Embryonic Signaling Pathways and Rhabdomyosarcoma: Contributions to Cancer Development and Opportunities for Therapeutic Targeting

Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood and adolescence, accounting for approximately 7% of childhood cancers. Current therapies include nonspecific cytotoxic chemotherapy regimens, radiation therapy, and surgery; however, these multimodality strategies are unsuccessful in the majority of patients with high-risk disease. It is generally believed that these tumors represent arrested or aberrant skeletal muscle development, and, accordingly, developmental signaling pathways critical to myogenesis such as Notch, WNT, and Hedgehog may represent new therapeutic targets. In this paper, we summarize the current preclinical studies linking these embryonic pathways to rhabdomyosarcoma tumorigenesis and provide support for the investigation of targeted therapies in this embryonic cancer

The role of peri-hepatic drain placement in liver surgery: a prospective analysis

AbstractBackgroundThe standard use of an intra-operative perihepatic drain (IPD) in liver surgery is controversial and mainly supported by retrospective data. The aim of this study was to evaluate the role of IPD in liver surgery.MethodsAll patients included in a previous, randomized trial were analysed to determine the association between IPD placement, post-operative complications (PC) and treatment. A multivariate analysis identified predictive factors of PC.ResultsOne hundred and ninety-nine patients were included in the final analysis of which 114 (57%) had colorectal liver metastases. IPD (n = 87, 44%) was associated with pre-operative biliary instrumentation (P = 0.023), intra-operative bleeding (P < 0.011), Pringle's manoeuver(P < 0.001) and extent of resection (P = 0.001). Seventy-seven (39%) patients had a PC, which was associated with pre-operative biliary instrumentation (P = 0.048), extent of resection (P = 0.002) and a blood transfusion (P = 0.001). Patients with IPD had a higher rate of high-grade PC (25% versus 12%, P = 0.008). Nineteen patients (9.5%) developed a post-operative collection [IPD (n = 10, 11.5%) vs. no drains (n = 9, 8%), P = 0.470]. Seven (8%) patients treated with and 9(8%) without a IPD needed a second drain after surgery, P = 1. Resection of ≥3 segments was the only independent factor associated with PC [odds ratio (OR) = 2, P = 0.025, 95% confidence interval (CI) 1.1–3.7].DiscussionIn spite of preferential IPD use in patients with more complex tumours/resections, IPD did not decrease the rate of PC, collections and the need for a percutaneous post-operative drain. IPD should be reserved for exceptional circumstances in liver surgery

Multiple-look effects on temporal discrimination within sound sequences

The multiple-look notion holds that the difference limen (DL) decreases with multiple observations. We investigated this notion for temporal discrimination in isochronous sound sequences. In Experiment 1, we established a multiple-look effect when sequences comprised nine standard time intervals (S) followed by an increasing number of comparison time intervals (C), but no multiple-look effect when one trailing C interval was preceded by an increasing number of S intervals. In Experiment 2, we extended the design. There were four sequential conditions: (a) 9 leading S intervals followed by 1, 2, …, or 9 C-intervals; (b) 9 leading C intervals followed by 1, 2, …, or 9 S intervals; (c) 9 trailing C-intervals preceded by 1, 2, …, or 9 S-intervals; and (d) 9 trailing S-intervals preceded by 1, 2, …, or 9 C-intervals. Both the interval accretions before and after the tempo change caused multiple-look effects, irrespective of the time order of S and C. Complete deconfounding of the number of intervals before and after the tempo change was accomplished in Experiment 3. The multiple-look effect of interval accretion before the tempo change was twice as big as that after the tempo change. The diminishing returns relation between the DL and interval accretion could be described well by a reciprocal function

The adequacy of Hepato‐Pancreato‐Biliary training: how closely do perceptions of fellows and programme directors align?

