bluuebunny/crossref_metadata_2025 huggingface dataset:
Procedural Pain in Palliative Care
Authors: Magnani Caterina , Giannarelli Diana , Casale Giuseppe
Published: October 2016

Objective:

To assess the prevalence of breakthrough pain (BTP) provoked by 6 common procedures in patients with advanced disease.

Methods:

A prospective, cross-sectional, multicenter, national study was performed in 23 palliative care units in Italy. Patients were recruited if they were undergoing one of the following procedures as part of normal care: turning, personal hygiene care, transfer from bed to chair, bladder catheterization, pressure ulcer care, and subcutaneous drug administration. The Numerical Rating Scale was used to measure pain intensity before, during, and after the procedure.

Results:

One thousand seventy-nine eligible patients were enrolled: 49.7% were male and their mean age was 78.0±11.2 years. Of all patients, 20.9% had experienced a BTP episode within the 24 hours before recruitment. The overall prevalence of procedure-induced BTP was 11.8%, and the mean intensity score (Numeric Rating Scale) was 4.72±1.81. Notably, patients experienced a significant increase in pain intensity during all procedures (P<0.0001). A small proportion of patients (12.7%) received analgesics before undergoing any of the procedures, and almost none (1.7%) received analgesics during the procedures to alleviate acute pain.

Discussion:

Our findings highlight that simple daily care procedures can lead to BTP among patients with advanced disease. Because such procedures are performed very often during palliative care, more individualized attention to procedural pain control is necessary. Additional research on procedural pain in patients with advanced disease should be encouraged to provide further evidence-based guidance on the use of the available medication for predictable pain flares.
USE OF FIBEROPTIC-GUIDED CO2 LASER IN THE TREATMENT OF UVEAL EFFUSION
Authors: Bausili Maria M. , Raja Harish , Kotowski Jacek , Nadal Jeroni , Salomao Diva R. , Keenum Deborah , Pulido Jose S.
Published: October 2016

Background/Purpose:

To report a new technique for treating patients with uveal effusion syndrome by the fiberoptic-guided CO2 laser.

Methods:

Interventional case report. A 74-year-old man presented with exudative detachment of the choroid secondary to uveal effusion syndrome. Partial-thickness sclerotomy and full-thickness sclerotomy were performed to treat the disease using a fiberoptic-guided CO2 laser.

Results:

After the surgery, the patient's visual acuity improved and choroidal folds disappeared.

Conclusion:

This technique allows concomitant coagulation and cutting, thereby reducing the risk of bleeding and providing better depth control.
Retrobulbar Injection of Amphotericin B for Orbital Mucormycosis
Authors: Hirabayashi Kristin E. , Kalin-Hajdu Evan , Brodie Frank L. , Kersten Robert C. , Russell Matthew S. , Vagefi M. Reza
Published: October 2016

A 68-year-old immunocompromised man with rhino-orbital-cerebral mucormycosis was treated with retrobulbar injections of amphotericin B deoxycholate in conjunction with intravenous antifungals and endoscopic sinus debridement. Transient episodes of orbital inflammation were noted after retrobulbar injections, but progression of orbital infection was halted and visual acuity restored with eventual hospital discharge. To the authors’ knowledge, clearance of orbital mucormycosis with retrobulbar amphotericin B injections has not been previously reported. This intervention may be a viable therapeutic option in cases of orbital mucormycosis where aggressive orbital debridement is not favored and/or the burden of orbital disease is not substantial. However, physicians should be aware of the risk of transient orbital inflammation secondary to retrobulbar amphotericin B deoxycholate.
Long-Term Outcome of Bodily Distress Syndrome in Primary Care: A Follow-Up Study on Health Care Costs, Work Disability, and Self-Rated Health
Authors: Rask Mette Trollund , Ørnbøl Eva , Rosendal Marianne , Fink Per
Published: October 2016

Objective

The upcoming International Classification of Diseases, 11th Revision for primary care use suggests inclusion of a new diagnostic construct, bodily (di)stress syndrome (BDS), for individuals with medically unexplained symptoms. We aimed to explore the long-term outcome of BDS in health care costs, work disability, and self-rated health.

Methods

Consecutive patients consulting their family physician for a new health problem were screened for physical and mental symptoms by questionnaires (n = 1785). A stratified subsample was examined with a standardized diagnostic interview (n = 701). Patients with single-organ BDS (n = 124) and multiorgan BDS (n = 35), and a reference group with a family physician–verified medical condition (n = 880) were included. All included patients completed a questionnaire at 3, 12, and 24 months of follow-up. Register data on health care costs and work disability were obtained after 2 and 10 years of follow-up, respectively.

Results

Patients with BDS displayed poorer self-rated health and higher illness worry at index consultation and throughout follow-up than the reference group (p ≤ .001). The annual health care costs were higher in the BDS groups (2270 USD and 4066 USD) than in the reference group (1392 USD) (achieved significance level (ASL) ≤ 0.001). Both BDS groups had higher risk of sick leave during the first 2 years of follow-up (RRsingle-organ BDS = 3.0; 95% confidence interval [CI] = 1.8–5.0; RRmultiorgan BDS = 3.4; 95% CI = 1.5–7.5) and substantially higher risk of newly awarded disability pension than the reference group (HRsingle-organ BDS = 4.9; 95% CI = 2.8–8.4; HRmultiorgan BDS = 8.7; 95% CI = 3.7–20.7).

