A generation of research has led to this inescapable conclusion. A vast body of literature including complete textbooks, chapters, and aggressive public and professional education campaigns fully explicate this positive message.1-3 Yet, among ourselves, we are

generally- less positive about the impact of our treatments on our patients’ lives. We will agree that most patients do pretty well most of the time on most treatments. But we will also agree that this is not nearly good enough and much more needs to be learned about Inhibitors,research,lifescience,medical how treatments work. What, in particular, don’t we know as well as we would like? Why do treatments rarely work as well in practice as they do in clinical trials? Why are the approaches Inhibitors,research,lifescience,medical to treatment that are studied in research settings rarely the

ones that are used in practice? Does treatment enhance functioning? Docs early treatment predict a more favorable response? How can we keep people well once they have been made well? What approaches should be used for the treatment-resistant patient? These are the sorts of questions that are raised within the context of what has been called a public health model of treatment.4 These are questions we cannot yet answer as well as we would like, however, largely because the direction and culture of treatment research has been determined by a more narrowly defined regulatory Inhibitors,research,lifescience,medical model.5 This regulatory model has been Inhibitors,research,lifescience,medical the dominant force shaping treatment research in the past and we will explore some of its limitations below. Traditional (regulatory) clinical trials: strengths and weaknesses Most treatment studies are done with a very specific purpose in mind: to gain Afatinib mouse approval or acceptance of a particular therapeutic modality. These studies are usually referred to as trials to establish efficacy. This type of consideration

is appropriately referred to as a “regulatory” one. Research following the regulatory model is specifically geared to the legal requirements of Inhibitors,research,lifescience,medical drug approval and registration. Although there is no equivalent to the Food and Drug Administration (FDA) for psychotherapy, the methodology of the regulatory model has been adopted in that from field as well. In order to establish efficacy, it is essential that pure disease entities are isolated. This has led to the practice of eliminating from clinical trials all patients with comorbid illnesses, coexisting conditions, and even potentially compromising psychosocial or environmental characteristics. Dimensions of outcome are limited to the direct symptomatic measures of that disease. Observation periods are, typically, very short. In order to prevent administrative or delivery problems from masking the effect of the treatment, clinicians are carefully selected and trained.

The iron atoms on the nanoparticle surface were coordinated via the 1,2-diols of the PGA block, which resulted in particle stabilization [159]. Iron oxide GSK1120212 supplier nanoparticles stabilized by carboxyl coordination of the surface oxide molecules were prepared by high-temperature decomposition of tris(acetylacetonate) iron(III) [Fe(acac)3] in the presence of monocarboxyl-terminated PEG [160]. Inhibitors,research,lifescience,medical Postproduction iron oxide nanoparticle decoration was performed using silane-terminating PEG. The silane group strongly interact with the oxide on the nanoparticle surface [161]. PEGs derivatised

with amino propyl trimethoxy silane (APTMS) or amino propyl triethoxy silane (APTES) were used. Phosphonic acid-terminated poly(oligoethylene glycol acrylate) [poly(OEGA)] was grafted to iron oxide nanoparticles

through the phosphonic acid end group that provide strong interaction with iron oxide nanoparticles. The poly(OEGA-) stabilized iron oxide nanoparticles showed significant stealth properties and exhibited Inhibitors,research,lifescience,medical low BSA adsorption (<30mgg−1 nanoparticles) over a wide range of protein concentration (0.05 to 10g L−1) [162]. Iron oxide nanoparticles synthesized by Fe(acac)3 decomposition in high-boiling organic solvents were postproduction PEGylated by the ligand exchange method. Inhibitors,research,lifescience,medical The nanoparticles produced with oleic acid, hexane, or trioctyl phosphine oxide (TOPO) coating were combined with PEG-silanes, PEG-PEI, PEG-PAMAM, PEG-fatty acid to allow Inhibitors,research,lifescience,medical for the coating exchange in aqueous medium [163–168]. Dopamine has been proposed as an alternative anchoring group to silane to coat magnetic

nanoparticles. Dopamine has high affinity for the iron oxide and can be conjugated to PEG through the amino Inhibitors,research,lifescience,medical group. PEG-dopamine was used to displace the oleate/oleylamine coating on the particles produced by high-temperature decomposition of Fe(acac)3 thereby converting the particle surface from hydrophobic to hydrophilic according to a postproduction protocol [169]. “Growing from” approaches based on living radical polymerization techniques such as Atom-Transfer Radical-Polymerization (ATRP) Thymidine kinase and Reversible Addition-Fragmentation chain-Transfer (RAFT) polymerization have been largely investigated to coat preformed iron oxide nanoparticles with PEG copolymers. ATRP polymerization of PEG-methacrylate (PEG-MA) was performed in aqueous solvent after a silane initiator (4-(chloromethyl) phenyl trichlorosilane) immobilization on iron oxide nanoparticle surface. After poly(PEG-MA) grafting, the uptake of the nanoparticles by macrophages was reduced from 158 to less than 2pg per cell confirming the excellent shielding capacity of this novel material [170]. Alternatively, the ATRP polymerization of the PEG-MA was performed according to a solvent-free protocol.

The extracts were subjected to phytochemical screening to determine the presence of alkaloid, Volasertib cost carbohydrate, phytosterols, fixed oils and saponins.

The inhibitors animals were administered orally with different doses of extract. The albino rats weighing 200–225 g were used for the study. The animals were continuously observed for the autonomic and behavioral changes for 12 h and mortality was observed for 24 h. No mortality was found even at 5000 mg/kg. The dose of 500 mg/kg b.w was selected for further activity. Stock solution 1 mg/ml of tannic acid was prepared in water. From the above solution 100 μg/ml was prepared. Different concentration ranging from 2 to 12 μg/ml was prepared. A volume of 1.25 ml FC reagent was added to each standard flask and kept for 5 min and then 2.5 ml of 20% sodium carbonate solution was added and made up to 10 ml with distilled water. The mixture was kept for 30 min and absorbance was recorded at 765 nm. The free radical scavenging activity of the extract was measured in terms of hydrogen Crizotinib concentration donating or radical scavenging ability using the stable radical DPPH. Solution

of DPPH (0.1 mM) in ethanol was prepared and 1 ml of this solution was added to 3 ml of the extract solution in water at different concentration (100–1000 μg/ml). Thirty minutes later, the absorbance was measured at 517 nm. Lower absorbance of the reaction mixture indicates higher free radical scavenging activity. Ascorbic acid was used as a standard drug. Rats were divided into five groups (n = 6). Group 1 (control) animals were administered a single dose of water (1 ml/kg body weight p. o) daily for 5 days and received olive oil (1 ml/kg body weight s. c.) on day 2 and 3.

Group II (CCl4) received water (1 ml/kg body weight p. o) once daily for 5 days and received CCl4: olive oil (1:1, 1 ml/kg body weight, s. c.) on day 2 and3. Group III received standard drug silymarin (25 mg/kg p. o.) once daily for 5 days. Test group animals, Group IV received isothipendyl 250 mg/kg body weight of chloroform extract and Group V received 500 mg/kg body weight of chloroform extract of CF p. o once daily for 5 days. Group III, IV and V received CCl4 and olive oil (1:1, 1 ml/kg body weight s. c.) on day 2 and 3 after 30 min of administration of the silymarin and extracts. Animals were sacrificed 24 h after the last treatment. Blood was collected, allowed to clot and serum was separated at 2500 rpm for 15 min and biochemical investigations were carried out. Liver was dissected out and used for histopathological studies. Blood sample was collected by retro-orbital puncture and centrifuged at 2000 rpm for 15 min. The serum was separated and used for the estimation of biochemical parameter like ALP, SGOT, SGPT and total bilirubin were assayed using assay kits (Coral Clinical Systems, Verna Ind Estate, Verna, Goa, India). The liver was dissected out and fixed in 10% formalin.

FUDR is the best drug for HAI because it has a short half life and a 94-99% first pass hepatic extraction. Drugs with high hepatic extraction (6) result in decreased systemic exposure. Prolonged exposure to FUDR in human cell lines greatly enhances its tumor inhibition (7). Nanashima et al. suggest that HAI- 5-FU or HAI-CPT may be better than HAI-FUDR, since their response Inhibitors,research,lifescience,medical rate was so high. Although the response rate was high in Nanashima’ study, investigators have found a 400 fold increase in tumor exposure using HAI-FUDR and only a 40-fold advantage with 5-FU (8). With 5-FU the extraction ratio may differ according to the mode of administration with a 11% extraction

rate with using usual administration but a 93% extraction rate with a 5-day infusion (9). Also, as the doses of 5-FU are increased the extraction rate decreases (10). HAI-CPT-11 seems to be not as effective as 5-FU or FUDR. With HAI-CPT there are increased systemic levels of SN-38 (which is the active metabolite) and lower levels of CPT compared Inhibitors,research,lifescience,medical to systemic CPT (11). This increase in SN-38 with HAI-CPT may be due to the high

carboxyl esterase content Inhibitors,research,lifescience,medical in the liver (12). A Phase II study showed low a partial response rate with HAI-CPT though toxicity was similar to systemic CPT (11). With Oxaliplatin, there is a steep dose response curve in human colon cancer cells. Oxaliplatin is a prodrug and the cytotoxic activity of oxaliplatin is initiated by formation of a DNA adducts. A liver extraction ratio of 0.47 for

oxaliplatin has been determined (13). To perform HAI therapy a catheter has to be placed to allow perfusion of the liver via Inhibitors,research,lifescience,medical the hepatic artery. These catheters can be connected to ports or to pumps. The ports can be placed by interventional radiology, while the pumps are usually placed by surgeons (14). The advantage to pumps is the ability of the pumps to remain patent, so there is continuous flow through the catheter, and one can deliver more cycles of chemotherapy. Inhibitors,research,lifescience,medical In one of the early randomized studies from England looking at HAI vs. systemic using a port, there were a lot of problems related to catheters and ports, so that 39% of patients were not able to receive HAI therapy (15). The study reported on the survival of all patients entered which included the 39% in HAI group who did not receive treatment and stated HAI did not improve results. They did not give the survival on the patients who those actually got HAI therapy. In the CALGB study, the investigators used a pump -which allows continuous flow into the perfused artery and therefore less thrombosis of the artery. Thus, 80% of patients were able to receive treatment in the HAI group. In the CALGB randomized study, there was an increase in overall survival, hepatic Selleck Olaparib progression-free survival and response rate with the HAI-FUDR + dexamethasone vs. systemic 5-FU/LV (4). Nanashima et al.

The results of the test are visible as gray-blue spots on the surface of the projections, and the visual results are determined semi-quantitatively by comparing the intensity of the color of the lower spot on each projection with the color scale provided by the manufacturer. The results of the samples were classified according to the cut-off point (10 IU/L) of the test. A spot with an intensity greater to or equal than the cut-off point indicated the presence of protecting anti-HAV levels. A spot with an intensity slightly less than that of the cut-off was considered an equivocal result, and the sample

was retested. A spot with a lower intensity than that of the cut-off was considered negative. The ImmunoComb® II HAV Ab assay has a limit of detection Selleck Y27632 of 10 IU anti-HAV antibodies/L, which is regarded as the minimum concentration of anti-HAV antibodies that PLX3397 in vitro indicates immunization has occurred. All of the samples were assayed three times, and identical visual readings for HAV were consistently observed by multiple investigators (three) for all samples. After determining the optimal salivary collection device, its applicability in a surveillance setting

was determined. This study was performed in four isolated communities in South Pantanal, Brazil, in difficult-to-access areas that are 661 km from the city of Campo Grande. This region is sparsely populated and is characterized by wetlands that hinder access to the coastal communities; access is only available by boat. For these reasons, fishing is the primary source of income and

livelihood for the majority of the population. The survey was conducted between April and June 2010, Metalloexopeptidase and the ChemBio® device was used to collect 224 matched serum and oral fluid samples using a non-probability sampling method from all consenting occupants of households. The entire population consisted of 691 individuals. The samples were placed in a cool box and returned to the laboratory after 15 days of collection for a total anti-HAV screening test. The sociodemographic characteristics of each member of the study were obtained with questionnaires. The influence of temperature and time exposure on the detection of anti-HAV antibodies in oral fluid samples was investigated. The parameters were based on the manufacturer’s storage instructions. Five concordant, matched samples (3 anti-HAV positive and 2 negative) that were collected in difficult-to-access areas of South Pantanal were selected for follow-up to evaluate anti-HAV antibody stability. Due to the unavailability of cooling in the surveillance setting, the oral fluid samples remained at unstable temperature conditions for 15 days. At the end of this exposure, the samples were sent to a laboratory in Rio de inhibitors Janeiro and were centrifuged and refrigerated at 2–8 °C until the first analysis (15 days after collection). The samples were stored for 210 days after collection and were retested every 30 days.

Neuropsychological testing allows the

differentiation of FDA approved Drug Library screening memory impairment with regard to age and education-specific normal values, eg, using the Wechsler Memory scale or the CERAD (Consortium to Establish a Registry for Alzheimer’s Disease) test. However, a normal score on such tests does not exclude memory impairment, since SMI has been revealed as a strong predictor of dementia and brain Inhibitors,research,lifescience,medical atrophy associated with dementia.13-17 In cases with SMI, or doubtful cases, repeated longitudinal testing to assess the course of the memory impairment is recommended. Amyloid imaging In 2004, a significant step towards an improvement of the ante-mortem diagnosis of AD and estimating the brain amyloid burden was made through the development of cerebral amyloid imaging using Pittsburgh compound B (PiB).18 Cerebral amyloid was not only detected in AD patients, but also in patients with LBD, which is in line Inhibitors,research,lifescience,medical with neuropathological findings of increased amyloid pathology in

LBD.19 In MCI patients an AD-like binding pattern of PiB was found in 60% of the patients20 and in longitudinal studies MCI patients who were PiB-positive had a higher risk of developing AD than patients with PiB-negative MCI.21 In cognitively healthy elderly patients, amyloid load was related to hippocampal atrophy Inhibitors,research,lifescience,medical and cognitive function, possibly indicative of preclinical AD.20 Recently AD and Parkinson’s disease-related dementia could successfully be distinguished due to different patterns of PiB binding.22 Since amyloid PET methodology is still under development, and the interpretation of results may be difficult in a single subject, criteria Inhibitors,research,lifescience,medical on the appropriate use of amyloid PET have been recently defined.23 In a recent study of a cohort of 64 clinically diagnosed AD patients, 14 of which were PiB-negative, CSF, MRI, and 18F-FDG-PET biomarkers were used to review the diagnosis.24 The results suggested argyrophilic grain disease in three cases, FTD in three cases, neurofibrillary Inhibitors,research,lifescience,medical tangle-predominant dementia in one case, and AD in two cases; however, there were no identified

cases of LBD. From these findings it may be concluded that the use of single biomarkers may GPX6 be misleading in the distinction between AD and non-AD, and the use of multiple biomarkers may reveal a clearer pattern that links to a specific underlying pathology. The distinction of AD and non-AD pathology using amyloid PET still seems to be limited with respect to single-subject analyses for clinical use; however, amyloid PET is a valuable research tool to study brain amyloid burden in vivo. Other imaging and cerebrospinal fluid biomarkers Other biomarkers that may help distinguish AD from non-AD related memory impairment include the CSF biomarkers Aβ42, t-tau, and p-tau, as well as imaging biomarkers such as MRI volumetry and 18F-FDG-PET.

407). Discussion Principal findings In this study it was possible to identify a combination of the BDI scale and a single item (Even while my relative was dying, I felt a sense of purpose in my life) answered at eight weeks post

loss to assess the propensity of bereaved individuals to develop complicated and www.selleckchem.com/products/BIBW2992.html prolonged reaction of grief after six months. Hence, we were able to construct a screening tool to identify people at risk of suffering complicated Inhibitors,research,lifescience,medical grief six months after bereavement and divide the risk of a pathological grief reaction of bereaved individuals into three distinct groups. This study points to the necessity of awareness of a depressive symptomatology among older people and family caregivers to deceased cancer patients in connection with bereavement as it might predict complications in the process of grief reactions. Strengths and weaknesses The sample Inhibitors,research,lifescience,medical size of this study was acceptable but a larger sample may have

added more statistical precision to the estimates. Though the sample in this study was population-based, there was a drop-out. Furthermore, part of this sample was Inhibitors,research,lifescience,medical recruited through a palliative care team, which means there is a risk of selection bias that need to be taken into account when considering the representativity of this population. Analyses showed that older people and females were underrepresented in this sample yet overall the mean age of the population Inhibitors,research,lifescience,medical in the sample was relatively

high. However, this means that the results might be underestimating the risk for older people and females, which should be taken into consideration when applying the screening tool and cut points might need adjustment in future studies. Another weakness that needs to be touched upon is the limitation in the performance of the screening tool. It was possible to identify a screening tool for early identification of individuals at risk of developing complicated grief, yet Inhibitors,research,lifescience,medical the tool seems to have some shortcomings that need to be taken into consideration when applying it in a clinical setting. The PPV of the potential screen was 40% for risk group 2 and the PPV for risk group 3 was 73% and therefore, we recommend to use only the cut off for risk group 3 in clinical practice when applied in addition to the clinical judgment of the professional. TCL A notable methodological weakness in this study and generally in studies on bereavement is the lack of a clear and distinct diagnosis and measure of pathological grief, which makes conclusions ambiguous to information bias and the lack of criterion validity. The ICG-R is a widely used self-report questionnaire on CG but still lacks research in validation of cut off points and in non-American populations. In this study we had to define a usable clinical cut off point, as the ICG-R is not standardised in a Danish population.

The HA ectodomain-encoding cDNA was cloned into the pCD5 expression vector for efficient expression in mammalian cells [9]. The pCD5-Cal/04/09 vector had been modified such

that the HA-encoding cDNA was cloned in frame with DNA sequences coding for a signal sequence, a GCN4 isoleucine zipper trimerization motif (KRMKQIEDKIEEIESKQKKIENEIARIKK) [10] and the Strep-tagII (WSHPQFEK; IBA, Germany). The HA ectodomain was expressed in HEK293T as previously described [11]. HA protein expression and secretion was confirmed by sodium dodecylsulfate (SDS)-polyacrylamide gel electrophoresis (PAGE) followed by western blotting using a mouse anti-Strep-tag antibody (IBA, Germany). Secreted HA proteins were purified Volasertib mouse using Strep-tactin sepharose beads according to the manufacturer’s instructions (IBA, Germany). The concentration of purified protein was determined by

using a Nanodrop 1000 spectrophotometer (Isogen Life Sciences) according the manufacturer’s instructions. Oligomeric status of the HA protein was determined by analyzing the elution profile using a Superdex200GL 10–300 column and by blue-native gel-electrophoresis. The vaccine was formulated with Specol [12] and [13] as an adjuvant, at 25 μg HA per dose of 2 ml. Pigs were vaccinated intramuscularly. Influenza virus A/Netherlands/602/2009 (H1N1)v was isolated from the first confirmed case in the Netherlands [14]. The patient was a 3-year old boy, developing a fever and symptoms of KPT-330 price respiratory disease after returning from Mexico with his family. A nasal swab was taken before the patient was treated with oseltamivir. Virus was initially grown on embryonated eggs, and subsequently passaged on Madin–Darby canine kidney (MDCK) cells before it was used to inoculate the pigs. This virus differs by 8 amino acids from the A/California/4/2009 Electron transport chain (H1N1)v strain [14]. Because it is, Libraries however, closer to the consensus sequence, it is considered representative of the circulating H1N1v influenza strains. Pigs were inoculated with a dose of 107.5 TCID50, suspended in 2 ml PBS, of which 1 ml was nebulised within

each nostril. Clinical symptoms and body temperature were recorded daily from day 3 before inoculation until the end of the experiment. At days 1–3 p.i. clinical symptoms and body-temperature were recorded twice per day with a 12 h interval. Serum samples were collected during both times of vaccination, at the time of inoculation, and 7, 10, 14 and 21 days p.i. Oropharyngeal and nasal swabs were collected daily from all animals still alive from day 0 to 11 p.i., and on days 14, 17 and 21 p.i. For oropharyngeal swabs multi-layered gauze dressings in a pair of tweezers were used to scrape the palatine tonsils at the dorsal pharyngeal wall, behind the soft palate. Nasal swabs were collected using sterile rayon swabs (Medical Wire & Equipment, Corsham, United Kingdom).

