Development of a novel algorithm for metal artifact reduction in digital tomosynthesis using projection-based dual-energy material decomposition for arthroplasty: A phantom study

In this study, a novel dual-energy (DE) material decomposition reconstruction algorithm (DEMDRA) was developed using projection data with the aim of reducing metal artifacts during digital tomosynthesis (DT) for implants. Using the three-material decomposition method and decomposition projection data specific for each material, a novel DEMDRA was implemented to reduce metal artifacts via weighted hybrid reconstructed images [maximum likelihood expectation maximization (MLEM) and shift-and-add (SAA)]. Pulsed X-ray exposures with rapid switching between low and high tube potential kVp were used for DE-DT imaging, and the images were compared using conventional filtered back projection (FBP), MLEM, the simultaneous algebraic reconstruction technique total variation (SART-TV), virtual monochromatic processing, and metal artifact reduction (MAR)-processing algorithms. The reductions in metal artifacts were compared using an artifact index (AI), Gumbel distribution of the largest variations, and the artifact spread functions (ASFs) for prosthesis phantom. The novel DEMDRA yielded an adequately effective overall performance in terms of the AI, and the resulting images yielded good results independently of the type of metal used in the prosthetic phantom, as well as good noise artifact removal, particularly at greater distances from metal objects. Furthermore, the DEMDRA represented the minimum in the model of largest variations. Regarding the ASF analysis, the novel DEMDRA yielded superior metal artifact reduction when compared with conventional reconstruction algorithms with and without MAR processing. Finally, the DEMDRA was particularly useful for reducing high-frequency artifacts.     

The economic effects of an estrus synchronization protocol using prostaglandin in beef heifers

We estimated the effect of estrus synchronization on reproduction, production and economic outcomes in 272 beef heifers randomly allocated to a synchronized Test group or an unsynchronized Control group. The Test group received AI upon estrus detection for 6 days followed by PGF2 treatment of heifers that had not shown estrus by day 6 (PGF/6). In both groups AI was continued for 50 days, followed by a 42-day bull breeding period. Heifers were followed through their second breeding season and until they had weaned their first calves. Synchronization resulted in a reduction in median days to first insemination (8 vs. 11 in the Test and Control groups, respectively, P < 0.01) and median days to calving of calves born to AI (14 vs. 20, P = 0.04). There was no significant difference in pregnancy rate to the AI period (60.0% vs. 51.8%, P = 0.18), final pregnancy rate (82.2% vs. 83.2%, P = 0.87) or pregnancy rate to the subsequent breeding season (96.0% vs. 95.0%, P = 1.00). Although mean calf weaning mass was not significantly different (207.0 kg vs. 201.4 kg, P = 0.32), the total mass of calves weaned in this study was 14,843 kg vs. 13,060 kg and the benefit: cost ratio for synchronization was 2.8. It was therefore concluded that a PGF/6 protocol may affect the total mass of calves weaned by changing days to calving, weaning rate, the ratio of male: female calves born and/or the birth mass of calves.     

Digital breast tomosynthesis: Dose and image quality assessment

The aim of this work was to evaluate how different acquisition geometries and reconstruction parameters affect the performance of four digital breast tomosynthesis (DBT) systems (Senographe Essential – GE, Mammomat Inspiration – Siemens, Selenia Dimensions – Hologic and Amulet Innovality – Fujifilm) on the basis of a physical characterization.Average Glandular Dose (AGD) and image quality parameters such as in-plane/in-depth resolution, signal difference to noise ratio (SDNR) and artefact spread function (ASF) were examined.Measured AGD values resulted below EUREF limits for 2D imaging. A large variability was recorded among the investigated systems: the mean dose ratio DBT/2D ranged between 1.1 and 1.9.In-plane resolution was in the range: 2.2 mm⁻¹–3.8 mm⁻¹ in chest wall-nipple direction. A worse resolution was found for all devices in tube travel direction.In-depth resolution improved with increasing scan angle but was also affected by the choice of reconstruction and post-processing algorithms. The highest z-resolution was provided by Siemens (50°, FWHM = 2.3 mm) followed by GE (25°, FWHM = 2.8 mm), while the Fujifilm HR showed the lowest one, despite its wide scan angle (40°, FWHM = 4.1 mm).The ASF was dependent on scan angle: smaller range systems showed wider ASF curves; however a clear relationship was not found between scan angle and ASF, due to the different post processing and reconstruction algorithms.SDNR analysis, performed on Fujifilm system, demonstrated that pixel binning improves detectability for a fixed dose/projection.In conclusion, we provide a performance comparison among four DBT systems under a clinical acquisition mode.     

A newly-developed metal artifact reduction algorithm improves the visibility of oral cavity lesions on 320-MDCT volume scans

PurposeTo investigate whether a newly-developed single-energy metal artifact reduction (SEMAR) algorithm applied to images acquired on a 320-MDCT volume scanner reduces image artifacts from dental metal.MethodsWe inserted the lower right teeth covered with a dental metal alloy and crown in a skull phantom and performed single-volume scanning on a second-generation 320-MDCT scanner. A 12-mm diameter spherical lesion was placed either close to or far from the dental metal. The tube voltage and current were 120 kVp and 80 or 155 mA, respectively. Images were reconstructed with filtered back projection (FBP) or iterative reconstruction (IR), with or without SEMAR. We calculated the signal-to-artifact ratios (SAR) to quantify the visibility of the lesion. Two radiologists inspected 96 images (48 with lesion and 48 without) for the presence or absence of the lesion using a 5-point ordinal scale (1 = definitely absent to 5 = definitely present).ResultsOn images reconstructed with FPB and IR with SEMAR, streak artifacts from the dental metal were reduced substantially compared to images without SEMAR. At 155 mA with the lesion near the dental metal, the SARs were better on FBP and IR images (FBP: 1.7 and 0.5 with and without SEMAR, respectively; IR: 1.6 and 0.9 with and without SEMAR, respectively). The observer visual scores improved with SEMAR (FBP: 4.2 and 3.2 with and without SEMAR, respectively; IR: 4.2 and 3.0).ConclusionThe SEMAR algorithm reduces dental metal artifacts and improves lesion detectability and image quality in patients with oral cavity lesions.     

Object shape dependency of in-plane resolution for iterative reconstruction of computed tomography

The present study aimed to investigate whether the in-plane resolution property of iterative reconstruction (IR) of computed tomography (CT) data is object shape-dependent by testing columnar shapes with diameters of 3, 7, and 10 cm (circular edge method) and a cubic shape with 5-cm side lengths (linear edge method). For each shape, objects were constructed of acrylic (contrast in Hounsfield units [ΔHU] = 120) as well as a soft tissue equivalent material (ΔHU = 50). For each shape, we measured the modulation transfer functions (MTFs) of IR and filtered back projection (FBP) using two multi-slice CT scanners at scan doses of 5 and 10 mGy. In addition, we evaluated a thin metal wire using the conventional method at 10 mGy. For FBP images, the MTF results of the tested objects and the wire method showed substantial agreement, thus demonstrating the validity of our analysis technique. For IR images, the MTF results of different shapes were nearly identical for each object contrast and dose combination, and we did not observe shape-dependent effects of the resolution properties of either tested IR. We conclude that both the circular edge method and linear edge method are equally useful for evaluating the resolution properties of IRs.     

Comparaison entre OSEM-3D et rétroprojection filtrée pour les images traitées par SISCOM dans l’épilepsie temporale

IntroductionWhen ictal and interictal brain SPECT are reconstructed with filtered backprojection (FBP), the noise level of subtraction images is frequently high and requires the use of thresholding methods. The aim of this study was to compare the subtraction images for cerebral SPECT reconstructed either with FBP or with a 3D iterative reconstruction method (OSEM-3D).Material and methodsAfter optimisation of the reconstruction parameters on phantom, the subtraction SPECT images, which were obtained with FBP or with OSEM-3D and coregistered with MRI images, were analyzed in 15 patients with refractory temporal epilepsy.ResultsOn phantom and with the constrain of high enough spatial resolution (full width at half of maximum for a punctual source less than or equal to 11 mm) were reached using: (i) a Butterworth filter with a cut-off frequency of 0.4 Nyquist at order 6 for FBP and (ii) five iterations, 16 subsets and a 9 mm gaussian filter for OSEM-3D. On the subtraction images, which were obtained with these optimal parameters, the temporal foci from patients were smaller with OSEM-3D than with FBP (11 ± 6 cm³ versus 17 ± 10 cm³, P = 0.02), mean voxel activities were equivalent between the two methods within temporal foci (6.30 ± 3.13 counts versus 6.34 ± 4.93 counts) but these activities were dramatically reduced by OSEM-3D within background regions (0.02 ± 0.02 counts versus 0.19 ± 0.12 counts, P < 0.001).ConclusionFor the ictal–interictal subtraction SPECT images, which are obtained in patients with refractory temporal epilepsy, the use of an optimized OSEM-3D method leads to dramatically reduce the volume of temporal foci, as well as the background noise level, two properties that are likely to facilitate the detection and localisation of epilepsy foci.     

