bluuebunny/crossref_metadata_2025 huggingface dataset:
Healthcare professionals' views on factors influencing end-of-life care in hospitals
Authors: Reid Colette , Bloor Sophia , Gibbins Jane , Burcombe Melanie , McCoubrie Rachel , Forbes Karen
Published: March 2012

Aims

The majority of patients die in hospitals, yet care delivered to the dying in the acute setting is variable and the underlying reasons for this are not documented well. The authors aimed to explore healthcare professionals' views on the factors influencing good quality end-of-life (EOL) care in an acute hospital trust.

Methods

Within a feasibility study examining the impact of a simple EOL care tool on the dying experience, the authors carried out qualitative interviews with healthcare professionals caring for dying patients.

Results

Five focus groups, nine face-to-face and two ‘think aloud’ interviews were analysed using the framework approach. The emerging themes were difficulties in diagnosing dying (staff felt that the decision to switch to comfort care was often made late which meant that patients received unnecessary treatments); hospital culture (reluctance to withdraw active treatments; it was ‘brave’ to state a patient was dying); hospital systems (patients moved frequently between wards which did not facilitate diagnosing dying and medical notes did not provide sufficient information to aid junior doctors out of hours when making decisions about sick patients) and the impact of the EOL tool on care (nurses found the regular symptom scoring required by the tool helped them approach patients and families and give more appropriate care).

Conclusion

This qualitative study has identified factors influencing care given to dying patients in an acute hospital setting. The authors suggest these factors need to be taken into account when trying to improve care for dying patients and in facilitating the use of EOL care pathways.
Narrative interventions with patients in healthcare: a literature review
Authors: Vedder Rachel , Winslow Michelle , Noble Bill
Published: March 2012

Background

Serious illness disrupts the narrative coherence central to maintaining our sense of self. In healthcare interactions, including palliative medicine consultations, paying close attention to patient narrative provides insight into the multi-dimensional impact illness has on the whole person, and can be therapeutic; helping a person make sense of their illness and engage in narrative repair. Co-construction of narrative in consultation reflects a shared understanding of a patient's problems and a plan for future action that is collaborative. This literature review is the first step in a study to develop and evaluate a narrative-based approach for palliative medicine consultations following the Medical Research Council guidance on development and evaluation of complex interventions.

Aim

To describe the scope and effectiveness of narrative interventions with patients in healthcare.

Methods

Literature was sought from three electronic databases, hand-searching of journals, citation lists and on recommendations. Sources include all types of papers from peer-reviewed journals and textbooks published in English that describe narrative practice in healthcare and evaluate narrative interventions with adult patients in healthcare settings.

Results

Of 1884 references initially identified 222 sources were included in the review. These were sorted into three categories: 1. Narrative theory applied in healthcare; 2. Biographical interventions; 3. Narrative therapy.

Conclusions

The application of narrative theory in healthcare has grown since the 1980s, has broad scope, and includes many different interventions with patients few of which have been evaluated. Biographical interventions in gerontology however predate this more general interest, and with regards to life review therapy have demonstrated benefit in emotional well-being and life satisfaction for older people. Life review interventions such as Dignity Therapy have been successfully adapted for use in palliative care.
A study of pain, peripheral neuropathy and psychosocial late effects in multiple myeloma patients
Authors: Cachia Elaine , Eiser Christine , Ezaydi Youssef , Greenfield Diana , Ahmedzai Sam , Snowden John
Published: March 2012

Background

While intensive and novel treatments have significantly extended life expectancy in multiple myeloma, the cumulative impact of disease and treatment related factors on quality of life in relapsed patients is poorly characterised.

Aims

To define the spectrum of quality of life, fatigue, pain, peripheral neuropathy and work disability affecting patients living with advanced relapsed myeloma.

Methods

The authors prospectively recruited patients with myeloma who had undergone intensive management of myeloma and had received at least one subsequent treatment for progressive disease. Patients were assessed for generic (SF-12) and cancer specific (EORTC) health related quality of life parameters, pain (BPI-SF), peripheral neuropathy (s-LANSS), and concerns (adapted from the Profile of Concern's Questionnaire).

Results

32 patients (median age 61 years) participated: median duration from diagnosis was 5.5 years (range 2–12) and the median number of lines of previous treatment was 3 (range 2-6). The majority (69%) of patients were on regular analgesia. Despite stable disease, ongoing fatigue and pain were predominant symptoms. Pain had a predominantly neuropathic element in half of the cohort. Other features of neuropathy, paraesthesiae and sensory loss, were also common. Physical functioning scores were highly correlated with pain (r=−0.671; p=0.001) and QoL (r=0.576; p=0.001) and fatigue (r=−0.558; p=0.001). Social functioning was also compromised and patients reported dwelling on their current and future illness, worried of recurrence and shortened lifespan. Work disability was reflected by a fall in active or recent employment from 72 to 44% from diagnosis to the date of assessment.