66 By and large, the F/S classification has not so far identified homogeneous groups for genetic research, possibly due to the likely presence of unexpressed genotypes in schizophrenia families.67 The present diagnostic classifications: DSM-IV and ICD-10 While European psychiatry rarely departed in a significant way from the nosological concepts formulated Inhibitors,research,lifescience,medical by Kraepelin and his followers, the practically undisputed dominance of psychodynamic psychiatry in North America over many decades came to an end with the “neo-Kraepelinian revolution” of the 1970s.68 The development of operational diagnostic

criteria,69,70 which were presumed to reflect the Kraepelinian categorical nosology, and their incorporation in the Third Edition of the Diagnostic and Statistical Manual of the American Inhibitors,research,lifescience,medical Psychiatric Association, DSM-III,19 was a turning point in the conceptualization of psychiatric disorders in general and of schizophrenia in particular. The likely gains in the reliability and reproducibility of diagnostic assessment based on explicit rules and criteria led to the Inhibitors,research,lifescience,medical adoption of a similar approach in the mental disorders chapter of the 10th revision of the World Health Organization’s

International Classification of Diseases, ICD-10,20 which in turn provided a stimulus for the development of DSM-IV.71 The diagnostic Inhibitors,research,lifescience,medical criteria of ICD-10 and DSM-IV were originally conceived with a view to achieving three fundamentally different goals: (i) to identify groups of patients with broadly similar clinical presentation and prognosis; (ii) to facilitate early diagnosis and choice of treatment; and (iii) to define a homogeneous heritable diagnostic category for genetic and other aetiological research.72 While the the first two goals have, by and large, been achieved as regards clinical utility of the criteria, attainment

of the Inhibitors,research,lifescience,medical third goal remains remote. There are both similarities Calpain and differences in the way the two classifications define schizophrenia. In contrast to DSM-IV, which provides a single set of “operational” diagnostic criteria for all users, ICD-10 was designed as a “family” of inter-related versions addressing different users. While the ICD-10 volume Clinical Descriptions and Diagnostic Guidelines is the conceptual “core” of the system, the ICD-10 Diagnostic Criteria for Research and the WHO Guide to Mental Health in Primary Care are derivatives for use in selleck screening library specific context.72 A comparison of the two sets of diagnostic criteria (in an abridged format) is provided in Tables IV and V. Table IV Table IV. ‘Candidate’ endophenotype markers in schizophrenia research (reviewed in ref 72). Table V Table V. ICD-10 / F2 group of disorders.

It is also possible that patients had had such conversations but either did not recall these when asked in the interview or perhaps did not want, at that point in time, to revisit those conversations. In an interview with the nominated HCPs providing P103 with care, they reported raising the topic of future care when first involved in her case (not mentioned by the patient in her interview) but had subsequently found it very difficult

to know how or whether to broach the topic again. Other participants reported some initial conversations about future plans but indicated that these had not been revisited for some time. One patient with heart Inhibitors,research,lifescience,medical failure reported some conversations with HCPs during a period when he was seriously ill and required hospitalisation but he had not subsequently followed up on these conversations: P203: I’ve Inhibitors,research,lifescience,medical been selleck compound feeling pretty good now for about two or three months I suppose. IV: So do those sorts of issues about (future plans) – do they go to the back of your mind when you’re feeling a bit better? P203: Oh yeah, I don’t

give them a thought … (P203 – first interview) This patient reported that when these conversations were initiated by HCPs, he wondered if they did so because he was close to dying; this may explain in part why he and the HCPs involved in his care had not revisited the discussions Inhibitors,research,lifescience,medical since, or had been reluctant to do so when he was feeling relatively better. Another cancer Inhibitors,research,lifescience,medical patient reported not having had any conversations with HCPs about preferences for where he wanted to be cared for. However, in the interview he revealed that he had given some thought to future plans about where he wanted to be cared for and die. IV: Has anybody talked to you about where you want to be cared for? In terms of staying at home or, has anyone had Inhibitors,research,lifescience,medical those sort of conversations with you? P101: No, no, not yet. No. I certainly want to stay

at home. I’ll be quite frank with you. If I’m going to die, I want to die at home; I don’t want to die in hospital. And the family, I think, understand that. In a follow up interview with the nominated HCPs involved in the care of this patient (after his death), they else recalled difficulties in knowing how and when to initiate conversations with him about his preferences: He never really, up until the very end, particularly considered himself to be palliative. Only near the end did he say ’I don’t think I’m winning this’ and that was the first indication I had that he was thinking along the lines of ’I’m going to die from this’. (HCP. S1 FU). This patient died suddenly from a heart attack. It can be very difficult for HCPs to judge timing of initiating conversations with patients. As identified by the HCPs in this case, that may mean that discussions about preferences are never raised: … we never actually asked him where he would like to die. It was always a case of let’s see what’s happening with you and he steered you away from that all the time (HCP2, S1 FU).