Distal femoral extension osteotomy and patellar tendon advancement to treat persistent crouch gait in cerebral palsy.
Hallmarks of a persistent crouched walking pattern exhibited by individuals with cerebral palsy usually include loss of an adequate plantar flexion/knee extension couple, hamstring and/or psoas tightness, or contracture in conjunction with quadriceps insufficiency. Traditional treatment addresses the muscle-tightness component, but not the contracture or the muscle insufficiency. This study was performed to evaluate the effectiveness of distal femoral extension osteotomy and/or patellar tendon advancement in the treatment of crouch gait in patients with cerebral palsy. A retrospective, nonrandomized, repeated-measures design was used. Individuals with a diagnosis of cerebral palsy were included if they had had (1) a distal femoral extension osteotomy in combination with a distal patellar tendon advancement (thirty-three patients), (2) a distal femoral extension osteotomy without patellar tendon advancement (sixteen), or (3) a distal patellar tendon advancement only (twenty-four). All subjects were evaluated with preoperative and postoperative gait analysis. Gait, radiographic, strength, and functional measures were included in the analysis to assess changes in knee function. Seventy-three individuals met the criteria for inclusion. A single side was chosen for the analysis of each subject. Ninety percent of the subjects had additional, concurrent surgery. Improvements were noted in the index assessing the level of gait pathology and in functional variables across all groups, and pain was consistently decreased. All preoperative stress fractures healed. Strength levels were maintained across all groups. The Koshino index of patellar height improved from 1.4 to -2.3 in the group treated with patellar tendon advancement only and from 1.5 to -2.9 in the group treated with both osteotomy and tendon advancement. The range of knee flexion improved an average of 15 degrees to 20 degrees, and stance-phase knee flexion was restored to the typical range (9 degrees to 10 degrees) in the groups that had advancement of the patellar tendon as part of the procedure. Individuals who underwent a distal femoral osteotomy only were still in a crouch (a mean of 31 degrees of knee flexion in midstance) at the final assessment. Inclusion of patellar tendon advancement is necessary to achieve optimal results in the surgical management of a persistent crouch gait exhibited by adolescents and young adults with cerebral palsy. When this procedure is done alone or in combination with a distal femoral extension osteotomy (for the treatment of a knee flexion contracture), knee function in gait can be restored to values within typical limits, with gains in community function.


The search for an autoimmune origin of psychotic disorders: Prevalence of autoantibodies against hippocampus antigens, glutamic acid decarboxylase and nuclear antigens.
The etiology of psychotic disorders is still unknown, but in a subgroup of patients symptoms might be caused by an autoimmune reaction. In this study, we tested patterns of autoimmune reactivity against potentially novel hippocampal antigens. Serum of a cohort of 621 individuals with psychotic disorders and 257 controls were first tested for reactivity on neuropil of rat brain sections. Brain reactive sera (67 diseased, 27 healthy) were further tested for antibody binding to glutamic acid decarboxylase (GAD) isotype 65 and 67 by cell-based assay (CBA). A sub-cohort of 199 individuals with psychotic disorders and 152 controls was tested for the prevalence of anti-nuclear antibodies (ANA) on HEp2-substrate as well as for reactivity to double-stranded DNA, ribosomal P (RPP), and cardiolipin (CL). Incubation of rat brain with serum resulted in unidentified hippocampal binding patterns in both diseased and control groups. Upon screening with GAD CBA, one of these patterns was identified as GAD65 in one individual with schizophrenia and also in one healthy individual. Two diseased and two healthy individuals had low antibody levels targeting GAD67 by CBA. Antibody reactivity on HEp-2-substrate was increased in patients with schizoaffective disorder, but only in 3 patients did antibody testing hint at a possible diagnosis of systemic lupus erythematosus. Although reactivity of serum to intracellular antigens might be increased in patients with psychotic disorder, no specific targets could be identified. GAD antibodies are very rare and do not seem increased in serum of patients with psychotic disorders.


Introduction to a new inspiratory threshold loading device.
Inspiratory threshold loading is an important tool in assessing inspiratory muscle function and has been widely used in studies of respiratory mechanics. A simple system was designed to provide a pure and precise inspiratory threshold load. The inspiratory threshold loading system comprises a flow generator attached via a pressure chamber, to the inspiratory port of a Hans-Rudolph valve. By limiting the circulation of air generated by the flow generator between the room and the pressure chamber, different levels of negative pressure are produced in the pressure chamber and applied to the inspiratory valve. An inspiratory pressure equal to the negative pressure in the chamber has to be generated to open the inspiratory valve for flow. The system was tested in four subjects by measuring mouth pressure (Pm), threshold pressure (Pth) and valve resistance (R). The Pm at the beginning of inspiratory flow was defined as the opening pressure (Pop). The Pth was constant throughout inspiration. Pop was linearly related to Pth (p<0.0001), with slopes within 2% of identity and intercepts within +/-0.2 cmH2O. R was between 0.7-1.1 cmH2O x L(-1) x s(-1) under all conditions and was independent of both Pth (p=0.76) and inspiratory flow (p=0.24). The results demonstrate that this system can provide a constant inspiratory threshold load throughout inspiration with little flow resistance, and is therefore ideal for respiratory studies.


The distribution of large herbivore hotspots in relation to environmental and anthropogenic correlates in the Mara region of Kenya.
1. The distributions of large herbivores in protected areas and their surroundings are becoming increasingly restricted by changing land use, with adverse consequences for wildlife populations. 2. We analyse changes in distributions of herbivore hotspots to understand their environmental and anthropogenic correlates using 50 aerial surveys conducted at a spatial resolution of 5 × 5 km(2) (n = 289 cells) in the Mara region of Kenya during 1977-2010. We compare the distributions across seasons, land use types (protection, pastoralism and agro-pastoralism) and 10 species with different body sizes and feeding styles. 3. Small herbivores that are the most susceptible to predation and dependent on high-quality forage concentrate in the greenest and wet areas and close to rivers in Masai pastoral ranches in both seasons. Livestock grazing creates conditions favouring small herbivores in these ranches, including high-quality short grasses and better visibility, implying facilitation. But in the reserve, they concentrate in browner, drier and flatter areas and farther from rivers, suggesting facilitation by large grazers in the wet season, or little competition with migratory herbivores occupying the reserve in the dry season. 4. In the wet season, medium herbivores concentrate in similar areas to small herbivores in the ranches and reserve. However, in the dry season, they stay in the reserve, and also concentrate in green and wet areas close to rivers when migrants occur in the reserve. As such areas typically have higher predation risk, this suggests facilitation by the migrants by absorbing most predation pressure or, alternatively, competitive displacement by the migrants from preferred habitats. 5. Large herbivores, which suffer the least predation, depend on bulk forage and are the most likely to engender conflicts with people, concentrate in the reserve all year. This suggests attraction to the taller and denser grass and perceived greater safety in the reserve in both seasons. 6. These results reveal how predation risk, forage quantity and quality, water, competition with and facilitation by livestock interact with individual life-history traits, seasons and land use in shaping the dynamics of herbivore hotspots in protected and human-dominated savannas.


Changing the path of least resistance, or access to endo-dig products via a sequence of three exo-trig transition states: electronic effects in homoallyic ring expansion cascades of alkenyl isonitriles.
Chemoselective addition of radicals to isonitriles can be harnessed for initiating reaction cascades designed to overcome the stereoelectronic restrictions on homoallylic ring expansion in alkyne reactions and to develop a new general route for the preparation of N-heteroaromatics. This method utilizes alkenes as synthetic equivalents of alkynes by coupling homoallylic ring expansion to yield the formal "6-endo" products with aromatization via stereoelectronically assisted C-C bond scission. Detailed computational analysis of the individual steps of the homoallylic expansion sequence maps effects of substituents and structural constraints on this multi-step potential energy surface.


Monitoring O3 with solar-blind Raman lidars.
The benefits of retrieving ozone concentration profiles by a use of a single Raman signal rather than the Raman differential absorption lidar (DIAL) technique are investigated by numerical simulations applied either to KrF- (248 nm) or to quadrupled Nd:YAG- (266 nm) based Raman lidars, which are used for both daytime and nighttime monitoring of the tropospheric water-vapor mixing ratio. It is demonstrated that ozone concentration profiles of adequate accuracy and spatial and temporal resolution can be retrieved under low aerosol loading by a single Raman lidar because of the large value of the ozone absorption cross section both at 248 nm and at 266 nm. Then experimental measurements of Raman signals provided by the KrF-based lidar operating at the University of Lecce (40 degrees 20'N, 18 degrees 6'E) are used to retrieve ozone concentration profiles by use of the Raman DIAL technique and the nitrogen Raman signal.


AAV-mediated gene transfer in the perinatal period results in expression of FVII at levels that protect against fatal spontaneous hemorrhage.
We explored adeno-associated viral vector (AAV)-mediated gene transfer in the perinatal period in animal models of severe congenital factor VII (FVII) deficiency, a disease associated with early postnatal life-threatening hemorrhage. In young adult mice with plasma FVII < 1% of normal, a single tail vein administration of AAV (1 × 10(13) vector genomes [vg]/kg) resulted in expression of murine FVII at 266% ± 34% of normal for ≥ 67 days, which mediated protection against fatal hemorrhage and significantly improved survival. Codon optimization of human FVII (hFVIIcoop) improved AAV transgene expression by 37-fold compared with the wild-type hFVII cDNA. In adult macaques, a single peripheral vein injection of 2 × 10(11) vg/kg of the hFVIIcoop AAV vector resulted in therapeutic levels of hFVII expression that were equivalent in males (10.7% ± 3.1%) and females (12.3% ± 0.8%). In utero delivery of this vector in the third trimester to fetal monkeys conferred expression of hFVII at birth of 20.4% ± 3.7%, with a gradual decline to > 1% by 7 weeks. Re-administration of an alternative serotype at 12 months postnatal age increased hFVII levels to 165% ± 6.2% of normal, which remained at therapeutic levels for a further 28 weeks without toxicity. Thus, perinatal AAV-mediated gene transfer shows promise for disorders with onset of pathology early after birth.


