Draize testing also fails to elucidate the underpinning cellular and molecular mechanisms Pirfenidone clinical trial of toxicology. Since Draize assessments are based upon penlight or slit-lamp assessments,

they provide very little information regarding the primary or secondary responses in the cornea, iris or conjunctiva (Maurer et al., 2002). Despite its “gold standard” status, Draize testing was never formally validated to any significant degree (Freeberg et al., 1986b). Since the anatomy of the rabbit eye differs from the human eye structurally, physiologically and biochemically, differences in sensitivity to irritants can occur. For example, in comparison to humans, rabbit corneas are thinner, have lower tear production, blinking frequency and ocular surface sensitivity (Huhtala et al., 2008). Rabbits have larger conjunctival sacs and a nictitating membrane (third eyelid), which may aid the removal of a test substance from the ocular surface (Calabrese, 1987). There is almost no other field of science in which the fundamental experimental protocols have remained relatively unchanged for more than 40 years (Hartung, 2009), and yet consumers continually expect increased BIBF 1120 chemical structure safety and information

regarding their products. Worldwide, approximately £10 billion is spent on animal experimentation per annum, approximately £2 billion of which is on toxicological studies (Hartung, 2009). The cost associated with using, housing and maintaining colonies of live animals for toxicology testing of a single compound can exceed millions of pounds (Davila et al., 1998). Ethical (animal welfare), business (time and cost), scientific advances (reproducibility, mechanistic understanding) and legal concerns have all driven the demand for alternative, preferably animal-free testing platforms and protocols which are more precise and relevant to humans. There has been more focus on developing alternative testing techniques to Draize than all other in vivo

toxicity tests combined ( Huhtala et al., 2008). However, the development of alternative Quisqualic acid models has not advanced in a steady or continuous manner ( Dholakiya and Barile, 2013), although the ban on animal testing for cosmetics use (Regulation (EC) No. 1223/2009) has acted as a key driver for the development of alternative methods since this sector is constantly having to provide innovative and safe products. In Europe, with directive 2010/63/EU, there is a legal requirement to use alternatives where they exist. However, the reduction of animal use is primarily concentrated on toxicology studies since no government agency to date has eliminated animal use in basic biomedical research or pharmaceutical development. Low-volume eye-irritation tests (LVET) were developed in response to a recommendation from the National Research Council (NRC, 1977).

3 (20%) lesions could be snared without dissection, 3 lesions had to be dissected completely, and the remaining 9 had partial dissection followed by snaring. All lesions were nonpolypoid (IIa=60%, IIb=33%, and IIc=7%). They were precisely isolated in the patients with long-segment (33% of patients), short-segment (20%) and islands (47%) of Barretts. Pathology showed HGD in 4, T1a in 5, T1b in 4 and LGD in 2 patients. There was no residual in any patient; one follow-up is pending. Standardized ESD-U of early neoplasia of Barretts is feasible, safe and able to achieve R0 resection rates. The border of the neoplasia can

be identified using currently check details available IEE techniques. “
“Possibility of submucosal endoscopic myotomy for esophageal achalasia was reported by Pasricha

J et al. using porcine model, and then present authors developed clinical application of peroral endoscopic myotomy (P.O.E.M) for esophageal stenotic motility disorders including achalasia. A single institute registered prospectively study (UMIN 000001901) was carried out in Showa University Northern Yokohama Hospital. From September 2008 and November 2012, 300 consecutive cases (except one) of esophageal achalasia received POEM. Only one case received laparoscopic Heller Dor surgery because of patient’s SGI-1776 ic50 wish. Male was 127 cases and female was 173 cases. Average age was 45 y.o. (from 3 to 87 y.o.). Suffering period from dysphagia was 10.1 years on average (0.4-62.4). 41 cases of sigmoid achalasia were involved. Ten consecutive surgical failures also received POEM. Initial success rate of POEM was 98.2% (Eckerdt score<3)

and final success rate was 100%. In 5 cases second POEM procedure was successfully carried out. The reasons for second POEM procedure were either incomplete myotomy at primary POEM (2 cases) or advanced sigmoid achalasia (3 cases). Second POEM improved Eckerd score below 3 in all cases. Operating time was 110.2 (50-245 min). Length of myotomy was 14.1 cm on average (esophagus 11.2 cm, stomach 2.9 cm). Major complication was nothing. isometheptene 9 minor complications were experienced; one pneumothorax due to air insufflation, one intramucosal hematoma, one local peritonitis at lessor omentum and 6 mucosal injuries during the procedure. All of them are conservatively treated. Eckerdt score was 6.13 before POEM and dramatically decreased 1.37 in 2 months later, and 1.33 in one year later (statistically significant, Wilcoxon, Signed-ranks test, P<0.01). LES resting pressure was 27.3 mmHg before POEM and reduced to 13.4 mmHg after POEM (statistically significant, Paired T test, P<0.01). 4.9% in 300 cases received regular dose PPI to control post-POEM GERD. In all cases GERD symptom were easily controlled. There is no severe GERD which needs laparoscopic fundoplication. Final success rate (Eckerdt score<3) of POEM in 300 cases was 100% and middle-term outcome of POEM was excellent with no recurrence of dysphagia.

For comparison purposes, these analyses were repeated for the duplicate pairs in which neither video was presented with clinical details. Analysis of variance with terms for investigator and pair type were used to compare absolute differences. Reliability ratios for the UCEIS and overall severity, and intraobserver agreement at the descriptor level, were calculated as described previously. Bowker’s test for symmetry 11 tested for presentation order effects (ie, impact of viewing videos with clinical details before or after the blinded

version) on responses to descriptors. Two additional methods for calculating the buy PS-341 UCEIS were examined: 1. A normalized sum was used, in which descriptors were combined so as to contribute equally, as one-half “vascular pattern” plus one-third “bleeding” and one-third “erosions and ulcers”; the range of normalized UCEIS scores was then 0 to 3, with 17 possible scores. The design of this study did not permit a direct evaluation of the UCEIS in terms of sensitivity to change between videos at the individual patient level. Nevertheless, the data can be analyzed to assess the power of differentiation across patients (videos). All possible pairings of the 57 videos were formed, for a total of 1596 distinct pairings. Each video was evaluated by between 6 and 15 investigators in the main analysis

set. For each pair, mean differences in the UCEIS and overall endoscopic severity on the VAS, and 2-sample t tests for differences between videos for evaluation of overall severity on Selleck GSK3 inhibitor the VAS and the UCEIS were calculated. Proportions of significantly different scores (confirmed Fossariinae by t tests) were studied globally and as a function of the difference in endoscopic severity on the VAS. To compare the UCEIS with established clinical measures for UC, Spearman

rank correlation tests were performed between the UCEIS and full Mayo score, partial Mayo score (excluding endoscopic evaluation),12 stool frequency/rectal bleeding, and patient functional assessment. Statistical analyses were performed using Statistical Analysis System (SAS, Cary, NC) software version 9.2. Twenty-nine investigators from 14 countries were screened for participation in the study. Eleven of the 29 succeeded on first qualification and 14 on their second attempt. One investigator failed both times, and 3 were withdrawn due to noncompliance with procedures, resulting in a total of 25 investigators (11 from North America, 9 from Central Europe, and 5 from Western Europe; see Acknowledgments). In total, 698 of the planned 700 evaluations were performed. Each video was assessed by 6 to 15 investigators. The response rate was 100% for assessment of overall severity on the VAS and for all descriptors of these 698 evaluations. The analyses that follow exclude 50 videos from the second evaluation of repeat pairs and the 100 evaluations used for clinical details/no clinical details evaluation, unless stated otherwise.

