Malignant peripheral nerve sheath tumor of the spine after radiation therapy for Hodgkin's lymphoma.
We report the development of a malignant peripheral nerve sheath tumor (MPNST) in 2 patients after irradiation for Hodgkin's lymphoma. Clinicians should be aware of this uncommon, but important fatal complication of radiation therapy. The first case is a 37-year-old man who was diagnosed with nodular sclerosing (NS) Hodgkin's lymphoma and underwent successful mantle radiation. He presented to our neurosurgery service with a left C6 radiculopathy 6 years later. The second case is a 30-year-old female diagnosed with NS Hodgkin's lymphoma. She did well with extensive radiotherapy until 5 years later when she developed severe right arm and chest pain secondary to recurrent lymphoma. After aggressive radio- and chemotherapy, she presented to the neurosurgery service with a right Horner's syndrome, right C6 radiculopathy, and weakness of her right triceps and wrist extensors. Both patients obtained magnetic resonance imaging revealing intradural extramedullary cervical nerve root associated mass lesions. Two years after radiation therapy for his Hodgkin's lymphoma, the first patient underwent a C6 laminectomy at an outside institution for resection of a benign neurofibroma. Four years later, he underwent a posterior C5-7 laminectomy with lateral mass plate fusion and partial excision of a recurrent mass diagnosed as a MPNST. The second patient underwent a C5-6 hemilaminectomy and partial resection of a tumor also pathologically consistent with MPNST. We present 2 case reports of patients who developed neurofibrosarcomatous tumors with malignant transformation after undergoing radiation therapy for Hodgkin's lymphoma. Despite prompt surgical resection, these tumors exhibited aggressive behavior. Numerous cases of soft tissue tumors have been described to arise in areas of prior radiation therapy; however, there have been rare reports of de novo MPNST after radiation therapy, especially in the setting of Hodgkin's lymphoma. Postirradiation MPNST should be considered in the differential diagnosis of a painful, enlarging mass in a previously irradiated area.


Antimicrobial resistance of rapidly growing mycobacteria in western Taiwan: SMART program 2002.
To understand the resistance patterns of rapidly growing mycobacteria (RGM) in Taiwan, antimicrobial resistance of clinical isolates was determined as part of the SMART (Surveillance from Multicenter Antimicrobial Resistance in Taiwan) program. During the period from January 2002 to December 2003, clinical isolates were collected from eight hospitals located on the west side of Taiwan and one reference laboratory. Broth microdilution minimum inhibitory concentrations of 11 antimicrobial agents were determined for 312 clinical isolates of RGM, including the Mycobacterium fortuitum group (110 isolates), Mycobacterium abscessus group (168 isolates), and Mycobacterium chelonae group (34 isolates). Nearly all of the RGM were susceptible to amikacin and ofloxacin (= 90%) and resistant to doxycycline (less than 3% susceptible). Tobramycin showed similar in vitro activity against the M. fortuitum and M. chelonae (77%) groups, but was less active against the M. abscessus group (58%). Ciprofloxacin was active mainly against M. fortuitum (95%). Nearly all RGM were resistant to erythromycin and doxycycline. However, around half of the RGM isolates remained susceptible to minocycline (50-54%). Clarithromycin was active against the M. abscessus group (53% susceptible), with a high rate of resistance in the M. chelonae (38% susceptible) and M. fortuitum (15% susceptible) group. Cefoxitin was more active against the M. fortuitum group (65%) than the other two RGM (40-44%), and les than 40% of the RGM isolates remained susceptible to imipenem (21-38%). The resistance of RGM in Taiwan is not as high as previously reported (notably for tobramycin, ciprofloxacin and cefoxitin), but reduction in the susceptibility rates of clarithromycin and imipenem for the M. fortuitum and M. abscessus groups demonstrates the importance of in vitro susceptibility testing of clinically important isolates, as susceptibility may differ in different geographical areas, even regionally, and over time.


Effect of community size on eligibility for early intervention for infants with a neonatal intensive care experience.
To determine if population density (rural vs urban) in a child's home community influenced the decision of eligibility for early intervention (EI) services. The sample included 356 infants with a gestational age of <31 weeks referred from a statewide child find program for an evaluation for EI services. A binary logistic regression analysis was completed to determine which variables predicted acceptance into EI services. Infants less than 31 weeks gestation residing in rural areas were more likely to be eligible for EI services than premature infants (ie, <31 weeks gestation) with similar birth characteristics from urban areas. A binary logistic regression analysis revealed an odds ratio for eligibility for EI services among children living in rural areas compared to those living in urban areas was 3.007 (95% CI, 1.497 to 6.040). Additionally, the odds ratio for eligibility for males as compared to females was 1.908 (95% CI, 1.017 to 3.578). Participants who lived in a rural area and were male were more likely to be eligible for EI services than those who lived in urban locations and were female. Factors such as community support, experience with high-risk populations, and differences in interpreting eligibility criteria may influence the differences found between the rural and urban populations. Analysis of intervention cost versus effectiveness will be needed to determine whether the system as adopted in the rural versus urban environment is more appropriate for the provision of EI services.


Evolution of individual versus social learning on social networks.
A number of studies have investigated the roles played by individual and social learning in cultural phenomena and the relative advantages of the two learning strategies in variable environments. Because social learning involves the acquisition of behaviours from others, its utility depends on the availability of 'cultural models' exhibiting adaptive behaviours. This indicates that social networks play an essential role in the evolution of learning. However, possible effects of social structure on the evolution of learning have not been fully explored. Here, we develop a mathematical model to explore the evolutionary dynamics of learning strategies on social networks. We first derive the condition under which social learners (SLs) are selectively favoured over individual learners in a broad range of social network. We then obtain an analytical approximation of the long-term average frequency of SLs in homogeneous networks, from which we specify the condition, in terms of three relatedness measures, for social structure to facilitate the long-term evolution of social learning. Finally, we evaluate our approximation by Monte Carlo simulations in complete graphs, regular random graphs and scale-free networks. We formally show that whether social structure favours the evolution of social learning is determined by the relative magnitudes of two effects of social structure: localization in competition, by which competition between learning strategies is evaded, and localization in cultural transmission, which slows down the spread of adaptive traits. In addition, our estimates of the relatedness measures suggest that social structure disfavours the evolution of social learning when selection is weak.


Temporal stability and accuracy of motivational profiles.
The sensitivity theory of motivation proposes individual differences in the strength of 15 fundamental motives. A central assumption of the theory is that individual differences are stable across time. The first objective of this study was to estimate the stability of motivational profiles across time by retesting 79 individuals with mental retardation at a 3-year interval. The second objective of this study was to evaluate the accuracy of motivational profiles. We presented three motivational profiles to raters and asked them to identify which one corresponded to the person they had rated. Results indicated good to excellent stability and very good accuracy. This is the first study to examine the long-term stability of motivational variables in individuals with mental retardation.


HIV gp120 Protein Increases the Function of Connexin 43 Hemichannels and Pannexin-1 Channels in Astrocytes: Repercussions on Astroglial Function.
At least half of human immunodeficiency virus (HIV)-infected individuals suffer from a wide range of cognitive, behavioral and motor deficits, collectively known as HIV-associated neurocognitive disorders (HAND). The molecular mechanisms that amplify damage within the brain of HIV-infected individuals are unknown. Recently, we described that HIV augments the opening of connexin-43 (Cx43) hemichannels in cultured human astrocytes, which result in the collapse of neuronal processes. Whether HIV soluble viral proteins such as gp120, can regulate hemichannel opening in astrocytes is still ignored. These channels communicate the cytosol with the extracellular space during pathological conditions. We found that gp120 enhances the function of both Cx43 hemichannels and pannexin-1 channels in mouse cortical astrocytes. These effects depended on the activation of IL-1β/TNF-α, p38 MAP kinase, iNOS, cytoplasmic Ca2+ and purinergic signaling. The gp120-induced channel opening resulted in alterations in Ca2+ dynamics, nitric oxide production and ATP release. Although the channel opening evoked by gp120 in astrocytes was reproduced in ex vivo brain preparations, these responses were heterogeneous depending on the CA1 region analyzed. We speculate that soluble gp120-induced activation of astroglial Cx43 hemichannels and pannexin-1 channels could be crucial for the pathogenesis of HAND.


The role of executive functioning in memory performance in pediatric focal epilepsy.
Learning and memory are essential for academic success and everyday functioning, but the pattern of memory skills and its relationship to executive functioning in children with focal epilepsy is not fully delineated. We address a gap in the literature by examining the relationship between memory and executive functioning in a pediatric focal epilepsy population. Seventy children with focal epilepsy and 70 typically developing children matched on age, intellectual functioning, and gender underwent neuropsychological assessment, including measures of intelligence (Wechsler Abbreviated Scale of Intelligence [WASI]/Differential Ability Scales [DAS]), as well as visual Children's Memory Scale (CMS Dot Locations) and verbal episodic memory (Wide Range Assessment of Memory and Learning [WRAML] Story Memory and California Verbal Learning Test for Children [CVLT-C]). Executive functioning was measured directly (WISC-IV Digit Span Backward; Clinical Evaluation of Language Fundamentals, Fourth Edition (CELF-IV) Recalling Sentences) and by parent report (Behavior Rating Inventory of Executive Function [BRIEF]). Children with focal epilepsy had lower delayed free-recall scores than controls across visual and verbal memory tasks (p = 0.02; partial η2 = 0.12). In contrast, recognition memory performance was similar for patients and controls (p = 0.36; partial η2 = 0.03). Children with focal epilepsy demonstrated difficulties in working memory (p = 0.02; partial η2 = 0.08) and planning/organization (p = 0.02) compared to controls. Working memory predicted 9-19% of the variance in delayed free recall for verbal and visual memory; organization predicted 9-10% of the variance in verbal memory. Patients with both left and right focal epilepsy demonstrated more difficulty on verbal versus visual tasks (p = 0.002). Memory performance did not differ by location of seizure foci (temporal vs. extratemporal, frontal vs. extrafrontal). Children with focal epilepsy demonstrated memory ability within age-level expectations, but delayed free recall was inefficient compared to typically developing controls. Memory difficulties were not related to general cognitive impairment or seizure localization. Executive functioning accounted for significant variance in memory performance, suggesting that poor executive control negatively influences memory retrieval.


Evaluation of linear accelerator-based stereotactic radiosurgery in the management of glomus jugulare tumors.
Although mostly benign and slow-growing, glomus jugulare tumors have a high propensity for local invasion of adjacent vascular structures, lower cranial nerves and the inner ear, which may result in substantial morbidity and even mortality. Treatment strategies for glomus jugulare tumors include surgery, preoperative embolization followed by surgical resection, conventionally fractionated external beam radiotherapy, radiosurgery in the form of stereotactic radiosurgery or fractionated stereotactic radiation therapy, and combinations of these modalities. In the present study, we evaluate the use of linear accelerator (LINAC)-based stereotactic radiosurgery in the management of glomus jugulare tumors and report our 15-year single center experience. Between May 1998 and May 2013, 21 patients (15 females, 6 males) with glomus jugulare tumors were treated using LINAC-based stereotactic radiosurgery at the Department of Radiation Oncology, Gulhane Military Medical Academy. The indication for stereotactic radiosurgery was the presence of residual or recurrent tumor after surgery for 5 patients, whereas 16 patients having growing tumors with symptoms received stereotactic radiosurgery as the primary treatment. Median follow-up was 49 months (range, 3-98). Median age was 55 years (range, 24-77). Of the 21 lesions treated, 13 (61.9%) were left-sided and 8 (38.1%) were right-sided. Median dose was 15 Gy (range, 10-20) prescribed to the 85%-100% isodose line encompassing the target volume. Local control defined as either tumor shrinkage or the absence of tumor growth on periodical follow-up neuroimaging was 100%. LINAC-based stereotactic radiosurgery offers a safe and efficacious management strategy for glomus jugulare tumors by providing excellent tumor growth control with few complications.


Diagnostic criteria and follow-up in neuroendocrine cell hyperplasia of infancy: a case series.
Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease characterized by tachypnea, retractions, crackles, and hypoxia. The aim of this study was to report and discuss the clinical, imaging, and histopathological findings in a series of NEHI cases at a tertiary pediatric hospital, with an emphasis on diagnostic criteria and clinical outcomes. Between 2003 and 2011, 12 full-term infants were diagnosed with NEHI, based on clinical and tomographic findings. Those infants were followed for 1-91 months. Four infants were biopsied, and the histopathological specimens were stained with bombesin antibody. In this case series, symptoms appeared at birth in 6 infants and by 3 months of age in the remaining 6. In all of the cases, NEHI was associated with acute respiratory infection. The most common initial chest HRCT findings were ground-glass opacities that were in the middle lobe/lingula in 12 patients and in other medullary areas in 10. Air trapping was the second most common finding, being observed in 7 patients. Follow-up HRCT scans (performed in 10 patients) revealed normal results in 1 patient and improvement in 9. The biopsy findings were nonspecific, and the staining was positive for bombesin in all samples. Confirmation of NEHI was primarily based on clinical and tomographic findings. Symptoms improved during the follow-up period (mean, 41 months). A clinical cure was achieved in 4 patients. In this sample of patients, the diagnosis of NEHI was made on the basis of the clinical and tomographic findings, independent of the lung biopsy results. Most of the patients showed clinical improvement and persistent tomographic changes during the follow-up period, regardless of the initial severity of the disease or type of treatment.


Acute aortic valvular regurgitation with pulmonary haemorrhage in Wegener's granulomatosis presenting as dyspnoea: a rare presentation.
A 40-year-old man with Wegener's granulomatosis with renal and ocular involvement was admitted with symptoms of fever, malaise and cough not responding to oral antibiotics. On initial assessment, he had patchy consolidation but was also found to have a new cardiac murmur. He was mildly anaemic. Within 2 days of hospital stay his haemoglobin dropped and he became tachypnoeic. High-resolution CT found extensive pulmonary infiltrates, which suggested pulmonary haemorrhage, and blood cultures were negative. He was on antibiotics because of suspected infective endocarditis and this made any immunosuppressive treatment for active Wegener's granulomatosis very difficult. After extensive discussion with tertiary centres he had pulse methylprednisolone for 3 days. His echo detected aortic regurgitation but no vegetations. His antibiotics were stopped and he had cyclophosphomide to control his active Wegener's granulomatosis. He improved remarkably with immunosuppression and non-invasive ventilation and was discharged. He had a further echo, which confirmed moderate aortic regurgitation. He is awaiting cardiac catheter studies but the fact is acute aortic regurgitation has happened due to active Wegener's granulomatosis along with pulmonary haemorrhage. This is a very rare presentation.


Urban stormwater quality: A review of methods for continuous field monitoring.
Urban stormwater is contaminated by a wide range of substances whose concentrations vary greatly between locations, as well as between and during rain events. This literature review evaluates advantages and limitations of current methods for using continuous water quality monitoring for stormwater characterization and control. High-temporal-resolution measurements have been used to improve the understanding of stormwater quality dynamics and pollutant pathways, facilitate the performance evaluation of stormwater control measures and improve operation of the urban drainage system with real-time control. However, most sensors used to study stormwater were developed for either centralized water treatment or natural water contexts and adaptation is necessary. At present, the primary application of interest in stormwater - characterization of pollutant concentrations - can only be achieved through the use of indirect measurements with site-specific relationships of pollutants to basic physical-chemical parameters. In addition, various problems arise in the field context, associated with intermittent or variable flow rates, the accumulation of debris and sediment, adverse conditions for electrical equipment and human factors. Obtaining reliable continuous stormwater quality data requires the adoption of best practices, including the calibration and regular maintenance of sensors, verification of data and accounting for the considerable uncertainties in data; however, the literature review showed that improvement is needed among the scientific community in implementing and documenting these practices.


Proactive approach at the limits of viability improves the short-term outcome of neonates born after 23 weeks' gestation.
The aim of this single-center study was to identify factors that affect the short-term outcome of newborns delivered around the limits of viability. A group of 137 pregnant women who gave birth between 22+0/7 and 25+6/7 weeks of gestation was retrospectively studied. The center supports a proactive approach to infants around the limits of viability. Perinatal and neonatal characteristics were obtained and statistically evaluated. A total of 166 live-born infants were enrolled during a 6-year period; 162 (97.6%) of them were admitted to the neonatal intensive care unit (ICU) and 119 (73.5%) survived until discharge. The decrease in neonatal mortality was associated with an advanced gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Neonatal morbidities were common among infants of all gestational ages. The incidence of severe intraventricular hemorrhage significantly depended on gestational age (P<0.001) and a completed course of corticosteroids (P=0.002). Survival without severe neonatal morbidities was 39.5% and occurred mostly after 24+0/7 weeks of gestation. The short-term outcome of newborns delivered around the limits of viability is mostly affected by gestational age and antenatal corticosteroid treatment. A consistently proactive approach improves the survival of infants at the limits of viability. This is most pronounced in cases where the delivery is delayed beyond 24 completed gestational weeks.


Salts employed in hydrophobic interaction chromatography can change protein structure - insights from protein-ligand interaction thermodynamics, circular dichroism spectroscopy and small angle X-ray scattering.
Key requirements of protein purification by hydrophobic interaction chromatography (HIC) are preservation of the tertiary/quaternary structure, maintenance of biological function, and separation of the correctly folded protein from its unfolded forms or aggregates. This study examines the relationship between the HIC retention behavior of hen egg white lysozyme (HEWL) in high concentrations of several kosmotropic salts and its conformation, assessed by circular dichroism (CD) spectroscopy. Further, the physicochemical properties of HEWL in the presence of high concentrations of ammonium sulfate, sodium chloride and magnesium chloride were investigated by small angle X-ray scattering (SAXS) at different temperatures. Radii of gyration were extrapolated from Guinier approximations and the indirect transform program GNOM with protein-protein interaction and contrast variation taken into account. A bead model simulation provided information on protein structural changes using ab initio reconstruction with GASBOR. These results correlated to the secondary structure content obtained from CD spectroscopy of HEWL. These changes in SAXS and CD data were consistent with heat capacity ΔCp -values obtained from van't Hoff plot analyses of the retention data. Collectively, these insights enable informed decisions to be made on the choice of chromatographic conditions, leading to improved separation selectivity and opportunities for innovative column-assisted protein refolding methods.


