bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of the structural changes in two cellobiohydrolases, CcCel6A and CcCel6C, from Coprinopsis cinerea – a tweezer‐like motion in the structure of CcCel6C
Authors: Tamura Mizuki , Miyazaki Takatsugu , Tanaka Yutaro , Yoshida Makoto , Nishikawa Atsushi , Tonozuka Takashi
Published: March 2012

The basidiomycete Coprinopsis cinerea produces five cellobiohydrolases belonging to glycoside hydrolase family 6 (GH6). Among these enzymes, C. cinerea cellulase 6C (CcCel6C), but not C. cinerea cellulase 6A (CcCel6A), can efficiently hydrolyze carboxymethyl cellulose and is constitutively expressed in C. cinerea. In contrast, CcCel6A possesses a cellulose‐binding domain, and is strongly induced by cellobiose. Here, we determined the crystal structures of the CcCel6A catalytic domain complexed with a Hepes buffer molecule, with cellobiose, and with p‐nitrophenyl β‐d‐cellotrioside (pNPG3). A notable feature of the GH6 cellobiohydrolases is that the active site is enclosed by two loops to form a tunnel, and the loops have been demonstrated to open and close in response to ligand binding. The enclosed tunnel of CcCel6A–Hepes is seen as the open form, whereas the tunnels of CcCel6A–cellobiose and CcCel6A–pNPG3 adopt the closed form. pNPG3 was not hydrolyzed by CcCel6A, and bound in subsites +1 to +4. On the basis of this observation, we constructed two mutants, CcCel6A D164A and CcCel6C D102A. Neither CcCel6A D164A nor CcCel6C D102A hydrolyze phosphoric acid‐swollen cellulose. We have previously determined the crystal structures of CcCel6C unbound and in complex with ligand, both of which adopt the open form. In the present study, both CcCel6A and CcCel6C mutants were identified as the closed form. However, the motion angle of CcCel6C was more than 10‐fold greater than that of CcCel6A. The width of the active site cleft of CcCel6C was narrowed, owing to a tweezer‐like motion.

Database
 The coordinates and structure factors described in this article have been deposited in the Protein Data Bank under the accession codes 3VOG, 3VOH, 3VOI, 3VOJ, and 3VOF
Transient Rise of Serum Testosterone Level After Single Sildenafil Treatment of Adult Male Rats
Authors: Janjic Marija M. , Stojkov Natasa J. , Bjelic Maja M. , Mihajlovic Aleksandar I. , Andric Silvana A. , Kostic Tatjana S.
Published: March 2012

Introduction

Phosphodiesterase type 5 (PDE5) inhibitors have been established in therapy for a variety of physiological disorders including erectile dysfunction. Despite its popularity and wide usage in erectile dysfunction treatment, the short-term effect of PDE5 inhibition on Leydig cell functionality and testosterone dynamics is missing.

Aim

This study was designed to assess the acute in vivo effects of sildenafil citrate (Viagra) treatment on testosterone production.

Methods

Male adult rats were given sildenafil (1.25 mg/kg BW) per os, and testosterone production were analyzed 30, 60, 120, and 180 minutes after treatment. Additionally, in vitro effect of sildenafil extract on Leydig cell steroidogenesis was estimated.

Main Outcome Measures

The formation of testicular interstitial fluid (TIF), and testosterone, cyclic guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP) content was followed. Occurrence and phosphorylation of mature steroidogenic acute regulatory protein (StAR) and interaction with protein kinase G 1 (PRKG1) were assessed by immunoprecipitation and Western blot.

Results

Serum testosterone was increased 60 and 120 minutes after sildenafil treatment. In 60 minutes, TIF volume was doubled and stayed increased till the end of the experimental period. cGMP and testosterone content in TIF were increased 30 minutes after treatment, and cAMP decreased in 60 minutes. Further, sildenafil-induced stimulation of testosterone production was abolished by ex vivo addition of PRKG1 inhibitor but not by protein kinase A inhibitor. Sildenafil treatment increased the level of phosphorylated and total StAR protein. Moreover, co-immunoprecipitation of StAR and PRKG1 was increased following sildenafil treatment suggesting the active role of this kinase in initiation of testosterone synthesis. Additionally, sildenafil extract applied in vitro on primary Leydig cell culture increased cGMP accumulation and testosterone production in time- and dose-dependent manner without effect on cAMP level.

Conclusion

Acute sildenafil treatment enlarged TIF volume but also stimulated testosterone production which may be significant considering the positive testosterone effect in regulation of sexual activity.
Antimalarial Activity of Newly Synthesized Chalcone Derivatives In Vitro
Authors: Yadav Neesha , Dixit Sandeep K. , Bhattacharya Amit , Mishra Lokesh C. , Sharma Manish , Awasthi Satish K. , Bhasin Virendra K.
Published: March 2012