Conclusion

The late effects of myeloma and its treatments result in compromised quality of life with fatigue, pain, peripheral neuropathy and functional disability despite disease control with modern therapy. Models for comprehensive care of myeloma should actively address physical and social quality of life in this expanding population of patients.
‘Me I feel proud in my uniform’: the personal value of being a palliative care community volunteer
Authors: Jack Barbara , Kirton Jennifer , Merriman Anne , Birakurataki Jerith
Published: March 2012

Background

Approx 27 000 new cases of cancer are reported in Uganda in each year affecting 1.5% of the population. A shortage of Doctors, wide geographical distribution, and poor transport systems lead to many patients experiencing severe uncontrolled symptoms. Hospice Africa Uganda developed a community volunteer worker programme where local villagers are trained to identify patients with palliative care needs. The volunteers refer patients to the hospice and provide basic care and support for patients and families. A training course with ongoing support has resulted in 85 volunteers practicing out of the hospice in Kampala (40) and Hoima (45).The volunteers receive no payment, except for a bicycle enabling them to reach remote areas.

Aim

To explore personal impact of being a palliative care community volunteer.

Methodology

A qualitative methodology using semi structured individual and group tape recorded interviews was adopted for the study. Data was collected from the volunteers based in two sites (Hoima and Kampala). A purposive sample of 32 volunteers participated in the study. Data was analysed for emerging themes using thematic analysis.

Results

The volunteers all reported how they found the role to be of great value to themselves, including having an increased knowledge and satisfaction at helping the dying in their villages. Interestingly they all commented on the pride of being a volunteer, how they felt when they put on their uniform and the resulting respect they received.

Discussion

This paper will discuss these findings as well as the challenges that the volunteers are finding regarding language barriers and old bicycles.
From abstract to publication: the fate of research presented at the EAPC Congress Meeting
Authors: Hanchanale Sarika , Jordan Alice
Published: March 2012

Objective

The fate of oral presentations presented at a palliative meeting has not been assessed to date. Our aim was to determine the number of peer-reviewed publications arising from the abstracts presented at the European Association for Palliative Care (EAPC) Congress Meeting, Aachen (2005).

Methods

All abstracts (Oral and poster) presented at the EAPC Congress, Aachen (2005) were included in the study. Invited abstracts were excluded from the study. Pubmed search was performed to identify a matching journal article. Topics, country of origin, abstract type, type of journal and publication time (month–year) were tabulated and analysed.

Results

At EAPC Congress Meeting, 661 abstracts were presented. After exclusion of 123 invited articles a total of 140 oral and 398 poster abstracts were presented EAPC Congress at Aachen in 2005. 230 (43%) abstracts were published as full paper in peer-reviewed journals (77 oral abstracts (55%) and 153 poster abstracts (38%)). Nearly fifth of articles were published in 6 months and quarter within 12 months. Thirty-nine per cent of articles were published within 36 months. Majority of articles were published in palliative journals (29%) followed by pain (18%), oncology (13%), medicine (8%) and psychiatry (4%) journals. Top five countries with maximum abstracts were UK (30%), Netherlands (9%), Germany (7%), Italy (5%) and Norway (5%). The conversion rate from abstract to publication for these countries was UK (43%), Netherlands (47%), Germany (40%), Italy (19%) and Norway (69%).

Conclusion

The conversion rate from EAPC Care Congress Meeting presentation to peer-reviewed publication better than emergency medicine and rehabilitation medicine; and it was similar on other specialities. Oral presentations had better publication rate than poster presentations. The level of conversion from presentation at the EAPC to publication in peer reviewed journal highlights the conference's importance in promoting the palliative medicine research.
The use of the edmonton symptom assessment scale to measure symptoms at the end of life
Authors: Reid Colette , Gibbins Jane , Burcombe Melanie , Bloor Sophia , McCoubrie Rachel , Forbes Karen
Published: March 2012

Aims

There is currently no tool available to capture symptom control in the dying. The Edmonton Symptom Assessment Scale (ESAS) has been validated for patient and care giver-rated scoring of patients' symptoms, enabling recording to continue as patients deteriorate. However, it has not been used specifically to measure symptoms in the last days of life. The aim was to assess the utility of ESAS in scoring symptoms in the dying patient as measured by completion rates in a ‘before and after’ study investigating the impact of an end-of-life (EOL) care tool.

Methods

70 patients were recruited; 40 before and 30 following the introduction of the EOL tool. Nursing staff were asked to complete 12-hourly ESAS scores from the time the ‘diagnosis of dying’ was made until death.

Results

54% of the ESAS forms were completed but some were not fully scored. 77% of patients recruited had an ESAS form completed in the last 24 h of life. The number of patients with a score for each of the individual symptoms within ESAS varied in both groups. Core EOL symptoms (pain, shortness of breath, nausea, chest secretions and agitation) were scored more frequently when the EOL tool was in place. The frequency of completion of these core symptoms ranged from 75–97% for patients receiving care directed by the EOL tool versus 28–58% for patients receiving usual care.

Conclusion

The proportion of missing data suggests 12 hourly symptom scoring was onerous for ward staff. The improved completion rate for core EOL symptoms suggests either that the introduction of the tool improved the nurses' ability or confidence to measure symptoms, or that scoring improved because the task was ‘learnt’ during the study. A shortened ESAS containing only core EOL symptoms might have better utility as an outcome measure for the last days of life.
Does the distress thermometer work? A systematic review of the evidence for its use and validity
Authors: Stewart-Knight Kirsten , Parry Ruth , Abey Anne , Seymour Jane
Published: March 2012

Background

The Distress Thermometer is the most widely used rapid screening tool for assessing psychological distress in people affected by cancer. Use of such tools to assess patients emotional and physical needs is a requirement of the NICE guidelines for supportive and palliative care.

Aims

To explore the assumption that the Distress Thermometer improves clinicians' understanding of the concerns of people affected by cancer. Two questions were posed: 1. In what settings and with what populations has the Distress Thermometer been used? 2. What evidence concerning validity exists for this tool and what is the strength of evidence?

Methods

A systematic review using a framework for mixed evidence (Hawkeret al. 2005) across 11 databases. Inclusion criteria: Question 1: papers documenting use of the Distress Thermometer with people affected by cancer, in English, published in peer reviewed journals after 1st January 1998. Question 2: papers (ie, subset of the main search) reporting assessments of the validity of the Distress Thermometer.

Results

The authors identified 86 papers reporting use of the Distress Thermometer. Populations included: patients with a specific tumour site, older people, children, adult survivors of childhood cancer, caregivers, relatives/partners of cancer patients and people with new diagnoses and advanced disease. Of 86 papers, 33 examined the validity of the Distress Thermometer, with most comparing the tool with other measures, most commonly the Hospital Anxiety and Depression scale.

Conclusions

Although the Distress Thermometer is widely used in cancer supportive and palliative care across a diverse range of settings and in many populations, there is little evidence to support its validity and little is known about what the tool actually measures. Future research must compare the Distress Thermometer with qualitative interviews and the true ‘gold standard’ of asking patients how distressed they feel and what concerns are contributing to that distress.
iWantGreatCare Survey: analysis of free text responses by patients and carers
Authors: Finlay Ilora , Byrne Anthony , Sampson Cathy , Nelson Annmarie
Published: March 2012

Background

Palliative care is based on the principles of holistic care, incorporating pain and symptom management, provision of psychological, social and spiritual support and achievement of the best quality of life for the patient and their family (NICE 2011). The iWGC survey is designed to measure patient satisfaction with palliative care in Wales. In addition to nine questions on a Likert scale it includes a free text box within which a patient or family member is invited to write about any aspect of their care. This acknowledges that measuring satisfaction is predicated on an understanding of care from the perspective of the patient and their family.

Aims

To analyse free text data from a Wales-wide questionnaire survey of patient satisfaction with care.

Methods

Analysis of free text responses (n=595) using qualitative methods allowed for the emergence of key themes from the point of view of service users, rather than based upon prior assumptions or hypotheses.

Results

Analytic themes related to concerns, features, resources and consequences of care. This led to a focus on the emotional experience of care, and the language used by respondents to construct their understanding of palliative care. Patients and family members, usually also carers, recognised and prioritised good palliative care and highlighted the significance of the palliative care service in facilitating as well as providing care.

Conclusions

Analysis highlighted that respondents distinguished between their personal experiences and their concerns about continued funding of palliative care, provision of more palliative care staff, better resources and facilities and a desire for access to palliative care on a continuous basis.
Effects of opioids on cellular immunity: implications for palliative care
Authors: Boland Jason , Foulds Gemma , Ahmedzai Sam , Pockley Graham
Published: March 2012

Background

Opioids are commonly used in the management of pain, diarrhoea, cough and dyspnoea. However, their ability to modulate the ubiquitous endogenous opioid system can lead to many side effects. A potentially covert side effect which has been attracting increasing interest relates to opioid-induced immune suppression. This may be of particular importance in patients with cancer or infection. The immunomodulatory effects of opioids require an increased awareness within palliative care given that patients are potentially living longer with a palliative diagnosis.

Aims

To systematically evaluate the in vitro effects on opioids on human immune system.

Methods

Peripheral blood was obtained from healthy volunteers and the influence of clinically relevant concentrations of morphine, tramadol, fentanyl, buprenorphine, methadone oxycodone codeine and diamorphine on innate and adaptive immunity were evaluated. These tests included investigation of neutrophil and monocyte bacterial defence mechanisms, the capacity of natural killer (NK) cells to kill tumour cells and T cell responsiveness to stimulation.

Results

None of the opioids had a consistent effect on any of the immune parameters tested when analysed on a group basis. However, there was marked variability between individuals, both in their baseline and the effect of opioids. This was particularly evident with respect to the influence of morphine, tramadol, fentanyl and buprenorphine on neutrophil and monocyte bacterial defence mechanisms.

Conclusion

These in vitro findings suggest that although morphine, tramadol, fentanyl and buprenorphine have little direct effect on anticancer or antiviral protection they could influence the susceptibility to bacterial infection. Clinical studies aimed at assessing the in vivo effects of opioid administration on innate and adaptive immune capacity in relevant patient groups are required in order to assess the potential clinical significance of opioids used for palliation.
An evaluation of hospice staffs' knowledge of organ and tissue donation
Authors: Wale Jane , Faull Christina
Published: March 2012

Background

The latest version of the Liverpool Care Pathway directs staff to confirm whether or not the dying patient has previously expressed a wish to donate organs. Staff require basic knowledge of organ and tissue donation to be able to answer any questions that may arise as a result of such a discussion.

Aims

The study aims to explore the knowledge hospice staff have of organ and tissue donation.

Methods

A questionnaire based on the knowledge and attitude questionnaire developed by Vitris1 was mailed to all hospice doctors, nurses and healthcare assistants. Staff were then invited to participate in focus groups so their knowledge could be explored in greater depth.

Results

76/94 questionnaires were completed. 35/76 people who replied had known someone who had needed an organ donation. Most (93%) staff realised that patients with metastatic malignant disease could donate their corneas for transplantation and some also thought that these patients could donate heart valves (13/76) and bones (10/76). Staff were less sure about what patients dying of non-malignant disease could donate. 39/76 people realised that the corneas needed to be retrieved within 24 h of death. 20/76 were unsure whether the procedure would cause disfiguration. Only 24/76 people realised that a patients' family can override the patients' wishes to donate.

Conclusions

This study has identified gaps in hospice workers knowledge of organ and tissue donation. This may be a contributing factor to why the subject is not routinely discussed at LOROS and very few patients donate.
Talking to patients in a hospice
Authors: Gadoud Amy , Adcock Yousef , Jones Lesley , Koon Sim , Johnson Miriam
Published: March 2012

Background

Medical students have opportunities to learn about palliative care from talking to patients in a hospice (1). This resource is not fully used, in part due to concerns about patient and student welfare(2). The authors aimed to explore the perceptions and experiences of students talking to patients in a hospice.

Method

Semistructured ‘indepth’ interviews of 14 medical students, from a medical school in the North East of England, who had spoken with hospice patients as part of their undergraduate education.

Findings

Overall students found the experience very valuable. Themes arising from the data included: student emotional and personal issues; effect of the hospice environment, staff and patients; learning opportunities and impact of the experience. Despite prior anxieties that the hospice would be depressing and that they would struggle emotionally talking to hospice patients, the visit transformed this view. Other concerns included facing death and dying. After their experience the students felt they would be more able to care for people at the end of life when they qualified. They found that the hospice staff and patients were very supportive and contributed to this change. Opinion varied about the best time to attend hospice during their training but the overall view was that this was less important than the availability of adequate support. The main criticism was that there was insufficient time in the programmed hospice visit and there was a preference for the immersion possible during the longer placement of a student selected component. Illustrative quotes will be used throughout.

Conclusion

Students are overwhelmingly positive about communicating with patients in a hospice and see it as unique environment in which they can learn vital skills.
Evaluation of a distance learning tool to teach GPs about metastatic spinal cord compression
Authors: Seaman Siwan , Pease Nikki
Published: March 2012

Background

A delay in diagnosis/treatment of metastatic spinal cord compression (MSCC) adversely influences functional outcomes and a significant proportion of this delay is attributable to its recognition in primary care. Delays in diagnosis and treatment were the drive behind development of the 2008 NICE guideline. In the process of implementing the NICE guidance locally we recognised that increasing awareness and delivering education to GPs was key to implementing changes. A distance learning tool that would also serve as a continuing reference was proposed as a cost-effective means of achieving this goal.

Aims

To measure the effectiveness of introducing a distance learning workbook on MSCC to GPs as a method of providing information on the recognition and management of suspected MSCC.

Methods

A 45-page stand alone interactive workbook was designed covering spinal anatomy, pathophysiology, diagnosis and management of MSCC. The workbook was issued to 39 Welsh GPs attending a short course in palliative medicine in 2011. They were asked to complete pre and post workbook questionnaires to record competence on a scale of 1 to 5.

Results

62% (n=24) completed postworkbook questionnaires were returned. There was a statistically significant (p<0.05) increase in average pre and post scores in all domains assessed (anatomy, assessment, diagnosis, pharmacological and non-pharmacological management, ability to communicate information). The greatest increases were recorded in ‘ability to communicate information to patients, carers and healthcare staff’. Of participants who had managed a patient with suspected MSCC in the past 5 years 92.8% (n=13) reported that they would ‘do things differently’ next time as a result of completing the workbook.

Conclusions

Participants reported increases in competence across all areas questioned. The findings support the roll out of this education tool to GPs across the Principality and opens up the possibility of using a similar tool for teaching other palliative care topics.
Mineralogic evidences of a mid-Paleozoic tectono-thermal event in the Zonguldak terrane, northwest Turkey: implications for the dynamics of some Gondwana-derived terranes during the closure of the Rheic Ocean
Authors: Bozkaya Ömer , Yalçın Hüseyin , Göncüoğlu Mehmet Cemal
Published: March 2012

The Zonguldak terrane is a Gondwana-derived continental microplate along the Black Sea coast in northwest Anatolia. It includes a Cadomian basement, with oceanic- and island-arc sequences, unconformably overlain by siliciclastic rocks of Ordovician to Middle Silurian age. After a period of deformation and erosion, late Lower Devonian (Emsian) quartzites and shallow-marine limestones unconformably cover Middle Silurian (Wenlock) graptolitic shales. Along several cross sections across the unconformity plane, the mineralogical characteristics of the Paleozoic sedimentary rocks in the Zonguldak terrane are studied to check whether this regional unconformity is only of epeirogenic nature or the result of a thermal event. In addition to the appearance of kaolinite in Devonian units, crystal-chemical data of illites show a sudden jump at the unconformity plane. The b cell dimension values of illites of Ordovician–Silurian units are somewhat higher than those of Devonian–Carboniferous units and show a drastic drop between the Silurian and Devonian units. The new mineralogic data indicate that the pre-Emsian rocks in the Zonguldak terrane experienced a thermodynamo event, prior to the Emsian transgression. This Caledonian-time event is also reported in east Moesian terrane but not noticed in the neighboring Istanbul–Zonguldak and in the west Moesian – Balkan – Kreishte terranes. By this, it is suggested that Zonguldak and east Moesian terranes behaved independently from the Istanbul–Balkan terranes during the closure of the Rheic Ocean. They very likely docked to Laurussia during Emsian by strike-slip faults and remained thereon at its platform margin, where the Middle–Late Devonian shallow-platform conditions were followed by fluvial (lagoon and delta) conditions and deposition of coal during Late Carboniferous.
The Cabot Head Archipelago: evidence of glacial Lake Algonquin on the Northern Bruce Peninsula, Ontario
Authors: Kor Philip S.G. , Cowell Daryl W. , Karrow Paul F. , Kristjansson F.J. Rik
Published: March 2012

The occurrence of abandoned shoreline bedrock erosional features at the edge of the Niagara Escarpment at Cabot Head indicates the existence of a group of islands in glacial Lake Algonquin during early postglacial time, referred to herein as the Cabot Head Archipelago. The abandoned shoreline features are situated as much as 80 m above the level of contemporary Georgian Bay. The range of abandoned shoreline bedrock erosional features, including shoreline cliffs, adjacent wave-cut platforms, wave-cut notches, shore stacks, shore caves, and other features, are described. The occurrence of these features is thought to be the result of the interaction between wave action in glacial Lake Algonquin and two distinct lithological facies representing the Wiarton – Colpoy Bay and Lions Head members of the Amabel Formation. The exceptional development of the abandoned shoreline bedrock erosional features in massive reefal dolostone between elevations of ∼250 and 255 m above sea level (asl) is interpreted as representing the relatively long-lived and stable Main stage of glacial Lake Algonquin (∼11 000–10 200 years BP). Shoreline erosional forms at elevations between ∼240 and 250 m asl may be indicative of declining lake levels partially controlled by bedrock structural factors. The final abandonment of the glacial Lake Algonquin shoreline in this area occurred when the eastern outlets of the lake became ice-free and its level dropped rapidly some 10 200 years BP. The Cabot Head Archipelago and the associated suite of raised and abandoned shoreline bedrock erosional features represent a rare assemblage of landforms within the Great Lakes basin, and possibly within Canada.
A 3D MODEL FOR FIBER LAY-DOWN IN NONWOVEN PRODUCTION PROCESSES
Authors: KLAR AXEL , MARINGER JOHANNES , WEGENER RAIMUND
Published: March 2012

In this paper a three-dimensional stochastic model for the lay-down of fibers on a moving conveyor belt in the production process of nonwoven materials is derived. The model is based on stochastic differential equations describing the resulting position of the fiber on the belt under the influence of turbulent air flows. The model presented here is an extension of an existing surrogate model, see Refs. 6 and 3.
REDUCTION OF SLOW–FAST PERIODIC SYSTEMS WITH APPLICATIONS TO POPULATION DYNAMICS MODELS
Authors: MARVÁ M. , POGGIALE J.-C. , BRAVO DE LA PARRA R.
Published: March 2012

This work deals with the approximate reduction of a nonautonomous two time scales ordinary differential equations system with periodic fast dynamics. We illustrate this technique with the analysis of two models belonging to different fields in ecology. On the one hand, we deal with a two patches periodic predator–prey model with a refuge for prey. Considering migrations between patches to be faster than local interaction allows us to study a three-dimensional system by means of a two-dimensional one. On the other hand, a two time scales periodic eco-epidemic model is addressed by considering two competing species, one of them being affected by a periodic SIR epidemic process which is faster than inter-species interactions. The difference between time scales allows us to study the asymptotic behavior of the four-dimensional system by means of a planar, reduced one. Furthermore, we propose a methodology straightforwardly applicable to a very large class of two time scales periodic systems.
REAL-TIME OPTICAL MONITORING OF CAPILLARY GRID SPATIAL PATTERN IN EPITHELIUM BY SPATIALLY RESOLVED DIFFUSE REFLECTANCE PROBE
Authors: SAIKO GUENNADI , DOUPLIK ALEXANDRE
Published: March 2012

We developed a novel method for real-time monitoring of alteration of the local epithelium vessel/capillary and blood oxygenation spatial pattern in epithelium exploiting a compact fibre sensor system based on spatially and spectrally resolved diffuse reflectance. The method is based on collection of spatially resolved diffuse reflectance R(λ) by fiber sensors. The spatial resolution is provided as a dependence of R(λ) on a set of distances ρ between the source and detector (attenuation curve). It is expected that the new method can reasonably extract the minor spatial deviations of oxygenation and local blood volume fraction — parameters, directly related to the local vessel density and capillary spatial patterns in the epithelium. Light scattering in visible range is naturally taken into account in the proposed method.
Bipolar Resistive Switching Behavior of a Pt/NiO/TiN Device for Nonvolatile Memory Applications
Authors: Seong Tae-Geun , Joung Mi-Ri , Sun Jong-Woo , Yang Min Kyu , Lee Jeon-Kook , Moon Ji Won , Roh Jaesung , Nahm Sahn
Published: March 2012

Bipolar resistive switching behavior was observed in a Pt/NiO/TiN device. The device exhibited switching behavior that was stable over 100 cycles and did not degrade after 104s. An electroforming process was required to obtain these bipolar resistive switching properties, and the conduction behavior of the low resistance state followed Ohm's law, indicating that conductive filaments formed during the electroforming process. The conductive filaments consisted of oxygen vacancies and the Pt electrode behaved as an oxygen reservoir. The bipolar resistive switching of the Pt/NiO/TiN device was explained by the generation and annihilation of oxygen vacancies in the filaments.
Indium–Tin Oxide/Al Reflective Electrodes for Ultraviolet Light-Emitting Diodes
Authors: Takehara Kosuke , Takeda Kenichiro , Ito Shun , Aoshima Hiroki , Iwaya Motoaki , Takeuchi Tetsuya , Kamiyama Satoshi , Akasaki Isamu , Amano Hiroshi
Published: March 2012

We investigated indium–tin oxide (ITO)/Al reflective electrodes for improving the light extraction efficiency of UV light-emitting diodes (LEDs). The ITO layer showed high transparency in the UV region upon optimization of the thickness and annealing temperature. As a result, the ITO/Al electrode exhibited both high reflectivity in the UV region and good contact characteristics simultaneously. Using this electrode, we succeeded in improving the light output power of a 350 nm UV-A LED.
Nitric oxide and l-arginine metabolism in a devascularized porcine model of acute liver failure
Authors: Sharma Vikram , Ten Have Gabriella A. M. , Ytrebo Lars , Sen Sambit , Rose Christopher F. , Dalton R. Neil , Turner Charles , Revhaug Arthur , van-Eijk Hans M. H. , Deutz Nicolaas E. P. , Jalan Rajiv , Mookerjee Rajeshwar P. , Davies Nathan A.
Published: March 2012

In acute liver failure (ALF), the hyperdynamic circulation is believed to be the result of overproduction of nitric oxide (NO) in the splanchnic circulation. However, it has been suggested that arginine concentrations (the substrate for NO) are believed to be decreased, limiting substrate availability for NO production. To characterize the metabolic fate of arginine in early-phase ALF, we systematically assessed its interorgan transport and metabolism and measured the endogenous NO synthase inhibitor asymmetric dimethylarginine (ADMA) in a porcine model of ALF. Female adult pigs (23–30 kg) were randomized to sham ( N = 8) or hepatic devascularization ALF ( N = 8) procedure for 6 h. We measured plasma arginine, citrulline, ornithine levels; arginase activity, NO, and ADMA. Whole body metabolic rates and interorgan flux measurements were calculated using stable isotope-labeled amino acids. Plasma arginine decreased >85% of the basal level at t = 6 h ( P < 0.001), whereas citrulline and ornithine progressively increased in ALF ( P < 0.001 and P < 0.001, vs. sham respectively). No difference was found between the groups in the whole body rate of appearance of arginine or NO. However, ALF showed a significant increase in de novo arginine synthesis ( P < 0.05). Interorgan data showed citrulline net intestinal production and renal consumption that was related to net renal production of arginine and ornithine. Both plasma arginase activity and plasma ADMA levels significantly increased in ALF ( P < 0.001). In this model of early-phase ALF, arginine deficiency or higher ADMA levels do not limit whole body NO production. Arginine deficiency is caused by arginase-related arginine clearance in which arginine production is stimulated de novo.
Functional recovery of fluid drainage precedes lymphangiogenesis in acute murine foreleg lymphedema
Authors: Mendez Uziel , Brown Emily M. , Ongstad Emily L. , Slis Justin R. , Goldman Jeremy
Published: March 2012

Secondary lymphedema in humans is a common consequence of axillary lymph node dissection (ALND) to treat breast cancer. It is commonly hypothesized that lymphatic growth is required to increase fluid drainage and ameliorate lymphedema. Although there is a pronounced alteration in the balance of interstitial forces regulating fluid transport that sustains the chronic form of lymphedema, it is presently unknown whether changes occur to the balance of interstitial forces during acute lymphedema that may play a role in the recovery of fluid drainage. Here, we compared the relative importance of lymphangiogenesis of lymphatic vessels and interstitial flows for restoring fluid drainage and resolving acute lymphedema in the mouse foreleg after ALND. We found that removal of the axillary lymph nodes reduced lymph drainage in the foreleg at days 0 and 5 postsurgery, with fluid tracer spreading interstitially through subcutaneous tissues. Interstitial fluid drainage returned to normal by day 10, whereas functional regrowth of lymphatic vessels was first detected by indocyanine green fluorescence lymphography at day 15, demonstrating that the recovery of interstitial fluid drainage preceded the regrowth of lymphatic vessels. This was confirmed by the administration of VEGF receptor-3-neutralizing antibodies, which completely blocks lymphatic regrowth. It was found that the recovery of interstitial fluid drainage and the natural resolution of acute lymphedema produced by ALND were not hindered by VEGF receptor-3 neutralization, demonstrating that interstitial fluid drainage recovery and the resolution of acute lymphedema are lymphangiogenesis independent. The data highlight the central role of the interstitial environment in adapting to lymphatic injury to increase fluid drainage.
Shedding Light on Melanocyte Pathobiology In Vivo
Authors: Zaidi M. Raza , De Fabo Edward C. , Noonan Frances P. , Merlino Glenn
Published: March 2012

