A novel low-temperature resistive NO gas sensor based on InGaN/GaN multi-quantum well-embedded p-i-n GaN nanorods.
In gas sensors, metal oxide semiconductors have been considered as favorable resistive-type toxic gas sensing materials. However, the higher temperature operation of metal oxides becomes a barrier for their wide range of applications in explosive and flammable gas environments. In this regard, great efforts have been devoted to reducing the operating temperature of the sensor. We demonstrated a chemical resistor-type NO gas sensor based on p-i-n GaN nanorods (NRs) consisting of InGaN/GaN multi-quantum wells (MQW). The sensor exhibited superior NO gas sensing performance to p-type GaN NRs. Furthermore, it also showed a remarkably improved response and fast recovery under UV irradiation (λ = 367 nm) of different UV intensities (7 to 20 mw cm-2) under reverse bias. The sensing performance of MQW-embedded p-i-n GaN NRs was enhanced with the boosted response by 4-fold at 35 °C under UV irradiation. The significant decrease in the resistance of the sensor under UV irradiation was mainly due to the extraction of photo-generated carriers under reverse bias, which can enhance the ionization of oxygen molecules. In addition, the effect of relative humidity (30%-60%) on the gas sensing performance was also manifested in this study. The selectivity of the sensor was determined by using other gases (NO, NO2, O2, NH3, H2S, CO, and H2), which exhibited a low response towards all tested gases other than NO. The experimental results demonstrated that p-i-n GaN NRs with InGaN/GaN MQW is a promising material for the detection of NO gas. Specific emphasis was laid on the enhanced response of p-i-n GaN NRs in reverse bias under UV irradiation.


Infectious disease hospitalizations in the United States.
Infectious diseases (IDs) cause widespread morbidity and mortality. We describe the epidemiology of ID hospitalizations in the United States with use of a nationally representative database. First-listed ID hospitalizations in the United States were analyzed using the Nationwide Inpatient Sample for 1998-2006. Hospitalization rates were calculated overall for IDs and for specific ID groups. An estimated 40,085,978 (standard error, 255,418) hospitalizations with a first-listed ID occurred during 1998-2006, for an age-adjusted hospitalization rate of 154.4 (95% confidence interval, 153.3-155.5) hospitalizations per 10,000 persons. The rate increased slightly over the study period (152.5 [95% confidence interval, 149.6-155.4] in 1998 vs 162.2 [95% confidence interval, 158.7-165.5] in 2006); an increase was seen for both sexes, for older patients, and for Hispanic patients. Among those aged 5-39 years, female patients had a significantly higher hospitalization rate than did male patients; male patients had higher rates among the youngest children and adults aged > or = 40 years. Approximately 4.5 million hospital days and $865 billion in hospital charges were associated with primary ID hospitalizations over the study period. Lower respiratory tract infections were the most commonly listed ID (34.4%), followed by kidney, urinary tract, and bladder infections; cellulitis; and abdominal and rectal infections. The ID hospitalization rate increased during 1998-2006, reflecting an increase in ID hospitalizations among adults aged > or = 30 years, particularly older adults. Differences in trends and patterns of ID hospitalizations were noted by sex, age group, and race. Lower respiratory tract infections accounted for the largest proportion of ID hospitalizations. Future efforts should focus on preventive measures and improving early interventions for IDs.


Differentiation of Small (≤ 4 cm) Renal Masses on Multiphase Contrast-Enhanced CT by Deep Learning.
OBJECTIVE. This study evaluated the utility of a deep learning method for determining whether a small (≤ 4 cm) solid renal mass was benign or malignant on multiphase contrast-enhanced CT. MATERIALS AND METHODS. This retrospective study included 1807 image sets from 168 pathologically diagnosed small (≤ 4 cm) solid renal masses with four CT phases (unenhanced, corticomedullary, nephrogenic, and excretory) in 159 patients between 2012 and 2016. Masses were classified as malignant (n = 136) or benign (n = 32). The dataset was randomly divided into five subsets: four were used for augmentation and supervised training (48,832 images), and one was used for testing (281 images). The Inception-v3 architecture convolutional neural network (CNN) model was used. The AUC for malignancy and accuracy at optimal cutoff values of output data were evaluated in six different CNN models. Multivariate logistic regression analysis was also performed. RESULTS. Malignant and benign lesions showed no significant difference of size. The AUC value of corticomedullary phase was higher than that of other phases (corticomedullary vs excretory, p = 0.022). The highest accuracy (88%) was achieved in corticomedullary phase images. Multivariate analysis revealed that the CNN model of corticomedullary phase was a significant predictor for malignancy compared with other CNN models, age, sex, and lesion size. CONCLUSION. A deep learning method with a CNN allowed acceptable differentiation of small (≤ 4 cm) solid renal masses in dynamic CT images, especially in the corticomedullary image model.


A role for nuclear lamins in nuclear envelope assembly.
The molecular interactions responsible for nuclear envelope assembly after mitosis are not well understood. In this study, we demonstrate that a peptide consisting of the COOH-terminal domain of Xenopus lamin B3 (LB3T) prevents nuclear envelope assembly in Xenopus interphase extracts. Specifically, LB3T inhibits chromatin decondensation and blocks the formation of both the nuclear lamina-pore complex and nuclear membranes. Under these conditions, some vesicles bind to the peripheral regions of the chromatin. These "nonfusogenic" vesicles lack lamin B3 (LB3) and do not bind LB3T; however, "fusogenic" vesicles containing LB3 can bind LB3T, which blocks their association with chromatin and, subsequently, nuclear membrane assembly. LB3T also binds to chromatin in the absence of interphase extract, but only in the presence of purified LB3. Additionally, we show that LB3T inhibits normal lamin polymerization in vitro. These findings suggest that lamin polymerization is required for both chromatin decondensation and the binding of nuclear membrane precursors during the early stages of normal nuclear envelope assembly.


Improved allometric models to estimate the aboveground biomass of tropical trees.
Terrestrial carbon stock mapping is important for the successful implementation of climate change mitigation policies. Its accuracy depends on the availability of reliable allometric models to infer oven-dry aboveground biomass of trees from census data. The degree of uncertainty associated with previously published pantropical aboveground biomass allometries is large. We analyzed a global database of directly harvested trees at 58 sites, spanning a wide range of climatic conditions and vegetation types (4004 trees ≥ 5 cm trunk diameter). When trunk diameter, total tree height, and wood specific gravity were included in the aboveground biomass model as covariates, a single model was found to hold across tropical vegetation types, with no detectable effect of region or environmental factors. The mean percent bias and variance of this model was only slightly higher than that of locally fitted models. Wood specific gravity was an important predictor of aboveground biomass, especially when including a much broader range of vegetation types than previous studies. The generic tree diameter-height relationship depended linearly on a bioclimatic stress variable E, which compounds indices of temperature variability, precipitation variability, and drought intensity. For cases in which total tree height is unavailable for aboveground biomass estimation, a pantropical model incorporating wood density, trunk diameter, and the variable E outperformed previously published models without height. However, to minimize bias, the development of locally derived diameter-height relationships is advised whenever possible. Both new allometric models should contribute to improve the accuracy of biomass assessment protocols in tropical vegetation types, and to advancing our understanding of architectural and evolutionary constraints on woody plant development.


