Outros tipos de amiloidose são: a amiloidose relacionada com a diálise (Aβ2MG), causada pela deposição de β2-microglobulina; a amiloidose hereditária, nomeadamente a polineuropatia amiloidótica familiar (FAP), causada pela deposição de transtirretina; a amiloidose senil; e as formas localizadas de amiloidose no esófago, estômago, intestino delgado e/ou no cólon2, 6, 7 and 8. O envolvimento gastrointestinal na AL é comum, sendo estimado em 98%

em algumas series de autópsias5. Contudo, a apresentação inicial da AL como hemorragia digestiva é raramente reportada na literatura5 and 9. Os sinais e sintomas dependem da localização do trato this website gastrointestinal que está envolvida2. O envolvimento do estômago e do duodeno é incomum, sendo a maioria dos doentes assintomáticos. Os sintomas podem incluir náuseas, vómitos, epigastralgias e hematemeses2. No presente caso o doente apresentou um episódio de vómitos coincidente temporalmente com a hemorragia digestiva baixa. A hepatomegália é comum nos doentes com AL1. Na presença de insuficiência cardíaca pode ser difícil diferenciar a congestão hepática da infiltração por amiloide, contudo, a presença de hepatomegália dura e irregular, particularmente se associada a elevação da fosfatase alcalina, fortemente selleck sugere esta última entidade1. No presente caso,

o doente apresentava elevação da fosfatase alcalina e das transaminases, mas sem alterações da imagiologia hepática. A deposição de amiloide, quando presente, é maior a nível do intestino delgado. Clinicamente pode traduzir-se por diarreia, esteatorreia, enteropatia perdedora de proteínas, isquemia mesentérica, hemorragia, intussusceção, pneumatose intestinal, obstrução ou pseudo-obstrução4, 6, 9, 10 and 11. Os achados endoscópicos mais frequentes incluem aparência granular fina, pólipos, erosões, ulcerações ou friabilidade

da mucosa10, 12, 13 and 14. As manifestações clínicas da amiloidose see more do cólon podem mimetizar outras doenças, tais como doença inflamatória intestinal, neoplasias, colite isquémica ou colite colagenosa. Endoscopicamente podemos encontrar protusões polipoides, úlceras, hematomas da submucosa, nódulos, colite bolhosa hemorrágica, estreitamento luminal, perda das haustrações e espessamento das pregas mucosas do cólon3, 4, 15, 16 and 17. A hemorragia digestiva baixa, que pode ser a manifestação inicial da amiloidose do cólon em cerca de 25-45% dos doentes, tal como aconteceu no presente caso clínico, pode ser causada por isquemia, enfarte, ulceração, lesão infiltrativa ou secundária a hemorragia em babamento generalizada sem uma fonte identificável. Geralmente ocorre na ausência de distúrbios da coagulação4 and 9. Contudo, as doenças hemostáticas são comuns na AL, estando descritas na história de 28% destes doentes.

5%. This is comparable Baf-A1 research buy to a study in central Greece assessing 11-year-olds weight status where a total of 30.3% were reported

to be overweight and 6.7% obese [13]. The fact that parental BMI was positively associated with their child’s BMI highlights the importance of family history and environment in the development of obesity. The overweight and obese children in the current study had significantly higher arterial blood pressure, lower HDL-C levels, higher TG and increased insulin compared to their the normal weight counterparts. Higher Tanner scores and heights of the overweight and obese group also suggest earlier onset of puberty, which is often frequently observed in overweight and obese children [14]. JNK inhibitor solubility dmso Any interaction between sexual maturity and effects of allelic variation on lipid levels that may have occurred could be accounted for in analyses from the Tanner measures. Genetic factors are considered important determinants of plasma lipid levels in adults, demonstrated in several of the recent genome wide association studies (GWAS) in which a number of candidate genes have been confirmed [15] and [16]. The meta-analysis of 3 GWAS by Willer et al. (2008) identified strong associations with variants in APOA5/A4/C3/A1 cluster, APOE, CETP and LPL influencing plasma lipid concentrations. Although a number

