Retrospective observational cohort study on innovation in oncology and progress in survival: how far have we gotten in the two decades of treating patients with advanced non-small cell lung cancer as a single population?

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973–2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991–2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98–0.98], HRMMV-Patient = 0.98 [0.97–0.98], and HRMMV-State = 0.98 [0.98–0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04–1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival

Treatment of Septic arthritis of the coxofemoral joint in 12 foals

Objective: To describe the clinical signs, surgical treatment, and outcome of septic arthritis of the coxofemoral joint in foals. Study Design: Retrospective clinical study. Sample Population: Foals (n = 12) with confirmed sepsis of the coxofemoral joint. Methods: Lameness was localized to the coxofemoral joint based on physical examination. Sepsis was confirmed by cytological analysis of synovial fluid obtained under ultrasonographic guidance, during general anesthesia or standing sedation. Intra-articular analgesia was used as an adjunct diagnostic modality in 2 foals. Surgical lavage of the affected joint was performed via arthroscopy or needle lavage, with repeated lavage performed in 7 foals. Results: Synovial fluid contained 4.4 to 173 × 109/L white blood cells (WBCs), and 38-63 g/L total protein. Cultures were positive in 10/12 foals. Isolated organisms included Salmonella spp., Streptococcus spp., Rhodococcus spp., Enterococcus spp., Escherichia spp., Staphylococcus spp., Acinetobacter spp., Methicillin-resistant Staphylococcus aureus and Bacillus spp. Ten foals were discharged from hospital (83%). One of these was euthanized 15 days later due to chronic intestinal salmonellosis and renal failure, and 9 foals survived with no residual lameness detected 1 year after discharge from hospital. Conclusions: Sepsis of the coxofermoral joint can be effectively treated with a combination of arthroscopic lavage and the use of systemic and local antimicrobials

Substance-specific readiness to change among sexual and gender minority men who use crystal methamphetamine

A patient-oriented approach to addressing high levels of polysubstance use among sexual and gender minority men (SGM) who use crystal methamphetamine (CM) requires an understanding of which drugs they would like to change their use of. We examined readiness to change for 24 separate substances. Participants were SGM, aged 18+, living with Canada, who used CM in the past six months that were recruited through advertisements on socio-sexual networking applications. Frequency of use and readiness to change were descriptively analyzed and associations between frequency of use and readiness to change were assessed. Only slightly more than half (53.1%) of CM-using SGM were ready now, soon, or in the future to change substance use. Participants were most ready to change their tobacco, methamphetamine, and barbiturate use. Greater frequency of use was associated with greater readiness to change for all drugs in which daily or almost daily use was common. SGM participants reported high levels of comfort being asked about their substance use from primary care, mental health, and queer-identified health professionals. Interventions addressing multiple and specific substances are needed in health care settings serving SGM who use CM. Screening, brief interventions, and referral to treatment (SBIRT) in these settings may help identify those ready to address their substance use. Harm reduction interventions should offer supports for those not wanting to change their substance use—which includes most SGM for most of the drugs they use

The Role of Early Life Experience and Species Differences in Alcohol Intake in Microtine Rodents

Social relationships have important effects on alcohol drinking. There are conflicting reports, however, about whether early-life family structure plays an important role in moderating alcohol use in humans. We have previously modeled social facilitation of alcohol drinking in peers in socially monogamous prairie voles. We have also modeled the effects of family structure on the development of adult social and emotional behaviors. Here we assessed whether alcohol intake would differ in prairie voles reared by both parents compared to those reared by a single mother. We also assessed whether meadow voles, a closely related species that do not form lasting reproductive partnerships, would differ in alcohol drinking or in the effect of social influence on drinking. Prairie voles were reared either bi-parentally (BP) or by a single mother (SM). BP- and SM-reared adult prairie voles and BP-reared adult meadow voles were given limited access to a choice between alcohol (10%) and water over four days and assessed for drinking behavior in social and non-social drinking environments. While alcohol preference was not different between species, meadow voles drank significantly lower doses than prairie voles. Meadow voles also had significantly higher blood ethanol concentrations than prairie voles after receiving the same dose, suggesting differences in ethanol metabolism. Both species, regardless of rearing condition, consumed more alcohol in the social drinking condition than the non-social condition. Early life family structure did not significantly affect any measure. Greater drinking in the social condition indicates that alcohol intake is influenced similarly in both species by the presence of a peer. While the ability of prairie voles to model humans may be limited, the lack of differences in alcohol drinking in BP- and SM-reared prairie voles lends biological support to human studies demonstrating no effect of single-parenting on alcohol abuse

Range-wide experiment to investigate nutrient and soil moisture interactions in loblolly pine plantations

The future climate of the southeastern USA is predicted to be warmer, drier and more variable in rainfall, which may increase drought frequency and intensity. Loblolly pine (Pinus taeda) is the most important commercial tree species in the world and is planted on ~11 million ha within its native range in the southeastern USA. A regional study was installed to evaluate effects of decreased rainfall and nutrient additions on loblolly pine plantation productivity and physiology. Four locations were established to capture the range-wide variability of soil and climate. Treatments were initiated in 2012 and consisted of a factorial combination of throughfall reduction (approximate 30% reduction) and fertilization (complete suite of nutrients). Tree and stand growth were measured at each site. Results after two growing seasons indicate a positive but variable response of fertilization on stand volume increment at all four sites and a negative effect of throughfall reduction at two sites. Data will be used to produce robust process model parameterizations useful for simulating loblolly pine growth and function under future, novel climate and management scenarios. The resulting improved models will provide support for developing management strategies to increase pine plantation productivity and carbon sequestration under a changing climate.Peer reviewedNatural Resource Ecology and Managemen

Property and Contract Rights in Autocracies and Democracies

We present and test empirically a new theory of property and contract rights. Any incentive an autocrat has to respect such rights comes from his interest in future tax collections and national income and increases with his planning horizon. We find a compelling empirical relationship between property and contract rights and an autocrat's time in power. In lasting -- but not in new -- democracies, the same rule of law and individual rights that ensure continued free elections entail extensive property and contract rights. We show that the age of a democratic system is strongly correlated with property and contract rights

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead