Developing a pan-European high-resolution groundwater recharge map - Combining satellite data and national survey data using machine learning.
Groundwater recharge quantification is essential for sustainable groundwater resources management, but typically limited to local and regional scale estimates. A high-resolution (1 km × 1 km) dataset consisting of long-term average actual evapotranspiration, effective precipitation, a groundwater recharge coefficient, and the resulting groundwater recharge map has been created for all of Europe using a variety of pan-European and seven national gridded datasets. As an initial step, the approach developed for continental scale mapping consists of a merged estimate of actual evapotranspiration originating from satellite data and the vegetation controlled Budyko approach to subsequently estimate effective precipitation. Secondly, a machine learning model based on the Random Forest regressor was developed for mapping groundwater recharge coefficients, using a range of covariates related to geology, soil, topography and climate. A common feature of the approach is the validation and training against effective precipitation, recharge coefficients and groundwater recharge from seven national gridded datasets covering the UK, Ireland, Finland, Denmark, the Netherlands, France and Spain, representing a wide range of climatic and hydrogeological conditions across Europe. The groundwater recharge map provides harmonised high-resolution estimates across Europe and locally relevant estimates for areas where this information is otherwise not available, while being consistent with the existing national gridded datasets. The Pan-European groundwater recharge pattern compares well with results from the global hydrological model PCR-GLOBWB 2. At country scale, the results were compared to a German recharge map showing great similarity. The full dataset of long-term average actual evapotranspiration, effective precipitation, recharge coefficients and groundwater recharge is available through the EuroGeoSurveys' open access European Geological Data Infrastructure (EGDI).


Disentangling Physical Activity and Sedentary Behavior Patterns in Children with Low Motor Competence.
Children with low motor competence (MC) are at high-risk for physical inactivity, yet little is known about their physical activity (PA) and sedentary behavior (SB) patterns throughout the day. The purpose of this study is to disentangle PA and SB patterns among children with low MC across segmented day periods taking into account differences in gender and age. Data collection took place between May and July 2017. The Athletic Skills Track was used to measure MC. PA levels were objectively measured using accelerometers (ActiGraph, GT3X+) on school days. Data were segmented for (1) time before school, (2) time during school (based on school schedules), and (3) time after school. In total, data from 117 7-to-11 years-old children with low MC were eligible for analyses (N = 58 girls; N = 59 boys). Differences in moderate-to-vigorous PA (MVPA) and SB between segmented periods, gender, and grade were analyzed by ANOVAs with post hoc tests (Tukey) and Independent Sample T-tests respectively. Time spent at school is the major contributor of time spent in SB in children with low MC. Low MC is equally distributed among gender, but large differences exist among boys and girls in both MVPA and SB, indicating low-MC girls as most inactive group. This pattern is found in all segmented periods of the school day, i.e., before, during, and after school. This study stresses the negative contribution of current school curricula on PA and SB in children with low MC, indicating the most efficient period of the day to intervene. Future school-based PA and SB interventions should particularly focus on specific high-risk populations, i.e., children with low MC, and girls in particular.


[Health in the prison system: representations and practices by prison guards in Rio de Janeiro, Brazil].
The role of prison guards in limiting access to health services by inmates and the impact of their representations on daily health practices were investigated through an action-research program. The program aimed to produce knowledge and improve the guards' involvement in tuberculosis and HIV/AIDS control by raising their awareness. Developed in three prisons and two hospitals, the study included individual interviews and group discussions and showed that representations of health and illness, risk hierarchy, and preventive strategies are related to actors' status in the prison's social organization, the conflicts and tensions between them, and the sense of group belonging that reinforces identities and antagonisms. Such representations have a major influence on the guards' daily practices and inmates' access to health services. The denial of inmates' right to health and their limited autonomy contributed to the implementation of essentially prescriptive health actions. The guards' awareness of their own health representations and practices may contribute to the deconstruction of stereotypes and increase their involvement in prevention and care. Further, improvement of inmates' health depends on changes in prison conditions.


Dopamine D2-like receptors in the rat kidney: effect of denervation.
The effects of monolateral denervation induced by renal artery occlusion on dopamine D2-like receptors were assessed in rat kidney using radioligand binding assay and autoradiographic techniques. [3H]spiperone was used as a ligand. [3H]spiperone was bound specifically to sections of control innervated kidneys with a dissociation constant (Kd) value of 0.07 +/- 0.003 nM and a maximum density of binding sites (Bmax) value of 35.4 +/- 0.16 fmol/mg tissue. Light microscope autoradiography showed the accumulation of silver grains both in the arterial tree and in cortical tubules. At the vascular level, [3H]spiperone binding sites were accumulated primarily in the adventitia and in adventitia-media transitional zone. In cortical tubules, the higher density of [3H]spiperone binding sites was noticeable in proximal convoluted tubules. A few binding sites were also found in the glomerular tuft. In denervated kidneys, noradrenaline and dopamine levels were reduced by about 90% and 60% respectively in comparison with control innervated kidneys. Denervation reduced the density of [3H]spiperone binding sites by more than 85%. In denervated kidneys, light microscope autoradiography showed the disappearance of specific vascular binding sites and a remarkable reduction of tubular [3H]spiperone binding sites. The above results indicate that the largest majority of renal dopamine D2-like receptors labelled by [3H]spiperone is prejunctional in location.


A dodecylamine derivative of cyanocobalamin potently inhibits the activities of cobalamin-dependent methylmalonyl-CoA mutase and methionine synthase of Caenorhabditis elegans.
In this study, we showed that cyanocobalamin dodecylamine, a ribose 5'-carbamate derivative of cyanocobalamin, was absorbed and accumulated to significant levels by Caenorhabditis elegans and was not further metabolized. The levels of methylmalonic acid and homocysteine, which serve as indicators of cobalamin deficiency, were significantly increased in C. elegans treated with the dodecylamine derivative, indicating severe cobalamin deficiency. Kinetic studies show that the affinity of the cyanocobalamin dodecylamine derivative was greater for two cobalamin-dependent enzymes, methylmalonyl-CoA mutase and methionine synthase, compared with their respective coenzymes, suggesting that the dodecylamine derivative inactivated these enzymes. The dodecylamine derivative did not affect the levels of mRNAs encoding these enzymes or those of other proteins involved in intercellular cobalamin metabolism, including methylmalonyl-CoA mutase (mmcm-1), methylmalonic acidemia cobalamin A complementation group (mmaa-1), methylmalonic aciduria cblC type (cblc-1), and methionine synthase reductase (mtrr-1). In contrast, the level of the mRNAs encoding cob(I)alamin adenosyltransferase (mmab-1) was increased significantly and identical to that of cobalamin-deficient C. elegans. These results indicate that the cyanocobalamin-dodecylamine derivative acts as a potent inhibitor of cobalamin-dependent enzymes and induces severe cobalamin deficiency in C. elegans.


Nerve conduction velocity distributions: a method for estimation based upon two compound action potentials.
A model was presented describing the nerve-bundle CAP in terms of its constituent SFAPs. The model has a general structure capable of accommodating a large variety of specific assumptions regarding the nature of the CAP. Using this model, several techniques were presented for estimating the DCV of a nerve bundle. One method, refered to as the 2CAP method, was presented in detail. This method does not require explicit knowledge of the SFAP waveshapes in order to yield an estimate of the DCV, but does require that the CAP be recorded at two sites along the course of the nerve. In order to evaluate the clinical utility of the 2CAP method of DCV analysis, the following factors were studied: reproducibility, sensitivity to temperature and stimulus intensity, and variation within a normal population. The results indicate that the 2CAP method, when controlled for stimulus intensity and temperature, provides a reproducible measure of nerve function with the capacity to distinguish subtle differences in conduction properties of normal human nerves. Further application of this technique to patients with diabetes mellitus indicates that the DCV can demonstrate subtle electrophysiologic abnormality, even in patients with normal conventional nerve conduction studies. Although DCV analysis cannot accurately characterize all types of nerve abnormalities (such as focal nerve lesions), it will likely become a tool for earlier detection and more accurate diagnosis of many nerve diseases, and provide a key to the better understanding of the dynamics of nerve growth, development, damage, healing, and response to treatment.


A gene regulatory network model for cell-fate determination during Arabidopsis thaliana flower development that is robust and recovers experimental gene expression profiles.
Flowers are icons in developmental studies of complex structures. The vast majority of 250,000 angiosperm plant species have flowers with a conserved organ plan bearing sepals, petals, stamens, and carpels in the center. The combinatorial model for the activity of the so-called ABC homeotic floral genes has guided extensive experimental studies in Arabidopsis thaliana and many other plant species. However, a mechanistic and dynamical explanation for the ABC model and prevalence among flowering plants is lacking. Here, we put forward a simple discrete model that postulates logical rules that formally summarize published ABC and non-ABC gene interaction data for Arabidopsis floral organ cell fate determination and integrates this data into a dynamic network model. This model shows that all possible initial conditions converge to few steady gene activity states that match gene expression profiles observed experimentally in primordial floral organ cells of wild-type and mutant plants. Therefore, the network proposed here provides a dynamical explanation for the ABC model and shows that precise signaling pathways are not required to restrain cell types to those found in Arabidopsis, but these are rather determined by the overall gene network dynamics. Furthermore, we performed robustness analyses that clearly show that the cell types recovered depend on the network architecture rather than on specific values of the model's gene interaction parameters. These results support the hypothesis that such a network constitutes a developmental module, and hence provide a possible explanation for the overall conservation of the ABC model and overall floral plan among angiosperms. In addition, we have been able to predict the effects of differences in network architecture between Arabidopsis and Petunia hybrida.


