Establishing optimal quantitative-polymerase chain reaction assays for routine diagnosis and tracking of minimal residual disease in JAK2-V617F-associated myeloproliferative neoplasms:a joint European LeukemiaNet/MPN&MPNr-EuroNet (COST action BM0902) study

Reliable detection of JAK2-V617F is critical for accurate diagnosis of myeloproliferative neoplasms (MPNs); in addition, sensitive mutation-specific assays can be applied to monitor disease response. However, there has been no consistent approach to JAK2-V617F detection, with assays varying markedly in performance, affecting clinical utility. Therefore, we established a network of 12 laboratories from seven countries to systematically evaluate nine different DNA-based quantitative PCR (qPCR) assays, including those in widespread clinical use. Seven quality control rounds involving over 21,500 qPCR reactions were undertaken using centrally distributed cell line dilutions and plasmid controls. The two best-performing assays were tested on normal blood samples (n=100) to evaluate assay specificity, followed by analysis of serial samples from 28 patients transplanted for JAK2-V617F-positive disease. The most sensitive assay, which performed consistently across a range of qPCR platforms, predicted outcome following transplant, with the mutant allele detected a median of 22 weeks (range 6-85 weeks) before relapse. Four of seven patients achieved molecular remission following donor lymphocyte infusion, indicative of a graft vs MPN effect. This study has established a robust, reliable assay for sensitive JAK2-V617F detection, suitable for assessing response in clinical trials, predicting outcome and guiding management of patients undergoing allogeneic transplant.

‘Emergent reconstruction’ in grounded theory: learning from team-based interview research

Constructivist grounded theory (CGT) methods render an interpretive portrayal, a construction of reality, strengthened when the process of construction is acknowledged. An Irish team study uses CGT to explore intergenerational solidarity at individual, familial and societal levels, and their interface. The study data comprise interviews with 100 people from diverse socio-economic and
age groups. The article contributes insights on applying CGT in team-based interview research on a topic with such breadth of scope. This contrasts with the more usual focused inquiry with a defined population. Adapting the method’s guidelines to the specific inquiry involved challenges in: framing the topic conceptually; situating research participants in contrasting social contexts to
provide interpretive depth; and generating interview data with which to construct theory. We argue that interrogating the very premise of the inquiry allowed for emergent reconstruction, a goal at the heart of the method.

Accuracy of shoulder joint and subacromial injections in cadavers.

OBJECTIVE:

"Blind" shoulder injections are often inaccurate and infiltrate untargeted structures. We tested a hypothesis that optimizing certain anatomical and positional factors would improve accuracy and reduce dispersal.

METHODS:

We evaluated one subacromial and one glenohumeral injection technique on cadavers.

RESULTS:

Mean accuracy was 91% for subacromial-targeted and 74 and 91% (worst- and best-case scenarios) for joint-targeted injections. Mean dispersal was 19% for subacromial-targeted and 16% for joint-targeted injections. All results bettered those reported previously.

CONCLUSION:

These "optimized" techniques might improve accuracy and limit dispersal of blind shoulder injections in clinical situations, benefiting efficacy and safety. However, evaluation is required in a clinical setting.

Finite element modelling of the formation of pre-load damage in cement mantles of orthopaedic joint replacements

Finite element modeling of the formation of pre-loaded damage in cement mantles of orthopaedic joint replacements was presented. The existence of cracking suggested a high level of residual stress. The direction of maximum principal stress vectors corresponded well with the observed crack orientation. Results suggested that cracking depends upon a combination of residual stress, porosity and temperature rise during polymerization.

Multiuser Cognitive Relay Networks: Joint Impact of Direct and Relay Communications

In this paper, we propose a multiuser cognitive relay network, where multiple secondary sources communicate with a secondary destination through the assistance of a secondary relay in the presence of secondary direct links and multiple primary receivers. We consider the two relaying protocols of amplify-and-forward (AF) and decode-and-forward (DF), and take into account the availability of direct links from the secondary sources to the secondary destination. With this in mind, we propose an optimal solution for cognitive multiuser scheduling by selecting the optimal secondary source, which maximizes the received signal-to-noise ratio (SNR) at the secondary destination using maximal ratio combining. This is done by taking into account both the direct link and the relay link in the multiuser selection criterion. For both AF and DF relaying protocols, we first derive closed-form expressions for the outage probability and then provide the asymptotic outage probability, which determines the diversity behavior of the multiuser cognitive relay network. Finally, this paper is corroborated by representative numerical examples.

Cognitive Single Carrier Systems: Joint Impact of Multiple Licensed Transceivers

In this paper, the impact of interference from multiple licensed transceivers on cognitive underlay single carrier systems is examined. Specifically, the situation is considered in which the secondary network is limited by three key parameters: 1) maximum transmit power at the secondary transmitter, 2) peak interference power at the primary receivers, and 3) interference power from the primary transmitters. For this cognitive underlay single carrier system, the signal-to-interference ratio (SIR) of the secondary network is obtained for transmission over frequency selective fading channels. Based on this, a new closedform expression for the cumulative distribution function of the SIR is evaluated, from which the outage probability and the ergodic capacity are derived. Further insights are established by analyzing the asymptotic outage probability and the asymptotic ergodic capacity in the high transmission power regime. In particular, it is corroborated that the asymptotic outage diversity gain is equal to the multipath gain of the frequency selective channel in the secondary network. The asymptotic ergodic capacity also gives new insight into the additional power cost for different network parameters while maintaining a specified target ergodic capacity. Illustrative numerical examples are presented to validate the outage probability and ergodic capacity under different interference power profiles.