Objective assessment of low-contrast computed tomography images with iterative reconstruction

ObjectiveThis study aims to assess low-contrast image quality using a low-contrast object specific contrast-to-noise ratio (CNR_LO) analysis for iterative reconstruction (IR) computed tomography (CT) images.MethodsA phantom composed of low-contrast rods placed in a uniform material was used in this study. Images were reconstructed using filtered back projection (FBP) and IR (Adaptive Iterative Dose Reduction 3D). Scans were performed at six dose levels: 1.0, 1.8, 3.1, 4.6, 7.1 and 13.3 mGy. Objective image quality was assessed by comparing CNR_LO with CNR using a human observer test.ResultsCompared with FBP, IR yielded increased CNR at the same dose levels. The results of CNR_LO and observer tests showed similarities or only marginal differences between FBP and IR at the same dose levels. The coefficient of determination for CNR_LO was significantly better (R² = 0.86) than that of CNR (R² = 0.47).ConclusionFor IR, CNR_LO could potentially serve as an objective index reflective of a human observer assessment. The results of CNR_LO test indicated that the IR algorithm was not superior to FBP in terms of low-contrast detectability at the same radiation doses.     

Dosimetric impact of 4DCT artifact in carbon-ion scanning beam treatment: Worst case analysis in lung and liver treatments

IntroductionWe evaluated the impact of 4DCT artifacts on carbon-ion pencil beam scanning dose distributions in lung and liver treatment.Methods & materials4DCT was performed in 20 liver and lung patients using area-detector CT (original 4DCT). 4DCT acquisition by multi-detector row CT was simulated using original 4DCT by selecting other phases randomly (plus/minus 20% phases). Since tumor position can move over the respiratory range in original 4DCT, mid-exhalation was set as reference phase. Total prescribed dose of 60 Gy (RBE) was delivered to the clinical target volume (CTV). Reference dose distribution was calculated with the original CT, and actual dose distributions were calculated with treatment planning parameters optimized using the simulated CT (simulated dose). Dose distribution was calculated by substituting these parameters into the original CT.ResultsFor liver cases, CTV-D95 and CTV-Dmin values for the reference dose were 97.6 ± 0.5% and 89.8 ± 0.6% of prescribed dose, respectively. Values for the simulated dose were significantly degraded, to 88.6 ± 14.0% and 46.3 ± 26.7%, respectively. Dose assessment results for lung cases were 84.8 ± 12.8% and 58.0 ± 24.5% for the simulated dose, showing significant degradation over the reference dose of 95.1 ± 1.5% and 87.0 ± 2.2%, respectively.Conclusions4DCT image quality should be closely checked to minimize degradation of dose conformation due to 4DCT artifacts. Medical staff should pay particular attention to checking the quality of 4DCT images as a function of respiratory phase, because it is difficult to recognize 4DCT artifact on a single phase in some cases     

CT dose reduction using Automatic Exposure Control and iterative reconstruction: A chest paediatric phantoms study