0 software package for Windows. Lodging resistance was used as the dependent variable, while lignin, cellulose, AOVB, NOVB, AOT and WOMT were used as independent variables. Potential microsatellite markers linked to stem solidness genes were identified by screening the F2 population using bulked segregant analysis. DNA was extracted from young leaf tissues using the CTAB method. The solid and hollow stem DNA pools were composed of 5 solid and 5 hollow stemmed F2 plants, respectively. Along with the parental DNA, the bulked DNA samples were used to screen 607 SSR markers (210 GWM [19] and 397 BARC [20]). The PCR mixture

(20 μL) consisted of 2.0 μL of 10 × buffer, 1.6 μL of Mg2 + (25 mmol L− 1), 2.0 μL of dNTP (2 mmol L− 1), 2.0 μL of DNA (10–20 ng μL− 1), 2.0 μL of primer (2 μmol L− 1), 0.2 μL of Taq DNA polymerase (5 Z-VAD-FMK mouse U μL− 1), and 10.2 μL of ddH2O and was subjected to a thermocycler program of 94 °C for 5 min; ABT888 followed by 30 cycles at 94 °C for 1 min, 60, 55, or 50 °C for 1 min (depending on each primer set), and 72 °C for 1 min; with a final extension at 72 °C for 5 min. The PCR products were electrophoresed in 4% polyacrylamide gels and detected by silver staining [21]. Marker-trait associations were identified by single factor ANOVA and the proportion of phenotypic variation explained by single marker loci was determined as

the ratio of sum of squares for marker class divided

by sum of squares of entries [12]. The characteristics PAK5 of stem pith varied significantly among the four genotypes examined (Fig. 1). Solid stemmed XNSX showed the greatest amount of pith material (Fig. 1B), whereas CS and Line 3159 had hollow stems (Fig. 1A and C), and the characteristics of F1 plants were similar to the solid-stemmed parent except for the third and fourth internodes (Fig. 1D). Significant differences were also detected in the anatomical characteristics of the four genotypes, especially the transverse sections of solid stemmed wheat XNSX, which had more mechanical and parenchyma tissues (Fig. 2C and D) than the other three genotypes (Fig. 2A, B, E and F); F1 plants were almost intermediate between their parents in the corresponding values (Fig. 2G and H). The morphological data for the four wheat genotypes are shown in Table 1. AOT in the solid stemmed and F1 plants were significantly larger than that of CS. In contrast, there were only minor differences in AOVB among the four genotypes (Table 1). The widths of stem walls in XNSX and F1 were 2.7- and 2.6-fold that in CS, and WOMT values were 2.1- and 1.7-fold that in CS. Only slight differences were observed in TNVB among the four genotypes, but the WOL of XNSX and F1 plants were significantly higher than those of Line 3159 and CS (Table 1). The contents of cellulose and lignin showed slight differences among the four genotypes.

[31] ergaben, dass auf die Haut aufgetragenes Quecksilber(II)-chlorid innerhalb von 5 h zu 8% aufgenommen werden kann. In Experimenten mit Ratten wurde gezeigt, dass sich Quecksilber im Nervensystem ungleich verteilt [32]. In Neuronen wurde mehr Quecksilber gefunden als in Gliazellen, wobei sich das Quecksilber in Lysosomen angereichert hatte. Die Motoneuronen enthielten mehr Quecksilber

als die sensorischen Neuronen. Darüber hinaus wurde festgestellt, dass das Cerebellum Quecksilber enthielt, buy Belinostat jedoch nicht in den Purkinje-Zellen. Die von einer akuten Quecksilbervergiftung am stärksten betroffenen Organe sind der Darm und die Nieren. Im Darm herrschen ätzende Effekte vor. In der Niere kann es aufgrund der Nekrose des Tubulusepithels innerhalb von 24 h zum Versagen kommen. Bereits 1 g kann für einen erwachsenen Menschen tödlich sein. Der auffälligste Effekt von zweiwertigem Quecksilber AZD5363 research buy ist die Nekrose der Nierentubuli. Nach längerer Exposition wird darüber hinaus Glomerulonephritis beobachtet. Zweiwertiges Quecksilber kann darüber hinaus Autoimmunerkrankungen verursachen. Siehe dazu den Übersichtsartikel von Pollar und Hultman [33]. Unter den organischen Quecksilberverbindungen galt das Hauptinteresse sowohl bei epidemiologischen als auch bei experimentellen Untersuchungen dem Methylquecksilber.