Joint measurements on qubits and cloning of observables

Cloning of observables, unlike standard cloning of states, aims at copying the information encoded in the statistics of a class of observables rather then on quantum states themselves. In such a process the emphasis is on the quantum operation (evolution plus measurement) necessary to retrieve the original information. We analyze, for qubit systems, the cloning of a class generated by two noncommuting observables, elucidating the relationship between such a process and joint measurements. This helps in establishing an optimality criterion for cloning of observables. We see that, even if the cloning machine is designed to act on the whole class generated by two noncommuting observables, the same optimal performances of a joint measurement can be attained. Finally, the connection with state dependent cloning is enlightened.

Skin-reducing mastectomy and one-stage implant reconstruction with a myodermal flap: A safe and effective technique in risk-reducing and therapeutic mastectomy

Introduction: Immediate reconstruction following mastectomy for breast cancer has been shown to be oncologically safe and associated with improved psychosocial outcomes for patients. Bostwick described a technique for one-stage implant based reconstruction, combining skin-sparing mastectomy with concurrent reduction of the skin envelope. This report reviews the experience of a single centre using skin-reducing mastectomy and one-stage implant reconstruction in both early stage breast cancer and risk-reducing mastectomy, with specific reference to frequency of complications, implant loss and oncological outcomes.

Methods and results: A retrospective review was undertaken to identify women who had undergone skin-reducing mastectomy and one-stage implant reconstruction using a de-epithelialised dermal flap, between October 2008 and October 2012. One hundred and four consecutive mastectomies, with reconstruction, were performed by two surgeons on 64 patients. No complications were seen in 43.8% of patients. At three months, four implants were lost (3.8% of breast reconstructions, 6.3% of patients), due to either peri-implant infection or mastectomy skin flap necrosis. One patient required unplanned return to theatre for evacuation of a haematoma. Minor mastectomy skin flap necrosis was seen in 10 breasts (9.6% of reconstructed breasts) and superficial wound infection in 8 breasts (7.7% of reconstructed breasts). All of these complications were managed conservatively and none required operative intervention. At a median follow up of 35 months (4-53 months) there had been one episode of ipsilateral axillary nodal recurrence.

Conclusion: One-stage implant reconstruction using a myo-dermal flap technique following skin-reducing mastectomy is safe and should be considered in selected patients. Most complications are minor and will resolve with conservative management. Major complications such as implant failure or immediate reoperation, were relatively uncommon (6.3% patients, 3.8% of reconstructed breasts). Early follow-up suggests that oncological outcomes are satisfactory, but longer follow-up is required to substantiate this. (C) 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

Immediate breast reconstruction after mastectomy for cancer

Background: Immediate breast reconstruction after mastectomy has increased over the past decade following the unequivocal demonstration of its oncological safety and the availability of reliable methods of reconstruction. Broadly, it is undertaken in the treatment of breast cancer, after prophylactic mastectomy in high-risk patients, and in the management of treatment failure after breast-conserving surgery and radiotherapy. Immediate breast reconstruction can be achieved reliably with a variety of autogenous tissue techniques or prosthetic devices. Careful discussion and evaluation remain vital in choosing the correct technique for the individual patient.

Methods: This review is based primarily on an English language Medline search with secondary references obtained from key articles.

Results and conclusion: Immediate breast reconstruction is a safe and acceptable procedure after mastectomy for cancer; there is no evidence that it has untoward oncological consequences. In the appropriate patient it can be achieved effectively with either prosthetic or autogenous tissue reconstruction. Patient selection is important in order to optimize results, minimize complications and improve quality of life, while simultaneously treating the malignancy. Close cooperation and collaboration between the oncological breast and reconstructive achieve these objectives.

Palynological perspectives on vegetation survey: a critical step for model-based reconstruction of Quaternary land cover

1. Quantitative reconstruction of past vegetation distribution and abundance from sedimentary pollen records provides an important baseline for understanding long term ecosystem dynamics and for the calibration of earth system process models such as regional-scale climate models, widely used to predict future environmental change. Most current approaches assume that the amount of pollen produced by each vegetation type, usually expressed as a relative pollen productivity term, is constant in space and time.
2. Estimates of relative pollen productivity can be extracted from extended R-value analysis (Parsons and Prentice, 1981) using comparisons between pollen assemblages deposited into sedimentary contexts, such as moss polsters, and measurements of the present day vegetation cover around the sampled location. Vegetation survey method has been shown to have a profound effect on estimates of model parameters (Bunting and Hjelle, 2010), therefore a standard method is an essential pre-requisite for testing some of the key assumptions of pollen-based reconstruction of past vegetation; such as the assumption that relative pollen productivity is effectively constant in space and time within a region or biome.
3. This paper systematically reviews the assumptions and methodology underlying current models of pollen dispersal and deposition, and thereby identifies the key characteristics of an effective vegetation survey method for estimating relative pollen productivity in a range of landscape contexts.
4. It then presents the methodology used in a current research project, developed during a practitioner workshop. The method selected is pragmatic, designed to be replicable by different research groups, usable in a wide range of habitats, and requiring minimum effort to collect adequate data for model calibration rather than representing some ideal or required approach. Using this common methodology will allow project members to collect multiple measurements of relative pollen productivity for major plant taxa from several northern European locations in order to test the assumption of uniformity of these values within the climatic range of the main taxa recorded in pollen records from the region.