BackgroundHepatopancreatobiliary fellowship programmes have recently undergone significant changes with regards to training standards, case‐volume thresholds and multimodality educational platforms. The goals of this study were to compare the perspectives of fellows and programme directors (PDs) on perceptions of readiness to enter practice and identify core Hepato‐Pancreato‐Biliary (HPB) procedures that require increased emphasis during training.MethodsThis survey targeted PDs and trainees participating in the Fellowship Council/AHPBA pathway. Data related to demographics, education and career plans were collected. Analysis of PD and fellow opinions regarding their confidence to perform core HPB procedures was completed.ResultsThe response rate was 88% for both fellows (21/24) and PDs (23/26). There was good agreement between PDs and fellows in the perception of case volumes. Select differences where PDs ranked higher perceptions included major hepatectomies (PDs: 87% versus fellows: 57%, P = 0.04), pancreaticoduodenectomies (100% versus 81%, P = 0.04) and laparoscopic distal pancreatectomies (78% versus 43%, P = 0.03). ‘Good or excellent’ case volumes translated into increased fellow readiness, except for some pancreatitis procedures, laparoscopic distal pancreatectomies and potentially major hepatectomies.ConclusionsThis study provides insight into content domains that may require additional attention to achieve an appropriate level of proficiency and confidence upon completion of training.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/113116/1/hpb12457.pd

Visual onset expands subjective time

We report a distortion of subjective time perception in which the duration of a first interval is perceived to be longer than the succeeding interval of the same duration. The amount of time expansion depends on the onset type defining the first interval. When a stimulus appears abruptly, its duration is perceived to be longer than when it appears following a stationary array. The difference in the processing time for the stimulus onset and motion onset, measured as reaction times, agrees with the difference in time expansion. Our results suggest that initial transient responses for a visual onset serve as a temporal marker for time estimation, and a systematic change in the processing time for onsets affects perceived time

Adiabatically coupled systems and fractional monodromy

We present a 1-parameter family of systems with fractional monodromy and adiabatic separation of motion. We relate the presence of monodromy to a redistribution of states both in the quantum and semi-quantum spectrum. We show how the fractional monodromy arises from the non diagonal action of the dynamical symmetry of the system and manifests itself as a generic property of an important subclass of adiabatically coupled systems

A fuzzy multi-criteria decision making approach for managing performance and risk in integrated procurement-production planning

Nowadays in Supply Chain (SC) networks, a high level of risk comes from SC partners. An effective risk management process becomes as a consequence mandatory, especially at the tactical planning level. The aim of this article is to present a risk-oriented integrated procurement–production approach for tactical planning in a multi-echelon SC network involving multiple suppliers, multiple parallel manufacturing plants, multiple subcontractors and several customers. An originality of the work is to combine an analytical model allowing to build feasible scenarios and a multi-criteria approach for assessing these scenarios. The literature has mainly addressed the problem through cost or profit-based optimisation and seldom considers more qualitative yet important criteria linked to risk, like trust in the supplier, flexibility or resilience. Unlike the traditional approaches, we present a method evaluating each possible supply scenario through performance-based and risk-based decision criteria, involving both qualitative and quantitative factors, in order to clearly separate the performance of a scenario and the risk taken if it is adopted. Since the decision-maker often cannot provide crisp values for some critical data, fuzzy sets theory is suggested in order to model vague information based on subjective expertise. Fuzzy Technique for Order of Preference by Similarity to Ideal Solution is used to determine both the performance and risk measures correlated to each possible tactical plan. The applicability and tractability of the proposed approach is shown on an illustrative example and a sensitivity analysis is performed to investigate the influence of criteria weights on the selection of the procurement–production plan

Phase transition between synchronous and asynchronous updating algorithms

We update a one-dimensional chain of Ising spins of length $L$ with algorithms which are parameterized by the probability $p$ for a certain site to get updated in one time step. The result of the update event itself is determined by the energy change due to the local change in the configuration. In this way we interpolate between the Metropolis algorithm at zero temperature for $p$ of the order of 1/L and for large $L$, and a synchronous deterministic updating procedure for $p=1$. As function of $p$ we observe a phase transition between the stationary states to which the algorithm drives the system. These are non-absorbing stationary states with antiferromagnetic domains for $p>p_c$, and absorbing states with ferromagnetic domains for $p\leq p_c$. This means that above this transition the stationary states have lost any remnants to the ferromagnetic Ising interaction. A measurement of the critical exponents shows that this transition belongs to the universality class of parity conservation.Comment: 5 pages, 3 figure