Cutaneous malignant melanoma is rapidly increasing in the developed world and continues to be a challenge in the clinic. Although extensive epidemiologic evidence points to solar UV as the major risk factor for melanoma, there is a significant gap in our knowledge about how this most ubiquitous environmental carcinogen interacts with the largest organ of the mammalian body (skin) at the microenvironmental and molecular level. We review some recent advances that have started to close this gap. Cancer Res; 72(7); 1591–5. ©2012 AACR.
Chromatin Remodeling Underlies the Senescence-Associated Secretory Phenotype of Tumor Stromal Fibroblasts That Supports Cancer Progression
Authors: Pazolli Ermira , Alspach Elise , Milczarek Agnieszka , Prior Julie , Piwnica-Worms David , Stewart Sheila A.
Published: March 2012

Age is a major risk factor for the development of cancer. Senescent fibroblasts, which accumulate with age, secrete protumorigenic factors collectively referred to as the senescence-associated secretory phenotype (SASP). Here, we examined the molecular mechanisms that control SASP activation, focusing on the known SASP factor osteopontin (OPN). We found that expression of the canonical SASP members interleukin (IL)-6 and IL-8, but not OPN, were dependent upon a persistent DNA damage response (DDR) as evidenced by ATM and NF-κB activation. Treatment with several histone deacetylase (HDAC) inhibitors robustly activated SASP in the absence of DNA breaks, suggesting that DDR-dependent SASP activation occurs in response to chromatin remodeling rather than physical breaks in DNA. In the setting of HDAC inhibition, IL-6 and IL-8 expression remained dependent upon ATM and NF-κB, while OPN expression remained independent of these factors. Further analysis revealed that HDAC1 inhibition was sufficient to induce OPN expression, which is interesting given that loss of HDAC1 expression correlates with increased OPN expression within the stromal compartment of invasive breast cancers. Importantly, fibroblasts treated with HDAC inhibitors promoted tumor growth in vivo. Our findings therefore indicate that HDAC modulation plays an important role in stromal cell activation, with important implications for the use of HDAC inhibitors in the treatment of cancer. Cancer Res; 72(9); 2251–61. ©2012 AACR.
Reconsidering the Paradigm of Cancer Immunotherapy by Computationally Aided Real-time Personalization
Authors: Kogan Yuri , Halevi–Tobias Karin , Elishmereni Moran , Vuk-Pavlović Stanimir , Agur Zvia
Published: March 2012

Although therapeutic vaccination often induces markers of tumor-specific immunity, therapeutic responses remain rare. An improved understanding of patient-specific dynamic interactions of immunity and tumor progression, combined with personalized application of immune therapeutics would increase the efficacy of immunotherapy. Here, we developed a method to predict and enhance the individual response to immunotherapy by using personalized mathematical models, constructed in the early phase of treatment. Our approach includes an iterative real-time in-treatment evaluation of patient-specific parameters from the accruing clinical data, construction of personalized models and their validation, model-based simulation of subsequent response to ongoing therapy, and suggestion of potentially more effective patient-specific modified treatment. Using a mathematical model of prostate cancer immunotherapy, we applied our model to data obtained in a clinical investigation of an allogeneic whole-cell therapeutic prostate cancer vaccine. Personalized models for the patients who responded to treatment were derived and validated by data collected before treatment and during its early phase. Simulations, based on personalized models, suggested that an increase in vaccine dose and administration frequency would stabilize the disease in most patients. Together, our findings suggest that application of our method could facilitate development of a new paradigm for studies of in-treatment personalization of the immune agent administration regimens (P-trials), with treatment modifications restricted to an approved range, resulting in more efficacious immunotherapies. Cancer Res; 72(9); 2218–27. ©2012 AACR.
Detection of Tumor PIK3CA Status in Metastatic Breast Cancer Using Peripheral Blood
Authors: Higgins Michaela J. , Jelovac Danijela , Barnathan Evan , Blair Brian , Slater Shannon , Powers Penny , Zorzi Jane , Jeter Stacie C. , Oliver George R. , Fetting John , Emens Leisha , Riley Carol , Stearns Vered , Diehl Frank , Angenendt Philipp , Huang Peng , Cope Leslie , Argani Pedram , Murphy Kathleen M. , Bachman Kurtis E. , Greshock Joel , Wolff Antonio C. , Park Ben H.
Published: March 2012

Purpose: We sought to evaluate the feasibility of detecting PIK3CA mutations in circulating tumor DNA (ctDNA) from plasma of patients with metastatic breast cancer using a novel technique called BEAMing.

Experimental Design: In a retrospective analysis, 49 tumor and temporally matched plasma samples from patients with breast cancer were screened for PIK3CA mutations by BEAMing. We then prospectively screened the ctDNA of 60 patients with metastatic breast cancer for PIK3CA mutations by BEAMing and compared the findings with results obtained by screening corresponding archival tumor tissue DNA using both sequencing and BEAMing.

Results: The overall frequency of PIK3CA mutations by BEAMing was similar in both patient cohorts (29% and 28.3%, respectively). In the retrospective cohort, the concordance of PIK3CA mutation status by BEAMing between formalin-fixed, paraffin-embedded (FFPE) samples and ctDNA from temporally matched plasma was 100% (34 of 34). In the prospective cohort, the concordance rate among 51 evaluable cases was 72.5% between BEAMing of ctDNA and sequencing of archival tumor tissue DNA. When the same archival tissue DNA was screened by both sequencing and BEAMing for PIK3CA mutations (n = 41 tissue samples), there was 100% concordance in the obtained results.

