First Measurement Using Elliptically Polarized Photons of the Double-Polarization Observable E for γp→pπ

We report the measurement of the helicity asymmetry E for the pπ^{0} and nπ^{+} final states using, for the first time, an elliptically polarized photon beam in combination with a longitudinally polarized target at the Crystal Ball experiment at MAMI. The results agree very well with data that were taken with a circularly polarized photon beam, showing that it is possible to simultaneously measure polarization observables that require linearly (e.g., G) and circularly polarized photons (e.g., E) and a longitudinally polarized target. The new data cover a photon energy range 270-1400 MeV for the pπ^{0} final state (230-842 MeV for the nπ^{+} final state) and the full range of pion polar angles, θ, providing the most precise measurement of the observable E. A moment analysis gives a clear observation of the pη cusp in the pπ^{0} final state.

Cold seep formation from salt diapir-controlled deep biosphere oases.

Deep sea cold seeps are sites where hydrogen sulfide, methane, and other hydrocarbon-rich fluids vent from the ocean floor. They are an important component of Earth's carbon cycle in which subsurface hydrocarbons form the energy source for highly diverse benthic micro- and macro-fauna in what is otherwise vast and spartan sea scape. Passive continental margin cold seeps are typically attributed to the migration of hydrocarbons generated from deeply buried source rocks. Many of these seeps occur over salt tectonic provinces, where the movement of salt generates complex fault systems that can enable fluid migration or create seals and traps associated with reservoir formation. The elevated advective heat transport of the salt also produces a chimney effect directly over these structures. Here, we provide geophysical and geochemical evidence that the salt chimney effect in conjunction with diapiric faulting drives a subsurface groundwater circulation system that brings dissolved inorganic carbon, nutrient-rich deep basinal fluids, and potentially overlying seawater onto the crests of deeply buried salt diapirs. The mobilized fluids fuel methanogenic archaea locally enhancing the deep biosphere. The resulting elevated biogenic methane production, alongside the upward heat-driven fluid transport, represents a previously unrecognized mechanism of cold seep formation and regulation.

Association of Baseline Patient-reported Health-related Quality of Life Metrics with Outcome in Localised Prostate Cancer.

AIMS: Although health-related quality of life (HR-QoL) outcomes are pivotal in oncology, the prognostic significance of patient-reported HR-QoL metrics is largely undefined in localised prostate cancer. We report the association of baseline HR-QoL metrics with overall survival and toxicity in localised prostate cancer. MATERIALS AND METHODS: This was a secondary analysis of a phase III randomised controlled study conducted in a single-payer health system. Patients with Gleason score ≤7, clinical stage T1b-T3a and prostate-specific antigen <30 ng/ml were randomised to neoadjuvant and concurrent androgen deprivation therapy (ADT) for 6 months starting 4 months before prostate radiotherapy or concurrent and adjuvant ADT for 6 months starting simultaneously with prostate radiotherapy. HR-QoL scores were estimated using the European Organisation for Research and Treatment of Cancer QoL questionnaire. A multistate Markov model was used to determine the association of baseline HR-QoL metrics with overall survival and a multilevel multivariable Cox regression was used to determine the association with the incidence of delayed-onset grade ≥3 radiotherapy-related toxicities. To adjust for multiple analyses, P < 0.025 was considered as statistically significant. RESULTS: Overall, 393 patients with baseline HR-QoL data were included in this analysis: 194 in the neoadjuvant arm and 199 in the adjuvant arm. Baseline financial difficulty (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.02) and dyspnoea (hazard ratio 1.020, 95% confidence interval 1.003-1.030, P = 0.01) were associated with inferior overall survival. Baseline dyspnoea was associated with a higher incidence of grade ≥3 toxicity (hazard ratio 1.020, 95% confidence interval 1.010-1.030, P = 0.023). CONCLUSION: In a cohort of localised prostate cancer patients treated with radiotherapy and short-term ADT, a 10-point higher baseline financial difficulty or dyspnoea was associated with a 20% increased risk of death. With each 10-point increase in baseline dyspnoea, we noted a 20% increase in the associated risk of grade ≥3 delayed-onset radiotherapy-related toxicity.

Canadian consensus: oligoprogressive, pseudoprogressive, and oligometastatic non-small-cell lung cancer.

