Ultrasonic Communication in Rats: Can Playback of 50-kHz Calls Induce Approach Behavior?

Rats emit distinct types of ultrasonic vocalizations, which differ depending on age, the subject's current state and environmental factors. Since it was shown that 50-kHz calls can serve as indices of the animal's positive subjective state, they have received increasing experimental attention, and have successfully been used to study neurobiological mechanisms of positive affect. However, it is likely that such calls do not only reflect a positive affective state, but that they also serve a communicative purpose. Actually, rats emit the highest rates of 50-kHz calls typically during social interactions, like reproductive behavior, juvenile play and tickling. Furthermore, it was recently shown that rats emit 50-kHz calls after separation from conspecifics. The aim of the present study was to test the communicative value of such 50-kHz calls. In a first experiment, conducted in juvenile rats situated singly on a radial maze apparatus, we showed that 50-kHz calls can induce behavioral activation and approach responses, which were selective to 50-kHz signals, since presentation of 22-kHz calls, considered to be aversive or threat signals, led to behavioral inhibition. In two other experiments, we used either natural 50-kHz calls, which had been previously recorded from other rats, or artificial sine wave stimuli, which were identical to these calls with respect to peak frequency, call length and temporal appearance. These signals were presented to either juvenile (Exp. 2) or adult (Exp. 3) male rats. Our data clearly show that 50-kHz signals can induce approach behavior, an effect, which was more pronounced in juvenile rats and which was not selective to natural calls, especially in adult rats. The recipient rats also emitted some 50-kHz calls in response to call presentation, but this effect was observed only in adult subjects. Together, our data show that 50-kHz calls can serve communicative purposes, namely as a social signal, which increases the likelihood of approach in the recipient conspecific

Solving Continuous Control via Q-learning

While there has been substantial success for solving continuous control with actor-critic methods, simpler critic-only methods such as Q-learning find limited application in the associated high-dimensional action spaces. However, most actor-critic methods come at the cost of added complexity: heuristics for stabilisation, compute requirements and wider hyperparameter search spaces. We show that a simple modification of deep Q-learning largely alleviates these issues. By combining bang-bang action discretization with value decomposition, framing single-agent control as cooperative multi-agent reinforcement learning (MARL), this simple critic-only approach matches performance of state-of-the-art continuous actor-critic methods when learning from features or pixels. We extend classical bandit examples from cooperative MARL to provide intuition for how decoupled critics leverage state information to coordinate joint optimization, and demonstrate surprisingly strong performance across a variety of continuous control tasks

Learning to Plan via Deep Optimistic Value Exploration

Deep exploration requires coordinated long-term planning. We present a model-based reinforcement learning algorithm that guides policy learning through a value function that exhibits optimism in the face of uncertainty. We capture uncertainty over values by combining predictions from an ensemble of models and formulate an upper confidence bound (UCB) objective to recover optimistic estimates. Training the policy on ensemble rollouts with the learned value function as the terminal cost allows for projecting long-term interactions into a limited planning horizon, thus enabling deep optimistic exploration. We do not assume a priori knowledge of either the dynamics or reward function. We demonstrate that our approach can accommodate both dense and sparse reward signals, while improving sample complexity on a variety of benchmarking tasks. Keywords: Reinforcement Learning; Deep Exploration; Model-Based; Value Function; UCBOffice of Naval Research; Qualcomm; Toyota Research Institut

The Effect of Cyclooxygenase Inhibition on Tendon-Bone Healing in an In Vitro Coculture Model

The effects of cyclooxygenase (COX) inhibition following the reconstruction of the anterior cruciate ligament remain unclear. We examined the effects of selective COX-2 and nonselective COX inhibition on bone-tendon integration in an in vitro model. We measured the dose-dependent effects of ibuprofen and parecoxib on the viability of lipopolysaccharide- (LPS-) stimulated and unstimulated mouse MC3T3-E1 and 3T3 cells, the influence on gene expression at the osteoblast, interface, and fibroblast regions measured by quantitative PCR, and cellular outgrowth assessed on histological sections. Ibuprofen led to a dose-dependent suppression of MC3T3 cell viability, while parecoxib reduced the viability of 3T3 cultures. Exposure to ibuprofen significantly suppressed expression of Alpl (P < 0.01), Bglap (P < 0.001), and Runx2 (P < 0.01), and although parecoxib reduced expression of Alpl (P < 0.001), Fmod (P < 0.001), and Runx2 (P < 0.01), the expression of Bglap was increased (P < 0.01). Microscopic analysis showed a reduction in cellular outgrowth in LPS-stimulated cultures following exposure to ibuprofen and parecoxib. Nonselective COX inhibition and the specific inhibition of COX-2 led to region-specific reductions in markers of calcification and cell viability. We suggest further in vitro and in vivo studies examining the biologic and biomechanical effects of selective and nonselective COX inhibition

