One decade ago, our laboratory provided the first direct evidence linking orexin/hypocretin signaling with drug seeking by showing that activation of these neurons promotes conditioned ...morphine-seeking behavior. In the years since, contributions from many investigators have revealed roles for orexins in addiction for all drugs of abuse tested, but only under select circumstances. We recently proposed that orexins play a fundamentally unified role in coordinating "motivational activation" under numerous behavioral conditions, and here we unpack this hypothesis as it applies to drug addiction. We describe evidence collected over the past 10 years that elaborates the role of orexin in drug seeking under circumstances where high levels of effort are required to obtain the drug, or when motivation for drug reward is augmented by the presence of external stimuli like drug-associated cues/contexts or stressors. Evidence from studies using traditional self-administration and reinstatement models, as well as behavioral economic analyses of drug demand elasticity, clearly delineates a role for orexin in modulating motivational, rather than the primary reinforcing aspects of drug reward. We also discuss the anatomical interconnectedness of the orexin system with wider motivation and reward circuits, with a particular focus on how orexin modulates prefrontal and other glutamatergic inputs onto ventral tegmental area dopamine neurons. Last, we look ahead to the next decade of the research in this area, highlighting the recent FDA approval of the dual orexin receptor antagonist suvorexant (Belsomra
) for the treatment of insomnia as a promising sign of the potential clinical utility of orexin-based therapies for the treatment of addiction.
Background Various methods of bony stabilization, including modifications of Bristow and Latarjet procedures, are considered gold-standard treatment for recurrent anterior shoulder instability but ...are associated with unique complications and risk of reoperation. The purpose of this study was to identify the prevalence of these complications. We hypothesized that the Bristow-Latarjet procedure would be a successful technique for treatment of shoulder instability but associated with a risk of recurrent postoperative instability, reoperation, and other complications. Methods A systematic review of multiple medical databases included studies reporting outcomes with complication and reoperation rates following original or modified versions of the Bristow or Latarjet shoulder stabilization surgeries. Results Forty-five studies were analyzed (1,904 shoulders) (all Level IV evidence). Most subjects were male (82%). The dominant shoulder was the operative shoulder in 64% of cases. Mean subject age was 25.8 years. Mean clinical follow-up was 6.8 years. Ninety percent of surgeries were done open; 9.3% were all-arthroscopic. Total complication rate was 30%. Recurrent anterior dislocation and subluxation rates were 2.9% and 5.8%, respectively. When reported, most dislocations occurred within the first year postoperatively (73%). Nearly 7% of patients required an unplanned reoperation following surgery. Conclusion Osseous stabilization shoulder surgery using original or modified Bristow and Latarjet procedures has a 30% complication rate. Rates of recurrent dislocation and reoperation were 2.9% and 7%, respectively. Mild loss of external rotation is common. Reoperation rates were lower following all-arthroscopic techniques. There was a greater loss of postoperative external rotation with all-arthroscopic surgery.
Broader distribution--in terms of geography and bacterial genera--of plasmid-associated mcr-1 is evident because it has now been identified outside Asia.1 Saliently, we describe its presence in an ...important foodborne pathogen recovered from food and animal environments and associated with well described phenotypic resistance (by disk diffusion, broth microdilution, and concentration gradient strips). 2013LSAL02374 12CEB4337SAL 12CEB2196SAL 2013LSAL04524 Serotype Derby Paratyphi B Paratyphi B 1,4,5,12:i:- Year 2013 2012 2012 2013 Sample type Chipolata sausage Ready-to-cook guinea fowl pie Chicken breast with skin Boot swabs from broiler farm French department 62 56 85 01 AMP Non-res Non-res Non-res Res AMC Non-res Non-res Non-res Non-res CAZ Non-res Non-res Non-res Non-res CHL Res Res Res Res CEF Non-res Non-res Non-res Non-res CIP Non-res Res Res Non-res CST Res Res Res Res CTX Non-res Non-res Non-res Non-res GEN Non-res Res Res Res KAN Non-res Non-res Non-res Non-res NAL Non-res Res Res Non-res OFX Non-res Non-res Non-res Non-res STR Res Res Res Res SSS Res Res Res Res SXT Res Res Res Res TET Res Res Res Res GenBank accession number LNCZ00000000 LKJK00000000 LKJJ00000000 LKJD00000000 Plasmid replicon harbouring mcr-1 IncP IncX4 IncX4 IncP Table Isolate information for mcr-1 positive isolates selected for whole genome sequencing AMP=ampicillin.