Conclusions

Patients with BDS have poor long-term outcome of health care costs, work disability, and subjective suffering. These findings stress the need for adequate recognition and management of BDS.
Measures to Improve Diagnostic Safety in Clinical Practice
Authors: Singh Hardeep , Graber Mark L. , Hofer Timothy P.
Published: October 2016

Timely and accurate diagnosis is foundational to good clinical practice and an essential first step to achieving optimal patient outcomes. However, a recent Institute of Medicine report concluded that most of us will experience at least one diagnostic error in our lifetime. The report argues for efforts to improve the reliability of the diagnostic process through better measurement of diagnostic performance. The diagnostic process is a dynamic team-based activity that involves uncertainty, plays out over time, and requires effective communication and collaboration among multiple clinicians, diagnostic services, and the patient. Thus, it poses special challenges for measurement. In this paper, we discuss how the need to develop measures to improve diagnostic performance could move forward at a time when the scientific foundation needed to inform measurement is still evolving. We highlight challenges and opportunities for developing potential measures of “diagnostic safety” related to clinical diagnostic errors and associated preventable diagnostic harm. In doing so, we propose a starter set of measurement concepts for initial consideration that seem reasonably related to diagnostic safety and call for these to be studied and further refined. This would enable safe diagnosis to become an organizational priority and facilitate quality improvement. Health-care systems should consider measurement and evaluation of diagnostic performance as essential to timely and accurate diagnosis and to the reduction of preventable diagnostic harm.
Virtual Global Transplant Laboratory Standard Operating Protocol for Donor Alloantigen-specific Interferon-gamma ELISPOT Assay
Authors: Carroll Robert , Troelnikov Alexander , Chong Anita S.
Published: October 2016

The quantification of frequency of IFN-γ–producing T cells responding to donor alloantigen using the IFN-γ enzyme linked immunosorbent spot (ELISPOT) holds potential for pretransplant and posttransplant immunological risk stratification. The effectiveness of this assay, and the ability to compare results generated by different studies, is dependent on the utilization of a standardized operating procedure (SOP). Key factors in assay standardization include the identification of primary and secondary antibody pairs, and the reading of the ELISPOT plate with a standardized automated algorithm. Here, we describe in detail, an SOP that should provide low coefficient of variation results. For multicenter trials, it is recommended that groups perform the ELISPOT assays locally but use a centralized ELISPOT reading facility, as this has been shown to be beneficial in reducing coefficient of variation between laboratories even when the SOP is strictly adhered to.
Antibody–drug conjugates and other nanomedicines: the frontier of gynaecological cancer treatment
Authors: Howard David , Garcia-Parra Jetzabel , Healey Gareth D. , Amakiri Cynthia , Margarit Lavinia , Francis Lewis W. , Gonzalez Deyarina , Conlan R. Steven
Published: October 2016

Gynaecological cancers: malignancies of the cervix, uterus, ovaries, vagina and vulva, are responsible for over 1.1 million new cancer cases and almost half a million deaths annually. Ovarian cancer in particular is difficult to treat due to often being diagnosed at a late stage, and the incidence of uterine and vulvar malignancies are both on the rise. The field of nanomedicine is beginning to introduce drugs into the clinic for oncological applications exemplified by the liposomal drugs, Doxil and Myocet, the nanoparticle, Abraxane and antibody–drug conjugates (ADCs), Kadcyla and Adcetris. With many more agents currently undergoing clinical trials, the field of nanomedicine promises to have a significant impact on cancer therapy. This review considers the state of the art for nanomedicines currently on the market and those being clinically evaluated for the treatment of gynaecological cancers. In particular, it focuses on ADCs and presents a methodology for their rational design and evaluation.
Recent advances in the preparation and application of multifunctional iron oxide and liposome-based nanosystems for multimodal diagnosis and therapy
Authors: Marciello Marzia , Pellico Juan , Fernandez-Barahona Irene , Herranz Fernando , Ruiz-Cabello Jesus , Filice Marco
Published: October 2016

Nowadays, thanks to the successful discoveries in the biomedical field achieved in the last two decades, a deeper understanding about the complexity of mechanistic aspects of different pathological processes has been obtained. As a consequence, even the standard therapeutic protocols have undergone a vast redesign. In fact, the awareness about the necessity to progress towards a combined multitherapy in order to potentially increase the final healing chances has become a reality. One of the crucial elements of this novel approach is that large amounts of detailed information are highly needed and
in vivo
imaging techniques represent one of the most powerful tools to visualize and monitor the pathological state of the patient. To this scope, due to their unique features, nanostructured materials have emerged as attractive elements for the development of multifunctional tools for diagnosis and therapy. Hence, in this review, the most recent and relevant advances achieved by applying multifunctional nanostructures in multimodal theranosis of different diseases will be discussed. In more detail, the preparation and application of single multifunctional nano-radiotracers based on iron oxides and enabling PET/MRI dual imaging will be firstly detailed. After that, especially considering their highly promising clinical potential, the preparation and application of multifunctional liposomes useful for multimodal imaging and therapy will be reviewed. In both cases, a special focus will be set on the application of such a multifunctional nanocarriers in cancer as well as cardiovascular diseases.
Assessing the hyperthermic properties of magnetic heterostructures: the case of gold–iron oxide composites
Authors: Fantechi Elvira , Castillo Paula M. , Conca Erika , Cugia Francesca , Sangregorio Claudio , Casula Maria Francesca
Published: October 2016

