Finally, the ImpNon scale examines impulsive, antisocial and eccentric forms of behaviour (Cochrane et al., 2010 and Mason and Claridge, 2006). A 2 (Group) × 4 (Schizotypal Factor) mixed ANOVA was used to explore differences on each component of schizotypy between the groups.

A main effect of group was observed [F(1, 58) = 7.49, p = <.01], with synaesthetes scoring higher overall compared to controls. There was also a significant interaction [F(3, 174) = 3.37, p = <.05]. Bonferroni corrected post-hoc t-tests revealed that this was because synaesthetes showed significantly higher levels of positive (UnEx) [t(58) = 2.58, p = <.05, d = .68] and disorganised schizotypy (CogDis) [t(58) = 2.65, p = <.05, d = .70] relative to the matched control group ( Fig. 1A). No significant differences were found between the groups selleck products in their levels of negative schizotypy (IntAn) [t(58) = .289, p = n.s, d = .08] or their ImpNon ( Fig. 1A) [t(58) = 1.53, p = n.s, d = .40]. Synaesthetes and controls also showed

significant positive correlations between UnEx scores and CogDis scores (synaesthetes: r = .490, p = <.01; controls: r = .486, p = <.01). Synaesthetes, but not controls, showed a significant positive correlation between UnEx scores Venetoclax concentration and ImpNon scores (r = .367, p = <.05). These findings show that synaesthesia for colour is linked to

an increase in positive and disorganized schizotypy, implying that the presence of synaesthesia is associated with widespread differences in cognition that extend beyond the synaesthetic experience itself. There are at least two potential mechanisms that may contribute to this effect: (i) the effect is modulated by co morbidity between synaesthesia and ID-8 other cognitive traits that are related to schizotypy; (ii) there maybe similarities in the underlying mechanisms that give rise to the perceptual reports associated with schizotypy and synaesthesia. In relation to cognitive traits, previous findings have linked heightened positive schizotypy to creativity (Nelson and Rawlings, 2010) and mental imagery vividness (Oertel et al., 2009). Synaesthesia has also been linked to higher levels of these cognitive manifestations (e.g., Barnett and Newell, 2008 and Ward et al., 2008). Therefore, in conjunction with mental imagery and creativity, increased positive and disorganised schizotypy may reflect a constellation of trait markers that are linked to synaesthesia. In this context, it is interesting to note that one mechanism that has been suggested to explain the relationship between increased schizotypy and both creativity and mental imagery is a difference in levels of inhibition/excitation (e.g., Grossberg, 2000 and Nelson and Rawlings, 2010).

This is because hip fracture patients made use of more health care resources, whereas

the general population did not require health care services. Therefore, the general population mortality rate would not be impacted by the national insurance program as heavily as the peri-operative mortality and short-term postoperative mortality. The estimated 1-year, 2-year, 3-year, 5-year, and 10-year follow-up mortalities were 16.32, 25.84, 33.40, 44.12, and 53.50, respectively. Compared with the general population, the highest SMR occurred at the first year after hip fracture and then decreased gradually for follow-up from the second year up to the 10th year after fracture. Gennaro et al. also reported very similar findings [31]. Furthermore, we analyzed the causes of death stratified by year of death for up to ten years following the index day (Appendix ZD1839 research buy 1). We found that cancer, diabetes, cardiovascular disease, cerebrovascular

disease, renal disease and pneumonia were the major causes, each of which is highly related to the aging process. Though they fluctuated slightly from year to year, overall each one’s contribution to death remained stable. Furthermore, we calculated the average age of death for every year and the results showed an increased age of death selleck compound in hip fracture patients (Appendix 4). We calculated the surgery type distribution every year and found that it remained stable (Appendix 2). Finally, we calculated the prevalence RVX-208 of comorbidities and found that Chronic Obstructive Pulmonary Disease (18.2%), Cerebrovascular disease (20.4%), Diabetes mellitus (24.1%) and peptic ulcer disease (10.1%) were most prevalent in the hip fracture cohort (Appendix 3). Annual mortality decreased gradually from 18.10% to 13.98%, whereas annual SMR also decreased from 13.80 to 2.98 during the study period. This finding may be attributed to the improvement in medical care and technology. The 1-month, 3-month, 6-month, 1-year, 2-year,