Enamel microarchitecture of a tribosphenic molar.
The tribosphenic molar is a dental apomorphy of mammals and the molar type from which all derived types originated. Its enamel coat is expected to be ancestral: a thin, evenly distributed layer of radial prismatic enamel. In the bat Myotis myotis, we reinvestigated the 3D architecture of the dental enamel using serial sectioning combined with scanning electron microscopy analyses, biometrics of enamel prisms and crystallites, and X-ray diffraction. We found distinct heterotopies in enamel thickness (thick enamel on the convex sides of the crests, thin on the concave ones), angularity of enamel prisms, and in distribution of particular enamel types (prismatic, interprismatic, aprismatic) and demonstrated structural relations of these heterotopies to the cusp and crest organization of the tribosphenic molar. X-ray diffraction demonstrated that the crystallites composing the enamel are actually the aggregates of much smaller primary crystallites. The differences among particular enamel types in degree of crystallite aggregation and the variation in structural microstrain of the primary crystallites (depending upon the duration and the mechanical context of mineralization) represent factors not fully understood as yet that may contribute to the complexity of enamel microarchitecture in a significant way.


Structural equation modeling of factors contributing to quality of life in Japanese patients with multiple sclerosis.
To improve quality of life (QOL) in patients with multiple sclerosis (MS), it is important to decrease disability and prevent relapse. The aim of this study was to examine the causal and mutual relationships contributing to QOL in Japanese patients with MS, develop path diagrams, and explore interventions with the potential to improve patient QOL. Data of 163 Japanese MS patients were obtained using the Functional Assessment of MS (FAMS) and Nottingham Adjustment Scale-Japanese version (NAS-J) tests, as well as four additional factors that affect QOL (employment status, change of income, availability of disease information, and communication with medical staff). Data were then used in structural equation modeling to develop path diagrams for factors contributing to QOL. The Expanded Disability Status Scale (EDSS) score had a significant effect on the total FAMS score. Although EDSS negatively affected the FAMS symptom score, NAS-J subscale scores of anxiety/depression and acceptance were positively related to the FAMS symptom score. Changes in employment status after MS onset negatively affected all NAS-J scores. Knowledge of disease information improved the total NAS-J score, which in turn improved many FAMS subscale scores. Communication with doctors and nurses directly and positively affected some FAMS subscale scores. Disability and change in employment status decrease patient QOL. However, the present findings suggest that other factors, such as acquiring information on MS and communicating with medical staff, can compensate for the worsening of QOL.


Convergent recruitment of TALE homeodomain life cycle regulators to direct sporophyte development in land plants and brown algae.
Three amino acid loop extension homeodomain transcription factors (TALE HD TFs) act as life cycle regulators in green algae and land plants. In mosses these regulators are required for the deployment of the sporophyte developmental program. We demonstrate that mutations in either of two TALE HD TF genes, OUROBOROS or SAMSARA, in the brown alga Ectocarpus result in conversion of the sporophyte generation into a gametophyte. The OUROBOROS and SAMSARA proteins heterodimerise in a similar manner to TALE HD TF life cycle regulators in the green lineage. These observations demonstrate that TALE-HD-TF-based life cycle regulation systems have an extremely ancient origin, and that these systems have been independently recruited to regulate sporophyte developmental programs in at least two different complex multicellular eukaryotic supergroups, Archaeplastida and Chromalveolata.


Benefit of an association of an antioxidative substrate and a traditional chinese medicine on telomere elongation.
Telomere shortening is involved in age-related disorders, such as cancer and cardiovascular diseases. Recently, telomerase re-activation strategies have been proposed to counteract telomere shortening and its consequences. Here, we investigated the benefit of dietary supplementation with a mix of S-adenosyl-methionine (SAMe) and a polysaccharide extract of Astragalus (APS) on telomere length of circulating lymphocytes of healthy volunteers. Blood lymphocytes of a cohort of 26 healthy volunteers who were administrated the mix of SAMe and APS in a food supplement for one year were collected. In vitro treatment of blood lymphocytes of healthy volunteers with the mix was also performed. A cohort of 150 healthy volunteers was used as a control. Telomere length was measured by Q-FISH. The micronucleus assay was performed to detect genotoxicity of the mix. The telomeres of circulating lymphocytes of the cohort of 26 donors supplemented with the mix were significantly longer than those of matched controls (p < 10-4). This elongation was essentially observed in the lymphocytes of older donors. Similarly, in vitro treatment of circulating lymphocytes with the mix significantly increased telomere length and decrease the proportion of cells with short telomeres. Here, we observed an increase in telomere length after in vivo and in vitro administration of a mix with SAMe and APS. The benefit of dietary supplementation with this mix opens a new horizon for the battle against aging and could be used in the treatment of chronic age-related disorders.


Imaging of disorders of the spine.
Although many papers were published during the past year on disorders of the spine, in this review, papers were chosen and grouped under five broad headings: 1) spinal trauma, 2) disk disease, 3) neoplastic disease, 4) spinal arthritis, and 5) other studies of interest. Although some of the articles chosen for review dealt with conventional radiography, the majority were on applications of CT and MR imaging to conditions affecting the spine.


Research on high proportion of clean energy grid-connected oscillation risk prediction technology based on CNN and trend feature analysis.
Oscillations, commonly known as a universal, propagative, and intricate event in the new power system, often give rise to generator tripping and load shedding, not only adversely affecting the power flow limit and the power angle stability but also posing threats to the lines of defense for stability and protection. Traditionally, emphasis has been laid on post-fault oscillation management, an emergency measure to deal with the impact and damage that have already affected the power grid. As such, this paper focuses on an oscillation prediction technique to detect oscillation energy early and intervene proactively to prevent further faults. This technique effectively lessens the damage caused by impacts and disconnects to the power grid. Firstly, this paper proposes the concept of disturbance power density and establishes the correlation between disturbance energy and the time domain, thereby exploring a method for evaluating the pattern of electrical quantities before power system oscillation. Secondly, it speeds up the time it takes to detect faults by catching nuances of voltage-current phase angle and impedance. Lastly, it puts forward a technique to cope with the intricacy and variety of power grid equipment using the convolutional neural network (CNN). This technique incorporates an integrated attention mechanism within a one-dimensional CNN model to capture the implicit mapping between voltage, active power, and reactive power at any time in the power system. This enables the model to self-learn multi-device characteristics and enhances the possibility of using theory in practical ways. Moreover, practical case studies also show that the prediction technique proposed in this paper can effectively issue warnings eight minutes before the occurrence of oscillation.


Sequence amplification and gene rearrangement in parasitic nematode mitochondrial DNA.
The nematode Romanomermis culicivorax, an obligate mosquito parasite, possesses a 26 kilobase (kb) mitochondrial genome. The unusually large size is due to transcriptionally active DNA sequences present as 3.0 kb direct tandem repeats and as inverted portions of the repeating unit located elsewhere in the mitochondrial DNA (mtDNA). The genome rearrangements involved in establishing this unusual sequence organization may have dramatically altered conventional mitochondrial gene order. Genes for subunits of the cytochrome c oxidase complex (COI and COII) are normally closely linked in animal mtDNAs, but are separated by approximately 8 kb in this mitochondrial genome.


Mutational analysis of the extracellular disulphide bridges of the atypical chemokine receptor ACKR3/CXCR7 uncovers multiple binding and activation modes for its chemokine and endogenous non-chemokine agonists.
The atypical chemokine receptor ACKR3/CXCR7 plays crucial roles in numerous physiological processes but also in viral infection and cancer. ACKR3 shows strong propensity for activation and, unlike classical chemokine receptors, can respond to chemokines from both the CXC and CC families as well as to the endogenous peptides BAM22 and adrenomedullin. Moreover, despite belonging to the G protein coupled receptor family, its function appears to be mainly dependent on β-arrestin. ACKR3 has also been shown to continuously cycle between the plasma membrane and the endosomal compartments, suggesting a possible role as a scavenging receptor. So far, the molecular basis accounting for these atypical binding and signalling properties remains elusive. Noteworthy, ACKR3 extracellular domains bear three disulphide bridges. Two of them lie on top of the two main binding subpockets and are conserved among chemokine receptors, and one, specific to ACKR3, forms an intra-N terminus four-residue-loop of so far unknown function. Here, by mutational and functional studies, we examined the impact of the different disulphide bridges for ACKR3 folding, ligand binding and activation. We showed that, in contrast to most classical chemokine receptors, none of the extracellular disulphide bridges was essential for ACKR3 function. However, the disruption of the unique ACKR3 N-terminal loop drastically reduced the binding of CC chemokines whereas it only had a mild impact on CXC chemokine binding. Mutagenesis also uncovered that chemokine and endogenous non-chemokine ligands interact and activate ACKR3 according to distinct binding modes characterized by different transmembrane domain subpocket occupancy and N-terminal loop contribution, with BAM22 mimicking the binding mode of CC chemokine N terminus.


A genome-wide association study for canine cryptorchidism in Siberian Huskies.
Cryptorchidism is a condition whereby one or both testes fail to descend into the scrotal sac. Here, we performed a genome-wide association study (GWAS) with both a case-control analysis using the GEMMA software accounting for population structure and a BayesB approach in the GenSel software applied to every 1 Mb window of SNPs or haplotypes. The haplotypes were constructed from a genealogical tree using the population of 204 Siberian Huskies. The BayesB analyses identified six putative genomic candidate regions on CFA6, 9, 24, 27 and X. These regions explained a high percentage of genetic variance when compared with other genomic regions. The positional candidate genes Q9TSI5_CANFA (matrix metalloproteinase 9 precursor) on CFA24, ADAMTS20 (ADAM metallopeptidase with thrombospondin type 1 motif, 20) on CFA27 and MID1IP1 (MID1 interacting protein 1) on CFAX are known to be functionally related to extracellular matrix remodelling, which might be important for gubernaculum elongation and thus interrupting normal testicular descent. Further mutation screening in these candidate regions on CFA6, 9, 24, 27 and X is needed. Next generation sequencing will help to uncover rare variants associated with cryptorchidism in this dog population.