Twenty‐seven novel chalcone derivatives were synthesized using Claisen‐Schmidt condensation and their antimalarial activity against asexual blood stages of Plasmodium falciparum was determined. Antiplasmodial IC50 (half‐maximal inhibitory concentration) activity of a compound against malaria parasites in vitro provides a good first screen for identifying the antimalarial potential of the compound. The most active compound was 1‐(4‐benzimidazol‐1‐yl‐phenyl)‐3‐(2, 4‐dimethoxy‐phenyl)‐propen‐1‐one with IC50 of 1.1 μg/mL, while that of the natural phytochemical, licochalcone A is 1.43 μg/mL. The presence of methoxy groups at position 2 and 4 in chalcone derivatives appeared to be favorable for antimalarial activity as compared to other methoxy‐substituted chalcones. Furthermore, 3, 4, 5‐trimethoxy groups on chalcone derivative probably cause steric hindrance in binding to the active site of cysteine protease enzyme, explaining the relative lower inhibitory activity.
Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients
Authors: Tran Dat , Science Michelle , Dix David , Portwine Carol , Zelcer Shayna , Johnston Donna L. , Yanofsky Rochelle , Gassas Adam , Ethier Marie‐Chantal , Sung Lillian
Published: March 2012

Please cite this paper as: Tran et al. (2012) Pandemic (H1N1) 2009 influenza in Canadian pediatric cancer and hematopoietic stem cell transplant patients. Influenza and Other Respiratory Viruses 6(601), e105–e113.

Background  The impact of pandemic H1N1 influenza (pH1N1) virus in pediatric cancer is uncertain. The objectives of this study were to characterize the clinical course of pH1N1 and identify factors associated with severe outcomes.

Methods  We conducted a Canadian multicenter retrospective review of children with cancer and stem cell transplant (SCT) recipients who were diagnosed with laboratory‐confirmed pH1N1 infection between May 1, 2009 and January 31, 2010.

Results  We identified 100 (19 in wave 1 and 81 in wave 2) cases of pH1N1 infection. Median age was 8·7 years. 71% had a hematologic malignancy, and 20% received SCT. Median duration of fever and illness was 2 and 12·5 days, respectively. 51 (51·5%) were hospitalized for a median of 5 days, with no deaths and only 1 requiring admission to the intensive care unit. Radiologically confirmed pneumonia was diagnosed in 10 (10%). Interruption of chemotherapy or conditioning occurred in 43 patients. In multivariable analyses, age <5 years (relative to ≥10 years) and neutropenia were associated with hospitalization while neutropenia was associated with pneumonia. Despite oseltamivir use in 89%, viral shedding was prolonged (median, 46 days) and often persisted after symptom resolution. However, an extended treatment course (>5 days) correlated with shortened duration of viral shedding (P = 0·041).

Conclusions  pH1N1 infection in pediatric cancer and SCT patients infrequently caused complications but commonly interrupted cancer treatment. Persistent shedding of virus after illness resolution was common. Further research is needed to verify this finding as it could have implications for treatment guidelines and infection control practices.
In Situ Determination of Au and Cu in Natural Pyrite by Near‐Infrared Femtosecond Laser Ablation‐Inductively Coupled Plasma‐Quadrupole Mass Spectrometry: No Evidence for Matrix Effects
Authors: Velásquez German , Borisova Anastassia Y. , Salvi Stefano , Béziat Didier
Published: March 2012

Gold and copper concentrations were determined in natural pyrite by near‐infrared femtosecond LA‐ICP‐QMS, using both sulfide reference materials (pyrrhotite Po‐726 and in‐house natural chalcopyrite Cpy‐RM) and NIST SRM 610 as external calibrators. Firstly, using NIST SRM 610 as the external calibrator, we calculated the Au concentration in Po‐726 and the Cu concentration in Cpy‐RM. The calculated concentration averages for Au and Cu were similar to the values published for Po‐726 and Cpy‐RM, respectively. Secondly, we calculated Au and Cu concentrations taking NIST SRM 610 as an unknown sample and using Po‐726 and Cpy‐RM as external calibrators. Again, the average values obtained closely reflected the preferred concentrations for NIST SRM 610. Finally, we calculated Au and Cu concentrations in natural pyrite using sulfide and silicate reference materials as external calibrators. In both cases, calculated concentrations were very similar, independent of the external calibrator used. The aforementioned data, plus the fact that we obtained very small differences in relative sensitivity values (percentage differences are between 5% and 17% for 57Fe, 63Cu and 197Au) on analyses of silicate and sulfide RMs, indicate that there were no matrix effects related to the differences in material composition. Thus, it is possible to determine Au and Cu in natural sulfides using NIST silicate glasses as an external calibrator.
The use of prisms for vision rehabilitation after macular function loss: an evidence‐based review
Authors: Markowitz Samuel N. , Reyes Sophia V. , Sheng Li
Published: March 2012

To determine the efficacy of prisms used for redirection of incoming images towards the peripheral retina in cases with macular function loss. Meta‐analysis of published work reporting outcomes from interventions using prisms was performed. The primary outcome measure selected for analysis was visual acuity (VA) used for viewing distance targets. Pooled data from 449 cases where prisms were prescribed for wearing in distance glasses were analysed. Visual acuity was better after using prisms (1.05 versus 0.89 logMAR units, p < 0.044). Mean effect size for improving VA was 79 bigger than the effect size calculated for the control group (0.158 versus 0.002). Most patients (76%) reported compliance with the therapy and also reported other benefits directly derived from the realized VA improvement. Published studies collectively offer positive evidence in support of using prisms for low vision rehabilitation after macular function loss. Further research is required to reach definitive binding conclusions.
Age‐related change in contrast sensitivity among Australian male adults: Florey Adult Male Ageing Study
Authors: Sia David I. T. , Martin Sean , Wittert Gary , Casson Robert J.
Published: March 2012

Purpose:  To describe the age‐related change in contrast sensitivity seen in 35‐ to 80‐year‐old men in an Australian population.

