the pharmaceutical properties and mechanism of action of IOA-289. A phase I clinical study in healthy volunteers was carried out to determine the pharmacokinetics and pharmacodynamics of IOA-289 following a single oral dose. Results: In vitro and in vivo studies showed that IOA-289 is a potent inhibitor of ATX and, as a monotherapy, is able to slow progression of lung fibrosis and tumor growth in mouse models. In a clinical study, IOA-289 showed a dose-dependent increase in plasma exposure levels and a corresponding decrease in circulating LPA. Conclusions: Our data show that IOA-289 is a novel ATX inhibitor with a unique chemical structure, excellent potency and an attractive safety profile. Our data support the further development of IOA-289 as a novel therapeutic approach for the treatment of cancer, particularly those with a high fibrotic and immunologically cold phenotype.

Validation of an LC-MS/MS method for the quantification IOA-289 in human plasma and its application in a first-in-human clinical trial.

IOA-289 is a novel small molecule inhibitor of autotaxin developed as a first-in-class therapy of fibrotic pathologies including cancer. A method for quantitation of IOA-289 in human plasma was developed using a stable isotope labeled compound ([13C4]IOA-289) as internal standard. The analytes were extracted from human plasma by protein precipitation and the analysis was performed by liquid chromatography coupled with tandem mass spectrometric detection (LCMS/MS). The chromatographic separation was performed with a gradient elution from a BEH C18 column and under these conditions the retention time and the run time were 1 and 2 min, respectively. The assay was fully validated over the range 3-3000 ng/mL, proved to be accurate, precise and selective and was successfully applied to quantitate IOA-289 in plasma samples from subjects in a first-in-humanclinical trial.

Tooth Loss and Nutritional Status in Older Adults: A Systematic Review and Meta-analysis.

BACKGROUND/OBJECTIVE: Older adults are at risk for tooth loss and compromised nutritional status. Our objective was to conduct a systematic review and meta-analysis to answer the following question: Among adults aged ≥60 y living in developed countries, what are the associations between tooth loss and nutritional status as assessed by a validated nutrition screening or assessment tool? METHODS: PRISMA guidelines were followed. PubMed, Scopus, CINAHL, Web of Science, and MEDLINE were searched for studies published in English between 2009 and 2019 that met inclusion criteria. Data extracted included study and participant characteristics, dentition, and nutritional status. Risk of bias was assessed with a modified Newcastle-Ottawa Scale. Random effects meta-analysis was used. RESULTS: Of the 588 unduplicated articles identified, 78 were reviewed in full text, and 7 met inclusion criteria. Six studies were combined for a meta-analysis, which revealed that individuals who were completely edentulous or who lacked functional dentition had a 21% increased likelihood of being at risk of malnutrition or being malnourished, as compared with those who were dentulous or had functionally adequate dentition (risk ratio, 1.21; 95% CI, 1.11 to 1.32; I2 = 70%). Whether the article statistically adjusted for medical history explained most of the heterogeneity in the pooled effect. CONCLUSIONS AND IMPLICATIONS: Findings suggest that older adults with tooth loss are at greater risk of malnutrition than those with functionally adequate dentition. Use of validated tools to assess risk of malnutrition in older adults with tooth loss is important to promote early intervention and referral to optimize nutrition and oral health status. Findings were limited by heterogeneity, risk of bias, and overall quality of the studies reviewed. Cohort studies that adjust for known confounders and use consistent approaches to assess tooth loss and nutritional status are needed. KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that older adults with tooth loss are at greater risk of malnutrition than those with functionally adequate dentition. Screening of this population for malnutrition by health care professionals, including dentists and dietitians, may result in corresponding referrals to optimize nutrition and oral health status. Further research is needed with consistent approaches to assess tooth loss and nutritional status.

The Acceptability of HPV Vaccines and Perceptions of Vaccination against HPV among Physicians and Nurses in Hong Kong.

Background: Human papillomavirus (HPV) is one of the most common sexually transmitted infections nationwide. Methods: This is the first cross-sectional survey assessing physicians' and nurses' knowledge of HPV and recording their attitudes to HPV vaccination in Hong Kong. Survey questions were derived from the Health Belief Model. Results: 1152 clinicians (170 physicians and 982 nurses) aged 21 and 60 participated in this study. A multiple stepwise regression model was used to examine associations between cognitive factors (clinicians' attitudes) and subjects' intention to HPV vaccine uptake. Results showed that only 30.2% of physicians and 21.2% nurses found vaccinating for HPV acceptable. Conclusions: Perceived self-efficacy was the only significant background and cognitive variable associated with physicians' and nurses' accepting HPV vaccines. Further, when nurses found HPV vaccination acceptable, cues to action was featured as a significant background variable in their choice.

Acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among male baccalaureate students in Hong Kong.

OBJECTIVES: The highly infectious human papillomavirus (HPV) causes both genital warts and cervical cancer in women. In 2009, the prevalence of genital warts in Hong Kong was 203.7 per 100,000 person-years. Cervical cancer, more seriously, was the eight most common cancer among women and girls in Hong Kong, accounting for 2.3% of all new cancer cases in females in 2014. Cervical cancer is a significant global public health problem and HPV is a major risk factor leading to the development of cervical cancer. HPV is also the most common sexually transmitted disease among university students. This is the first study to examine the acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among the male baccalaureate student population locally. METHODS: A self-administrative cross-sectional survey was used to assess whether male baccalaureate students from eight local Hong Kong universities intended to be immunized for HPV. The study also asked questions concerning how its subjects perceived HPV and HPV vaccines using the Health Belief Model. Data collection spanned from June to September 2015. A multiple stepwise regression model was used to examine associations between cognitive factors and subjects' intention to take up the HPV vaccine. RESULTS: A total of 1,004 (83.7%) students aged 18 and 26 participated in this study. 23.3% found vaccinating for HPV acceptable, a level correlating with a number of indicators. Subjects were more likely to find vaccinating acceptable if 1) they knew something about HPV vaccines; 2) they understood that men were susceptible to infection by HPV; 3) they realised they could benefit by HPV vaccination, and 4) they were aware of the arguments for and against HPV vaccination, as disseminated by either the media or peers. CONCLUSIONS: HPV remains a significant public health concern in Hong Kong and China more broadly. This study's findings show a disconnect between the perceived and actual risk of being infected with the HPV vaccine among male baccalaureate students. This disconnect may be bridged by informing young men of the benefits of their being vaccinated against HPV, by removing the psychological and financial barriers that prevent them from taking up the vaccine and by improving how primary healthcare providers motivate them to get immunized.

Influence of dietary -arginine supplementation of sows during late pregnancy on piglet birth weight and sow and litter performance during lactation.

Two experiments were conducted to determine the effect of feeding supplemental -Arg during late pregnancy on piglet birth weight and preweaning performance. In Exp. 1, 97 gilts and sows were allotted (gestation d 93) to receive a control diet (CON; 19.8 g standardized ileal digestible [SID] Arg/d) or the CON + 1.0% -Arg (ARG; 46.6 g SID Arg/d). Gilts and sows were weighed on gestation d 93 and 110, 48 h after farrowing, and at weaning. Data, including number born alive, number weaned, individual birth and weaning weight, and placenta weight, were recorded. Blood samples were collected on d 93 and 110 and analyzed for plasma IGF-1, insulin, and blood urea nitrogen concentration. In a second experiment, 383 sows in a commercial research farm were allotted to receive CON or ARG. An -Arg premix was provided daily by top dress beginning at gestation d 81 (±0.1 d) and fed for an average of 35 d (±0.2 d). Sows received 2.73 kg feed/d with CON sows provided 17 g SID Arg/d and ARG sows receiving a total of 44 g SID Arg/d. Litter birth weight was recorded and average birth weight was computed. In a subset of 82 sows, individual birth weights were recorded. In Exp. 1, there was a tendency for greater late pregnancy maternal BW gain ( = 0.06) in ARG compared with CON. A tendency for a parity × treatment interaction was observed for late pregnancy BW gain, with first litter sows fed ARG gaining the most, gilts fed ARG intermediate, and all other treatments gaining the least ( = 0.10). No differences between treatment groups were observed for maternal plasma IGF-1, insulin, and urea nitrogen and in progeny performance to weaning ( > 0.28). In Exp. 2, piglet birth weight was more effectively tested because of the large number of multiparous sows involved. There was a tendency for individual birth weight to decline in ARG compared with CON ( < 0.08), but birth weight distribution between <0.80 and >2.8 kg was similar. No other differences were observed ( > 0.18). In conclusion, late pregnancy supplementation with -Arg had no effect on number of pigs born alive, piglet birth weight, or lactation performance.