Unravelling the Role of LncRNA WT1-AS/miR-206/NAMPT Axis as Prognostic Biomarkers in Lung Adenocarcinoma.
Lung cancer is the world's highest morbidity and mortality of malignant tumors, with lung adenocarcinoma (LUAD) as a major subtype. The competitive endogenous RNA (ceRNA) regulative network provides opportunities to understand the relationships among different molecules, as well as the regulative mechanisms among them in order to investigate the whole transcriptome landscape in cancer pathology. We designed this work to explore the role of a key oncogene, MYC, in the pathogenesis of LUAD, and this study aims to identify important long noncoding RNA (lncRNA)-microRNA (miRNA)- transcription factor (TF) interactions in non-small cell lung cancer (NSCLC) using a bioinformatics analysis. The Cancer Genome Atlas (TCGA) database, containing mRNA expression data of NSCLC, was used to determine the deferentially expressed genes (DEGs), and the ceRNA network was composed of WT1-AS, miR-206, and nicotinamide phosphoribosyltransferase (NAMPT) bashing on the MYC expression level. The Kaplan-Meier univariate survival analysis showed that these components may be closely related prognostic biomarkers and will become new ideas for NSCLC treatment. Moreover, the high expression of WT1-AS and NAMPT and low expression of miR-206 were associated with a shortened survival in NSCLC patients, which provided a survival advantage. In summary, the current study constructing a ceRNA-based WT1-AS/miR-206/NAMPT axis might be a novel important prognostic factor associated with the diagnosis and prognosis of LUAD.


Increased BBB Permeability Enhances Activation of Microglia and Exacerbates Loss of Dendritic Spines After Transient Global Cerebral Ischemia.
Ischemic stroke can induce rapid disruption of blood-brain barrier (BBB). It has been suggested that increased BBB permeability can affect the pathological progression of ischemic tissue. However, the impact of increased BBB permeability on microglial activation and synaptic structures following reperfusion after ischemia remains unclear. In this study, we investigated microglial activation, dendritic damage and plasticity of dendritic spines after increasing BBB permeability following transient global cerebral ischemia in the somatosensory cortices in mice. Bilateral common carotid artery ligation (BCAL) was used to induce transient global cerebral ischemia. Mannitol was used to increase the BBB permeability. Intravital two-photon imaging was performed to image the dendritic structures and BBB extravasation. Microglial morphology was quantitated using a skeletonization analysis method. To evaluate inflammation of cerebral cortex, the mRNA expression levels of integrin alpha M (CD11b), CD68, chemokine (C-X-C motif) ligand 10 (IP10) and tumor necrosis factor alpha (TNF-α) were measured by fluorescent quantitative PCR. Intravital two-photon imaging revealed that mannitol caused a drastic increase in BBB extravasation during reperfusion after transient global ischemia. Increased BBB permeability induced by mannitol had no significant effect on inflammation and dendritic spines in healthy mice but triggered a marked de-ramification of microglia; importantly, in ischemic animals, mannitol accelerated de-ramification of microglia and aggravated inflammation at 3 h but not at 3 days following reperfusion after ischemia. Although mannitol did not cause significant change in the percentage of blebbed dendrites and did not affect the reversible recovery of the dendritic structures, excessive extravasation was accompanied with significant decrease in spine formation and increase in spine elimination during reperfusion in ischemic mice. These findings suggest that increased BBB permeability induced by mannitol can lead to acute activation of microglia and cause excessive loss of dendritic spines after transient global cerebral ischemia.


A new histologic approach to the differentiation of enchondroma and chondrosarcoma of the bones. A clinicopathologic analysis of 51 cases.
Fifty-one cases of central, hyalin cartilage tumors of the long and flat bones were analyzed. Although Grade 2 and 3 chondrosarcomas could be diagnosed on the basis of cytologic features alone, low-grade chondrosarcoma could not be adequately differentiated from pure, benign enchondroma(s) by cytology alone. The tumors can be distinguished by a new histologic approach based on tissue patterns. The crucial enchondroma patterns consist of multiple nodules of hyalin cartilage separated by normal marrow in conjunction with partial to complete encompassing plates of lamellar bone that conform to the irregular shapes of the cartilage nodules. The chondrosarcomatous patterns consist of a single confluent mass of cartilage, which commonly permeates the marrow, "trapping" host lamellar bone on all sides, and which forms bands of fibrosis between the confluent peripheral cartilage lobules. Other less common patterns included cartilagenous infiltration of the Haversian systems or marrow fat and/or the development of a soft tissue mass. A central secondary chondrosarcoma is defined as one that shows the combination of both the enchondromatous and chondrosarcomatous patterns. All 18 of the pure enchondromas diagnosed by the methods proposed in this article behaved with strict benignity (i.e., without evidence of recurrence or metastasis with an average follow-up period of 7.2 years). The 33 primary and secondary chondrosarcomas diagnosed using the described patterns behaved with the predicted frequency of recurrence, metastasis, and patient demise.


Identification of cytosolic leucyl aminopeptidase (EC 22.214.171.124) as the major cysteinylglycine-hydrolysing activity in rat liver.
Cysteinylglycine hydrolysis is a step in the metabolism of glutathione and glutathione S-conjugates. We had previously observed that in rat liver the enzymatic activity is predominantly located in the cytosol. Here we demonstrate that cytosolic leucyl aminopeptidase (EC 188.8.131.52) is the major cysteinylglycine hydrolysing activity in rat liver. Evidence was obtained from the use of peptidase inhibitors and from immunoprecipitation studies using Pansorbin-coupled antibodies raised against hog kidney cytosolic leucyl aminopeptidase. Both isolated cytosolic leucyl aminopeptidase and the cysteinylglycine-hydrolysing activity in rat liver cytosol are bound with equal efficiency to the affinity matrix. We demonstrate that cytosolic leucyl aminopeptidase exhibits leucinamidase and cysteinylglycinase activity. Cysteinylglycine, cystinyl-bis-glycine, S-nitrosocysteinylglycine, and bimane-S-cysteinylglycine are hydrolysed at high rates; low activity is seen with leukotriene D4. Our findings establish a previously unrecognised physiological function of cytosolic leucyl aminopeptidase, participating in glutathione metabolism and in the degradation of glutathione S-conjugates via the mercapturic acid pathway.


Virtopsy-postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI) in a fatal scuba diving incident.
The body of a 44-year-old scuba diver was examined using postmortem multislice computed tomography (MSCT) and magnetic resonance imaging (MRI), and findings were verified by subsequent autopsy. The goal was to find out whether the important pathomorphological findings for the reconstruction of events and the identification of cause and manner of death could be identified using modem digital cross-sectioning techniques. The findings of a massive vital decompression with pulmonary barotrauma and lethal gas embolism were identified in the radiological images. MSCT and MRI were superior to autopsy in the demonstration of the extent and distribution of gas accumulation in intraparenchymal blood vessels of internal organs as well as in areas of the body inaccessible by standard autopsy.


[Little clinical relevance in routine pathological examination of uteri removed in women with prolapse symptoms].
To study the clinical usefulness of pathological examination of the uteri removed from women with complaints of prolapse of the uterus. Retrospective study. Department of Obstetrics and Gynaecology and Department of Pathology of the Medical Centre Alkmaar, the Netherlands. Between June 1st 1990 and August 31st 1994, 221 women underwent vaginal hysterectomy because of prolapse of the uterus. At the SIG Zorginformatie national reference data were collected from the pathology archives (PALGA). No malignancy or carcinoma in situ of cervix or endometrium was found in the 221 women; 7 times a cervical intraepithelial neoplasia (CIN) 1 with free hysterectomy resection margins was seen. In the national data of 5,739 comparable operated women a malignancy was found in 9 (0.16%) patients while 10 (0.17%) specimens showed a carcinoma in situ; in one of these cases an adenocarcinoma of the endometrium had not been removed completely in the area of the fallopian tube. The unexpected finding of a cervical or uterine malignancy at histological examination is extremely rare (1:717 hysterectomies nationwide) if the uterus was surgically removed because of prolapse. The idea of omitting histological examination under certain conditions needs further evaluation. A prospective study should ascertain under what circumstances, e.g. the combination of a normal menstrual bleeding pattern, or absence of postmenopausal bleeding, with a normal cervical smear preoperatively, and normal macroscopic appearance, judged by the pathologist, microscopic examination can safely be omitted.


Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model.
Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer's disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10-20 µM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased MT-bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin 1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission.


Nigellamines A3, A4, A5, and C, new dolabellane-type diterpene alkaloids, with lipid metabolism-promoting activities from the Egyptian medicinal food black cumin.
New dolabellane-type diterpene alkaloids, nigellamines A(3), A(4), A(5), and C, were isolated from the methanolic extract of an Egyptian medicinal food, black cumin (the seeds of Nigella sativa). Their absolute configurations were determined on the basis of chemical and physicochemical evidence. Nigellamines were found to lower triglyceride levels in primary cultured mouse hepatocytes, and in particular, the activity of nigellamine A(5) was equivalent to that of the hypolipidemic agent, clofibrate.


Drug transporters in the central nervous system.
Drug targets in the central nervous system (CNS) are numerous and important for drug therapy, e.g., of epilepsy or pain. Drugs and other xenobiotics as well as nutrients cannot freely cross the blood-brain barrier or freely enter cells across plasma membranes and therefore require transport systems. This overview summarizes the current knowledge on the expression of drug transporters in barriers shielding the CNS from the systemic circulation and as such controlling the pharmacokinetics of drugs in the CNS. The main drug transporter families covered are SLCO, SCL22A, ABCB, and ABCC, as genes of these families code for numerous drug transporters. While knowledge on messenger RNA expression in humans, rats, and mice is remarkable, there is clearly a gap in knowledge on the subcellular expression of transporters in specific cells in the CNS and in the barriers shielding the CNS from the systemic circulation. Recent methodologic developments including synthesis of drugs and endogenous substances for imaging will in the future allow the investigation of the function and physiologic role of transporters in the CNS including difficult-to-access systems such as the choroid plexus.


Combining topological and steric constraints for the preparation of heteroleptic copper(I) complexes.
Heteroleptic copper(I) complexes have been prepared from a macrocyclic ligand incorporating a 2,9-diphenyl-1,10-phenanthroline subunit (M30) and two bis-phosphines, namely bis[(2-diphenylphosphino)phenyl] ether (POP) and 1,3-bis(diphenylphosphino)propane (dppp). In both cases, the diphenylphosphino moieties of the PP ligand are too bulky to pass through the 30-membered ring of M30 during the coordination process, hence the formation of C2v-symmetrical pseudo-rotaxanes is prevented. When POP is used, X-ray crystal structure analysis shows the formation of a highly distorted [Cu(M30)(POP)](+) complex in which the POP ligand is only partially threaded through the M30 unit. This compound is poorly stable as the Cu(I) cation is not in a favorable coordination environment due to steric constraints. By contrast, in the case of dppp, the bis-phosphine ligand undergoes both steric and topological constraints and adopts a nonchelating coordination mode to generate [Cu2(M30)2(μ-dppp)](BF4)2. This compound exhibits metal-to-ligand charge transfer (MLCT) emission characterized by a very large Stokes' shift (≈200 nm) that is not attributed to a dramatic structural distortion between the ground and the emitting states but to very weak MLCT absorption transitions at longer wavelengths. Accordingly, [Cu2(M30)2(μ-dppp)](BF4)2 shows unusually high luminescence quantum yields for Cu(I) complexes, both in solution and in the solid state (0.5 and 7 %, respectively).


[Causes and correction of abnormal gait patterns due to prosthesis in above-knee amputees].
Abnormal gait patterns cause an increase in the energy cost of walking in above-knee amputees. Disturbances of the walking pattern are often caused both by the amputated patient himself and by incorrect prosthetic fitting. The early detection and correction of causative factors is of great importance for successful rehabilitation of these amputees. During the follow-up examinations the prosthesis must be inspected for a correct fitting and individually appropriate knee stabilizing components. Prior to any corrective measures it must be excluded that the artificial limb has been put on incorrectly by the amputee himself.


Synthesis, in vitro Anticancer and Antimicrobial Evaluation of Novel Substituted Dihydropyrimidines.
A series of 1,4-dihydropyrimidine derivatives 3(a-t) were prepared from Biginelli reactions by using ethyl acetoacetate, substituted benzaldehyde and thiourea in the presence of piperidine and ethanol. The compounds 3(a-t) were reacted with dimethylsulphate, diethylsulphate, butyl bromide and benzyl chloride to give the new series of compounds 4(a-t). The structures of the newly synthesized compounds 4(a-t) were established by IR, (1)H NMR, Mass spectra and elemental analysis. The synthesized compounds were evaluated for their in vitro anticancer activity by using Sulforhodamine B assay method against the growth of four humans cancer cell lines, antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and for antifungal activity against Candida albicans and Aspergillus niger. The compounds exhibited good anticancer activity and moderate antibacterial and antifungal activities. Compounds 4b, 4c, 4d, 4g, 4i, 4n, 4o, 4q and 4s showed significant anticancer activity when compared with the doxorubicin as a standard reference drug.


Dietary oil modifies the plasma proteome during aging in the rat.
Fatty acids and other components of the diet may modulate, among others, mechanisms involved in homeostasis, aging, and age-related diseases. Using a proteomic approach, we have studied how dietary oil affected plasma proteins in young (6 months) or old (24 months) rats fed lifelong with two experimental diets enriched in either sunflower or virgin olive oil. After the depletion of the most abundant proteins, levels of less abundant proteins were studied using two-dimensional electrophoresis and mass spectrometry. Our results showed that compared with the sunflower oil diet, the virgin olive oil diet induced significant decreases of plasma levels of acute phase proteins such as inter-alpha inhibitor H4P heavy chain (at 6 months), hemopexin precursor (at 6 and 24 months), preprohaptoglobin precursor (at 6 and 24 months), and α-2-HS glycoprotein (at 6 and 24 months); antioxidant proteins such as type II peroxiredoxin (at 24 months); proteins related with coagulation such as fibrinogen γ-chain precursor (at 24 months), T-kininogen 1 precursor (at 6 and 24 months), and apolipoprotein H (at 6 and 24 months); or with lipid metabolism and transport such as apolipoprotein E (at 6 and 24 months) and apolipoprotein A-IV (at 24 months). The same diet increased the levels of apolipoprotein A-1 (at 6 and 24 months), diminishing in general the changes that occurred with age. Our unbiased analysis reinforces the beneficial role of a diet rich in virgin olive oil compared with a diet rich in sunflower oil, modulating inflammation, homeostasis, oxidative stress, and cardiovascular risk during aging.


Cerebrospinal fluid tau levels are a marker for molecular subtype in sporadic Creutzfeldt-Jakob disease.
The molecular subtype of sporadic Creutzfeldt-Jakob disease (sCJD) is an important prognostic marker for patient survival. However, subtype determination is not possible during lifetime. Because the rate of disease progression is associated with the molecular subtype, this study aimed at investigating if total tau, a marker of neuronal death, allows premortem diagnosis of molecular subtype when codon 129 genotype is known. Two hundred ninety-six sCJD patients were tested for their cerebrospinal fluid total tau level at the time of diagnosis and were investigated for their sCJD subtype postmortem. There was a significant association between tau levels and the prion protein type in patients with codon 129 MM (p < 0.001), MV (p = 0.004), and VV (p = 0.001) genotype. Receiver operating characteristic analyses showed values of area under the curve of 0.76-0.80 for the different genotypes indicating a good diagnostic validity of the test. Total tau can be used as a diagnostic test for the assessment of prion protein type when codon 129 genotype is known. It provides valuable information for physicians and next of kin about the further course of disease.


8-Aza-7-deaza-2'-deoxy-2-(methylsulfanyl)adenosine.
In the title compound, 4-amino-1-(2-deoxy-beta-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine, C11H16N5O3S, the conformation of the glycosidic bond is between anti and high anti. The 2'-deoxyribofuranosyl moiety adopts the C3'-exo-C4'-endo conformation (3T4, S-type sugar pucker), and the conformation at the exocyclic C-C bond is +sc (+gauche). The exocyclic 6-amine group and the 2-methylsulfanyl group lie on different sides of the heterocyclic ring system. The molecules form a three-dimensional hydrogen-bonded network that is stabilized by O-H...N, N-H...O and C-H...O hydrogen bonds.


On-road exposure to highway aerosols. 1. Aerosol and gas measurements.
On-road experiments were conducted to determine the sensitivities of rats to real-world aerosol. This article summarizes the on-road aerosol and gas measurements and provides background information for the companion paper on the rat exposures. Measurements were carried out over 10 days, 6 h/day, driving a route from Rochester to Buffalo. Aerosol instrumentation used in this study included two scanning mobility particle sizers (SMPS) to determine the aerosol size distribution from 10 to 300 nm, 2 stand-alone condensation particle counters to determine the total aerosol number concentration, and an electrical aerosol detector to determine the aerosol length concentration. A thermal denuder (TD) was used with one of the SMPS instruments to determine the size distribution of the non-volatile fraction. Filter samples were collected and analyzed for elemental carbon, and gas analyzers measured ambient levels of CO, CO(2), and NO. Average daily total aerosol number concentration ranged from 200,000 to 560,000 particles/cm(3). Past studies on urban highways have measured total number concentrations ranging between 10(4) and 10(6) particles/cm(3). The average daily NO concentration ranged from 0.10 to 0.24 ppm and the corresponding CO(2) concentration ranged from 400 to 420 ppm. The average daily geometric number mean particle size determined by the SMPS ranged from 15 to 20 nm. The TD reduced the average SMPS number concentration between 87 and 95% and the SMPS volume between 54 and 83%, suggesting that most of the particles consisted of volatile material. The TD also increased the geometric number mean diameter from 15 to 20 nm to 30 to 40 nm.


Understanding Starch Metabolism in Pea Seeds towards Tailoring Functionality for Value-Added Utilization.
Starch is the most abundant storage carbohydrate and a major component in pea seeds, accounting for about 50% of dry seed weight. As a by-product of pea protein processing, current uses for pea starch are limited to low-value, commodity markets. The globally growing demand for pea protein poses a great challenge for the pea fractionation industry to develop new markets for starch valorization. However, there exist gaps in our understanding of the genetic mechanism underlying starch metabolism, and its relationship with physicochemical and functional properties, which is a prerequisite for targeted tailoring functionality and innovative applications of starch. This review outlines the understanding of starch metabolism with a particular focus on peas and highlights the knowledge of pea starch granule structure and its relationship with functional properties, and industrial applications. Using the currently available pea genetics and genomics knowledge and breakthroughs in omics technologies, we discuss the perspectives and possible avenues to advance our understanding of starch metabolism in peas at an unprecedented level, to ultimately enable the molecular design of multi-functional native pea starch and to create value-added utilization.


Retinoic acid and tumor necrosis factor-α induced monocytic cell gene expression is regulated in part by induction of transcription factor MafB.
All-trans-retinoic acid (RA), the major active metabolite of vitamin A, is a regulator of gene expression with many roles in cell differentiation. In the present study, we investigated RA in the regulation of MafB, a basic leucine-zipper transcription factor with broad roles in embryonic development, hematopoiesis and monocyte-macrophage differentiation. In RA-treated THP-1 human monocytic cells, MafB mRNA and protein levels were up-regulated by RA dose and time-dependently, while, additionally, RA and tumor necrosis factor (TNF)α, also known to induce monocyte to macrophage differentiation, increased MafB expression synergistically. Screening of potential targets containing Maf recognition elements (MARE motifs) in their promoter regions identified SPOCK1, Blimp1 and CCL2 as potential targets; these genes are related to cell communication, recruitment and differentiation, respectively. Across cell treatments, SPOCK1, Blimp1 and CCL2 mRNA levels were highly correlated (P<0.001) with MafB. ChIP assays demonstrated increased MafB protein binding to MARE elements in the promoter regions of SPOCK1, Blimp1 and CCL2 in RA and TNFα-treated cells, as well as acetylation of histone-H4 in MARE-containing regions, indicative of chromatin activation. Conversely, reducing MafB protein by microRNA silencing significantly decreased the expression of SPOCK1, Blimp1 and CCL2 (P<0.01). Moreover, the reduction in MafB expression and these downstream targets correlated with decreased cell differentiation as determined by cell-surface CD11b expression and phagocytic activity. We conclude that MafB may be a key factor in mediating the ability of RA and TNFα to regulate monocytic cell communication, recruitment and differentiation through regulation of MafB target genes including SPOCK1, CCL2 and Blimp1.