Alphavirus-based expression vectors: strategies and applications.
Alphaviruses are positive-strand RNA viruses that can mediate efficient cytoplasmic gene expression in insect and vertebrate cells. Through recombinant DNA technology, the alphavirus RNA replication machinery has been engineered for high-level expression of heterologous RNAs and proteins. Amplification of replication-competent alpha-virus RNAs (replicons) can be initiated by RNA or DNA transfection and a variety of packaging systems have been developed for producing high titers of infectious viral particles. Although normally cytocidal for vertebrate cells, variants with adaptive mutations allowing noncytopathic replication have been isolated from persistently infected cultures or selected using a dominant selectable marker. Such mutations have been mapped and used to create new alphavirus vectors for noncytopathic gene expression in mammalian cells. These vectors allow long-term expression at moderate levels and complement previous vectors designed for short-term high-level expression. Besides their use for a growing number of basic research applications, recombinant alphavirus RNA replicons may also facilitate genetic vaccination and transient gene therapy.


Ruxolitinib Ameliorates Airway Hyperresponsiveness and Lung Inflammation in a Corticosteroid-Resistant Murine Model of Severe Asthma.
Asthma prevalence has increased considerably over the decades and it is now considered as one of the most common chronic disorders in the world. While the current anti-asthmatic therapies are effective for most asthma patients, there are 5-10% subjects whose disease is not controlled by such agents and they account for about 50% of the asthma-associated healthcare costs. Such patients develop severe asthma (SA), a condition characterized by a dominant Th1/Th17 cytokine response that is accompanied by Type 2 (T2)-low endotype. As JAK (Janus Kinase) signaling is very important for the activation of several cytokine pathways, we examined whether inhibition of JAKs might lessen the clinical and laboratory manifestations of SA. To that end, we employed a recently described murine model that recapitulates the complex immune response identified in the airways of human SA patients. To induce SA, mice were sensitized with house dust mite extract (HDME) and cyclic (c)-di-GMP and then subsequently challenged with HDME and a lower dose of c-di-GMP. In this model, treatment with the JAK inhibitor, Ruxolitinib, significantly ameliorated all the features of SA, including airway hyperresponsiveness and lung inflammation as well as total IgE antibody titers. Thus, these studies highlight JAKs as critical targets for mitigating the hyper-inflammation that occurs in SA and provide the framework for their incorporation into future clinical trials for patients that have severe or difficult-to manage asthma.


IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis.
The HIV capsid is semipermeable and covered in electropositive pores that are essential for viral DNA synthesis and infection. Here, we show that these pores bind the abundant cellular polyanion IP6, transforming viral stability from minutes to hours and allowing newly synthesised DNA to accumulate inside the capsid. An arginine ring within the pore coordinates IP6, which strengthens capsid hexamers by almost 10°C. Single molecule measurements demonstrate that this renders native HIV capsids highly stable and protected from spontaneous collapse. Moreover, encapsidated reverse transcription assays reveal that, once stabilised by IP6, the accumulation of new viral DNA inside the capsid increases >100 fold. Remarkably, isotopic labelling of inositol in virus-producing cells reveals that HIV selectively packages over 300 IP6 molecules per infectious virion. We propose that HIV recruits IP6 to regulate capsid stability and uncoating, analogous to picornavirus pocket factors. HIV-1/IP6/capsid/co-factor/reverse transcription.


Elevated occupational transportation fatalities among older workers in Oregon: an empirical investigation.
Older workers have an elevated risk of being killed on the job, and transportation incidents involving vehicles or mobile machinery are especially deadly for this group. The present study was designed to address the research gap in understanding contributing factors to these incidents and recommend evidence-based guidelines for interventions. We gathered and analyzed data from several sources, including the Oregon Fatality Assessment and Control Evaluation program, the Oregon Workers' Compensation system, the Census of Fatal Occupational Injuries, the Bureau of Labor Statistics, and peer reviewed research literatures. Rates and rate ratios (RR) were used to evaluate excess risk among groups. The results of this study show that older workers in Oregon have an elevated risk of fatality both in all events (RR=3.0, 95% CI 2.2-4.0) and transportation events (RR=3.6, 95% CI 2.4-5.4). Additional analyses and extant literature supports our hypotheses that multiple risk factors contribute to the phenomenon, including (a) hazard exposure, (b) organization of work, (c) physical fragility, and (d) normative cognitive, sensory, and psychomotor changes that occur with age. The evidence-based framework proposed may provide valuable guidance for developing safety interventions that protect older workers.


Masticatory efficiency of shortened dental arch subjects with removable partial denture: A comparative study.
The objective of this study was to compare the masticatory efficiency in subjects with shortened dental arch (SDA) before and after restoration with removable partial denture (RPD). This was a prospective study carried out on 36 consecutive patients. The subjects were asked to chew 5 g of a measured portion of fresh raw carrot for 20 specified numbers of strokes. The raw carrot was recovered into a cup and strained through a standard mesh sieve of 5 mm by 1 mm, it was air dried for 30 min and weighed with FEM digital series weighing scale. The masticatory performance ratio was then determined. The age range of the subjects was 34-64 years with the mean age being 52.2 ± 8.2 years. The difference between the total masticatory performance score at the post- and pre-treatment phases was statistically significant (P = 0.001). The improvement in masticatory performance was marked among the younger age groups (P = 0.001), unilateral free end saddle subjects (P = 0.001), and among the male gender (P < 0.05). Masticatory performance improved with the provision of RPD. However, the improvement was marked among the younger age groups, unilateral free end saddle subjects, and the male gender; thereby supporting the need for RPDs in patients with SDA.


Chronic gliosis and behavioral deficits in mice following repetitive mild traumatic brain injury.
With the recent increasing interest in outcomes after repetitive mild traumatic brain injury (rmTBI; e.g., sports concussions), several models of rmTBI have been established. Characterizing these models in terms of behavioral and histopathological outcomes is vital to assess their clinical translatability. The purpose of this study is to provide an in-depth behavioral and histopathological phenotype of a clinically relevant model of rmTBI. The authors used a previously published weight-drop model of rmTBI (7 injuries in 9 days) in 2- to 3-month-old mice that produces cognitive deficits without persistent loss of consciousness, seizures, gross structural imaging findings, or microscopic evidence of structural brain damage. Injured and sham-injured (anesthesia only) mice were subjected to a battery of behavioral testing, including tests of balance (rotarod), spatial memory (Morris water maze), anxiety (open field plus maze), and exploratory behavior (hole-board test). After behavioral testing, brains were assessed for histopathological outcomes, including brain volume and microglial and astrocyte immunolabeling. Compared with sham-injured mice, mice subjected to rmTBI showed increased exploratory behavior and had impaired balance and worse spatial memory that persisted up to 3 months after injury. Long-term behavioral deficits were associated with chronic increased astrocytosis and microgliosis but no volume changes. The authors demonstrate that their rmTBI model results in a characteristic behavioral phenotype that correlates with the clinical syndrome of concussion and repetitive concussion. This model offers a platform from which to study therapeutic interventions for rmTBI.


Nonsteroidal anti-inflammatory therapy: changes on renal function of healthy dogs.
To evaluate the renal function in healthy dogs submitted to nonselective and preferential COX-2 nonsteroidal anti-inflammatory drug (NSAID) therapy. Twenty four healthy dogs were distributed into four groups (G) (n=6): ketoprofenG--treated with ketoprofen; nimesulideG--treated with nimesulid; meloxicanG--treated with meloxican; and etodolacG--treated with etodolaco. All the dogs received the NSAIDs for 10 days by oral route. Physical examination and renal function (urinalysis, urinary sodium and gamma-glutamyl transpeptidase (GGT), serum urea, creatinine, potassium and sodium, and endogenous creatinine clearance) were evaluated before, after five and ten days (T0, T5 and T10) of the treatment in all groups. Changes were observed in urinalysis, with a significant increase in renal cells in the urine at T5 and T10 in nimesulideG. Significant reduction in urinary sodium in nimesulideG at T5 was observed. The clearance values were lower in ketoprofenG at T10. Meloxicam and etodolac were the drugs that have proven to be safer for short-term therapy in healthy dogs in relation to renal function. NSAIDs ketoprofen and nimesulide should be used judiciously in dogs with renal dysfunction, since there are promoted changes in renal function.


[1H- and 2H-NMR relaxation in serum albumin solutions].
The proton and deuteron relaxation times T1 and T2 were investigated in water and heavy water solutions of fatless human serum albumin. The temperature, concentration and Larmor precession frequency dependences can be well described by the conception of fast exchange in a simple biphasic model of water molecules rotation in the first hydration layer with slight anisotropy of motion. In the protonated systems the intermolecular dipole-dipole relaxation mechanism must be taken into account.


[Anticoagulant therapy in stroke patients].
Stroke is a common disease, which is associated with high morbidity and high mortality. Up to 25% of cerebral ischaemic infarcts are caused by cardio-embolic events, most commonly associated with atrial fibrillation. It has previously been shown that antithrombotic therapy is insufficiently used in patients at increased risk of stroke. This article reviews evidence and practical management of anticoagulant therapy in stroke patients and provides an update on risk stratification for thromboembolism and bleeding complications in patients with atrial fibrillation.