Gold–iron oxide composites were obtained by
in situ
reduction of an Au(III) precursor by an organic reductant (either potassium citrate or tiopronin) in a dispersion of preformed iron oxide ultrasmall magnetic (USM) nanoparticles. X-ray diffraction, transmission electron microscopy, chemical analysis and mid-infrared spectroscopy show the successful deposition of gold domains on the preformed magnetic nanoparticles, and the occurrence of either citrate or tiopronin as surface coating. The potential of the USM@Au nanoheterostructures as heat mediators for therapy through magnetic fluid hyperthermia was determined by calorimetric measurements under sample irradiation by an alternating magnetic field with intensity and frequency within the safe values for biomedical use. The USM@Au composites showed to be active heat mediators for magnetic fluid hyperthermia, leading to a rapid increase in temperature under exposure to an alternating magnetic field even under the very mild experimental conditions adopted, and their potential was assessed by determining their specific absorption rate (SAR) and compared with the pure iron oxide nanoparticles. Calorimetric investigation of the synthesized nanostructures enabled us to point out the effect of different experimental conditions on the SAR value, which is to date the parameter used for the assessment of the hyperthermic efficiency.
Diagnosing clean margins through Raman spectroscopy in human and animal mammary tumour surgery: a short review
Authors: Birtoiu I. A. , Rizea C. , Togoe D. , Munteanu R. M. , Micsa C. , Rusu M. I. , Tautan M. , Braic L. , Scoicaru L. O. , Parau A. , Becherescu-Barbu N. D. , Udrea M. V. , Tonetto A. , Notonier R. , Grigorescu C. E. A.
Published: October 2016

Breast cancer frequency in human and other mammal female populations has worryingly increased lately. The acute necessity for taxonomy of the aetiological factors along with seeking for new diagnostic tools and therapy procedures aimed at reducing mortality have yielded in an intense research effort worldwide. Surgery is a regular method to counteract extensive development of breast cancer and prevent metastases provided that negative surgical margins are achieved. This highly technical challenge requires fast, extremely sensitive and selective discrimination between malignant and benign tissues even down to molecular level. The particular advantages of Raman spectroscopy, such as high chemical specificity, and the ability to measure raw samples and optical responses in the visible or near-infrared spectral range, have recently recommended it as a means with elevated potential in precise diagnostic in oncology surgery. This review spans mainly the latter 10 years of exceptional efforts of scientists implementing Raman spectroscopy as a nearly real-time diagnostic tool for clean margins assessment in mastectomy and lumpectomy. Although greatly contributing to medical discoveries for the wealth of humanity, animals as patients have benefitted less from advances in surgery diagnostic using Raman spectroscopy. This work also dedicates a few lines to applications of surface enhanced Raman spectroscopy in veterinary oncological surgery.
Bit-twiddling on Nucleotides
Authors: Klötzl Fabian
Published: October 2016

Bits, nucleotides and speed.
Robust background modelling in DIALS
Authors: Parkhurst James M. , Winter Graeme , Waterman David G. , Fuentes-Montero Luis , Gildea Richard J. , Murshudov Garib N. , Evans Gwyndaf
Published: October 2016

A method for estimating the background under each reflection during integration that is robust in the presence of pixel outliers is presented. The method uses a generalized linear model approach that is more appropriate for use with Poisson distributed data than traditional approaches to pixel outlier handling in integration programs. The algorithm is most applicable to data with a very low background level where assumptions of a normal distribution are no longer valid as an approximation to the Poisson distribution. It is shown that traditional methods can result in the systematic underestimation of background values. This then results in the reflection intensities being overestimated and gives rise to a change in the overall distribution of reflection intensities in a dataset such that too few weak reflections appear to be recorded. Statistical tests performed during data reduction may mistakenly attribute this to merohedral twinning in the crystal. Application of the robust generalized linear model algorithm is shown to correct for this bias.
Ethno-nationalism and impediments to cooperation in tourism in a post-settlement Cyprus?
Authors: Webster Craig , Jacobson David , Shapiro Kelsey
Published: October 2016

Purpose

The purpose of this paper is to clarify the position of Greek Cypriot and Turkish Cypriot professionals in the hotel and tourism industry on the island of Cyprus with regards to their expectations regarding the benefit of a political solution to the Cyprus problem on the island.

Design/methodology/approach

The paper uses data from two surveys in both political entities of the island. One survey is a survey of hotel owners, managers of hotels and travel agencies in both political entities on the island. The other is semi-structured interview with leading professionals in the hospitality and tourism industry in both political entities.

Findings

The surveys indicate that there is an expectation from professionals in both entities that tourism will benefit all following a solution, with large increases in incoming tourism to Cyprus.

Practical implications

The findings indicate that there are substantial expectations that there will be benefits for all following a solution to the Cyprus problem.