Methods:  The Florey Adelaide Male Ageing Study (FAMAS) is a prospective population‐based study of men aged 35–80 years randomly selected from the north‐west suburbs of Adelaide. We conducted a nested ophthalmic substudy of these men. Contrast sensitivity (CS) was measured at four spatial frequencies (3, 6, 12 and 18 cycles/degree [cpd]) using the Vectorvision CSV‐1000 contrast sensitivity test chart (Vectorvision, Dayton, OH, USA), and results were statistically analysed relative to age and cataract type.

Results:  There were 2650 eligible subjects in the FAMAS and 1195 participated (45.1%); 472 of those participated in the ophthalmic substudy. A statistically significant decrease in contrast sensitivity was seen with advancing age at each spatial frequency tested [Generalized estimating equations (GEE) multiple linear regression: p ≤ 0.01]. The decline with age was greatest in the highest spatial frequency (18 cpd) and least in the lowest spatial frequency (3 cpd). Posterior subcapsular cataract caused the greatest reduction in contrast sensitivity at all spatial frequencies, while nuclear cataract caused significant reduction only in the intermediate (12 cpd) and high (18 cpd) spatial frequencies. Cortical cataract failed to reach statistical significance in contrast sensitivity reduction at all spatial frequencies tested.

Conclusion:  Contrast sensitivity declines with age in all spatial frequencies tested with a greater decline occurring in the higher spatial frequencies. Age and cataracts are independently associated with contrast sensitivity decline, and posterior subcapsular cataracts caused the greatest reduction at all spatial frequencies.
Large cell neuroendocrine carcinoma: retrospective analysis of 24 cases from four oncology centers in Turkey
Authors: Ustaalioglu Bala Başak Oven , Ulas Arife , Esbah Onur , Turan Nedim , Bilici Ahmet , Demirci Umut , Alkıs Necati , Seker Mesut , Oksuzoglu Berna , Gumus Mahmut ,   ASMO (Anatolian Society of Medical Oncology)
Published: March 2012

Background:  Large cell neuroendocrine carcinoma (LCNEC) of the lung is classified as a variant of large cell lung carcinoma by the World Health Organization, however, the clinical and biological behavior of LCNEC resembles small cell lung carcinoma (SCLC) with a high mitotic index and a positivity of tumor cells with neuroendocrine markers. As there have only been a small number of patients with LCNEC recorded in literature, there is no consensus about the management of this subset. In the present study, we evaluated the incidence and prognosis of LCNEC in four oncology centers in Turkey.

Method:  We analyzed 24 patients with diagnoses of LCNEC from 3138 non‐small cell lung cancer patients who were diagnosed and treated between 2008 and 2010 in four different medical oncology centers in Turkey.

Results:  The median age was 56 (range; 36–64) and most patients were male, with three women included in the study. Ten out of 24 patients (41.6%) had locally advanced or metastatic disease, therefore, surgery could not be performed. Five patients (20.8%) were staged with stage I, six (25%) with stage II, five (20.8%) with stage III, and eight (33.3%) with stage IV. All patients had a history of smoking. Nine patients received chemotherapy postoperatively. At the 14.4‐month follow‐up period (range; 3–59) the median overall survival (OS) and progression‐free survival (PFS) rates were 32.7 and 9.5 months respectively. Tumor, node, metastasis (TNM) stage, performance status (PS) and the performance of surgery were significantly related to rates of both OS and PFS (P < 0.05).

Conclusion:  LCNEC was generally diagnosed postoperatively. Prognosis of LCNEC is poor and surgery has not proven an effective solution for long‐term survival, therefore, adjuvant chemotherapy has been suggested.
Comparison of four techniques of arthrocentesis of the lateral compartment of the femorotibial joint of the horse
Authors: Schumacher John , Schumacher Jim , Wilhite R.
Published: March 2012

Reasons for performing study:Clinical experiences indicate that centesis of the lateral compartment of the femorotibial joint is often unsuccessful.

Objective:To determine the accuracy of 2 published and 2 unpublished techniques of centesis of the lateral compartment of the femorotibial joint.

Hypothesis:It was hypothesised that a drug can be administered into the lateral compartment of the femorotibial joint via a diverticulum of this joint that surrounds the medial aspect of the long digital extensor tendon and that this technique is more accurate than described techniques of centesis of this compartment.

Methods:Twenty‐four stifles of 12 horses were divided equally into 4 groups and a radiocontrast medium injected into the lateral compartment of the femorotibial joint of each group using a hypodermic needle inserted: 1) caudal to the lateral patellar ligament and proximal to the tibial plateau, 2) caudal to the long digital extensor tendon and proximal to the tibial plateau, 3) between the long digital extensor tendon and bone of the extensor groove of the tibia or 4) directly through the long digital extensor tendon until it contacted bone. Twelve veterinary students who had no experience using any of these techniques performed the injections. Accuracy of each technique was determined by examining radiographs obtained after injecting the contrast medium.

Results:The most successful technique for arthrocentesis was by inserting a needle through the long digital extensor tendon. This approach was successful in all attempted cases, whilst other techniques had lower rates of success.