Biofeedback in the treatment of heart failure.
Biofeedback training can be used to reduce activation of the sympathetic nervous system (SNS) and increase activation of the parasympathetic nervous system (PNS). It is well established that hyperactivation of the SNS contributes to disease progression in chronic heart failure. It has been postulated that underactivation of the PNS may also play a role in heart failure pathophysiology. In addition to autonomic imbalance, a chronic inflammatory process is now recognized as being involved in heart failure progression, and recent work has established that activation of the inflammatory process may be attenuated by vagal nerve stimulation. By interfering with both autonomic imbalance and the inflammatory process, biofeedback-assisted stress management may be an effective treatment for patients with heart failure by improving clinical status and quality of life. Recent studies have suggested that biofeedback and stress management have a positive impact in patients with chronic heart failure, and patients with higher perceived control over their disease have been shown to have better quality of life. Our ongoing study of biofeedback-assisted stress management in the treatment of end-stage heart failure will also examine biologic end points in treated patients at the time of heart transplant, in order to assess the effects of biofeedback training on the cellular and molecular components of the failing heart. We hypothesize that the effects of biofeedback training will extend to remodeling the failing human heart, in addition to improving quality of life.


Caveolin-1 accumulation in the tongue cancer tumor microenvironment is significantly associated with poor prognosis: an in-vivo and in-vitro study.
Caveolin-1 (CAV1) may be upregulated by hypoxia and acts in a tumor-dependent manner. We investigated CAV1 in tongue squamous cell carcinoma (TSCC) and its association with clinical outcomes, and studied in vitro possible ways for CAV1 accumulation in the tumor microenvironment (TME). TSCC cases (N = 64) were immunohistochemically stained for CAV1. Scores were separately assessed in the tumor and TME and plotted for association with recurrence and survival (univariate analysis with log-rank test). In vitro studies were performed on a 3D myoma organotypic model, a mimicker of TME. Prior to monoculturing HSC-3 tongue cancer cells, the model underwent modifications in oxygenation level (1%O2 hypoxia to upregulate CAV1) and/or in the amount of natural soluble factors [deleted by 14-day rinsing (rinsed myoma, RM), to allow only HSC-3-derived factors to act]. Controls included normoxia (21%O2) and naturally occurring soluble factors (intact myoma, IM). HSC-3 cells were also co-cultured with CaDEC12 cells (fibroblasts exposed to human tongue cancer). CAV1 expression and cellular distribution were examined in different cellular components in hypoxic and rinsed myoma assays. Twist served as a marker for the process of epithelial-mesenchymal transition (EMT). Exosomes isolated from HSC-3 media were investigated for containing CAV1. Expression of CAV1 in TSCC had a higher score in TME than in the tumor cells and a negative impact on recurrence (p = 0.01) and survival (p = 0.003). Monocultures of HSC-3 revealed expression of CAV1 mainly in the TME-like myoma assay, similar to TSCC. CAV1+, alpha-smooth muscle actin (αSMA) + and Twist + CAF-like cells were observed surrounding the invading HSC-3, possibly reflecting EMT. RM findings were similar to IM, inferring action of HSC-3 derived factors, and no differences were seen when hypoxia was induced. HSC-3-CaDEC12 co-cultures revealed CAV1+, αSMA+ and cytokeratin-negative CAF-like cells, raising the possibility of CaDEC12 cells gaining a CAF phenotype. HSC-3-derived exosomes were loaded with CAV1. Accumulation of CAV1-TME in TSCC had a negative prognostic value. In vitro studies showed the presence of CAV1 in cancer cells undergoing EMT and in fibroblasts undergoing trans-differentiation to CAFs. CAV1 delivery to the TME involved cancer cell-derived exosomes.


The stepped cuboid.
The authors review a case presentation of a symptomatic cuboid metatarsal joint anomaly and discuss possible treatments, both conservative and surgical. The patient was treated conservatively and had some relief of symptoms.


[Infertility caused by ejaculation disturbances and anorgasmy].
Recent progress in andrology, reproduction biology and medical sexuology have led to a substantial increase of the proportions of pregnancy achieved by males with ejaculation disorders or anorgasmy. Impairment in libido and excitement usually has a psychic cause, apart from rare endocrinological abnormalities such as hyperprolactinaemia and androgen depletion. Another possible cause is chronic use of certain drugs. Causes of erection disorders can be classified on the basis of psychogenous, vascular and neurogenous factors. Ejaculation disorders are caused by embryonal anomalies, neurological disorders and use of certain (psychoactive) pharmaceutical agents. Collecting sperm proves to be virtually always possible. According to current views, the treatment of infertility in ejaculation disorders or anorgasmy should be if possible, elimination of the primary cause or else: in-vitro fertilisation (IVF)/intracytoplasmatic sperm injection (ICSI) with semen obtained after processing a retrograde ejaculate or by means of vibro-ejaculation or electro-ejaculation.


Health development meets the end of state socialism: visions of democratization, women's health, and social well-being for contemporary Russia.
As development organizations undertake the task of improving the public health in former socialist states, their interventions are shaped by a particular cultural logic and predetermined frame of possible action. In the context of local encounters, however, they often confront competing interpretations of a society's prevailing needs. How they manage such differences may not only explain the outcomes of a given project, but may also reveal the capacities and limitations of development agencies to engineer post-socialist change. This article examines a recent WHO project in St. Petersburg, Russia, which defined women's "social well-being" as a local health concern. While the project employed a discourse of "democracy" to promote women's empowerment in the clinic, its parameters of intervention neither incorporated local knowledge nor addressed the structural relations underlying clinic-level conflicts. Two kinds of results ensued: the ideology of democracy was rejected, while WHO's recommendations were partially appropriated as profit-making strategies.


Smoking prevalence of female nurses in the national hospitals of Japan.
To estimate the prevalence of smoking and the attitudes towards the restriction of smoking at work among female nurses in the national hospitals in Japan. Questionnaires mailed to 14 randomly selected national hospitals and sanitariums in Japan in 1993. 2207 female nurses. Smoking status and history, and attitudes towards the restriction of smoking at work. The prevalence of smoking among female nurses was 18.6%, which was higher than the age-adjusted prevalence of the general female population using this study's subjects as a standardised population. Banning smoking in the hospital in which they worked was supported by 15.0%, whereas 81.6% supported the restriction of smoking. The results showed that smoking is more common among female nurses than among the general female adult population. The survey suggested that nurses favour restriction, but not banning, of smoking.


Slow spindles are associated with cortical high frequency activity.
Thalamocortical network shows self-sustained oscillations in a broad frequency range especially during slow wave sleep when cortical neurons show synchronized transitions between a quiescent down state and an active up state with beta and gamma oscillations. Inconsistent with previous models, thalamocortical spindles are separated into slow spindles (8_12 Hz) and fast spindles (13_17 Hz) with differential properties. We proposed that cortical high frequency (∼ 25 Hz) activity during up states is the key ingredient for the generation of slow spindles. In fact, the nonlinear interaction between cortical high frequency and thalamic oscillations at fast spindle frequency reproduces oscillations in the range of the difference between the two frequencies that lies into the range of slow spindle. The developed simple deterministic thalamocortical model is able to reproduce up and down states with stochastic high-frequency up-state activity as well as both fast and slow spindles. In agreement with the previous experimental observations, the fast and slow spindles are generated at opposing phases of the up state. To further confirm the causal relationship between slow spindles and cortical high frequency oscillations, we next showed that externally applied high frequency stimulation enhanced the slow spindle activity. Moreover, the prediction of the model was validated experimentally by recording EEG from subjects during nap. Both model and experimental results show increase in high frequency activity before slow spindles. Our findings suggest the important role of cortical high frequency activity in the generation of slow spindles.


Arthroscopic Technique for Treatment of Schatzker Type III Tibia Plateau Fractures Without Fluoroscopy.
Accurate reduction and maintenance of the stability with correct implant positioning is critical for surgical treatment of tibial plateau fractures. Our technique includes an arthroscopic reduction and fixation of Schatzker type III tibial plateau fractures with a bulls-eye screw placement without fluoroscopy control. With the arthroscopic guidance, an anterior cruciate ligament drill guide is placed and a K-wire sent to the midpoint of the depressed fragment through the guide at a 40° angle to the coronal axis of the tibia. A tunnel is created with the drill over the K-wire. The depressed fragment is further augmented with gentle impacts over the K-wire. After arthroscopic reduction control, an appropriate-sized iliac graft is pushed until it is below the depressed fragment. The targeting device is adjusted at 130° so that it is parallel to the joint line and a K-wire sent through the device so that it would pass just below the graft. The graft is then supported with cannulated screws sent over the K-wire. This technique provides an arthroscopic reduction of the chondral surface and precise placement of the rafting screws without fluoroscopy.


Reasons for Interfacility Emergency Department Transfer and Care at the Receiving Facility.
The aims of this study were to (1) assess the reasons for pediatric interfacility transfers as identified by transferring providers and review the emergency medical care delivered at the receiving facilities and (2) investigate the emergency department (ED) care among the subpopulation of patients discharged from the receiving facility. We performed a multicenter, cross-sectional survey of ED medical providers transferring patients younger than 18 years to 1 of 4 US tertiary care pediatric hospitals with a subsequent medical record review at the receiving facility. Referring providers completed surveys detailing reasons for transfer. Eight hundred thirty-nine surveys were completed by 641 providers for 25 months. The median patient age was 5.7 years. Sixty-two percent of the patients required admission. The most common reasons for transfer as cited by referring providers were subspecialist consultation (62%) and admission to a pediatric inpatient (17%) or intensive care (6%) unit. For discharged patients, plain radiography (26%) and ultrasonography (12%) were the most common radiologic studies. Procedural sedation (16%) was the most common ED procedure for discharged patients, and 55% had a subspecialist consult at the receiving facility. Ten percent of interfacility transfers did not require subspecialty consult, ED procedure, radiologic study, or admission. Approximately 4 of 10 interfacility transfers are discharged by the receiving facility, suggesting an opportunity to provide more comprehensive care at referring facilities. On the basis of the care provided at the receiving facility, potential interventions might include increased subspecialty access and developing both ultrasound and sedation capabilities.