Originality/value

This is a first future-oriented paper regarding the expectations of major players in the hotel and tourism industry in both political entities on the island.
Multi‐Sector Nonparametric Production‐Frontier Analysis of the Economic Growth and the Convergence of the European Countries
Authors: Walheer Barnabé
Published: October 2016

In this paper, I apply the recent nonparametric multi‐sector production‐frontier methodology of Walheer (), tailored to analyse the economic growth and convergence of countries taking the sector heterogeneity and interdependence into account, to the European countries from 1995 to 2014. Thanks to a simple rewriting of his initial model, I also provide results at the sector level, which was not possible with the initial version of the methodology. My results confirm the non‐neutrality of technological change and highlight that human capital accumulation plays the biggest role in the increase of labour productivity. Technological change and capital accumulation also play an important, if smaller, role in the increase of output‐labour productivity. My results also confirm the presence of heterogeneity between sectors in Europe, which supports the use of multi‐sector analysis. Finally, my results confirm the presence of two groups, in terms of labour productivity, within the European counties: Eastern and Central European countries and the EU12. These two groups diverge over time. The results are not affected by robustness checks.
Cultural unconscious in research: integrating multicultural and depth paradigms in qualitative research
Authors: Yakushko Oksana , Miles Pekti , Rajan Indhushree , Bujko Biljana , Thomas Douglas
Published: October 2016

Culturally focused research has gained momentum in many disciplines, including psychology. However, much of this research fails to pay attention to the unconscious dynamics that underlie the study of culture and culturally influenced human beings. Such dynamics may be especially significant when issues of marginalization and oppression are present. Therefore, this paper seeks to contribute a framework for understanding cultural dynamics, especially unconscious cultural dynamics, within depth psychological qualitative research influenced by Jungian and post‐Jungian scholarship. Inquiry that is approached with a commitment to making the unconscious conscious seeks to empower and liberate not only the subject/object studied but also the researchers themselves. Following a brief review of multiculturalism in the context of analytically informed psychology, this paper offers several case examples that focus on researchers' integration of awareness of the cultural unconscious in their study of cultural beings and topics.
Falling into language life: a montage of pre‐faces in search of a text‐ual body
Authors: Schenk Ronald
Published: October 2016

Clinical work, as all of consciousness, is steeped in and emerges out of language. Language is the medium of our knowing, and knowing the medium of our relating. Language has us; words dream us. For the mythical Navajo as for John of the New Testament, in the Beginning was the Word. Before any kind of distinction of thought, feeling, sensation or intuition comes language – language, not as ‘just words’, but as image. Words are images, and images as encompassing worlds present themselves as and through language. As a determinant of identity, language undermines all cues as to individual subjectivity, Yahweh's ‘I am here’ rendering time and place relative, and subjectivity co‐constituted. This paper is a meditation on language for clinicians in the form that language presents itself, as a meandering flow of consciousness with associations and signposts leading onward.
Premenopausal abnormal uterine bleeding and risk of endometrial cancer
Authors: Pennant ME , Mehta R , Moody P , Hackett G , Prentice A , Sharp SJ , Lakshman R
Published: October 2016

Background

Endometrial biopsies are undertaken in premenopausal women with abnormal uterine bleeding but the risk of endometrial cancer or atypical hyperplasia is unclear.

Objectives

To conduct a systematic literature review to establish the risk of endometrial cancer and atypical hyperplasia in premenopausal women with abnormal uterine bleeding.

Search strategy

Search of PubMed, Embase and the Cochrane Library from database inception to August 2015.

Selection criteria

Studies reporting rates of endometrial cancer and/or atypical hyperplasia in women with premenopausal abnormal uterine bleeding.

Data collection and analysis

Data were independently extracted by two reviewers and cross‐checked. For each outcome, the risk and a 95% CI were estimated using logistic regression with robust standard errors to account for clustering by study.

Main results

Sixty‐five articles contributed to the analysis. Risk of endometrial cancer was 0.33% (95% CI 0.23–0.48%, n = 29 059; 97 cases) and risk of endometrial cancer or atypical hyperplasia was 1.31% (95% CI 0.96–1.80, n = 15 772; 207 cases). Risk of endometrial cancer was lower in women with heavy menstrual bleeding (HMB) (0.11%, 95% CI 0.04–0.32%, n = 8352; 9 cases) compared with inter‐menstrual bleeding (IMB) (0.52%, 95% CI 0.23–1.16%, n = 3109; 14 cases). Of five studies reporting the rate of atypical hyperplasia in women with HMB, none identified any cases.

Conclusions

The risk of endometrial cancer or atypical hyperplasia in premenopausal women with abnormal uterine bleeding is low. Premenopausal women with abnormal uterine bleeding should first undergo conventional medical management. Where this fails, the presence of IMB and older age may be indicators for further investigation. Further research into the risks associated with age and the cumulative risk of co‐morbidities is needed.

Tweetable abstract

Contrary to practice, premenopausal women with heavy periods or inter‐menstrual bleeding rarely require biopsy.
Access to Care for Medicare‐Medicaid Dually Eligible Beneficiaries: The Role of State Medicaid Payment Policies
Authors: Zheng Nan Tracy , Haber Susan , Hoover Sonja , Feng Zhanlian
Published: October 2016

Study Objectives

Medicaid programs are not required to pay the full Medicare coinsurance and deductibles for Medicare‐Medicaid dually eligible beneficiaries. We examined the association between the percentage of Medicare cost sharing paid by Medicaid and the likelihood that a dually eligible beneficiary used evaluation and management (E&M) services and safety net provider services.

