1 The main parameters relevant for the determination of the tank

1. The main parameters relevant for the determination of the tank volumes and the location of the transverse and longitudinal bulkheads are shown in Fig. 4. LA and LF are the horizontal distance from the aft perpendicular to the aft cargo tank compartment and the horizontal distance from the fore perpendicular to the frontmost cargo tank compartment. LT, BT and DT are the cargo tank compartment length, width and depth and Vi the volume of tank i. The double hull width is denoted w and the double bottom height has notation h. The volume Vi of a given

tank is determined CH5424802 as: equation(6) Vi=CiBTLTDTVi=CiBTLTDTwhere Ci is a volumetric coefficient, accounting for the actual shape of the tank in comparison with a rectangular prism. Values for this factor are given in Table 1, taken as averages of an analysis by Smailys and Česnauskis (2006). The tank length, width and depth LT, BT and DT are determined as: equation(7) LT=(L-LA-LF)n equation(8) BT=(B-2w)m selleck equation(9) DT=D-hDT=D-hwhere n is the number of tanks in the longitudinal direction and m the number of tanks

in the transversal direction. It is thus assumed that all tanks have the same width BT and length LT. Values for LA and LF are given in Table 1, taken as average values reported by Smailys and Česnauskis (2006). The double bottom height h and double hull width w are determined based on the relevant rules for classification of ships ( Det Norske Veritas, 2007). The above information can be used to determine the set of positions of the longitudinal and transversal bulkheads, respectively noted LBH and TBH, as follows: equation(10) TBH=LA+kLT,k=0…n equation(11) LBH=w+kBT,k=0…m As the procedure to determine

tank arrangement is based on a series of simplifying assumptions, the methodology presented in Section 4.2.1 is validated by comparing the total calculated cargo tank volume with the DWT as available from the data of the 219 tankers, see Fig. 3. Fig. 5 shows a SPTLC1 comparison between the DWT as available in the tanker database (DWTD) with the DWT as calculated from the cargo tank volume (DWTC), assuming an oil density of 0.9 tonne/m3. It is seen that the calculation procedure generally overestimates the cargo tonnage. The histogram shows that the cargo tonnage is overestimated by ca. 15% on average, ranging from an underestimate of ca. 20% to a maximum overestimate of ca. 35%. Overall, the procedure thus leads to a conservative estimate for the possible oil outflow. While important for the evaluation of the oil outflow, it is not possible to validate the methodology in terms of bulkhead locations as the detailed tanker layouts are not available. A limited study by Smailys and Česnauskis (2006) indicates reasonable agreement for this aspect as well. The oil outflow in a given damage scenario for a particular tanker size and tank configuration is illustrated in Fig. 6.

5 cm2, respectively The median Dose 1 and 2 (boost) were 1500 cG

5 cm2, respectively. The median Dose 1 and 2 (boost) were 1500 cGy (range, 1250–1750 cGy) and 1750 cGy (range, 1750–1850 cGy), respectively. In all cases, the dose was prescribed to 0.5-cm depth from the applicator surface. The median treatment time was 36.5 min (range, 12–98 min). The median followup was 14.9 months (range, 1–41 months) and OS was 17.5 months (range, 6–34 months). The 2-year actuarial LC and OS for all patients were 80% and 20%, respectively (Figs. 6a and 6b). Eleven patients (68.7%) developed distant metastasis (DM) and had died owing to the progression of disease at the time of last followup. Among the 4 patients who

had an R1 resection, 3 died of DM disease (75%) and RO4929097 cell line 2 (50%) had evidence of local recurrence. None of the patients who underwent an R0 resection had a definitive local recurrence as of the time of last followup or death. IORT-specific AC220 price complications were identified by any description in the medical record of sign or symptom that could specifically be related to previous radiation treatment. Three patients (19%) developed toxicity Grade 3 described as “related to HDR-IORT.” All of them also had recurrent colorectal neoplasm. One patient developed ureteral stricture requiring nephrostomy and stent placement. The second patient

developed a pelvic abscess and ileal pouch/colonic fistula and a third patient developed a rectovaginal fistula. No Grade 4 or 5 toxicity was identified. Local failure after combined modality therapy remains a clinical challenge for many types of cancer, as further local options are often limited owing to postoperative and postradiation fibrosis and adhesions, the absence of intact fascial planes, and highly infiltrative disease. Systemic therapy may also be less effective in the setting of prior surgery and radiotherapy owing to poor vascular supply to the irradiated postoperative bed. Locally recurrent malignancies can cause severe pain owing to compression or nerve involvement, bleeding,

or obstruction of adjacent structures such as gastrointestinal or urinary tract. Retreatment using EBRT is limited by dose constraints for previously treated normal tissue adjacent to the tumor bed. Surgical resection of a recurrent tumor in a previously Bupivacaine irradiated field may be very challenging and outcomes have historically been poor, with 5-year survival rates of 0% for patients undergoing surgery alone for pelvic recurrence from rectal cancer (3). Thus, at most institutions, patients are treated with palliative intent; however, this subset of patients should be considered for salvage treatment using a multimodality approach. Radical resection with IORT has the advantage of delivering tumoricidal doses of radiation to areas with very high risk for local failure, while minimizing the dose to adjacent normal organs [7] and [8]. The DP technique adds additional flexibility in delivering HDR-IORT to complex, deep, and previously irradiated areas, especially in recurrent colorectal tumors.

A single influenza B virus isolated from a participant during 200

A single influenza B virus isolated from a participant during 2008, and propagated in MDCK cells was used to assess serum for both the first and second seasons. The virus had EPZ015666 purchase a titer of 320 with B/Wisconsin/1/2010 (Yamagata) reference antisera and of <10 with B/Brisbane/60/2008

(Victoria) antisera. A reference antigen supplied by WHO (A/California/7/2009(H1N1)-like) was used to assess season 3/pandemic plasma. The HI titer was read as the reciprocal of the highest serum dilution causing complete inhibition of agglutination, partial agglutination was not scored as inhibition of agglutination. If there was no inhibition of HI at the highest serum concentration (1:10 dilution) the titer was designated as 5. Only one sample had a titer >1280 and this was not

adjusted. Influenza infection’ was defined as either the detection of influenza RNA in a swab sample by RT-PCR or a four fold or greater rise in HI titer, with a second titer of at least 40. Participants were excluded from analysis of each season if they were not present for ILI surveillance during the periods of LGK 974 confirmed influenza transmission or if paired-plasma were not collected. Additionally, participants were excluded from the analysis of effect of infection in one season on infection in subsequent season if they had not been available or fully assessed for infection in both seasons. The risk of an infection was modeled as depending on

the (log2-transformed) pre-season titer using a marginal logistic regression model, which takes into account potential household clustering. Unadjusted titer effects and titer effects adjusted for age (modeled as a natural cubic spline with 3 degrees of freedom and knots at 10 and 20 years) were calculated. We also tested for potential non-linear effects of the log2-titer on outcome by additionally including a quadratic term into the model and for titer–age interactions. The risk of infection was also modeled as depending on infection in the preceding season with each strain that did not induce HI antibodies (i.e. prior heterologous infections). As above, marginal logistic regression was used to account for potential household clustering and results adjusted for effects of age and pre-season HI titer. Statistical analyses Methane monooxygenase were performed with the statistical software R version 2.15.0 (R foundation for Statistical Computing, Vienna, Austria) and the companion R package geepack version 1.1-6. A detailed description of the cohort and of the infections and illnesses detected has been presented previously.21 In brief, 940 individuals were studied for three consecutive influenza seasons, from December 2007 through April 2010, resulting in 1793 person-seasons of influenza surveillance. The age of participants ranged from <1 to 90 years and none had ever received influenza vaccination.

Revascularisation of the wound-related artery is associated with

Revascularisation of the wound-related artery is associated with higher limb salvage rates than revascularisation of the arteries running to other angiosomes [146] and [147]. Even in the case of surgical revascularisation by means of a bypass, Neville has shown that a direct bypass on the wound-related artery leads to higher

limb salvage rates [134]. If tibial artery treatment is technically Bioactive Compound Library ic50 impossible, angioplasty of the distal perforating branches of the peroneal artery is a successful practicable option. Neither complete nor wound-related artery revascularisation should be pursued uncritically, but both should be personalised on the basis of a realistic technical strategy, the type of tissue lesions and their orthopaedic surgical treatment and the patient’s general clinical condition. [148] • The main aim of revascularisation is to reopen all occluded arteries. There are

currently no unequivocal criteria that define with certainty Selleck BLZ945 the most appropriate follow-up methods for patients who have undergone revascularisation because of ischaemic DF. This is probably due to the heterogeneity of patients with CLI: these may be relatively young with a good life expectancy and be suitable for the application of severe follow-up criteria that consider vascular, tissue and general aspects. However, there are also patients characterised by a ‘terminal’ Glutamate dehydrogenase picture of widespread atherosclerotic disease, who therefore have a very limited life expectancy in whom the follow-up should be less invasive. Generally, the follow-up should be clinical, oximetric and/or ultrasonographic, and the examinations should take place 1, 3, 6 and 12 months after treatment, and every 12 months thereafter. However, just as the treatment of DF needing a multidisciplinary approach, we believe that the follow-up

of revascularised patients should also be global, multidisciplinary and personalised, and take into account the following key elements. The criteria indicating the purely haemodynamic success of revascularisation are primary and secondary patency, that is, the capacity of the revascularisation procedure to guarantee the continued patency of the treated vessel or bypass [41]. In the case of a bypass, the follow-up should include Doppler ultrasonography in order to detect any restenosis (generally of the anastomosis) or the upstream or downstream progression of bypass disease; the treatment of such obstructions is fundamental as it prolongs the life of the bypass itself [149].

1 e) This ascending branch lies entirely within the parietal lob

1 e). This ascending branch lies entirely within the parietal lobe and is considered as part of the angular gyrus. The adjacent posterior vertical sulcus is the anterior occipital sulcus [posterior intermediate parietal sulcus] (k; see Wernicke (1881)). This sulcus considered representing

the border between the parietal and the occipital lobes. This sulcus can appear in different shapes. Usually, it continuous ventrally into the continuation of the superior temporal sulcus [e] and thus gives rise to a second ascending branch of PD332991 the latter. At times, however, it appears as a very short indentation without connection to any other gyri. It is, nonetheless, found in every brain and is readily identifiable, when following the occipito-parietal INCB024360 manufacturer sulcus (o) on the convexity (Fig. 1) to the inferior transitional gyrus (above k) (Fig. 1) between the parietal and the occipital lobes. The opening of this

gyrus is the anterior occipital sulcus. Within the occipital lobe there are three deep sulci that are almost horizontal to each other before they separate anteriorly (Ecker, 1869). The superior/first occipital sulcus (s. o. I) is an extension of the intraparietal sulcus (i), which usually reaches the occipital pole, though interrupted. The middle/second occipital sulcus (s. o. II) reaches anteriorly towards the horizontal branch of the superior temporal sulcus (e). The inferior/third occipital sulcus (s. o. III) runs towards the Niclosamide second or third temporal sulcus. The inferior occipital sulcus often runs adjacent to the inferior convexity of the hemisphere and sometimes even at the basal surface. The middle occipital sulcus corresponds mostly to the lower occipital sulcus of Wernicke. Whereas both vertical sulci and the first horizontal sulcus are consistent and readily identifiable; the middle and inferior

occipital sulci are often interrupted and branch off, and are therefore less clear. The occipital lobe is delineated on the medial surface of the hemisphere (Fig. 2) by the occipito-parietal sulcus [o] separating the cuneus and precuneus, and by the calcarine fissure (f.c.), which adheres anteriorly with the abovementioned sulcus [o]. Both sulci are rarely simple incisions. Usually, their stem forms a surface similar to the insula with secondary gyri. Nevertheless, this morphology is variable. The “posterior incision” of the occipito-parietal sulcus may extend many centimetres into the occipital lobe. Adjacent to the calcarine fissure a short gyrus extending rostro-caudally can be seen superimposed on the top and bottom surfaces facing each other. In the depth of the fissure three vertical short gyri extend dorso-ventrally. Two of these can continue to the convexity of the sulcus and merge with the above-mentioned gyri; whereas the third sulcus, that is the middle or the posterior, never extends to the convexity. Such a short gyrus can reach at times the convexity and thus interrupt the fissure.

In total, 70 neonatal GFP-expressing transgenic rats (“green rat”

In total, 70 neonatal GFP-expressing transgenic rats (“green rat” CZ-004, SD-Tg(Act-EGFP) CZ-004Osb; Japan SLC, Shizuoka, Japan) were used for harvesting the primary NSPCs.

The animals were housed in a well-controlled environment with a 12-hour/12-hour light/dark cycle and controlled humidity and temperature. Rats were triple housed in plastic cages with ad libitum access to food and water. All experimental procedures were approved by the Institute of Animal check details Care and Utilization Committee at Academia Sinica (Taipei, Taiwan). The pregnant Sprague-Dawley rats were placed into a restrainer and injected intraperitoneally with 50 mg/kg ENU (Sigma-Aldrich, St Louis, MO) at 18 days of gestation using a 26-gauge needle for several minutes. MRI was applied to 120-day-old offspring to confirm the location and size of the tumors. Rats with similar-sized tumors (~ 1 mm3) near the corpus callosum were selected for experiments. Rats with trigeminal neurinoma and pituitary tumors or with obvious physiological defects were excluded from this study.

GFP-NSPCs were harvested from both lateral walls of the ventricle in neonatal GFP-expressing transgenic rats and cultured as described elsewhere [31] and [32]. In brief, pooled tissues isolated from the lateral walls were dissociated by mechanical trituration in NSPC medium, which consists of Dulbecco’s modified Eagle’s medium/F12 (Invitrogen/Gibco BRL, Grand Island, NY) with 0.3% glucose, 23 μg/ml insulin, 92 μg/ml apotransferrin, 55 μM putrescine, 25 nM sodium selenite, 6.28 ng/ml progesterone, AZD2281 ic50 20 ng/ml epidermal growth factor, and 20 ng/ml fibroblast growth factor. The cells were then counted and plated at a density of 1.5 × 106 cells in T75 flasks (Orange Scientific, Brussels, Belgium) with 20 ml of medium. The Fossariinae cultures were replenished with 20 ml of NSPC medium every 2 days. The

cultures were maintained at 37°C in a humidified atmosphere of 5% CO2/95% air. At 5 to 7 days after isolation, the cells grew as free-floating neurospheres, which were dissociated into single cells for transplantation when they reached diameters of 140 to 160 μm. The rats were randomly assigned to the following treatment groups: 1) NSPC only (n = 6), 2) CXCL12 only (n = 6), 3) CXCL12-NSPC (n = 6), and 4) sham (n = 6). The animals were anesthetized with chloral hydrate (450 mg/kg; Sigma-Aldrich) and positioned in a stereotaxic apparatus. In the case of GFP-NSPC transplantation (i.e., NSPC and CXCL12-NSPC groups), the cells were freshly prepared [1 × 106 in 5 μl of phosphate-buffered saline (PBS), pH 7.4] and implanted into the lateral ventricle ipsilateral to the site of tumors (bregma = –0.5 mm; lateral = –1.5 or 1.5 mm; and depth = 3.5 mm) using a 10-μl Hamilton syringe with a 30S-gauge needle at a rate of 0.5 μl/min.

, 2006) Veraart׳s group are continuing testing of their device (

, 2006). Veraart׳s group are continuing testing of their device (Brelen et al., 2010), and have since been joined by two others developing optic nerve prostheses using electrodes stimulating either the optic nerve or the optic disk (Lu

et al., 2013, Sakaguchi et al., 2009 and Wu et al., 2010). The lateral geniculate nucleus (LGN) is considered a favorable stimulation target due to its compact dimensions, retinotopic organization and the physical separation of pathways specific to color and motion (Mullen et al., 2008 and Wiesel and Hubel, 1966). The Protease Inhibitor Library mouse proximity of the LGN to structures targeted surgically for pain control and movement disorders resulted in reports of visual phenomena experienced during thalamic stimulation procedures over three decades ago. Some of these reports were published by Marg and Driessen (1965), with their patients describing highly complex visual phenomena during deep brain stimulation. In a recent macaque study however, it was shown that simple, discrete visual percepts could be elicited by microstimulation of LGN (Pezaris and Reid, 2007). While in that study Pezaris et al. analyzed visual saccades in response to LGN stimulation, Panetsos et al. (2011) recently analyzed rat and rabbit Volasertib cortical responses to LGN stimulation, concluding that such stimulation could generate visual cortical responses resembling those elicited

by natural vision. While much work remains to be done, both groups report plans for further studies in support of developing a functionally useful visual prosthesis based on LGN stimulation (Panetsos et al., 2011 and Pezaris and Eskandar, 2009). Reports exist of complex visual percepts elicited 4��8C by stimulation of the optic radiations during neurosurgical procedures (Chapanis et al., 1973 and Marg and Driessen, 1965), however to date there are no groups known to us for whom this site is a stimulation target for developing a visual prosthesis. Primary visual cortex, or V1, is an area of the occipital lobe that encompasses the buried

portions of cortex in the calcarine sulcus and its upper and lower banks, extending posterolaterally to the occipital pole. The reported surface area of V1 varies between 1400 and 6300 mm2, depending on the method of estimation (Andrews et al., 1997, Genc et al., 2014 and Stensaas et al., 1974), with approximately 67% of that area buried inside the calcarine fissure (Stensaas et al., 1974). Most efferent fibers from the LGN synapse with layer 4 of V1, from which numerous connections to other layers within V1 and those of higher visual centers are made (Troncoso et al., 2011). Human trials of visual cortex electrical stimulation with both surface and penetrating electrodes have demonstrated the viability of this brain region as a target for a visual prosthesis (Dobelle, 2000 and Schmidt et al., 1996).

This is the first head-to-head assessment

This is the first head-to-head assessment Buparlisib datasheet of PCR and a selection of widely-applied commercial serological assays (NS-1 antigen, IgM and IgG antibodies). It is also the first diagnostic assessment that has demonstrated the improved diagnostic accuracy when selections of PCR, NS-1 antigen, IgM and IgG antibody test results are combined. Shoklo Malaria Research Unit (SMRU) undertakes surveillance for malaria and other infectious diseases, and provides general

medical care for the migrant and refugee population, in five clinics in rural Thailand, on the Thailand-Myanmar (Burma) border. We conducted dengue surveillance from April to August 2008 in the SMRU clinics at Mawker Thai village (MKT) and Maela refugee camp (MLA), both located

in rural Tak province approximately 500 km northwest of Bangkok. Adult patients (age ≥15 years old) presenting BAY 80-6946 cell line to the clinics with fever ≥38°C of less than seven days duration and any clinical symptoms or physical signs consistent with dengue (abnormal bleeding, eye redness, headache, myalgia or rash) were included in the surveillance and blood was drawn to inform clinical management (blood culture, complete blood count, and plasma for serology). Patients who had a clear alternative diagnosis such as malaria, urinary tract infection or pneumonia were excluded from the surveillance. In addition to dengue virus, patients were serologically investigated for leptospirosis (ELISA with confirmation by the microscopic agglutination test) and rickettsial infection (ELISA with confirmation by indirect immunofluorescence assay), the other common causes of undifferentiated fever in SE Asia. A 6 ml acute venous blood specimen was collected

from each patient in a sterile EDTA tube (Becton Dickinson, Franklin Lakes, NJ, USA) for dengue rRT-PCR, NS-1 antigen detection, and dengue IgM and IgG antibody detection tests. The patients were reviewed at a 10–14 day follow-up PAK5 visit and a repeat 6 ml convalescent venous blood specimen was collected for dengue IgM and IgG antibody tests. Plasma was separated by centrifugation and frozen at −80 °C prior to the assays. Viral RNA was extracted from 150 μl of the acute plasma specimens using the NucleoSpin RNA virus extraction kit (Macherey Nagel, Düren, Germany) according to the manufacturer’s instructions and was stored at −80 °C prior to testing. One-step SYBR Green-based rRT-PCR, modified from Shu et al., was performed using the RotorGene 6000 real-time PCR system (Corbett Research, San Francisco, CA, USA).11 The reaction volume was 25 μl, comprising 10 μl of extracted RNA, 1 μl of each primer (10 μM), 12.5 μl of 2X SYBR Green reaction mix (containing 0.

ABA significantly inhibited the synthesis of ATP at 10 μM and rea

ABA significantly inhibited the synthesis of ATP at 10 μM and reached a maximum effect at 15 μM. The ANT is an important component of the mitochondrial machinery of ATP synthesis because of its intrinsic adenine nucleotide translocase activity. ANT participates in both pathological (mitochondrial permeability

transition selleck compound formation/regulation and cell death) and physiological (adenine nucleotide exchange) mitochondrial events, making it a prime target for drug-induced toxicity (Oliveira and Wallace, 2006). To demonstrate ABA-induced inhibition of ATPase and/or ANT, we evaluated its effects in the activity of ATPase using intact-uncoupled and freeze–thawing-disrupted mitochondria with an excess of ATP, a condition that drives the enzyme to operate in the reverse direction, hydrolyzing ATP (Bracht et al., 2003), and also in the ADP-induced depolarization of Δψ. We saw more significant stimulation of ATPase activity in intact-uncoupled mitochondria than in disrupted mitochondria, which taken together with the observed inhibition of ADP-induced depolarization of Δψ indicates that abamectin more specifically inhibits ANT than FoF1-ATPase.

Adriamycin In conclusion, the present study shows that ABA perturbs the mitochondrial bioenergetics through different mechanisms and that its effect on the adenine nucleotide translocator (ANT) is more potent than on FoF1-ATPase. These effects constitute a potential mechanism for ABA toxicity in liver cells, which could contribute to the toxicological effects of ABA described in animals and human. The authors declare that there are no conflicts of interest. This work was supported by grants from Fundação de Amparo

à Pesquisa do Estado de São Paulo (FAPESP). Results will be presented by Juliana Carla Castanha click here Zanoli to the Faculdade de Medicina Veterinária de Araçatuba, Universidade Estadual Paulista “Júlio de Mesquita Filho”, in partial fulfillment of the requirements for the Master degree in Ciência Animal. “
“Phthalocyanines (PCs) are macrocyclic complexes whose π systems (bonds in which the atomic orbitals overlap in parallel, forming an electron density cloud above and below the internuclear axis) (Graham Solomons and Fryhle, 2001 and Pine et al., 1982) are delocalized over an arrangement of conjugated carbon and nitrogen atoms, providing for their unique chemical and physical properties (Fig. 1) (Leznoff and Lever, 2004 and Mckeown, 1998). Due to the significance of the structural component of the π system in PCs, studies on the nature of the π system and attempts to modulate it have been intensively investigated (Day et al., 1975 and Svetlana et al., 1996). Many of the properties of PCs are highly dependent on the extent of intermolecular π–π stacking interactions between the planar faces of the macrocycles.

Marine management has the central aim of protecting the health of

Marine management has the central aim of protecting the health of the system, whether that health relates to natural functioning or the wellbeing of Man. Therefore it is helpful to think of health as defined under FOUR categories: medical, biological, societal and economic, each of which requires protecting. If our main aim in marine management is to protect health then, as far as the biology is concerned, we can consider health at each of SIX different levels of biological organisation and judge changes in these against uncertainty and variability in the system (McLusky

and Elliott, 2004 and Borja et al., 2010a): • Health of the cell – as functioning, at a molecular/biochemical level, maintenance of cellular beta-catenin inhibitor processes; as structure as the integrity of the organelles. In essence,

the detection of change in health and consequent aim by management is to ensure those levels are fit-for-survival. We take the precautionary approach which assumes that stress will be transferred through the natural system but in reality the system can absorb stress, termed environmental homeostasis ( Elliott and selleck chemical Quintino, 2007). As we go through each of these SIX levels, the complexity increases, it is more difficult to detect a response, a greater level of stress is needed to create a response and the response times increase. We assume, through the precautionary principle, that the effects Idoxuridine at one biological level, e.g. cell, will be transmitted to another, e.g. population if the stress is not removed although systems have an inherent ability to reduce or remove the effects of stress (individual or environmental homeostasis) ( Elliott and Quintino, 2007). We can then adopt the language of health for wider environmental change and the means of addressing problems: hence we can regard adverse change as SEVEN symptoms of marine ecosystem pathology for wider use and identify a few indicators of change for a wide and general application across human-derived problems (Box 3). It is interesting that the determination of unhealthy ecosystems

is analogous with medicine which uses diagnosis, prognosis, treatment and prevention which can be directly translated to environmental systems in which we carry out FIVE stages: of assessment, prediction, remediation/creation/restoration, recovery and prevention. We manage in order to deliver a healthy system which we can define as a system fit-for-purpose – i.e. the big idea fulfilling ecology and social-economy. Taking ideas from the human, medical system, we can show the similarities in approach whereby we make a diagnosis of change or a prognosis of future change – if the system becomes or is likely to become degraded then we bring in treatment or prevention of change, we may even have to restore the system to health by various measures ( Elliott et al., 2007 and Borja et al.