5-year, and 10-year follow-up mortality rates were 2.49, 6.45, 10.40, 16.32, 25.84, 33.40, 44.12, and 53.50, respectively. The 1-month mortality was 2.49% in Taiwan, lower than that of England (9.6%), Scotland (7%), and the US (8.9%, 5.2% to 9.3%) [10], [32], [33] and [34]. The 3-month mortality was 6.45% in Taiwan, lower than that of Norway (10%), Sweden (10%–20%), and the US (17.5%) [26], [33], [35] and [36]. The 1-year mortality was 16.32% in Taiwan, lower than that of Korea (17.8), Japan (19%), the US (16.9%, 12% to 32%), England (33%), Canada (30.8%), Denmark (29.2%), Finland (27.3%), and Sweden (21% to 33%) [9], [14], [25], [32], [34], [37], [38] and [39]. Haleem et al. reviewed published articles from 1996 to 1998 and found that mortality at six months and one year were 11% to 23% and 22% to 29%, respectively [11]. Haentjens et al.

The training protocol was started at this time to evaluate the role of physical training in reversing or decreasing the harmful effects of the estrogen deficiency.

Exercise training was performed in a swimming pool (180 cm × 70 cm × 60 cm) filled with tap water warmed to approximately 30–32 °C at the same time of day (14:00–16:00 pm) in all training sessions during 8 weeks. The exercise intensity was progressively increased over the first two weeks. learn more In the first day, the rats swam for 10 min, and swim time was increased until the rats were swimming for thirty minutes on the fifth day. In the second week, the swim time was increased each day until the animals could swim for 60 min while wearing a caudal dumbbell, weighing 5% of their body weight (overload) [43]. This protocol has previously been characterized as low to moderate intensity (with a long duration) based on improvements in muscle oxidative capacity [33]. The coronary function of rats was evaluated using the Langendorff preparation (Hugo Sachs Electronics™, March-Hugstetten, Germany). Forty-eight hours after the last exercise session, the animals were killed

by decapitation. After decapitation, their thorax was opened and the hearts were rapidly excised and placed in ice-cold modified Krebs buffer. The aorta was immediately cannulated with a 21 G needle and perfused with a modified Krebs buffer (composed of 120 mM NaCl, 1.26 mM CaCl2·2H2O, 5.4 mM KCl, 2.5 mM MgSO4·7H2O, 2 mM NaH2PO4·H2O, Olopatadine Entinostat 27 mM NaHCO3, 1.2 mM Na2SO4, 0.03 mM EDTA, and 11 mM glucose). The Krebs buffer was equilibrated with a carbogen mixture (O2

95% + CO2 5%, White-Martins Ind., RJ, Brazil) at a constant pressure of 100 mmHg to give a pH of 7.4 and kept at 37 °C. The perfusion flow was maintained at a rate of 10 mL/min by a peristaltic pump (MS-Reglo 4-channel, Hugo Sachs Electronics™), according to the Langendorff methods [35] and [47]. After a small surgical incision in the left atrium, isovolumetric cardiac pressure was recorded with a water-filled latex balloon (Durex, London, UK) inserted into the left ventricle (LV) through a steel catheter connected to a transducer (TPS-2 Statham transducer – Incor, Sao Paulo, SP, Brazil). The LV end-diastolic pressure was set at 8–10 mmHg by adjusting the balloon volume through a spindle syringe. The coronary perfusion pressure (CPP) and intrinsic heart rate (IHR) were continuously recorded with a sidearm of the aortic cannula with a pressure transducer (P23Db Statham transducer – Incor, Sao Paulo, SP, Brazil) connected to data acquisition system (PowerLab™, ADI Instruments, Bela Vista, NSW, Australia). After a stabilization period of 40 min, baseline values of CPP and IHR were determined. Then, the responsiveness of the coronary vascular bed was evaluated. A bolus injection (100 μl) of modified Krebs’s buffer was applied to determine volume-injection-induced changes in CPP and IHR.

g., Annamalai et al., 2007, Fan et al., 2010, Kripalani et al., 2007, Kumar et al., 2011 and Sabade et al., 2011). The simulated rainfall response to global warming by climate models is actually accompanied by a weakening of the southwest monsoon (e.g., Kripalani et al., 2003, Krishnan et al., 2013, Sabade et al., 2011, Stowasser et al., 2009 and Ueda et al., 2006). However, Rupakumar et al. (2006) have studied the effect of climate change in India by evaluating the present day simulation (1961–1990) of the