Es sind verschiedene ausgezeichnete Übersichtsartikel verfügbar, die sich mit selektiver Neurotoxizität im Allgemeinen [34], [35] and [36] sowie mit der Neurotoxizität von Methylquecksilber im Besonderen [37], [38], [39], [40], [41], [42], [43], [44], [45] and [46] befassen. Die Forschung zur Toxikologie organischer

Quecksilberverbindungen beim Menschen hat eine lange Geschichte, wobei auch neurotoxische Effekte untersucht wurden. Der erste Fall einer berufsbedingten tödlichen Vergiftung mit MeHg wurde 1863 veröffentlicht. Laborpersonal, das mit der Synthese von organischen Quecksilberverbindungen beschäftigt war, erkannte offenbar nicht die toxischen Eigenschaften der Verbindungen, mit denen gearbeitet wurde [47] and [48]. Später beschrieben aminophylline Hunter et al. [49] and [50] ausführlich die berufsbedingten Risiken durch organisches Quecksilber und dessen toxikologische Eigenschaften. In der früheren Arbeit wurde über vier Krankheitsfälle bei Menschen berichtet sowie über Experimente, die an Nagern und Affen durchgeführt wurden. Dabei wurden u. a. folgende wichtige Beobachtungen gemacht: • Auftreten einer Verzögerungsphase vor dem Einsetzen von Symptomen; In der späteren Publikation von Hunter und Russel [50] wurden die Befunde beim Menschen bestätigt: Es kam zu einem starken Verlust von Körnerzellen, während die Purkinje-Zellen nicht betroffen waren. Die beobachtete Einschränkung des Sehfeldes wurde mit der Atrophie von Körnerzellen in der Area striata erklärt.

DNA extraction, PCR amplification, and SSR genotyping were performed as previously described [5] and [30]. PCR amplification was performed on a PTC-200 Thermocycler (MJ Research/Bio-Rad, USA) with 5′ fluorescent end-labeled

primers and PCR products were visualized by silver staining after separation by 6% SDS-polyacrylamide gel electrophoresis. The products were used for genotypic analysis on a Mega BACETM 1000 (Amersham Biosciences, USA) and allele fragment sizes were obtained with software BioCalculator 2.0 (QIAGEN, Germany). A total of 14 phenotypic traits (nine qualitative and five quantitative Obeticholic Acid solubility dmso traits) were used for phenotypic diversity analysis. The proportions of different classes of nine qualitative phenotypic traits (seed coat color, cotyledon color, seed shape, growth habit, stem termination, pubescence color, flower color, leaf shape and hilum color) in the 159 accessions and a PIC   (polymorphic information content) value for each trait were calculated. Chi-square tests were used for detecting similarity of distribution with the accessions in the established MCC. Seed coat has five colors

including yellow, green, black, brown and di-color, designated as 1–5. Cotyledon has yellow and green colors, designated as 1 and 2. The codes for seed shape are 1–6 and refer to spherical, spherical flattened, ellipse, flat ellipse, long ellipse and reniform. Codes 1–4 of growth habit refer to erect, semi-erect, semi-rampant, and rampant, and codes 1–3 of stem termination refer to determinate, semi-determinate, and indeterminate. Codes INCB024360 clinical trial 1–2 of pubescence color and flower color refer to gray and tawny pubescence and to white and purple flower, respectively. The four leaf shapes (lanceolate, ovoid, ellipse and round) are designated