Clusterin: a potential target for improving response to antiestrogens.
Antiestrogens represent the first line of therapy in the treatment of estrogen receptor-positive (ER+) breast cancer patients. Unfortunately, up to 40% of patients develop resistance associated with progression and frequently die for metastatic breast cancer. The molecular events leading to pharmacological resistance are not completely understood. We attempted to verify in an experimental model the role of cytoplasmic clusterin (CLU), a cytoprotective protein found to be up-regulated in antiestrogen-resistant patients, following neoadjuvant treatment with toremifene. The role of cytoplasmic clusterin in modulating response to two antiestrogens (toremifene and tamoxifen) was studied in two ER+ anti-estrogen-sensitive cell lines (MCF-7, 734B) and one ER+ antiestrogen-resistant cell line (T47D) using siRNA strategy. Resistant cells were characterised by higher levels of cytoplasmic clusterin than sensitive cells, and antiestrogen treatments up-regulated clusterin levels in both sensitive and resistant cell lines. Treatment with siRNA completely abolished cytoplasmic clusterin expression in all cell lines, but its down-regulation resulted in a significant decrease of cell growth only in the resistant line. We therefore concluded that: i) basal clusterin levels are higher in antiestrogen resistant cells, ii) clusterin is up-regulated following antiestrogen treatment independently of the sensitivity of the cell line, iii) down-regulation of cytoplasmic clusterin restores sensitivity to toremifene in the antiestrogen-resistant cell line. Such results support the concept that targeting CLU could represent a promising therapeutic strategy in association with antiestrogen treatment in breast cancer patients.


Emergent runaway into an avoidance area in a swarm of soldier crabs.
Emergent behavior that arises from a mass effect is one of the most striking aspects of collective animal groups. Investigating such behavior would be important in order to understand how individuals interact with their neighbors. Although there are many experiments that have used collective animals to investigate social learning or conflict between individuals and society such as that between a fish and a school, reports on mass effects are rare. In this study, we show that a swarm of soldier crabs could spontaneously enter a water pool, which are usually avoided, by forming densely populated part of a swarm at the edge of the water pool. Moreover, we show that the observed behavior can be explained by the model of collective behavior based on inherent noise that is individuals' different velocities in a directed group. Our results suggest that inherent noise, which is widely seen in collective animals, can contribute to formation and/or maintenance of a swarm and that the dense swarm can enter the pool by means of enhanced inherent noise.


Health Benefits of Carotenoids: A Role of Carotenoids in the Prevention of Non-Alcoholic Fatty Liver Disease.
Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases with a prevalence of ~25% worldwide. NAFLD includes simple hepatic steatosis, non-alcoholic steatohepatitis, fibrosis, and cirrhosis, which can further progress to hepatocellular carcinoma. Therefore, effective strategies for the prevention of NAFLD are needed. The pathogenesis of NAFLD is complicated due to diverse injury insults, such as fat accumulation, oxidative stress, inflammation, lipotoxicity, and apoptosis, which may act synergistically. Studies have shown that carotenoids, a natural group of isoprenoid pigments, prevent the development of NAFLD by exerting antioxidant, lipid-lowering, anti-inflammatory, anti-fibrotic, and insulin-sensitizing properties. This review summarizes the protective action of carotenoids, with primary focuses on astaxanthin, lycopene, β-carotene, β-cryptoxanthin, lutein, fucoxanthin, and crocetin, against the development and progression of NAFLD.


An Investigation of First-Year Students' and Lecturers' Expectations of University Education.
Transition from school to university can cause concern for many students. One issue is the gap between students' prior expectations and the realities of university life, which can cause significant distress, poor academic performance and increased drop-out rates if not managed effectively. Research has shown several similarities in the expectations of staff and students in regards to which factors determine academic success, but there is also evidence of dissonance. For example, staff consider independent study and critical evaluation as key factors, whereas students view feedback on drafts of work and support from staff as being most important. The aim of the current study was to determine what expectations students hold when starting university education, and what expectations university lecturers have of students entering university. Lecturers (n = 20) and first year students (n = 77) completed a series of questionnaires concerning their expectations of learning in HE (staff and students) and their approach to teaching (staff). Results revealed that students have largely realistic expectations of university. For example, the majority expected to be in charge of their own study. Some unrealistic expectations were also evident, e.g., most expected that teaching would be the same at university as it had been at school. The expectation that lecturers would provide detailed notes varied as a function of student age. Lecturers reported modifying their expectations of students and adapting their teaching approach according to year of study. Information-transmission/teacher-focused style was more common when teaching 1st year students; a more concept-changing/student-focused approach tended to be used when teaching 2nd year students (and above). Lecturer's expectations of student engagement did not differ according to year. Less experienced lecturers reported more negative expectations of student engagement than did experienced lecturers. In line with previous work, we observed overlap in expectations of staff and students, but some clear differences too.


Glenoid osteophyte and rotator cuff tears: an anatomic study.
The purpose of this study was to determine the morphologic characteristics of the glenoid osteophyte and its relationship to rotator cuff tears. Eighty-six cadaveric shoulders were studied. After inspection of cuff pathology, the glenoid was examined with soft x-rays. Histologically, degenerative changes of the articular cartilage and the labrum were assessed. There were 30 shoulders with rotator cuff tears (35%). Two types of glenoid osteophyte were identified: angular and hooked. Both osteophytes were commonly observed in the anterior to inferior portions of the glenoid. The length of hooked osteophytes was significantly greater in shoulders with full-thickness tears (2.7 +/- 2.2 mm [mean plus minus SD]) than in those with other cuff conditions (P =.0058). The hooked osteophyte was more commonly observed in shoulders with full-thickness tears (43%) and associated with degenerative changes of the cartilage and labrum. We conclude that the hooked osteophyte of the glenoid is characteristic in shoulders with full-thickness tears of the rotator cuff.


Carbodiimide-based benzimidazole library method.
Using carbodiimide reagents [1,3-diisopropylcarbodiimide or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)], we have developed a mild, generalized, one-pot method that delivers N-2-arylaminobenzimidazole esters from commercially available aryl isothiocyanates and o-phenylenediamines. Following saponification and acidifying, the benzimidazole acids were isolated in overall yields ranging from 75 to 88% from the starting aryl isothiocyanates. Nine benzimidazole acids were converted into a library consisting of 180 benzimidazole amides following EDC coupling with commercially available amines. The National Institute of General Medical Science will dispense these benzimidazole amides to academia groups for pilot scale biomedical studies. Using these mild conditions and environmentally safe reagents, we demonstrated that these pharmaceutically ornate heterocycles can also be constructed on solid support.


Orbiviruses and bunyaviruses from a seabird colony in Scotland.
Viruses isolated from ticks (Ixodes uriae) and a kittiwake (Rissa tridactyla) from a seabird colony at St. Abb's Head, Scotland, were shown by complement fixation tests (CFT) to be antigenically related to the Uukuniemi and Kemerovo serogroups. Electron microscopic examination of cell cultures infected with the Kemerovo group viruses revealed particles characteristic of orbiviruses, 72 +/- 3 nm in diam., with an inner core 37 +/- 3 nm in diam., in association with intracytoplasmic, densely staining granular areas, and with fibrillar and tubular structures. Cell cultures infected with the Uukuniemi group viruses revealed characteristic bunyavirus particles, 94 +/- 7 nm in diam., with a closely adherent envelope. Both orbi- and bunyaviruses were isolated from two tick pools and the kittiwake. A third tick pool contained an orbivirus which cross-reacted with the other isolates in CFT and fluorescent antibody tests, but was distinguished from them by neutralization tests.


The association of hormone replacement therapy and coronary calcium as determined by electron beam tomography.
Observational studies have shown that hormone replacement therapy (HRT) is associated with lower coronary heart disease (CHD), and animal studies demonstrate potent antiatherosclerotic estrogen effects. Paradoxically, recent clinical trials have not demonstrated a protective effect. This paradox may be explained by a healthy woman effect bias. Women using HRT have improved health outcomes unrelated to underlying atherosclerotic burden. Examination of the association between coronary calcium (CC), a marker of atherosclerotic plaque burden, and the use of HRT in postmenopausal women may help address this paradox. The study population comprised 641 asymptomatic postmenopausal women, 425 (66%) of whom were taking HRT. Data obtained from a self-administered questionnaire and blood samples were analyzed. Electron beam tomography (EBT) for CC was performed on each subject. Analysis of variance (ANOVA) was used to evaluate adjusted means. Independent t tests found that age, low-density lipoproteins (LDL), high-density lipoproteins (HDL), body mass index (BMI), vitamin use, coronary calcium score (CCS), coronary calcified volume (CCV), and the number of coronary calcium lesions (CCL) were significantly different between the HRT group and the non-HRT group. However, after controlling for potential confounders, no significant differences were observed in CCS, CCV, or the number of CCL between the HRT and non-HRT groups. Stratifying by BMI shows that obese/overweight women taking HRT have lower adjusted CCS and fewer CCL than the obese/overweight women not taking HRT. These findings demonstrate no association between HRT use and CCS, CCV, and CCL after adjusting for measurable confounders in postmenopausal women. Our failure to demonstrate an independent association between HRT use and a marker of atherosclerotic plaque burden suggests that a healthy woman effect may explain the beneficial association between HRT use and CHD in observational studies.


Object crowding in age-related macular degeneration.
Crowding, the phenomenon of impeded object identification due to clutter, is believed to be a key limiting factor of form vision in the peripheral visual field. The present study provides a characterization of object crowding in age-related macular degeneration (AMD) measured at the participants' respective preferred retinal loci with binocular viewing. Crowding was also measured in young and age-matched controls at the same retinal locations, using a fixation-contingent display paradigm to allow unlimited stimulus duration. With objects, the critical spacing of crowding for AMD participants was not substantially different from controls. However, baseline contrast energy thresholds in the noncrowded condition were four times that of the controls. Crowding further exacerbated deficits in contrast sensitivity to three times the normal crowding-induced contrast energy threshold elevation. These findings indicate that contrast-sensitivity deficit is a major limiting factor of object recognition for individuals with AMD, in addition to crowding. Focusing on this more tractable deficit of AMD may lead to more effective remediation and technological assistance.


What are the barriers to warfarin use in atrial fibrillation?: Development of a questionnaire.
Despite evidence of their benefit and efforts to increase usage, anticoagulation for stroke prophylaxis in atrial fibrillation (AF) patients remains underutilized. Previous surveys have assessed reasons for underuse of anticoagulation but have limitations including non-structured approach for eliciting barriers and use of clinical vignettes and not patient-level data. The objectives of this study were to develop a questionnaire to assess barriers to anticoagulation use for stroke prophylaxis in AF patients at a patient- and physician-level and to conduct a preliminary field-test of the instrument. Barriers to warfarin use were identified from a literature review, input from clinical experts, and a physician focus group. A sample of US physicians who treat AF patients completed the questionnaire. Physicians ranked their reluctance on a 1-10 scale (10 = very reluctant) in general to prescribe warfarin if a specific barrier was present in a patient and then indicated critical barriers to prescribing warfarin in a sample of their own AF patients not receiving warfarin. Forty-one barriers to warfarin use were identified and classified into 4 groups: patient medical characteristics (n = 17), health care system factors (n = 7), patient capability (n = 12), and patient preference (n = 5). Several new items were developed (e.g., difficulty in obtaining venous access), existing items were revised (e.g., timeframe for bleeding episodes subdivided into > or <or= 3 months), and multi-factorial barriers (e.g., dementia, epilepsy) were explored. The factor that most strongly influenced physicians' (n = 30) decisions not to prescribe warfarin was severe bleeding < 3 months ago (mean +/- SD: 9.2 +/- 1.3) while the most prevalent critical barriers to prescribing warfarin in specific AF patients (n = 24) was patient unwilling to undergo repeat testing (29%). This questionnaire has the potential to assist in better understanding barriers to warfarin use with a view to addressing and then overcoming warfarin underutilization. Preliminary data suggest patient preference and capabilities are at least as important as medical characteristics as barriers to prescribing warfarin in AF patients.


Rskalpha-actin/hIGF-1 transgenic mice with increased IGF-I in skeletal muscle and blood: impact on regeneration, denervation and muscular dystrophy.
Human IGF-I was over-expressed in skeletal muscles of C57/BL6xCBA mice under the control of the rat skeletal alpha-actin gene promoter. RT-PCR verified expression of the transgene in skeletal muscle but not in the liver of 1- and 21-day old heterozygote transgenic mice. The concentration of endogenous mouse IGF-I, measured by an immunoassay which does not detect human IGF-I, was not significantly different between transgenic mice and wild-type littermates (9.5 +/- 0.8 and 13.3 +/- 1.9 ng/g in muscle; 158.3 +/- 18.6 and 132.9 +/- 33.1 ng/ml in plasma, respectively). In contrast, quantitation with antibodies to human IGF-I showed an increase in IGF-I of about 100 ng/ml in plasma and 150 ng/g in muscle of transgenic mice at 6 months of age. Transgenic males, compared to their age matched wild-type littermates, had a significantly higher body weight (38.6 +/- 0.53 g vs. 35.8 +/- 0.64 g at 6 months of age; P < 0.001), dry fat-free carcass mass (5.51 +/- 0.085 vs. 5.08 +/- 0.092 g; P < 0.001) and myofibrillar protein mass (1.62 +/- 0.045 vs. 1.49 +/- 0.048 g; P < 0.05), although the fractional content of fat in the carcass was lower (167 +/- 7.0 vs. 197 +/- 7.7 g/kg wet weight) in transgenic animals. There was no evidence of muscle hypertrophy and no change in the proportion of slow type I myofibres in the limb muscles of Rskalpha-actin/hIGF-I transgenic mice at 3 or 6 months of age. Phenotypic changes in Rskalpha-actin/hIGF-I mice are likely to be due to systemic as well as autocrine/paracrine effects of overproduction of IGF-I due to expression of the human IGF-I transgene. The effect of muscle specific over-expression of Rskalpha-actin/hIGF-I transgene was tested on: (i) muscle regeneration in auto-transplanted whole muscle grafts; (ii) myofibre atrophy following sciatic nerve transection; and (iii) sarolemmal damage and myofibre necrosis in dystrophic mdx muscle. No beneficial effect of muscle specific over-expression of Rskalpha-actin/hIGF-I transgene was seen in these three experimental models.


Variation in Phenolic Chemistry in Zostera marina Seagrass Along Environmental Gradients.
Chemical ecology has been suggested as a less time-consuming and more cost-efficient monitoring tool of seagrass ecosystems than traditional methods. Phenolic chemistry in Zostera marina samples was analyzed against latitude, sea depth, sample position within a seagrass meadow (periphery or center) and wave exposure. Multivariate data analysis showed that rosmarinic acid correlated moderately positively with depth, while the flavonoids had an overall strong negative correlation with increasing depth-possibly reflecting lack of stress-induced conditions with increasing depth, rather than a different response to light conditions. At a molecular level, the flavonoids were separated into two groups; one group is well described by the variables of depth and wave exposure, and the other group that was not well described by these variables-the latter may reflect biosynthetic dependencies or other unrevealed factors. A higher flavonoid/rosmarinic acid ratio was seen in the periphery of a seagrass meadow, while the contrary ratio was seen in the center. This may reflect higher plant stress in the periphery of a meadow, and the flavonoid/rosmarinic acid ratio may provide a possible molecular index of seagrass ecosystem health. Further studies are needed before the full potential of using variation in phenolic chemistry as a seagrass ecosystem monitoring tool is established.


Arabidopsis CP12 mutants have reduced levels of phosphoribulokinase and impaired function of the Calvin-Benson cycle.
CP12 is a small, redox-sensitive protein, the most detailed understanding of which is the thioredoxin-mediated regulation of the Calvin-Benson cycle, where it facilitates the formation of a complex between glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and phosphoribulokinase (PRK) in response to changes in light intensity. In most organisms, CP12 proteins are encoded by small multigene families, where the importance of each individual CP12 gene in vivo has not yet been reported. We used Arabidopsis thaliana T-DNA mutants and RNAi transgenic lines with reduced levels of CP12 transcript to determine the relative importance of each of the CP12 genes. We found that single cp12-1, cp12-2, and cp12-3 mutants do not develop a severe photosynthetic or growth phenotype. In contrast, reductions of both CP12-1 and CP12-2 transcripts lead to reductions in photosynthetic capacity and to slower growth and reduced seed yield. No clear phenotype for CP12-3 was evident. Additionally, the levels of PRK protein are reduced in the cp12-1, cp12-1/2, and multiple mutants. Our results suggest that there is functional redundancy between CP12-1 and CP12-2 in Arabidopsis where these proteins have a role in determining the level of PRK in mature leaves and hence photosynthetic capacity.


A high-throughput fluorimetric assay for 2-hydroxyglutarate identifies Zaprinast as a glutaminase inhibitor.
Recently identified isocitrate dehydrogenase (IDH) mutations lead to the production of 2-hydroxyglutarate (2HG), an oncometabolite aberrantly elevated in selected cancers. We developed a facile and inexpensive fluorimetric microplate assay for the quantitation of 2HG and performed an unbiased small-molecule screen in live cells to identify compounds capable of perturbing 2HG production. Zaprinast, a phosphodiesterase 5 inhibitor, was identified as an efficacious modulator of 2HG production and confirmed to lower 2HG levels in vivo. The mechanism of action was not due to cGMP stabilization, but rather, profiling of metabolites upstream of mutant IDH1 pointed to targeted inhibition of the enzyme glutaminase (GLS). Zaprinast treatment reversed histone hypermethylation and soft-agar growth of IDH1-mutant cells, and treatment of glutamine-addicted pancreatic cancer cells reduced growth and sensitized cells to oxidative damage. Thus, Zaprinast is efficacious against glutamine metabolism and further establishes the therapeutic linkages between GLS and 2HG-mediated oncogenesis. Gain-of-function IDH mutations are common events in glioma, acute myelogenous leukemia, and other cancer types, which lead to the accumulation of the oncometabolite 2HG. We show that the drug Zaprinast is capable of reducing cellular 2HG levels by inhibiting the upstream enzyme GLS, thus identifying a new strategy to target 2HG production in selected IDH-mutant cancers.


Lability of drinking water treatment residuals (WTR) immobilized phosphorus: aging and pH effects.
Time constraints associated with conducting long-term (>20 yr) field experiments to test the stability of drinking water treatment residuals (WTR) sorbed phosphorus (P) inhibit improved understanding of the fate of sorbed P in soils when important soil properties (e.g., pH) change. We used artificially aged samples to evaluate aging and pH effects on lability of WTR-immobilized P. Artificial aging was achieved through incubation at elevated temperatures (46 or 70 degrees C) for 4.5 yr, and through repeated wetting and drying for 2 yr. Using a modified isotopic ((32)P) dilution technique, coupled with a stepwise acidification procedure, we monitored changes in labile P concentrations over time. This technique enabled evaluation of the effect of pH on the lability of WTR-immobilized P. Within the pH range of 4 to 7, WTR amendment, coupled with artificial aging, ultimately reduced labile P concentrations by > or = 75% relative to the control (no-WTR) samples. Soil samples with different physicochemical properties from two 7.5-yr-old, one-time WTR-amended field sites were utilized to validate the trends observed with the artificially aged samples. Despite the differences in physicochemical properties among the three (two field-aged and one artificially aged) soil samples, similar trends of aging and pH effects on lability of WTR-immobilized P were observed. Labile P concentrations of the WTR-amended field-aged samples of the two sites decreased 6 mo after WTR amendment and the reduction persisted for 7.5 yr, ultimately resulting in > or = 70% reduction, compared to the control plots. We conclude that WTR application is capable of reducing labile P concentration in P-impacted soils, doing so for a long time, and that within the commonly encountered range of pH values for agricultural soils WTR-immobilized P should be stable.


Use of the Preparedness for Caregiving Scale in Palliative Care: A Rasch Evaluation Study.
Studies have shown that family carers who feel more prepared for the caregiver role tend to have more favorable experiences. Valid and reliable methods are needed to identify family carers who may be less prepared for the role of supporting a person who needs palliative care. The aim of this study was to evaluate the measurement properties of the original English version and a Swedish version of the Preparedness for Caregiving Scale (PCS). The sample (n = 674) was taken from four different intervention studies from Australia and Sweden, all focused on improving family carers' feelings of preparedness. Family carers of patients receiving palliative home care were selected, and baseline data were used. The measurement properties of the PCS were evaluated using the Rasch model. Both the English and Swedish versions of the PCS exhibit sound measurement properties according to the Rasch model. The items in the PCS captured different levels of preparedness. The response categories were appropriate and corresponded to the level of preparedness. No significant differential item functioning for age and sex was detected. Three items demonstrated differential item functioning by language but did not impact interpretation of scores. Reliability was high (>0.90) according to the Person Separation Index. The PCS is valid for use among family carers in palliative care. Data provide support for its use across age and gender groups as well as across the two language versions.


Diagnostic pathology of selected diseases in wildlife.
The prompt detection and effective management of infectious disease in wildlife rely greatly on field diagnosis. Although clinical work is sometimes of value, the cornerstone of diagnosis is pathological examination (gross necropsy with supporting laboratory investigations). The approach and rationale to gross post-mortem examination are common to all species, despite possible significant differences in technique. Likewise, the principles of sampling are usually comparable, with emphasis on standardisation, the correct use of equipment, and consistency in methods of storage and transportation of specimens. However, the type of sample taken and the laboratory tests required differ, depending upon the circumstances and possible diagnosis. Retention of material is always important. The principles of diagnostic pathology are discussed, with reference to selected diseases, namely: mycobacteriosis, Rift Valley fever, rabies, spongiform encephalopathies, morbillivirus and poxvirus infections, viral encephalitides, West Nile virus infection and chytridiomycosis. The importance of being able to perform certain investigations in the field, efficiently and safely, is emphasised.


The path from mitochondrial ROS to aging runs through the mitochondrial permeability transition pore.
Excessive production of mitochondrial reactive oxygen species (mROS) is strongly associated with mitochondrial and cellular oxidative damage, aging, and degenerative diseases. However, mROS also induces pathways of protection of mitochondria that slow aging, inhibit cell death, and increase lifespan. Recent studies show that the activation of the mitochondrial permeability transition pore (mPTP), which is triggered by mROS and mitochondrial calcium overloading, is enhanced in aged animals and humans and in aging-related degenerative diseases. mPTP opening initiates further production and release of mROS that damage both mitochondrial and nuclear DNA, proteins, and phospholipids, and also releases matrix NAD that is hydrolyzed in the intermembrane space, thus contributing to the depletion of cellular NAD that accelerates aging. Oxidative damage to calcium transporters leads to calcium overload and more frequent opening of mPTP. Because aging enhances the opening of the mPTP and mPTP opening accelerates aging, we suggest that mPTP opening drives the progression of aging. Activation of the mPTP is regulated, directly and indirectly, not only by the mitochondrial protection pathways that are induced by mROS, but also by pro-apoptotic signals that are induced by DNA damage. We suggest that the integration of these contrasting signals by the mPTP largely determines the rate of cell aging and the initiation of cell death, and thus animal lifespan. The suggestion that the control of mPTP activation is critical for the progression of aging can explain the conflicting and confusing evidence regarding the beneficial and deleterious effects of mROS on health and lifespan.


Oxygen gas-filled microparticles provide intravenous oxygen delivery.
We have developed an injectable foam suspension containing self-assembling, lipid-based microparticles encapsulating a core of pure oxygen gas for intravenous injection. Prototype suspensions were manufactured to contain between 50 and 90 ml of oxygen gas per deciliter of suspension. Particle size was polydisperse, with a mean particle diameter between 2 and 4 μm. When mixed with human blood ex vivo, oxygen transfer from 70 volume % microparticles was complete within 4 s. When the microparticles were infused by intravenous injection into hypoxemic rabbits, arterial saturations increased within seconds to near-normal levels; this was followed by a decrease in oxygen tensions after stopping the infusions. The particles were also infused into rabbits undergoing 15 min of complete tracheal occlusion. Oxygen microparticles significantly decreased the degree of hypoxemia in these rabbits, and the incidence of cardiac arrest and organ injury was reduced compared to controls. The ability to administer oxygen and other gases directly to the bloodstream may represent a technique for short-term rescue of profoundly hypoxemic patients, to selectively augment oxygen delivery to at-risk organs, or for novel diagnostic techniques. Furthermore, the ability to titrate gas infusions rapidly may minimize oxygen-related toxicity.


Photonic metal-polymer resin nanocomposites with chiral nematic order.
Mesoporous resins with chiral nematic order were used as scaffolds to construct novel iridescent metal-polymer composites. Gold, silver and palladium nanoparticles were formed by an in situ reduction reaction. We have investigated the effects of concentration and time on the deposition. As a proof-of-concept, we demonstrate that this process can be extended to patterning photonic resins by inkjet printing.


Development and validation of a spike detection and classification algorithm aimed at implementation on hardware devices.
Neurons cultured in vitro on MicroElectrode Array (MEA) devices connect to each other, forming a network. To study electrophysiological activity and long term plasticity effects, long period recording and spike sorter methods are needed. Therefore, on-line and real time analysis, optimization of memory use and data transmission rate improvement become necessary. We developed an algorithm for amplitude-threshold spikes detection, whose performances were verified with (a) statistical analysis on both simulated and real signal and (b) Big O Notation. Moreover, we developed a PCA-hierarchical classifier, evaluated on simulated and real signal. Finally we proposed a spike detection hardware design on FPGA, whose feasibility was verified in terms of CLBs number, memory occupation and temporal requirements; once realized, it will be able to execute on-line detection and real time waveform analysis, reducing data storage problems.


Transmission of Toxoplasma gondii in Panama City, Panama: a five-year prospective cohort study of children, cats, rodents, birds, and soil.
A cohort of more than 500 children from Panama City, Panama was studied prospectively over five years for acquisition of antibody to Toxoplasma gondii. The direct agglutination test showed that 72 of 571 children seroconverted between one and six years of age, for a cumulative incidence of 12.6%. Children were examined by pediatricians quarterly, and illnesses that had occurred in the interval and their activities were noted on questionnaires. Thirty-eight variables were examined for their role as risk factors for seroconversion. There was a higher correlation between children's seroconversion and contact with dogs than with cats. Combinations of significant predictors without dogs explained only 67% of the seroconversions, but the same factors with dogs explained 90%. On the other hand, ingestion of raw or rare meat or eggs appeared to play no role in transmission. Cats were examined and 110 (45.6%) of 241 had Toxoplasma antibody on the first bleeding. Only two (0.5%) of 383 cat fecal specimens, when tested in mice, resulted in seroconversion. Ten (1.1%) of 924 soil samples resulted in seroconversion in mice that had been injected. Antibody to Toxoplasma was found in 52 (23.3%) of 226 rats (Rattus norvegicus) and two (0.035%) of 571 mice (Mus musculus). Two hundred sixteen birds of 16 different species were bled. Antibody to Toxoplasma was found in 13.4% of these birds, mostly in grackles, blue-gray tanagers, and doves. The rate of isolation of Toxoplasma was low: one of 23 in rats and three of 201 in birds. High relative risks (RRs) of transmission to children were predicted by contact histories with nursing dogs (RR = 5.8), weaned dogs (RR = 4.7), many flies (RR = 3.6), 6-12-month-old dogs (RR = 3.4), weaned cats (RR = 3.0), 6-12-month-old cats (RR = 2.7), nursing cats (RR = 2.5), much garbage (RR = 2.4), and many roaches (RR = 2.2). The high statistical correlation of dog contact with seroconversion in children suggests the possibility that dogs, by eating and rolling in cat feces, are instrumental in mechanically transmitting Toxoplasma infection. In addition, flies, and to a lesser extent, cockroaches, may have practically important roles in transmission.


A component of the ARC/Mediator complex required for TGF beta/Nodal signalling.
The transforming growth factor beta (TGF beta) family of cytokines, including Nodal, Activin and bone morphogenetic protein (BMP), have essential roles in development and tumorigenesis. TGF beta molecules activate the Smad family of signal transducers, which form complexes with specific DNA-binding proteins to regulate gene expression. Two discrete Smad-dependent signalling pathways have been identified: TGF beta, Activin and Nodal signal via the Smad2 (or Smad3)-Smad4 complex, whereas BMP signals via the Smad1-Smad4 complex. How distinct Smad complexes regulate specific gene expression is not fully understood. Here we show that ARC105, a component of the activator-recruited co-factor (ARC) complex or the metazoan Mediator complex, is essential for TGF beta/Activin/Nodal/Smad2/3 signal transduction. Expression of ARC105 stimulates Activin/Nodal/Smad2 signalling in Xenopus laevis embryos, inducing axis duplication and mesendoderm differentiation, and enhances TGF beta response in human cells. Depletion of ARC105 inhibits TGF beta/Activin/Nodal/Smad2/3 signalling and Xenopus axis formation, but not BMP/Smad1 signalling. ARC105 protein binds to Smad2/3-Smad4 in response to TGF beta and is recruited to Activin/Nodal-responsive promoters in chromatin in a Smad2-dependent fashion. Thus ARC105 is a specific and key ARC/Mediator component linking TGF beta/Activin/Nodal/Smad2/3 signalling to transcriptional activation.


Regional function analysis of left atrial appendage using motion estimation CT and risk of stroke in patients with atrial fibrillation.
The aim of this article is to determine the association between left atrial appendage (LAA) regional dysfunction using image-based motion-estimation computed tomography (CT) (iME) and a prior history of stroke or transient ischaemic attack (TIA) in patients with atrial fibrillation (AF). In this single-centre retrospective case-control study, among patients referred for AF ablation who underwent pre-ablation cardiac CT with retrospective ECG gating, we identified 18 patients with a prior history of stroke or TIA at the time of CT scan and 18 age- and gender-matched controls. All the patients were in sinus rhythm at the time of CT scan. Four-dimensional motion vector field was estimated from the CT images using iME. To assess myocardial deformation, area change ratio (A) and area change rate (AR) were calculated over the endocardial surface of the LAA. There was no significant difference in the baseline patient characteristics between the stroke/TIA group and the control group (67.6 ± 8.1 years old, 66.7% male, 16.7% persistent AF). LAA maximum (Amax; 23.8 ± 33.0 vs. 52.9 ± 41.2%, P = 0.02) and pre-atrial contraction area change ratio (ApreA; 13.7 ± 17.7 vs. 30.9 ± 29.2%, P = 0.04) were significantly lower in the stroke/TIA group than in the control group, respectively. The difference in LAA Amax and ApreA remained significant in multivariate analysis (P = 0.03 and P = 0.04, respectively). LAA regional dysfunction is associated with stroke/TIA in AF patients. Our results offer a basis for a prospective study to determine the role of LAA regional dysfunction by iME in predicting cerebrovascular events such as stroke or TIA.


Stereopsis from contrast envelopes.
We report two experiments concerning the site of the principal nonlinearity in second-order stereopsis. The first exploits the asymmetry in perceiving transparency with second-order stimuli found by Langley et al. (1998) (Proceedings of the Royal Society of London B, 265, 1837-1845) i.e. the product of a positive-valued contrast envelope and a mean-zero carrier grating can be seen transparently only when the disparities are consistent with the envelope appearing in front of the carrier. We measured the energy at the envelope frequencies that must be added in order to negate this asymmetry. We report that this amplitude can be predicted from the envelope sidebands and not from the magnitude of compressive pre-cortical nonlinearities measured by other researchers. In the second experiment, contrast threshold elevations were measured for the discrimination of envelope disparities following adaptation to sinusoidal gratings. It is reported that perception of the envelope's depth was affected most when the adapting grating was similar (in orientation and frequency) to the carrier, rather than to the contrast envelope. These results suggest that the principal nonlinearity in second-order stereopsis is cortical, occurring after orientation- and frequency-selective linear filtering.


The Association of Long-Term Exposure to Particulate Matter Air Pollution with Brain MRI Findings: The ARIC Study.
Increasing evidence links higher particulate matter (PM) air pollution exposure to late-life cognitive impairment. However, few studies have considered associations between direct estimates of long-term past exposures and brain MRI findings indicative of neurodegeneration or cerebrovascular disease. Our objective was to quantify the association between brain MRI findings and PM exposures approximately 5 to 20 y prior to MRI in the Atherosclerosis Risk in Communities (ARIC) study. ARIC is based in four U.S. sites: Washington County, Maryland; Minneapolis suburbs, Minnesota; Forsyth County, North Carolina; and Jackson, Mississippi. A subset of ARIC participants underwent 3T brain MRI in 2011-2013 (n=1,753). We estimated mean exposures to PM with an aerodynamic diameter less than 10 or 2.5μm (PM10 and PM2.5) in 1990-1998, 1999-2007, and 1990-2007 at the residential addresses of eligible participants with MRI data. We estimated site-specific associations between PM and brain MRI findings and used random-effect, inverse variance-weighted meta-analysis to combine them. In pooled analyses, higher mean PM2.5 and PM10 exposure in all time periods were associated with smaller deep-gray brain volumes, but not other MRI markers. Higher PM2.5 exposures were consistently associated with smaller total and regional brain volumes in Minnesota, but not elsewhere. Long-term past PM exposure in was not associated with markers of cerebrovascular disease. Higher long-term past PM exposures were associated with smaller deep-gray volumes overall, and higher PM2.5 exposures were associated with smaller brain volumes in the Minnesota site. Further work is needed to understand the sources of heterogeneity across sites. https://doi.org/10.1289/EHP2152.


Cross-talk between adherens junctions and desmosomes depends on plakoglobin.
Squamous epithelial cells have both adherens junctions and desmosomes. The ability of these cells to organize the desmosomal proteins into a functional structure depends upon their ability first to organize an adherens junction. Since the adherens junction and the desmosome are separate structures with different molecular make up, it is not immediately obvious why formation of an adherens junction is a prerequisite for the formation of a desmosome. The adherens junction is composed of a transmembrane classical cadherin (E-cadherin and/or P-cadherin in squamous epithelial cells) linked to either beta-catenin or plakoglobin, which is linked to alpha-catenin, which is linked to the actin cytoskeleton. The desmosome is composed of transmembrane proteins of the broad cadherin family (desmogleins and desmocollins) that are linked to the intermediate filament cytoskeleton, presumably through plakoglobin and desmoplakin. To begin to study the role of adherens junctions in the assembly of desmosomes, we produced an epithelial cell line that does not express classical cadherins and hence is unable to organize desmosomes, even though it retains the requisite desmosomal components. Transfection of E-cadherin and/or P-cadherin into this cell line did not restore the ability to organize desmosomes; however, overexpression of plakoglobin, along with E-cadherin, did permit desmosome organization. These data suggest that plakoglobin, which is the only known common component to both adherens junctions and desmosomes, must be linked to E-cadherin in the adherens junction before the cell can begin to assemble desmosomal components at regions of cell-cell contact. Although adherens junctions can form in the absence of plakoglobin, making use only of beta-catenin, such junctions cannot support the formation of desmosomes. Thus, we speculate that plakoglobin plays a signaling role in desmosome organization.


Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents.
Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of critical illness. We developed a population pharmacokinetic model of milrinone using nonlinear mixed-effects modeling in NONMEM to perform dose-exposure simulations in children with variable renal function. We included children aged <21 years who received intravenous milrinone per clinical care. Plasma milrinone concentrations were measured using a validated liquid chromatography-tandem mass spectrometry assay (range 1-5000 ng/mL). We performed dose-exposure simulations targeting steady-state therapeutic concentrations of 100-300 ng/mL previously established in adults and children with cardiac dysfunction. We simulated concentrations over 48 hours in typical subjects with decreasing creatinine clearance (CrCl), estimated using the updated bedside Schwartz equation. Seventy-four patients contributed 111 plasma samples (concentration range, 4-634 ng/mL). The median (range) postmenstrual age (PMA) was 3.7 years (0-18), and median weight (WT) was 13.1 kg (2.6-157.7). The median serum creatinine and CrCl were 0.5 mg/dL (0.1-3.1) and 117.2 mL/min/1.73 m2 (13.1-261.3), respectively. A 1-compartment model characterized the pharmacokinetic data well. The final model parameterization was: Clearance (L/h) = 15.9*(WT [kg] / 70)0.75 * (PMA1.12 / (67.71.12 +PMA1.12 )*(CrCl / 117)0.522 ; and Volume of Distribution (L) = 32.2*(WT [kg] / 70). A loading dose of 50 µg/kg followed by a continuous infusion of 0.5 µg/kg/min resulted in therapeutic concentrations, except when CrCl was severely impaired at ≤30 mL/min/1.73 m2 . In this setting, a 25 µg/kg loading dose and 0.25 µg/kg/min continuous infusion resulted in therapeutic exposures.


Interpreting human behavior from depositional rates and combustion features through the study of sedimentary microfacies at site Pinnacle Point 5-6, South Africa.
Using fine and coarse resolution geoarchaeological studies at the Middle Stone Age site of PP5-6 at Pinnacle Point, Mossel Bay, South Africa, we discovered different patterns of anthropogenic input and changes in behavior through time. Through the microfacies approach, we documented the various geogenic and anthropogenic processes that formed the deposits of the site. By deciphering large scale rate differences in the production of these microfacies we estimated anthropogenic input rates and therefore gained understanding of occupational duration and intensity. The PP5-6 sediments document occupations characterized by small groups and short visits during Marine Isotope Stage (MIS) 5. This part of the sequence is characterized by numerous single (and mostly intact) hearth structures in a roofspall-rich matrix. During this time the sea was very close to the site and the people were focused on exploiting the rocky shores. With the advent of the glacial conditions of MIS4, the occupation of the site became much more intense. The occurrence of thick palimpsests of burnt remains, sometimes disturbed by small-scale sedimentary gravity processes, supports this conclusion. As sea level dropped and the coastline retreated, the geogenic input shifted to predominately aeolian sediments, implying an exposed shelf probably associated with a rich but more distant coastal environment. The occupants of PP5-6 turned their preference to silcrete as a raw material and they began to make microlithic stone tools. Since sites dating to MIS4 are abundant in the Cape, we suggest that populations during MIS4 responded to glacial conditions with either demographic stability or growth as well as technological change.


Asymmetry of lateral lamella of the cribriform plate: a software-based analysis of coronal computed tomography and its clinical relevance in endoscopic sinus surgery.
Endoscopic sinus surgery is a known approach for sinonasal pathologies. Due to close proximity of sinuses to orbits and brain, surgeon should be aware of sinonasal anatomy and associated variations. The roof of ethmoid (fovea ethmoidalis) separates the ethmoidal cells from the anterior cranial fossa. Medially the fovea attaches to the lateral lamella of the cribriform plate, which is the thinnest bone of the skull base. Hence, it is at a high risk of getting damaged during surgery. To ascertain the quantitative analysis of height of lateral lamella according to Keros classification in the computed tomographic (CT) images of patients presenting to our clinic. It was retrospective review of 77 CT scans using computerized software known as picture archiving and communication system. The height of lateral lamella was examined for both sides and then classified according to Keros classification. Asymmetry between two sides was also reported. Keros type I was seen in 46 sides (29.8%), type II in 75 sides (48.7%) and type III was seen in 33 (21.4%) sides. Keros type I was seen in 38 sides in males and 8 sides in females. Type II was seen in 46 and 29 sides in males and females, respectively. Type III was seen in 18 sides in males and in 15 sides in females. Understanding of the anatomy of ethmoid roof with its possible variation is crucial to give the surgeon optimal information about the possible risk that one can face during the surgery. Hence dreadful complications can be avoided.