PRECIS climate model and have reported an increase in extreme rainfall along the west coast and check details western parts of central India. Several studies have investigated the vulnerability of Mumbai in the present and future climatic scenarios. Over the coming

decades, the pressures of urbanisation may be aggravated by manmade climate change and increase in greenhouse gases. In the future, an increase in rainfall volume and/or intensity could increase the risk of severe flooding. Global Climate Models (GCMs) give a divergent picture of how precipitation will change in Northwest India over this century. The ensemble mean of the GCM projections assessed in IPCC (2007) suggests a small average increase in the summer precipitation (roughly 5% of 1990 levels by the 2090s), however this small average masks large positive and negative changes projected by individual models. Ranger et al. (2011) have presented

a grim picture of Mumbai flooding and consequent economic losses during July 2005 floods and further analysed the situation selleckchem in future scenarios. Further the authors have stressed the need to consider the implications of PAK5 uncertainties in climate projections for adaptation planning in Mumbai. The authors have advocated the use of multiple projections from a range of available Global Climate Models and Regional Climate Models as a single scenario of future climate is by itself not adequate to inform robust adaptation decisions. This present study, to the knowledge of the authors, is the only study being conducted to investigate the effects of climate change on the potential impacts of extreme rainfall in study area using data from several climate models. Many studies worldwide have described the possible impacts of climate change on urban drainage infrastructures and analysed the specific impacts on various urban areas, e.g. (Mailhot et al., 2007 and Willems et al., 2012). These possible impacts could have serious implications for Mumbai, the economic hub of India. In this study, we analyse the change of various precipitation statistics due to climate change for the city of Mumbai. General circulation models (GCMs) are currently the best way to model the complex climate processes that occur at the global scale, i.e. for studying possible future changes in climate mean, variability, and extremes (Huntingford et al., 2005).

All experimental animals were observed once a day for signs of toxicity, mortality, and morbidity until the completion

of the treatment. The body weight of each animal was recorded at the initiation of the click here treatment and prior to bone marrow sampling. Peripheral blood samples (3 to 4 μL) from tail vein were collected at 48 h and 72 h after dosing and then applied to acridine orange-coated slides for 3 to 4 h at room temperature. The smear samples were microscopically examined with a fluorescent microscope (Zeiss, Oberkochen, Germany) for the number of reticulocytes (orange-red signal), and reticulocytes that contained at least one positive micronucleus (yellow-green signal). The results were expressed as the

frequency of reticulocytes per 1000 red blood cells and micronucleated reticulocytes per 1000 reticulocytes. All values presented throughout this manuscript were expressed as mean ± standard error of mean (SEM). Mean differences between the control and the treatment groups were analyzed by one-way ANOVA followed by Duncan’s test. Aberrant cells from each concentration were compared to the negative control values using Chi-square analyses. http://www.selleckchem.com/products/nutlin-3a.html A value of p < 0.05 was considered to be statistically significant. A resurgence of interest in natural products is spreading across many parts of the world currently as they are thought to be new alternative medicines for conventional therapies with fewer side effects. In East Asian countries and more recently in the United States, intensive research has increasingly demonstrated the potential beneficial health properties of compounds extracted from mushrooms for the prevention and management of cancer and other life-debilitating

diseases. For such reasons, the genotoxicity of culinary-medicinal mushrooms that are Adenosine used by the general population should be warranted in order to identify the ingredients that pose mutagenic and carcinogenic risks. To our knowledge, there have been no reports on the mutagenicity of H. erinaceus prior to this paper. Therefore, this is the first report undertaken to evaluate the genotoxicity of a standardized H. erinaceus mycelium enriched with 5 mg/g erinacine A by using the Ames test, the chromosomal aberration test, and the erythrocyte micronucleus test. The Ames test is widely used as an initial screening method to determine the mutagenic potential of newly discovered products since there is a high correlation between the positive responses in test mutagenicity and carcinogenicity [33] and [34]. The proximate analysis and HPLC analysis of EAHE mycelium are shown in Table S1 and Figure S1, respectively. These results are in line with those previously published [27].