The FoxO1-ATGL axis alters milk lipolysis homeostasis through PI3K/AKT signaling pathway in dairy goat mammary epithelial cells.
Goat milk is enriched in fatty acids which are beneficial to human health. Previous research has revealed that 98% of milk fat is composed of triglycerides. However, the mechanisms regulating milk fat composition remain unclear. Forkhead box protein O1 (FoxO1) is a crucial regulatory factor involved in lipid metabolism across various cell types. Chromatin immunoprecipitation sequencing (ChIP)-seq data) and RNA sequencing (RNA-seq) data revealed that have indicated a close association between FoxO1 was closely related to lipid metabolism during lactation in dairy goats. The objective of this study was to investigate the mechanisms by which FoxO1 regulates lipid metabolism in goat mammary epithelial cells (GMECs). FoxO1 knockdown significantly downregulated the expression of adipose triglyceride lipase (ATGL) and suppressed the activity of the ATGL promoter. Consistently, the number of lipid droplets decreased significantly in FoxO1-overexpressing cells and increased in ATGL-knockdown cells. To further verify the effect of FoxO1 on ATGL promoter activity, cells were transfected with four promoter fragments of different lengths. We found that the core region of the ATGL promoter was located between -882 bp and -524 bp, encompassing two FoxO1 binding sites (FKH1 and FKH2). Mutations in the FoxO1 binding sites significantly downregulated ATGL promoter activity in GMECs. Luciferase reporter assays demonstrated that FoxO1 overexpression markedly enhanced ATGL promoter activity. Furthermore, site-directed mutation confirmed that FKH1 and FKH2 sites were simultaneously mutated significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activities simultaneous mutation of FKH1 and FKH2 sites significantly attenuated the stimulatory effect of FoxO1 on ATGL promoter activity. ChIP assays showed that FoxO1 directly binds to the FKH2 element located in the ATGL promoter in vivo. Finally, immunofluorescence staining revealed that insulin promotes the translocation of FoxO1 from the nucleus to the cytoplasm, thereby attenuating the FoxO1-induced activation of the ATGL promoter. Collectively, these findings uncover a novel pathway where by FoxO1 may regulate lipid metabolism in GMECs specifically by modulating the transcriptional activity of ATGL.


Dealing with Magnetic Disturbances in Human Motion Capture: A Survey of Techniques.
Magnetic-Inertial Measurement Units (MIMUs) based on microelectromechanical (MEMS) technologies are widespread in contexts such as human motion tracking. Although they present several advantages (lightweight, size, cost), their orientation estimation accuracy might be poor. Indoor magnetic disturbances represent one of the limiting factors for their accuracy, and, therefore, a variety of work was done to characterize and compensate them. In this paper, the main compensation strategies included within Kalman-based orientation estimators are surveyed and classified according to which degrees of freedom are affected by the magnetic data and to the magnetic disturbance rejection methods implemented. By selecting a representative method from each category, four algorithms were obtained and compared in two different magnetic environments: (1) small workspace with an active magnetic source; (2) large workspace without active magnetic sources. A wrist-worn MIMU was used to acquire data from a healthy subject, whereas a stereophotogrammetric system was adopted to obtain ground-truth data. The results suggested that the model-based approaches represent the best compromise between the two testbeds. This is particularly true when the magnetic data are prevented to affect the estimation of the angles with respect to the vertical direction.


Postoperative occlusion degree after flow-diverter placement with adjunctive coiling: analysis of complications.
Although coiling with a flow diverter may provide immediate dome protection, no studies have evaluated the effect on complications of postoperative occlusion degree immediately postoperatively. The purpose of this study was to determine whether postoperative occlusion degree immediately after flow-diverter placement with adjunctive coiling was associated with complications. All patients' data were collected from the post-market multi-center cohort study of embolization of intracranial aneurysms with a pipeline embolization device (PED) in China (PLUS) registry. We divided patients into those treated with a PED alone (PED-only (PO) group), those treated with a PED with coils and incomplete occlusion (PED + coils + incomplete occlusion (PCIO) group), and those treated with a PED with coils and complete occlusion (PED + coils + complete occlusion (PCCO) group). We evaluated 1171 consecutive patients with 1322 aneurysms treated with a PED: 685 aneurysms were treated with PO, 444 with PCIO, and 193 with PCCO. The PCCO group had a higher rate of aneurysm occlusion at the last follow-up than the PCIO and PO groups (P<0.0001). Multivariate analysis of the predictors of ischemic stroke and modified Rankin Scale score (mRS) deterioration showed that PCCO was an independent predictor of ischemic stroke (HR, 2.03; 95% CI, 1.12 to 3.67; P=0.019) and mRS deterioration (HR, 2.59; 95% CI, 1.57 to 4.26; P<0.0001). Although postoperative complete occlusion with a PED and adjunctive coiling can increase the rate of aneurysm occlusion, this approach may also increase the risk of ischemic stroke and lead to poor postoperative functional outcomes.


Dynamic Reorganization of the Cortical Functional Brain Network in Affective Processing and Cognitive Reappraisal.
Emotion and affect play crucial roles in human life that can be disrupted by diseases. Functional brain networks need to dynamically reorganize within short time periods in order to efficiently process and respond to affective stimuli. Documenting these large-scale spatiotemporal dynamics on the same timescale they arise, however, presents a large technical challenge. In this study, the dynamic reorganization of the cortical functional brain network during an affective processing and emotion regulation task is documented using an advanced multi-model electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) technique. Sliding time window correlation and [Formula: see text]-means clustering are employed to explore the functional brain connectivity (FC) dynamics during the unaltered perception of neutral (moderate valence, low arousal) and negative (low valence, high arousal) stimuli and cognitive reappraisal of negative stimuli. Betweenness centralities are computed to identify central hubs within each complex network. Results from 20 healthy subjects indicate that the cortical mechanism for cognitive reappraisal follows a 'top-down' pattern that occurs across four brain network states that arise at different time instants (0-170[Formula: see text]ms, 170-370[Formula: see text]ms, 380-620[Formula: see text]ms, and 620-1000[Formula: see text]ms). Specifically, the dorsolateral prefrontal cortex (DLPFC) is identified as a central hub to promote the connectivity structures of various affective states and consequent regulatory efforts. This finding advances our current understanding of the cortical response networks of reappraisal-based emotion regulation by documenting the recruitment process of four functional brain sub-networks, each seemingly associated with different cognitive processes, and reveals the dynamic reorganization of functional brain networks during emotion regulation.


Alleviating Class-Wise Gradient Imbalance for Pulmonary Airway Segmentation.
Automated airway segmentation is a prerequisite for pre-operative diagnosis and intra-operative navigation for pulmonary intervention. Due to the small size and scattered spatial distribution of peripheral bronchi, this is hampered by a severe class imbalance between foreground and background regions, which makes it challenging for CNN-based methods to parse distal small airways. In this paper, we demonstrate that this problem is arisen by gradient erosion and dilation of the neighborhood voxels. During back-propagation, if the ratio of the foreground gradient to background gradient is small while the class imbalance is local, the foreground gradients can be eroded by their neighborhoods. This process cumulatively increases the noise information included in the gradient flow from top layers to the bottom ones, limiting the learning of small structures in CNNs. To alleviate this problem, we use group supervision and the corresponding WingsNet to provide complementary gradient flows to enhance the training of shallow layers. To further address the intra-class imbalance between large and small airways, we design a General Union loss function that obviates the impact of airway size by distance-based weights and adaptively tunes the gradient ratio based on the learning process. Extensive experiments on public datasets demonstrate that the proposed method can predict the airway structures with higher accuracy and better morphological completeness than the baselines.


Plectranthias alcocki, a new anthiine fish species (Perciformes: Serranidae) from the Arabian Sea, off southwest India.
A new species of anthiine fish, Plectranthias alcocki n. sp. is described and illustrated based on two specimens, (63.7-72.5 mm SL), recently collected from deep-waters of the Arabian Sea, off Kollam, Kerala, India. The following combination of characters distinguishes it from all other congeners: Dorsal-fin rays X, 15; anal-fin rays III, 7; pectoral-fin rays 14, all unbranched; pelvic-fin rays I, 5; lateral-line complete, the pored lateral-line scales 28; scales above lateral line to origin of dorsal fin 1; scales dorsally on head extending to posterior nostrils; no scales on maxilla or chin; gill rakers 5 + 11 (2 + 7 developed); circumpeduncular scales 10; fourth dorsal spine longest, 2.8 (2.6) in head length (HL), longest dorsal-fin soft ray (second) 2.4 (2.7) in head length; body depth 34.4 (35)% SL; head length 46 (49.8)% SL; orbital length 8.6 in SL; margin of preopercle finely serrate, the serrae 33 (28), ventral edge without antrorse spines; dorsal fin continuous and notched; first anal-fin spine 4.9 (5.6) in HL, second anal-fin spine 2.2 (2.6) in HL; pelvic fins relatively short, 4.0-4.3 in SL; the dorsal fin with a black blotch at base of fourth to eighth spines, one at base of the last three spines, and two at base of soft portion of fin, the dark pigment extending onto adjacent body.


Association between perinatal factors, genetic susceptibility to obesity and age at adiposity rebound in children of the EDEN mother-child cohort.
Early adiposity rebound (AR) has been associated with increased risk of overweight or obesity in adulthood. However, little is known about early predictors of age at AR. We aimed to study the role of perinatal factors and genetic susceptibility to obesity in the kinetics of AR. Body mass index (BMI) curves were modelled by using mixed-effects cubic models, and age at AR was estimated for 1415 children of the EDEN mother-child cohort study. A combined obesity risk-allele score was calculated from genotypes for 27 variants identified by genome-wide association studies of adult BMI. Perinatal factors of interest were maternal age at delivery, parental education, parental BMI, gestational weight gain, maternal smoking during pregnancy, and newborn characteristics (sex, prematurity, and birth weight). We used a hierarchical level approach with multivariable linear regression model to investigate the association between these factors, obesity risk-allele score, and age at AR. A higher genetic susceptibility to obesity score was associated with an earlier age at AR. At the most distal level of the hierarchical model, maternal and paternal educational levels were positively associated with age at AR. Children born to parents with higher BMI were more likely to exhibit earlier age at AR. In addition, higher gestational weight gain was related to earlier age at AR. For children born small for gestational age, the average age at AR was 88 [±39] days lower than for children born appropriate for gestational age and 91 [±56] days lower than for children born large for gestational age. The timing of AR seems to be an early childhood manifestation of the genetic susceptibility to adult obesity. We further identified low birth weight and gestational weight gain as novel predictors of early AR, highlighting the role of the intrauterine environment in the kinetics of adiposity.


Estimating the cost of unmet HIV-prevention needs in the United States.
Although new HIV infection cases have dropped from over 160,000 per year in the mid-1980s to 40,000 per year in the 1990s, HIV incidence has been relatively unchanged for a decade. This number of annual incident infections suggests that substantial, unmet HIV-prevention needs continue to fuel the HIV epidemic in the United States. This study estimates the cost of addressing the unmet HIV-prevention needs in the United States and establishes a performance standard by estimating the number of HIV infections that would have to be prevented in order for these programs to be considered cost saving to society. Standard methods of cost and threshold analysis were employed in this study. Interventions needed to address unmet behavioral risks include services to reduce sexual risk of HIV infection, services to provide access to sterile syringes for people who cannot stop injecting drugs, HIV counseling and testing, and intensive preventive services to help HIV-seropositive people avoid transmitting the virus to others. If brief interventions are utilized to address sexual behavior risk, the total program cost (over and above current resource levels) is just over $817 million; and if more expensive multisession, small-group interventions are used, the costs increase to over $1.85 billion. However, even the higher-cost program has a threshold of only 12,000 infections that must be prevented in order for the program to be considered a cost saving to society. Addressing the remaining unmet HIV-preventive needs in the United States will require a substantial commitment of resources. However, even a greatly expanded HIV-preventive program in the United States could pay for itself through savings in averted medical care costs.


A comparison of nonlinear methods for predicting earnings surprises and returns.
We compare four nonlinear methods on their ability to learn models from data. The problem requires predicting whether a company will deliver an earnings surprise a specific number of days prior to announcement. This problem has been well studied in the literature using linear models. A basic question is whether machine learning-based nonlinear models such as tree induction algorithms, neural networks, naive Bayesian learning, and genetic algorithms perform better in terms of predictive accuracy and in uncovering interesting relationships among problem variables. Equally importantly, if these alternative approaches perform better, why? And how do they stack up relative to each other? The answers to these questions are significant for predictive modeling in the financial arena, and in general for problem domains characterized by significant nonlinearities. In this paper, we compare the four above-mentioned nonlinear methods along a number of criteria. The genetic algorithm turns out to have some advantages in finding multiple "small disjunct" patterns that can be accurate and collectively capable of making predictions more often than its competitors. We use some of the nonlinearities we discovered about the problem domain to explain these results.


Adenosine and the control of lipolysis in rat adipocytes during pregnancy and lactation.
The rate of noradrenaline-stimulated lipolysis is lower in fat-cells from lactating than from pregnant rats; this difference is eliminated by the addition of adenosine deaminase [Aitchison, Clegg & Vernon (1982) Biochem. J. 202, 243-247]. The activity of 5'-nucleotidase, and hence the capacity of the cells to synthesize adenosine, was the same in fat-cells and also stromal cells of adipose tissue from pregnant, lactating and male rats. The response and sensitivity of fat-cells to the anti-lipolytic effects of adenosine were measured by incubating cells in the presence of noradrenaline, adenosine deaminase (to remove endogenous adenosine) and various concentrations of the adenosine analogue N6-phenylisopropyladenosine (PIA). PIA caused a greater inhibition of the rate of noradrenaline-stimulated lipolysis in adipocytes from lactating than from pregnant rats. The concentration of PIA required to inhibit by 50% the rate of noradrenaline-stimulated lipolysis fell from over 100 nM for fat-cells from pregnant rats to 30 nM for fat-cells from lactating rats. The decreased rate of noradrenaline-stimulated lipolysis during lactation was not due to the smaller mean cell volume of adipocytes during this state.


Financial Fraud against Older People in Hong Kong: Assessing and Predicting the Fear and Perceived Risk of Victimization.
While the majority of studies on the fear of crime focus on the impact of violent and property crimes at the population level, financial fraud against senior citizens is often under-investigated. This study uses data collected from 1061 older citizens in the community through a cross-sectional survey in Hong Kong to examine the levels of fear and perceived risk among Chinese senior citizens toward financial fraud and the factors behind them. Logistic regression analyses were conducted to assess the explanatory power of four theoretical perspectives (vulnerability, victimization, social integration, and satisfaction with police) on fear and perceived risk of fraud victimization. The results indicate significant predictive effects of victimization experience and satisfaction with police fairness and integrity on both the fear and the perceived risk of fraud among respondents. The findings not only confirm the differential impact of theoretical explanations on these constructs but can also contribute to crime prevention policy and practice in an aging society.


Insomnia in Tinnitus Patients: A Prospective Study Finding a Significant Relationship.
Tinnitus is a highly prevalent medical disorder occurring in 10-30% of the general population. This disorder often becomes chronic and severe effecting quality of life contributing to significant psychiatric consequences; one that we have written about recently is comorbid insomnia. The latter can predispose effected persons to depressive episodes and a worsening of their total functioning. We have reported in the past that comorbid insomnia occurs in 10-80% of tinnitus patients with most reports finding over a 40% frequency. Unfortunately, these prior studies tended to evaluate only insomnia as a symptom and not as a diagnosis; therefore its seriousness and implications could not be assessed. Furthermore, most studies utilized only open-ended questionnaires with many being sent via the mail. Our study evaluated 72 tinnitus patients who were prospectively evaluated over the telephone for a tinnitus treatment study program at our center focusing on possible co-morbid insomnia symptoms as well as whether the insomnia satisfied a diagnosis with its accompanying dysfunctional state. The interview included questions regard a full range of questions assessing sleep onset, sleep continuity, early morning awakening, sleep duration as well as daytime consequences necessary for a diagnosis of insomnia. We found that not only were insomnia symptoms highly prevalent, but 60% of the tinnitus sample met strict diagnostic criteria (DSM-IV-TR) of insomnia secondary to a general medical condition, i.e., tinnitus. Alarmingly, only 4 % were being treated for their insomnia. In addition, our data suggests that tinnitus patients with co-morbid insomnia have a more severe form of tinnitus and thus, may need further care and treatment.


Molecular Biomarkers in Fragile X Syndrome.
Fragile X syndrome (FXS) is the most common inherited form of intellectual disability (ID) and a known monogenic cause of autism spectrum disorder (ASD). It is a trinucleotide repeat disorder, in which more than 200 CGG repeats in the 5' untranslated region (UTR) of the fragile X mental retardation 1 (FMR1) gene causes methylation of the promoter with consequent silencing of the gene, ultimately leading to the loss of the encoded fragile X mental retardation 1 protein, FMRP. FMRP is an RNA binding protein that plays a primary role as a repressor of translation of various mRNAs, many of which are involved in the maintenance and development of neuronal synaptic function and plasticity. In addition to intellectual disability, patients with FXS face several behavioral challenges, including anxiety, hyperactivity, seizures, repetitive behavior, and problems with executive and language performance. Currently, there is no cure or approved medication for the treatment of the underlying causes of FXS, but in the past few years, our knowledge about the proteins and pathways that are dysregulated by the loss of FMRP has increased, leading to clinical trials and to the path of developing molecular biomarkers for identifying potential targets for therapies. In this paper, we review candidate molecular biomarkers that have been identified in preclinical studies in the FXS mouse animal model and are now under validation for human applications or have already made their way to clinical trials.


The role of topoisomerase II beta on breakage and proximity of RUNX1 to partner alleles RUNX1T1 and EVI1.
Rearrangements involving the RUNX1 gene account for approximately 15% of balanced translocations in therapy-related acute myeloid leukemia (t-AML) patients and are one of the most common genetic abnormalities observed in t-AML. Drugs targeting the topoisomerase II (TOP2) enzyme are implicated in t-AML; however, the mechanism is not well understood and to date a single RUNX1-RUNX1T1 t-AML breakpoint junction sequence has been published. Here we report an additional five breakpoint junction sequences from t-AML patients with the RUNX1- RUNX1T1 translocation. Using a leukemia cell line model, we show that TOP2 beta (TOP2B) is required for induction of RUNX1 chromosomal breaks by the TOP2 poison etoposide and that, while TOP2 alpha (TOP2A) and TOP2B proteins are both present on RUNX1 and RUNX1T1 chromatin, only the TOP2B enrichment reached significance following etoposide exposure at a region on RUNX1 where translocations occur. Furthermore, we demonstrate that TOP2B influences the separation between RUNX1 and two translocation partners (RUNX1T1 and EVI) in the nucleus of lymphoid cells. Specifically, we identified a TOP2B-dependent increase in the number of nuclei displaying juxtaposed RUNX1 and RUNX1T1 loci following etoposide treatment.


Governance of forest resource use in western Nepal: Current state and community preferences.
Improved governance of natural resource use is critical to the sustainability and maintenance of environmental quality. In western Nepal, unsustainable resource extraction is seen by the local community as a major threat to forest sustainability. While most respondents to a survey of 243 households inside and outside a protected area (PA) thought the laws for managing resource use were adequate and appropriate, a far smaller proportion thought they were achieving their objectives. Disenchantment with the existing governance regime was strongest outside the PA, probably because there was greater investment in community engagement within the PA. The most likely reason for this failure is the deeply embedded corruption within the forest governance system. Devolution of power to local communities by increasing governance participation is one of the most likely means of containing corruption. It was therefore not surprising that governance participation was rated as the most important governance principle by respondents in a best-worst scaling experiment. Respondents also regarded effectiveness, accountability and transparency as important governance principle to improve management of forest resource extraction from red panda habitat.


Measuring hypoxia-induced RNA in maternal blood: a new way to identify critically hypoxic fetuses in utero?
Severe fetal hypoxia causes stillbirth and permanent childhood disability. Unfortunately, none of the current tests is precise at determining the degree of fetal hypoxia in utero. We recently showed that hypoxia-induced RNA abundance in the maternal circulation (of likely fetoplacental origin) was tightly correlated with the degree of fetal hypoxia, suggesting it may be possible to generate a maternal blood test to more precisely determine the severity of fetal hypoxia. Such a test could drastically improve outcomes and decrease stillbirth rates. We are running a large prospective study to validate this test, and will use microarrays, RNA-seq and digital PCR to identify RNA transcripts that best correlate with the severity of fetal hypoxia. Finally, we note our data hints at the possibility of measuring dynamic changes in the fetoplacental transcriptome, measured in serial maternal blood samples. This could afford exciting new insights into the pathology of major obstetric diseases.