Neighborhood Mixup Experience Replay: Local Convex Interpolation for Improved Sample Efficiency in Continuous Control Tasks

Experience replay plays a crucial role in improving the sample efficiency of deep reinforcement learning agents. Recent advances in experience replay propose using Mixup (Zhang et al., 2018) to further improve sample efficiency via synthetic sample generation. We build upon this technique with Neighborhood Mixup Experience Replay (NMER), a geometrically-grounded replay buffer that interpolates transitions with their closest neighbors in state-action space. NMER preserves a locally linear approximation of the transition manifold by only applying Mixup between transitions with vicinal state-action features. Under NMER, a given transition's set of state action neighbors is dynamic and episode agnostic, in turn encouraging greater policy generalizability via inter-episode interpolation. We combine our approach with recent off-policy deep reinforcement learning algorithms and evaluate on continuous control environments. We observe that NMER improves sample efficiency by an average 94% (TD3) and 29% (SAC) over baseline replay buffers, enabling agents to effectively recombine previous experiences and learn from limited data.Comment: Accepted to L4DC 202

Surgical complications following ESIN for clavicular mid-shaft fractures do not limit functional or patient-perceived outcome

Elastic intramedullary nailing (ESIN) has been proposed as an alternative minimal-invasive method for the operative management of mid-shaft fractures of the clavicle. However, a relevant complication rate has been reported in previous cohorts. The present retrospective single-centre study aimed to analyse the complications following ESIN in adult patients with clavicular mid-shaft fractures (Allman type I) and their impact on functional and patient-perceived outcome measures. Results were compared to a control group receiving locking plate osteosynthesis. The clinical course and outcome of operatively managed patients with clavicular mid-shaft fractures were retrospectively analysed. Patients were assigned to group A (ESIN) and group B (plate fixation). Radiological, functional (Constant Murley Shoulder Outcome Score (CS), the Disabilities of the Arm, Shoulder and Hand (DASH) Score, the Oxford Shoulder Score (OSS)), and patient perceived aesthetic and clinical outcome were measured. A total of 47 (33 male, 14 female) operatively managed patients with a mean age of 26.7 +/- 14.9 years and a follow up time of 38.1 +/- 19.4 months were analysed. 36 patients were treated by ESIN (Group A), whereas 11 patients received open reduction and internal plate fixation (Group B). Patients were operatively treated with a mean delay of 7.4 +/- 9.3 days (group A: 6.6 +/- 8.7 days, group B: 10.2 +/- 11.1 days, p = 0.326) between trauma and the surgical index procedure. There were no significant differences in the functional (CS: p = 0.338, DASH: p = 0.247, OSS: p = 0.434) and patient-perceived (p = 0.346) outcome measures between both groups. Surgical complications were noted in 14 patients (group A: 12, group B: 2) and non-union in 4 patients (group A: 3, group B: 1). There was no correlation between the recorded complications as assessed by the Clavien and Dindo classification and the functional as well as the patient-perceived outcome measures. Despite a relevant incidence rate of surgical complications, ESIN provides good to excellent functional and patient-perceived results in the treatment of clavicular mid-shaft fractures. (C) 2015 Elsevier Ltd. All rights reserved

The influence of pre-existing radiographic osteoarthritis on functional outcome after trochanteric fracture

Purpose It is crucially important to optimise functional outcome after fixation of trochanteric femoral fractures. While a number of risk factors that predict a poor clinical course have been identified, the influence of pre-existing radiographic osteoarthritis (OA) of the hip is unclear. Methods The influence of pre-existing radiographic OA of the hip on short- to mid-term functional outcome was prospectively analysed in a cohort of patients undergoing proximal femoral nailing for trochanteric fracture. OA was graded according to Kellgren and Lawrence; functional outcome was assessed at six and 12 months by the Harris hip score (HHS), the timed up and go (TUG) test and the Barthel Index. Results Our cohort comprised 188 patients (58 were male and 130 female), with a mean age of 82 years. At six and 12 months postoperatively, the HHS (p < 0.001 and p = 0.008, respectively) and Barthel Index (p < 0.001 and p = 0.02, respectively) correlated significantly with the grade of pre-existing OA. After adjustment for confounding variables, there was a significant association between the grade of pre-existing OA and the HHS at six months (p = 0.02). Although we observed trends suggestive of other relationships, none reached statistical significance. Conclusions Pre-existing radiographic OA of the hip is an important determinant of clinical outcome in elderly patients with a trochanteric femoral fracture. Further studies will be needed to establish the most effective means of restoring hip function after trochanteric femoral fracture in patients with radiographic OA of the hip