of associations comparable to those seen in adults were confirmed in this study, the role of genetic factors in the heterogeneity of plasma lipid levels in children is less clear. Replication of these variants in cohorts of children is needed. In GENDAI, APOE genotypes were associated with differences in TC and LDL-C plasma levels and the TC: HDL-C ratio. The LDL-C and TC lowering

effect of the ɛ2 allele reported in the recent meta-analysis [17] was also observed in this cohort of young Greek children. Carriers of the ɛ4 allele had LDL-C and TC levels that were 19.9% and 12.2% higher than carriers of the ɛ2 allele and 2.8% and 1.3% higher than ɛ3/ɛ3 subjects. The results of a 21-year longitudinal study on changes in serum lipids in 1233 Finns followed from childhood to adulthood mafosfamide consistently observed the ɛ2 allele to be associated with lower LDL-C levels and the ɛ4 allele with higher TC and LDL-C levels (p < 0.001 for all associations) in childhood. The LDL-C-lowering effect of the ɛ2 allele was an association that was tracked through to adulthood, having a greater effect with increasing age (p = 0.039). The association of the APOE genotype with plasma TC and LDL-C has been reported in children as young as 3 years old [18]. The fact that differences in lipid levels cannot be detected in children at birth by the APOE genotype leads to the conclusion that lipid levels are influenced by genetic and environmental factors in a child’s very first years of life [18].

During the task, participants were presented with a coloured (red or green) or achromatic grapheme, which acted as a congruent, incongruent, or neutral condition (achromatic grapheme trials). After participants had read the grapheme aloud, they were presented

with three coloured diamonds (either red Nintedanib supplier or green) each missing either the left or the right side (Fig. 1a). Two of the diamonds were the same colour and one was odd. The participants’ task was to indicate which side of the odd coloured diamond was missing. Stimulation was delivered via a figure of eight coil with a 70 mm diameter using a Magstim Super Rapid Stimulator (Magstim, UK). An offline cTBS paradigm was used (see Banissy et al., 2010 for TMS parameters). Locations for cTBS were identified using Brainsight TMS-magnetic resonance coregistration system (Rogue Research, Montreal, Canada). The left V4 site was selected based on coordinates from neurologically normal participants in an functional magnetic resonance imaging (fMRI) study investigating colour perception (36, −56, −14; Morita et al., 2004). The coordinates

for V5/MT (44, −67, 0) were the averages of neurologically normal participants in an fMRI study of motion processing and were confirmed functionally through phosephenes (Dumoulin et al., 2000). The vertex was identified as the point midway between the inion and the nasion, equidistant from the left and right intertragal notches. As per previous perceptual priming studies (Walsh et al., 2000, Campana Tyrosine Kinase Inhibitor Library high throughput et al., 2002, Kristjánsson et al., 2005 and Kristjánsson et al., 2007), we expected participants O-methylated flavonoid to respond faster to the odd coloured diamond when this was congruent with the prime grapheme. This was found to be the case in all baseline conditions [V4 group: t(5) = 3.07, p = .028; V5/MT group: t(5) = 2.94, p = .032; Vertex group: t(5) = 4.67, p = .005]

and the size of the priming effect (i.e., incongruent stimulus median reaction time minus congruent stimulus median reaction time) was similar across sites [F(2, 15) = 1.70, p = .216]. To examine the effects of cTBS on priming, we firstly compared the size of the colour priming effect (incongruent reaction time minus congruent reaction time) in the baseline condition with the size of the colour priming effect following cTBS to each site separately by using paired t-tests. This revealed that cTBS to V4 [t(5) = 4.59, p ≤ .01], but not MT/V5 [t(5) = .446, p = 0.67] or the vertex [t(5) = .174, p = 0.87], reduced colour priming. To ensure that this effect was not due to ceiling effects in reaction time or accuracy following V4 stimulation we also compared accuracy and overall reaction time performances at baseline and following cTBS in the V4 group. This revealed no significant effect on accuracy performance [t(5) = .349, p = .741]. There was a significant facilitation of overall reaction times following V4 stimulation [Baseline mean ± s.e.m = 612 ± 38.81; V4 TMS mean ± s.e.m = 565.