Conclusions:The lateral compartment of the femorotibial joint can be accessed accurately by inserting a needle through the long digital extensor tendon as it lies within the extensor groove. Other techniques may not be as accurate for clinicians inexperienced in arthrocentesis of the lateral compartment of the femorotibial joint.
Development of a gastroretentive pulsatile drug delivery platform
Authors: Thitinan Sumalee , McConville Jason T
Published: March 2012

Objectives

To develop a novel gastroretentive pulsatile drug delivery platform by combining the advantages of floating dosage forms for the stomach and pulsatile drug delivery systems.

Methods

A gastric fluid impermeable capsule body was used as a vessel to contain one or more drug layer(s) as well as one or more lag-time controlling layer(s). A controlled amount of air was sealed in the innermost portion of the capsule body to reduce the overall density of the drug delivery platform, enabling gastric floatation. An optimal mass fill inside the gastric fluid impermeable capsule body enabled buoyancy in a vertical orientation to provide a constant surface area for controlled erosion of the lag-time controlling layer. The lag-time controlling layer consisted of a swellable polymer, which rapidly formed a gel to seal the mouth of capsule body and act as a barrier to gastric fluid ingress.

Key findings

By varying the composition of the lag-time controlling layer, it was possible to selectively program the onset of the pulsatile delivery of a drug.

Conclusions

This new delivery platform offers a new method of delivery for a variety of suitable drugs targeted in chronopharmaceutical therapy. This strategy could ultimately improve drug efficacy and patient compliance, and reduce harmful side effects by scaling back doses of drug administered.
Characterization of efflux transport of the PDE5 inhibitors, vardenafil and sildenafil
Authors: Choi Min-Koo , Song Im-Sook
Published: March 2012

Objectives

We aimed to characterize the efflux transport properties of vardenafil and sildenafil, and to compare the kinetics of these compounds via efflux transporters such as P-gp, BCRP and MRP2.

Methods

We measured the basal-to-apical and apical-to-basal transport of vardenafil and sildenafil within the concentration range of 1–100 µm using MDCKII cells overexpressing P-gp, BCRP and MRP2, and Caco-2 cells.

Key findings

Vardenafil had a much greater basal-to-apical than apical-to-basal transport rate in MDCKII cells overexpressing P-gp, BCRP and MRP2. Sildenafil showed P-gp- and BCRP-mediated efflux transport, but did not seem to be pumped out via MRP2 transporters. Consequently, the absorptive transport of vardenafil and sildenafil in Caco-2 cells increased linearly over the concentration range of 1–100 µm, whereas the secretory transport of these drugs was saturable and inhibited by the presence of specific inhibitors of P-gp and BCRP. MK571, a representative MRP2 inhibitor, inhibited the basal-to-apical transport of vardenafil, but not of sildenafil.

Conclusion

The involvement of P-gp, BCRP and MRP2 for vardenafil and the involvement of P-gp and BCRP for sildenafil in the secretory transport with linear absorptive transport may contribute to the limited intestinal absorption of these drugs.
The effect of voxel size on high‐resolution peripheral computed tomography measurements of trabecular and cortical bone microstructure
Authors: Tjong Willy , Kazakia Galateia J. , Burghardt Andrew J. , Majumdar Sharmila
Published: March 2012

Purpose:

Accurate quantification of bone microstructure plays a significant role in understanding bone mechanics and response to disease or treatment. High‐resolution peripheral quantitative computed tomography (HR‐pQCT) allows for the quantification of trabecular and cortical structurein vivo, with the capability of generating images at multiple voxel sizes (41, 82, and 123 μm). The aim of this study was to characterize the effect of voxel size on structural measures of trabecular and cortical bone and to determine accuracy in reference to micro‐CT (µCT), the gold standard for bone microstructure quantification.

Methods:

Seventeen radii from human cadaver specimens were imaged at each HR‐pQCT voxel size and subsequently imaged using µCT. Bone density and microstructural assessment was performed in both the trabecular and cortical compartments, including cortical porosity quantification. Two distinct analysis techniques were applied to the 41 μm HR‐pQCT data: the standard clinical indirect analysis and a direct analysis requiring no density or structural model assumptions. Analysis parameters were adjusted to enable segmentation and structure extraction at each voxel size.

Results:

For trabecular microstructural measures, the 41 μm HR‐pQCT data displayed the strongest correlations and smallest errors compared to µCT data. The direct analysis technique applied to the 41 μm data yielded an additional improvement in accuracy, especially for measures of trabecular thickness. The 123 μm data performed poorly, with all microstructural measures either having moderate or nonsignificant correlations with µCT data. Trabecular densitometric measures showed strong correlations to µCT data across all voxel sizes. Cortical thickness was strongly correlated with µCT values across all HR‐pQCT voxel sizes. The accuracy of cortical porosity parameters was highly dependent on voxel size; again, the 41 μm data was most strongly correlated. Measures of cortical density and pore diameter at all HR‐pQCT voxel sizes had either weak or nonsignificant correlations.