as 1–4 and six hilum colors (yellow, buff, brown, dark brown, blue, imperfect black and black) as 1–6. Mean value, standard deviation (SD  ) and coefficient of variation (CV  ) of five quantitative phenotypic traits (growth duration, 100-seed weight, plant height, protein content and fat content) were calculated using Microsoft Excel software. A large-sample Z  -test was used for detecting the similarity of distributions to those of accessions in the MCC. Numbers of observations, allele number, gene diversity, observed heterozygosity, and PIC  -value of molecular Smoothened markers were calculated with PowerMarker V3.25 [31].The PIC  -value was calculated as: PIC=1−∑i−1nPi2, where Pi is the frequency of the ith allele.The chi-square value was calculated as X2=∑i−1nAi−Ti2Tiwhere Ai is the frequency of the ith allele among soybean accessions in IACC and Ti is the frequency of the ith allele among soybean accessions in MCC. The Z  -value was calculated as: Z=X1¯−X2¯S12n1+S22n2Where X1¯/X2¯, S1/S2 and n1/n2 refer to mean, standard deviation, and sample size of soybean accessions in the IACC or MCC, respectively.

2d), and as a band with low radiopacity adjacent to bands with an even lower radiopacity (thin arrow in Fig. 3d). Some teeth had somewhat long extensions along

the main axis of the buccal surface without pigmented bands, where the superficial enamel layer uninterruptedly displayed higher positive birefringence with a vivid blue colour (Fig. 2c) and lower radiopacity (Fig. 3c) compared with normal enamel. Cavities with the bottom in dentine (enamel–dentine see more junction) were seen in some teeth, outlined by enamel with higher positive birefringence compared with normal enamel (Fig. 2e and f). As illustrated in Fig. 3, control and Pb group animals did not display signs of fluorosis in their teeth (score 1). All the animals from the F or F + Pb groups, on the other hand, presented enamel with various degrees of defects (Fig. 4). Whilst the F group animals

had the typical rodent fluorotic enamel appearance (scores 2–4), the animals exposed click here to F + Pb exhibited significantly higher degree of fluorosis as evidenced by the Enamel Defect Index proposed in this study (P < 0.001). The median of the F group animals was 2.0 (2.0; 3.0) (minimum; maximum) in upper incisors, and the F + Pb group animals furnished a median score of 3.25 (2.5; 4.5)(P < 0.0001). For the lower incisors, higher fluorosis scores were also obtained in the F + Pb group animals: the F-exposed animals presented a median of 2.0 (2.0;4.0), whereas the F + Pb group animals had a median of 4.0 (2.5; 5.0) (P < 0.0001, Fig. 4). This study shows for the first time that the fluoride effects on enamel formation can be altered by the co-exposure of rats to lead, resulting

in worse enamel defects in both lower and upper incisors. Data on F and Pb tissue levels have been reported previously,13 and it was demonstrated that: (i) animals from F and F + Pb GPX6 groups exhibited increased concentrations of fluoride in calcified tissues compared with the control and Pb groups, in all analysed tissues (P < 0.0001) ( Fig. 3 of Sawan et al., 2010) 13; (ii) there were no differences between the F and F + Pb groups (P > 0.1) in terms of the concentrations of fluoride in whole bone, dentine, or enamel; and (iii) Pb levels in blood and calcified tissues were higher in the F + Pb group (blood Pb level of 76.7 ± 11 μg/dL) compared with the other groups (blood Pb level of 22.6 ± 8.5 μg/dL in the Pb group and below 5 μg/dL in the control and F groups) (P < 0.001) (Figs. 1 and 2 of Sawan et al., 2010). 13 The modified Fluorosis/Enamel Defects Index for rodent teeth employed here allowed for discrimination of a wider range of defects than that previously observed in rat fluorosis.15 White lines and white islets were defined as hypomineralization, as evidenced by the altered birefringence detected by means of polarizing microscopy, in agreement with a recent report,15 and by the lower X-ray absorbance seen on microradiographs.