Suppression of ACTH-induced steroidogenesis by supernatants from LPS-treated peritoneal exudate macrophages.
The results from a number of clinical and experimental studies have suggested that during endotoxemia, suppression of adrenocortical steroidogenesis may occur. We have examined the possibility that macrophages are the source of a factor that suppresses adrenocortical steroidogenesis. Resident and peptone-elicited peritoneal exudate macrophages (PEM) from C3HeB/FeJ mice were incubated for 4 hr at 37 degrees C in the presence or absence of T cell hybridoma-derived lymphokine (LK) that contained high concentrations of MAF activity (assessed by induction of nonspecific tumoricidal activity in PEM). The LK was removed by rinsing, and fresh medium was added, followed by Salmonella minnesota R595 LPS (final concentration 10 micrograms/ml). After 18 hr at 37 degrees C the PEM supernatants and control medium from flasks without cells were harvested and stored at -20 degrees C. Explanted rabbit adrenocortical cells in 96-well plates were exposed to 30 microliters of PEM supernatant or control medium and ACTH (10 or 100 mU/ml) in a final volume of 120 microliters for 3 consecutive days. The adrenocortical cell supernatants were harvested each day, followed by replenishment of medium, PEM supernatant, and ACTH. Fluorogenic steroid production in wells that received control medium or supernatants from PEM not treated with LPS was normal (0.22 microgram +/- 0.010 (SD) per 5 X 10(4) cells). However, as much as 75 to 95% suppression of steroidogenesis was observed in wells that received supernatants from PEM treated with LK and LPS, compared to 40% suppression in wells that received supernatant from PEM treated with LPS alone. Continued exposure (over 3 days) of adrenocortical cells to supernatants from LPS-treated PEM resulted in progressively decreasing response to ACTH. Comparable suppressive activity was observed in supernatants from LPS-treated bone marrow-derived macrophages. In further experiments, suppression was observed in wells that were pretreated (22 hr) with the appropriate PEM supernatant, and evidence was obtained that the suppressive activity was not due to carry-over LPS. Finally, results from control experiments demonstrated that suppressive PEM supernatants neither inactivate ACTH nor interfere with the assay of fluorogenic steroids. Thus, these results suggest that during endotoxemia, products from LPS-stimulated macrophages may suppress adrenocortical function.


Multiple endocrine neoplasia type 2B (mucosal neuroma syndrome, Wagenmann-Froboese syndrome).
Multiple endocrine neoplasia type 2B (MEN 2B), or the mucosal neuroma syndrome, is an autosomal dominant hamartoneoplastic syndrome. Features include multiple mucosal neuromas, phaeochromocytoma, medullary thyroid carcinoma, and Marfanoid body habitus with a characteristic dysmorphic facies. The gene responsible is the receptor tyrosine kinase (RET) proto-oncogene on chromosome 10. The mutational spectrum of MEN 2B is remarkably narrow, with over 95% of cases being caused by a single methionine to threonine substitution in the intracellular tyrosine kinase domain. Recent biochemical evidence suggests that this mutation alters the substrate specificity of intracellular signal transduction.


Tundra be dammed: Beaver colonization of the Arctic.
Increasing air temperatures are changing the arctic tundra biome. Permafrost is thawing, snow duration is decreasing, shrub vegetation is proliferating, and boreal wildlife is encroaching. Here we present evidence of the recent range expansion of North American beaver (Castor canadensis) into the Arctic, and consider how this ecosystem engineer might reshape the landscape, biodiversity, and ecosystem processes. We developed a remote sensing approach that maps formation and disappearance of ponds associated with beaver activity. Since 1999, 56 new beaver pond complexes were identified, indicating that beavers are colonizing a predominantly tundra region (18,293 km2 ) of northwest Alaska. It is unclear how improved tundra stream habitat, population rebound following overtrapping for furs, or other factors are contributing to beaver range expansion. We discuss rates and likely routes of tundra beaver colonization, as well as effects on permafrost, stream ice regimes, and freshwater and riparian habitat. Beaver ponds and associated hydrologic changes are thawing permafrost. Pond formation increases winter water temperatures in the pond and downstream, likely creating new and more varied aquatic habitat, but specific biological implications are unknown. Beavers create dynamic wetlands and are agents of disturbance that may enhance ecosystem responses to warming in the Arctic.


Professionalism and performance issues during neurosurgical training and job satisfaction after training: a single training center 50-year experience.
Neurosurgery is often self-selecting. Concern has been raised that residents in the millennial era (born between 1982 and 2004) may have more serious professionalism and performance issues (PPIs) during training compared to prior trainees. Serious PPIs were defined as concerns that led to specific resident disciplinary actions ranging from initial warnings to termination. In order to evaluate this concern, the authors retrospectively reviewed a 50-year experience at a single training center. They then prospectively surveyed living graduates of the program to assess variations in practice patterns and job satisfaction over 5 decades. The PPIs of 141 residents admitted for training at the University of Pittsburgh (subsequently UPMC) Department of Neurological Surgery were reviewed by decade starting in 1971 when the first department chair was appointed. The review was conducted by the senior author, who served from 1975 to 1980 as a resident, as a faculty member since 1980, and as the resident director since 1986. A review of resident PPIs between 1971 and 1974 was performed in consultation with a senior faculty member active at that time. During the last decade, electronic reporting of PPIs was performed by entry into an electronic reporting system. In order to further evaluate whether the frequency of PPIs affected subsequent job satisfaction and practice patterns after completion of training, the authors surveyed living graduates. There was no statistically significant difference by decade in serious PPIs. Although millennial residents had no significant increase in the reporting of serious PPIs, the increased use of electronic event reporting over the most recent 2 decades coincided with a trend of increased reporting of all levels of suspected PPIs (p < 0.05). Residents surveyed after completion of training showed no difference by decade in types of practice or satisfaction-based metrics (p > 0.05) but reported increasing concerns related to the impact of their profession on their own lifestyle as well as their family's. There was no statistically significant difference in the incidence of serious PPIs over 5 decades of training neurosurgery residents at the authors' institution. During the millennial era, serious PPIs have not been increasing. However, reporting of all levels of PPIs is increasing coincident with the ease of electronic reporting. There was remarkably little variance in satisfaction metrics or type of practice over the 5 decades studied.


Asymmetric stem-cell division ensures sustained keratinocyte hyperproliferation in psoriatic skin lesions.
Excessive expansion of the transit-amplifying (TA) cell compartment is a distinct morphological characteristic of psoriatic epidermal hyperplasia. In order to examine the activation of basal stem cells and how they replenish such an enlarged compartment of TA cells in psoriatic epidermis, we utilized a BrdU labeling method to monitor mitotic stem cells in a mouse model of psoriasiform dermatitis, which was induced by imiquimod. Our results showed that perpendicular and parallel cell division characteristics of dividing stem cells existed in the inflamed epidermis. When we analyzed template‑DNA strand segregation in trypsin-dissociated human psoriatic keratinocytes using BrdU pulse-chase labeling, we found that the percentage of asymmetric segregation of BrdU was significantly increased in the cell pairs of psoriatic epidermal cells compared with normal epidermal cells. Furthermore, we also examined the effects of both interleukin (IL)-17A and IL-22 cytokines on the differentiation status of cultured human keratinocytes. The results indicated that both cytokines had synergistic effects on passage-one epidermal cell sheets derived from skin explants and also on cultured keratinocytes, were involved in the maintenance of the undifferentiated stem cell phenotype, and these results suggest an efficient mechanism for preventing the premature loss of basal stem-cell pools in the pro-inflammatory cytokine-enriched milieu of the psoriatic epidermis. Our findings suggest that inhibition of hyperactive stem cells represents a potential therapeutic target to combat recalcitrant epidermal hyperplasia in psoriasis.


Oxytocin for preventing postpartum haemorrhage (PPH) in non-facility birth settings.
Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review. To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports. All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review. Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy. We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported. It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.


Loss of sea ice in the Arctic.
The Arctic sea ice cover is in decline. The areal extent of the ice cover has been decreasing for the past few decades at an accelerating rate. Evidence also points to a decrease in sea ice thickness and a reduction in the amount of thicker perennial sea ice. A general global warming trend has made the ice cover more vulnerable to natural fluctuations in atmospheric and oceanic forcing. The observed reduction in Arctic sea ice is a consequence of both thermodynamic and dynamic processes, including such factors as preconditioning of the ice cover, overall warming trends, changes in cloud coverage, shifts in atmospheric circulation patterns, increased export of older ice out of the Arctic, advection of ocean heat from the Pacific and North Atlantic, enhanced solar heating of the ocean, and the ice-albedo feedback. The diminishing Arctic sea ice is creating social, political, economic, and ecological challenges.


[Recombinant interferon-alpha suppression of Karelian fever virus replication in human blood cells].
The active replication of Karelian fever virus (KFV) in human blood vessels and the protective activity of the Russian agent reaferon were first shown. KFL was highly susceptible to interferon (IFN)-alpha. In control (uninfected) cells, reaferon caused low gene expressions of the IFN-dependent enzymes dsRNA-dependent protein kinase and 2'5'-oligoadenylate synthetase, by exerting a little effect on the activity of its family genes. KFV suppressed the reaferon-induced gene expression of IFN-dependent enzymes, but IFN-alpha gene transcription was increased in the reaferon-treated infected cells.


Prognostic factors for survival in dogs with pituitary-dependent hypercortisolism treated with trilostane.
Pituitary-dependent hypercortisolism (PDH) is one of the most frequent endocrinopathies in dogs, but prognostic factors are largely unknown. The aim of this retrospective case series study was to determine the prognostic value of different clinical and clinicopathological variables evaluated in dogs newly diagnosed with PDH that were subsequently treated with trilostane. Medical records from one referral centre were evaluated. Eighty-five dogs with PDH were included. The median survival time was 852 days (range 2-3210 days); 60/85 (70 per cent) and 25/85 (29 per cent) dogs survived more than one and three years, respectively. In multivariable model analysis the length of survival of older dogs (HR 1.24, 95% CI 1.09 to 1.40) and dogs with higher serum phosphate concentrations (HR 1.35, 95% CI 1.01 to 1.81) was shorter. Serum phosphate concentrations were above the reference range in 37/85 (44 per cent) of animals. Clinical signs, liver enzymes, serum cortisol concentrations of the endocrine tests, proteinuria, systolic hypertension, the presence of concomitant disorders, and the frequency of trilostane administration were not associated with survival time. Hyperphosphataemia is a common finding in dogs with newly diagnosed PDH and represents a negative prognostic factor.


Telemedicine Video Follow-Up for Bariatric Surgery Patients: What Do Patients Prefer? A Prepandemic Pilot Randomized Clinical Trial.
While the safety of video follow-up in bariatric surgery is established, patients' perception of telemedicine visits remained unknown. A randomized clinical trial evaluating patients' perception of video postoperative follow-up (F/U) visits was conducted in the pre COVID-19 era. 24 patients were randomized in the preoperative clinic to receive either in-person or video F/U, and then surveyed about their experience and preference. The majority reported that if they had to do it over, they would prefer a video visit. Among those who received video visits, 11/12 reported that the lack of physical contact was acceptable. 82% of the video group expressed that their visit was better or as good as an in-person visit, while 9% were not sure, and 9% reported that video was worse. This finding suggests that postoperative video follow-up visits are acceptable among bariatric surgery patients and should be offered as an alternative to traditional visits.


Multi-Organ Nutrigenomic Effects of Dietary Grapes in a Mouse Model.
As a whole food, the potential health benefits of table grapes have been widely studied. Some individual constituents have garnered great attention, particularly resveratrol, but normal quantities in the diet are meniscal. On the other hand, the grape contains hundreds of compounds, many of which have antioxidant potential. Nonetheless, the achievement of serum or tissue concentrations of grape antioxidants sufficient to mediate a direct quenching effect is not likely, which supports the idea of biological responses being mediated by an indirect catalytic-type response. We demonstrate herein with Hsd:ICR (CD-1® Outbred, 18-24 g, 3-4 weeks old, female) mice that supplementation of a semi-synthetic diet with a grape surrogate, equivalent to the human consumption of 2.5 servings per day for 12 months, modulates gene expression in the liver, kidney, colon, and ovary. As might be expected when sampling changes in a pool of over 35,000 genes, there are numerous functional implications. Analysis of some specific differentially expressed genes suggests the potential of grape consumption to bolster metabolic detoxification and regulation of reactive oxygen species in the liver, cellular metabolism, and anti-inflammatory activity in the ovary and kidney. In the colon, the data suggest anti-inflammatory activity, suppression of mitochondrial dysfunction, and maintaining homeostasis. Pathway analysis reveals a combination of up- and down-regulation in the target tissues, primarily up-regulated in the kidney and down-regulated in the ovary. More broadly, based on these data, it seems logical to conclude that grape consumption leads to modulation of gene expression throughout the body, the consequence of which may help to explain the broad array of activities demonstrated in diverse tissues such as the brain, heart, eye, bladder, and colon. In addition, this work further supports the profound impact of nutrigenomics on mammalian phenotypic expression.


A multidimensional evaluation of the benefits of an ecologically realistic training based on pretend play for preschoolers' cognitive control and self-regulation: From behavior to the underlying theta neuro-oscillatory activity.
To what extent can cognitive control, self-regulation, and the underlying midfrontal theta oscillatory activity of preschool children be modified by an ecologically realistic training based on pretend play? To answer this question, 70 children aged 4-6 years (37 boys) were assigned to a training group or a control group using a pairing randomization procedure. Children were administered 20 play sessions over 10 weeks. Benefits were evaluated with a pre-post design. The intervention helped children to engage more in self-regulation within the training activities. However, the intervention did not promote self-regulation outside of the training context, nor did it influence cognitive control and theta activity. These results provide a better understanding of the limitations of an ecologically realistic approach to cognitive control training.


Specific Patient Features Affect Antiepileptic Drug Therapy Decisions: Focus on Gender, Age, and Psychiatric Comorbidities.
Patient features, apart from the type of seizures/epilepsy, affect markedly antiepileptic drug (AED) choice and dosage. The present review focuses on gender, age and psychiatric comorbidities which play a leading role in influencing antiepileptic treatment. Reviews with large population of patients, controlled clinical trials, observational investigations, experimental studies and experimental reviews of experimental data, where appropriated, were analysed and illustrated to produce the most homogeneous indications possible. Different and also contradictory observations have been highlighted to stimulate a critical approach to specific aspects. Women of childbearing age should avoid valproic (VPA), acid, since this drug doubles the risk of major malformations and causes in the exposed offspring reduced intellectual development and disorders of autistic spectrum. The drug is also associated with hormonal disorders, polycystic ovary and reduced fertility. Children treated with valproic acid or phenobarbital can exhibit hyperactivity, nervousness and attention disorders. As a consequence of increased drug elimination, younger children require higher doses as compared to adults and older patients. Elderly patients treated with phenobarbital may face the risk of cognitive disorders and/or falls resulting in bone fractures. Fractures are also facilitated by carbamazepine-induced osteoporosis. Psychiatric disorders are frequently associated with epilepsy and evidence has been gained that common pathological steps underlie these conditions. Depressed patients should avoid drugs like phenobarbital, topiramate, levetiracetam, zonisamide and perampanel since these drugs can induce mood disorders. Although not conclusive, literature data indicate that topiramate and levetiracetam and also tiagabine and vigabatrin, are associated with suicidal thought/behaviour. Conversely, lamotrigine, carbamazepine, VPA and oxcarbazepine exert beneficial effects on mood. Bupropion, clomipramine, amoxapine and maprotyline among antidepressants, and clozapine, olanzapine and quietapine among antipsychotics have been observed to lower seizure threshold. Serum AED concentration monitoring is of help in dosage adjustments, especially in very young children, in patients with cognitive decline and in patients with psychiatric comorbidities. A careful evaluation of the patient variables analysed in the present review is useful to personalize and optimize AED therapy.


Moral personality of brave and caring exemplars.
Two contrasting types of moral exemplars were examined so as to identify personality variables associated with moral action. The sample comprised 50 Canadian awardees for either exceptional bravery or caring, as well as 50 comparison participants. Participants responded to a set of personality questionnaires and a life-review interview. Personality variables were found to substantially augment moral cognition in the prediction of exemplary action. In support of the notion that there is a personological core to the moral domain, it was found that moral exemplars were distinguished from the comparison groups by themes embodied in their life narratives. Specifically, moral exemplars had stronger motivational themes of both agency and communion, were more likely to construe critical life events redemptively, more frequently identified helpers in early life, and reported more secure attachments. Furthermore, the personality of caring exemplars was more nurturant, generative, and optimistic than that of brave exemplars; these somewhat divergent personality profiles imply multiple ideals of moral maturity.


Prostate specific antigen screening for prostate cancer: knowledge of, attitudes towards, and utilization among primary care physicians.
Prostate specific antigen (PSA) screening for prostate cancer screening is not uniformly recommended by national organizations or primary care physicians (PCPs). Given this lack of consensus, we sought to identify patterns in physician knowledge of and attitudes towards PSA screening and to determine how these patterns along with patient and provider demographics influence PSA screening practices. A self-administered questionnaire, which assessed provider's knowledge of prostate cancer, confidence in his/her knowledge, and PSA screening practices, was mailed to PCPs at an academic medical center. Frequencies of responses were summarized and 3 outcome variables (knowledge, confidence, and propensity to screen) were derived. Association of covariates with the outcome variables was determined using multivariable logistic regression. Eight-two (30.4%) physicians completed the survey; 98% identified African-American race as a prostate cancer risk factor, 42% identified digital rectal exam and PSA as the accepted screening method, and 59% underestimated the likelihood of prostate cancer in a man with a PSA level > 4 ng/ml; 19% were confident in their knowledge of prostate cancer; 86% screened fewer than 60% of their male patients over 50. A knowledge score above the median was not associated with a higher propensity to screen (r = 0.06, P = 0.61). Confidence in one's knowledge was correlated with ordering PSA testing (r = 0.33, P < 0.01). Physician (e.g., ethnicity) and patient (e.g., request for PSA testing) related factors, as well as practice guidelines, particularly those of the US Preventative Services Task Force, influenced providers' decision to offer PSA screening. Respondents correctly identified prostate cancer risk factors but were less knowledgeable about prostate cancer screening tests and overall prostate cancer risk. Most respondents were not confident in their knowledge and did not screen men over 50. Multiple patient- and provider-specific factors influence the decision to offer or not offer PSA screening.