Conclusions:

This study demonstrates the effect of voxel size on the accuracy of HR‐pQCT measurements of trabecular and cortical microstructure and presents parameters for HR‐pQCT analysis at nonstandard resolutions. For all parameters measured, correlations were strongest at 41 μm. Weak correlations for porosity measures indicate that a better understanding of pore structure and resolution dependence is needed.
Image‐based spectral distortion correction for photon‐counting x‐ray detectors
Authors: Ding Huanjun , Molloi Sabee
Published: March 2012

Purpose:

To investigate the feasibility of using an image‐based method to correct for distortions induced by various artifacts in the x‐ray spectrum recorded with photon‐counting detectors for their application in breast computed tomography (CT).

Methods:

The polyenergetic incident spectrum was simulated with the tungsten anode spectral model using the interpolating polynomials (TASMIP) code and carefully calibrated to match the x‐ray tube in this study. Experiments were performed on a Cadmium‐Zinc‐Telluride (CZT) photon‐counting detector with five energy thresholds. Energy bins were adjusted to evenly distribute the recorded counts above the noise floor. BR12 phantoms of various thicknesses were used for calibration. A nonlinear function was selected to fit the count correlation between the simulated and the measured spectra in the calibration process. To evaluate the proposed spectral distortion correction method, an empirical fitting derived from the calibration process was applied on the raw images recorded for polymethyl methacrylate (PMMA) phantoms of 8.7, 48.8, and 100.0 mm. Both the corrected counts and the effective attenuation coefficient were compared to the simulated values for each of the five energy bins. The feasibility of applying the proposed method to quantitative material decomposition was tested using a dual‐energy imaging technique with a three‐material phantom that consisted of water, lipid, and protein. The performance of the spectral distortion correction method was quantified using the relative root‐mean‐square (RMS) error with respect to the expected values from simulations or areal analysis of the decomposition phantom.

Results:

The implementation of the proposed method reduced the relative RMS error of the output counts in the five energy bins with respect to the simulated incident counts from 23.0%, 33.0%, and 54.0% to 1.2%, 1.8%, and 7.7% for 8.7, 48.8, and 100.0 mm PMMA phantoms, respectively. The accuracy of the effective attenuation coefficient of PMMA estimate was also improved with the proposed spectral distortion correction. Finally, the relative RMS error of water, lipid, and protein decompositions in dual‐energy imaging was significantly reduced from 53.4% to 6.8% after correction was applied.

Conclusions:

The study demonstrated that dramatic distortions in the recorded raw image yielded from a photon‐counting detector could be expected, which presents great challenges for applying the quantitative material decomposition method in spectral CT. The proposed semi‐empirical correction method can effectively reduce these errors caused by various artifacts, including pulse pileup and charge sharing effects. Furthermore, rather than detector‐specific simulation packages, the method requires a relatively simple calibration process and knowledge about the incident spectrum. Therefore, it may be used as a generalized procedure for the spectral distortion correction of different photon‐counting detectors in clinical breast CT systems.
A novel curvilinear approach for prostate seed implantation
Authors: Podder Tarun K. , Dicker Adam P. , Hutapea Parsaoran , Darvish Kurosh , Yu Yan
Published: March 2012

Purpose:

A new technique called “curvilinear approach” for prostate seed implantation has been proposed. The purpose of this study is to evaluate the dosimetric benefit of curvilinear distribution of seeds for low‐dose‐rate (LDR) prostate brachytherapy.

Methods:

Twenty LDR prostate brachytherapy cases planned intraoperatively with VariSeed planning system and I‐125 seeds were randomly selected as reference rectilinear cases. All the cases were replanned by using curved‐needle approach keeping the same individual source strength and the volume receiving 100% of prescribed dose 145 Gy (V100). Parameters such as number of needles, seeds, and the dose coverage of the prostate (D90, V150, V200), urethra (D30, D10) and rectum (D5, V100) were compared for the rectilinear and the curvilinear methods. Statistical significance was assessed using two‐tailed student's t‐test.

Results:

Reduction of the required number of needles and seeds in curvilinear method were 30.5% (p < 0.001) and 11.8% (p < 0.49), respectively. Dose to the urethra was reduced significantly; D30 reduced by 10.1% (p < 0.01) and D10 reduced by 9.9% (p < 0.02). Reduction in rectum dose D5 was 18.5% (p < 0.03) and V100 was also reduced from 0.93 cc in rectilinear to 0.21 cc in curvilinear (p < 0.001). Also the V150 and V200 coverage of prostate reduced by 18.8% (p < 0.01) and 33.9% (p < 0.001), respectively.

Conclusions:

Significant improvement in the relevant dosimetric parameters was observed in curvilinear needle approach. Prostate dose homogeneity (V150, V200) improved while urethral dose was reduced, which might potentially result in better treatment outcome. Reduction in rectal dose could potentially reduce rectal toxicity and complications. Reduction in number of needles would minimize edema and thereby could improve postimplant urinary incontinence. This study indicates that the curvilinear implantation approach is dosimetrically superior to conventional rectilinear implantation technique.
A Fine-Scale Chimpanzee Genetic Map from Population Sequencing
Authors: Auton Adam , Fledel-Alon Adi , Pfeifer Susanne , Venn Oliver , Ségurel Laure , Street Teresa , Leffler Ellen M. , Bowden Rory , Aneas Ivy , Broxholme John , Humburg Peter , Iqbal Zamin , Lunter Gerton , Maller Julian , Hernandez Ryan D. , Melton Cord , Venkat Aarti , Nobrega Marcelo A. , Bontrop Ronald , Myers Simon , Donnelly Peter , Przeworski Molly , McVean Gil
Published: March 2012

Going Ape Over Genetic Maps

Recombination is an important process in generating diversity and producing selectively advantageous genetic combinations. Thus, changes in recombination hotspots may influence speciation. To investigate the variation in recombination processes in humans and their closest existing relatives,

Auton
et al.