The Kaplan-Meier method and the log-rank test for evaluable patients at the endpoint were used for differences in stent patency and survival on an intention to treat basis. Between 05/ 2009 and 06/ 2012, 400 patients were randomized at 9 sites. Currently 390 patients are evaluable, 197 patients in nSEMS group and 193 in sSEMS have reached the endpoint. 7 patients refused follow-up and 17 patients were eventually operated upon. Median age was 77 (38-99) years in nSEMS and 78 (35-96) in sSEMS. Pancreatic cancer was the cause of obstruction in 152 (78.4%) nSEMS and 148 (78.3%) sSEMS. ERCP-related complications occurred in 15 (7.6%)

nSEMS and GSK2126458 in vivo 10 (5.3%) sSEMS, p= 0.35. Protocol violations consisted of too close distance of the stricture to hilus (<2cm), too short or wrong stent, occurred in 11 (5.9%) nSEMS and 23 (12.4%) sSEMS, p=0.03. Death within 300 days with patent stent occurred in 124 (62.9%) nSEMS and 108 (56.0%) sSEMS, p=0.18. Alive at 300 days with patent stent were 44 (22.3%) nSEMS and 38 (19.7%) sSEMS, p=0.54. Stent failure confirmed by new ERCP,

occurred in 14 (7.1%) nSEMS and 30 (15.5%) sSEMS, p=0.01. Stent dislocation was observed in 4 (2.6%) nSEMS and 14 (5.5%) sSEMS and tumour overgrowth in 7 (2.6%) nSEMS and 10 (4.4%) sSEMS. The results of this randomized trial shows significantly prolonged find more patency time and less failure rate in nSEMS compare to sSEMS in the palliation of malignant distal biliary obstruction. “
“Accurate diagnosis of indeterminate biliary strictures remains a clinical challenge. The aim of this study was to assess the operating characteristics of fluorescence in situ hybridization (FISH) compared to cholangioscopic (Spyglass) targeted biopsies for the detection

of malignancy in biliary tract strictures. We conducted a retrospective analysis of data from two tertiary medical centers of patients who underwent evaluation of indeterminate biliary strictures between 2008 to 2012. Only those patients with a final pathologic diagnosis or a conclusive >12 months follow-up were included in the final analysis. Patients were divided into 2 groups: patients who underwent biliary stricture brushing for cytology and FISH assessment (C-FISH) PFKL nd patients who underwent Spyglass targeted biopsies of biliary strictures after inconclusive brush cytology (SB). Spyglass biopsies were considered positive for malignancy when adenocarcinoma cells were identified (atypical or suspicious results were considered negative). FISH was considered positive for malignancy when either CEP3, 7, 17 polysomy and/or 9p21 deletion was observed. The comparison of the operating characteristics of FISH versus cholangioscopic targeted biopsies for the diagnosis of malignant strictures were performed with the use of a Chi-squared test and Fisher exact test.

, 2012). In this context, this study, to the best of our knowledge, was the first to show that tDCS can reverse the effects of maladaptive plasticity as expressed by behavioral changes and measured by TNFα levels. On the other hand, one limitation of the study was the lack of difference between one of the analysis for von Frey test – S vs. SN – probably because of less sensitivity of this measurement as compared to hot plate test and also because of differences what these measurements index such as hot plate related to hyperalgesia and von Frey related to allodynia. In summary, we showed that

tDCS was able to reverse completely the detrimental effects of chronic stress find more on the pain system, as expressed by hyperalgesia and allodynia, and that this effect continued for 24 h. Serum levels of corticosterone and interleukin-1β were not changed by tDCS sessions or chronic restraint stress, but hippocampal TNFα levels decreased. Given that, in this study, animals were exposed to the same level of stress under the same