Association of an In-House Blood Bank with Therapy and Outcome in Severely Injured Patients: An Analysis of 18,573 Patients from the TraumaRegister DGU®

Introduction Hemorrhagic shock remains one of the most common causes of death in severely injured patients. It is unknown to what extent the presence of a blood bank in a trauma center influences therapy and outcome in such patients. Material and Methods We retrospectively analyzed prospectively recorded data from the TraumaRegister DGU® and the TraumaNetzwerk DGU®. Inclusion criteria were Injury Severity Score (ISS) ≥ 16, primarily treated patients, and hospital admission 2 years before or after the audit process. Results Complete data sets of 18,573 patients were analyzed. Of 457 hospitals included, 33.3% had an in-house blood bank. In trauma centers with a blood bank (HospBB), packed red blood cells (PRBCs) (21.0% vs. 17.4%, p < 0.001) and fresh frozen plasma (FFP) (13.9% vs. 10.2%, p <0.001) were transfused significantly more often than in hospitals without a blood bank (Hosp0). However, no significant difference was found for in-hospital mortality (standard mortality ratio [SMR, 0.907 vs. 0.945; p = 0.25). In patients with clinically apparent shock on admission, no difference of performed transfusions were present between HospBB and Hosp0 (PRBCs, 51.4% vs. 50.4%, p = 0.67; FFP, 32.7% vs. 32.7%, p = 0.99), and no difference in in-hospital mortality was observed (SMR, 0.907 vs. 1.004; p = 0.21). Discussion In HospBB transfusions were performed more frequently in severely injured patients without positively affecting the 24h mortality or in-house mortality. Easy access may explain a more liberal transfusion concept

Prevalence and influence of tibial tunnel widening after isolated anterior cruciate ligament reconstruction using patella-bone-tendon-bone-graft: long-term follow-up

The aim of the present study was to evaluate incidence, degree and impact of tibial tunnel widening (TW) on patient-reported long-term clinical outcome, knee joint stability and prevalence of osteoarthritis (OA) after isolated anterior cruciate ligament (ACL) reconstruction. On average, 13.5 years after ACL reconstruction via patella-bone-tendon-bone autograft, 73 patients have been re-evaluated. Inclusion criteria consisted of an isolated anterior cruciate ligament rupture and reconstruction, a minimum of 10-year follow-up and no previous anterior cruciate ligament repair or associated intra-articular lesions. Clinical evaluation was performed via the International Knee Documentation Committee (IKDC) score and the Tegner and Lysholm scores. Instrumental anterior laxity testing was carried out with the KT-1000™ arthrometer. The degree of degenerative changes and the prevalence of osteoarthritis were assessed with the Kellgren-Lawrence score. Tibial tunnel enlargement was radiographically evaluated on both antero-posterior and lateral views under establishment of 4 degrees of tibial tunnel widening by measuring the actual tunnel diameters in mm on the sclerotic margins of the inserted tunnels on 3 different points (T1-T3). Afterwards, a conversion of the absolute values in mm into a 4 staged ratio, based on the comparison to the results of the initial drill-width, should provide a better quantification and statistical analysis. Evaluation was performed postoperatively as well as on 2 year follow-up and 13 years after ACL reconstruction. Minimum follow-up was 10 years. 75% of patients were graded A or B according to IKDC score. The mean Lysholm score was 90.2 ± 4.8 (25-100). Radiological assessment on long-term follow-up showed in 45% a grade I, in 24% a grade II, in 17% a grade III and in additional 12% a grade IV enlargement of the tibial tunnel. No evident progression of TW was found in comparison to the 2 year results. Radiological evaluation revealed degenerative changes in sense of a grade II OA in 54% of patients. Prevalence of a grade III or grade IV OA was found in 20%. Correlation analysis showed no significant relationship between the amount of tibial tunnel enlargement (P&gt;0.05), long-term clinical results, anterior joint laxity or prevalence of osteoarthritis. Tunnel widening remains a radiological phenomenon which is most commonly observed within the short to midterm intervals after anterior cruciate ligament reconstruction and subsequently stabilises on mid and long- term follow-up. It does not adversely affect long-term clinical outcome and stability. Furthermore, tunnel widening doesn’t constitute an increasing prevalence of osteoarthritis