(p.
193
, published online 15 March) prepared a fine-scale genetic map of the Western chimpanzee and compared it with that of humans. While rates of recombination are comparable between humans and chimpanzees, the locations and genetic motifs associated with recombination differ between the species.
The preferred place of death between terminally ill cancer patients and their families in Shanghai
Authors: Gu Xiaoli , Cheng Wenwu , Cheng Menglei , Liu Minghui
Published: March 2012

Purpose

Where people die may influence the quality of their death, little is known about the choice for place of death of cancer patients in Shanghai, China. Considering the culture difference and palliative care implement, we organised a prospective questionnaire based on the choice death place between terminally ill cancer patients and their families. Methods: Among 4 years, 352 Patient-family care giver dyads were surveyed. The main outcome variables of the study were age, sex, income, marital status, living condition, religious beliefs, medical resources, the choice of the place of death and its reason. Descriptive statistics, χ2, κ coefficients were used. Determinants of congruence on preferences were identified by multivariate logistic regression.

Results

The majority choice of death place was home (82.5% and 72.3%). Patient-care giver dyads achieved 68.5% agreement on the preferred place of death. The κ coefficient of congruence was 0.59 (95% CI 0.54 to 0.66) For patients, worries of being a burden to others is the first reason for the choice of home; for families, the first reason was culture concerns. The Logistic regression analysis revealed the following independent predictors of preferring to die at home: age and living conditions.

Conclusion

This study described the preference of the death place choice and potential influencing factors and revealed the possibility for the integration of effective home care model in Shanghai Palliative Care programs. Effective interventions need to be developed avoid unnecessary re-hospitalisations and unfavourable hospital deaths, and improve accordance with the patients' wishes. Acknowledge for the funding form helped the hospice: The preference of place of death between terminally ill cancer patients. (Funding NO: 2005383)
Medical identity in psychotherapy training: effect on medical practice
Authors: Meystre Chantal
Published: March 2012

Background

Medical identity is formed intrapsychically and intrapersonally during training. Maintaining empathy in students and doctors in senior years is challenging. Empathy loss and use of defences may cause stress and isolation. Palliative care doctors become involved with patients and relatives more than other specialties. Integration of psychotherapy theory with medical knowledge has demonstrable benefits.

Aims

To explore the effect of a pre-existing medical identity on the experience of training and working as an integrative psychotherapist and the effect of psychotherapy training on medical practice.

Methods

Interpretative phenomenological analysis (IPA) explores daily events given meaning. The hermeneutic uses reflection and cyclical bracketing allowing preconceptions to rise to consciousness. As analysis arises from within the text, it is a robust method for working with identity. IPA has an ideographic base so the method supports small sample size research. Four medical consultants who also worked as integrative therapists, (two palliative medicine, one haematology, one diabetes and endocrinology) gave 90 min semistructured interviews. Ethical code and confidentiality followed the practice of UKCP. Interviews transcribed with prosodic information were analysed line by line demonstrating emergent patterns. Data coding linked themes into super-ordinate groups. Supervision and collegial interaction encouraged reflexivity.

Results

Emergent themes were Unpreparedness for medical school experiences and relating with patients prior to a medical identity; vulnerabilities were not discussed and defences against them formed a medical ‘shell’ psychotherapy training permitted expression of vulnerabilities, boundary setting, and personal closeness to patients and family. Transferences, resistances and the archetypal shadow of the medical profession were avoided by suppression of medical qualifications. The emergent true therapist self benefited both medicine and psychotherapy.

Conclusion

Psychotherapy training may benefit palliative care doctors retain empathy by limiting the use of unconscious defences, enhancing boundaries and maintaining holistic professionalism.
Facing death with a loved one
Authors: Lowes Julia
Published: March 2012

Background

This study explored the experience of caring for a loved one with terminal cancer who had expressed a wish to die at home. Interest was both professional, and personal from the experience I had supporting my mother with her terminal cancer diagnosis. End of life care is a major discussion point and is central to service improvements on an international scale. Literature reviewed, revealed some statistical data related to preference and actual place of death, together with limited research of the study topic. Studies note that carers are concerned with facilitating a home death, but rarely relate to the participants having expressed a wish themselves to die at home.

Aim and methodology

The aim was to explore carers' dilemmas in relation to facilitating dying at home for a close relative who had terminal cancer and expressed a wish to die at home, whether this was achieved or not. This was a qualitative, retrospective, phenomenological study, using the heuristic approach to investigate the true meaning of caring for a dying person at home. Data were collected through six unstructured interviews with bereaved carers. Ethical approval was received from the relevant bodies. Data were analysed using Collaizis procedural steps.

Results

The overarching theme was that the experience was that of a journey, and this journey was not being taken alone, but was integral to the relationships that the dying person had with others. The descriptions were of a situation that was wholly influenced by and impacted on the individuals involved and their relationships with one another. Four key themes emerged and were divided into sub themes these are interlinked and described through the participants own words.