PurposeTo evaluate the impact of Automatic Exposure Control (AEC) on radiation dose and image quality in paediatric chest scans (MDCT), with or without iterative reconstruction (IR).MethodsThree anthropomorphic phantoms representing children aged one, five and 10-year-old were explored using AEC system (CARE Dose 4D) with five modulation strength options. For each phantom, six acquisitions were carried out: one with fixed mAs (without AEC) and five each with different modulation strength. Raw data were reconstructed with Filtered Back Projection (FBP) and with two distinct levels of IR using soft and strong kernels. Dose reduction and image quality indices (Noise, SNR, CNR) were measured in lung and soft tissues. Noise Power Spectrum (NPS) was evaluated with a Catphan 600 phantom.ResultsThe use of AEC produced a significant dose reduction (p < 0.01) for all anthropomorphic sizes employed. According to the modulation strength applied, dose delivered was reduced from 43% to 91%. This pattern led to significantly increased noise (p < 0.01) and reduced SNR and CNR (p < 0.01). However, IR was able to improve these indices. The use of AEC/IR preserved image quality indices with a lower dose delivered. Doses were reduced from 39% to 58% for the one-year-old phantom, from 46% to 63% for the five-year-old phantom, and from 58% to 74% for the 10-year-old phantom. In addition, AEC/IR changed the patterns of NPS curves in amplitude and in spatial frequency.ConclusionsIn chest paediatric MDCT, the use of AEC with IR allows one to obtain a significant dose reduction while maintaining constant image quality indices.     

Synthesis of 1-(methanesulfonyl- and aminosulfonylphenyl)acetylenes that possess a 2-(N-difluoromethyl-1,2-dihydropyridin-2-one) pharmacophore: Evaluation as dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity

A hitherto unknown class of linear acetylene regioisomers were designed such that a SO₂Me or SO₂NH₂ group was located at the ortho-, meta- or para-position of the acetylene C-1 phenyl ring, and a N-difluoromethyl-1,2-dihydropyridin-2-one moiety was attached via its C-5 position to the C-2 position on an acetylene template (scaffold). All three SO₂Me regioisomers, and the 4-SO₂NH₂ analog, were potent inhibitors of 5-lipoxygenase (5-LOX IC₅₀ = 3.2–3.5 μM range) relative to the reference drug caffeic acid (IC₅₀ = 4.0 μM). The SO₂Me regioisomers exhibited weak cyclooxygenease-1 (COX-1) and -2 (COX-2) inhibitory activity with a modest COX-2 selectivity index. The most potent 3-SO₂Me, 4-SO₂Me and 4-SO₂NH₂ compounds, with respective ED₅₀ values of 66.1, 68.5 and 86.5 mg/kg po, exhibited comparable oral anti-inflammatory (AI) activity to that of the reference drug ibuprofen (ED₅₀ = 67.4 mg/kg po). The N-difluoromethyl-1,2-dihydropyridin-2-one moiety provides a novel pharmacophore for the design of cyclic hydroxamic mimetics capable of inhibiting 5-LOX for exploitation in the development of 5-LOX inhibitory AI drugs.     

A new Suzuki synthesis of triphenylethylenes that inhibit aromatase and bind to estrogen receptors α and β

The design and synthesis of dual aromatase inhibitors/selective estrogen receptor modulators (AI/SERMs) is an attractive strategy for the discovery of new breast cancer therapeutic agents. Previous efforts led to the preparation of norendoxifen (4) derivatives with dual aromatase inhibitory activity and estrogen receptor binding activity. In the present study, some of the structural features of the potent AI letrozole were incorporated into the lead compound (norendoxifen) to afford a series of new dual AI/SERM agents based on a symmetrical diphenylmethylene substructure that eliminates the problem of E,Z isomerization encountered with norendoxifen-based AI/SERMs. Compound 12d had good aromatase inhibitory activity (IC₅₀ = 62.2 nM) while also exhibiting good binding activity to both ER-α (EC₅₀ = 72.1 nM) and ER-β (EC₅₀ = 70.8 nM). In addition, a new synthesis was devised for the preparation of norendoxifen and its analogues through a bis-Suzuki coupling strategy.     

Rectification of SEMG as a tool to demonstrate synchronous motor unit activity during vibration

The use of surface electromyography (SEMG) in vibration studies is problematic since motion artifacts occupy the same frequency band with the SEMG signal containing information on synchronous motor unit activity. We hypothesize that using a harsher, 80–500 Hz band-pass filter and using rectification can help eliminate motion artifacts and provide a way to observe synchronous motor unit activity that is phase locked to vibration using SEMG recordings only. Multi Motor Unit (MMU) action potentials using intramuscular electrodes along with SEMG were recorded from the gastrocnemius medialis (GM) of six healthy male volunteers. Data were collected during whole body vibration, using vibration frequencies of 30 Hz, 35 Hz, 40 Hz or 50 Hz. A computer simulation was used to investigate the efficacy of filtering under different scenarios: with or without artifacts and/or motor unit synchronization. Our findings indicate that motor unit synchronization took place during WBV as verified by MMU recordings. A harsh filtering regimen along with rectification proved successful in demonstrating motor unit synchronization in SEMG recordings. Our findings were further supported by the results from the computer simulation, which indicated that filtering and rectification was efficient in discriminating motion artifacts from motor unit synchronization. We suggest that the proposed signal processing technique may provide a new methodology to evaluate the effects of vibration treatments using only SEMG. This is a major advantage, as this non-intrusive method is able to overcome movement artifacts and also indicate the synchronization of underlying motor units.     

Aromatase Inhibitor Increases the Height of Patients with Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency

Objective: Patients with 21-hydroxylase deficiency (21OHD) typically suffer from short stature due to early exposure to adrenal-derived androgen. The aim of this study was to investigate whether adding aromatase inhibitor (AI) to gonadotropin-releasing hormone (GnRH) analogue (GnRHa) and recombinant human growth hormone (rhGH) therapy would increase the height of patients with 21OHD.Methods: This retrospective study included 15 patients with 21OHD. The AI/GnRHa/rhGH group consisted of 9 patients, who were treated with AI for at least 12 months in addition to GnRHa/rhGH therapy. The other 6 patients, who received GnRHa/rhGH therapy only, were defined as the GnRHa/rhGH group.Results: Patients were 6.3 ± 1.7 years old, and 7/15 of patients were male. Among them, 12 patients exhibited simple virilization type, and 3 patients were salt-wasting type. In the AI/GnRHa/rhGH group, patients were 6.6 ± 2.0 years old when AI therapy was initiated. Their bone age was 5.9 ± 2.2 years ahead of their chronological age. They received the AI letrizole for an average of 25.1 months (range, 12 to 37 months). In the GnRHa/rhGH group, the patients were 5.9 ± 0.9 years old when they started GnRHa/rhGH therapy, and their bone age was 6.2 ± 1.7 years ahead of their chronological age. Patients received GnRHa/rhGH therapy for an average of 24.5 months (range, 12 to 41 months). The predicted final height increased from 145.9 ± 7.9 to 158.0 ± 8.4 cm in the AI/GnRHa/rhGH group (P = .001, compared with the baseline) and from 141.7 ± 2.7 to 150.7 ± 4.7 cm in the GnRHa/rhGH group (P = .001, compared with the baseline). Bone age progression was 0.15 ± 0.05 per year versus 0.44 ± 0.13 per year in the two groups, respectively (P = .032).Conclusion: Addition of letrizole to GnRHa/rhGH therapy significantly delays bone maturation and may increase the final height.     

Adsorptive removal of cadmium ions by Spirulina platensis dry biomass

Cadmium is one of the most toxic substances found in aquatic ecosystems. This metal tends to accumulate in photosynthetic plants and fish and is transferred to humans causing many diseases. It has to be removed from our environment to reduce any health risks. Dry biomass of the microalga (cyanobacterium) Spirulina platensis was used as biosorbent for the removal of cadmium ions (Cd²⁺) from aqueous solutions. The effects of different levels of pH (3–9), biomass concentration (0.25–2 g), temperature (18–46 °C), metal concentration (40–200 mg/l) and contact time (30–120 min) were tested. Batch cultures were carried out in triplicate in an orbital shaker at 150 rpm. After centrifuging the biomass, the remaining levels of cadmium ions were measured in the supernatant by Atomic Absorption Spectrometer. Very high levels of removal, reaching up to 87.69% were obtained. The highest percentage of removal was reached at pH 8, 2 g of biosorbent, 26 °C, and 60 mg/l of cadmium concentration after 90 min of contact time. Langmuir and Freundlich isotherm models were applied to describe the adsorption isotherm of the metal ions by S. platensis. Langmuir model was found to be in better correlation with experimental data (R² = 0.92). Results of this study indicated that S. platensis is a very good candidate for the removal of heavy metals from aquatic environments. The process is feasible, reliable and eco-friendly.     