Genetics of Heading Time in Wheat (TRITICUM AESTIVUM L.). I. the Inheritance of Photoperiodic Response.
The inheritance of photoperiodic response was studied in crosses involving four spring wheats (Sonora 64, Pitic 62, Justin and Thatcher) and three winter wheats (Blackhull, Early Blackhull and Extra Early Blackhull). The parental cultivars were classified into a photoperiod-sensitive group (Justin, Thatcher, Blackhull and Early Blackhull) and a relatively photoperiod-insensitive group (Sonora 64, Pitic 62 and Extra Early Blackhull) based on their heading response when vernalized and grown under different daylength regimes.-F(1) data indicated that daylength insensitivity is not always dominant over day-length sensitivity and that the dominance relationship with respect to photoperiodic response depends on the alleles present in the parents. The heading patterns after vernalization and growth under short days of F(1), F(2), F(3) and backcross generations of a 4-parent diallel cross involving Justin, Sonora 64, Extra Early Blackhull and Blackhull could be satisfactorily explained on the basis of two major loci with three alleles at each locus. The genotype for each parent was suggested in terms of these loci. Genes with minor effects also influenced the photoperiodic response in a quantitative manner.-Diallel cross analysis of the number of days to heading (log scale) indicated significant additive and dominance genetic variances, a high average degree of dominance for earliness (photoperiod insensitivity) and a preponderance of recessive alleles in the parents acting in the direction of lateness (photoperiod sensitivity). Estimation of the genetic components of variation contained in the generation means of individual crosses (untransformed data) showed that, besides additivity and dominance, epistasis was also an important factor in the genetic control of photoperiodic response in wheat.


Cell-specific transmembrane injection of molecular cargo with gold nanoparticle-generated transient plasmonic nanobubbles.
Optimal cell therapies require efficient, selective and rapid delivery of molecular cargo into target cells without compromising their viability. Achieving these goals ex vivo in bulk heterogeneous multi-cell systems such as human grafts is impeded by low selectivity and speed of cargo delivery and by significant damage to target and non-target cells. We have developed a cell level approach for selective and guided transmembrane injection of extracellular cargo into specific target cells using transient plasmonic nanobubbles (PNB) as cell-specific nano-injectors. As a technical platform for this method we developed a laser flow cell processing system. The PNB injection method and flow system were tested in heterogeneous cell suspensions of target and non-target cells for delivery of Dextran-FITC dye into squamous cell carcinoma HN31 cells and transfection of human T-cells with a green fluorescent protein-encoding plasmid. In both models the method demonstrated single cell type selectivity, high efficacy of delivery (96% both for HN31 cells T-cells), speed of delivery (nanoseconds) and viability of treated target cells (96% for HN31 cells and 75% for T-cells). The PNB injection method may therefore be beneficial for real time processing of human grafts without removal of physiologically important cells.


Granular activated carbon for removal of organic matter and turbidity from secondary wastewater.
A range of commercial granular activated carbon (GAC) media have been assessed as pretreatment technologies for a downstream microfiltration (MF) process. Media were assessed on the basis of reduction in both organic matter and turbidity, since these are known to cause fouling in MF membranes. Isotherm adsorption analysis through jar testing with supplementary column trials revealed a wide variation between the different adsorbent materials with regard to organics removal and adsorption kinetics. Comparison with previous work using powdered activated carbon (PAC) revealed that for organic removal above 60% the use of GAC media incurs a significantly lower carbon usage rate than PAC. All GACs tested achieved a minimum of 80% turbidity removal. This combination of turbidity and organic removal suggests that GAC would be expected to provide a significant reduction in fouling of a downstream MF process with improved product water quality.


Racial and Ethnic Disparities in Rates of Continuous Glucose Monitor Initiation and Continued Use in Children With Type 1 Diabetes.
Racial/ethnic disparities in continuous glucose monitor (CGM) use exist among children with type 1 diabetes. It is not known whether differential rates of device initiation or sustained use are the cause of this disparity. Our objective was to compare CGM initiation rates and continued use among non-Hispanic White (NHW), non-Hispanic Black (NHB), and Hispanic children. We conducted a retrospective review including children with type 1 diabetes attending the Children's Hospital of Philadelphia between 1 January 2015 and 31 December 2018. Of 1,509 eligible children, 726 (48%) started CGM during the study period. More NHW (54%) than NHB (31%) and Hispanic (33%) children started CGM (P < 0.001). One year after starting, fewer NHB (61%) than NHW (86%) and Hispanic (85%) children were using CGM (P < 0.001). Lower CGM use in NHB children was due to lower rates of device initiation and higher rates of discontinuation. Interventions to address both of these barriers are needed to reduce disparities in CGM use.


The use of syndromic surveillance for decision-making during the H1N1 pandemic: a qualitative study.
Although an increasing number of studies are documenting uses of syndromic surveillance by front line public health, few detail the value added from linking syndromic data to public health decision-making. This study seeks to understand how syndromic data informed specific public health actions during the 2009 H1N1 pandemic. Semi-structured telephone interviews were conducted with participants from Ontario's public health departments, the provincial ministry of health and federal public health agency to gather information about syndromic surveillance systems used and the role of syndromic data in informing specific public health actions taken during the pandemic. Responses were compared with how the same decisions were made by non-syndromic surveillance users. Findings from 56 interviews (82% response) show that syndromic data were most used for monitoring virus activity, measuring impact on the health care system and informing the opening of influenza assessment centres in several jurisdictions, and supporting communications and messaging, rather than its intended purpose of early outbreak detection. Syndromic data had limited impact on decisions that involved the operation of immunization clinics, school closures, sending information letters home with school children or providing recommendations to health care providers. Both syndromic surveillance users and non-users reported that guidance from the provincial ministry of health, communications with stakeholders and vaccine availability were driving factors in these public health decisions. Syndromic surveillance had limited use in decision-making during the 2009 H1N1 pandemic in Ontario. This study provides insights into the reasons why this occurred. Despite this, syndromic data were valued for providing situational awareness and confidence to support public communications and recommendations. Developing an understanding of how syndromic data are utilized during public health events provides valuable evidence to support future investments in public health surveillance.


High-density localization of ANP receptors in chondrocytes of eel gill cartilage.
Very high levels of atrial natriuretic peptide (ANP) receptor were found in a quite unexpected tissue, i.e., the chondrocyte of the eel gill cartilage. 125I-labeled ANP binding assay indicated that the eel gill contains large amounts of the receptor and its levels are much higher (> 10-fold) than those in the other tissues examined, including the brain, kidney, head kidney including steroidogenic interrenal cells, and gut. Autoradiography using gill sections revealed dense localization of ANP receptors in the chondrocytes of the cartilage as well as moderate localization in the parenchymal cells. Biochemical and pharmacological characterization of the chondrocyte receptor indicated that most of the receptors are type C receptors, having a broad ligand specificity and a reduced M(r) of 68,000. Because a hyaline cartilage in which chondrocytes reside lacks blood vessels, and all metabolic exchange is by slow diffusion through the matrix, the chondrocyte localization of the type C ANP receptor is notable and may stimulate not only chondrocyte research but also studies on physiological significance of the type C receptor, which is generally considered to be merely a clearance (silent) receptor.


Clinical approaches to treat peri-implant mucositis and peri-implantitis.
Therapies proposed for the treatment of peri-implant diseases are primarily based on the evidence available from treating periodontitis. The primary objective is elimination of the biofilm from the implant surface, and nonsurgical therapy is a commonly used treatment. A number of adjunctive therapies have been introduced to overcome accessibility problems or difficulties with decontamination of implant surfaces as a result of specific surface characteristics. It is now accepted that following successful decontamination, clinicians can attempt to regenerate the bone that was lost as a result of infection. The ultimate goal is re-osseointegration, and a number of regenerative techniques have been introduced. By reviewing the existing evidence, it seems that peri-implant mucositis is reversible when appropriately treated. Additionally, a combined therapy (mechanical therapy with local antimicrobials as adjuncts) can serve as an alternative to surgical intervention when treating peri-implantits in cases not suitable for surgery. Surgical therapy is an effective method for treating peri-implantitis, and various degrees of success of the use of regenerative procedures have been reported, regardless of whether or not radiographic evidence of defect fill has been achieved. Finally, no matter which therapy is employed, a prerequisite for the long-term stability of treatment results obtained is the ability of the patient to maintain good oral hygiene.


Morphological characteristics of the symphyseal region in adult skeletal Class III crossbite and openbite malocclusions.
To evaluate the relationship of the morphological characteristics of the symphyseal region of adult Class III malocclusion to the differences in overjet and overbite. The basal and symphyseal widths along with the alveolar and symphyseal heights were evaluated using data from the lateral cephalograms of Korean adult male skeletal Class III, divided into crossbite (n = 28) and openbite (n = 41) groups. Korean male normal occlusion samples (n = 32) were used as controls. The width of the symphyseal region including the basal width, point B width, Id width, symphyseal thickness, and pogonion width were similar in adult Class III crossbite and normal occlusion groups, but significantly less in the adult Class III openbite group (P < .001). The alveolar height was similar in the adult Class III crossbite and control groups, but significantly less in the adult Class III openbite group (P < .05). However, the symphyseal height was similar in all three groups. An openbite, rather than a negative overjet, is the major factor influencing the symphyseal morphology in an adult Class III malocclusion.


Uptake of the neurotoxin, 4-methylphenylpyridinium, into chromaffin granules and synaptic vesicles: a proton gradient drives its uptake through monoamine transporter.
Energy dependence for uptake of 4-methyphenylpyridinium (MPP+), a neurotoxin causing Parkinsonism-like symptoms, by adrenal chromaffin granule membrane vesicles and brain synaptic vesicles was studied. The compound was actively taken up by the chromaffin vesicles dependent on hydrolysis of ATP with a Km value of 22 microM and maximum velocity of 2.9 nmol/min/mg protein. The uptake was sensitive to reserpine (1 microM) and bafilomycin (50 nM) (inhibitors of the vesicular monoamine transporter and vacuolar-type H(+)-ATPase, respectively) and substrates for monoamine transporters, but insensitive to imipramine (an inhibitor of the monoamine transporter present in the plasma membrane). The uptake was greatly reduced upon dissipation of the proton gradient by ammonium ion or nigericin with KCl, but stimulated 1.6-fold by valinomycin plus K+. Dissipation of the proton gradient also induced rapid efflux of MPP+ from the vesicles. The MPP+ (monoamine) transporter was solubilized from chromaffin vesicles and reconstituted into liposomes with purified bacterial F0F1-ATPase. MPP+ was taken up by the liposomes coupled with ATP hydrolysis by F0F1, and the uptake was sensitive to reserpine, dissipation of the proton gradient, and azide. Brain synaptic vesicles also accumulated MPP+, showing similar kinetics, inhibitor sensitivities, and energy coupling to those of chromaffin vesicles. Furthermore, MPP+ inhibited the uptake of dopamine without affecting the uptake of glutamate or gamma-aminobutyrate. These results indicated that MPP+ was taken up through the reserpine-sensitive monoamine transporter into chromaffin vesicles and synaptic vesicles and that the energy for accumulation of MPP+ was supplied as a proton gradient (acidic inside) established by H(+)-ATPase.


Non-Hodgkin's lymphomas of Waldeyer's ring: a clinicopathological and immunological study of 64 cases in the western Cape.
The clinicopathological and immunological features of 64 cases of primary extranodal non-Hodgkin's lymphoma (NHLs) that occurred in Waldeyer's ring (WR) were examined. The objective was to compare the findings of this study with those of previous studies. The age at presentation, sex ratio, and site of occurrence of these tumours within WR concurred with that of other studies. Diffuse large cell lymphomas were the most prevalent in this study. Most T-cell NHLs occurred in the nasopharynx where they constituted 28% of all NHLs in that site. This indicates a higher incidence of nasopharyngeal T-cell NHLs in South Africa as compared with other Western countries.


Air oxidation of sulfur mustard gas simulants using a pyrene-based metal-organic framework photocatalyst.
We demonstrate a microporous metal-organic framework NU-400 based on a 2,7-disubstituted pyrene linker as a highly efficient photosensitizer for generating singlet oxygen and subsequent oxidative degradation of chemical warfare agents (CWAs). The high activity of NU-400 permits photocatalytic conversion of the 2-chloroethyl ethyl sulfide (CEES) mustard gas simulant into a benign sulfoxide derivative, in air, with less than 15 minutes' half-life. This is a considerable improvement to NU-1000, based on a 1,3,6,8-tetrasubstituted pyrene unit, demonstrating how variation of the substitution pattern of a metal-organic framework linker permits modification of its photoactive behavior.


Real-time three-dimensional object recognition with multiple perspectives imaging.
A novel system for recognizing three-dimensional (3D) objects by use of multiple perspectives imaging is proposed. A 3D object under incoherent illumination is projected into an array of two-dimensional (2D) elemental images by use of a microlens array. Each elemental 2D image corresponds to a different perspective of the 3D object. Multiple perspectives imaging based on integral photography has been used for 3D display. In this way, the whole set of 2D elemental images records 3D information about the input object. After an optical incoherent-to-coherent conversion, an optical processor is employed to perform the correlation between the input and the reference 3D objects. Use of micro-optics allows us to process the 3D information in real time and with a compact optical system. To the best of our knowledge this 3D processor is the first to apply the principle of integral photography to 3D image recognition. We present experimental results obtained with both a digital and an optical implementation of the system. We also show that the system can recognize a slightly out-of-plane rotated 3D object.


Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism.
Obesity is becoming a global epidemic in both children and adults. It is associated with numerous comorbidities such as cardiovascular diseases (CVD), type 2 diabetes, hypertension, certain cancers, and sleep apnea/sleep-disordered breathing. In fact, obesity is an independent risk factor for CVD, and CVD risks have also been documented in obese children. Obesity is associated with an increased risk of morbidity and mortality as well as reduced life expectancy. Health service use and medical costs associated with obesity and related diseases have risen dramatically and are expected to continue to rise. Besides an altered metabolic profile, a variety of adaptations/alterations in cardiac structure and function occur in the individual as adipose tissue accumulates in excess amounts, even in the absence of comorbidities. Hence, obesity may affect the heart through its influence on known risk factors such as dyslipidemia, hypertension, glucose intolerance, inflammatory markers, obstructive sleep apnea/hypoventilation, and the prothrombotic state, in addition to as-yet-unrecognized mechanisms. On the whole, overweight and obesity predispose to or are associated with numerous cardiac complications such as coronary heart disease, heart failure, and sudden death because of their impact on the cardiovascular system. The pathophysiology of these entities that are linked to obesity will be discussed. However, the cardiovascular clinical evaluation of obese patients may be limited because of the morphology of the individual. In this statement, we review the available evidence of the impact of obesity on CVD with emphasis on the evaluation of cardiac structure and function in obese patients and the effect of weight loss on the cardiovascular system.


Physical and chemical transformations of highly compressed carbon dioxide at bond energies.
Carbon dioxide exhibits a richness of high-pressure polymorphs with a great diversity in intermolecular interaction, chemical bonding, and crystal structures. It ranges from typical molecular solids to fully extended covalent solids with crystal structures similar to those of SiO2. These extended solids of carbon dioxide are fundamentally new materials exhibiting interesting optical nonlinearity, low compressibility and high energy density. Furthermore, the large disparity in chemical bonding between the extended network and molecular structures results in a broad metastability domain for these phases to room temperature and almost to ambient pressure and thereby offers enhanced opportunities for novel materials developments. Broadly speaking, these molecular-to-non-molecular transitions occur due to electron delocalization manifested as a rapid increase in electron kinetic energy at high density. The detailed mechanisms, however, are more complex with phase metastabilities, path-dependent phases and phase boundaries, and large lattice strains and structural distortions - all of which are controlled by well beyond thermodynamic constraints to chemical kinetics associated with the governing phases and transitions. As a result, the equilibrium phase boundary is difficult to locate precisely (experimentally or theoretically) and is often obscured by the presence of metastable phases (ordered or disordered). This paper will review the pressure-induced transformations observed in highly compressed carbon dioxide and present chemistry perspectives on those molecular-to-non-molecular transformations that can be applied to other low-Z molecular solids at Mbar pressures where the compression energy rivals the chemical bond energies.


Loss of heterozygosity and tumor suppressor activity of Bin1 in prostate carcinoma.
The genetic events underlying the development of prostate cancer are poorly defined. c-Myc is often activated in tumors that have progressed to metastatic status, so events that promote this process may be important. Bin1 is a nucleocytoplasmic adaptor protein with features of a tumor suppressor that was identified through its ability to interact with and inhibit malignant transformation by c-Myc. We investigated a role for Bin1 loss or inactivation in prostate cancer because the human Bin1 gene is located at chromosome 2q14 within a region that is frequently deleted in metastatic prostate cancer but where no tumor suppressor candidate has been located. A novel polymorphic microsatellite marker located within intron 5 of the human Bin1 gene was used to demonstrate loss of heterozygosity and coding alteration in 40% of informative cases of prostate neoplasia examined. RNA and immunohistochemical analyses indicated that Bin1 was expressed in most primary tumors, even at slightly elevated levels relative to benign tissues, but that it was frequently missing or inactivated by aberrant splicing in metastatic tumors and androgen-independent tumor cell lines. Ectopic expression of Bin1 suppressed the growth of prostate cancer lines in vitro. Our findings support the candidacy of Bin1 as the chromosome 2q prostate tumor suppressor gene.


Structure-property relationships in protic ionic liquids: a study of solvent-solvent and solvent-solute interactions.
The ionic nature of a functionalized protic ionic liquid cannot be rationalized simply through the differences in aqueous proton dissociation constants between the acid precursor and the conjugate acid of the base precursor. The extent of proton transfer, i.e. the equilibrium ionicity, of a tertiary ammonium acetate protic ionic liquid can be significantly increased by introducing an hydroxyl functional group on the cation, compared to the alkyl or amino-functionalized analogues. This increase in apparent ionic nature correlates well with variations in solvent-solute and solvent-solvent interaction parameters, as well as with physicochemical properties such as viscosity.


Reactive Oxygen Species Generation Linked to Sources of Atmospheric Particulate Matter and Cardiorespiratory Effects.
Exposure to atmospheric fine particulate matter (PM2.5) is associated with cardiorespiratory morbidity and mortality, but the mechanisms are not well understood. We assess the hypothesis that PM2.5 induces oxidative stress in the body via catalytic generation of reactive oxygen species (ROS). A dithiothreitol (DTT) assay was used to measure the ROS-generation potential of water-soluble PM2.5. Source apportionment on ambient (Atlanta, GA) PM2.5 was performed using the chemical mass balance method with ensemble-averaged source impact profiles. Linear regression analysis was used to relate PM2.5 emission sources to ROS-generation potential and to estimate historical levels of DTT activity for use in an epidemiologic analysis for the period of 1998-2009. Light-duty gasoline vehicles (LDGV) exhibited the highest intrinsic DTT activity, followed by biomass burning (BURN) and heavy-duty diesel vehicles (HDDV) (0.11 ± 0.02, 0.069 ± 0.02, and 0.052 ± 0.01 nmol min(-1) μg(-1)source, respectively). BURN contributed the largest fraction to total DTT activity over the study period, followed by LDGV and HDDV (45, 20, and 14%, respectively). DTT activity was more strongly associated with emergency department visits for asthma/wheezing and congestive heart failure than PM2.5. This work provides further epidemiologic evidence of a biologically plausible mechanism, that of oxidative stress, for associations of adverse health outcomes with PM2.5 mass and supports continued assessment of the utility of the DTT activity assay as a measure of ROS-generating potential of particles.


Forward scattering induced by water drops on a transmissive substrate.
In this study the scattering of radiation by condensation drops deposited on a single glass plate is dealt with. Experiments were carried out in the visible radiation range by means of a laboratory measuring unit as a function of three parameters, namely, the phase of the condensation process, the wavelength of the incident radiation, and the radiation incidence angle. The experiments indicated that during the condensation process a steady state in the scattering pattern of single glass occurred after a transition phase. Owing to the condensate, more than 80% of the transmitted visible radiation was scattered. The scattering slightly diminished with increasing wavelength, from 400 to 700 nm, and the asymmetry of the scattering pattern enlarged with increasing incidence angle of the radiation.


Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men.
Study associations between three measures of alcohol consumption (recent, typical/habitual, binging), semen quality and serum reproductive hormones. Cross-sectional population based study. 1221 young Danish men, aged 18-28 years were recruited when they attended a compulsory medical examination to determine their fitness for military service from 2008 to 2012. Total alcohol consumption: (1) in the week preceding (habitual/typical) the visit (recent alcohol intake), (2) in a typical week and (3) frequency of 'binge drinking' (consuming more than 5 units/day)) in the past 30 days was estimated. Semen quality (volume, sperm concentration, total sperm count, and percentages of motile and morphologically normal spermatozoa) and serum concentration of reproductive hormones (follicle-stimulating hormone, luteinising hormone, testosterone, sex hormone binding globulin, oestradiol, free testosterone and inhibin B). Sperm concentration, total sperm count and percentage of spermatozoa with normal morphology were negatively associated with increasing habitual alcohol intake. This association was observed in men reporting at least 5 units in a typical week but was most pronounced for men with a typical intake of more than 25 units/week. Men with a typical weekly intake above 40 units had a 33% (95% CI 11% to 59%) reduction in sperm concentration compared to men with an intake of 1-5 units/week. A significant increase in serum free testosterone with increasing alcohol consumption the week preceding the visit was found. Binging was not independently associated with semen quality. Our study suggests that even modest habitual alcohol consumption of more than 5 units per week had adverse effects on semen quality although most pronounced associations were seen in men who consumed more than 25 units per week. Alcohol consumption was also linked to changes in testosterone and SHBG levels. Young men should be advised to avoid habitual alcohol intake.


Recent Advances in Biomedical, Therapeutic and Pharmaceutical Applications of Microbial Surfactants.
The spread of antimicrobial-resistant pathogens typically existing in biofilm formation and the recent COVID-19 pandemic, although unrelated phenomena, have demonstrated the urgent need for methods to combat such increasing threats. New avenues of research for natural molecules with desirable properties to alleviate this situation have, therefore, been expanding. Biosurfactants comprise a group of unique and varied amphiphilic molecules of microbial origin capable of interacting with lipidic membranes/components of microorganisms and altering their physicochemical properties. These features have encouraged closer investigations of these microbial metabolites as new pharmaceutics with potential applications in clinical, hygiene and therapeutic fields. Mounting evidence has indicated that biosurfactants have antimicrobial, antibiofilm, antiviral, immunomodulatory and antiproliferative activities that are exploitable in new anticancer treatments and wound healing applications. Some biosurfactants have already been approved for use in clinical, food and environmental fields, while others are currently under investigation and development as antimicrobials or adjuvants to antibiotics for microbial suppression and biofilm eradication strategies. Moreover, due to the COVID-19 pandemic, biosurfactants are now being explored as an alternative to current products or procedures for effective cleaning and handwash formulations, antiviral plastic and fabric surface coating agents for shields and masks. In addition, biosurfactants have shown promise as drug delivery systems and in the medicinal relief of symptoms associated with SARS-CoV-2 acute respiratory distress syndrome.


Algorithm validation using multicolor phantoms.
We present a framework for hyperspectral image (HSI) analysis validation, specifically abundance fraction estimation based on HSI measurements of water soluble dye mixtures printed on microarray chips. In our work we focus on the performance of two algorithms, the Least Absolute Shrinkage and Selection Operator (LASSO) and the Spatial LASSO (SPLASSO). The LASSO is a well known statistical method for simultaneously performing model estimation and variable selection. In the context of estimating abundance fractions in a HSI scene, the "sparse" representations provided by the LASSO are appropriate as not every pixel will be expected to contain every endmember. The SPLASSO is a novel approach we introduce here for HSI analysis which takes the framework of the LASSO algorithm a step further and incorporates the rich spatial information which is available in HSI to further improve the estimates of abundance. In our work here we introduce the dye mixture platform as a new benchmark data set for hyperspectral biomedical image processing and show our algorithm's improvement over the standard LASSO.


Probiotic potency of Lactobacillus plantarum KX519413 and KX519414 isolated from honey bee gut.
The Indian honey bee Apis cerana indica, which harbors an abundant and diverse range of lactic acid bacteria (LAB) in their gut with beneficial effects, was used as the source for the isolation of LAB. In the present study, two LAB isolates from honey bee gut were selected primarily based on their phenotypic and selective biochemical characterization, followed by PCR and identified using 16S rRNA sequencing as Lactobacillus plantarum and were registered in National Centre for Biotechnology Information under accession number KX519413 and KX519414. The probiotic potency of test strains indicated their survivability at acidic pH, bile salts and viability in simulated gastric juice enabling them to withstand gastrointestinal tract conditions. Evaluation of cell surface properties suggested that they possess an important defense mechanism against the pathogen since they are hydrophobic, auto-aggregative and have co-aggregative ability. Further, efficient exopolysaccharide production by them indicates not only their ability to enrich biofilm formation and auto-aggregation, but also enhances bacterial adhesion and colonization on the host intestinal tract. The present study concluded that L. plantarum from the gut of Apis cerana indica possesses probiotic potency, and potential candidates for use as food besides application in nutraceutical and pharmaceutical industries.


Critical adsorption of periodic and random polyampholytes onto charged surfaces.
How different are the properties of critical adsorption of polyampholytes and polyelectrolytes onto charged surfaces? How important are the details of polyampholyte charge distribution on the onset of critical adsorption transition? What are the scaling relations governing the dependence of critical surface charge density on salt concentration in the surrounding solution? Here, we employ Metropolis Monte Carlo simulations and uncover the scaling relations for critical adsorption for quenched periodic and random charge distributions along the polyampholyte chains. We also evaluate and discuss the dependence of the adsorbed layer width on solution salinity and details of the charge distribution. We contrast our findings to the known results for polyelectrolyte adsorption onto oppositely charged surfaces, in particular, their dependence on electrolyte concentration.


Regulated cleavage of a contact-mediated axon repellent.
Contact-mediated axon repulsion by ephrins raises an unresolved question: these cell surface ligands form a high-affinity multivalent complex with their receptors present on axons, yet rather than being bound, axons can be rapidly repelled. We show here that ephrin-A2 forms a stable complex with the metalloprotease Kuzbanian, involving interactions outside the cleavage region and the protease domain. Eph receptor binding triggered ephrin-A2 cleavage in a localized reaction specific to the cognate ligand. A cleavage-inhibiting mutation in ephrin-A2 delayed axon withdrawal. These studies reveal mechanisms for protease recognition and control of cell surface proteins, and, for ephrin-A2, they may provide a means for efficient axon detachment and termination of signaling.


Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 A.
The high resolution three-dimensional x-ray structure of the metal sites of bovine heart cytochrome c oxidase is reported. Cytochrome c oxidase is the largest membrane protein yet crystallized and analyzed at atomic resolution. Electron density distribution of the oxidized bovine cytochrome c oxidase at 2.8 A resolution indicates a dinuclear copper center with an unexpected structure similar to a [2Fe-2S]-type iron-sulfur center. Previously predicted zinc and magnesium sites have been located, the former bound by a nuclear encoded subunit on the matrix side of the membrane, and the latter situated between heme a3 and CuA, at the interface of subunits I and II. The O2 binding site contains heme a3 iron and copper atoms (CuB) with an interatomic distance of 4.5 A; there is no detectable bridging ligand between iron and copper atoms in spite of a strong antiferromagnetic coupling between them. A hydrogen bond is present between a hydroxyl group of the hydroxyfarnesylethyl side chain of heme a3 and an OH of a tyrosine. The tyrosine phenol plane is immediately adjacent and perpendicular to an imidazole group bonded to CuB, suggesting a possible role in intramolecular electron transfer or conformational control, the latter of which could induce the redox-coupled proton pumping. A phenyl group located halfway between a pyrrole plane of the heme a3 and an imidazole plane liganded to the other heme (heme a) could also influence electron transfer or conformational control.


The effect of nutrient intake on bone mineral status in young adults: the Northern Ireland young hearts project.
Optimizing peak bone mass in early life may reduce osteoporosis risk in later life. Such optimization may be partly dependent upon diet. In the present study, nutrient intakes and selected lifestyle parameters were assessed in adolescent subjects (238 males, 205 females; aged 15 y) and again, in the same subjects, on one occasion in young adulthood (aged between 20 and 25 y). The extent of the relationships between these parameters and bone mineral density (BMD), dual energy X-ray absorptiometry (DXA), lumbar spine (L2-L4), and femoral neck measured concurrently with diet in young adulthood only, was assessed. Adjusted linear regression models were constructed. Variables included a measure of pubertal status (at age 15 y), age (at young adulthood), height, weight, physical activity, smoking, and mean daily intakes of energy, calcium, protein, vitamin D, phosphorus, total fat, and alcohol. In both sexes, body weight at adolescence and young adulthood was the only factor consistently positively associated with BMD at both measurement sites. Effects of nutrient intake on BMD were inconsistent. Vitamin D and calcium intakes reported by female adolescents showed significant positive relationships with BMD measured in young adulthood (vitamin D measured at the lumbar spine; calcium measured at the femoral neck). The positive relationship between vitamin D and BMD remained significant at young adulthood, but at the femoral neck rather than at the lumbar spine. Also in females, intakes of phosphorus and the calcium:phosphorus ratio (Ca:P) at adolescence were strongly negatively related to femoral neck BMD measured at young adulthood. In males, however, Ca:P reported at young adulthood had a significant positive relationship with lumbar spine BMD, whereas Ca:protein was negatively associated with BMD at the lumbar spine. Intakes of Ca reported by adolescent males also had a strong negative effect on lumbar spine BMD measured at young adulthood.


Importance of consensus region of multiple-ligand templates in a virtual screening method.
We discuss methods and ideas of virtual screening (VS) for drug discovery by examining the performance of VS-APPLE, a recently developed VS method, which extensively utilizes the tendency of single binding pockets to bind diversely different ligands, i.e. promiscuity of binding pockets. In VS-APPLE, multiple ligands bound to a pocket are spatially arranged by maximizing structural overlap of the protein while keeping their relative position and orientation with respect to the pocket surface, which are then combined into a multiple-ligand template for screening test compounds. To greatly reduce the computational cost, comparison of test compound structures are made only with limited regions of the multiple-ligand template. Even when we use the narrow regions with most densely populated atoms for the comparison, VSAPPLE outperforms other conventional VS methods in terms of Area Under the Curve (AUC) measure. This region with densely populated atoms corresponds to the consensus region among multiple ligands. It is typically observed that expansion of the sampled region including more atoms improves screening efficiency. However, for some target proteins, considering only a small consensus region is enough for the effective screening of test compounds. These results suggest that the performance test of VS methods sheds light on the mechanisms of protein-ligand interactions, and elucidation of the protein-ligand interactions should further help improvement of VS methods.