Unusual ocular presentations of ocular phaeohyphomycosis.

PurposePhaeohyphomycosis are melanin-containing fungi that rarely infect the eye. We describe three cases of ocular infection with some unusual clinical features.MethodsSeries of three case reports describing three different presentations of phaeohyphomycosis of the eye, their histopathology, and management.ResultsCase 1 mimicked an inflamed conjunctival naevus and was excised on this basis, revealing a conjunctival retention cyst containing pigmented fungal hyphae. Case 2 showed a wooden foreign body incidentally associated with pigmented fungal hyphae, which required treatment with topical antifungal therapy. Case 3 clinically was thought to be a perforated uveal melanoma and comprised an extensive plaque of pigmented fungal hyphae over ulcerated cornea.ConclusionThe pigmented melanin containing hyphae of phaeohyphomycosis mimicked melanocytic lesions in two cases and was an incidental finding in the context of a surface foreign body.

Oxytocin-dependent consolation behavior in rodents.

Consolation behavior toward distressed others is common in humans and great apes, yet our ability to explore the biological mechanisms underlying this behavior is limited by its apparent absence in laboratory animals. Here, we provide empirical evidence that a rodent species, the highly social and monogamous prairie vole (Microtus ochrogaster), greatly increases partner-directed grooming toward familiar conspecifics (but not strangers) that have experienced an unobserved stressor, providing social buffering. Prairie voles also match the fear response, anxiety-related behaviors, and corticosterone increase of the stressed cagemate, suggesting an empathy mechanism. Exposure to the stressed cagemate increases activity in the anterior cingulate cortex, and oxytocin receptor antagonist infused into this region abolishes the partner-directed response, showing conserved neural mechanisms between prairie vole and human.

Disc in flames: Roles of TNF-α and IL-1ß in intervertebral disc degeneration.

The intervertebral disc is an important mechanical structure that allows range of motion of the spinal column. Degeneration of the intervertebral disc--incited by aging, traumatic insult, genetic predisposition, or other factors--is often defined by functional and structural changes in the tissue, including excessive breakdown of the extracellular matrix, increased disc cell senescence and death, as well as compromised biomechanical function of the tissue. Intervertebral disc degeneration is strongly correlated with low back pain, which is a highly prevalent and costly condition, significantly contributing to loss in productivity and health care costs. Disc degeneration is a chronic, progressive condition, and current therapies are limited and often focused on symptomatic pain relief rather than curtailing the progression of the disease. Inflammatory processes exacerbated by cytokines tumour necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) are believed to be key mediators of disc degeneration and low back pain. In this review, we describe the contributions of TNF-α and IL-1ß to changes seen during disc degeneration at both cellular and tissue level, as well as new evidence suggesting a link between infection of the spine and low back pain, and the emerging therapeutic modalities aimed at combating these processes.

Antagonism of corticotrophin-releasing factor type 1 receptors attenuates caloric intake of free feeding subordinate female rhesus monkeys in a rich dietary environment.

Social subordination in macaque females is a known chronic stressor and previous studies have shown that socially subordinate female rhesus monkeys consume fewer kilocalories than dominant animals when a typical laboratory chow diet is available. However, in a rich dietary environment that provides access to chow in combination with a more palatable diet (i.e. high in fat and refined sugar), subordinate animals consume significantly more daily kilocalories than dominant conspecifics. Substantial literature is available supporting the role of stress hormone signals in shaping dietary preferences and promoting the consumption of palatable, energy-dense foods. The present study was conducted using stable groups of adult female rhesus monkeys to test the hypothesis that pharmacological treatment with a brain penetrable corticotrophin-releasing factor type 1 receptor (CRF1) antagonist would attenuate the stress-induced consumption of a palatable diet among subordinate animals in a rich dietary environment but would be without effect in dominant females. The results show that administration of the CRF1 receptor antagonist significantly reduced daily caloric intake of both available diets among subordinate females compared to dominant females. Importantly, multiple regression analyses showed that the attenuation in caloric intake in response to Antalarmin (Sigma-Aldrich, St Louis, MO, USA) was significantly predicted by the frequency of submissive and aggressive behaviour emitted by females, independent of social status. Taken together, the findings support the involvement of activation of CRF1 receptors in the stress-induced consumption of excess calories in a rich dietary environment and also support the growing literature concerning the importance of CRF for sustaining emotional feeding.