We used the same initial dose of 10 μg/mL as used for the contact treatment. The insects were fed with blood containing parasites (2 × 106T. cruzi Dm28c clone/mL of blood) (group FPC) or not (FP), and were placed over the physalin B treated papers (25–30 insects/176 cm2) during the whole experiment period. Parasites adhesion to the perimicrovillar membrane of the insect vector posterior midgut is an important stage for parasite development in the host. Therefore perimicrovillar membrane of the treated insects was dissected and prepared in saline buffer to count the number of

parasites adhered under an optic microscope. We used membranes of control (C) and physalin B treated orally groups (F). The parasites, T. cruzi epimastigotes, were washed three times in PBS, and then resuspended in fresh BHI to a concentration of 3.0 × 106 cells/mL. The parasite suspension (200 μL) was incubated with the perimicrovillar membrane Olaparib manufacturer of each insect group inside microtubes for 30 min at 25 °C. Then the midgut preparations Lumacaftor solubility dmso were spread onto glass slides and the number of attached parasites was counted under a microscope ( Nogueira et al., 2007). A hundred randomly chosen epithelial cells from 10 different sites of each midgut preparation were counted. For

each experimental group 10 insect midguts were used. The microbiota of the R. prolixus digestive tract was assessed by counting bacteria colony forming units (CFU) that grew in brain heart infusion agar (BHI agar). The kinetics of microbiota growth in infected and non-infected insects was investigated daily for 30 days after feeding. The results demonstrated a peak of bacteria concentration at 8 days after feeding and a significant difference between infected and non-infected insects ( Castro et al., 2012). Therefore the entire digestive tract was dissected under sterile conditions (without contact of the samples with the outside cuticle of the insect and inside a biological

safety flow cabinet) eight days after treatments and homogenized in 1 mL of sterile PBS. Samples were then immediately transferred to Thalidomide ice, diluted 10−5, 10−7 or 10−9 with PBS, and 20 μL aliquots were spread onto BHI agar plates, and then incubated overnight at 30 °C. After this the CFUs were counted. We analyzed the effects of physalin B in the anterior midgut nine days after feeding because in our recent research (Castro et al., 2012), the antibacterial activity is more intense in this condition. The TB assay was modified from Thomas et al., 1999 and Bexfield et al., 2004. Each anterior midgut dissected was placed in a tube with 200 μL of Milli-Q water, and then it was homogenized and centrifuged at 8000 g for 1 min at 4 °C. Aliquots of 70 μL from supernatant were transferred into tubes containing 630 μL of Milli-Q water. They were then sterilized in 0.22 mm sterile filters and frozen at −20 °C.

Following intra-cranial administration, levels of H435A in the brain hemispheres did not change over a 24 h period while the levels of N434A significantly decreased over time. Intranasal-to-CNS delivery was used initially because it is a non-invasive technique. For maximal delivery to the brain hemispheres, the test article had to be

applied directly to the olfactory epithelium of the nose (Thorne et al., 2004). Test article then moves in a paracellular fashion, driven by diffusion, past the olfactory epithelium, and into the nasal lamina propria beneath (Dhuria et Dasatinib al., 2010). This space is contiguous with channels through the cribriform plate, which contain the axons of the olfactory neurons. Earlier studies have shown that a certain percentage of cerebrospinal fluid (CSF) exits the

brain through the cribriform plate and enters nasal lymphatics which drain into the cervical lymph nodes (Bradbury et al., 1981, Bradbury and Westrop, 1983 and Cserr et al., 1992). This process could represent a hindrance to molecular flow into the brain. However, subsequent ultra-structural studies have demonstrated the existence of neuronal channels that traverse the subarachnoid space (Field et al., 2003 and Li et al., 2005) thus preventing direct interaction with CSF. These channels are believed to provide direct access into the parenchyma of the brain hemispheres (Dhuria et al., 2010 and Lochhead and Thorne, 2012). Functional studies using both small and large molecules have shown delivery to the hemispheres via this mechanism despite this potential hindrance. Ipilimumab The main driving force for uptake is the concentration gradient