Inhibition of U6 snRNA Transcription by PTEN.
PROBLEM STATEMENT: RNA polymerase III (RNA pol III) is responsible for transcribing many of the small structural RNA molecules involved in RNA processing and protein translation, thereby regulating the growth rate of a cell. RNA pol III transcribes both gene internal (tRNA) and gene external (U6 snRNA) promoters and proper initiation by RNA polymerase III requires the transcription initiation factor TFIIIB. TFIIIB has been shown to be a target of repression by tumor suppressors such as ARF, p53, RB and the RB-related pocket proteins. Also, TFIIIB activity is stimulated by the oncogenes c-Myc and the ERK mitogen-activated protein kinase. Recently, two TFIIIB subunits, BRF1 and BRF2, have been demonstrated to behave as oncogenes, making deregulation of TFIIIB activity and thus RNA pol III transcription an important step in tumor development. PTEN is a commonly mutated tumor suppressor regulating cell growth, proliferation and survival. Thus, we sought to examine the potential role of PTEN in regulating U6 snRNA transcription. APPROACH: We examined the potential for PTEN to regulate U6 snRNA transcription using in vitro RNA pol III luciferase assays, western blotting and deletion analysis in cancer cell lines differing in their PTEN status. RESULTS: Using breast, cervical, prostate and glioblastoma cancer cells we demonstrate: (1) PTEN inhibition of gene external RNA pol III transcription is cell type specific, (2) PTEN-mediated inhibition of U6 transcription occurs via the C2 lipid-binding domain and (3) PTEN repression of U6 transcription occurs, at least in part, through the TFIIIB subunit BRF2. CONCLUSION/RECOMMENDATIONS: Our data demonstrates that regulation of the U6 snRNA gene by PTEN is mediated, in part by the TFIIIB oncogene BRF2, potentially identifying novel targets for chemotherapeutic drug design.


Development, implementation and quality assurance of biokinetic models within CONRAD.
The work of the Task Group 5.2 'Research Studies on Biokinetic Models' of the CONRAD project is presented. New biokinetic models have been implemented by several European institutions. Quality assurance procedures included intercomparison of the results as well as quality assurance of model formulation. Additionally, the use of the models was examined leading to proposals of tuning parameters. Stable isotope studies were evaluated with respect to their implications to the new models, and new biokinetic models were proposed on the basis of their results. Furthermore, the development of a biokinetic model describing the effects of decorporation of actinides by diethylenetriaminepentaacetic acid treatment was initiated.


Seromuscular enteric pedicles and prosthetic aortic graft complications in a porcine abdominal trauma model. An experimental study.
Abdominal vascular trauma may require prosthetic grafting despite peritoneal contamination by concurrent visceral injury. This study tested the use of vascularized, seromuscular enteric pedicles (VSEP) against the development of vascular prosthetic complications, in a porcine abdominal trauma model. Eight pigs underwent aortic transection and reconstruction with a Dacron interposition graft (DIG). A standard bacterial inoculum soaked the DIG in situ. An enteric segment was isolated on its mesenteric pedicle, and the mucosa stripped. This VSEP was wrapped around the DIG and oversewn. Animals received antibiotics for 5 days. Endpoints were 2-week survival, or evidence of sepsis. The animals underwent explantation of the DIG, VSEP, and native aorta for the purposes of histological, and microbiological analyses, and scanning electron microscopy (SEM). Outcome measures were graft infection, graft thrombosis, tissue incorporation, and anastomotic integrity. Two pigs were excluded for perioperative death. All study group animals (n = 6), survived 2 weeks. Infection and thrombosis were found in 0/6 (0%). Incorporation and anastomotic integrity were evident in 6/6 (100%). VSEP had intact blood supplies. SEM demonstrated viable muscle, microcirculation, and fibroplasia in VSEP. We conclude that VSEP may help prevent prosthetic graft complications in the contaminated setting.


Deep Direct Reinforcement Learning for Financial Signal Representation and Trading.
Can we train the computer to beat experienced traders for financial assert trading? In this paper, we try to address this challenge by introducing a recurrent deep neural network (NN) for real-time financial signal representation and trading. Our model is inspired by two biological-related learning concepts of deep learning (DL) and reinforcement learning (RL). In the framework, the DL part automatically senses the dynamic market condition for informative feature learning. Then, the RL module interacts with deep representations and makes trading decisions to accumulate the ultimate rewards in an unknown environment. The learning system is implemented in a complex NN that exhibits both the deep and recurrent structures. Hence, we propose a task-aware backpropagation through time method to cope with the gradient vanishing issue in deep training. The robustness of the neural system is verified on both the stock and the commodity future markets under broad testing conditions.


Estimation of Radiation Dose in CT Based on Projection Data.
Managing and optimizing radiation dose has become a core problem for the CT community. As a fundamental step for dose optimization, accurate and computationally efficient dose estimates are crucial. The purpose of this study was to devise a computationally efficient projection-based dose metric. The absorbed energy and object mass were individually modeled using the projection data. The absorbed energy was estimated using the difference between intensity of the primary photon and the exit photon. The mass was estimated using the volume under the attenuation profile. The feasibility of the approach was evaluated across phantoms with a broad size range, various kVp settings, and two bowtie filters, using a simulation tool, the Computer Assisted Tomography SIMulator (CATSIM) software. The accuracy of projection-based dose estimation was validated against Monte Carlo (MC) simulations. The relationship between projection-based dose metric and MC dose estimate was evaluated using regression models. The projection-based dose metric showed a strong correlation with Monte Carlo dose estimates (R (2) > 0.94). The prediction errors for the projection-based dose metric were all below 15 %. This study demonstrated the feasibility of computationally efficient dose estimation requiring only the projection data.


RNA helix stability in mixed Na+/Mg2+ solution.
A recently developed tightly bound ion model can account for the correlation and fluctuation (i.e., different binding modes) of bound ions. However, the model cannot treat mixed ion solutions, which are physiologically relevant and biologically significant, and the model was based on B-DNA helices and thus cannot directly treat RNA helices. In the present study, we investigate the effects of ion correlation and fluctuation on the thermodynamic stability of finite length RNA helices immersed in a mixed solution of monovalent and divalent ions. Experimental comparisons demonstrate that the model gives improved predictions over the Poisson-Boltzmann theory, which has been found to underestimate the roles of multivalent ions such as Mg2+ in stabilizing DNA and RNA helices. The tightly bound ion model makes quantitative predictions on how the Na+-Mg2+ competition determines helix stability and its helix length-dependence. In addition, the model gives empirical formulas for the thermodynamic parameters as functions of Na+/Mg2+ concentrations and helix length. Such formulas can be quite useful for practical applications.


[Dynamic expressions of IL-22 and hepatic stellate cells senescence in mice infected with Schistosoma japonicum].
To investigate the dynamic expressions of interleukin-22 (IL-22) , Interleukin-22 receptor 1 (IL-22R1), and hepatic stellate cells (HSC) senescence in mice with Schistosoma japonicum infection. A murine model of S. japonicum infection was established and the serum samples and liver tissues were collected 4, 6, 8, 12 weeks post-infection. The serum samples were detected for the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The pathological changes and proliferation of hepatic collagen fibers in the liver tissue were observed after HE staining and Masson staining. The HSC senescence in fibrotic livers was determined by the detection of senescence-associated beta-galactosidase (SA-beta-Gal). Sandwich ELISA was used to measure the expressions of IL-22, and Real-time PCR was used to test the mRNA levels of IL-22 and IL-22R1. The control group without S. japonicum infection was set up. The serum levels of ALT and AST significantly increased 8 weeks and 12 weeks after the infection (vs. 0 week, all P < 0.05). The level of IL-22 increased 4 weeks and 6 weeks after the infection (vs. 0 week, both P < 0.05), but reduced 8 weeks post-infection, and was even lower 12 weeks post-infection (vs. 4 weeks and 6 weeks, both P < 0.01). Being consistent with the dynamic expression of IL-22 protein, the mRNA expression of IL-22 began to increase 4 weeks and reached the peak 6 weeks after the infection (vs. 0 week, both P < 0.05), and continuously declined 8 weeks and 12 weeks post-infections (vs. 6 weeks, both P< 0.05). The increase of the expression of IL-22R1 mRNA was correlated with the progression of fibrosis, and the peak was in 12 weeks post-infections (vs. 0 week and 6 weeks, both P < 0.05). The number of senescence-associated beta-galactosidase-positive HSCs was reduced with the decreasing expression of IL-22 in the advanced liver fibrosis. IL-22 and IL-22R1 are involved in the pathogenesis of schistosomiasis liver fibrosis. As an inflammation factor, IL-22 significantly increases in the early stage of fibrosis. The expression of IL-22 decreases in the late stage of fibrosis, which may contribute to HSC senescence and restrict liver fibrosis.


Report of the Skin Research Workgroups from the GRAPPA 2019 Annual Meeting.
The International Dermatology Outcome Measures (IDEOM) initiative is a nonprofit organization dedicated to enhancing clinical care and research in dermatology by developing evidence-based, patient-centered outcome measures. At the 2019 annual meeting of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA), the IDEOM psoriasis working group presented an overview of its selected deliverables and discussed its efforts to agree on meaningful, valid, and feasible outcome measures for quality measurement in psoriasis. The psoriatic arthritis (PsA) workgroup focused on the measurement of PsA symptoms in psoriasis clinical trials, and the measurement of nonspecific musculoskeletal symptoms among patients with psoriasis in psoriasis longitudinal clinical trials and cohort studies.


Millimeter-long carbon nanotubes: outstanding electron-emitting sources.
We are reporting the fabrication of a very efficient electron source using millimeter-long and highly crystalline carbon nanotubes. These devices start to emit electrons at fields as low as 0.17 V/μm and reach threshold emission at 0.24 V/μm. In addition, these electron sources are very stable and can achieve a peak current density of 750 mA cm(-2) at only 0.45 V/μm. In order to demonstrate intense electron beam generation, these devices were used to produce visible light by cathodoluminescence. Finally, density functional theory calculations were used to rationalize the measured electronic field emission properties in open carbon nanotubes of different lengths. The modeling establishes a clear correlation between length and field enhancement factor.


