Dry Eye: Age-related prevalence, correlation between symptoms and diagnoses, and significant associations

This study determined the prevalence of dry eye (DE) symptoms and clinical diagnosis over the age range of the human lifespan, the correlation of symptoms with diagnosis, and factors associated with DE. Data was abstracted from WatES, a retrospective file review (n=6397) of patient examinations at the University of Waterloo Optometry Clinic. The prevalence of DE symptoms and diagnosis were determined overall, in five year age groups and for individual symptoms. Using logistic regression, each symptom was analyzed for a significant association with DE diagnosis. Ocular and systemic factors, and common medications were analyzed for association with DE symptoms or diagnosis. Of all patients (0-93 years) 543 (8.5%) presented with DE symptoms. Prevalence within age groups was greatest for patients 30<35 (11.4 %) and 75<80 years (13.7 %). DE was diagnosed in 1140 patients (17.8%). Prevalence increased by 3.0% per year of age. No sex-related differences in meibomian gland dysfunction as a function of age were found. Less than half (43.5%) of symptomatic patients were diagnosed with DE. The following symptoms were associated with a DE diagnosis: dryness (OR= 7.56, 5.30-10.77 95% CI), injection (OR=3.62, 2.04-6.43 95%CI), burning/stinging/soreness (OR=2.67, 1.69-4.23 95%CI), and watery eyes/tearing (OR=1.66, 1.12-2.45 95%CI). Anterior blepharitis (OR=2.46, 2.05-2.95), being female (OR=1.24, 1.06-1.40 95%CI), contact lens wear (OR=1.34, 1.06-1.70 95%CI), and environmental allergies (OR=1.18, 1.00-1.41 95% CI) were statistically associated with a diagnosis of DE. In summary, specific presenting symptoms predicted DE diagnosis, DE was diagnosed in patients of all ages, and its prevalence increased steadily with age

Sécheresse oculaire: Prévalence liée à l’âge, corrélation entre les symptômes et les diagnostics, et associations importantes

Cette étude canadienne a permis de déterminer la prévalence des symptômes de la sécheresse oculaire (SO) et le diagnostic clinique au cours de la vie humaine, la corrélation des symptômes avec un diagnostic et les facteurs associés à la SO. Les données ont été tirées de WatES, un examen rétrospectif des dossiers (n=6 397) d’examens de patients à la clinique d’optométrie de l’Université de Waterloo. La prévalence des symptômes et du diagnostic de la SO a été déterminée globalement, dans les groupes d’âge de cinq ans et pour les symptômes individuels. Chaque symptôme a été analysé par régression logistique afin de déterminer s’il y avait un lien significatif avec un diagnostic de SO. On a analysé les facteurs oculaires et systémiques ainsi que les médicaments courants en vue de déterminer leur association avec les symptômes ou le diagnostic de la SO. Parmi tous les patients (0 à 93 ans), 543 (8,5 %) présentaient des symptômes de SO. En ce qui concerne les groupes d’âge, la prévalence la plus élevée a été observée chez les patients de 30 à 35 ans (11,4 %) et de 75 à 80 ans (13,7 %). La SO a été diagnostiquée chez 1 140 patients (17,8 %). La prévalence augmentait de 3,0 % par année d’âge. Aucune différence liée au sexe dans le dysfonctionnement des glandes de Meibomius en fonction de l’âge n’a été décelée. Moins de la moitié (43,5 %) des patients symptomatiques ont reçu un diagnostic de SO. Les symptômes suivants ont été associés à un diagnostic de SO : sécheresse (RC = 7,56, 5,30-10,77 IC à 95 %), yeux rouges (RC = 3,62, 2,04-6,43 IC à 95 %), brûlure/piqûre/douleur (RC = 2,67, 1,69-4,23 IC à 95 %) et larmoiement des yeux (RC = 1,66, 1,12-2,45 IC). La blépharite antérieure (RC=2,46, 2,05-2,95), les femmes (RC=1,24, 1,06-1,40 IC à 95 %), le port de lentilles de contact (RC=1,34, 1,06-1,70 IC à 95 %) et les allergies environnementales (RC=1,18, 1,00-1,41 IC à 95 %) étaient associés de façon significative à un diagnostic de SO. Cette étude est unique en ce sens qu’elle couvre toute la durée de vie humaine pour le diagnostic de la sécheresse oculaire, les symptômes et le dysfonctionnement des glandes de Meibomius (DGM) et qu’elle fournit des données sur la prévalence de la sécheresse oculaire au Canada

The marketing firm and co‐creation: An empirical study of marketer and customer's co‐creation process

This study empirically investigates the marketer and customer's co‐creation process within the context of the marketing firm. Based on principles from bilateral contingencies, findings from a conjoint study (n = 98) indicate that utilitarian and informational reinforcing consequences from the marketer have a stronger impact on customers' co‐creation behavior relative to informational reinforcing consequences from other customers. Consequently, analyzing the impact of important reinforcing contingencies through the lens of bilateral contingencies expands our understanding of how and why co‐creation outcomes might occur. Also, a good co‐creation process may increase the business companies' research and intelligence and, as a consequence, strengthen their competitiveness.The marketing firm and co‐creation: An empirical study of marketer and customer's co‐creation processacceptedVersio

