A PD stent that migrates within a nondilated PD may be difficult

A PD stent that migrates within a nondilated PD may be difficult to remove endoscopically. JQ1 We performed endoscopic retrieval of proximally migrated PD stents after EP in 5 patients. Endoscopic retrieval was performed immediately after EP in one patient, the next day in 3 patients, and 2 weeks later in one patient. Wire-guided endoscopic retrieval was attempted in 4 patients, and the migrated stents were removed successfully in these 4

patients. No significant procedure-related complications occurred, other than mild pancreatitis in a single patient. In one patient, endoscopic retrieval performed immediately after EP failed when using the conventional method, and the migrated

stent was removed using a minisnare without a guidewire the next day; this patient developed severe pancreatitis. Wire-guided endoscopic snare retrieval seems to be a safe and effective method for removing proximally migrated PD stents after EP. (Gut Liver 2011;5:532-535)”
“We studied locomotor activity rhythms of C57/Bl6 mice under a chronic jet lag (CJL) protocol (ChrA(6/2)), which consisted of 6-hour phase advances of the light-dark schedule (LD) every 2 days. Through periodogram analysis, we found 2 components of the activity rhythm: a short-period component (21.01 +/- 0.04 h) that was entrained by the LD schedule and a long-period component (24.68 +/- 0.26 h). We developed a mathematical model comprising 2 coupled circadian oscillators that was tested experimentally PF-3084014 with different CJL schedules.

Our simulations suggested that under CJL, the system behaves as if it were under a zeitgeber with a period determined by (24 -[phase shift size/days between shifts]). Desynchronization within the system arises according to whether this effective zeitgeber is inside or outside the range of SB203580 entrainment of the oscillators. In this sense, ChrA(6/2) is interpreted as a (24 – 6/2 = 21 h) zeitgeber, and simulations predicted the behavior of mice under other CJL schedules with an effective 21-hour zeitgeber. Animals studied under an asymmetric T = 21 h zeitgeber (carried out by a 3-hour shortening of every dark phase) showed 2 activity components as observed under ChrA(6/2): an entrained short-period (21.01 +/- 0.03 h) and a long-period component (23.93 +/- 0.31 h). Internal desynchronization was lost when mice were subjected to 9-hour advances every 3 days, a possibility also contemplated by the simulations. Simulations also predicted that desynchronization should be less prevalent under delaying than under advancing CJL. Indeed, most mice subjected to 6-hour delay shifts every 2 days (an effective 27-hour zeitgeber) displayed a single entrained activity component (26.92 +/- 0.11 h).

Methods Waist to height ratio (waist circumference/height,

Methods Waist to height ratio (waist circumference/height,

both in centimetres) and body mass index (weight (kg)/height (m2)) were collected from 896 children aged 5.00-7.99 years. Mothers of these children reported on early feeding behaviour and indicated their highest level of education attained. The 75th and 95th percentiles were used to define high and very high waist to height ratio. Overweight and obesity defined by body mass index were also included in the analyses. Results There were a higher proportion of children 75th percentile for waist to height ratio among the never breastfed group compared to breastfed children. This was statistically significant only in females (P = 0.002). Females predominantly breastfed for 4-6 months (P INCB28060 manufacturer = 0.003) and >12 months

(P = 0.006) had significantly lower mean waist to height ratio than those never breastfed. A similar pattern emerged with body mass index. Among Selleckchem LY3023414 males, delaying solids for 6 months was associated with significant decreases in waist to height ratio and body mass index. Females were six times more likely to have waist to height ratio 95th percentile than children predominantly breastfed for 4-6 months. This was statistically significant. Increasing maternal education was related to breastfeeding duration. Conclusion Prevalence of overweight and high abdominal adiposity was significantly greater among females who were never breastfed. Females who were predominantly breastfed for at least 4-6 months had the lowest mean waist to height ratio and body mass index and also the greatest reduction in the risk of very high