Oestradiol differentially influences feeding behaviour depending on diet composition in female rhesus monkeys.

In females, cyclical changes in the ovarian hormone oestradiol are known to modulate feeding behaviour. However, what is less clear is how these behavioural effects of oestradiol are modified by the macronutrient content of a diet. In the present study, we report data showing that oestradiol treatment results in both significantly smaller meals and a reduced total calorie intake in ovariectomised, socially-housed female rhesus macaques when only chow diet is available. Conversely, during a choice dietary condition where both palatable and chow options are available, oestradiol treatment had no observable, attenuating effect on calorie intake. During this choice dietary phase, all animals consumed more of the palatable diet than chow diet; however, oestradiol treatment appeared to further increase preference for the palatable diet. Finally, oestradiol treatment increased snacking behaviour (i.e. the consumption of calories outside of empirically defined meals), regardless of diet condition. These findings illustrate how oestradiol differentially influences feeding behaviour depending on the dietary environment and provides a framework in which we can begin to examine the mechanisms underlying these observed changes.

Immunogenetic Management Software: a new tool for visualization and analysis of complex immunogenetic datasets.

Here we describe the Immunogenetic Management Software (IMS) system, a novel web-based application that permits multiplexed analysis of complex immunogenetic traits that are necessary for the accurate planning and execution of experiments involving large animal models, including nonhuman primates. IMS is capable of housing complex pedigree relationships, microsatellite-based MHC typing data, as well as MHC pyrosequencing expression analysis of class I alleles. It includes a novel, automated MHC haplotype naming algorithm and has accomplished an innovative visualization protocol that allows users to view multiple familial and MHC haplotype relationships through a single, interactive graphical interface. Detailed DNA and RNA-based data can also be queried and analyzed in a highly accessible fashion, and flexible search capabilities allow experimental choices to be made based on multiple, individualized and expandable immunogenetic factors. This web application is implemented in Java, MySQL, Tomcat, and Apache, with supported browsers including Internet Explorer and Firefox on Windows and Safari on Mac OS. The software is freely available for distribution to noncommercial users by contacting Leslie.kean@emory.edu. A demonstration site for the software is available at http://typing.emory.edu/typing_demo , user name: imsdemo7@gmail.com and password: imsdemo.

Selective thermal emission from patterned steel.

Patterned metal films have been shown to possess unique optical properties resulting from the excitation of surface plasmon polaritons at the patterned metal surface. Here we demonstrate spectrally selective thermal emission from patterned steel substrates. The materials and processes used in this work were chosen for their potential scalability to large-area and low cost production of metal films with distinct and designable thermal signatures. The samples studied were characterized by reflection and emission spectroscopy, and a factor of 2.6 emission enhancement is demonstrated for the design wavelength. These results are compared to numerical simulations.

Resources for genetic management and genomics research on non-human primates at the National Primate Research Centers (NPRCs).

The National Primate Research Centers (NPRCs) established Working Groups (WGs) for developing resources and mechanisms to facilitate collaborations among non-human primate (NHP) researchers. Here we report the progress of the Genome Banking and the Genetics and Genomics WGs in developing resources to advance the exchange, analysis and comparison of NHP genetic and genomic data across the NPRCs. The Genome Banking WG has established a National NHP DNA bank comprising 1250 DNA samples from unrelated animals and family trios from the 10 NHP species housed within the NPRC system. The Genetics and Genomics WG is developing SNP arrays that will provide a uniform, highly informative, efficient and low-cost method for rhesus and long-tailed macaque genotyping across the eight NPRCs. This WG is also establishing a Biomedical Informatics Research Network-based portal for shared bioinformatics resources including vital statistics, genotype and population data and information on the National NHP DNA bank.

Fecal egg count reduction and control trial determinations of anthelmintic efficacies for several parasiticides utilizing a single set of naturally infected calves.