of the test article (Barakat et al., 2006, Evseev et al., 2010, Furrer acetylcholine et al., 2009, Gorbatov et al., 2010, Hoekman and Ho, 2011, Romanova et al., 2010 and Sipos et al., 2010). However, there are two main factors that do impinge on the efficiency of CNS uptake of a molecule using this technique: those related to formulation, and those related to physicochemical characteristics. The formulation considerations include the type, pH, and tonicity of the buffer, and/or the presence of excipients representing transport enhancers, stabilizers, and muco-adhesives (Pujara et al., 1995 and Washington et al., 2000). The important physicochemical characteristics include molecular size, hydrophobicity/hydrophilicity, surface charge, and mucus compatibility (Vyas et al., 2006). The test articles used in these studies are similar in terms of their physicochemical characteristics. Both H435A and N434A have pI values of 7.2, differ by just one amino acid, and have virtually identical secondary and tertiary structures as measured by circular dichroism. Functionally, they only differ in their affinity for the FcRn receptor, have no known targets in the brain and therefore are uniquely suited to use address the role of FcRn in IgG efflux from the brain.

Although currently accruing trials have included patients with limited nodal disease, it will be several years Selleck PLX-4720 before mature data are available. Although tumor size has been used in the past to

risk stratify BCT patients, recent data suggest that it may not be associated with IBTR in patients undergoing APBI [82] and [83]. An analysis of more than 1800 patients treated with BCT and WBI found pathologic tumor size to be associated with IBTR and DM; however, a recent pooled analysis of outcomes from the ASBS Registry and WBH did not find tumor size to be associated with IBTR, with nearly 2000 patients evaluated (83). ABS Guideline: Tumor size should be less than or equal to 3 cm (including pure DCIS). To date, limited research has been performed to determine the ideal tumor size criteria for patients undergoing APBI. As noted previously, because of paucity of data available, limited conclusions can be drawn. Furthermore, because of selection bias, published studies are of limited value with a preponderance of subcentimeter tumors. Based on these findings, and consistent with previously published consensus criteria and guidelines along with clinical trial inclusion criteria, the guideline remains 3 cm. In addition, the panel does not believe that APBI

should be PD-0332991 mouse applied off-protocol in the neoadjuvant setting. Previous randomized trials of women undergoing BCT have documented increased rates of IBTR with younger women (8). An analysis of the Christie Hospital randomized trial with partial breast irradiation did not find age to be associated with breast recurrence on multivariate analysis (84). However, the pooled analysis

previously discussed found a trend for increased rates of IBTR for patients under 50 years old (83). ABS Guideline: Patients should be 50 years or older. To date, limited research has been completed to determine the ideal age criteria for patients undergoing APBI. As noted previously, because of paucity of data available, limited conclusions can be drawn but in light of the pooled analysis finding a trend for increased rates of IBTR in patients under age 50 years and similar data seen in patients undergoing WBI, the guideline has been left at 50 years old. The panel did not believe that Olopatadine there were sufficient data to specifically exclude younger patients from being treated with APBI but felt that caution was still warranted. Nonetheless, implicit in this recommendation is the acknowledgment by the panel that further data from Phase III trials will be needed to conclusively establish the efficacy of APBI in younger patients. Although no recent data documenting an increased risk of IBTR in these patients when treated with APBI (beyond that seen when WBI is used) have been conclusively identified, the panel felt that the inclusion of women less than age 50 years was not appropriate at this time. Increasing data have suggested that estrogen receptor negativity is associated with IBTR in women undergoing APBI.

Australia) that converts the digitized images to grayscale images (black and white) after color selection ( Solomon, 2009). Fig. 1A and B illustrates the color segmentation which Anti-cancer Compound Library cost allows the selective capture of the immunoreactive sites against the desired antibody and measures their pixel densities. Quantitative analysis was accomplished by calculating the percentage of pixels of the anti-AQP4 and anti-GFAP in the white matter and granular, Purkinje and molecular layers of the cerebellar cortex separately. All numerical results were analyzed using the GraphPad Prism software package (San Diego, CA, USA) and expressed

as the mean ± standard error (S.E.). Differences between data means of saline-treated and PNV-treated groups were determined by the unpaired Student t-test with a p value ≤ 0.05 indicating statistical significance. Two-way analysis find more of variance

was used when appropriate to test age/temporal differences in the response to venom effect. The AQP4 and GFAP immunoreactivity of astrocytes was co-localized among the neuron bodies of the granular and Purkinje layers and widespread throughout the width of the molecular layer with the difference that the glial processes appeared well-defined in the anti-GFAP reaction. The anti-AQP4 reaction, although strong, was more diffuse. In animals injected with PNV, there was gradual time-dependent increase in the intensity of the immunolabeling in the white matter and layers of the cerebellar cortex for both P14 and adults. Fig. 2, Fig. 3 and Fig. 4 were chosen to illustrate the reaction pattern at two time intervals

