National Football League Skilled and Unskilled Positions Vary in Opportunity and Yield in Return to Play After an Anterior Cruciate Ligament Injury.

BACKGROUND: Anterior cruciate ligament (ACL) injuries pose a significant risk to the careers of players in the National Football League (NFL). The relationships between draft round and position on return to play (RTP) among NFL players are not well understood, and the ability to return to preinjury performance levels remains unknown for most positions. PURPOSE: To test for differences in RTP rates and changes in performance after an ACL injury by position and draft round. We hypothesized that skilled positions would return at a lower rate compared to unskilled positions. We further hypothesized that early draft-round status would relate to a greater rate of RTP and that skilled positions and a lower draft round would correlate with decreased performance for players who return to sport. STUDY DESIGN: Case-control study; Level of evidence, 3. METHODS: Utilizing a previously established database of publicly available information regarding ACL tears among NFL players, athletes with ACL tears occurring between the 2010 and 2013 seasons were identified. Generalized linear models and Kaplan-Meier time-to-event models were used to test the study hypotheses. RESULTS: The overall RTP rate was 61.7%, with skilled players and unskilled players returning at rates of 64.1% and 60.4%, respectively (P = .74). Early draft-round players and unskilled late draft-round players had greater rates of RTP compared to skilled late draft-round players and both unskilled and skilled undrafted free agents (UDFAs). Skilled early draft-round players constituted the only cohort that played significantly fewer games after an injury. Unskilled UDFAs constituted the only cohort to show a significant increase in the number of games started and ratio of games started to games played, starting more games in which they played, after an injury. CONCLUSION: Early draft-round and unskilled players were more likely to return compared to their later draft-round and skilled peers. Skilled early draft-round players, who displayed relatively high rates of RTP, constituted the only cohort to show a decline in performance. Unskilled UDFAs, who exhibited relatively low rates of RTP, constituted the only cohort to show an increase in performance. The significant effect of draft round and position type on RTP may be caused by a combination of differences in talent levels and in opportunities given to returning to play

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

The Protection of Animals through Human Rights. The Case-Law of the European Court of Human Rights

The chapter discusses the potential of a human rights framework to contribute to the growth and development of global animal law. It takes as example the jurisprudence of the European Court of Human Rights, and examine the major trends in the Court’s judgments and admissibility decisions that directly or indirectly concern the rights or welfare of animals. It is concluded that the Court is not indifferent to the welfare of animals, but that animal welfare is instrumentalised: it is understood not as a good in itself, but is instead valued for its implications for human welfare and rights. The chapter then considers the obstacles that the anthropocentrism of the human rights idea and the instrumentalisation of animal concerns present to the use of human rights frameworks to further the development of global animal law, as well as the opportunities that exist in the meeting of these paradigms. It concludes that although the telos of human rights law is different from that of animal law, nevertheless there exist many overlapping concerns within which mutually beneficial interactions are possible

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

HLA antibody incompatible renal transplantation : long-term outcomes similar to deceased donor transplantation

Background. HLA incompatible renal transplantation still remains one of best therapeutic options for a subgroup of patients who are highly sensitized and difficult to match but not much is known about its long-term graft and patient survival. Methods. One hundred thirty-four HLA incompatible renal transplantation patients from 2003 to 2018 with a median follow of 6.93 y were analyzed retrospectively to estimate patient and graft survivals. Outcomes were compared with groups defined by baseline crossmatch status and the type and timings of rejection episodes. Results. The overall patient survival was 95%, 90%, and 81%; and graft survival was 95%, 85%, and 70% at 1, 5, and 10 y, respectively. This was similar to the first-time deceased donor transplant cohort. The graft survival for pretreatment cytotoxic-dependent crossmatch (CDC) positive crossmatch group was significantly low at 83%, 64%, and 40% at 1, 5, and 10 y, respectively, compared with other groups (Bead/CDC, P = 0.007; CDC/Flow, P = 0.001; and microbead assay/flow cytometry crossmatch, P = 0.837), although those with a low CDC titer (<1 in 2) have comparable outcomes to the CDC negative group. Female patients in general fared worse in both patient and graft survival outcomes in each of the 3 groups based on pretreatment crossmatch, although this did not reach statistical significance. Antibody-mediated rejection was the most frequent type of rejection with significant decline in graft survival by 10 y when compared with no rejection (P < 0.001). Rejection that occurred or continued to occur after the first 2 wk of transplantation caused a significant reduction in graft survivals (P < 0.001), whereas good outcomes were seen in those with a single early rejection episode. Conclusions. One-, 5-, and 10-y HLA incompatible graft and patient survival is comparable to deceased donor transplantation and can be further improved by excluding high-CDC titer cases. Antibody-positive female patients show worse long-term survival. Resolution of early rejection is associated with good long-term graft survival

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

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

Homing and Long-Term Engraftment of Long- and Short-Term Renewal Hematopoietic Stem Cells

Long-term hematopoietic stem cells (LT-HSC) and short-term hematopoietic stem cells (ST-HSC) have been characterized as having markedly different in vivo repopulation, but similar in vitro growth in liquid culture. These differences could be due to differences in marrow homing. We evaluated this by comparing results when purified ST-HSC and LT-HSC were administered to irradiated mice by three different routes: intravenous, intraperitoneal, and directly into the femur. Purified stem cells derived from B6.SJL mice were competed with marrow cells from C57BL/6J mice into lethally irradiated C57BL/6J mice. Serial transplants into secondary recipients were also carried out. We found no advantage for ST-HSC engraftment when the cells were administered intraperitoneally or directly into femur. However, to our surprise, we found that the purified ST-HSC were not short-term in nature but rather gave long-term multilineage engraftment out to 387 days, albeit at a lower level than the LT-HSC. The ST-HSC also gave secondary engraftment. These observations challenge current models of the stem cell hierarchy and suggest that stem cells are in a continuum of change