Here, we report on the unique observation of flaring coronal loops at the solar limb using high-resolution imaging spectropolarimetry from the Swedish 1 m Solar Telescope. The vantage position, ...orientation, and nature of the chromospheric material that filled the flare loops allowed us to determine their magnetic field with unprecedented accuracy using the weak-field approximation method. Our analysis reveals coronal magnetic field strengths as high as 350 G at heights up to 25 Mm above the solar limb. These measurements are substantially higher than a number of previous estimates and may have considerable implications for our current understanding of the extended solar atmosphere.
Overeating ranges in severity from casual overindulgence to an overwhelming drive to consume certain foods. At its most extreme, overeating can manifest as clinical diagnoses such as binge eating ...disorder or bulimia nervosa, yet subclinical forms of overeating such as emotional eating or uncontrolled eating can still have a profoundly negative impact on health and wellbeing. Although rodent models cannot possibly capture the full spectrum of disordered overeating, studies in laboratory rodents have substantially progressed our understanding of the neurobiology of overconsumption. These experimental approaches range from simple food-exposure protocols that promote binge-like eating and the development of obesity, to more complex operant procedures designed to examine distinct ‘addiction-like’ endophenotypes for food. This review provides an overview of these experimental approaches, with the view to providing a comprehensive resource for preclinical investigators seeking to utilize behavioural models for studying the neural systems involved in food overconsumption.
•Overeating can manifest as diagnosable eating disorders or subclinical pathology.•We review approaches for studying overeating and pathological feeding in rodents.•These approaches are helpful for studying the neural basis of overeating.
ABSTRACT During a period of three days beginning 2013 January 17, twelve recurrent reconnection events occur within a small region of opposing flux embedded within one footpoint of an active region, ...accompanied by flares and jets observed in EUV and fast and faint structureless "puffs" observed by coronagraphs. During the same period a slow structured CME gradually erupts, with one end anchored close to, or within, the jetting region. Four of the jet events occur in pairs-a narrow, primary jet followed within a few tens of minutes by a wider, more massive, jet. All the jets are slow, with an apparent speed of ∼100 km s−1. The speed of the wide puffs in the coronagraph data is ∼300 km s−1, and the timing of their appearance rules out a direct association with the EUV jetting material. The jet material propagates along large-scale closed-field loops and does not escape to the extended corona. The rapid reconfiguration of the closed loops following reconnection causes an outwardly propagating disturbance, or wave front, which manifests as puffs in coronagraph data. Furthermore, the newly expanded closed flux tube forms a pressure imbalance, which can result in a secondary jet. The reconnection events, through recurrent field reconfiguration, also leads to the gradual eruption of the structured flux tube appearing as the slow CME. Faint propagating coronal disturbances resulting from flares/jets may be common, but are usually obscured by associated ejections. Occasionally, the associated material ejections are absent, and coronal puffs may be clearly observed.
Context.
Coronal bright points (BPs) are numerous, bright, small-scale dynamical features found in the solar corona. Bright points have been observed to exhibit intensity oscillations across a wide ...range of periodicities and are likely an important signature of plasma heating and/or transport mechanisms.
Aims.
We present a novel and efficient wavelet-based method that automatically detects and tracks the intensity evolution of BPs using images from the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory (SDO) in the 193 Å bandpass. Through the study of a large, statistically significant set of BPs, we attempt to place constraints on the underlying physical mechanisms.
Methods.