waist to height ratios.”
“BACKGROUND AND OBJECTIVES: Lifting presents a significant risk for the development of low back pain. It is not known what effect lifting from a supermarket shopping trolley has on sagittal spinal curvature. The aim of this study is to determine the effect of lifting from a shopping trolley on sagittal spinal curvature. METHODS: Fifteen female subjects (height 1.67 +/- 0.04 m, weight 64.3 +/- 5.0 kg) completed lifts of 9 kg from a shopping trolley and a surface matched for height whilst sagittal spinal curvature MI-503 mw was measured using Qualysis motion analysis system. Seven retro-reflective markers were placed along spine with angle between three markers representing regional curvature. No constraints on lifting technique were instigated. RESULTS: Results demonstrate no difference in sagittal range of motion or spinal curvature across the two lifts. A small but significant difference in knee flexion angle was observed. These results demonstrate that the chosen lifting strategy was not influenced by the constraint imposed by the shopping trolley. Furthermore the function of knee flexion did not result in change in sagittal curvature during the lifts.

Vitrification of fish spermatozoa without permeable cryoprotectan

Vitrification of fish spermatozoa without permeable cryoprotectants is a prospective direction for investigations: these cells can be successfully vitrified with 1% BSA + 40% seminal plasma.”
“Balaglitazone

is a novel thiazolidinedione in clinical development for the treatment of type 2 diabetes. Common side effects associated with PPAR gamma receptor agonists are weight gain, oedema and adipogenesis. Balaglitazone is a selective partial PPAR gamma agonist and it has been speculated that such compounds have a more favourable safety margin than full agonists. We Z-VAD-FMK in vivo have compared impact of equi-efficacious antihyperglycaemic doses of balaglitazone with full PPAR gamma agonist rosiglitazone on body fluid accumulation, cardiac enlargement, and adipogenesis. Equi-efficacious antihyperglycaemic doses (ED90) of balaglitazone (3 mg/kg/day) and rosiglitazone (6 mg/kg/day) were determined in male diabetic db/db mice. In adult male rats treated for up to 42 days, feeding, drinking, anthropometry, and plasma volumes were measured. Total plasma volume was measured with dye dilution technique. Compared to vehicle, rosiglitazone consistently increased food intake throughout the 42 day treatment period. In contrast, balaglitazone increased food intake in the last week of the experiment. However,

both rosiglitazone and balaglitazone increased water intake. Cyclosporin A purchase After 42 days, rosiglitazone treated rats displayed significantly elevated adiposity. Rosiglitazone selleck products increased total blood and plasma volumes throughout the treatment. Twenty-one days of balaglitazone treatment had no significant impact on blood or plasma volumes, whilst 42 days of balaglitazone increased plasma volume but to a significantly lesser extent than seen for rosiglitazone (vehicle: 46.1 +/- 1.5; balaglitazone: 50.8 +/- 1.21: rosiglitazone: 54.6 +/- 1.6 ml/kg). Heart weight was significantly elevated only in rosiglitazone treated animals. At doses inducing comparable antihyperglycaemic control, the full PPAR gamma agonist, rosiglitazone, induces more pronounced body fluid retention and heart enlargement

than seen for the partial PPAR gamma agonist, balaglitazone. Thus, partial agonists may pose safer alternative to current antidiabetic therapy with full PPAR gamma agonist. (C) 2008 Elsevier B.V. All rights reserved.”
“Background: Adding adjuvants such as MF59 (R) to influenza vaccines can enhance the immune response. This analysis evaluated the safety profile of MF59-adjuvanted [(+)MF59] compared with non adjuvanted [(-)MF59] vaccines in a large clinical database.\n\nMethods: Safety data were pooled from 64 clinical trials involving (+)MF59 seasonal and pandem ic influenza vaccines. Safety outcomes were analysed in the overall population and in subjects aged >= 65 years, in all clinical trials and in controlled trials only.

5 to 48 6 mg Fe (g dry tissue)(-1) The mean total scan time at r

5 to 48.6 mg Fe (g dry tissue)(-1). The mean total scan time at repetition time 1000 ms was 42% of that at repetition time 2500 ms. The repeatability coefficients for the two protocols were not significantly different from each other. A systematic difference in the measured R2 using each protocol was found indicating that an adjustment factor is required when one protocol is used to replace the other. The 95% limits of agreement between the two protocols were not significantly different from their repeatability coefficients ZIETDFMK indicating that the protocols can be interchanged without any

significant change in accuracy or precision of liver iron concentration measurement. Magn Reson Med 65:1346-1351, 2011. (c) 2010 Wiley-Liss, Inc.”
“Background and Objectives: Sound enamel manifests transparency in the near-IR (NIR) at 1310-nm, therefore the near-IR is ideally suited for high contrast imaging of dental caries.