signaling pathway conditions, our findings support further exploration of tDCS as a therapeutic tool early in the exposure to stressful situations that may lead to chronic pain, such as post-traumatic stress disorder, and demonstrate one possible pathway of anodal tDCS treatment. Future studies should also consider assessing other outcomes of stress response, including other behavioral outcomes, as well as measurement of other biochemical variables, such as PCPA (inhibitor of serotonin synthesis), AMPT (inhibitor of tyrosine hydroxylase) and naloxone, to provide a better understanding of the effects of chronic restraint stress on mood and anxiety and further elucidate and

optimize this intervention into a potential clinical tool for stress-related conditions. Sixty-day-old male Wistar rats weighing 180–230 g were used. Experimentally naive animals were housed in groups of five in 49×34×16 cm polypropylene home cages. All animals were kept on a standard 12-hour light/dark cycle (lights Ureohydrolase on at 07:00 a.m. and lights off at 07:00 p.m.) in a temperature-controlled environment (22±2 °C). Animals had access to water and chow ad libitum. All experiments and procedures were approved by the Institutional Committee for Animal Care and Use (GPPG-HCPA protocol No. 100.381) and performed in accordance with the Guide for the Care and Use of Laboratory Animals 8th edition (2011). Animal handling and all experiments were performed in accordance with International Guidelines for Animal Welfare and Measures were taken to minimize animal pain and discomfort. The experiment used the minimum number of animals required to produce reliable scientific data. To control the possible effect of outliers, we excluded rats which did not present any response on behavioral testing. All the experimenters were blinded to condition (active or sham tDCS) during post-treatment behavioral testing.

The current MMO draft marine plan for selected English waters in the North

Sea [111] designates ‘areas of potential’ for CO2 storage, in which marine licence applicants: should demonstrate in order of preference: (a) that they will not, wherever possible, prevent carbon dioxide storage An equivalent policy is notably absent from the Consultation Draft of Scotland׳s National Marine Plan, which sets out clear objectives to develop CO2 storage, but does not identify in detail how this objectives is to be reconciled with clear objectives to develop a wide range of other marine activities (e.g. marine renewable energy) [108]. It does however contemplate the preservation of spatial opportunity for CCTS projects by requiring that ‘Consideration Trichostatin A datasheet should be given to the development of marine utility corridors which will allow [CCTS] to capitalise on current infrastructure

in the North Sea including shared use of spatial corridors and pipelines.’ [108]. The UK׳s approach to planning and regulation of offshore CO2 storage (and its interaction with other marine activities) is illustrative of three key points that may be of particular interest selleck kinase inhibitor to other countries and jurisdictions: First, how a diverse array of coordination measures can be used to promote coherence within a complex and CYTH4 sectorally fragmented regulatory framework. As highlighted in Section 4 above, coherence can be promoted hierarchically (e.g. legal requirements to act consistently with certain policy instruments); or non-hierarchically (e.g. operational coordination arrangements; careful scope delineation of sector-specific permitting requirements).

A distinctive feature of the UK׳s approach is the cross-sectoral planning activity undertaken by the Crown Estate Commissioners, acting their capacity as a public but non-governmental owner of a broad portfolio of offshore property interests. As far as the author is aware, the Commissioners׳ cross-sectoral marine management and planning functions, exercised at arms length from government,8 do not have an equivalent in any other country or jurisdiction. Second, coherent cross-sectoral planning and regulation of marine activities can be promoted with limited centralisation of regulatory frameworks and associated government agencies. As noted in Section 4 above, decentralisation may yield beneficial outcomes provided coherence is maintained, including: inclusive decision-making, improved institutional memory, diversification of risk, and systemic resilience. Finally, a coherent planning framework may be necessary but not sufficient to deliver on high-level policy objectives to deploy offshore CO2 storage.