CarSite: identifying carbonylated sites of human proteins based on a one-sided selection resampling method.
Protein carbonylation is one of the most important biomarkers of oxidative protein damage and such protein damage is linked to various diseases and aging. It is thus vital that carbonylation sites are identified accurately. In this study, CarSite, a novel bioinformatics tool, was established to identify carbonylation sites in human proteins. The one-sided selection (OSS) resampling method was used to establish balanced training datasets and this resampling method is demonstrated to perform better than a Monte Carlo resampling method via 10-fold cross-validation tests on the Jia dataset. Moreover, the hybrid combination of position-specific amino acid propensity (PSAAP), composition of k-spaced amino acid pairs (CKSAAP), amino acid composition (AAC), and composition of hydrophobic and hydrophilic amino acids (CHHAA) was selected to optimize the performance of the predictor. On 10-fold cross-validation of the Jia dataset, CarSite obtained rates of sensitivity corresponding to K/P/R/T-type peptides of ∼21%, 22%, 19%, or 18% higher than those obtained by iCar-PseCp, respectively, which was previously considered as the best predictor for identifying carbonylation sites in human proteins. Furthermore, compared with other existing predictors, CarSite obtained much higher sensitivity and accuracy when tested on the same dataset.


Seed dispersal limitations shift over time in tropical forest restoration.
Past studies have shown that tropical forest regeneration on degraded farmlands is initially limited by lack of seed dispersal, but few studies have tracked changes in abundance and composition of seed rain past the first few years after land abandonment. We measured seed rain for 12 months in 10 6-9-year-old restoration sites and five mature, reference forests in southern Costa Rica in order to learn (1) if seed rain limitation persists past the first few years of regeneration; (2) how restoration treatments influence seed community structure and composition; and (3) whether seed rain limitation is contingent on landscape context. Each restoration site contained three 0.25-ha treatment plots: (1) a naturally regenerating control, (2) tree islands, and (3) a mixed-species tree plantation. Sites spanned a deforestation gradient with 9-89% forest area within 500 m around the treatment plots. Contrary to previous studies, we found that tree seeds were abundant and ubiquitous across all treatment plots (585.1 ± 142.0 seeds · m(-2) · yr(-1) [mean ± SE]), indicating that lack of seed rain ceased to limit forest regeneration within the first decade of recovery. Pioneer trees and shrubs comprised the vast majority of seeds, but compositional differences between restoration sites and reference forests were driven by rarer, large-seeded species. Large, animal-dispersed tree seeds were more abundant in tree islands (4.6 ± 2.9 seeds · m(-2) · yr(-1)) and plantations (5.8 ± 3.0 seeds · m(-2) · yr(-1)) than control plots (0.2 ± 0.1 seeds · m(-2) · yr(-1)), contributing to greater tree species richness in actively restored plots. Planted tree species accounted for < 1% of seeds. We found little evidence for landscape forest cover effects on seed rain, consistent with previous studies. We conclude that seed rain limitation shifted from an initial, complete lack of tree seeds to a specific limitation on large-seeded, mature forest species over the first decade. Although total seed abundance was equal among restoration treatments, tree plantations and tree islands continued to diversify seed rain communities compared to naturally regenerating controls. Compositional differences between regenerating plots and mature forests suggest that large-seeded tree species are appropriate candidates for enrichment planting.


Cannabis consumption as a prognostic factor in schizophrenia.
Data were analysed from 62 schizophrenic patients between 18 and 30 years of age, treated at the community mental health centres in Navarra, who had relapsed and then completed a one-year follow-up study. Factors influencing the course of illness during follow-up were: continuing cannabis consumption; previous cannabis intake; non-compliance with treatment; and stress.


Pushing the wrong buttons: men's and women's attitudes toward online and offline infidelity.
Despite current researchers' interest in the study of online sexual addiction, there is a dearth of research available on what constitutes online infidelity. This paper attempts to redress this balance by comparing 1,117 participants' attitudes toward online and offline acts of infidelity. A factor analysis was carried out that yielded three components of infidelity: sexual infidelity, emotional infidelity, and pornography. More importantly, this study revealed that online acts of betrayal do not fall into a discrete category of their own. A MANOVA was performed and revealed a statistically significant difference on the combined dependent variables for the interaction of gender by age, age by relationship status, and Internet sexual experience. The hypotheses were, in part, supported. However, counter to what was predicted, in the main younger people were more likely to rate sexual acts as acts of betrayal than older individuals. It is concluded here that individuals do perceive some online interactions to be acts of betrayal. In contrast to some researchers' claims, it is suggested here that we do need to consider how bodies are reconstructed online. Moreover, these results have important implications for any treatment rationale for infidelity (both online and offline).


Diagnosis of Schistosoma haematobium by detection of specific DNA fragments from filtered urine samples.
Definitive diagnosis of Schistosoma haematobium infection in adult patients is a clinically important challenge. Chronically infected adults pass few eggs in the urine, which are often missed when current diagnostic methods are used. In the work presented here, we report on an alternative diagnostic method based on presence of the S. haematobium-specific Dra 1, 121 bp repeat fragment in human urine. A novel method of collecting the urine specimens in the field and filtering them through heavy Whatman No. 3 paper was introduced. After drying, the samples remained viable for several months at room temperature. To test the potential use of this method, 89 urine specimens from school children in Kollo District, Niger, were examined. In all, 52 of 89 (58.4%) were positive for hematuria, 4 of 89 (49.4%) were positive for eggs, and 51 of 89 (57.3%) showed parasite-specific DNA. These were compared with 60 filtered urine specimens obtained from random samples of adults from two study sites in Nigeria, one endemic and one non-endemic for S. haematobium. In the 30 patients from the endemic site, all 10 samples with detectable eggs and 7 of the 20 egg-negative samples were DNA positive. It was concluded that the urine filter paper method was sufficiently sensitive to detect low and cryptic infections, that DNA detection was more sensitive than egg detection, and that the filtration method facilitated specimen collection and transport from the field.


Design of annular photonic crystal slabs.
We present the design of realistic annular photonic-crystal (APC) structures of finite thickness aiming to obtain a complete photonic bandgap (PBG). The APC is composed of dielectric rods and circular air holes in a triangular lattice such that each rod is centered within each hole. The optical and geometrical values of the structure are studied, and the interplay between various design parameters is highlighted. The coupled role of the inner-dielectric-rod radius, material types, and slab thickness is investigated. It is shown that the slab thickness is vital to obtain a complete photonic bandgap below the light line, and the specific value of the inner-dielectric-rod radius to sustain the maximum PBG if the hole radius is fixed at proper value is found.