Soft-tissue flap coverage maximizes limb salvage after allograft bone extremity reconstruction.
Limb salvage after extremity tumor ablation may include the use of allograft bone. The primary complication of this method is infection of the allograft, which can lead to limb loss in up to 50 percent of cases. The purpose of this study is to evaluate the efficacy of primary muscle flap coverage in the setting of allograft bone limb salvage surgery. This study is a prospective review of all patients with flap coverage of extremity allografts over the 10-year period 1991 to 2001. There were 20 patients (11 male and nine female patients) with an average age of 28 years (range, 6 to 72 years). Flap coverage was primary in 16 patients and delayed in four. Delayed coverage was performed for failed wounds that did not have a primary soft-tissue flap. Pathologic findings included osteosarcoma in nine patients, Ewing sarcoma in five patients, malignant fibrohistiocytoma in two patients, chondrosarcoma in two patients, synovial sarcoma in one patient, and leiomyosarcoma in one patient. Allograft reconstruction was performed for the upper extremity in 12 patients and for the lower extremity in eight patients. Flap reconstruction was accomplished with 20 pedicle flaps in 17 patients (latissimus dorsi, 12; gastrocnemius, four; soleus, three; and fasciocutaneous flap, one) and four free flaps (rectus abdominis, three; latissimus dorsi, one) in four patients. All pedicled flaps survived. There was one flap failure in the entire series, which was a free rectus abdominis flap. This case resulted in the only limb loss noted. The follow-up period ranged from 1 to 50 months (average, 12.35 months). At the time of final follow-up, three patients were dead of disease and 17 were alive with intact extremities. The overall limb salvage rate in the setting of bone allograft and soft-tissue flap coverage was 95 percent (19 of 20). Reoperation for bone-related complications was required in 50 percent (two of four) of cases receiving delayed flap coverage compared with 19 percent (three of 16) of patients with primary flap coverage (statistically not significant). The results of this study support the use of soft-tissue flap coverage for allograft limb reconstruction. In this series, no limb was lost in the setting of a viable flap. Reoperation was markedly reduced in the setting of primary flap coverage. Pedicled or microvascular transfer of well-vascularized muscle can be used to wrap the allograft and minimize devastating wound complications potentially leading to loss of allograft and limb.


Detailed protein sequence alignment based on Spectral Similarity Score (SSS).
The chemical property and biological function of a protein is a direct consequence of its primary structure. Several algorithms have been developed which determine alignment and similarity of primary protein sequences. However, character based similarity cannot provide insight into the structural aspects of a protein. We present a method based on spectral similarity to compare subsequences of amino acids that behave similarly but are not aligned well by considering amino acids as mere characters. This approach finds a similarity score between sequences based on any given attribute, like hydrophobicity of amino acids, on the basis of spectral information after partial conversion to the frequency domain. Distance matrices of various branches of the human kinome, that is the full complement of human kinases, were developed that matched the phylogenetic tree of the human kinome establishing the efficacy of the global alignment of the algorithm. PKCd and PKCe kinases share close biological properties and structural similarities but do not give high scores with character based alignments. Detailed comparison established close similarities between subsequences that do not have any significant character identity. We compared their known 3D structures to establish that the algorithm is able to pick subsequences that are not considered similar by character based matching algorithms but share structural similarities. Similarly many subsequences with low character identity were picked between xyna-theau and xyna-clotm F/10 xylanases. Comparison of 3D structures of the subsequences confirmed the claim of similarity in structure. An algorithm is developed which is inspired by successful application of spectral similarity applied to music sequences. The method captures subsequences that do not align by traditional character based alignment tools but give rise to similar secondary and tertiary structures. The Spectral Similarity Score (SSS) is an extension to the conventional similarity methods and results indicate that it holds a strong potential for analysis of various biological sequences and structural variations in proteins.


A Test of Social Cognitive Theory to Increase Hearing Protection Use in Swine Buildings.
Farming ranks among the top occupations for which workers are at risk for noise-induced hearing loss (NIHL), an irreversible yet preventable condition. Hearing Protection Devices (HPDs) (i.e., earmuffs and ear plugs) are effective at preventing expo- sure to noise; however, few farmers report consistent use. The purpose of this study was to test an intervention based on Social Cognitive Theory with interactive smartphone technology to increase the use of HPDs among swine facility workers. A pilot, quasi-experimental study was implemented among 72 younger adult swine workers. Participants were randomly assigned to one of three groups. Group 1 received HPDs (e.g., earmuffs and ear plugs). Group 2 received the same HPDs as Group 1 and was also instructed to use a smartphone application to track their use of hearing protection for 60 days. Group 3 received the HPDs and instructions on using a smartphone app for tracking the use of hearing protection and setting daily goals for hearing protection use. Use of hearing protection was assessed via an online survey prior to the intervention (i.e., "baseline"), immediately after the post-intervention, and at a 3-month follow-up. Compared to baseline use, all three groups reported increased use of hearing protection immediately post-intervention. However, this increase was not maintained at a 3-month follow-up for two of the study groups. Group 3 (HPD, tracking, and goal-setting app) showed the greatest increase in the use of HPDs from baseline to immediate post-intervention; however, Group 1 (HPD only) showed the greatest sustained increase from baseline to the 3-month follow-up. Modifying the environment by supplying HPDs was effective in increasing HPD use among swine facility workers. Improving access to hearing protection devices alone may lead to sustained changes in behavior.


Local Morphological Response of the Distal Femoral Articular-Epiphyseal Cartilage Complex of Young Foals to Surgical Stab Incision and Potential Relevance to Cartilage Injury and Repair in Children.
Describe the local morphological response of the articular-epiphyseal cartilage complex to surgical stab incision in the distal femur of foals, with emphasis on the relationship between growth cartilage injury, enchondral ossification, and repair. Nine foals were induced into general anesthesia at the age of 13 to 15 days. Four full-thickness stab incision defects were created in the cartilage on the lateral aspect of the lateral trochlear ridge of the left distal femur. Follow-up examination was carried out from 1 to 49 days postoperatively, including examination of intact bones, sawed slabs, and histological sections. Incision defects filled with cells displaying fibroblast-, chondrocyte-, and osteoblast-like characteristics, potentially validating the rationale behind the drilling of stable juvenile osteochondritis dissecans lesions in children. Incisions induced necrosis within the cartilage on the margins at all depths of the defects. Sharp dissection may therefore be contraindicated in cartilage repair in young individuals. Incisions caused a focal delay in enchondral ossification in 2 foals, apparently related to the orientation of the incision defect relative to the direction of ossification. Defects became progressively surrounded by subchondral bone, in which granulation tissue containing clasts and foci of osteoblast-like cells was observed. Continued enchondral ossification was therefore likely to result in healing of uncomplicated defects to morphologically normal bone. Epiphyseal growth cartilage injury had the potential to exert a negative effect on enchondral ossification. Enchondral ossification exerted a beneficial effect on repair. This relationship warrants consideration in future studies of cartilage injury and repair within the articular-epiphyseal cartilage complex of all species.


Effect of self-management education using pictogram-based content of health information on outcomes in Korean patients with chronic obstructive pulmonary disease: A randomized controlled trial.
This study aimed to evaluate the effects of pictogram-based self-management education on the symptom experience, self-efficacy, self-management adherence, and health-related quality of life (HRQoL) in individuals with chronic obstructive pulmonary disease (COPD). Sixty COPD patients were enrolled from a pulmonology clinic at C hospital in southwestern Korea and subsequently randomized into two groups. A significant improvement in self-efficacy scores was noted (t = -2.16, p = .035) in the intervention group compared to the control group. No significant differences were observed in symptom experience (t = 0.48, p = .637), self-management adherence (t = -0.33, p = .742), and HRQoL (t = -0.52, p = .608). Our findings suggest that the utilization of pictogram-based content in self-management education can be an effective tool for enhancing self-efficacy among COPD patients. Further research is required to evaluate the long-term effects on a broader sample size.


Three-Dimensional Acoustic Double-Zero-Index Medium with a Fourfold Degenerate Dirac-like Point.
We report the first realization of a three-dimensional (3D) acoustic double-zero-index medium (DZIM) made of a cubic lattice of metal rods. While the past decade has seen several realizations of 2D DZIM, achieving such a medium in 3D has remained an elusive challenge. Here, we show how a fourfold degenerate point with conical dispersion can be induced at the Brillouin zone center, such that the material becomes a 3D DZIM with the effective mass density and compressibility simultaneously acquiring near-zero values. To demonstrate the functionalities of this new medium, we have fabricated an acoustic waveguide of 3D DZIM in form of a "periscope" with two 90° turns and observed tunneling of a normally incident planar wave through the waveguide yielding undistorted planar wave front at the waveguide exit. Our findings establish a practical route to realize 3D DZIM as an effective acoustic "void space" that offers unprecedented control over acoustic wave propagation.