The purpose of this study was to acquire images of early demineralized enamel on the buccal and occlusal surfaces of extracted human teeth using NIR reflectance imaging and compare the contrast or those images with the contrast of images taken using other methods.\n\nMaterials and Methods: Fifteen human molars were used in this in vitro study. Teeth were painted with a clear acid-resistant. varnish, leaving two 2 mm x 2 mm windows oil the buccal and occlusal beta-catenin activation surfaces of each tooth for demineralization. Artificial lesions Were produced ill the. exposed windows after a 2-day exposure to a demineralizing solution at pH 4.5. Lesions were imaged using NIR transillumination, NIR and visible light reflectance, and fluorescence

imaging methods. Crossed polarizers were, used where appropriate to improve contrast. Polarization sensitive optical coherence tomography (PS-OCT) was also Used to non-destructively assess the depth and severity of demineralization in each sample window.\n\nResults: NIR reflectance imaging had the highest image contrast for both the buccal and occlusal groups and it was significantly higher contrast learn more than visible light reflectance (P < 0.05).\n\nConclusion: The results of the study suggest that NIR reflectance imaging is a promising new method for acquiring, high contrast images of early demineralization on tooth surfaces. Lasers Surg. Med. 41:208-213, 2009. (C) 2009 Wiley-Liss, Inc.”
“We present a generalization of the numerical self-consistent mean-field theory of polymers to the case of grafted polymers under simple shear. The general theoretical framework is presented, and then applied to three different chain models: rods, Gaussian chains, and finitely extensible nonlinear elastic (FENE) chains. The approach is self-consistent at two levels.

Since the announcement awareness grew in Europe, with extensive p

Since the announcement awareness grew in Europe, with extensive public media dissemination and regulatory actions. This resulted in a steep increase in the spontaneous reports of exposed cases, a decrease in diagnostic lag times of this rare, underdiagnosed disease and finally victim compensation.

The signaling countries conducted rapid risk assessment studies to quantify the signal to the best of their abilities, in the midst of the public awareness, most of which could not distinguish between a vaccine and an awareness effect. Due to the strong but variable associations from the epidemiological studies, the search for biological mechanisms started. Currently it is not yet understood how Pandemrix might cause narcolepsy, and whether it would be specific to Pandemrix. The paper describes the current evidence and puts forward the questions that check details remain to be answered, find more which are relevant for future pandemic preparedness when adjuvants may be

used for dose sparing. (C) 2015 Published by Elsevier Ltd.”
“This work presents a modified method, namely coaxial electrohydrodynamic atomization, for the preparation of microspheres with distinct core/shell structures. This allows the encapsulation of two drugs with different characteristics in hydrophilic properties in one single step. Variation of ratios between outer flow and inner flow produces polymer microspheres with different core/shell ratios, and consequently

results in variable release rates of drugs. Significant changes in release patterns were demonstrated when the distributions of the two drugs in microspheres were swapped. Moreover, cell culture experiments and animal experiments have been carried out to testify the performances of different CUDC-907 concentration microspheres in cytotoxicity, cellular apoptosis in vitro and tumor inhibition against subcutaneous U87 glioma xenograft in BALB/c nude mice. These findings present the advantages and possible application of this kind of multi-drug release system in treating brain tumors. Moreover, the release rates and characteristic sequences of multi-drugs can be tailored and tuned according to treatment necessity and applied in treating other kinds of tumors. (C) 2010 Elsevier Ltd. All rights reserved.”
“Platelet glycoprotein Ib alpha (GpIb alpha) interactions with von Willebrand factor (VWF) are a critical early event in platelet adhesion, which contributes to hemostasis and thrombosis. Here we report the structure of a complex between GpIb alpha and a potent peptide inhibitor. The cyclic peptide (CTERMALHNLC) was isolated from a cysteine-constrained phage display library, and in the complex this forms one and a half turns of an amphipathic alpha-helix, the curvature of which facilitates contacts with the curved concave face of the GpIb alpha leucine-rich repeats. The peptide has only limited overlap with the VWF binding site.