Robert Nozick on nonhuman animals : rights, value and the meaning of life

In his chapter, Josh Milburn argues that Robert Nozick considers nonhuman animals in his philosophical writings, but that these discussions are downplayed in animal ethics and Nozick scholarship. This is regrettable, Milburn proposes, as Nozick is far more sympathetic to animal rights than many other libertarians. Milburn thus offers an analysis of Nozick’s animal ethics. Nozick’s arguments concerning vegetarianism and speciesism are considered, and Milburn argues that tensions in Nozick’s political philosophy potentially open the door to animal rights. Whatever their place in his political philosophy, Milburn contends, nonhuman animals find a comfortable home in Nozick’s axiology and ethics, with their value and the significance of our duties towards them affirmed. Milburn concludes that animal ethicists could learn from Nozick’s distinctive arguments and approaches and find an unexpected ally

Failure to normalize lymphopenia following trauma is associated with increased mortality, independent of the leukocytosis pattern

INTRODUCTION: Following trauma and systemic inflammatory response syndrome (SIRS), the typical response is an elevation of the total complete blood count (CBC) and a reduction of the lymphocyte count. This leukocytosis typically returns to normal within 48 hours. The persistence of a leukocytosis following trauma is associated with adverse outcomes. Although lymphocyte anergy and dysfunction following trauma is associated with increased risk for infection and sepsis, there is a paucity of data regarding the impact of a persistence of a low lymphocyte count in trauma patients. METHODS: This is a retrospective review of prospectively collected data from trauma patients collected over the 5 years of September 2003 to September 2008. Patients were included if the injury severity score (ISS) was >/=15, and they survived at least 3 days. Demographic data, mechanism and injury severity score, mortality, and length of stay were collected from the medical record. Laboratory values for the first 4 hospital days were collected. Leukocyte, neutrophil and lymphocyte counts were extracted from the daily complete blood count (CBC). Patients were then grouped based on response (elevation/depression) of each component of the CBC, and their return, or failure thereof, to normal. Proportional hazards regression with time-varying covariates as well as Kaplan-Meier curves were used to predict risk of death, time to death and time to healthy discharge based on fluctuations of the individual components of the CBC. RESULTS: There were 2448 patients admitted over the 5 years included in the analysis. When adjusting for age, gender and ISS the relative risk of death was elevated with a persistent leukocytosis (2.501 (95% CI = 1.477-4.235)) or failure to normalize lymphopenia (1.639 (95% CI = 10.17-2.643)) within the first 4 days following admission. Similar results were seen when Kaplan-Meier curves were created. Persistent lymphopenia was associated with shortest time to death. Paradoxically in survivors persistent lymphopenia was associated with the shortest time to discharge. CONCLUSIONS: Persistently abnormal CBC responses are associated with a higher mortality following trauma. This is the first report noting that a failure to normalize lymphopenia in severely injured patients is associated with significantly higher mortality

Publication and related biases in health services research: a systematic review of empirical evidence

Background: Publication and related biases (including publication bias, time-lag bias, outcome reporting bias and p-hacking) have been well documented in clinical research, but relatively little is known about their presence and extent in health services research (HSR). This paper aims to systematically review evidence concerning publication and related bias in quantitative HSR. Methods: Databases including MEDLINE, EMBASE, HMIC, CINAHL, Web of Science, Health Systems Evidence, Cochrane EPOC Review Group and several websites were searched to July 2018. Information was obtained from: (1) Methodological studies that set out to investigate publication and related biases in HSR; (2) Systematic reviews of HSR topics which examined such biases as part of the review process. Relevant information was extracted from included studies by one reviewer and checked by another. Studies were appraised according to commonly accepted scientific principles due to lack of suitable checklists. Data were synthesised narratively. Results: After screening 6155 citations, four methodological studies investigating publication bias in HSR and 184 systematic reviews of HSR topics (including three comparing published with unpublished evidence) were examined. Evidence suggestive of publication bias was reported in some of the methodological studies, but evidence presented was very weak, limited in both quality and scope. Reliable data on outcome reporting bias and p-hacking were scant. HSR systematic reviews in which published literature was compared with unpublished evidence found significant differences in the estimated intervention effects or association in some but not all cases. Conclusions: Methodological research on publication and related biases in HSR is sparse. Evidence from available literature suggests that such biases may exist in HSR but their scale and impact are difficult to estimate for various reasons discussed in this paper. Systematic review registration: PROSPERO 2016 CRD42016052333

MAIA, Fc receptor–like 3, supersedes JUNO as IZUMO1 receptor during human fertilization

Gamete fusion is a critical event of mammalian fertilization. A random one-bead one-compound combinatorial peptide library represented synthetic human egg mimics and identified a previously unidentified ligand as Fc receptor–like 3, named MAIA after the mythological goddess intertwined with JUNO. This immunoglobulin super family receptor was expressed on human oolemma and played a major role during sperm-egg adhesion and fusion. MAIA forms a highly stable interaction with the known IZUMO1/JUNO sperm-egg complex, permitting specific gamete fusion. The complexity of the MAIA isotype may offer a cryptic sexual selection mechanism to avoid genetic incompatibility and achieve favorable fitness outcomes

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR