A most pronounced 6-fold increase was obtained for adenomas in th

A most pronounced 6-fold increase was obtained for adenomas in the female MS-300 group, whereas the increase for carcinomas was only up to 4-fold (Fig. 3). The proliferative lesions were distributed across the five lung lobes in general accordance with

the respective tissue mass (data not shown). The size of the proliferative lesions increased with the tumorigenic progression from the nodular hyperplasia to adenoma to carcinoma (Fig. 4). There was a numerical trend towards lower tumor sizes with increasing MS concentration, similar to the observations in the previous Study 1 (Stinn et al., 2012). Metastatic tumors were found in the lungs of three mice: an undifferentiated mesenchymal tumor with pronounced hemorrhage was found in the lungs of a sham-exposed male mouse; the respective MS275 primary neoplasm was not found. A squamous cell carcinoma was identified as a metastasis in the lung of a female mouse of the MS-75 group; the respective primary neoplasm was located within the stomach with additional metastases in diaphragm and spleen. In a male mouse of the MS-300 group, three adenomas were found in the left lung and approximately 50 presumably bronchogenic metastases in the

right anterior lobe. These mice were not included in the click here determination of the primary lung tumor multiplicity. Type, incidence, and severity of all other non-neoplastic findings observed in smoke-exposed animals did not differ significantly from those seen in the sham control animals and were similar for animals dissected after 18 months of inhalation as well as for animals that died during the course of the study or were killed in a moribund status. These alterations were considered to be within the normal range of background pathology commonly observed in mice of this strain and age. The only MS inhalation-dependent effect observed was an increase in incidence and severity of histiocytosis and yellow-brown

pigment accumulation in the bronchial lymph nodes of mice of the MS-150 and MS-300 groups (data not shown). The major non-respiratory neoplastic findings were rhabdomyosarcomas. This neoplasm invaded the skeletal muscle surrounding either the axial or proximal appendicular skeleton and was characterized Reverse transcriptase by pleomorphic cells with abundant eosinophilic cytoplasm, multiple nuclei, and cross striations. In mice dissected after 18 months of MS inhalation, rhabdomyosarcomas were found in moderate incidence in all groups including the sham control group. In mice that died spontaneously during the course of the study or were killed in a moribund state, the incidence of this fatal tumor was much higher. This resulted in overall incidences of 43, 26, 30, and 36% in male mice and 27, 33, 23, and 19% in female mice in the sham, MS-75, MS-150, and MS-300 groups.

Each measure is standardised to a mean of 10 and SD of 3 Procedu

Each measure is standardised to a mean of 10 and SD of 3. Procedural memory was assessed using a version of Nissen and Bullemer’s (1987) SRT Task. This task is designed to test implicit visuo-spatial sequence learning in procedural memory. In SRT tasks, participants are typically asked to press one of four response buttons, KU-60019 mouse each of which matches the location of a visual

stimulus presented on a computer monitor. Unbeknownst to participants, the visual stimulus follows a predefined sequence. After multiple exposures to the sequence, a random pattern of visual stimuli (rather than the predefined sequence) is presented. In neurologically intact children and adults, reaction times (RTs), which are the principal dependent measure of interest in SRT tasks, typically decrease during the repeated presentation of the sequence, and increase from the final sequence presentations to the random patterns (e.g., Nissen and Bullemer, 1987 and Thomas et al., 2004). This RT increase is taken as evidence that knowledge of the sequence has been learned. To determine whether the knowledge is purely implicit, explicit knowledge of the sequence is probed. Substantial neuroimaging and neurological evidence suggests that implicit sequence learning

in SRT depends on the procedural memory system (Knopman and Nissen, 1991, Siegert et al., 2006 and Thomas et al., 2004). For example, patients with neural pathology affecting the basal ganglia and cerebellum perform more poorly on implicit sequence learning than control groups, with the sequence-to-random increase either missing or decreased as compared Z-VAD-FMK manufacturer to controls (Knopman and Nissen, 1991, Nissen, 1992, Nissen and Bullemer, 1987, Nissen et al., 1989 and Siegert Metalloexopeptidase et al., 2006). Note that in the current study, unlike working and declarative memory, no verbal or auditory analogue of this task was

given to participants. This was, first of all, because auditory SRT tasks require participants to discriminate between tones of different frequencies (e.g., Zhuang et al., 1998), which might be problematic for children with SLI (Hill et al., 2005 and McArthur and Bishop, 2004). Additionally, our focus on a visuo-spatial SRT task was not considered to be problematic for testing the PDH, since, as we have seen above, the classic (and much more widely studied) visuo-spatial version of this task has been shown to depend on procedural memory structures, including those structures implicated by Ullman and Pierpont (2005). In the SRT Task used here, children were seated in front of a computer monitor, on which a visual stimulus (a yellow smiley face) repeatedly appeared in one of four horizontally arranged spatial locations. The children were instructed to press one of four horizontally arranged buttons (on a response box) that corresponded to each of the four locations on the screen. Presentation of the visual stimulus was divided into five blocks, each comprising 90 stimulus presentations.

However, the researchers did not observe a decrease in the mitoch

However, the researchers did not observe a decrease in the mitochondrial membrane potential as was observed in this study. A possible explanation for the dissipation in the membrane potential caused by ABA in isolated hepatocytes may be related to a loss of intracellular Ca2+ homeostasis (Skulachev, 1999). When hepatocytes were exposed to 25 μM ABA, a loss of intracellular ion homeostasis occurred. As the Ca2+ concentration increased in the cell cytoplasm, the mitochondria selleck chemical captured the surplus using the uniporter (UP)

channel. According to Brookes et al. (2004), the UP ion uptake is dependent on the membrane potential, so the movement of charges due to the uptake of calcium consumes the membrane potential that was formed. Furthermore, ABA-induced mitochondrial dysfunction reduces cellular ATP levels and can promote in other organelles such as endoplasmic reticulum, the inactivation of the pump responsible for the maintenance of the Ca2+ ion gradient in the cytoplasm. Invariably, the result of inhibition of the transport system is the disruption of intracellular calcium homeostasis. The increase in intracellular Ca2+ can activate proteases, phospholipases and ion-dependent endonucleases (Trump and Berzesky, 1992). The activation of proteases and phospholipases induces changes in the cytoskeleton and plasma membrane. When selleck chemicals combined, these processes culminate in the disruption of cytoskeleton-plasma membrane interactions,

which results in destabilization of the lipid bilayer, bleb formation on the cell surface and, in more severe cases, leakage and cellular necrosis (Nicotera et al., 1986, Gores et al., 1990 and Sakaida et al., 1992). The enzymes ALT and AST are used as indicators of damage

to hepatic parenchymal cells (Klaassen and Eaton, 1991 and Kaplowitz, 2001). According to Grisham (1979), an efflux of these enzymes in the liquid incubation of cells in not culture indicates that there was a loss of membrane integrity. However, this efflux is not only associated with cell death and lysis but also with modifications that can be reversible (Grisham and Smith, 1984). ABA increased the concentration of ALT and AST in the liquid incubation of hepatocytes, and this effect was also influenced by pre-incubation of the cells with proadifen. The changes observed in the release of these enzymes may be a reflection of the influence of ABA on mitochondrial activity. A decrease in the efficiency of energy production by the organelle affects cellular functions that are dependent on energy, and the disruption of these functions may result in cell death (Nicotera et al., 1998, Wallace and Starkov, 2000 and Szewczyk and Wojtczak, 2002). In in vivo studies performed by Lowenstein et al., 1996 and Hsu et al., 2001, ABA caused an elevation in the concentration of the AST in blood serum. El-Shenawy (2010) performed an in vitro study with isolated rat hepatocytes to compare the toxic action of several insecticides.

Moderate melting of a few meters per year occurs adjacent

Moderate melting of a few meters per year occurs adjacent www.selleckchem.com/products/cobimetinib-gdc-0973-rg7420.html to the ice front, especially between 1.5°W and 0°E where the ice shelf overhangs the continental shelf break. Enhanced melting in this region was inferred from oceanographic observations (Walkden et al., 2009), and recently this feature, which is consistently seen in modeling studies (Nicholls et al., 2008 and Smedsrud et al., 2006), has also been confirmed by remote sensing based (Rignot et al.,