The role of a short post-lunch nap in improving cognitive, motor, and sprint performance in participants with partial sleep deprivation.
The aim of this study was to determine the effects of a post-lunch nap on subjective alertness and performance following partial sleep loss. Ten healthy males (mean age 23.3 years, s = 3.4) either napped or sat quietly from 13:00 to 13:30 h after a night of shortened sleep (sleep 23:00-03:00 h only). Thirty minutes after the afternoon nap or control (no-nap) condition, alertness, short-term memory, intra-aural temperature, heart rate, choice reaction time, grip strength, and times for 2-m and 20-m sprints were recorded. The afternoon nap lowered heart rate and intra-aural temperature. Alertness, sleepiness, short-term memory, and accuracy at the 8-choice reaction time test were improved by napping (P < 0.05), but mean reaction times and grip strength were not affected (P > 0.05). Sprint times were improved. Mean time for the 2-m sprints fell from 1.060 s (s(x) = 0.018) to 1.019 s (s(x) = 0.019) (P = 0.031 paired t-test); mean time for the 20-m sprints fell from 3.971 s (s(x) = 0.054) to 3.878 s (s(x) = 0.047) (P = 0.013). These results indicate that a post-lunch nap improves alertness and aspects of mental and physical performance following partial sleep loss, and have implications for athletes with restricted sleep during training or before competition.


Developmental dysplasia of the hip practice guideline: technical report. Committee on Quality Improvement, and Subcommittee on Developmental Dysplasia of the Hip.
To create a recommendation for pediatricians and other primary care providers about their role as screeners for detecting developmental dysplasia of the hip (DDH) in children. Theoretical cohorts of newborns. Model-based approach using decision analysis as the foundation. Components of the approach include the following: Primary care provider. DDH, avascular necrosis of the hip (AVN). Newborn screening by pediatric examination; orthopaedic examination; ultrasonographic examination; orthopaedic or ultrasonographic examination by risk factors. Intercurrent health supervision-based screening. PREFERENCES: 0 for bad outcomes, 1 for best outcomes. Influence diagram assessed by the Subcommittee and by the methodology team, with critical feedback from the Subcommittee. EVIDENCE SOURCES: Medline and EMBASE search of the research literature through June 1996. Hand search of sentinel journals from June 1996 through March 1997. Ancestor search of accepted articles. EVIDENCE QUALITY: Assessed on a custom subjective scale, based primarily on the fit of the evidence to the decision model. After discussion, explicit modeling, and critique, an influence diagram of 31 nodes was created. The computer-based and the hand literature searches found 534 articles, 101 of which were reviewed by 2 or more readers. Ancestor searches of these yielded a further 17 articles for evidence abstraction. Articles came from around the globe, although primarily Europe, British Isles, Scandinavia, and their descendants. There were 5 controlled trials, each with a sample size less than 40. The remainder were case series. Evidence was available for 17 of the desired 30 probabilities. Evidence quality ranged primarily between one third and two thirds of the maximum attainable score (median: 10-21; interquartile range: 8-14). Based on the raw evidence and Bayesian hierarchical meta-analyses, our estimate for the incidence of DDH revealed by physical examination performed by pediatricians is 8.6 per 1000; for orthopaedic screening, 11.5; for ultrasonography, 25. The odds ratio for DDH, given breech delivery, is 5.5; for female sex, 4.1; for positive family history, 1.7, although this last factor is not statistically significant. Postneonatal cases of DDH were divided into mid-term (younger than 6 months of age) and late-term (older than 6 months of age). Our estimates for the mid-term rate for screening by pediatricians is 0.34/1000 children screened; for orthopaedists, 0.1; and for ultrasonography, 0.28. Our estimates for late-term DDH rates are 0.21/1000 newborns screened by pediatricians; 0.08, by orthopaedists; and 0.2 for ultrasonography. The rates of AVN for children referred before 6 months of age is estimated at 2.5/1000 infants referred. For those referred after 6 months of age, our estimate is 109/1000 referred infants. The decision model (reduced, based on available evidence) suggests that orthopaedic screening is optimal, but because orthopaedists in the published studies and in practice would differ, the supply of orthopaedists is relatively limited, and the difference between orthopaedists and pediatricians is statistically insignificant, we conclude that pediatric screening is to be recommended. The place of ultrasonography in the screening process remains to be defined because there are too few data about postneonatal diagnosis by ultrasonographic screening to permit definitive recommendations. These data could be used by others to refine the conclusions based on costs, parental preferences, or physician style. Areas for research are well defined by our model-based approach.


Interferon gamma receptor deficient mice are resistant to endotoxic shock.
Antibody neutralization studies have established interferon gamma (IFN-gamma) as a critical mediator of endotoxic shock. The advent of IFN-gamma receptor negative (IFN gamma R-/-) mutant mice has enabled a more direct assessment of the role of IFN-gamma in endotoxin (lipopolysaccharide [LPS]-induced shock. We report that IFN gamma R-/- mice have an increased resistance to LPS-induced toxicity, this resistance manifesting well before the synthesis and release of LPS-induced IFN-gamma. LPS-induced lymphopenia, thrombocytopenia, and weight loss seen in wild-type mice were attenuated in IFN gamma R-/- mice. IFN gamma R-/- mice tolerated 100-1,000 times more LPS than the minimum lethal dose for wild-type mice in a D-galactosamine (D-GalN)/LPS model. Serum tumor necrosis factor (TNF) levels were 10-fold reduced in mutant mice given LPS or LPS/D-GalN. Bone marrow and splenic macrophages from IFN gamma R-/- mice had a four- to sixfold decreased LPS-binding capacity which correlated with similar reduction in CD14. Serum from mutant mice reduced macrophage LPS binding by a further 50%, although LPS binding protein was only 10% reduced. The expression of TNF receptor I (p55) and II (p75) was identical between wild-type and mutant mice. Thus, depressed TNF synthesis, diminished expression of CD14, and low plasma LPS-binding capacity, in addition to blocked IFN-gamma signaling in the mutant mice, likely to combine to manifest in the resistant phenotype of IFN gamma R-/- mice to endotoxin.


The national incidence of PML in Sweden, 1988-2013.
To investigate the incidence of progressive multifocal leukoencephalopathy (PML) and patient characteristics in Sweden between 1988 and 2013. All PML diagnoses in Sweden between 1988 and 2013 were identified in the National Patient Register. Information to validate the diagnosis and patient characteristics was obtained from medical records. Medical record review classified 108 out of 250 patients (43%) as definite (n = 84), probable (n = 4), or possible (n = 20) PML according to diagnostic criteria. Accurate diagnoses were more common in records obtained from neurology departments (82% of patients seen in neurology departments) compared with other departments (31%) (p < 0.001). The incidence of PML increased from a largely stable level at 0.026 (95% confidence interval [CI] 0.021-0.031) per 100,000 individuals per year during 1988-2010 to 0.11 (95% CI 083-0.137) during 2011-2013, during which time there was a notable increase (p < 0.001). Hematologic malignancies (n = 34), HIV/AIDS (n = 33), and autoimmune disease (n = 23) were the most common underlying diseases. Treatment with a monoclonal antibody prior to PML diagnosis was identified in 26 patients. An increased incidence of PML in Sweden was observed and coincided with the prior use of monoclonal antibody treatment. The high level of misdiagnosis emphasizes the importance of immediate contact with a neurology center upon suspicion of PML.


Air Pollution Exposure in Relation to the Commute to School: A Bradford UK Case Study.
Walking School Buses (WSBs) provide a safe alternative to being driven to school. Children benefit from the contribution the exercise provides towards their daily exercise target, it gives children practical experience with respect to road safety and it helps to relieve traffic congestion around the entrance to their school. Walking routes are designed largely based in road safety considerations, catchment need and the availability of parent support. However, little attention is given to the air pollution exposure experienced by children during their journey to school, despite the commuting microenvironment being an important contributor to a child's daily air pollution exposure. This study aims to quantify the air pollution exposure experienced by children walking to school and those being driven by car. A school was chosen in Bradford, UK. Three adult participants carried out the journey to and from school, each carrying a P-Trak ultrafine particle (UFP) count monitor. One participant travelled the journey to school by car while the other two walked, each on opposite sides of the road for the majority of the journey. Data collection was carried out over a period of two weeks, for a total of five journeys to school in the morning and five on the way home at the end of the school day. Results of the study suggest that car commuters experience lower levels of air pollution dose due to lower exposure and reduced commute times. The largest reductions in exposure for pedestrians can be achieved by avoiding close proximity to traffic queuing up at intersections, and, where possible, walking on the side of the road opposite the traffic, especially during the morning commuting period. Major intersections should also be avoided as they were associated with peak exposures. Steps to ensure that the phasing of lights is optimised to minimise pedestrian waiting time would also help reduce exposure. If possible, busy roads should be avoided altogether. By the careful design of WSB routes, taking into account air pollution, children will be able to experience the benefits that walking to school brings while minimizing their air pollution exposure during their commute to and from school.


Dehydroepiandrosterone attenuates allergic airway inflammation in Dermatophagoides farinae-sensitized mice.
Dehydroepiandrosterone, an androgen abundant in circulation, has important immunomodulating effects. In this study the therapeutic effect of dehydroepiandrosterone on established allergic inflammation was examined in a dust mite (Dermatophagoides farinae)-induced asthma model. Airway inflammation was provoked in D. farinae-sensitized BALB/c mice by repetitive intratracheal challenge (3 times, once a week). Three days after the first challenge, mice were fed a diet incorporated with 1.5% (w/w) dehydroepiandrosterone and were examined at days 3 and 6 after the last challenge. Airway challenge resulted in pulmonary eosinophilic inflammation accompanied by elevated blood eosinophil counts and elevated serum and bronchoalveolar lavage immunoglobulin E antibody levels in control diet-fed mice. However, the D. farinae-induced airway inflammation and blood eosinophilia was significantly reduced in dehydroepiandrosterone-fed mice, which was associated with a decrease in serum interleukin-4, interleukin-5, and interferon-gamma levels. Total immunoglobulin E antibody concentrations in serum and bronchoalveolar lavage fluids were not affected by the dehydroepiandrosterone treatment. These results demonstrated that dehydroepiandrosterone could suppress preexisting allergic airway inflammation.