(2 h and 24 h) for either P14 rats or adults; the figures also display the calculation of the density of pixels relative to the immunoreaction intensity throughout the period of observation. There is no significant difference in the physiological expression of AQP4 and GFAP in the white matter of adult and P14 rats at the different time-points after saline solution injection (Fig. 2C and F). However, rats administered PNV showed a 103.8% increase of AQP4 expression in adult animals (*p ≤ 0.05) and a 77.5% (**p ≤ 0.01) in neonate animals after 24 h ( Fig. 2C). The venom also caused a 57.3% increase in the GFAP expression after 24 h only in the astrocytes ID-8 of P14 animals (*p ≤ 0.05). Although not significantly, AQP4 expression was 11%–20% higher in P14 PNV-treated animals (ranging from 16.48 ± 1.06 at 2 h to 27.73 ± 2.57 at 24 h, respectively) than in adult PNV-treated ones (where it ranged from 13.68 ± 2.03 at 2 h to 24.94 ± 3.55 at 24 h, respectively). In contrast, the values for GFAP were in general slightly higher for adults than for P14 animals. The two-way analysis of variance showed that the time elapsed between envenomation and animal euthanasia interfered with the expression of AQP4 and GFAP in the white matter of neonates and adults (*p ≤ 0.05). Also, there was interference of the age variable in the expression of AQP4 and GFAP at 24 h only.

It is possible that the lower viral load in the 3TC group at baseline resulted in a lower rate of virological failure and the detection of resistance mutation, however as the difference between the two groups was non-significant (p = 0.27) we would not expect this to significantly influence our results. A major limitation to our study concerns the unsystematic approach to resistance testing performed in failing patients. This may partly reflect the changing advice from clinical guidelines on resistance testing over time. As less than a fifth of patients check details had resistance tests

performed at the time of virological failure we may have underestimated the incidence of resistance mutation. Additionally, a significantly higher proportion of patients failing on 3TC had resistance tests performed compared to those failing on FTC containing regimens (19.1% v 14.0% (p = 0.03)) which may have selected towards a higher

frequency of resistance detection in the FTC group. In conclusion, although there is a trend towards increased risk of development of M184V or K65R resistance mutations in patients taking 3TC rather than FTC, this fails to reach significance. Overall we observed very low rates of virological failure in patients taking either regimen which suggests that other factors, including cost and patient acceptability, may become increasingly important when choosing between these agents. Steering Committee: Celia Aitken, Gartnavel General Hospital, Glasgow; David Asboe, Anton Pozniak, Chelsea & Westminster Hospital, London; Clare Booth, Royal Free NHS Trust, London; Patricia Cane, PLX-4720 research buy Health Protection RANTES Agency, Porton Down; Hannah Castro, David Dunn, David Dolling, Esther Fearnhill, Kholoud Porter, MRC Clinical Trials Unit, London; David Chadwick, South Tees Hospitals NHS Trust, Middlesbrough; Duncan Churchill, Brighton and Sussex University Hospitals NHS Trust; Duncan Clark, St Bartholomew’s and The London NHS Trust; Simon Collins, HIV i-Base, London; Valerie

Delpech, Health Protection Agency, Centre for Infections, London; Anna Maria Geretti, University of Liverpool; David Goldberg, Health Protection Scotland, Glasgow; Antony Hale, Leeds Teaching Hospitals NHS Trust; Stéphane Hué, University College London; Steve Kaye, Imperial College London; Paul Kellam, Wellcome Trust Sanger Institute & UCL Medical School; Linda Lazarus, Expert Advisory Group on AIDS Secretariat, Health Protection Agency, London; Andrew Leigh-Brown, University of Edinburgh; Nicola Mackie, Imperial NHS Trust; Chloe Orkin, St. Bartholomew’s Hospital, London; Philip Rice, St George’s Healthcare Trust, London; Deenan Pillay, Andrew Phillips, Caroline Sabin, University College London Medical School; Erasmus Smit, Health Protection Agency, Birmingham Heartlands Hospital; Kate Templeton, Royal Infirmary of Edinburgh; Peter Tilston, Manchester Royal Infirmary; William Tong, Guy’s and St.