Data Sources

Medicare and Medicaid Analytic eXtract enrollment and claims data for 2009.

Study Design

Multivariate analyses used fee‐for‐service dually eligible and Medicare‐only beneficiaries in 20 states. A comparison group of Medicare‐only beneficiaries controlled for state factors that might influence utilization.

Principal Findings

Paying 100 percent of the Medicare cost sharing compared to 20 percent increased the likelihood (relative to Medicare‐only) that a dually eligible beneficiary had any E&M visit by 6.4 percent. This difference in the percentage of cost sharing paid decreased the likelihood of using safety net providers, by 37.7 percent for federally qualified health centers and rural health centers, and by 19.8 percent for hospital outpatient departments.

Conclusions

Reimbursing the full Medicare cost‐sharing amount would improve access for dually eligible beneficiaries, although the magnitude of the effect will vary by state and type of service.
Endoscopic radiofrequency ablation may be preferable in the management of malignant biliary obstruction: A systematic review and meta‐analysis
Authors: Zheng Xiao , Bo Zhi Yuan , Wan Wei , Wu Ye Chen , Wang Tian Tian , Wu Jun , Gao Dao Jian , Hu Bing
Published: October 2016

Objective

Endoscopic biliary radiofrequency ablation (RFA) has been increasingly used to treat unresectable malignant biliary obstruction (MBO). We aimed to perform this systematic review and meta‐analysis to evaluate the efficacy and safety for the treatment of malignant biliary obstruction (MBO) and its impact on patient's survival.

Methods

A comprehensive search of the Cochrane Library, PubMed and EMBASE databases was conducted. A meta‐analysis was performed by extracting the data from the included studies with regard to technical effectiveness, overall survival, adverse events and mortality of endoscopic RFA.

Results

A total of nine studies comprising 263 patients with MBO were included in the analysis. There was a significant increase in the diameter of stricture (3.446 mm, 95% confidence interval [CI] 3.356–3.536 mm) after the endoscopic biliary RFA. The overall survival time was 9.62 months, with pooled 30‐day, 90‐day and 2‐year mortality rates of 2% (95% CI 0.5–5.9%), 21% (95% CI 5–37%), and 48% (95% CI 37–59%), respectively. The pooled rate of adverse events was 17% (95% CI 10–25%), and most complications were mild and managed conservatively. Severe adverse events occurred in three patients (two deaths due to hemobilia and one with partial liver infarction).

Conclusions

Endoscopic biliary RFA is effective and generally safe in the management of unresectable biliary malignancies, and may improve patients’ overall survival. Prospective, randomized controlled studies are required to further support the results.
The sequence capture by hybridization: a new approach for revealing the potential of mono‐aromatic hydrocarbons bioattenuation in a deep oligotrophic aquifer
Authors: Ranchou‐Peyruse Magali , Gasc Cyrielle , Guignard Marion , Aüllo Thomas , Dequidt David , Peyret Pierre , Ranchou‐Peyruse Anthony
Published: October 2016

The formation water of a deep aquifer (853 m of depth) used for geological storage of natural gas was sampled to assess the mono‐aromatic hydrocarbons attenuation potential of the indigenous microbiota. The study of bacterial diversity suggests that Firmicutes and, in particular, sulphate‐reducing bacteria (Peptococcaceae) predominate in this microbial community. The capacity of the microbial community to biodegrade toluene and m‐ and p‐xylenes was demonstrated using a culture‐based approach after several hundred days of incubation. In order to reveal the potential for biodegradation of these compounds within a shorter time frame, an innovative approach named the solution hybrid selection method, which combines sequence capture by hybridization and next‐generation sequencing, was applied to the same original water sample. The bssA and bssA‐like genes were investigated as they are considered good biomarkers for the potential of toluene and xylene biodegradation. Unlike a PCR approach which failed to detect these genes directly from formation water, this innovative strategy demonstrated the presence of the bssA and bssA‐like genes in this oligotrophic ecosystem, probably harboured by Peptococcaceae. The sequence capture by hybridization shows significant potential to reveal the presence of genes of functional interest which have low‐level representation in the biosphere.
A framework for developing and validating taxon‐specific primers for specimen identification from environmental DNA
Authors: MacDonald Anna J. , Sarre Stephen D.
Published: October 2016

Taxon‐specific DNA tests are applied to many ecological and management questions, increasingly using environmental DNA (eDNA). eDNA facilitates noninvasive ecological studies but introduces additional risks of bias and error. For effective application, PCR primers must be developed for each taxon and validated in each system. We outline a nine step framework for the development and validation of taxon‐specific primers for eDNA analysis in ecological studies, involving reference database construction, phylogenetic evaluation of the target gene, primer design, primer evaluation in silico, and laboratory evaluation of primer specificity, sensitivity and utility. Our framework makes possible a rigorous evaluation of likely sources of error. The first five steps can be conducted relatively rapidly and (where reference DNA sequences are available) require minimal laboratory resources, enabling assessment of primer suitability before investing in further work. Steps six to eight require more costly laboratory analyses but are essential to evaluate risks of false‐positive and false‐negative results, while step 9 relates to field implementation. As an example, we have developed and evaluated primers to specifically amplify part of the mitochondrial ND2 gene from Australian bandicoots. If adopted during the early stages of primer development, our framework will facilitate large‐scale implementation of well‐designed DNA tests to detect specific wildlife from eDNA samples. This will provide researchers and managers with an understanding of the strengths and limitations of their data and the conclusions that can be drawn from them.
Detection limits of quantitative and digital PCR assays and their influence in presence–absence surveys of environmental DNA
Authors: Hunter Margaret E. , Dorazio Robert M. , Butterfield John S. S. , Meigs‐Friend Gaia , Nico Leo G. , Ferrante Jason A.
Published: October 2016