2013) and in situ measurements (Langley et al., in preparation) of basal melting at the FIS. While errors in our simulations are likely to be introduced by the artificially enhanced minimum water column thickness of 100 m at the grounding line, the simulated maximum melt rate of about 15 m year−1 in the southernmost part of Jutulstraumen is in good agreement with estimates from glaciological mass flux divergence estimates in this location (Humbert, 2012). Test runs with a more realistic, but numerically less stable water column thickness of 50 m showed only minor variations of the simulated melt rates under forcing conditions similar to the ANN-100 experiment. Smaller areas of net freezing are also observed, mostly in regions where the buoyant ISW ascends along steeper parts of the ice base and becomes supercooled as it reaches shallower depth. But the amount of freezing contributes

less than 5% to the total basal mass balance Selleck AZD1208 in the ANN-100 experiment, suggesting that no substantial accretion of marine ice occurs beneath the FIS. However, freezing processes are incomplete, with no frazil ice processes being included in the model. The ANN-100 experiment features a seasonality of basal melt rates that suggests a distinct contribution of melting at different depths beneath the FIS. In order to illustrate this, Fig. 7(b) and (c) show the vertical distribution of ice shelf area and the basal melting contribution in various experiments. While the details of the depth-dependent melting response to

different model forcings will be discussed in Section 5.2, the histogram HSP90 of horizontal ice shelf area as a function of depth,2 shown by the dashed curve (left axis) in Fig. 7(b), reveals large areas of shallow ice at about 250 m depth and large areas of deep ice at about 350 m depth, with a natural separation at the local minimum of the curve at 300 m depth. As indicated by the thick 300 m contour in Fig. 7(a), this pronounced bi-modal distribution reflects the difference between the thicker body of the eastern FIS and the Jutulstraumen keel, and the large area of shallow ice in the central and western part of the FIS. Fig. 5 suggests that the melt rates within these two different portions of the FIS are controlled by the varying amounts of ASW and WDW that enter the cavity at different times of the year in the ANN-100 experiment. In addition to the synthetic mooring data in Fig. 5(a), Fig.

2), but our analyses were not designed to quantify their expressi

2), but our analyses were not designed to quantify their expression levels. Thus, we proceeded to de-orphanize the newly cloned ORs with a panel of 90 compounds, including oviposition attractants, plant-derived kairomones, repellents from natural sources, and mosquito attractants. We subcloned CquiOR1, CquiOR44, CquiOR73, and CquiOR161 into pGEMHE, expressed them along with the obligatory co-receptor CquiOrco in Xenopus oocytes, and then click here performed electrophysiological recordings by subjecting oocytes to our panel of test compounds. CquiOR1·CquiOrco-expressing oocytes behaved

like a generic OR ( Fig. 3), i.e., an OR that does not have a specific ligand, but responds to multiple compounds. Albeit responses were small

in general, the strongest current amplitudes were recorded when CquiOR1 was challenged with 1-hexanol, 1-octen-3-ol, 2-phenoxyethanol, or benzaldehyde ( Fig. 3, Fig. 4). Likewise, CquiOR44 was activated by multiple odorants at low level, but interestingly the strongest responses were recorded when CquiOR44·CquiOrco-expressing oocytes were challenged with plant kairomones ( Fig. 3), including known natural repellents like p-menthane-3,8-diol ( www.selleckchem.com/products/AZD6244.html Paluch et al., 2010) and eucalyptol ( Omolo et al., 2004). The most active ligand was fenchone ( Fig. 4), but there was apparently no chiral discrimination as responses to (+)- and (−)-fenchone did not differ. When challenged with the same panel

of compounds CquiOR73·CquiOrco-expressing oocytes responded differently. Robust responses were seen with eugenol, smaller responses to phenolic compounds, particularly 4-methylphenol (Fig. 4), and no significant response to the majority of compounds in the panel, except for octyl acetate. Then, we repeated these experiments by focusing on phenolic compounds, including dimethylphenols Interleukin-2 receptor (Fig. 4). These experiments showed strong responses elicited by 3,5-dimethylphenol (Fig. 3), stronger than those generated by other phenolic compounds, including methylphenols, but eugenol was the best ligand identified for this OR (Fig. 4). Based on these experiments we concluded that CquiOR73 is an eugenol-detecting OR, but the significance of a receptor tuned to phenolic compounds remains an interesting topic for future research. It did not escape our attention, however, that eugenol has been identified as a plant-derived insect repellent (Kafle and Shih, 2013). Lastly, we attempted to de-orphanize CquiOR161, but in marked contrast to the above-mentioned ORs, it did not respond to any of the test compounds. Despite several attempts at the UC Davis laboratory, CquiOR161 remained silent.

The law did not empower to the MFW to judge on violations instead

The law did not empower to the MFW to judge on violations instead of lengthy court cases. When

it comes to companies and industrial fleets, sanctions for violations include provisions for the revocation or suspension of the authorization to fish and are sometimes as severe as the confiscation of the boat and its equipment. However, on-board observers and inspectors rarely report the INK-128 violations and are sometimes forced not to report. If violations are indeed communicated to authorities, penalties are rarely enforced. Similarly, reporting of violations and enforcement of regulations is largely lacking within the small-scale sector, which affects compliance levels among fishermen. In fact, the level of compliance of fishermen with laws and regulations has been negatively affected by the widespread corruption Selleckchem MDV3100 in the

policymaking authorities, in the judicial systems, and in everyday local administrations. It is obvious that fish stocks have been depleted in many areas in the world׳s oceans and seas due to poaching, smuggling, overfishing, and violation of local, regional, and international laws [47] and [48]. IUU fishing is most detrimental and most likely occurs in countries where governance is weak and corruption is rampant, such as most developing countries [49] and [50]. This widespread IUU fishing in many developing countries has several severe only environmental, social, and economic consequences, including unfair competition, loss of biodiversity, loss of income, and even loss of human lives [48]. IUU fishing is a major issue and a source of serious concern for Yemeni fisheries. Such fishing undermines the contribution of fisheries to the food security, to income and livelihood and to the national economy. The widespread IUU fishing in Yemen is one of the major consequences of the weak governance reflected in the weak legislative, policy, and regulatory frameworks. There is no national plan to combat

IUU fishing. Sanctions are not specified for different types of violations and, where stated, are not sufficient to act as deterrents with the level of violations. The drivers behind IUU fishing include the lack of political will to prevent, deter, and eliminate IUU fishing, low levels of fines, the absence of effective monitoring, control, and surveillance (MCS) activities, and the weak enforcement of the laws and the regulations. IUU fishing in Yemen may occur in different forms. Illegal fishing practices within the small-scale sector include discarding of significant quantities of fish during bottom trawling and purse seining, the use of light when fishing using purse seines, the use of small-mesh nets, and the use of destructive fishing gear (particularly in sensitive habitats such as coral reef areas).

5A) These vesicles were not seen in fresh or frozen morulaes of

5A). These vesicles were not seen in fresh or frozen morulaes of same quality. Cytoplasm discontinuities, as well as organelle-free

areas were common after vitrification (Fig. 5B), as in frozen embryos. Vitrified grade III and also frozen embryos had heterogeneous cytoplasm in addition to mitochondrial LGK-974 cell line and SER swelling (Fig. 5C). Large vesicles occupying great areas of the cytoplasm (Fig. 5D) and degenerated cells among viable embryonic cells (not shown) were characteristics found only in the vitrified group. In this study, fresh embryos revealed intense mitochondrial activity. Active mitochondria were distributed throughout the cytoplasm, regardless of the embryonic developmental stage. However, no mitochondrial activity could be observed in cryopreserved embryos, either frozen or vitrified. The evaluation of mitochondrial activity after cryopreservation are unpublished in this species and it is known that mitochondrial dysfunctions check details or abnormalities may compromise developmental processes by inducing chromosomal segregation disorders, maturation and fertilization failures or even embryo fragmentation [4]. Sohn et al. [35] studied the effect of two frequencies of liquid N2 infusion on the cryopreservation of mice two-cell embryos on the mitochondrial activity and actin filaments distribution using

fluorescent markers similar to those used on the present work. Very similar to what this study revealed, those authors [35] showed that the number of mitochondria with high membrane potential decreased on cryopreserved embryos, and described gaps or discontinuities in the peripheral actin fibers (those in close association with the cell membrane), especially on the low frequency N2 infusion treatment. Disturbances in function and distribution of mitochondria, as well as changes in the organization of cytoskeleton related to insufficient culture conditions or cryopreservation are expected to occur and may reduce developmental capacity [12] and [15]. Previous studies have demonstrated succesfull cryopreservation

of mitochondria isolated from rat liver [17], muscles [25] and brain [29]. In brain tissue, mitochondria showed a reduction in respiratory activity after cryopreservation. However, this effect was not due to mitochondrial membranes rupture [29]. Penetration of the fluorochrome used in this experiment is proportional to the inner mitochondrial Thymidine kinase membrane activity and equilibrium [28], which was surely altered. However, in the present work no rupture of mitochondrial membranes was seen on the ultrastructural analysis. Nukala et al. [29] also found that freezing mitochondria without any cryoprotective agent destroyed their structural integrity and functional viability, and that the use of a cryopretective agent prevents most but not all damages. Moreover, the ability to restore a satisfactory metabolic activity or regenerate damaged structures after exposure to low temperatures requires time. For example, Leoni et al.

Processed data were imported to the ODV database (Ocean Data View

Processed data were imported to the ODV database (Ocean Data View, Schlitzer 2005) for further manipulation and export to relevant databases (e.g., WOCE, WOD, etc.). Horizontal maps of selected variables were produced using DIVA gridding software

(Data Interpolating Variational Analysis), an algorithm that considers coastlines and bathymetry features for domain subdivision and performs better in the case of sparse and heterogeneous data coverage (signal-to-noise ratio = 40; quality limit = 1.5; excluding outliers). Meridional sections were produced for each parameter using VG gridding, utilizing data from the original sampling stations and not reconstructing them from the 3-D parameter ZD1839 field. Meteorological data (air temperature, atmospheric pressure, wind speed and direction) for the period commencing fifteen days prior to the cruise start until the end of each annual cruise, were obtained from all the main airports of the broader North Aegean Sea area (Thessaloniki, Kavala, Alexandroupolis, Chios I., Lemnos I., Skyros I. and Istanbul). These data were combined with the surface wind vectors obtained from the NOAA 3-D atmospheric model, based on systematic satellite observations over the North Aegean Sea (http://www.arl.noaa.gov/ready/amet.html). Figure 3 presents a synoptic view of the surface wind vectors prevailing over the North Aegean Sea during each cruise period.

The significant impact of the Etesians (north to north-easterly 17-AAG research buy winds) during the 1998 to 2000 cruises is shown. Strong south to south-westerly winds, changing rapidly to northerlies,

dominate during the 2001 sampling period. The sea surface temperature displays a zonal distribution, with lower values (20–21°C) in the Thracian Sea and higher ones (23.2°C) in the Chios Basin (Figure 4a). This distinct north-to-south gradient is disrupted by the presence of cooler water (19–20°C) in the area south of Lemnos Island, corresponding to the BSW U0126 mouse core. Relatively colder water occupies the surface layer along the eastern coastline of the North and Central Aegean Sea, with values 22–23°C near Lesvos and Chios Islands, compared to the warmer water (24.5°C) near the Sporades Islands. A similar zonal pattern is also exhibited by the surface salinity, with minimum values in an extended area south of Lemnos Island (28.7–29.3), occupied by the BSW. From this minimum, the surface salinity showed gradually increasing values of 33.0–34.5 towards the Thracian Sea and to the south-west towards the Sporades Basin (33.8–36.3) (Figure 4b). The very distinctive frontal zone separating the BSW and the LIW appears to be located in the vicinity of Agios Efstratios Island. However, the ‘closed-bull-eye’ pattern in this area is mostly the result of the sparse and heterogeneous data coverage in this area, representing the exit of the BSW from the Dardanelles, rather than an existing hydrographic feature.

7 Since UNCLOS entered into force in 1994 it has become “the lega

7 Since UNCLOS entered into force in 1994 it has become “the legal framework within which all activities in the selleck compound oceans and seas must be carried out.”8 The convention reflects “sets of implicit or explicit principles, norms, rules, and decision-making procedures around which actors׳ expectations converge” concerning activity in the water column, on the seabed, on the surface of the ocean, and in the airspace above it.9 Creation of the EEZ, which is neither

territorial sea nor high seas, was one of the greatest innovations in UNCLOS, and it created the right and expectation among coastal states that they have exclusive sovereign rights in living resources to a distance of 200 nautical miles (nm) from shore, as well as jurisdiction over MSR in the zone. UNCLOS also recognizes a 12 nm territorial sea, over which the coastal state may exercise sovereignty. Consequently, bio-logging potentially implicates coastal state sovereignty find protocol in the territorial sea, and two coastal states interests in the EEZ: exclusive sovereign rights in the living resources and jurisdiction over MSR. Marine migratory species, however, are oblivious to the coastal zones established by UNCLOS,

and the legal regimes that apply within them. Coastal states enjoy sovereignty over the water column, airspace, and seabed of the territorial sea. Other states may access the territorial sea for the purpose of innocent passage – the “continuous and expeditious” transit of the zone in a manner that does not affect the “peace, good order o security of the coastal state.”10 Research and survey activities are inconsistent with innocent passage.11 The “express consent” of the coastal state is required for the conduct of MSR in the territorial sea.12 There is no exception to the requirement to receive coastal state consent for the conduct of MSR by ships engaged in innocent passage. Furthermore, in the territorial sea all states enjoy a right of entry, and

the right to render assistance to mariners in distress, under conditions of force majeure.13 These rules appear on their face to suggest MTMR9 marine scientists should seek and obtain coastal state consent for MSR in the territorial sea. This proscription, however, is limited to the physical presence of a vessel or scientist within the territorial sea. Merely studying the territorial sea remotely, either through satellite or from aircraft in flight beyond the outer limits of the territorial sea – or marine bio-logging – does not undermine the sovereignty of the coastal state. The EEZ constitutes about 40 per cent of the world׳s oceans – the coastal zone that includes estuarine, green and brown water habitat and the most productive marine ecosystems. These areas are under the resource jurisdiction of coastal states.14 Coastal states have sovereign rights for the purpose of exploring or exploiting, conserving and managing living resources in the EEZ.

Nevertheless, vertebral hypoplasia as a possible risk factor for

Nevertheless, vertebral hypoplasia as a possible risk factor for pathology, particularly of stroke in the vertebrobasilar circulation territory, was little emphasized yet. The aim of this preliminary study is to evaluate a hypothesis of a possible causal link between the learn more anatomical findings of VAH and the incidence of posterior circulation stroke. For this purpose, we assessed the relative

frequencies of posterior circulation strokes in patients with VAH as compared to patients without VAH, and also the relative frequencies of the conventional vascular risk factors (hypertension, diabetes, hyperlipidemia and smoking). Additionally, we determined the possible mechanism of stroke in our patients. A group of 44 patients (30 men, 14 women; mean age 67 years [range 44–88]) with acute ischemia in the vertebrobasilar territory had a full ultrasonographic examination of the extra- and intracranial arteries between September

2009 and February 2011. The location RG7204 mw of the acute ischemic infarct was judged clinically and confirmed by CT scan or MRI. We excluded patients with transient ischemic attacks (TIA), patients with other vertebral artery findings (such as atheromatosis, stenosis or occlusion) or other cerebral lesions, as well as those in whom a full ultrasonographic examination of the vertebral arteries was not possible. We used a 7.5-MHz linear array transducer for the duplex ultrasonographic examination of the vertebral arteries (B-mode and color-coded duplex flow imaging). In the V1 (prevertebral) and V2 (intervertebral) segments of the extracranial vertebral artery the distance between the internal layers of the parallel walls of the vessel (caliber of VA) and the hemodynamic characteristics of blood flow were

measured. The diameter equal or less than 2.5 mm, respectively the side difference equal or greater than 1:1.7 were set as a feature of vertebral artery hypoplasia. Additionally, reduced flow velocities as compared to the contralateral side, and higher peripheral resistance ipsilaterally (RI equal or greater than 0.75) were considered. MRA, CTA or conventional angiography was performed to confirm the presence or absence of the anatomic variation of hypoplasia. We also investigated the occurrence of other concomitant vascular risk factors such as hypertension, diabetes, hyperlipidemia TCL and smoking. In the group of 44 posterior circulation stroke patients, 9 (20%) had a hypoplastic vertebral artery and 35 (80%) were without VAH (Fig. 1A). There was more frequent right-sided VAH in 7 (78%), as compared to left-sided VAH in 2 (22%) cases (Fig. 1B). One patient had bilateral VAH (both vertebral arteries had a diameter of less than 2.5 mm), more significant on the right side. None of the patients had basilar artery hypoplasia. In the group of non-VAH patients were 22 men and 13 women, in the VAH group 8 men and 1 woman (Fig. 1C). There was a slight difference for age between the non-VAH (mean age 68.