Background: Little evidence has been generated for how best to manage patients with non-small-cell lung cancer (nsclc) presenting with rarer clinical scenarios, including oligometastases, oligoprogression, and pseudoprogression. In each of those scenarios, oncologists have to consider how best to balance efficacy with quality of life, while maximizing the duration of each line of therapy and ensuring that patients are still eligible for later options, including clinical trial enrolment. Methods: An expert panel was convened to define the clinical questions. Using case-based presentations, consensus practice recommendations for each clinical scenario were generated through focused, evidence-based discussions. Results: Treatment strategies and best-practice or consensus recommendations are presented, with areas of consensus and areas of uncertainty identified. Conclusions: In each situation, treatment has to be tailored to suit the individual patient, but with the intent of extending and maximizing the use of each line of treatment, while keeping treatment options in reserve for later lines of therapy. Patient participation in clinical trials examining these issues should be encouraged.

Assessing the educational impact of the dementia champions programme in Scotland: Implications for evaluating professional dementia education.

Increasing numbers of people with dementia are living longer with a higher likelihood of requiring hospital care for physical conditions including falls, infections and stroke (Boaden, 2016). However, the literature is replete with descriptions of poor care and hospital care experiences that have fallen well below the expectations of people with dementia, their families and friends. Although poor care is unacceptable, it is unsurprising given that dementia education for health and social care professionals is often inadequate and inconsistent. This results in most healthcare staff being ill-equipped and lacking the confidence to work with people living with dementia. The first of Scotland's National Dementia Strategies committed to "improve the response to dementia in general hospital settings including alternatives to admission and better planning for discharge" (Scottish Government, 2010). The educational response was the commissioning of the Dementia Champions programme. Since 2011, the programme has developed over 800 health and social care professionals working in general hospital and related settings to be change agents in dementia care. This article will outline the theoretical underpinning of the programme and present pooled results from four cohorts (2014-2017) (n = 524). A repeated measure design (pre and post programme) was used to measure attitudes towards people with dementia; self-efficacy and knowledge of dementia. The findings suggest that the education had a statistically significant positive effect on all intended outcomes, indicating the potential for practice change. We discuss these findings in relation to the literature, and respond to the calls for high quality evaluation to measure the effectiveness of dementia education, the challenges and potential directions for measuring educational effectiveness and capturing transfer of learning.

Study of η and η' Photoproduction at MAMI.

The reactions γp→ηp and γp→η^{'}p are measured from their thresholds up to the center-of-mass energy W=1.96 GeV with the tagged-photon facilities at the Mainz Microtron, MAMI. Differential cross sections are obtained with unprecedented statistical accuracy, providing fine energy binning and full production-angle coverage. A strong cusp is observed in the total cross section for η photoproduction at the energies in the vicinity of the η^{'} threshold, W=1896 MeV (E_{γ}=1447 MeV). Within the framework of a revised ηMAID isobar model, the cusp, in connection with a steep rise of the η^{'} total cross section from its threshold, can only be explained by a strong coupling of the poorly known N(1895)1/2^{-} state to both ηp and η^{'}p. Including the new high-accuracy results in the ηMAID fit to available η and η^{'} photoproduction data allows the determination of the N(1895)1/2^{-} properties.

Effect of unconventional curing conditions and storage on pellets coated with Aquacoat ECD.

PURPOSE: Purpose of this study was to develop storage stable pellets coated with the aqueous ethylcellulose dispersion Aquacoat ECD. METHODS: The influence of accelerated curing/storage conditions on the release behavior of Aquacoat/HPMC-coated drug pellets were investigated as a function of various formulations (sealing, plasticizer content, and pore-former type/amount) and process parameters (process humidity, thermal curing, and organic processing). RESULTS: Conventionally cured Aquacoat/hydroxypropyl methylcellulose- coated pellets were storage stable at ambient conditions and 25 degrees C/60% relative humidity (RH) but showed a decreasing drug release at 40 degrees C/75% RH, which is a required test condition according to ICH guidelines. CONCLUSION: Only organic processing of dried Aquacoat or unconventionally harsh curing conditions (60 degrees C/75% RH or 80 degrees C) improved the storage stability of Aquacoat-coated pellets at accelerated conditions.

The emerging role of IG-IMRT for palliative radiotherapy: a single-institution experience.