A set of universal guidelines is needed to determine the limit of detection (LOD) in PCR‐based analyses of low‐concentration DNA. In particular, environmental DNA (eDNA) studies require sensitive and reliable methods to detect rare and cryptic species through shed genetic material in environmental samples. Current strategies for assessing detection limits of eDNA are either too stringent or subjective, possibly resulting in biased estimates of species’ presence. Here, a conservative LOD analysis grounded in analytical chemistry is proposed to correct for overestimated DNA concentrations predominantly caused by the concentration plateau, a nonlinear relationship between expected and measured DNA concentrations. We have used statistical criteria to establish formal mathematical models for both quantitative and droplet digital PCR. To assess the method, a new Grass Carp (Ctenopharyngodon idella) TaqMan assay was developed and tested on both PCR platforms using eDNA in water samples. The LOD adjustment reduced Grass Carp occupancy and detection estimates while increasing uncertainty—indicating that caution needs to be applied to eDNA data without LOD correction. Compared to quantitative PCR, digital PCR had higher occurrence estimates due to increased sensitivity and dilution of inhibitors at low concentrations. Without accurate LOD correction, species occurrence and detection probabilities based on eDNA estimates are prone to a source of bias that cannot be reduced by an increase in sample size or PCR replicates. Other applications also could benefit from a standardized LOD such as GMO food analysis and forensic and clinical diagnostics.
The titles of Petra in the sixth century: the evidence from the Petra papyri
Authors: Al‐Nasarat Mohammed I. , Twissi Sa'ad A.
Published: October 2016

Since their discovery in 1993, the Petra papyri have drawn the attention of both historians and archaeologists because of the amount of information they contain. The content of the papyri essentially deals with the property inheritance and transaction of a certain Theodoros son of Obodianos and his family in Petra and its vicinity, in the period between AD 537 and 593. The present paper focuses on the titles of Petra mentioned in these papyri and on their importance for the understanding of Petra in the Roman and Byzantine periods. Petra's full titles are: ‘Imperial Colony Antoniana, Distinguished, Holy (?), Mother of the Colonies, Hadriana Petra, and Metropolis of [the Province] Tertia Palaestina Salutaris’. The main components of these titles are attested elsewhere, but they appear in their entirety in the Petra papyri for the first time.

The various titles of Petra as they appear in the papyri concerned clearly indicate that Petra continued to style itself as an important place in the Byzantine Empire. The picture that emerges from Petra's titles and other evidence from the papyri is that, in the sixth century Petra was still a place inhabited by relatively wealthy people, which had a major role in the economy of the Byzantine Empire.
Transoral robotic surgery: implementation as a tool in head and neck surgery – a single‐centre Australian experience
Authors: Hirshoren Nir , Ruskin Olivia , Fua Tsien , Kleid Stephen , Magarey Matthew , Dixon Benjamin
Published: October 2016

Background

Transoral robotic surgery (TORS) is now a well‐validated technique for resection of head and neck cancers. Benefits include reduced patient morbidity, swallowing preservation and rationalization of adjuvant therapies.

Methods

This was a single‐centre, retrospective review of 35 patients who underwent TORS of oro‐, retro‐ and parapharyngeal tumours between March 2014 and August 2015. Outcome measures included resection margins, swallowing function and impact on post‐operative radiotherapy.

Results

Median age was 63.7 years and the number of male patients was 22 (62.9%). Tongue base was the most common site (51.4%), followed by tonsil (25.7%). Nine patients (25.7%) had previous radiotherapy. A total of 24 patients had squamous cell carcinoma and the clear margin rate for primary TORS was 93.3%. Median hospital stay was 5.5 days, longer for previously irradiated patients (9 days). Median nasogastric tube dependence was 3.5 days. Four patients (11.4%) received a gastrostomy and two patients remained dependent on the tube at the time of last review. There were two major complications (5.7%): bleeding requiring return to theatre (1) and pulmonary embolism (1). Post‐operative radiotherapy was either avoided or reduced in 22 patients (81.5%).

Conclusion

TORS is a safe and effective tool, providing surgical access to oropharyngeal and other difficult to access areas. Patient selection and a multidisciplinary approach are essential to ensure adequate margins can be achieved and therefore to reduce adjuvant therapies.
Micrometastasis in colorectal cancer: does it affect staging?
Authors: Mohajeri Gholamreza , Hejab Kavak , Sheikhbahaei Saba , Mohajeri Mohammadreza , Niknam Negar , Mohammadi Alireza
Published: October 2016

Background

Micrometastasis (MM) in colorectal cancer (CRC) is not considered in tumour‐node‐metastasis (TNM) staging currently and also the prognostic significance of these occult tumoural cells is not proven yet. This study was designed to find whether MM to bone marrow (BM) and/or liver cause upstaging of the tumour according to conventional staging system and if it may alter the survival rate.

