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

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

Seasonality of MRSA Infections

Using MRSA isolates submitted to our hospital microbiology laboratory January 2001–March 2010 and the number of our emergency department (ED) visits, quarterly community-associated (CA) and hospital-associated (HA) MRSA infections were modeled using Poisson regressions. For pediatric patients, approximately 1.85x (95% CI 1.45x–2.36x, adj. p<0.0001) as many CA-MRSA infections per ED visit occurred in the second two quarters as occurred in the first two quarters. For adult patients, 1.14x (95% CI 1.01x–1.29x, adj.p = 0.03) as many infections per ED visit occurred in the second two quarters as in the first two quarters. Approximately 2.94x (95% CI 1.39x–6.21x, adj.p = 0.015) as many HA-MRSA infections per hospital admission occurred in the second two quarters as occurred in the first two quarters for pediatric patients. No seasonal variation was observed among adult HA-MRSA infections per hospital admission. We demonstrated seasonality of MRSA infections and provide a summary table of similar observations in other studies

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

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

Distinguishing Characteristics between Pandemic 2009–2010 Influenza A (H1N1) and Other Viruses in Patients Hospitalized with Respiratory Illness

BACKGROUND: Differences in clinical presentation and outcomes among patients infected with pandemic 2009 influenza A H1N1 (pH1N1) compared to other respiratory viruses have not been fully elucidated. METHODOLOGY/PRINCIPAL FINDINGS: A retrospective study was performed of all hospitalized patients at the peak of the pH1N1 season in whom a single respiratory virus was detected by a molecular assay targeting 18 viruses/subtypes (RVP, Luminex xTAG). Fifty-two percent (615/1192) of patients from October, 2009 to December, 2009 had a single respiratory virus (291 pH1N1; 207 rhinovirus; 45 RSV A/B; 37 parainfluenza; 27 adenovirus; 6 coronavirus; and 2 metapneumovirus). No seasonal influenza A or B was detected. Individuals with pH1N1, compared to other viruses, were more likely to present with fever (92% & 70%), cough (92% & 86%), sore throat (32% & 16%), nausea (31% & 8%), vomiting (39% & 30%), abdominal pain (14% & 7%), and a lower white blood count (8,500/L & 13,600/L, all p-values<0.05). In patients with cough and gastrointestinal complaints, the presence of subjective fever/chills independently raised the likelihood of pH1N1 (OR 10). Fifty-five percent (336/615) of our cohort received antibacterial agents, 63% (385/615) received oseltamivir, and 41% (252/615) received steroids. The mortality rate of our cohort was 1% (7/615) and was higher in individuals with pH1N1 compared to other viruses (2.1% & 0.3%, respectively; p = 0.04). CONCLUSIONS/SIGNIFICANCE: During the peak pandemic 2009-2010 influenza season in Rhode Island, nearly half of patients admitted with influenza-like symptoms had respiratory viruses other than influenza A. A high proportion of patients were treated with antibiotics and pH1N1 infection had higher mortality compared to other respiratory viruses

Parametric exploration of the liver by magnetic resonance methods

MRI, as a completely noninvasive technique, can provide quantitative assessment of perfusion, diffusion, viscoelasticity and metabolism, yielding diverse information about liver function. Furthermore, pathological accumulations of iron and lipids can be quantified. Perfusion MRI with various contrast agents is commonly used for the detection and characterization of focal liver disease and the quantification of blood flow parameters. An extended new application is the evaluation of the therapeutic effect of antiangiogenic drugs on liver tumours. Novel, but already widespread, is a histologically validated relaxometry method using five gradient echo sequences for quantifying liver iron content elevation, a measure of inflammation, liver disease and cancer. Because of the high perfusion fraction in the liver, the apparent diffusion coefficients strongly depend on the gradient factors used in diffusion-weighted MRI. While complicating analysis, this offers the opportunity to study perfusion without contrast injection. Another novel method, MR elastography, has already been established as the only technique able to stage fibrosis or diagnose mild disease. Liver fat content is accurately determined with multivoxel MR spectroscopy (MRS) or by faster MRI methods that are, despite their widespread use, prone to systematic error. Focal liver disease characterisation will be of great benefit once multivoxel methods with fat suppression are implemented in proton MRS, in particular on high-field MR systems providing gains in signal-to-noise ratio and spectral resolution

Cataract in patients with diabetes mellitus—incidence rates in the UK and risk factors

Aims: To analyze the risk of incident cataract (diagnosis or extraction) in patients with or without diabetes focusing on other comorbid conditions, antidiabetic drug use, and diabetes duration. Methods: The study population comprised newly diagnosed diabetes patients (≥40 years) from the UK-based Clinical Practice Research Datalink (CPRD) between 2000 and 2015, and a random sample of the general population matched for age, sex, general practice, and year of diabetes diagnosis. We assessed cataract incidence rates (IRs) and performed a nested case-control analysis in the diabetic cohort to assess potential risk factors for a cataract. Results: There were 56,510 diabetes patients included in the study. IRs of cataract were 20.4 (95% CI 19.8-20.9) per 1000 person-years (py) in patients with diabetes and 10.8 (95% CI 10.5-11.2) per 1000 py in the general population. IRs increased considerably around the age of 80 years and with a concomitant diagnosis of macular edema. The incidence rate ratio (IRR) was highest in patients of the age group of 45-54 years. In the nested case-control study, we identified 5800 patients with cataract. Risk of cataract increased with increasing diabetes duration (adj. OR 5.14, 95% CI 4.19-6.30 diabetes for ≥10 years vs. diabetes <2 years). Conclusions: According to our study, diabetes is associated with an approximately two-fold increased detection rate of cataract. The risk of cataract associated with diabetes is highest at younger ages. Patients with diabetic macular edema are at an increased risk for cataract as well as patients with long-standing diabetes