Many modern radiotherapy centers now have image-guided intensity-modulated radiotherapy (IG-IMRT) tools available for clinical use, and the technique offers many options for patients requiring palliative radiotherapy. We describe a single-institution experience with IG-IMRT for short-course palliative radiotherapy, highlighting the unique situations in which the technique can be most effectively used.

Diagnosis and laparoscopic management of 12 consecutive cases of ovarian pregnancy and review of literature.

We sought to determine the outcome of the laparoscopic management of ovarian ectopic pregnancy (OEP) in a United Kingdom district general hospital and reviewed the literature. We conducted a 5-year prospective cohort study of the management of OEP cases between January 2003 and January 2008. Twelve patients had OEP confirmed with histology among a cohort of 421 ectopic pregnancies. The mean gestational age was 45 days. All 12 patients had abdominal pain and 4 (33%) had vaginal bleeding. One (8%) patient became hypovolemic before laparoscopy. Four (33%) women had risk factors for ectopic pregnancy, 2 of whom were current intra-uterine contraceptive users. Preoperative diagnosis of ectopic pregnancy was made in 11 (92%) of 12 patients by transvaginal ultrasonography and OEP in 9 (75%) patients. All cases were managed by laparoscopic surgery with no conversion to laparotomy. The ovarian pregnancy was resected and the ovary conserved in 11 (92%) patients with only 1 requiring an oophorectomy. The mean operating time was 49 minutes. None of the patients needed further treatment. No complications occurred after laparoscopic surgery and the mean hospital stay was 2 days. Considering the rarity of ovarian pregnancy, this is one of the largest series of patients with OEP treated exclusively by laparoscopic surgery and highlights our recent experience of performing conservative laparoscopic surgery for most of our patients.

A single 10-min bout of cold-water immersion therapy after strenuous plyometric exercise has no beneficial effect on recovery from the symptoms of exercise-induced muscle damage.

The purpose of this study was to examine the effectiveness of a single bout of cold-water immersion on recovery from exercise-induced muscle damage. Eighteen physically active female volunteers (age 19.9 (+/-0.97 years), height 1.66 (+/-0.05 m), mass 63.7 (+/-10 kg), completed 10 sets of 10 counter-movement jumps to induce muscle damage and were randomly allocated to a control or treatment group. The treatment group was given a single 10-min bout of lower limb cold-water immersion therapy at 10 degrees C immediately following damage-inducing exercise. Indicators of muscle damage (plasma creatine kinase activity, perceived soreness and maximal voluntary contraction of the quadriceps) were assessed immediately prior to counter-movement jumps, and at 1, 24, 48, 72 and 96 h, following the damaging exercise. Significant (p = 0.05) time effects were recorded on all indicators of muscle damage, but there were no significant group or group x time interaction effects found on any of the measured variables. The results indicate that a single bout of cold-water immersion after a damaging bout of exercise has no beneficial effects on the recovery from exercise-induced muscle damage.

Diagnosis and laparoscopic management of 11 consecutive cases of cornual ectopic pregnancy.

OBJECTIVE: To determine the pre-operative diagnosis by two dimensional ultrasound scan and the outcome of the laparoscopic management of cornual ectopic pregnancy. DESIGN: Prospective database cohort study. SETTING: Whipps Cross University Hospital, UK (District General Hospital). PATIENTS: Eleven patients with cornual ectopic pregnancy presenting in our hospital between January 2003 and December 2007. INTERVENTIONS: Laparoscopic cornuostomy or cornual resection. OUTCOME MEASURES: Pre-operative diagnosis by ultrasound scan, conversion rate to laparotomy, successful laparoscopy (not requiring further treatment), complication rate and duration of hospital stay. RESULTS: The mean gestational age was 8 +/- 2 weeks. All 11 patients presented with abdominal pain and vaginal bleeding and two (18%) patients became haemodynamically unstable before laparoscopy. There were five (45%) patients with risk factors for ectopic pregnancy. The mean serum beta-human chorionic gonadotropin (beta-hcg) was 15,263 +/- 12,045 microm/ml. One patient did not have a transvaginal scan as it was decided to proceed to surgery on clinical grounds. The diagnosis of ectopic pregnancy was correct at initial scan in nine (90%) of the ten patients who had transvaginal scans as one patient was misdiagnosed at the first scan. However, an ectopic pregnancy was diagnosed on a second ultrasound scan assessment. Initial laparoscopy was negative in one of the nine patients diagnosed as having an ectopic pregnancy. The diagnosis was later confirmed following serial serum beta-hcg monitoring, a repeat scan and a second laparoscopy. Ten (91%) of the 11 patients had successful operative laparoscopy as one (9%) patient had conversion to laparotomy. Among patients who had laparoscopic surgery, cornuostomy was performed in three (30%) patients while cornual resection was performed in the other seven (70%) patients. One (10%) of the patients who had laparoscopic surgery needed further treatment with systemic methotrexate. This patient had a cornual resection and was the only complication following laparoscopic surgery. The mean hospital stay was 2 days. CONCLUSION: This presentation of one of the larger series of patients with cornual ectopic pregnancy managed by laparoscopic surgery reveals that experience at ultrasonography and laparoscopic technique can lead to earlier diagnosis and few cases requiring laparotomy or further treatment. In addition laparoscopic surgery for cornual ectopic is safe and lends itself to conservative approach (cornuostomy) in selected cases.

Scintigraphic study to investigate the effect of food on a HPMC modified release formulation of UK-294,315.

The objective of the study was to use the combined approach of gamma scintigraphy and pharmacokinetics, in order to understand the mechanisms explaining the pharmacokinetic differences observed for a modified release (MR) formulation, when administered either in the fed or fasted state. Ten healthy subjects were recruited into a randomized three period single dose study, each subject receiving UK-294,315 40 mg IR (fasted), 100 mg MR (fasted) or 100 mg MR (after a high fat meal). C(max) values were markedly higher for the MR tablet in the fed state versus fasted and mean residence time was about 3 h longer for fasted versus fed; there was little difference in apparent oral clearance. In the fasted state, average gastric emptying of the intact tablet occurred at 1.2 h postdose, with gastric emptying of intact tablet observed in all subjects. In the fed state, rapid disintegration of the MR tablet was observed by scintigraphy, with 7/9 subjects showing complete disintegration in the stomach. Complete disintegration occurred 10.1 h postdose in the fasted state versus 5.9 h after a high fat meal. The study showed that in the fed state, the MR tablet eroded more rapidly than in the fasted state, leading to an overall increase in the rate of absorption.

Evaluating nuchal translucency scans performed for trisomy screening in a district general hospital between July 1998 and January 2004.

In October 2003, The National Institute for Clinical Excellence recommended screening tests for Down's syndrome (DS) to come into effect from April 2007. These tests were recommended based on studies performed in research centres. Some of the recommended tests have a fetal nuchal translucency scan component. In this retrospective study at the Basildon and Thurrock University Hospital we have evaluated nuchal translucency (NT) scans performed between July 1998 and January 2004 on 18,965 fetuses with a view to comparing our findings with research centres. In spite of our high standards, our detection rate for DS was 72.0% (95% CI 56.0-83.8%) for a 5% false positive rate. This was much lower than the 85% reported from the seminal paper in 1994. We believe that the advice given to women should be based on data from working programmes and not research units.

Changing trends in the laparoscopic management of ectopic pregnancy in a London district general hospital: 7-years experience.

We set out to evaluate the effect of a programme introduced in January 2003 to make operative laparoscopy the standard surgical treatment for women requiring surgery for ectopic pregnancy. This was a retrospective and prospective clinical data analysis performed at The Whipps Cross University Hospital in London, with a comparison of data taken before and after the introduction of the programme. A total of 116 women who had surgical management for ectopic pregnancy from January 2000 to December 2002 and 313 women who had surgery for ectopic pregnancy between January 2003 and December 2006 took part in the study. A programme was started in January 2003 to make operative laparoscopy the surgical management of choice. The main outcome measure was the proportion of women requiring surgery who had operative laparoscopy in the two study periods. The chi(2)-test was used to determine if there was any statistically significant difference between proportions. A difference was deemed statistically significant if p < 0.05. The results showed that there was a progressive rise in the proportion of ectopic pregnancies managed by operative laparoscopy following the change in January 2003. A total of 34% of women were managed laparoscopically between 2000 and 2002, increasing to 90% between 2003 and 2006. This difference was statistically significant (p < 0.001). In 2006, some 96% of women requiring surgery were managed by laparoscopic surgery. The findings of this study indicate that it is possible to implement changes which increase and sustain a high rate of laparoscopic surgery for women with ectopic pregnancy requiring surgery in a district general hospital setting.