Methods

Thirty‐eight CRC patients who were candidates of surgical procedure were enrolled in our cross‐sectional study. Liver and BM biopsy were obtained during the surgery to be looked for tissue‐specific marker of CRC, CK20. CK20 expression in BM and liver was assessed by the two methods of reverse transcriptase polymerase chain reaction and immunohistochemistry.

Results

Among the 38 submitted patients, a total number of 14 MM, including 10 BM (23%) and seven hepatic (18%) were detected. There was no significant difference in clinicopathological aspects including size, location, stage, grade, local invasion to vessels and neurons, TNM staging and relapse rate of tumour among patients with/without disseminated tumoural cells. The result did not demonstrate a survival difference between patients receiving neoadjuvant chemotherapy compared to other patients.

Conclusion

Our study did not confirm that the presence of MM influences TNM staging and overall survival of the patients. Additional clinical investigations with longer follow‐up period and larger number of cases are required to decide on administration of neoadjuvant therapy in CRC patients.
Popular Resistance in Cambodia: The Rationale Behind Government Response
Authors: Sokphea Young
Published: October 2016

Agrarian resistance often occurs as a result of expropriation and dispossession of poor farmers’ land and other properties. This paper examines how cost‐benefit rational choice determined the government of Cambodia's response to poor farmers’ resistance to large‐scale land acquisition for an agro‐industrial investment. Theoretically, whatever mechanism a government chooses to respond to resistance, the aim is to retain more benefits, especially political legitimacy. In this study, the government, in collaboration with private companies, opted for a combination of strong repression and partial concession in response to the resistance by the communities. The study argues that this response is basically determined by cost‐benefit calculations. However, the purpose is not to retain political legitimacy as theoretically argued, but to protect the economic interests of the client‐patron networks that had developed between foreign companies and the powerful local politico‐commercial personages associated with the regime.
Misplaced Paternalism and other Mistakes in the Debate over Kidney Sales
Authors: Semrau Luke
Published: October 2016

Erik Malmqvist defends the prohibition on kidney sales as a justifiable measure to protect individuals from harms they have not autonomously chosen. This appeal to ‘group soft paternalism’ requires that three conditions be met. It must be shown that some vendors will be harmed, that some will be subject to undue pressure to vend, and that we cannot feasibly distinguish between the autonomous and the non‐autonomous. I argue that Malmqvist fails to demonstrate that any of these conditions are likely to obtain. His argument involves two common errors. First, he, like many, proceeds on a mistaken understanding of how to assess harm. What matters is not the balance of costs and benefits of vending, but a comparison of potential vendors’ welfare across two possible courses of action. Second, Malmqvist's concerns about third‐party pressure are predicated on an empirically unrealistic understanding of the operation of a regulated market. A widely underappreciated fact is that kidney sales will be relatively rare, and most who try to vend will be unable to. Because pressure on another to vend will not result in the desired outcome, few will exert it.
Assisted Suicide in Switzerland: Clarifying Liberties and Claims
Authors: Hurst Samia A. , Mauron Alex
Published: October 2016

Assisting suicide is legal in Switzerland if it is offered without selfish motive to a person with decision‐making capacity. Although the ‘Swiss model’ for suicide assistance has been extensively described in the literature, the formally and informally protected liberties and claims of assistors and recipients of suicide assistance in Switzerland are incompletely captured in the literature. In this article, we describe the package of rights involved in the ‘Swiss model’ using the framework of Hohfeldian rights as modified by Wenar. After outlining this framework, we dissect the rights involved in suicide assistance in Switzerland, and compare it with the situation in England and Germany. Based on this approach, we conclude that in Switzerland, claim rights exist for those requesting suicide assistance, and for those who are considering providing such assistance, even though no entitlements exist toward suicide assistance. We then describe the implementation of the ‘Swiss model’ and difficulties arising within it. Clarifying these issues is important to understand the Swiss situation, to evaluate what features of it may or may not be worth correcting or emulating, and to understand how it can impact requests for suicide assistance in other countries due to ‘suicide tourism’. It is also important to understand exactly what sets Switzerland apart from other countries with different legislations regarding suicide assistance.
Survival differences between patients with Hodgkin lymphoma treated inside and outside clinical trials. A study based on the EORTC‐Netherlands Cancer Registry linked data with 20 years of follow‐up
Authors: Liu Lifang , Giusti Francesco , Schaapveld Michael , Aleman Berthe , Lugtenburg Pieternella , Meijnders Paul , Hutchings Martin , Lemmens Valery , Bogaerts Jan , Visser Otto
Published: October 2016