The intervention was initiated at a Level

I trauma center

The intervention was initiated at a Level

I trauma center and aimed to link AI/AN patients to their distant tribal communities. Thirty AI/AN patients were randomized to the intervention or to usual care. Assessments at baseline, 3 months, and 6 months included self-reported lifetime cumulative trauma burden, Native healing requests, and symptoms of posttraumatic stress, depression, and alcohol use. Generalized estimating equations ascertained differences between groups over time. Ninety-four percent of eligible patients participated; follow-up at 3 and 6 Panobinostat molecular weight months was 83%. Participants had high numbers of lifetime traumas (mean = 5.1, standard deviation = 2.6). No differences between the intervention and control groups were observed in posttraumatic stress symptoms, depression symptoms, or alcohol use at baseline or follow-up time points. Among intervention patients, 60% either requested or participated in traditional Native healing practices and 75% reported that the intervention was helpful. This effectiveness trial demonstrated learn more the feasibility of recruiting and randomizing injured AI/AN patients. Future efforts

could integrate evidence-based interventions and traditional Native healing into stepped collaborative care treatment programs.”
“Aims and objectives To search for instruments to measure compliance with infection control practices and to report on which dimensions and contents the instruments evaluate, their psychometric characteristics, compliance and factors influencing compliance. Background Low compliance with infection control practices has been reported among healthcare professionals

around the world over the years. Existing data concerning health professionals’ compliance with standard Selleck PLX4032 precautions are based on measuring instruments. Design Integrative review. Methods The descriptors were identified and used separately and in combination to search in the following databases: Lilacs, PubMed (MEDLINE), ISI Web of Knowledge, Scopus and CINAHL. The selected articles complied with inclusion and exclusion criteria. Results Twenty-three studies were analysed, resulting in the identification of 18 instruments. No instrument addressed all compliance topics, and the most commonly addressed topics were the use of personal protective equipment, hand hygiene and safe practices in the handling of cutting material. Most authors explored content validity and some performed reliability analysis by means of Cronbach’s alpha and test-retest. Countries in the sample have different human development indices, and countries with medium and low human development indices show less compliance. Some variables were strong predictors of compliance: training, perceptions of safe environment, perception of obstacles to comply with standard precautions and knowledge. Conclusions Compliance is below the recommended levels.

On day 21, cell counts of total cells, macrophages, neutrophils a

On day 21, cell counts of total cells, macrophages, neutrophils and lymphocytes, alone with TNF- in bronchoalveolar lavage fluid (BALF) were measured. HE staining and Belnacasan Masson’s trichrome (MT) staining were used to observe the histological alterations of lungs. The Ashcroft

score and hydroxyproline content of lungs were also measured. TGF-1 and -SMA mRNA and protein were analyzed. Activation of NF-B was determined by western blotting and electrophoretic mobility shift assay (EMSA). On day 21 after bleomycin stimulation, andrographolide dose-dependently inhibited the inflammatory cells and TNF- in BALF. Meanwhile, our data demonstrated that the Ashcroft score and hydroxyproline content of the bleomycin-stimulated lung were reduced by andrographolide administration. Furthermore, andrographloide suppressed

TGF-1 and -SMA mRNA and protein expression in bleomycin-induced pulmonary fibrosis. Meanwhile, andrographolide significantly dose-dependently inhibited the ratio of phospho-NF-B p65/total NF-B p65 and NF-B p65 DNA binding activities. Our findings indicate that andrographolide compromised bleomycin-induced pulmonary inflammation and fibrosis possibly through inactivation of NF-B. Andrographolide holds promise as a novel drug to treat the devastating disease of pulmonary fibrosis.”
“Heart failure after a myocardial infarction continues to be a leading killer in the Western world.