In this study, a single set of naturally infected calves was used for the conduct of a fecal egg count reduction test (FECRT) immediately followed by a control trial; all, to evaluate the efficacies of several commonly used, non-generic anthelmintics. Ten animals were allocated into each of the five treatment groups; untreated control (UTC), injectable 1% moxidectin given at 0.2 mg kg(-1)BW (MXD), injectable 1% ivermectin given at 0.2 mg kg(-1)BW (IVM), 9.06% oxfendazole given orally at 4.5 mg kg(-1)BW (OXF), and 10.0% fenbendazole given orally at 5.0 mg kg(-1)BW (FBZ). Confinement of animals to clean, concrete-floored pens was initiated on day -7 and continued until animal necropsy (2 animals were necropsied per treatment group per day on days 35-39 for nematode collections). All treatments were given on day 0, and the FECRT was conducted on all animals until necropsy. From days 2 to 14, FECR %'s for the combined strongyle egg counts were >or=90% for all anthelmintic groups. At the time of necropsy, FECRT %'s for the combined strongyle egg counts continued to be >or=90% for all treatments with the exception of IVM (84%). After adjustment of the strongyle egg counts in accordance with coproculture larvae percentages, FECRT %'s at the time of necropsy for Haemonchus, Ostertagia and Cooperia were found to be >or=94% for MXD and OXF, but <90% for FBZ (Ostertagia) and IVM (Haemonchus and Cooperia). At necropsy, more than six of the ten untreated animals were infected with Ostertagia ostertagi (adults, EL(4) and LL(4)), and adult Haemonchus placei, Trichostrongylus axei, Cooperia oncophora, C. surnabada and C. punctata. Based on geometric means: all of the above populations were removed by >or=96% by MXD; were removed by >or=90% by IVM except for O. ostertagi LL(4) (81.9%), C. oncophora and C. surnabada adults (77.4%) and C. punctata adults (84.8%); were removed by >or=90% by OXF except for O. ostertagi adults, EL(4) and LL(4) (89.9, 70.2 and 48.1%, respectively); and were removed by >or=90% by FBZ except for O. ostertagi adults, EL(4) and LL(4) (72.5, 0.0 and 21.9%, respectively). Judging from the above data, FECR and control trial results can be extremely similar given the proper experimentation and, despite varied degrees of nematode resistance, targeted nematode burdens commonly carried by Midwestern beef cattle are effectively removed by the parasiticides that are available today.

Effects of salt, BHA/BHT, and differing phosphate types on quality and sensory characteristics of beef longissimus muscles.

USDA Select striploins (n = 20) were cut into thirds (anterior, medial, and posterior) and randomly assigned to 1 of 6 treatments. Treatments included: (1) control (C); (2) 0.006% BHA (butylated hydroxyl anisole)/BHT (butylated hydroxytoluene) (70%/30%) (BB); (3) 0.4% trisodiumphosphate (CT); (4) 0.4% sodiumtripolyphosphate with 0.5% salt (BH); (5) sodiumtripolyphosphate, 0.5% salt, and 0.006% BHA/BHT (70%/30%) (SB); (6) 0.2% sodiumtripolyphosphate, 0.2% trisodiumphosphate, and 0.5% salt (STB). Muscle sections were injected to 110% (10% pump) of their weight with their respective treatments. Inclusion of BHA/BHT allowed for lower mean oxidation values. Regardless of phosphate type, muscles treated with both phosphate and salt had lower retail purge (P < 0.05). Sensory panelists rated (P < 0.05) STB, SB, and BH to be juicier than all other treatments. These data suggest that inclusion of both salt and phosphate can enhance palatability, lower cook loss, and retail purge.

Effects of conjugated linoleic acid, salt, and sodium tripolyphosphate on physical, sensory, and instrumental color characteristics of beef striploins.

USDA Select striploins (IMPS 180; n= 24) were cut into thirds (anterior, medial, and posterior) and assigned to 1 of 8 treatments utilizing a randomized incomplete block design. Treatments included (1) control (C); (2) 1.5% conjugated linoleic acid (conjugated linoleic acid = CLA) (CGA); (3) 0.4% sodium tripolyphosphate (PHO); (4) 0.5% salt (SAL); (5) 0.4% sodium tripolyphosphate, 0.5% salt (SPH); (6) 0.4% sodium tripolyphosphate, 1.5% CLA (PCL); (7) 0.5% salt, 1.5% CLA (SCL); and (8) 0.4% sodium tripolyphosphate, 0.5% salt, 1.5% CLA (SPC). Treatments were injected with solutions to 110% (10% pump) of their original weight. Treatments with CLA had higher (P < 0.05) marbling scores than treatments that did not. Not including SAL, treatments with salt, or phosphate or a combination of the two had higher tenderness values when sampled by panelists. Fresh steaks with inclusion of CLA had greater amounts (P < 0.05) of the CLA isomers than steaks not having CLA. Cooked steaks having CLA also had greater amounts (P < 0.05) of CLA, except for SCL, which were not different (P > 0.05) from the non-CLA treatments. Day was a significant source of variability for a*, b*, and saturation index. Treatment x day interactions were significant (P < 0.05) for hue angle and L* values. These data suggest that inclusion of CLA can increase amounts of CLA isomers without major deleterious effects to instrumental, physical, and quality characteristics of beef striploin steaks.