Chronic histopathological consequences of fluid-percussion brain injury in rats: effects of post-traumatic hypothermia.
Early outcome measures of experimental traumatic brain injury (TBI) are useful for characterizing the traumatic severity as well as for clarifying the pathomechanisms underlying patterns of neuronal vulnerability. However, it is increasingly apparent that acute outcome measures may not always be accurate predictors of chronic outcome, particularly when assessing the efficacy of potential therapeutic regimens. This study examined the chronic histopathological outcome in rats 8 weeks following fluid-percussive TBI coupled with moderate post-traumatic brain hypothermia, a protocol that provides acute neuronal protection. Animals received a moderate parasagittal percussive head injury (2.01-2.38 atm) or sham procedure followed immediately by 3 h of brain hypothermia (30 degrees C) or normothermia (37 degrees C). Eight weeks following TBI, serial tissue sections were stained with hematoxylin and eosin or immunostained for glial fibrillary acidic protein. Tissue damage, gliosis and immunoreactive astrocytes were observed in the ipsilateral thalamus, hippocampus, and in the neocortex lateral to the injury site. Within the thalamus, focal necrosis was restricted to selective thalamic nuclei. Significant hippocampal cell loss was found in the ipsilateral dentate hilar region of both TBI groups. Quantitative volume measurements revealed significant decreases in cortical, thalamic and hippocampal volume ipsilateral to the impact in both TBI groups. Lateral ventricles were substantially enlarged in the TBI-normothermia group, an effect which was significantly attenuated by post-TBI hypothermia. The attenuation of lateral ventricular dilation by post-traumatic hypothermia is indicative of chronic neuroprotection in this TBI model. These data provide new information concerning the chronic histopathological consequence of experimental TBI and the relevance of this trauma model to chronic human head injury.


Bacteremia associated with tunneled dialysis catheters: comparison of two treatment strategies.
Tunneled dialysis catheters are often used for temporary vascular access in hemodialysis patients, but are complicated by frequent systemic infections. The treatment of bacteremia associated with infected tunneled catheters requires both antibiotic therapy and catheter replacement. We compared the outcomes of two treatment strategies for catheter-associated bacteremia: exchange of the existing catheter with a new one over a guidewire versus catheter removal with delayed replacement. We retrospectively analyzed the outcomes of all cases of tunneled dialysis catheter-associated bacteremia during a two-year period. The infection-free survival time of the subsequent catheter was evaluated in two groups of patients: group A (31 catheters), exchange of the existing infected catheter with a new catheter over a guidewire, and group B (38 catheters), removal of the infected catheter followed by delayed catheter replacement 3 to 10 days later. Patients in both groups received three weeks of systemic antibiotic therapy. Cox proportional hazard models were used to evaluate the factors predictive of infection-free survival time of the replacement catheter. On univariate proportional hazard regression analysis, the infection-free survival time of the replacement catheter was similar for groups A and B (P = 0.72), whereas the hazard of infection was significantly greater for patients with hypoalbuminemia (serum albumin < 3.5 g/dL), as compared with patients with a normal serum albumin (hazard ratio 2.81, 95% CI, 1. 21, 6.53, P = 0.016). The infection-free survival time was not affected by patient age, sex, diabetic status, or type of organism (gram-positive coccus vs. gram-negative rod). The infection-free survival time associated with the subsequent catheter is similar for the two treatment strategies. However, exchanging the catheter for a new one over a guidewire minimizes the number of separate procedures required by the patient. Hypoalbuminemia is the major risk factor for recurrent bacteremia in the replacement catheter.


[Affinity modification of creatine kinase from rabbit skeletal muscles using gamma-(p-azidoanilide)-ATP].
Ultraviolet irradiation of creatine kinase (adenosine 5'-triphosphate: creatine-N-phosphotransferase, EC 22.214.171.124) in the presence of gamma-(p-azidoanilide)-[14C]-ATP results in a complete enzyme inactivation and covalent binding of two moles of analog per mole of enzyme. MgADP strongly protects the enzyme against inactivation. However, in the presence of MgADP the covalent binding of 0.9 moles of analog per mole of enzyme occurs without the enzyme inactivation. The rate of enzyme inactivation and covalent modification decreases in the presence of MgATP and creatine. These results indicate that gamma-(p-azidoanilide)-ATP is an affinity label for the active site of creatine kinase.


Visuospatial memory computations during whole-body rotations in roll.
We used a memory-saccade task to test whether the location of a target, briefly presented before a whole-body rotation in roll, is stored in egocentric or in allocentric coordinates. To make this distinction, we exploited the fact that subjects, when tilted sideways in darkness, make systematic errors when indicating the direction of gravity (an allocentric task) even though they have a veridical percept of their self-orientation in space. We hypothesized that if spatial memory is coded allocentrically, these distortions affect the coding of remembered targets and their readout after a body rotation. Alternatively, if coding is egocentric, updating for body rotation becomes essential and errors in performance should be related to the amount of intervening rotation. Subjects (n = 6) were tested making saccades to remembered world-fixed targets after passive body tilts. Initial and final tilt angle ranged between -120 degrees CCW and 120 degrees CW. The results showed that subjects made large systematic directional errors in their saccades (up to 90 degrees ). These errors did not occur in the absence of intervening body rotation, ruling out a memory degradation effect. Regression analysis showed that the errors were closely related to the amount of subjective allocentric distortion at both the initial and final tilt angle, rather than to the amount of intervening rotation. We conclude that the brain uses an allocentric reference frame, possibly gravity-based, to code visuospatial memories during whole-body tilts. This supports the notion that the brain can define information in multiple frames of reference, depending on sensory inputs and task demands.


Estimating potential risks to terrestrial invertebrates and plants exposed to bisphenol A in soil amended with activated sludge biosolids.
Bisphenol A (BPA) is a high production volume substance primarily used to produce polycarbonate plastic and epoxy resins. During manufacture and use, BPA may enter wastewater treatment plants. During treatment, BPA may become adsorbed to activated sludge biosolids, which may expose soil organisms to BPA if added to soil as an amendment. To evaluate potential risks to organisms that make up the base of the terrestrial food web (i.e., invertebrates and plants) in accordance with international regulatory practice, toxicity tests were conducted with potworms (Enchytraeids) and springtails (Collembolans) in artificial soil, and six plant types using natural soil. No-observed-effect concentrations (NOEC) for potworms and springtails were equal to or greater than 100 and equal to or greater than 500 mg/kg (dry wt), respectively. The lowest organic matter-normalized NOEC among all tests (dry shoot weight of tomatoes) was 37 mg/kg-dry weight. Dividing by an assessment factor of 10, a predicted-no-effect concentration in soil (PNEC(soil)) of 3.7 mg/kg-dry weight was calculated. Following international regulatory guidance, BPA concentrations in soil hypothetically amended with biosolids were calculated using published BPA concentrations in biosolids. The upper 95th percentile BPA biosolids concentration in North America is 14.2 mg/kg-dry weight, and in Europe is 95 mg/kg-dry weight. Based on recommended biosolids application rates, predicted BPA concentrations in soil (PEC(soil)) would be 0.021 mg/kg-dry weight for North America and 0.14 mg/kg-dry weight for Europe. Hazard quotients (ratio of PEC(soil) and PNEC(soil)) for BPA were all equal to or less than 0.04. This indicates that risks to representative invertebrates and plants at the base of the terrestrial food web are low if exposed to BPA in soil amended with activated sludge biosolids.


The Wellcome Foundation lecture, 1981. Nuclear magnetic resonance imaging in medicine: physical principles.
In recent years nuclear magnetic resonance (n.m.r.) has become a means of providing excellent images of the interior of the human body which are proving useful in medical practice. The development of n.m.r. imaging, much of which was pioneered in Britain, is outlined. Proton image resolution of human anatomy is comparable with X-ray computed tomography images, but without the hazard of ionizing radiation. There is improved soft tissue discrimination and pathological contrast through the basic imaging parameters of the proton density and the relaxation times T1 and T2, whose differences from one tissue to another are exploited by use of appropriate radiofrequency pulse sequences. Images may be obtained directly of transverse, coronal and sagittal sections of the head and body. Single slices or multiple slices may be imaged and imaging may be done in three dimensions. The lecture describes the more important imaging techniques and gives illustrative examples of images obtained. The efficient use of time in n.m.r. imaging is discussed, particularly mentioning the multiecho-multislice procedure and the development of real-time n.m.r. imaging. Magnetic field strengths in current use for proton n.m.r. imaging range from 0.02 to 2 T. At the lower end of the range resistive magnets are used, while for higher fields superconducting magnets are needed. A considerable improvement in image quality is obtained by use of special receiver coils.


Enthalpy-based multiple-relaxation-time lattice Boltzmann method for solid-liquid phase-change heat transfer in metal foams.
In this paper, an enthalpy-based multiple-relaxation-time (MRT) lattice Boltzmann (LB) method is developed for solid-liquid phase-change heat transfer in metal foams under the local thermal nonequilibrium (LTNE) condition. The enthalpy-based MRT-LB method consists of three different MRT-LB models: one for flow field based on the generalized non-Darcy model, and the other two for phase-change material (PCM) and metal-foam temperature fields described by the LTNE model. The moving solid-liquid phase interface is implicitly tracked through the liquid fraction, which is simultaneously obtained when the energy equations of PCM and metal foam are solved. The present method has several distinctive features. First, as compared with previous studies, the present method avoids the iteration procedure; thus it retains the inherent merits of the standard LB method and is superior to the iteration method in terms of accuracy and computational efficiency. Second, a volumetric LB scheme instead of the bounce-back scheme is employed to realize the no-slip velocity condition in the interface and solid phase regions, which is consistent with the actual situation. Last but not least, the MRT collision model is employed, and with additional degrees of freedom, it has the ability to reduce the numerical diffusion across the phase interface induced by solid-liquid phase change. Numerical tests demonstrate that the present method can serve as an accurate and efficient numerical tool for studying metal-foam enhanced solid-liquid phase-change heat transfer in latent heat storage. Finally, comparisons and discussions are made to offer useful information for practical applications of the present method.