Conclusion

Informal carers play a significant role in facilitating dying at home, without this support this would be more difficult and distressing.
Perceptions of specialist psychology services for minority ethnic groups in East Berkshire
Authors: Ryninks Kirsty , Smith Paula , Bebb Katie
Published: March 2012

Background

Specialist Palliative Care Services (SPCS) face many challenges as palliative care expands to support people from different ethnic, cultural and religious backgrounds. In spite of high populations of Minority Ethnic Groups (MEGs) in East Berkshire, an audit of referrals to the Specialist Psychological Service for Oncology and Palliative Care (SPSOPC) accounted for only 8% of total referrals to the Psychology Service from 2010–2011.

Aims

To investigate referring Healthcare Professionals' (HPs) perceptions and experiences of cultural issues when working in oncology and palliative care. A further aim was to explore potential reasons behind low referrals of MEGs to SPSOPC.

Method

Semistructured interviews with a purposive sample of nine HPs (consultants, clinical nurse specialists, advanced nurse practitioners, social worker) who had referred to SPSOPC were conducted and analysed using Interpretative Phenomenological Analysis.

Results

Healthcare Professionals reported a number of tensions in their work with MEGs and SPCS. This included difficulty treating patients from MEGs, assumptions and misconceptions about their care, and a conflict between traditional eastern values and western medicine. They also reported challenges to their sense of professionalism, feeling overwhelmed and out-of-their-depth and fear of causing offence when treating MEGs. There was an apparent lack of understanding of SPCS and of Specialist Psychological Services in particular, which could result in a ‘conveyor belt mentality’ in respect of service delivery.

Conclusions

Healthcare Professionals would benefit from increased education about MEGs and ways to accommodate cultural differences in service delivery. It is vital that SPCS and Specialist Clinical Health Psychology become more culturally competent and language-appropriate in today's multi-ethnic society. Enhancing understanding, awareness and delivery of culturally appropriate psychological services for MEGs has the potential to increase referrals of MEGs to SPSOPC, and to improve the quality of end-of-life care for this patient population.
Male carers' perceptions of support for themselves: findings from a national survey
Authors: Sibley Andrew , Payne Sheila , Addington-Hall Julia
Published: March 2012

Background

Multiple sclerosis (MS) is more prevalent in women than men. Men are particularly likely to take on the role of carers in MS but this has been rarely researched. The EAPC Carer White Paper notes the paucity of research into carer subgroups' support needs.

Aim

To identify the perceptions of support for themselves of men caring for adults severely affected by MS.

Method

Questionnaire survey design. Questionnaire developed from initial qualitative interviews. Widely disseminated via UK MS Society.

Findings

231 men completed the questionnaire. The majority cared for an adult with secondary progressive MS (44.2%) or primary progressive MS (36.8%). Men lived in 45 UK counties and the mean age was 60 years. Most men stated it was ‘quite easy’ (45.8%) to access support for their own needs but a quarter said it was ‘quite difficult’ (26.0%). Older (p=0.05) and retired (p=0.012) men had significantly less difficulty. Many reported ‘no need’ (67.5%) but a quarter ‘would like’ (25.5%) some training. Men still working (p=0.05) and from Southern England (p=0.004) reported a greater desire for training. Half the men had to initiate contact with ‘most’ of the services (50.0%) they needed and a quarter with ‘some’ (25.5%). Few received pro-active support from ‘some’ (15.5%) or ‘most’ (9.5%) of the services they needed. Men still working had significantly less pro-active support (p=0.05). Men were divided having ‘no encouragement’ (38.1%), ‘some encouragement’ (34.1%), and ‘have encouragement’ (27.9%) respectively. Most men (69.3%) had not taken a break from caring, for more than 24hrs, in the last year but many that did were ‘very satisfied’ (50.0%) or ‘extremely satisfied’ (19.2%).

Conclusions

Many men appear isolated and unable to take a break. Younger men still working had more difficulties and needs. Interventions are required to support health professionals pro-actively engage with male carers' needs.
The West Northumberland Palliative Care Pathway – a primary care centred pathway
Authors: Cunningham Bill , Williamson Ian , Shovlin David , McNamara Paul
Published: March 2012

Aim

To describe the development and implementation of an Integrated Care Pathway (ICP) for those with life-limiting illness in one locality utilising continuous quality improvement (CQI) and chronic disease management (CDM) principles; commissioned by and centred in primary care.

Background

There is a need to develop an evidence-based, effective, sustainable primary care-centred model for those with life-limiting illness which starts well in advance of the terminal phase, links together other key providers of care and identifies and addresses patient care preferences.

Method

Following an NHS Improvement Foundation course a palliative care steering group was formed in West Northumberland involving all key organisations to plan the pathway. New commissioning powers were used to develop local enhanced services and the principles of CDM and CQI to identify and manage patients and promote change. Quantitative data was collected about important pathway processes and outcomes using Miquest software and an annual locality death audit.

Results

A locality partnership group oversaw three phases of commissioning and implementation: 1) The development of Palliative Care registers and data recording 2) Home care and community palliative care beds 3) Detailed pathway interventions. Improvements resulted in many clinical process and outcomes measures including an increase in registrations, the identification of patient preferences, use of ‘just in case’ drugs and Liverpool Care Pathway and a reduction in hospital deaths. However the use of advance care plans was suboptimal. Wide variations exist between practices.