The significance levels of PC, SV, and WGC were greater than 0.05 (1.000, 0.963, and 0.405, respectively), suggesting that there was no significant difference in wheat flour quality among varieties released in different periods. Table 4 shows comparisons of dough rheological properties among varieties released in different breeding periods. It is readily seen that

DT, ST, and FQN did not increase Bcl 2 inhibitor significantly (P > 0.05) in period II but improved significantly (P < 0.01) in period IV, as compared with period Ι. DT and FQN were significantly higher in period III than in either period I (P < 0.05) or II (P < 0.01). ST and FQN differed significantly between period II and period IV. OTX015 mw Although the average values of rheological properties increased from period III to period IV, no significant differences among them were found. All of these results suggest that the rheological properties of Chinese wheat genetic resources have greatly improved since 1949, but that the rate of improvement is slowing. The mean value of PC in our research was 13.2%, lower than that of bread wheat in the worldwide collection (14.5%) [19] and of North Dakota wheat in the U.S. (14.7%) [10], but higher than that of European wheat (10.3%) and American winter wheat (12.7%) [9] and [20]. In this study, the mean value of DT was 2.7 min, which is less than the average mixing time (defined as the midline peak time)

of American hard red spring wheat (3.1 min) [10] and American hard red winter wheat (3.7 min) [9], but similar to the average mixing time of the world’s wheat core collection (2.8 min) [19]. The mean value of SV in our study (30.3 mL) was consistent with that of the hard red

winter wheat cultivars Bacterial neuraminidase in Nebraska (30.69 mL) [9]. It could be concluded that the wheat quality of China was at a middle level in the worldwide ranking. Zhu et al. [21] reported that PC of Chinese wheat (12.9%) was slightly higher than that of Australian wheat (12.5%), but that STs were 2.32 min for China and 3.50 min for Australia. The CV values of DT and PC obtained in this study (40.5% and 9.1%) were higher than those of the American hard red winter wheat (14.8% and 5.7%) [9], but lower than those of the worldwide core collection (42.2% and 11.0%) [19]. The larger CV values from the world wheat core collection maybe attributed to the diversity of sources and cultivars, especially landraces. Thus, it is essential to extend the gene bank of wheat breeding by characterizing the genetic diversity of Chinese wheat landraces. The data of dough properties were analyzed by assuming both normal distribution and non-normal distribution. When a normal distribution was assumed, significant differences were found for DT, ST, and FQN. However, no significant difference was found for ST by assuming a non-normal distribution (statistical analyses are not shown).

Impacts of SMS mining are predicted to occur across all marine environments (benthic, bathypelagic, mesopelagic and epipelagic) ranging from site to regional scale over both short and prolonged durations (summarised in Table 2) (Gwyther, 2008b). Within the benthic environment alone, there is a range of habitats including both hard and soft substrata with different communities residing on or in each. The benthic organisms also span a range of sizes, including the microfauna (<63 μm), meiofauna, (63–500 μm), macrofauna (500 μm–5 cm) and megafauna (>5 cm), with different ecological characteristics, including the nature and extent of dispersal, mobility,

feeding strategies and trophic interactions. Such a suite of habitats, faunal assemblages and ecologies selleck inhibitor means that the response of benthic organisms to SMS mining will vary widely, complicating any attempt to generalise the identification and mitigation of impacts. The nature and the scale of those impacts (both spatial and temporal) are also likely to be different at different deposits. Table 2 summarises the only site-specific impact assessment currently available (see Gwyther (2008b) for full assessment), but different sites may have additional impacts to consider. The impacts from SMS mining will also vary