Effectiveness evaluation of several cattle anthelmintics via the fecal egg count reduction test.

Utilizing groups of cograzed, naturally infected beef-type heifers, three fecal egg count reduction tests were conducted in the later months of 2007 at the University of Arkansas. Each test was 28 days in length consisting of individual animal fecal nematode egg counts and coprocultures. Both original and generic ivermectin injectable formulations were used in two of the tests at 0.2 mg/kg BW, with FECR percentages never exceeding 90% in either test. Oral fenbendazole was evaluated at 5 and 10 mg/kg BW, with FECR%'s exceeding 90% on all occasions, but with a precipitous drop when recently treated animals were treated at the lower dose. Evaluated in one test, injectable moxidectin given at 0.2 mg/kg BW resulted in egg count reductions of 96-92% (days 7 to 28). Also evaluated in one test, albendazole delivered orally at 10 mg/kg BW was 98% and 97% effective at 17 and 28 days post-treatment. For all tests, coprocultures conducted post-treatment contained only Cooperia spp. larvae (benzimidazole use), relatively unmodified percentages of Cooperia spp. and Haemonchus spp. larvae (ivermectin use), and primarily Cooperia spp. larvae with a small percentage of Haemonchus spp. larvae (moxidectin use).

Fresh and cooked color of dark-cutting beef can be altered by post-rigor enhancement with lactic acid.

Fresh and cooked color of dark-cutting (DC) beef strip loins (mean pH=6.56) enhanced with 0.25, 0.50, 0.75 or 1.00% lactic acid (LA) were compared to non-enhanced DC and normal pH (NpH; mean pH=5.43) strip loins. Even though NpH steaks received the most (P<0.05) desirable fresh color scores, color scores for steaks from DC sections enhanced with 0.25% LA approached those of NpH steaks after the first day of retail display. Discoloration scores were also similar (P>0.05) among NpH and 0.25% LA-enhanced DC steaks throughout the 5 d of display. Fresh steaks from NpH strip loins were redder, as evidenced by greater (P<0.05) a(∗) values and lower (P<0.05) hue angles, than DC steaks and DC steaks enhanced with LA, regardless of concentration. However, cooked color scores and proportions of denatured myoglobin were similar (P>0.05) between untreated NpH steaks and DC steaks enhanced with 0.25% LA. Results from this study indicate that enhancing DC beef with LA may lead to the brightening of the fresh color and prevention of the persistent red cooked color, approaching that of NpH beef.

Detection of visual-field deterioration by Glaucoma Progression Analysis and Threshold Noiseless Trend programs.

BACKGROUND: To compare the ability of Glaucoma Progression Analysis (GPA) and Threshold Noiseless Trend (TNT) programs to detect visual-field deterioration. METHODS: Patients with open-angle glaucoma followed for a minimum of 2 years and a minimum of seven reliable visual fields were included. Progression was assessed subjectively by four masked glaucoma experts, and compared with GPA and TNT results. Each case was judged to be stable, deteriorated or suspicious of deterioration RESULTS: A total of 56 eyes of 42 patients were followed with a mean of 7.8 (SD 1.0) tests over an average of 5.5 (1.04) years. Interobserver agreement to detect progression was good (mean kappa = 0.57). Progression was detected in 10-19 eyes by the experts, in six by GPA and in 24 by TNT. Using the consensus expert opinion as the gold standard (four clinicians detected progression), the GPA sensitivity and specificity were 75% and 83%, respectively, while the TNT sensitivity and specificity was 100% and 77%, respectively. CONCLUSION: TNT showed greater concordance with the experts than GPA in the detection of visual-field deterioration. GPA showed a high specificity but lower sensitivity, mainly detecting cases of high focality and pronounced mean defect slopes.