this website Currently, there are no therapies that effectively prevent or reverse the cardiac damage and negative left ventricular remodeling process that follows a myocardial infarction. Because the heart has limited regenerative capacity, there has been considerable effort to develop new therapies that could repair and regenerate the myocardium. Although cell transplantation alone was initially studied, more recently, tissue engineering strategies using biomaterial scaffolds have been explored. In this review, we cover the different approaches to engineering the myocardium, including cardiac patches, which are in vitro-engineered constructs FRAX597 Cytoskeletal Signaling inhibitor of functional myocardium, and injectable scaffolds, which can either encourage endogenous repair and regeneration or act as vehicles to support the delivery of cells and other therapeutics. (C) 2013 Mayo Foundation for Medical Education and Research”
“Based on intuitive analyses and statistical calculations using data from orthogonal array experiments, the optimal concentrations of K(2)HPO(4), NaCl, MgSO(4)center dot 7H(2)O, and (NH(4))(2)SO(4) in cell growth medium of Aureobasidium pullulans HP-2001 were measured as 7.5, 1.0, 0.1, and 2.4 g/L, respectively, whereas those for the production of pullulan were 2.5, 0.25, 0.8, and 0.3 g/L, respectively. The most important factor for cell growth and production of pullulan by A. pullulans HP-2001 was identified as K(2)HPO(4).

The molecular profiles of TCRBV CDR3 were determined using gene m

The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak.\n\nResults: CD4(+)CD25(high) Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The prevalence of CD4(+)CD25(high) Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4(+)CD25(+) Tregs in ACLF and CHB

patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.\n\nConclusions: The CD4(+)CD25(high) Tregs prevalence in peripheral blood is indicative of disease severity in ACLF Quisinostat or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ”

may be used in helping diagnosis and treat patients with ACLF.”
“BACKGROUND: Internet addiction disorder is an interdisciplinary phenomenon and it has been studied from different viewpoints in terms of various sciences such as medicine, computer, sociology, law, ethics, and psychology. The aim of this study was to determine the association of psychiatric symptoms with Internet addiction while controlling for the effects of age, gender, marital status, and educational levels. It is hypothesized, that high levels of Internet addiction are associated with psychiatric LY3023414 clinical trial symptoms and are specially correlated with obsessive-compulsive disorder symptoms.\n\nMETHODS: In a cross-sectional study, a total number of 250 students from Isfahan’s universities were randomly selected. Subjects completed the demographic questionnaire, the Young Diagnostic 17DMAG chemical structure Questionnaire (YDQ) and the Symptom Checklist-90-Revision (SCL-90-R). Data was analyzed using the multiple logistic

regression method.\n\nRESULTS: There was an association between psychiatric symptoms such as somatization, sensitivity, depression, anxiety, aggression, phobias, and psychosis with exception of paranoia; and diagnosis of Internet addiction controlling for age, sex, education level, marital status, and type of universities.\n\nCONCLUSIONS: A great percentage of youths in the population suffer from the adverse effects of Internet addiction. It is necessary for psychiatrists and psychologists to be aware of the mental problems caused by Internet addiction.”
“Esophageal cancer is the third most common malignancy of the alimentary tract. The incidence of esophageal cancer has steadily increased over the past three decades. Almost all therapeutic modalities for esophageal cancer are associated with a considerable mortality and morbidity. Consequently, there has been growing concern regarding effective management of esophageal cancer.

Such limitation has led scientists to design clinically relevant,

Such limitation has led scientists to design clinically relevant, innovative and multifaceted solutions including the use of nanobiomaterials. Use of cytocompatible nanobiomaterials holds great promise and has gained attention of researchers, worldwide. Various nanobiomaterials are being explored to increase the survival efficiency and direct

differentiation of stem cells to generate tissue-specific cells for biomedical research and futuristic therapies. These materials have superior cytocompatability, mechanical, electrical, optical, catalytic and magnetic properties. Non-invasive visualization of the biological system has been developed CAL-101 inhibitor using magnetic nanoparticles and magnetic resonance imaging [MRI] approaches. Apart from viral vectors, non-viral carriers such as DNA nano carriers, single stranded RNA nanoparticles, liposomes and carbon CYT387 cell line nanotubes/wires are being exploited for gene delivery into stem cells. This article reviews potential application of various biocompatible nanomaterials in stem cell research and development.”
“AIM: The aim of this randomized study was to compare exercise program to control group regarding pain, back disability, behavioural outcomes, global health measures and back mobility who underwent microdiscectomy operation. MATERIAL and METHODS: Thirty patients who underwent lumbar