with the methods and equipment used. For example, the predicted impacts from the proposed SMS mining methods ZD1839 nmr of the Japan Deep Sea Technology Association (DESTA) are more varied with a greater risk of smothering (Fukushima and Okamatsu, 2010) than those for Solwara 1 outlined in Table 2. Modelling studies of the dispersal of unconsolidated sediment discharge at Solwara 1 indicated that increased sedimentation thicknesses of up to 500 mm may occur within 1 km of the discharge site (Gwyther, 2008b). Some particulate material

may extend up to 10 km from the site, but settle at lower than natural rates. Existing sediment thicknesses at and around Solwara 1 are 6 m deep in places (Gwyther, 2008b). Return water plumes may extend 5–10 km many from the mining site, with maximum deposit thickness of 0.1 mm and rates of settling less than existing deep-sea sedimentation rates (Gwyther, 2008b). Sediment and water column plumes will disperse with distance, and hence “downstream” effects will be less than at the site where they are formed. This dilution will mean there is a gradient of impact, with effects lessening with distance away from the mining site. The potential distance and depth of sedimentation effects will vary among sites, and will need to be assessed in any prospective mining area. With regards to the toxicity of these plumes, it is thought that high concentrations of heavy metals will pose minimal risk to the fauna adapted to active SMS deposits (Gwyther, 2008b).

035 in. diameter hydrophilic wires. The 6F guiding catheter was introduced subsequently into the target brain supplying vessel over the same hydrophilic wire and microcatheter with a support of a 0.014 in./300 microwire was advanced behind the occluded intracranial vessel segment. Occlusion of MCA or BA was classified according to the Thrombolysis in Cerebral Ischemie (TICI) criteria. The intraluminal position of the microcatheter was always checked. All catheters were continuously flushed with heparinized saline. The microcatheter was then replaced with the EKOS endovascular catheter terminated with the emitter of ultrasonic waves and connected to the central unit. The EndoWave System Ibrutinib manufactured

by EKOS Corporation (Bothell, WA, USA) was used (Fig. 2a and b). It consists of a 5.2F, 106 cm long

infusion catheter, an ultrasound core wire, and a control unit with catheter interface cables. The ultrasound wire delivers pulsed high frequency (1.7–2.1 MHz) and low-intensity (400 mW/cm2) ultrasound waves. Special care was taken for the location of a tip of the catheter into the occluded segment of the artery (Fig. 3). Both the insonation and the local administration of tPA directly into the thrombus were simultaneously started. In this study, a dose of 15 mg/h of tPA was delivered Selleck LY2109761 by an infusion pump with a maximal calculated total dosage not exceeding 20 mg of tPA. Patients with partial recanalization after EKOS

treatment were further treated by angioplasty and stent implantation. The recanalization status at the end of DSA was evaluated Rutecarpine by blinded independent radiologist using the TICI criteria. TICI IIc and III were evaluated as complete recanalization (Fig. 4), TICI IIa and IIb were evaluated as partial recanalization. Neurological and physical examinations were done before therapy start and 24 h, 30 and 90 days after the start of treatment. Certified neurologist performed evaluation of neurological symptoms using NIHSS in all visits. Modified Rankin score was used for the evaluation of disability at days 30 and 90. Good clinical outcome was defined as a mRS 0–3, poor clinical outcome as a mRS 4–6. All adverse events were recorded. All changes in physical examinations, worsening of neurological symptoms (>4 points in NIHSS) and all disorders prolonging or requiring hospitalization were recorded as adverse events. Intracranial bleeds detected in the control brain CT examination 24 h after therapy onset were recorded. Intracranial bleeding with worsening of neurological symptoms > 4 points in the NIHSS were evaluated as SICH (ECASS 3 criteria). Other intracranial bleeds were evaluated as asymptomatic intracranial hemorrhage (AICH). In the control brain CT scan, detected brain edema associated with worsening of neurological symptoms > 4 points in the NIHSS was evaluated as “symptomatic”.