Role of reoxygenation in induction of enhancement of tumor radioresponse by paclitaxel.
We reported previously (L. Milas et al., Cancer Res., 54: 3506-3510, 1994) that paclitaxel greatly enhances the response of a murine mammary carcinoma to subsequent irradiation and hypothesized that the enhanced radioresponse was mediated by tumor cell reoxygenation caused by treatment with paclitaxel. Because paclitaxel induced massive tumor cell destruction by apoptosis, it was reasoned that as apoptotic cells were removed from the tumor more hypoxic cells would have access to oxygen, be reoxygenated, and, thus, become more sensitive to radiation. The present study tested this hypothesis by assessing the effect of 60 or 40 mg/kg paclitaxel on radioresponse of an 8-mm MCA-4 tumor irradiated under air-breathing or hypoxic conditions 9, 24, 48, or 72 h after paclitaxel administration. If the hypothesis was correct, paclitaxel would enhance tumor radioresponse more under air breathing than under hypoxic conditions, and the enhancement would increase as the time between paclitaxel administration and tumor irradiation increased within a few days after paclitaxel treatment but only when radiation was given under air-breathing conditions. The effect of the treatments was determined by tumor growth delay and the radiation dose required to control 50% of the tumors (TCD50). Paclitaxel greatly enhanced tumor radioresponse under air-breathing (and not hypoxic) conditions, increasing tumor growth delay, and reducing TCD50. These effects increased as the time interval between paclitaxel administration and tumor irradiation increased within the observation period of 72 h after paclitaxel treatment. The enhancement factors for tumor growth delay ranged from 1.19 at 9 h to 1.86 at 48 h and for TCD50, from 1.16 at 9 h to 1.47 at 72 h after paclitaxel. Direct measurements of tumor pO2 showed a median value in untreated tumors of 6.2 mmHg, which increased to 10.5 mmHg at 24 h and to 31.2 mmHg at 48 h after paclitaxel administration. Overall, these results show that paclitaxel is a potent enhancer of tumor radioresponse and that its effect is mediated by reoxygenation of hypoxic tumor cells.


Ribosomal RNA multigene loci: nomads of the Triticeae genomes.
The nucleolus organizing regions (NORs) on the short arms of chromosomes 1A(m) and 5A(m) of diploid wheat, Triticum monococcum L., are at the most distal loci in the linkage maps of these two chromosome arms. This distal location differs from the interstitial location of the Nor loci on chromosome arms 1BS of tetraploid Triticum turgidum L. and hexaploid T. aestivum L., 5DS of T. aestivum and diploid Ae. tauschii Coss., and 5HS of barley. Moreover, the barley 5HS locus is at a different location than the 5DS locus. However, other markers, including the centromeres, are colinear. These findings showed that the major Nor loci have repeatedly changed position in the chromosome arms during the radiation of species in the tribe Triticeae without rearrangements of the linkage groups. It is suggested that Nor loci may change position via dispersion of minor loci, that are shown here to exist in the T. monococcum genome, magnification of gene copy numbers in these minor loci, and subsequent deletion of the original major loci. Implications of these findings for the use of rRNA nucleotide sequences in phylogenetic reconstructions are pointed out.


p14(ARF) regulates E2F activity.
The ARF protein product of the ink4a/arf locus is induced by a variety of oncogenic signals. ARF facilitates growth arrest through the p53 pathway by hindering the down-regulation of p53 activity mediated by MDM2, through the formation of a protein complex with MDM2. Here we have explored the possibility that human p14(ARF) activity is integrated with growth regulating pathways other than p53, and report our results that p14(ARF) can control the activity of the E2F transcription factor. p14(ARF) regulates E2F activity in different cell-types, including p53(-/-)/mdm(-/-) MEFs, thus excluding that the effects of p14(ARF) are indirectly caused through MDM2 modulation. p14(ARF) down-regulates E2F-dependent transcription, and in cells undergoing E2F-dependent apoptosis prompts cell cycle arrest. p14(ARF) possesses multiple binding domains for E2F-1, one of which resides within the N-terminal region and coincides with the regulation of E2F activity. A mutational analysis of p14(ARF) indicates that the E2F-1 and MDM2 binding domains can be distinguished. These results highlight the potential interplay between p14(ARF) and E2F, and establish p14(ARF) as a pleiotrophic regulator of cell growth that acts by targetting at least two key pathways in the control of proliferation, namely E2F and p53.


The disease burden of keratoconus in patients' lives: comparisons to a Japanese normative sample.
Keratoconus is a chronic, noninflammatory, degenerative disease of the cornea that has an onset in young adulthood. The objective of this study was to evaluate vision-related quality of life (VR-QOL) in patients with keratoconus by using the Japanese version of the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25). Forty-five patients diagnosed with keratoconus at the Keio University School of Medicine were enrolled. Patients were divided into three subgroups according to corrected visual acuity. Group A included patients whose best-corrected visual acuity was at least 20/20 in both eyes. Group B included patients with a best-corrected visual acuity of at least 20/20 in only one eye. Group C included patients whose best-corrected visual acuity was worse than 20/20 in both eyes. Thirty-six age-matched subjects were recruited as control subjects. The Japanese version of the NEI-VFQ-25 was administered to each subject. All NEI-VFQ-25 subscale scores were significantly lower (P<0.05) in patients with keratoconus than in the control subjects. Subscales evaluating general health, ocular pain, and vision-specific mental health showed particularly low values. Among patients with keratoconus, every subscale score other than color vision correlated with corrected visual acuity. The results support that and describe how multidimensional visual function and VR-QOL are impaired in patients with keratoconus, including those with normal visual acuity. Ophthalmologists and other clinicians should carefully evaluate and address the full range of quality of life issues that may affect patients with keratoconus.


Flow-induced [Ca2+]i increase depends on nucleotide release and subsequent purinergic signaling in the intact nephron.
Flow induces cytosolic Ca(2+) increases ([Ca(2+)](i)) in intact renal tubules, but the mechanism is elusive. Mechanical stimulation in general is known to promote release of nucleotides (ATP/UTP) and trigger auto- and paracrine activation of P2 receptors in renal epithelia. It was hypothesized that the flow-induced [Ca(2+)](i) response in the renal tubule involves mechanically stimulated nucleotide release. This study investigated (1) the expression of P2 receptors in mouse medullary thick ascending limb (mTAL) using P2Y(2) receptor knockout (KO) mice, (2) whether flow increases induce [Ca(2+)](i) elevations in mTAL, and (3) whether this flow response is affected in mice that are deplete of the main purinergic receptor. [Ca(2+)](i) was imaged in perfused mTAL with fura-2 or fluo-4. It is shown that luminal and basolateral P2Y(2) receptors are the main purinergic receptor in this segment. Moreover, the data suggest presence of basolateral P2X receptors. Increases of tubular flow were imposed by promptly rising the inflow pressure, which triggered a marked increase of [Ca(2+)](i). This [Ca(2+)](i) response was significantly reduced in P2Y(2) receptor KO tubules (fura-2 ratio increase WT 0.44 +/- 0.09 [n = 28] versus KO 0.16 +/- 0.04 [n = 13]). Furthermore, the flow response was greatly inhibited with luminal and basolateral scavenging of extracellular ATP (apyrase 7.5 U/ml) or blockage of P2 receptors (suramin 300 microM). The flow response could still be elicited in the absence of extracellular Ca(2+). These results strongly suggest that increase of tubular flow elevates [Ca(2+)](i) in intact renal epithelia. This flow response is caused by release of bilateral nucleotides and subsequent activation of P2 receptors.


Heart rate responses to Taekwondo training in experienced practitioners.
The purpose of this study was to evaluate the heart rate (HR) responses of specific Taekwondo training activities, practiced by experienced practitioners in a natural training environment. Eight male experienced Taekwondo practitioners, with 3- 13 years (5.4 +/- 3.2 years) experience took part in a 5-day Taekwondo training camp. Continuous HR measures were recorded at 5-second intervals during 6 training sessions; each session was observed and notated, and a diary of training activities was recorded. The HR responses were assimilated into 8 fundamental training activities for analysis: elastics, technical combinations, step sparring, pad work, forms, basic techniques and forms, sparring drills, and free sparring. Taekwondo training elicited HR into 64.7-81.4% of HR maximum (%HRmax). Moderate relative exercise intensities (64.7-69.4%HRmax) were elicited by elastics, technical combinations, and step sparring. The remaining 5 training activities elicited hard relative exercise intensities (74.7-81.4%HRmax). One-way repeated-measures analysis of variance with post hoc analysis revealed that elastics, technical combinations, and step sparring elicited significantly lower relative intensities than the remaining training activities (p < 0.05). Furthermore, forms, basic techniques and forms, sparring drills, and free sparring elicited significantly higher relative intensities than the remaining training activities (p < 0.05). In conclusion, all Taekwondo training activities in this study seemed suitable for cardiovascular conditioning, although different training activities stressed the cardiovascular system to different degrees. Practically, this suggests coaches need to structure Taekwondo training sessions based not only on the technical and tactical needs of practitioners but also in a manner that enables sufficient cardiovascular conditioning for competition.


Few electron limit of n-type metal oxide semiconductor single electron transistors.
We report the electronic transport on n-type silicon single electron transistors (SETs) fabricated in complementary metal oxide semiconductor (CMOS) technology. The n-type metal oxide silicon SETs (n-MOSSETs) are built within a pre-industrial fully depleted silicon on insulator (FDSOI) technology with a silicon thickness down to 10 nm on 200 mm wafers. The nominal channel size of 20 × 20 nm(2) is obtained by employing electron beam lithography for active and gate level patterning. The Coulomb blockade stability diagram is precisely resolved at 4.2 K and it exhibits large addition energies of tens of meV. The confinement of the electrons in the quantum dot has been modeled by using a current spin density functional theory (CS-DFT) method. CMOS technology enables massive production of SETs for ultimate nanoelectronic and quantum variable based devices.


A rapid assessment framework for food system shocks: Lessons learned from COVID-19 in the Indo-Pacific region.
The frequency and severity of shocks to food systems is accelerating globally, exemplified by the current COVID-19 outbreak. In low- and middle-income countries, the impacts have exacerbated existing food system vulnerabilities and poverty. Governments and donors must respond quickly, but few tools are available that identify interventions to build food system resilience, or emerging opportunities for transformation. In this paper we reflect on the application of a systems-based rapid assessment which we applied across 11 Indo-Pacific countries in May-July 2020. Our approach was shaped by three design parameters: the integration of key informants' perspectives engaged remotely within the countries, applicability to diverse food systems and COVID-19 experiences across the region, and the consideration of food systems as complex systems. For the rapid assessment we adopted an analytical framework proposed by Allen and Prosperi (2016). To include a development lens, we added the analysis of vulnerable groups and their exposure, impacts, recovery potential and resilience, and pro-poor interventions. We concluded that the framework and approach facilitated integration and triangulation of disparate knowledge types and data to identify priority interventions and was sufficiently flexible to be applied across food systems, at both national, sub-national and commodity scales. The step-wise method was simple and enabled structured inquiry and reporting. Although the systems concepts appeared more easily transferrable to key informants in some countries than others, potentially transformational interventions were identified, and also some risks of maladaptation. We present a refined framework that emphasises analysis of political, economic and institutional drivers of exposure and vulnerability, the constraints that they pose for building recovery potential and resilience, and trade-offs amongst winners and losers inherent in proposed interventions.


Trends in antimicrobial resistance in bloodstream infection isolates at a large urban hospital in Malawi (1998-2016): a surveillance study.
Bacterial bloodstream infection is a common cause of morbidity and mortality in sub-Saharan Africa, yet few facilities are able to maintain long-term surveillance. The Malawi-Liverpool-Wellcome Trust Clinical Research Programme has done sentinel surveillance of bacteraemia since 1998. We report long-term trends in bloodstream infection and antimicrobial resistance from this surveillance. In this surveillance study, we analysed blood cultures that were routinely taken from adult and paediatric patients with fever or suspicion of sepsis admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi from 1998 to 2016. The hospital served an urban population of 920 000 in 2016, with 1000 beds, although occupancy often exceeds capacity. The hospital admits about 10 000 adults and 30 000 children each year. Antimicrobial susceptibility tests were done by the disc diffusion method according to British Society of Antimicrobial Chemotherapy guidelines. We used the Cochran-Armitage test for trend to examine trends in rates of antimicrobial resistance, and negative binomial regression to examine trends in icidence of bloodstream infection over time. Between Jan 1, 1998, and Dec 31, 2016, we isolated 29 183 pathogens from 194 539 blood cultures. Pathogen detection decreased significantly from 327·1/100 000 in 1998 to 120·2/100 000 in 2016 (p<0·0001). 13 366 (51·1%) of 26 174 bacterial isolates were resistant to the Malawian first-line antibiotics amoxicillin or penicillin, chloramphenicol, and co-trimoxazole; 68·3% of Gram-negative and 6·6% of Gram-positive pathogens. The proportions of non-Salmonella Enterobacteriaceae with extended spectrum beta-lactamase (ESBL) or fluoroquinolone resistance rose significantly after 2003 to 61·9% in 2016 (p<0·0001). Between 2003 and 2016, ESBL resistance rose from 0·7% to 30·3% in Escherichia coli, from 11·8% to 90·5% in Klebsiella spp and from 30·4% to 71·9% in other Enterobacteriaceae. Similarly, resistance to ciprofloxacin rose from 2·5% to 31·1% in E coli, from 1·7% to 70·2% in Klebsiella spp and from 5·9% to 68·8% in other Enterobacteriaceae. By contrast, more than 92·0% of common Gram-positive pathogens remain susceptible to either penicillin or chloramphenicol. Meticillin-resistant Staphylococcus aureus (MRSA) was first reported in 1998 at 7·7% and represented 18·4% of S aureus isolates in 2016. The rapid expansion of ESBL and fluoroquinolone resistance among common Gram-negative pathogens, and the emergence of MRSA, highlight the growing challenge of bloodstream infections that are effectively impossible to treat in this resource-limited setting. Wellcome Trust, H3ABionet, Southern Africa Consortium for Research Excellence (SACORE).


Molecular Cytogenetics Guides Massively Parallel Sequencing of a Radiation-Induced Chromosome Translocation in Human Cells.
Chromosome rearrangements are large-scale structural variants that are recognized drivers of oncogenic events in cancers of all types. Cytogenetics allows for their rapid, genome-wide detection, but does not provide gene-level resolution. Massively parallel sequencing (MPS) promises DNA sequence-level characterization of the specific breakpoints involved, but is strongly influenced by bioinformatics filters that affect detection efficiency. We sought to characterize the breakpoint junctions of chromosomal translocations and inversions in the clonal derivatives of human cells exposed to ionizing radiation. Here, we describe the first successful use of DNA paired-end analysis to locate and sequence across the breakpoint junctions of a radiation-induced reciprocal translocation. The analyses employed, with varying degrees of success, several well-known bioinformatics algorithms, a task made difficult by the involvement of repetitive DNA sequences. As for underlying mechanisms, the results of Sanger sequencing suggested that the translocation in question was likely formed via microhomology-mediated non-homologous end joining (mmNHEJ). To our knowledge, this represents the first use of MPS to characterize the breakpoint junctions of a radiation-induced chromosomal translocation in human cells. Curiously, these same approaches were unsuccessful when applied to the analysis of inversions previously identified by directional genomic hybridization (dGH). We conclude that molecular cytogenetics continues to provide critical guidance for structural variant discovery, validation and in "tuning" analysis filters to enable robust breakpoint identification at the base pair level.


Antibiotic-associated diarrhea in a Turkish outpatient population: investigation of 288 cases.
Oral antibiotics are often prescribed, especially for respiratory tract infections in the community. The widespread use of broad-spectrum antibiotics causes an increased incidence of antibiotic-associated diarrhea (AAD). Although AAD has been studied in hospitalized patients, there is little available information concerning the characteristics of AAD in outpatient populations. The aim of this study was to investigate the clinical and laboratory findings of adult patients with community-acquired AAD. Between June 1998 and December 2003, the clinical reports of 288 patients were retrospectively reviewed. We observed that the duration between the start of antibiotic treatment and onset of symptoms was 7 days in most of the patients (86%), and the mean time was 9+/-1.0 days. The diarrhea was self-limited in all cases and mean duration of symptoms was 3 (+/-1.0) days (1-7 days). The most common symptoms were abdominal discomfort and tenesmus (61.1%), while elevated WBC counts and fever were detected rarely. We were able to perform microbiologic investigations in only 88 patients because of the financial problems. Of the 88 stool specimens tested, none of them were positive for pathogenic bacterial growth or toxin A production.


Disease Recapture Rates After Medication Discontinuation and Flare in Juvenile Idiopathic Arthritis: An Observational Study Within the Childhood Arthritis and Rheumatology Research Alliance Registry.
Children with well-controlled juvenile idiopathic arthritis (JIA) frequently experience flares after medication discontinuation, but the outcomes of these flares have not been well described. The objective of this study was to characterize the rates and predictors of disease recapture among children with JIA who restarted medication to treat disease flare. Children with JIA who discontinued conventional synthetic or biologic disease-modifying antirheumatic drugs for well-controlled disease but subsequently experienced a flare and restarted medication were identified from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) registry. The primary outcome was inactive disease (ID) (physician global assessment <1 and active joint count = 0) 6 months after flare. A total of 333 patients had complete data for ID at 6 months after flare. The recapture rate for the cohort was 55%, ranging from 47% (persistent oligoarthritis) to 69% (systemic arthritis) (P = 0.4). Approximately 67% of children achieved ID by 12 months. In the multivariable model, history and reinitiation of biologic drugs were associated with increased odds of successful recapture (odds ratio [OR] 4.79 [95% confidence interval (95% CI) 1.22-18.78] and OR 2.74 [95% CI 1.62-4.63], respectively). Number of joints with limited range of motion was associated with decreased odds (OR 0.83 per 1 joint increase [95% CI 0.72-0.95]). Approximately half of JIA flares post-discontinuation were recaptured within 6 months, but rates of recapture varied across JIA categories. These findings inform shared decision-making for patients, families, and clinicians regarding the risks and benefits of medication discontinuation. Better understanding of biologic predictors of successful recapture in JIA are needed.


Ocepeia (Middle Paleocene of Morocco): the oldest skull of an afrotherian mammal.
While key early(iest) fossils were recently discovered for several crown afrotherian mammal orders, basal afrotherians, e.g., early Cenozoic species that comprise sister taxa to Paenungulata, Afroinsectiphilia or Afrotheria, are nearly unknown, especially in Africa. Possible stem condylarth-like relatives of the Paenungulata (hyraxes, sea-cows, elephants) include only Abdounodus hamdii and Ocepeia daouiensis from the Selandian of Ouled Abdoun Basin, Morocco, both previously only documented by lower teeth. Here, we describe new fossils of Ocepeia, including O.grandis n. sp., and a sub-complete skull of O. daouiensis, the first known before the Eocene for African placentals. O.daouiensis skull displays a remarkable mosaic of autapomophic, ungulate-like and generalized eutherian-like characters. Autapomorphies include striking anthropoid-like characters of the rostrum and dentition. Besides having a basically eutherian-like skull construction, Ocepeia daouiensis is characterized by ungulate-like, and especially paenungulate-like characters of skull and dentition (e.g., selenodonty). However, some plesiomorphies such as absence of hypocone exclude Ocepeia from crown Paenungulata. Such a combination of plesiomorphic and derived characters best fits with a stem position of Ocepeia relative to Paenungulata. In our cladistic analyses Ocepeia is included in Afrotheria, but its shared derived characters with paenungulates are not optimized as exclusive synapomorphies. Rather, within Afrotheria Ocepeia is reconstructed as more closely related to insectivore-like afroinsectiphilians (i.e., aardvarks, sengis, tenrecs, and golden moles) than to paenungulates. This results from conflict with undetected convergences of Paenungulata and Perissodactyla in our cladistic analysis, such as the shared bilophodonty. The selenodont pattern best supports the stem paenungulate position of Ocepeia; that, however, needs further support. The remarkable character mosaic of Ocepeia makes it the first known "transitional fossil" between insectivore-like and ungulate-like afrotherians. In addition, the autapomorphic family Ocepeiidae supports the old--earliest Tertiary or Cretaceous--endemic evolution of placentals in Africa, in contrast to hypotheses rooting afrotherians in Paleogene Laurasian "condylarths".