Polymer blends for controlled release coatings.

The use of polymer blends as coating materials for controlled drug delivery systems can offer major advantages, including: (i) facilitated adjustment of desired drug release patterns, mechanical properties and drug release mechanisms, (ii) improved film formation and storage stability, and (iii) the possibility to develop novel strategies for site specific drug delivery within the gastro intestinal tract (e.g., colon targeting). However, these systems are more complex than coatings based on only one polymer and care has to be taken when using this type of formulations. For instance, the blended polymers can be incompatible, aqueous polymer dispersions might flocculate and plasticizers potentially redistribute from one polymer into the other during curing and/or long term storage. This article gives an overview on the current state of the art of the use of polymer blends as coating materials for controlled drug delivery, explaining the major advantages and potential pitfalls. Special emphasis is laid on the underlying drug release mechanisms and practical examples for various types of applications are given. Due to the higher complexity of the systems, a thorough understanding of the most important mass transport phenomena involved in the control of drug release can be very helpful to render the optimization of this type of advanced delivery systems more efficient.

Blends of aqueous polymer dispersions used for pellet coating: importance of the particle size.

Blends of aqueous dispersions of a water-insoluble and an enteric polymer, namely ethyl cellulose:hydroxypropyl methylcellulose acetate succinate (EC:HPMCAS) and ethyl cellulose:methacrylic acid ethyl acrylate copolymer (EC:Eudragit L), were used as coating materials to control theophylline release from matrix pellets. Varying the polymer blend ratio, broad ranges of drug release patterns were obtained at low as well as at high pH. Interestingly, the resulting release profiles were rather similar for both types of blends in 0.1 M HCl, whereas significant differences were observed in phosphate buffer pH 7.4. Surprisingly, drug release at high pH was much slower for EC:HPMCAS blends compared to EC:Eudragit L blends, although HPMCAS leached out more rapidly (and to a higher extent) from the film coatings than Eudragit L. To explain these phenomena and to better understand the underlying drug release mechanisms, thin polymeric films of identical composition as the pellet coatings were prepared and physicochemically characterized before and upon exposure to the release media. Importantly, the polymer particle size was identified to be a very crucial formulation parameter, determining the resulting film coating structure and properties. The Eudragit L particles are much smaller than the HPMCAS particles (nano- vs. micrometer size range) and, thus, more effectively hinder the formation of a continuous and mechanically stable EC network. Consequently, the EC structures remaining after enteric polymer leaching at high pH are mechanically much weaker in the case of Eudragit L. Upon exposure to phosphate buffer, water-filled cracks are formed, through which the drug rapidly diffuses out. In contrast, the EC structures remaining upon HPMCAS leaching are mechanically stronger and drug release is controlled by diffusion through the polymeric remnants.

Effect of SBE7-beta-cyclodextrin complexation on carbamazepine release from sustained release beads.

The effect of SBE7-beta-cyclodextrin together with hydroxypropylmethyl cellulose (HPMC) or polyvinylpyrrolidone (PVP) on the saturated solubility and delivery of carbamazepine (a poorly soluble drug) from sustained release (SR) beads was investigated. Carbamazepine solubility at room temperature increased from 0.1 to 5.4mg/ml by forming an inclusion complex with SBE7-beta-cyclodextrin (15%w/v). HPMC (0.1%w/v) also increased the aqueous solubility of carbamazepine, acting both alone and synergistically with SBE7-beta-cyclodextrin, to produce solubility values of 0.26 and 8.1mg/ml respectively. PVP (0.1-0.5%w/v) had no effect on carbamazepine solubility, either alone or in combination with SBE7-beta-cyclodextrin. The addition of SBE7-beta-cyclodextrin to SR beads increased the rate of carbamazepine release. In addition, comparable release rates where obtained when lower ratios of SBE7-beta-cyclodextrin together HPMC were incorporated in the SR bead. Therefore this ternary drug cyclodextrin polymer system was considered preferable over the binary drug cyclodextrin system for SR beads, as less cyclodextrin was required. However, both binary and ternary approaches were considered suitable techniques to improve the release rate and potentially the in vivo bioavailability of poorly soluble drugs that had previously exhibited slow or incomplete release from SR beads.