The increase in the scale of farms, export-oriented production, and the concentration of ownership are facts that exacerbate distributive conflicts because they are perceived to be linked to a significant decrease of the sector׳s contribution to local economies and see more connection to local communities [33]. This has been argued in different types of conflicts detected in South Evoikos Gulf in Greece, Charentais Sounds in France, Ireland, Scotland and Norway [30,31] (I13, I26, I19). The recognition aspect refers to whether

some groups of society are considered to be relevant actors for decisions on the development of fish farms. The exclusion of some actors from decision-making or counting their opinion as inferior or irrelevant is considered as injustice. The participation dimension of environmental justice is closely related to recognition, since lack of recognition directly leads to injustice

in participation. However, although find more some groups are recognized as actors, decision-making system may be established in a way that precludes some groups׳ participation, which depends on at what level and by whom the decision is made. In the conflicts detected in Finland, Scotland, Greece and Spain, actors explicitly highlight their demands for recognition and participation. In Finland, summerhouse residents have been complaining about not being included in the stakeholder consultation process, while in Scotland, local fishermen, the tourism sector and local population felt that

DOK2 their opinions were ignored [38,32,34] (I26, I27). In Greece and Spain, local people and fishermen claimed that local needs were not considered during decision-making, and injustices occurred through the absence of their recognition and participation (I12, I24). Socioenvironmental conflicts related to marine finfish aquaculture in Europe occur between different levels and bodies of public administration as well. Conflicts between public authorities, concerns on where the decision is made, and overruling of local decisions are perceived injustices related to participation, i.e. procedural injustice, as encountered in Greece, Ireland and Norway. In Greece, the local municipality of Lagkada came into conflict with the higher municipal authority of Chios, to which Lagkada belongs administratively (I12). The Lagkada municipality and the inhabitants it represents feel that they were isolated, and that local public administration׳s view was not taken into account by the Chios municipality, although there has been a great opposition since 2000s against fish farms mainly because of environmental degradation. This implies that the local public authority is not recognized as a real decision-making body, and hence the available means of participation at the local level remain inadequate.

Multiple small circular regions of interest (ROIs) of three voxels’ diameter

were positioned to sample the calculated T10, Et and Ct maps in white matter (84 ROIs), cortical gray matter (44 ROIs), deep gray matter (12 ROIs), CSF (10 ROIs) and major vessels (7 ROIs) on the pre-contrast 12° acquisition, using standard templates to ensure consistent sampling of brain regions blind to all other data including knowledge of post-contrast signal change. If necessary, the template ROI location was then adjusted slightly to avoid the recently ischemic lesion; however, ROIs were not adjusted to avoid white matter lesions. Measurements from all selleck ROIs were combined for each subject and tissue type to produce overall mean and standard deviation values for T10, Et and Ct. The mean

Et (Etave) and Ct (Ctave) were averaged over all post-contrast time points and along with T10 were averaged over all patients for each tissue type in each of the high- and low Fazekas-rated groups, to give overall mean and standard deviation values for each tissue in each group. A Student’s t test was performed http://www.selleckchem.com/products/KU-55933.html to look for significant differences in T10, Etave or Ctave between the low- and high Fazekas-rated groups in each tissue. The sensitivity of the FSPGR acquisition to scanner noise and drift was assessed using data acquired from volunteers and phantoms, processed in exactly the same way as the patient data. For the phantom data, ROIs were placed to cover the phantoms (cylindrical tubes of approximately 2 cm diameter and 10 cm length), and for volunteer data ROIs were placed as described above for the patient case. The contribution to the signal enhancement curves from scanner noise and drift was obtained by calculating the mean and standard deviation of Et for each tissue type (or phantom) over all time points and by analyzing the slope of