Phosphatidylinositol 3-kinase is involved in the protection of primary cultured human erythroid precursor cells from apoptosis.
Little is known about the physiologic role of phosphatidylinositol 3-kinase (PI-3K) in the development of erythrocytes. Previous studies have shown that the effects of the PI-3K inhibitor wortmannin on erythropoietin (EPO)-dependent cell lines differed depending on the cell type used. Wortmannin inhibited EPO-induced differentiation of some cell lines without affecting their proliferation; however, the EPO-induced proliferation of other cell lines was inhibited by wortmannin. In neither case were signs of apoptosis observed. We have previously reported that signaling in highly purified human colony forming units-erythroid (CFU-E), generated in vitro from CD34(+) cells, differed from that in EPO-dependent cell lines. In the current study, we examined the effects of a more specific PI-3K inhibitor (LY294002) on human CFU-E. We found that LY294002 dose-dependently inhibits the proliferation of erythroid progenitor cells with a half-maximal effect at 10 micromol/L LY294002. LY294002 at similar concentrations also induces apoptosis of these cells, as evidenced by the appearance of annexin V-binding cells and DNA fragmentation. The steady-state phosphorylation of AKT at Ser-473 that occurs as a result of PI-3K activation was also inhibited by LY294002 at similar concentrations, suggesting that the effects of LY294002 are specific. Interestingly, the acceleration of apoptosis by LY294002 was observed in the presence or absence of EPO. Further, deprivation of EPO resulted in accelerated apoptosis irrespective of the presence of LY294002. Our study confirms and extends the finding that signaling in human primary cultured erythroid cells is significantly different from that in EPO-dependent cell lines. These data suggest that PI-3K has an antiapoptotic role in erythroid progenitor cells. In addition, 2 different pathways for the protection of primary erythroid cells from apoptosis likely exist: 1 independent of EPO that is LY294002-sensitive and one that is EPO-dependent and at least partly insensitive to LY294002.


Design considerations for lithium-sulfur batteries: mass transport of lithium polysulfides.
Irreversible loss of soluble lithium polysulfides (LiPSs) is a major obstacle deteriorating the performance of lithium-sulfur batteries. Multiple innovative approaches have recently been developed to resolve these LiPS issues. Melt-diffusion of sulfur into porous carbon is a representative solution for preventing the diffusion out of LiPSs, which aims to coordinate the sulfur on the electrochemically active site, accordingly. However, it has been overlooked that the mass transport motion of LiPSs has a crucial role in achieving high-performance. In this paper, we highlight the importance of the mass transport of soluble sulfur in the cathode structure by introducing various starting materials, i.e., solid sulfur using melt-diffusion and a catholyte, using 3-dimensional ordered macroporous carbon. The capacity of the sulfur cathode using melt-diffusion is well conserved in carbon with small pores because LiPSs are slowly diffused away, however, the catholyte derived sulfur cathode shows superior performance in carbon with large pores due to their rapid mass transport. The comparison with the four different combinations that control the pore size and mass transport reveals that proper selection of the initial state of starting materials using porous carbons demonstrates the optimal cell performance.


One-dimensional nature of the magnetic fluctuations in YBa2Cu3O6.6
There is increasing evidence that inhomogeneous distributions of charge and spin--so-called 'striped phases'--play an important role in determining the properties of the high-temperature superconductors. For example, recent neutron-scattering measurements on the YBa2Cu3O(7-x) family of materials show both spin and charge fluctuations that are consistent with the striped-phase picture. But the fluctuations associated with a striped phase are expected to be one-dimensional, whereas the magnetic fluctuations observed to date appear to display two-dimensional symmetry. We show here that this apparent two-dimensionality results from measurements on twinned crystals, and that similar measurements on substantially detwinned crystals of YBa2Cu3O6.6 reveal the one-dimensional character of the magnetic fluctuations, thus greatly strengthening the striped-phase interpretation. Moreover, our results also suggest that superconductivity originates in charge stripes that extend along the b crystal axis, where the superfluid density is found to be substantially larger than for the a direction.


Association of hip and pelvic geometry with tibiofemoral osteoarthritis: multicenter osteoarthritis study (MOST).
Lateral tibiofemoral osteoarthritis (OA) is overall less common than medial tibiofemoral OA, but it is more prevalent in women. This may be explained by sex differences in hip and pelvic geometry. The aim of this study is to explore sex differences in hip and pelvic geometry and determine if such parameters are associated with the presence of compartment-specific knee OA. This case-control study reports on 1,328 hips/knees from 664 participants and is an ancillary to the Multicenter Osteoarthritis Study (MOST). Of the 1,328 knees, 219 had lateral OA, 260 medial OA, and 849 no OA. Hip and pelvic measurements were taken from full-limb radiographs on the ipsilateral side of the knee of interest. After adjusting for covariates, means were compared between sexes and also between knees with medial and lateral OA vs no OA using separate regression models. Women were shown to have a reduced femoral offset (FO) (mean 40.9 mm vs 45.9 mm; P = 0.001) and more valgus neck-shaft angle (mean 128.4° vs 125.9°; P < 0.001) compared to men. Compared to those with no OA, knees with lateral OA were associated with a reduced FO (P = 0.012), increased height of hip centre (HHC) (P = 0.003), more valgus neck-shaft angle (P = 0.042), and increased abductor angle (P = 0.031). Knees with medial OA were associated with a more varus neck-shaft angle (P = 0.043) and a decreased abductor angle (P = 0.003). These data suggest anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA.


Regulation of COX2 expression in mouse mammary tumor cells controls bone metastasis and PGE2-induction of regulatory T cell migration.
The targeting of the immune system through immunotherapies to prevent tumor tolerance and immune suppression are at the front lines of breast cancer treatment and research. Human and laboratory studies have attributed breast cancer progression and metastasis to secondary organs such as the bone, to a number of factors, including elevated levels of prostaglandin E2 (PGE2) and the enzyme responsible for its production, cyclooxygenase 2 (COX2). Due to the strong connection of COX2 with immune function, we focused on understanding how variance in COX2 expression manipulates the immune profile in a syngeneic, and immune-competent, mouse model of breast cancer. Though there have been correlative findings linking elevated levels of COX2 and Tregs in other cancer models, we sought to elucidate the mechanisms by which these immuno-suppressive cells are recruited to breast tumor and the means by which they promote tumor tolerance. To elucidate the mechanisms by which exacerbated COX2 expression potentiates metastasis we genetically manipulated non-metastatic mammary tumor cells (TM40D) to over-express COX2 (TM40D-COX2). Over-expression of COX2 in this mouse breast cancer model resulted in an increase in bone metastasis (an observation that was ablated following suppression of COX2 expression) in addition to an exacerbated Treg recruitment in the primary tumor. Interestingly, other immune-suppressive leukocytes, such as myeloid derived suppressor cells, were not altered in the primary tumor or the circulation. Elevated levels of PGE2 by tumor cells can directly recruit CD4+CD25+ cells through interactions with their EP2 and/or EP4 receptors, an effect that was blocked using anti-PGE2 antibody. Furthermore, increased Treg recruitment to the primary tumor contributed to the greater levels of apoptotic CD8+ T cells in the TM40D-COX2 tumors. Due to the systemic effects of COX2 inhibitors, we propose targeting specific EP receptors as therapeutic interventions to breast cancer progression.


Anti-Arthritic Effect Of Thymoquinone In Comparison With Methotrexate On Pristane Induced Arthritis In Female Sprague Dawley Rats.
Rheumatoid arthritis inflammatory joint disease which is chronic in nature. Since long various researches are carried out to find the remedy of this disease but still a lot of work needed to be done. This comparative study was performed from March to August 2013 at Postgraduate Medical Institute, Lahore. A total of thirty-two female Sprague-Dawley rats were randomly divided into four equal groups (n=8); group A was kept as healthy control, group B was kept as positive control, group C was treated with thymoquinone and group D was treated with methotrexate. Arthritis developed within two weeks in group B, group C and group D after giving a single shot of pristane intradermally. Treatment was started on day 15. At day 30 (time of dissection) paw weight and histopathological sections of ankle joints of all the animals were taken. The results shown significant rise in paw weight and score of histopathological parameters in group B, group C and group D when compared with healthy control rats. Thymoquinone and methotrexate treated groups shown reduction in paw weight and score of histopathological parameters when compared to positive control rats with p-value 0.001each. The difference between groups C and D was insignificant (p-value 0.062). Study results supported the anti-inflammatory and disease modifying activities of thymoquinone as it significantly reduces both paw weight and histological parameters of joint inflammation.


Exceptionalism as the rule? U.S. health policy innovation and cross-national learning.
American health care reformers, who often look to other nations for models of desirable health systems, are often surprised nowadays by cross-national infatuation with health policy innovations minted in the United States. American innovations appeal to policy makers abroad as they struggle with cost pressures, distinguish knowledge about how health systems work, and deal with changing images of what constitutes good public policy. These strategems are adapted, not adopted; however, the premises and practices with which other nations follow American directions differ deeply from those in the United States. Ironically, even cross-national experiments may end up offering instructive policy "rules" to the exceptionalist United States.


Substance-use screening and interventions in dental practices: survey of practice-based research network dentists regarding current practices, policies and barriers.
Dental visits represent an opportunity to identify and assist patients with unhealthy substance use, but little is known about how dentists are addressing patients' use of tobacco, alcohol and illicit drugs. The authors surveyed dentists to learn about the role their practices might play in providing substance-use screening and interventions. The authors distributed a 41-item Web-based survey to all 210 dentists active in the Practitioners Engaged in Applied Research and Learning Network, a practice-based research network. The questionnaire assessed dental practices' policies and current practices, attitudes and perceived barriers to providing services for tobacco, alcohol and illicit drug use. One hundred forty-three dentists completed the survey (68 percent response rate). Although screening was common, fewer dentists reported that they were providing follow-up counseling or referrals for substance use. Insufficient knowledge or training was the most frequently cited barrier to intervention. Many dentists reported they would offer assistance for use of tobacco (67 percent) or alcohol or illicit drugs (52 percent) if reimbursed; respondents who treated publicly insured patients were more likely to reply that they would offer this assistance. Dentists recognize the importance of screening for substance use, but they lack the clinical training and practice-based systems focused on substance use that could facilitate intervention. Practical Implications. The results of this study indicate that dentists may be willing to address substance use among patients, including use of alcohol and illicit drugs in addition to tobacco, if barriers are reduced through changes in reimbursement, education and systems-level support.