The survival of patients diagnosed with Hodgkin lymphoma (HL) has improved from 70% to 90% in clinical trials. However, population‐based data has shown lower survival. In this study, clinical trial data were linked with cancer registry to identify trial and non‐trial participants and differences in overall survival and associated factors were assessed. In 1986–2004, 27% of HL patients aged 15–70 years participated in clinical trials. Compared to non‐trial participants, trial participants were younger (median age, 31 vs. 34 years), had staging registered more accurately and had an 8% higher 20‐year survival rate (73% vs. 65%). After adjusting for baseline differences, no differences in survival (hazard ratio = 0·96, 95% confidence interval 0·82–1·12), or in subgroup analysis according to stage, remained. Over time, increased administration of chemotherapy in combination with radiotherapy, together with the decreased use of radiotherapy alone was observed among the trial population. This trend was later followed in non‐trial participants, coinciding with a similar ‘take‐up’ in survival. The observed superior survival among patients with HL treated in clinical trials can be largely explained by the differences in baseline characteristics, particularly younger age. High trial participation rate and centralized expertise facilitates the implementation of trial findings to real‐world practice.
Whole body magnetic resonance imaging in newly diagnosed multiple myeloma: early changes in lesional signal fat fraction predict disease response
Authors: Latifoltojar Arash , Hall‐Craggs Margaret , Rabin Neil , Popat Rakesh , Bainbridge Alan , Dikaios Nikolaos , Sokolska Magdalena , Rismani Ali , D'Sa Shirley , Punwani Shonit , Yong Kwee
Published: October 2016

Cross‐sectional imaging techniques are being increasingly used for disease evaluation in patients with multiple myeloma. Whole body magnetic resonance imaging (WB‐MRI) scanning is superior to plain radiography in baseline assessment of patients but changes following treatment have not been systematically explored. We carried out paired WB‐MRI scans in 21 newly diagnosed patients prior to, and 8‐weeks after, starting chemotherapy, and analysed stringently selected focal lesions (FLs) for parametric changes. A total of 323 FLs were evaluated, median 20 per patient. At 8 weeks, there was a reduction in estimated tumour volume (eTV), and an increase in signal fat fraction (sFF) and apparent diffusion coefficient (ADC) in the group as a whole (P < 0·001). Patients who achieved complete/very good partial response (CR/VGPR) to induction had a significantly greater increase in sFF compared to those achieving ≤ partial response (PR; P = 0·001). When analysed on a per‐patient basis, all patients achieving CR/VGPR had a significant sFF increase in their FL's, in contrast to patients achieving ≤PR. sFF changes in patients reaching maximal response within 100 days (fast responders) were greater compared to slow responders (P = 0·001). Receiver Operator Characteristic analysis indicated that sFF changes at 8 weeks were the best biomarker (area under the Curve 0·95) for an inferior response (≤PR). We conclude that early lesional sFF changes may provide important information on depth of response, and are worthy of further prospective study.
Strategies for reducing the treatment‐related physical burden of childhood acute myeloid leukaemia – a review
Authors: Hasle Henrik , Kaspers Gertjan J. L.
Published: October 2016

Over the last four decades the survival of paediatric patients with acute myeloid leukaemia has gradually increased to 70% in high‐income countries. The therapy is very intensive and associated with many acute and long‐term side effects. The early death rate has been reduced to 1–4%. The acute toxicity is a limiting factor for improving survival in low‐income countries. Transplant is associated with more endocrinological late effects while cardiotoxicity is more common after relapse. Reducing the physical costs of therapy without jeopardizing survival may be accomplished by optimal supportive care, less cardiotoxic anthracyclines, less consolidation courses and strict indications for stem cell transplantation. Analysing scenarios with different frequency of transplantation in first complete remission show similar overall survival rates, indicating that almost all patients can be spared the procedure in first remission. Reducing relapse risk is an effective way of reducing toxicity and more targeted therapy and improved risk group stratifications are needed.
Feminine Identity and Female Friendships in the ‘Neapolitan’ Novels of Elena Ferrante
Authors: Lee Alison
Published: October 2016

In this paper female‐to‐female friendship as depicted in the Neapolitan novels of Elena Ferrante is used to think about aspects of unconscious relating, and of feminine identity. The two girls in the stories ‘blur’ into one another, in a way that is at times a source of creative strength, and at times a quasi‐psychotic state. The idea of ‘merger’ as characterizing female relationships is considered through the narrative. Friendship stands outside conventional psychoanalytic models of family relating, but Ferrante explores their internal workings, particularly in the developing child and adolescent, and unfolds the importance of their place in growing up, asserting a unique psychic place for the female‐to‐female bond in identity formation. Psychoanalytic ideas of separation and individuation are brought to bear, alongside Juliet Mitchell's work on sibling relationships, and Rozsika Parker's work on the internal ‘other’ necessary for creativity.
Minimizing Intense Relational Dynamics to Enhance Safety: A Thematic Analysis of Literature on Sandtray Work with Adult Trauma Survivors
Authors: Claudia Kosanke Garjana , Puls Brigitte , Feather Jackie , Smith Jyoti
Published: October 2016

In work with adult trauma survivors the therapeutic relationship can become highly charged with trauma‐related transferential dynamics, placing severe strain on the therapist and potentially resulting in vicarious traumatization. This article reports on the findings of a thematic analysis of the literature on the use of sandtray when working with adult trauma survivors. The research confirms the benefits of using sandplay work as it increases safety for client and therapist, fosters communication of the often ‘unspeakable’ experience of trauma and, as a result of the activity involved in sandtray work, provides experiences of empowerment for the client, thus facilitating healing from traumatic experiences.