The fine structure of a microplate-microtubule array, microfilaments and polyhedral body associated microtubules in several species of Anabaena.
A microplate-microtubule array was observed in Anabaena sp. (B-378). This structure consists of an arched plate, about 8 nm thick, and various microtubules, 12 nm in diameter and 50 nm long, arranged in rows. The microtubules project at right angles from one side of the plate into the cytoplasm or towards the plasma membrane. Up to twelve microplate-microtubule arrays were observed in a single section of a cell. Microfilaments, about 2.8 nm in diameter and of undetermined length, were observed in four isolates of Anabaena. The microfilaments were always found in bundles, nwhich varied in size, up to 0.63 mum across and 0.91 mum long. Microtubules, 10 nm in diameter and about 150 nm in length, were observed associated with one facet of polyhedral bodies in 8 out of 20 isolates of Anabaena. The microtubules occurred in groups of up to 20 or more, and were always oriented with the long axis parallel to the facet of a polyhedral body. In cross section, the microtubules had an electron transparent lumen 5 nm wide and a wall 2.5 nm thick. These structures are compared to previously described microtubules and microfilaments.


[Surgery of lung carcinoma].
The author's review comprises cases with a total of 2452 patients who had suffered from lung cancer; most of them above 60 years of age. Overall mortality rate came up to 5.2%. The variations of surgical technique are dealt with in detail. In addition, preoperative irradiation in combination with surgery is referred to.


The German model for rescue of traumatized patients.
Accidents and their sequelae are the main cause of death in Germany among people under 40 years of age. The cost in disability payments and lost work averages $40 000 per injury. The author describes the German system for trauma rescue. The aims of rescue care in Germany are to reduce the interval between injury and hospital admission and to bring the patient to the right hospital, bypassing smaller hospitals if necessary. Ambulance rescue systems are of two types: the stationary, in which the physician travels with the ambulance, and the rendezvous, in which the physician and ambulance, travelling separately, meet at the accident site. At the beginning of the 1970s the air-rescue system was started and now comprises 32 stations and 25 BO-105 helicopters. The Hannover experience shows that of the initial diagnoses made at the accident site by helicopter rescue service, 51.9% of victims had head injuries, 35.5% fractures of extremities, 17.0% thoracic trauma, 10.2% abdominal trauma and 7.6% spinal fractures. Because of respiratory insufficiency or unconsciousness with danger of aspiration, 12.0% of the patients had to be intubated endotracheally. One hundred and twenty-two patients with a clinical diagnosis of death were successfully resuscitated at the accident scene. A study comparing the efficiency of the helicopter and ambulance systems showed that as the severity of the injuries increases, the death rate is greater in the group rescued by ambulance. Of 22 accidents involving rescue helicopters, 7 (32%) resulted in at least one death. Between 1973 and 1983, 16 doctors, pilots or attendants were killed.


Kinetic Sprint Asymmetries on a non-motorised Treadmill in Rugby Union Athletes.
The purpose of this study was to present a potential link between sprint kinetic (vertical [F V] and horizontal force [F H]) asymmetries and athletic performance during acceleration and maximal velocity (v max) sprinting. Thirty un-injured male rugby athletes performed 8-s sprints on a non-motorised treadmill. Kinetic data were divided into 'strong' and 'weak' legs based on individually averaged peak values observed during sprinting and were analysed to evaluate asymmetry. Large differences were found between the strong and weak legs in F H during acceleration (4.3 vs. 3.5 N·kg-1) and v max (3.7 vs. 2.8 N·kg-1) sprinting (both ES=1.2), but not in F V (21.8 vs. 20.8 N·kg-1, ES=- 0.6 for acceleration; 23.9 vs. 22.8 N·kg-1, ES=- 0.5 for v max, respectively). Group mean asymmetry was lower in F V compared to F H during acceleration (1.6 vs. 6.8%) and v max (1.6 vs. 8.2%). The range of asymmetry was much lower in F V (0.03-4.3%) compared to F H (0.2-28%). In un-injured rugby athletes, the magnitude and range of asymmetry scores in F H, occurring during acceleration and v max phases, where much greater than those found in F V. These findings highlight the potential for some un-injured athletes to possess kinetic asymmetries known as crucial components for acceleration performance in sprinting.


Brain targeting efficiency of antimigrain drug loaded mucoadhesive intranasal nanoemulsion.
Zolmitriptan (ZT) is a well-tolerated drug in migraine treatment suffering from low bioavailability due to low amount of the drug that reaches the brain after oral and nasal delivery. Development of new nasal mucoadhesive nanoemulsion formulation for zolmitriptan may success in delivering the drug directly from the nose to the brain to achieve rapid onset of action and high drug concentration in the brain which is required for treatment of acute migraine. ZT mucoadhesive nanoemulsion were prepared and characterized for drug content, zeta potential, particle size, morphology, residence time and permeation through the nasal mucosa. The selected formula was tested in-vivo in mice for its pharmacokinetics in comparison with intravenous and nasal solution of zolmitriptan. Results showed that addition of chitosan as mucoadhesive agent in 0.3% concentration to the nanoemulsion enhanced its residence time and zetapotential with no significant effect on the globule size. All tested formulations showed higher permeability coefficients than the zolmitriptan solution through the nasal mucosa. In-vivo studies showed that the mucoadhesive nanoemulsion formulation of zolmitriptan has higher AUC0-8 and shorter Tmax in the brain than the intravenous or the nasal solution. This was related to the small globule size and higher permeability of the formulation.


Observational Needs for Improving Ocean and Coupled Reanalysis, S2S Prediction, and Decadal Prediction.
Developments in observing system technologies and ocean data assimilation (DA) are symbiotic. New observation types lead to new DA methods and new DA methods, such as coupled DA, can change the value of existing observations or indicate where new observations can have greater utility for monitoring and prediction. Practitioners of DA are encouraged to make better use of observations that are already available, for example, taking advantage of strongly coupled DA so that ocean observations can be used to improve atmospheric analyses and vice versa. Ocean reanalyses are useful for the analysis of climate as well as the initialization of operational long-range prediction models. There are many remaining challenges for ocean reanalyses due to biases and abrupt changes in the ocean-observing system throughout its history, the presence of biases and drifts in models, and the simplifying assumptions made in DA solution methods. From a governance point of view, more support is needed to bring the ocean-observing and DA communities together. For prediction applications, there is wide agreement that protocols are needed for rapid communication of ocean-observing data on numerical weather prediction (NWP) timescales. There is potential for new observation types to enhance the observing system by supporting prediction on multiple timescales, ranging from the typical timescale of NWP, covering hours to weeks, out to multiple decades. Better communication between DA and observation communities is encouraged in order to allow operational prediction centers the ability to provide guidance for the design of a sustained and adaptive observing network.


Heartworm disease manifested by encephalomyelitis and myositis in a dog.
A 2-year-old Boston Terrier was referred because of depression and hindlimb and tail paresis. Clinical examination and serum biochemical analysis resulted in a diagnosis of encephalomyelitis and myositis. Results of testing for Dirofilaria immitis were positive. Gross and histologic examination revealed an aberrant adult heartworm infection resulting in thrombosis of the femoral artery and multiple muscular branches, with subsequent muscle necrosis and inflammation in one hindlimb. Additionally, an unusual larval-tissue interaction to microfilariae yielded a multifocal encephalomyelitis in the brain and spinal cord.


An evaluation of strength of composite resin restorations using different bonding agents--an in-vitro study.
In the recent years, the scope of conservative dentistry with emphasis on esthetics has increased by leaps and bounds in enhancing individual personality. Composite resins are important for aesthetic restorations in dentistry, specifically in operative dentistry. But without bonding agents the success of composite restorations is minimized. Researchers are constantly endeavoring to improve the quality of bonding agents. The advent of new bonding systems which are capable of bonding both enamel & dentin has opened new avenues in the field of restorative dentistry. With the market floating with new bonding agents claiming superior bonding properties, this study was undertaken to investigate the degree of bond strength produced by three commercially available bonding agents (Syntac, Scotchbond 1, & Clearfil SE) with composite resin (Esthet-X) taken for the experimental procedure.


SPECT/CT SUV-based metrics: A promising diagnostic tool in classifying patientswith suspected transthyretin cardiac amyloidosis among the different Perugini grades?
The purpose of this study was to evaluate the contribution of single photon emission computed tomography/computed tomography (SPECT/CT) standardized uptake value (SUV) metrics in classifying patients with suspected transthyretin cardiac amyloidosis (ATTR-CA) among the different Perugini grades. One hundred four patients suspected of ATTR-CA underwent planar scintigraphy with bone seeking tracer (99mTc pyrophosphate-PYP). Patients were classified according to the Perugini scale, the H/CL, H/Bone and H/Bkg ratios. A subset of 48 patients received additional SPECT/CT. Single photon emission computed tomography/CT SUV quantitative parameters, of the heart, myocardium, lungs, liver, soft tissues, bone, and SUV ratios (SUVmaxmyo, SUVmaxlungs, SUVmaxliver, SUVmaxbone and SUVmaxsoft tissue ratios), were evaluated in order to investigate potential metrics that could more clearly differentiate Perugini grades. A total of 33.7% of patients were considered grade 0, 34.6% grade 1 and 31.7% grade 2/3. A combination of H/CL >1.33 and H/Bone >0.85 showed the highest sensitivity 100%. Standardized uptake value-based metrics clearly differentiated grade 0 or 1 vs grades 2 or 3, whereas no significant difference was found between grades 0 and 1, or between grades 1 and 2. The combined cut-off values H/CL 1.33 and SUVmaxmyo 2.88 yielded 100% sensitivity and 84.6% specificity in differentiating ATTR-CA positives vs negatives. The metric SUVmaxmyo/SUVmaxliver was the best metric to classify patients with grade 1 as negative (grade 0) or positive (grade 2 or 3). Single photon emission computed tomography/CT SUV metrics could be complementary to planar scintigraphy in classifying patients among the different Perugini grades. The ratio SUVmaxmyo/SUVmaxliver was the only parameter with high affinity to differentiate patients with grade 1, as grade 0 or grade 2/3 for ATTR-CA.