microdiscectomy were

randomized into exercise and control groups. After surgery, patients in the exercise group undertook a 12-week home based exercise program, started immediately postsurgery and concentrated on improving strength and endurance of the back, abdominal muscles, lower extremities and mobility of the spine and hips. Outcome measures were: Oswestry Disability Index (ODI), Beck Depression scale, lumbar schober, Visual Analogue Scale (VAS), return to work (return-to-work selleck chemicals status), generic functional status (SF-36). RESULTS: Treatment compliance was high in both groups. Surgery improved pain, disability, general health status, lumbar mobility and behavioural status. After the exercise program, the exercise group showed further improvements in these measures at 12 week after surgery. CONCLUSION: A 12-week postoperative exercise program starting immediately after surgery can improve pain, disability, and spinal function in patients who have undergone microdiscectomy.”
“Objectives: Oxytocin (OT) has long been implicated in maternal bonding, sexual behavior and social affiliation behaviors. This paper reviews the wide effects of oxytocin and its key role in well-being.\n\nMethods: Studies were identified through Medline, Pubmed, and PsychINFO search of the English-language literature from the past sixty years (1959 to 2009) using the key word “oxytocin” in human studies.

81; 95% CI, 2 11 to 3 75; P=0 001) Conclusions-For the treatm

81; 95% CI, 2.11 to 3.75; P=0.001).\n\nConclusions-For the treatment of multivessel coronary artery disease, percutaneous coronary intervention with DES implantation showed equivalent long-term mortality as CABG.”
“CD47, a receptor for thrombospondin-1, limits two important regulatory axes: nitric oxide-cGMP signaling and cAMP signaling, both of which can promote mitochondrial biogenesis. Electron microscopy revealed increased mitochondria( find more densities in skeletal muscle from both CD47 null and thrombospondin-1 null mice. We further assessed the mitochondria status of CD47-null vs WT mice. Quantitative RT-PCR of RNA extracted from tissues of 3 month old mice revealed dramatically

elevated expression of mRNAs encoding mitochondrial proteins and PGC-1 alpha in both fast and slow-twitch skeletal muscle from CD47-null mice, but modest to no elevation in other tissues. These observations were confirmed by Western blotting of mitochondria! proteins. Relative amounts of electron transport enzymes and ATP/O-2 ratios of isolated mitochondria were not different between mitochondria AICAR supplier from CD47-null and WT cells. Young CD47-null mice displayed enhanced treadmill endurance relative to WTs and CD47-null gastrocnemius had undergone fiber type switching to a slow-twitch pattern of myoglobin and myosin heavy chain expression. In 12 month old mice, both skeletal muscle mitochondrial volume density and

endurance had decreased to wild type levels. Expression of myosin heavy chain isoforms and myoglobin also reverted to a fast twitch pattern in gastrocnemius. Both CD47 and TSP1 null mice are leaner than WTs, use CYT387 cell line less oxygen and produce less heat than WT mice. CD47-null cells produce substantially less reactive oxygen species than WT cells. These data indicate that loss of signaling from the TSP1-CD47 system promotes accumulation of normally functioning mitochondria in a tissue-specific and age-dependent fashion leading to enhanced physical performance, lower reactive oxygen species production and more efficient metabolism. (C) 2011 Elsevier

B.V. All rights reserved.”
“Some epidemiological studies suggest that vitamin A (retinol), vitamin E, and vitamin D (total 25-hydroxyvitamin D, 25(OH)D; 1,25-dihydroxyvitamin, 1,25(OH)(2)D) are protective against prostate cancer. However, the evidence is not conclusive, with positive and null associations reported for all three vitamins. Limitations of previous studies include small sample size, lack of population controls, and reliance on self-reported dietary intake. Few studies have explored the interactions of circulating 25(OH)D with 1,25(OH)(2)D or retinol, which are biologically plausible interactions.\n\nWe investigated the associations of circulating retinol, vitamin E, and 1,25(OH)(2)D with PSA-detected prostate cancer risk, stage, and grade in a case-control study nested within the Prostate Testing for Cancer and Treatment (ProtecT) trial.