Conclusions: Analysis of plasma-derived ctDNA for the detection of PIK3CA mutations in patients with metastatic breast cancer is feasible. Our results suggest that PIK3CA mutational status can change upon disease recurrence, emphasizing the importance of reassessing PIK3CA status on contemporary (not archival) biospecimens. These results have implications for the development of predictive biomarkers of response to targeted therapies. Clin Cancer Res; 18(12); 3462–9. ©2012 AACR.
Combined Medical and Surgical Therapy Improves Olfaction in Patients with Nasal Polyposis
Authors: Ayçiçek Abdullah , Kahveci Orhan Kemal , Miman Murat Cem , Duran Abidin , Yıldız Hüseyin
Published: March 2012

Objective: The aim of the present study was to evaluate the outcomes of combined oral steroid, nasal steroid and surgical therapy in patients with impaired olfaction due to nasal polyposis. Patients and Methods: This prospective observational study was undertaken in the otolaryngology department of a university hospital. During the study, 19 nasal polyposis patients were evaluated three times, i.e. before oral steroid therapy, before surgery (after steroid therapy) and after surgery, with smell identification tests, acoustic rhinometry, subjective smell score, endoscopic grading and a visual analog scale for nasal obstruction. Results: All subjective and objective measures were significantly improved after medical and surgical therapy (p < 0.01). The median smell identification score improved from 2 (interquartile range 0–4) to 5 (interquartile range 4–7) after combined therapy. Smell identification scores were found to be modestly correlated with all other examination findings. Conclusion: Combined therapy seems efficient in improving smell identification scores of nasal polyposis patients.
The Interferon Stimulated Gene 12 Inactivates Vasculoprotective Functions of NR4A Nuclear Receptors
Authors: Papac-Milicevic Nikolina , Breuss Johannes M. , Zaujec Jan , Ryban Lubos , Plyushch Tatiana , Wagner Gabriel A. , Fenzl Sabine , Dremsek Paul , Cabaravdic Muris , Steiner Marianne , Glass Christopher K. , Binder Christoph J. , Uhrin Pavel , Binder Bernd R.
Published: March 2012

Rationale:

Innate and adaptive immune responses alter numerous homeostatic processes that are controlled by nuclear hormone receptors. NR4A1 is a nuclear receptor that is induced in vascular pathologies, where it mediates protection.

Objective:

The underlying mechanisms that regulate the activity of NR4A1 during vascular injury are not clear. We therefore searched for modulators of NR4A1 function that are present during vascular inflammation.

Methods and Results:

We report that the protein encoded by
interferon stimulated gene 12
(ISG12), is a novel interaction partner of NR4A1 that inhibits the transcriptional activities of NR4A1 by mediating its Crm1-dependent nuclear export. Using 2 models of vascular injury, we show that ISG12-deficient mice are protected from neointima formation. This effect is dependent on the presence of NR4A1, as mice deficient for both ISG12 and NR4A1 exhibit neointima formation similar to wild-type mice.

Conclusions:

These findings identify a previously unrecognized feedback loop activated by interferons that inhibits the vasculoprotective functions of NR4A nuclear receptors, providing a potential new therapeutic target for interferon-driven pathologies.
Twenty-Two–Year Trends in Incidence of Myocardial Infarction, Coronary Heart Disease Mortality, and Case Fatality in 4 US Communities, 1987–2008
Authors: Rosamond Wayne D. , Chambless Lloyd E. , Heiss Gerardo , Mosley Thomas H. , Coresh Josef , Whitsel Eric , Wagenknecht Lynne , Ni Hanyu , Folsom Aaron R.
Published: March 2012

Background—

Knowledge of trends in the incidence of and survival after myocardial infarction (MI) in a community setting is important to understanding trends in coronary heart disease (CHD) mortality rates.

Methods and Results—

We estimated race- and gender-specific trends in the incidence of hospitalized MI, case fatality, and CHD mortality from community-wide surveillance and validation of hospital discharges and of in- and out-of-hospital deaths among 35- to 74-year-old residents of 4 communities in the Atherosclerosis Risk in Communities (ARIC) Study. Biomarker adjustment accounted for change from reliance on cardiac enzymes to widespread use of troponin measurements over time. During 1987–2008, a total of 30 985 fatal or nonfatal hospitalized acute MI events occurred. Rates of CHD death among persons without a history of MI fell an average 4.7%/y among men and 4.3%/y among women. Rates of both in- and out-of-hospital CHD death declined significantly throughout the period. Age- and biomarker-adjusted average annual rate of incident MI decreased 4.3% among white men, 3.8% among white women, 3.4% among black women, and 1.5% among black men. Declines in CHD mortality and MI incidence were greater in the second decade (1997–2008). Failure to account for biomarker shift would have masked declines in incidence, particularly among blacks. Age-adjusted 28-day case fatality after hospitalized MI declined 3.5%/y among white men, 3.6%/y among black men, 3.0%/y among white women, and 2.6%/y among black women.

Conclusions—

Although these findings from 4 communities may not be directly generalizable to blacks and whites in the entire United States, we observed significant declines in MI incidence, primarily as a result of downward trends in rates between 1997 and 2008.