the signal enhancement profiles using standard linear regression analysis performed with the regression function in Microsoft Excel. These findings were then compared to the patient data. Errors in the estimation of intrinsic tissue parameters (T10, T20, r1 and r2) on the calculation of contrast agent concentration 3-mercaptopyruvate sulfurtransferase have been extensively studied by Schabel and Parker [19] who derived analytical expressions for the relative bias in the concentration measurement resulting from a biased estimate of the intrinsic tissue parameters. They demonstrated that T10 produces a negative concentration bias that has the greatest influence of all the tissue parameters, r1 also results in a negative concentration bias but to a lesser degree than T10, while r2 produces a fairly negligible positive concentration bias, only becoming significant at very high concentrations. The concentration estimation is independent of T20 in the fast exchange regime and so this parameter need not be considered further.

6%, χ2 = 8.2, P = 0.0004). Anaemic children were younger than find more non-anaemic children (P = 0.006). After adjusting for age, anaemic children (n = 40) tended to be shorter, and heavier and had a greater BMI than non-anaemic children (n = 450) (P = 0.02, P = 0.02 and P = 0.006 respectively) ( Table 2). Plasma FGF23 and 1,25(OH)2D concentrations were higher in children with anaemia compared to those without

(P ≤ 0.0001 and P = 0.03 respectively). There was no significant difference in 25OHD or PTH between the two groups but iCa was higher in the anaemic children (P = 0.007). TmP:GFR tended to be lower and uCa:uCr was higher in anaemic children compared to non-anaemic children (P = 0.04 and P = 0.0003 respectively) but there was no difference in eGFR or in plasma P. Albumin was lower in anaemic children compared to those without AZD2281 chemical structure (P ≤ 0.0001). 27% of BD children (n = 29) had circulating concentrations of FGF23 above the upper limit of normal (> 125 RU/ml) compared to 13% of LC children (n = 48) (χ2 = 12.9, P = 0.0003). 8% of BD children (n = 9) had grossly elevated concentrations (> 1000 RU/ml) compared with 2% of LC children (n = 2) (χ2 = 11.3, P = 0.0008). There was no difference in the number of BD Index or BD Sibling children with concentrations of FGF23 > 125 or > 1000 RU/ml (P = 0.1

and P = 0.2 respectively). Children with high FGF23 were younger than children with FGF23 within the normal

range (P = 0.0001) independent of group. After adjusting for age, all children with high FGF23 (> 125 RU/ml) were shorter, tended to be heavier and had a greater BMI than children with FGF23 concentrations within the normal range (P ≤ 0.0001, P = 0.03 and P ≤ 0.0001 respectively) ( Table 3). 1,25(OH)2D and Cys C were higher in children with high FGF23 (P = 0.0002 and P = 0.02 respectively) and Hb was lower (P ≤ 0.0001). eGFR and TmP:GFR were lower, and uP:uCr and uCa:uCr were higher in children with high FGF23 concentrations compared to those BCKDHB with FGF23 within the normal range (P = 0.02, P = 0.05, P = 0.02 and P = 0.02 respectively). There was no significant difference in iCa, 25OHD, PTH, P, TALP or albumin between the two groups. In univariate regression models the dependent variable logeFGF23 was negatively associated with logeHb, logeTALP, logeeGFR, height and weight (logeHb: coefficient = − 2.54(SE 0.39), t-ratio = − 6.41, P ≤ 0.0001, R2 = 7.6%; logeTALP: coefficient = − 0.47(SE 0.15), t-ratio = 3.09, P = 0.002, R2 = 1.7%; logeeGFR: coefficient = − 0.46(SE 0.21), t-ratio = − 2.15, P = 0.03, R2 = 0.7%, height: coefficient = − 2.08(SE 0.21), t-ratio = − 9.58, P ≤ 0.0001, R2 = 15.7%; and weight: coefficient = − 0.03(SE 0.004), t-ratio = − 6.51, P ≤ 0.0001,R2 = 7.9%) and positively associated with loge1,25(OH)2D, cystatin C and logeuP:uCr (loge1,25(OH)2D: coefficient = 0.52(SE 0.12), t-ratio = 4.14, P ≤ 0.