Conclusions

It is feasible to commission and deliver an ICP centred in primary care to a defined population for those with life-limiting illness linking key providers of care. The use of CDM and CQI processes has enhanced this implementation. The authors need to increase the use of effective pathway interventions earlier to more patients and reduce variations between practices. Further research and work on cost-effectiveness is being planned.
Delayed discharges – staff views
Authors: Frampton Emma , Wee Bee
Published: March 2012

Title

Nursing staff and allied health professionals perceptions of delayed discharges from a specialist palliative care unit.

Background

Discharge delays from specialist palliative care units are a common problem for patients. A delay in discharge, for whatever reason, can have significant implications for patients, and can mean that they are not cared for in their preferred place. There has been little research looking specifically at discharge delays from specialist palliative care units. Nursing staff and allied health professionals are often at the forefront of discharge planning, and little is known on their beliefs about this.

Aim

To investigate the perceptions of nursing staff and allied health professionals about discharge delays from a specialist palliative care unit.

Methods

The participants (nursing staff and allied health professionals) worked in a specialist palliative care unit in South Central England, and were involved in discharge planning for inpatients. The critical incident technique was used as the methodology. One-to-one interviews were audio taped, and analysed by the process of thematic analysis. Six participants were interviewed in total (five nursing staff and one allied health professional). The critical incident was defined as the ‘delayed discharge’, and participants talked about actual cases where a patient's discharge from the unit had been delayed.

Results

The results were broadly split into six themes: patient and family issues, staff issues, communication, community care, equipment and ethical issues. Communication was raised so frequently by participants and was so pervasive that it was separated into a stand-alone theme.

Conclusions

The results illustrate the complexities of the discharge planning process and discharge delays, and there is unlikely to be a single causative factor in a patient's delayed discharge. It is a source of distress to patients, families and staff. Practical issues need to be addressed, and communication is vital at all stages.
Macmillan end of life discharge project: experiences of health professionals and carers
Authors: Jones Susan , Hamilton Sharon
Published: March 2012

Background

Many patients nearing the end of life (EoL) express a wish to be cared for outside the acute hospital environment. However, hospital discharge processes often cannot offer a quick transfer, with the result that valuable time is lost for the patient and their family. This, along with the national need for Trusts to save acute bed days, were drivers for the introduction of a Macmillan discharge pilot project at one acute hospital.

Aim

To identify the experiences of professional staff and carers who had been involved with the new service. To inform future developments of the service.

Methods

An action research approach informed the study design. Data was collected through seven focus groups and two individual interviews with professional staff from the hospital and community (n=53) and interviews with six carers. Data was thematically analysed using the approach of Braun and Clark (2006).

Results

A key finding was how small the window of opportunity was for achieving a good EoL discharge. This window formed part of a discharge continuum that not only comprised a rapid transfer from hospital but started with timely communication with patients and their families regarding preferred place of care. The new service brought a more co-ordinated approach along this continuum which made an impact on the timeliness of the discharge process. Aspects where improvements could be made were identified from the data and informed an action plan which was devised by the service.

Conclusion

A complex mesh of factors need to be drawn together to effect a good discharge. This requires an emphasis on co-ordination combined with expertise in EoL care. The new service was successful in promoting a good discharge for many patients. However, further development of the service is needed so that more patients are able to achieve their preferred place of care.
‘Many hands make light work’ or ‘too many cooks spoil the broth’? Achieving the tricky balance of appropriate involvement in palliative care for cancer
Authors: Porter Katerina , Jarrett Nikki , Addington-Hall Julia , Corner Jessica , Davis Carol , Duke Sue , Lathlean Judith
Published: March 2012

Background

Addressing the care needs of people with advanced cancer is often complex, requiring communication between different professional and lay care providers, across different geographical and professional boundaries. Achieving the right balance of support and autonomy can be difficult, needing to be tailored to each patient.

Aim

Identify and quantify the number of people involved in the care of people with cancer and palliative care needs, and explore the network of communication pathways between these different people.

Method

Case study methodology was employed, each case involving one patient and the (patient-identified) people involved in their care (PIPCs) within the past 6 months. During indepth interviews with patients (n=24; mean length 65 min) and PIPCs (n=100; mean length 30 min), respondents identified and described the network of communication pathways surrounding the patient's care. A map of each patient's care network was drawn during each interview, and was subsequently redrawn using social networking software.

Results

Patients (15 female, 9 male; age range: 48–85) had a range of primary tumours (mean time since diagnosis: 9.5 months; range: 0.5–61 months). All were described as receiving or needing specialist or generalist palliative care at the time of recruitment (through General Practice (n=5); Hospital Specialist Palliative Care Team (n=8); Specialist Palliative Care Unit (n=11)). Patients identified 9–45 (mean:26) different people/teams as being involved in their care; an average of six PIPCs per case (range:0–11) were subsequently interviewed about their contribution to the communication surrounding this patient.

Conclusion

Sample cases and selected communication maps are presented to illustrate the range of possibilities in numbers of PIPCs involved and the complexity of, and patient and PIPC satisfaction with, some patients' communication networks. The methodological utility of the mapping technique, and its potential contribution to achieving the right balance of involvement in palliative care, are considered.