We used a continuous wavelet transform (CWT) in 2D to detect the BPs within images. One-dimensional CWTs were used to analyse the individual BP time series to detect significant periodicities.
Results.
We find significant periodicity at 4, 8–10, 17, 28, and 65 min. Bright point lifetimes are shown to follow a power law with exponent −1.13 ± 0.07. The relationship between the BP lifetime and maximum diameter similarly follows a power law with exponent 0.129 ± 0.011.
Conclusions.
Our wavelet-based method successfully detects and extracts BPs and analyses their intensity oscillations. Future work will expand upon these methods, using larger datasets and simultaneous multi-instrument observations.
Research into social learning (learning from others) has expanded significantly in recent years, not least because of productive interactions between theoretical and empirical approaches. This has ...been coupled with a new emphasis on learning strategies, which places social learning within a cognitive decision-making framework. Understanding when, how and why individuals learn from others is a significant challenge, but one that is critical to numerous fields in multiple academic disciplines, including the study of social cognition.
Meiosis is unusual among cell divisions in shuffling genetic material by crossovers among homologous chromosomes and partitioning the genome into haploid gametes. Crossovers are critical for ...chromosome segregation in most eukaryotes, but are also an important factor in evolution, as they generate novel genetic combinations. The molecular mechanisms that underpin meiotic recombination and chromosome segregation are well conserved across kingdoms, but are also sensitive to perturbation by environment, especially temperature. Even subtle shifts in temperature can alter the number and placement of crossovers, while at greater extremes, structural failures can occur in the linear axis and synaptonemal complex structures which are essential for recombination and chromosome segregation. Understanding the effects of temperature on these processes is important for its implications in evolution and breeding, especially in the context of global warming. In this review, we first summarize the process of meiotic recombination and its reliance on axis and synaptonemal complex structures, and then discuss effects of temperature on these processes and structures. We hypothesize that some consistent effects of temperature on recombination and meiotic thermotolerance may commonly be two sides of the same coin, driven by effects of temperature on the folding or interaction of key meiotic proteins.
This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’.
Purpose The purpose of this study was to evaluate the effect of graft size on patient-reported outcomes and revision risk after anterior cruciate ligament (ACL) reconstruction. Methods A ...retrospective chart review of prospectively collected cohort data was performed, and 263 of 320 consecutive patients (82.2%) undergoing primary ACL reconstruction with hamstring autograft were evaluated. We recorded graft size; femoral tunnel drilling technique; patient age, sex, and body mass index at the time of ACL reconstruction; Knee Injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee score preoperatively and at 2 years postoperatively; and whether each patient underwent revision ACL reconstruction during the 2-year follow-up period. Revision was used as a marker for graft failure. The relation between graft size and patient-reported outcomes was determined by multiple linear regression. The relation between graft size and risk of revision was determined by dichotomizing graft size at 8 mm and stratifying by age. Results After we controlled for age, sex, operative side, surgeon, body mass index, graft choice, and femoral tunnel drilling technique, a 1-mm increase in graft size was noted to correlate with a 3.3-point increase in the KOOS pain subscale ( P = .003), a 2.0-point increase in the KOOS activities of daily living subscale ( P = .034), a 5.2-point increase in the KOOS sport/recreation function subscale ( P = .004), and a 3.4-point increase in the subjective International Knee Documentation Committee score ( P = .026). Revision was required in 0 of 64 patients (0.0%) with grafts greater than 8 mm in diameter and 14 of 199 patients (7.0%) with grafts 8 mm in diameter or smaller ( P = .037). Among patients aged 18 years or younger, revision was required in 0 of 14 patients (0.0%) with grafts greater than 8 mm in diameter and 13 of 71 patients (18.3%) with grafts 8 mm in diameter or smaller. Conclusions Smaller hamstring autograft size is a predictor of poorer KOOS sport/recreation function 2 years after primary ACL reconstruction. A larger sample size is required to confirm the relation between graft size and risk of revision ACL reconstruction. Level of Evidence Level III, retrospective comparative study.
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