8 (follow up of non small cell lung cancer).  2.3 CLINICAL STAGE IIA   2.3.1 Anatomical surgical resection with lobectomy or pneumonectomy and mediastinal lymph node sampling (EL-1) or dissection (EL-3).   2.3.2 Offer adjuvant therapy as per 2.2.3 (EL-1).   2.3.3 PD332991 If optimal surgery cannot be performed, consider limited surgery (wedge resection or segmentectomy) (EL-1).   2.3.4 For positive surgical margins perform re-resection (EL-1) and if not possible, offer curative radiotherapy (EL-2).   2.3.5 If surgical resection is not possible, offer curative radiotherapy (EL-1).   2.3.6 Follow up and surveillance per Section 2.8 (follow up of non small cell lung cancer).  2.4 CLINICAL STAGE IIB   2.4.1 Anatomical surgical resection

and mediastinal lymph node sampling (EL-1) or dissection (EL-3). EX 527 manufacturer   2.4.2 Offer adjuvant therapy similar to 2.2.3 (EL-1).   2.4.3 Superior sulcus tumors patients should be induced by cisplatin/etoposide with concurrent radiation therapy followed by surgical resection (EL-2). Assess disease extent by using MRI at baseline and pre-operative.   2.4.4 For T3 N0 M0 perform en-bloc resection (EL-1).   2.4.5 If optimal surgery cannot be performed, consider limited surgery (wedge resection or segmentectomy) (EL-1).   2.4.6 For positive surgical margins perform re-resection (EL-1) and if not possible, offer curative radiotherapy (EL-2).   2.4.7 If surgical resection is not possible, offer curative radiotherapy

(EL-1).   2.4.8 Follow up and surveillance per Section 2.8 (follow up of non small cell lung cancer).  2.5 CLINICAL STAGE IIIA   2.5.1 For T3 N1 M0 perform en-bloc resection (EL-1).   2.5.2 For superior sulcus tumor, offer treatment similar to 2.4.3 (EL-2).   2.5.3 For N2 disease offer neoadjuvant concurrent chemo-radiotherapy

(EL-1) assess response. If resectable, offer surgery. For non-resectable tumors, continue with the appropriate treatment based on disease status.   2.5.4 If positive N2 disease discovered during surgery by frozen section abort surgery if pneumonectomy is required (EL-2).   2.5.5 Incidental pathological N2 disease, adjuvant chemotherapy is indicated (EL-1) radiotherapy can be considered (EL-3).   2.5.6 For T4 (2 nodules in ipsilateral separate lobes), offer pneumonectomy followed by adjuvant chemotherapy. Nintedanib (BIBF 1120)   2.5.7 T4 (mediastinal involvement or main airway involvement), offer surgery if potentially curative, if not possible, offer definite concurrent chemoradiotherapy (2.5.1)   2.5.8 For non N2 stage IIIA, not specified above, offer surgical resection with adjuvant chemotherapy (EL-1). Adjuvant radiotherapy may be considered (EL-3).   2.5.9 Follow up and surveillance per Section 2.8 (follow up of non small cell lung cancer).  2.6 CLINICAL STAGE IIIB AND UNRESECTABLE IIIA   2.6.1 Offer concurrent chemo-radiotherapy (EL1) followed by chemotherapy (EL2). Surgical resection for selected cases can be offered.   2.6.2 Follow up and surveillance per Section 2.8 (follow up of non small cell lung cancer).