Celecoxib prodrugs possessing a diazen-1-ium-1,2-diolate nitric oxide donor moiety: Synthesis,biological evaluation and nitric oxide release studies

A new class of anti-inflammatory (AI) cupferron prodrugs was synthesized wherein a diazen-1-ium-1,2-diolato ammonium salt, and its O²-methyl and O²-acetoxyethyl derivatives, nitric oxide (NO) donor moieties were attached directly to an aryl carbon on a celecoxib template. The percentage of NO released from the O²-methyl and O²-acetoxyethyl compounds was higher (18.0–37.8% of the theoretical maximal release of one molecule of NO/molecule of the parent compound) upon incubation in the presence of rat serum, relative to incubation with phosphate buffer saline (PBS) at pH 7.4 (3.8–11.6% range). All compounds exhibited weak inhibition of the COX-1 isozyme (IC₅₀ = 5.8–17.0 μM range) in conjunction with weak or modest inhibition of the COX-2 isozyme (IC₅₀ = 1.6–14.4 μM range). The most potent AI agent 5-[4-(O²-ammonium diazen-1-ium-1,2-diolato)phenyl]-1-(4-sulfamoylphenyl)-3-trifluoromethyl-1H-pyrazole exhibited a potency that was about fourfold and twofold greater than that observed for the respective reference drugs aspirin and ibuprofen. These studies indicate that use of a cupferron template constitutes a plausible drug design approach targeted toward the development of AI drugs that do not cause gastric irritation, or elevate blood pressure and induce platelet aggregation that have been associated with the use of some selective COX-2 inhibitors.     

Multivariate morphometry and rates of morphologic evolution within the Pennsylvanian fusulinid Beedeina (Ardmore Basin,Oklahoma, USA)

Ten species in the genus Beedeina from Desmoinesian (Middle Pennsylvanian) rocks in the Ardmore Basin (southern Oklahoma, USA) were discriminated on the basis of 29 measured variates. Each species was characterized by its mean scores on the first and second axes in canonical variates analysis (CVA) and by its lowest stratigraphic occurrence in order to identify evolutionary lineages. The pumila → plattensis → erugata lineage involved overall size increase without appreciable changes in shape. The insolita → haworthi → aff. whitakeri → acme and insolita → cf. novamexicana → euryteines lineages both exhibited axial lengthening, but the former involved relative elongation and the latter involved relative inflation. CVA function coefficients were used to identify taxonomically important characters for the analysis of rates of morphologic evolution, and it was discovered that three of the five most important characters occur in the embryonic portion of the shell (proloculus diameter, half-length and wall thickness of the first volution). Rates of evolution are variable among ancestor-descendant pairs in the three lineages, but they do not differ significantly from rates documented in other groups of fossil and extant organisms. Apparent variation in rates is an artifact of the unequal time intervals over which morphologic change was measured, with shorter intervals resulting in faster rates. Among the five variates examined in all ancestor-descendant pairs (i.e., across a range of time intervals), proloculus size and half-length of the first and sixth volutions exhibited the fastest mean rates of change, whereas wall thickness in the first volution and radius vector of the fifth volution exhibited slower mean rates of change.     

1-(4-Methane(amino)sulfonylphenyl)-3-(4-substituted-phenyl)-5-(4-trifluoromethylphenyl)-1H-2-pyrazolines/pyrazoles as potential anti-inflammatory agents

2-Pyrazolins 14a–l and pyrazoles 15a–l were designed as celecoxib analogs for the evaluation of their in vitro COX-1/COX-2 inhibitory activity and the in vivo anti-inflammatory activity. Compounds 14i, 15a, 15d and 15f were the most COX-2 selective derivatives (S.I. = 5.93, 6.08, 5.03 and 5.27 respectively) while the pyrazoline derivatives 14g and 14i exhibited the highest AI activity (ED₅₀ = 190.5 and 160.1 μmol/kg po, respectively).     

Effects of medially posted insoles on foot and lower limb mechanics across walking and running in overpronating men

Anti-pronation orthoses, like medially posted insoles (MPI), have traditionally been used to treat various of lower limb problems. Yet, we know surprisingly little about their effects on overall foot motion and lower limb mechanics across walking and running, which represent highly different loading conditions. To address this issue, multi-segment foot and lower limb mechanics was examined among 11 overpronating men with normal (NORM) and MPI insoles during walking (self-selected speed 1.70 ± 0.19 m/s vs 1.72 ± 0.20 m/s, respectively) and running (4.04 ± 0.17 m/s vs 4.10 ± 0.13 m/s, respectively). The kinematic results showed that MPI reduced the peak forefoot eversion movement in respect to both hindfoot and tibia across walking and running when compared to NORM (p < 0.05–0.01). No differences were found in hindfoot eversion between conditions. The kinetic results showed no insole effects in walking, but during running MPI shifted center of pressure medially under the foot (p < 0.01) leading to an increase in frontal plane moments at the hip (p < 0.05) and knee (p < 0.05) joints and a reduction at the ankle joint (p < 0.05). These findings indicate that MPI primarily controlled the forefoot motion across walking and running. While kinetic response to MPI was more pronounced in running than walking, kinematic effects were essentially similar across both modes. This suggests that despite higher loads placed upon lower limb during running, there is no need to have a stiffer insoles to achieve similar reduction in the forefoot motion than in walking.     

Uncertainties in the identification of potential dispersal corridors: The importance of behaviour,sex, and algorithm

Modelling landscape connectivity represents one of the central challenges for conservation of natural resources, especially in human dominated landscapes. Many different methods have been developed to this effect, but their assumptions and limitations have been largely ignored. Using high resolution GPS tracking data from brown bears (Ursus arctos) in central Italy, we investigated the influence of behavioural state (movement vs other behaviours), sex, and algorithms, namely least cost path and circuit theory, on the identification of structural corridors. In particular, considering that most studies does not account for behavioural states and/or individual characteristics, and that basically all studies consider only a single corridor algorithm, we performed (1) a within-algorithm comparison, under the hypothesis that both behavioural states and sex would influence prediction of structural corridors, and (2) a between-algorithm comparison, under the hypothesis that different algorithms would predict different corridors. We found that the impact of sex and/or behavioural state was substantial. On average, least cost path corridors for moving females were 4.7 km apart (st.dev = 7.6 km) from corridors for moving males, and 5.0 km apart (st.dev = 7.2 km) from corridors not considering sex and behaviour. The same was true for circuit theory corridors. The between-algorithm comparison showed that the two corridor models yielded almost identical results, with >80% of the least cost path corridors falling into the two top deciles for the corresponding circuit theory corridors.Our results suggest that the failure to consider an animal’s behavioural state and/or intraspecific differences may result in misidentification of corridors, with potential misallocation of the limited conservation resources available.     

Synthesis and biological evaluation of salicylic acid and N-acetyl-2-carboxybenzenesulfonamide regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore: Dual inhibitors of cyclooxygenases and 5-lipoxygenase with anti-inflammatory activity

A novel class of salicylic acid and N-acetyl-2-carboxybenzenesulfonamide regioisomers possessing a N-difluoromethyl-1,2-dihydropyrid-2-one pharmacophore attached to its C-4 or C-5 position was designed for evaluation as anti-inflammatory (AI) agents. Replacement of the 2,4-difluorophenyl ring in diflunisal by the N-difluoromethyl-1,2-dihydropyrid-2-one moiety provided compounds showing dual selective cyclooxygenase-2 (COX-2)/5-lipoxygenase (5-LOX) inhibitory activities. AI structure–activity studies showed that the C-4 (14a) and C-5 (14b) salicylate regioisomers were 1.4- and 1.6-fold more potent than aspirin, and the C-5 N-acetyl-2-carboxybenzenesulfonamide regioisomer (22b) was 1.3- and 2.8-fold more potent than ibuprofen and aspirin, respectively. In vivo ulcer index (UI) studies showed that the 4- and 5-(N-difluoromethyl-1,2-dihydropyrid-2-one-4-yl)salicylic acids (14a and 14b) were completely non-ulcerogenic since no gastric lesions were present (UI = 0) relative to aspirin (UI = 57) at an equivalent μmol/kg oral dose. The N-difluoromethyl-1,2-dihydropyridin-2-one moiety provides a novel 5-LOX pharmacophore for the design of cyclic hydroxamic mimetics for exploitation in the development of dual COX-2/5-LOX inhibitory AI drugs.