Constitutive activity of NF-kappa B in myeloid cells drives pathogenicity of monocytes and macrophages during autoimmune neuroinflammation.
The NF-κB/REL-family of transcription factors plays a central role in coordinating the expression of a wide variety of genes controlling immune responses including autoimmunity of the central nervous system (CNS). The inactive form of NF-κB consists of a heterodimer which is complexed with its inhibitor, IκB. Conditional knockout-mice for IκBα in myeloid cells (lysMCreIκBα(fl/fl)) have been generated and are characterized by a constitutive activation of NF-κB proteins allowing the study of this transcription factor in myelin-oligodendrocyte-glycoprotein induced experimental autoimmune encephalomyelitis (MOG-EAE), a well established experimental model for autoimmune demyelination of the CNS.In comparison to controls, lysMCreIκBα(fl/fl) mice developed a more severe clinical course of EAE. Upon histological analysis on day 15 p.i., there was an over two fold increased infiltration of T-cells and macrophages/microglia. In addition, lysMCreIκBα(fl/fl) mice displayed an increased expression of the NF-κB dependent factor inducible nitric oxide synthase in inflamed lesions. These changes in the CNS are associated with increased numbers of CD11b positive splenocytes and a higher expression of Ly6c on monocytes in the periphery. Well in accordance with these changes in the myeloid cell compartment, there was an increased production of the monocyte cytokines interleukin(IL)-12 p70, IL-6 and IL-1beta in splenocytes. In contrast, production of the T-cell associated cytokines interferon gamma (IFN-gamma) and IL-17 was not influenced.In summary, myeloid cell derived NF-κB plays a crucial role in autoimmune inflammation of the CNS and drives a pathogenic role of monocytes and macrophages independently from T-cells.


An epidemiological assessment of problematic contacts to members of Congress.
In order to assess the nature of threat assessment activity pertaining to members of Congress, 4387 cases involving threatening and other problematic contact were analyzed. The cases were studied regarding subject characteristics, articulated motives, as well as several aspects of contact behavior in relation to approach behavior. Approachers were significantly less likely to have articulated threat language prior to or during their contacts and were also less likely to have stated a policy grievance (foreign or domestic) as the source of their concern. Further, approachers were substantially more likely to have expressed help seeking requests as part of their prior and approach-related contacts and were less likely to have had racial or sexualized content within their contacts. Approachers were also significantly more likely to have had a criminal record as well as displayed symptoms suggestive of major mental illness. Subjects engaging in approach behavior were also less likely to have used an alias, were less likely to be a direct constituent of the target and were more likely to have contacted multiple congressional targets. The implications for threat assessment activity are discussed.


Comparative morphological and morphometric description of the hominin calvaria from Bukuran (Sangiran, Central Java, Indonesia).
We describe the hominin skull (called here "Bukuran") discovered in the lower Kabuh (or "Bapang") series near Sendangbusik, from the Bukuran area in the Sangiran dome. The fossil, heavily mineralized, consists of the parieto-occipital and the left temporal, and the frontal bones. When combined, those two cranial parts represent a rather complete and well-preserved calvaria. Its stratigraphic position was established after the discovery. A detailed description is presented of the morphological and metric features of the Bukuran calvaria, and comparisons are made with Asian Homo erectus from Indonesia and China. The estimated cranial capacity of Bukuran, the general shape of its cranial vault, its ectocranial structures, and its morphological and metrical characters are in the range of Asian Homo erectus, and show clear affinities with other Indonesian members of the species. We discuss the evolutionary status of the Bukuran calvaria and its implication for hominin history on Java.


Induction of CYP3A4 by vinblastine: Role of the nuclear receptor NR1I2.
Several microtubule targeting agents are capable of inducing CYP3A4 via activation of the pregnane X receptor (PXR; NR1I2). To evaluate the CYP3A4 induction potential of vinblastine both clinically and in vitro and determine the involvement of the nuclear receptors NR1I2 and the constitutive androstane receptor (NR1I3). Midazolam pharmacokinetics were evaluated in 6 patients who were enrolled in a Phase 1/2 study of infusional vinblastine given in combination with the ABCB1 (P-glycoprotein) antagonist valspodar (PSC 833) and received the CYP3A4 phenotyping probe midazolam on more than 1 occasion. Genotyping was conducted in CYP3A4, CYP3A5, and ABCB1 to rule out potential pharmacogenetic influences. Clinical data were followed-up by Western blotting and reporter assays in HepG2 and NIH3T3 cells treated with vinblastine over a dose range of 150-4800 ng/mL for 48 hours. In 6 patients with cancer, vinblastine increased the median (95% CI) clearance of the CYP3A4 phenotyping probe midazolam from 21.7 L/h (12.6 to 28.1) to 32.3 L/h (17.3 to 53.9) (p = 0.0156, Wilcoxon signed-rank test). No obvious effect of polymorphisms in CYP3A4, CYP3A5, and ABCB1 on midazolam clearance was observed. In vitro, vinblastine induced CYP3A4 protein. Furthermore, cell-based reporter gene assays using transiently transfected HepG2 and NIH3T3 cells indicated that vinblastine (150-4800 ng/mL) weakly activated human and mouse full-length NR1I2, but had no influence on NR1I3. Collectively, these findings suggest that vinblastine is able to induce CYP3A4, at least in part, via an NR1I2-dependent mechanism, and thus has the potential to facilitate its own elimination and cause interactions with other CYP3A4 substrates.


Controlled electrochemical doping of graphene-based 3D nanoarchitecture electrodes for supercapacitors and capacitive deionisation.
Chemically-doped graphenes are promising electrode materials for energy storage and electrosorption applications. Here, an affordable electrochemical green process is introduced to dope graphene with nitrogen. The process is based on reversing the polarity of two identical graphene oxide (GO) electrodes in molten KCl-LiCl-Li3N. During the cathodic step, the oxygen functional groups on the GO surface are removed through direct electro-deoxidation reactions or a reaction with the deposited lithium. In the anodic step, nitrogen is adsorbed onto the surface of graphene and subsequently reacts to form nitrogen-doped graphene. The doping process is controllable, and graphene with up to 7.4 at% nitrogen can be produced. The electrochemically treated electrodes show a specific capacitance of 320 F g-1 in an aqueous KOH electrolyte and maintain 96% of this value after 10 000 cycles. The electrodes also display excellent electrosorption performance in capacitive deionisation devices with the salt removal efficiency reaching up to 18.6 mg g-1.


Overexpression of secreted frizzled-related protein 1 inhibits bone formation and attenuates parathyroid hormone bone anabolic effects.
Secreted frizzled-related protein 1 (sFRP1) is an antagonist of Wnt signaling, an important pathway in maintaining bone homeostasis. In this study we evaluated the skeletal phenotype of mice overexpressing sFRP1 (sFRP1 Tg) and the interaction of parathyroid hormone (PTH) treatment and sFRP1 (over)expression. Bone mass and microarchitecture were measured by micro-computed tomography (microCT). Osteoblastic and osteoclastic cell maturation and function were assessed in primary bone marrow cell cultures. Bone turnover was assessed by biochemical markers and dynamic bone histomorphometry. Real-time PCR was used to monitor the expression of several genes that regulate osteoblast maturation and function in whole bone. We found that trabecular bone mass measurements in distal femurs and lumbar vertebral bodies were 22% and 51% lower in female and 9% and 33% lower in male sFRP1 Tg mice, respectively, compared with wild-type (WT) controls at 3 months of age. Genes associated with osteoblast maturation and function, serum bone formation markers, and surface based bone formation were significantly decreased in sFRP1 Tg mice of both sexes. Bone resorption was similar between sFRP1 Tg and WT females and was higher in sFRP1 Tg male mice. Treatment with hPTH(1-34) (40 microg/kg/d) for 2 weeks increased trabecular bone volume in WT mice (females: +30% to 50%; males: +35% to 150%) compared with sFRP1 Tg mice (females: +5%; males: +18% to 54%). Percentage increases in bone formation also were lower in PTH-treated sFRP1 Tg mice compared with PTH-treated WT mice. In conclusion, overexpression of sFRP1 inhibited bone formation as well as attenuated PTH anabolic action on bone. The gender differences in the bone phenotype of the sFRP1 Tg animal warrants further investigation.


Down myeloid disorders: a paradigm for childhood preleukaemia and leukaemia and insights into normal megakaryopoiesis.
Newborns and children with Down Syndrome are predisposed to a range of blood disorders, which include acute lymphoblastic leukaemia and acute megakaryocytic leukaemia (AMKL). Over the last four years there has been considerable progress in our understanding of DS AMKL. Like other childhood leukaemias DS AMKL is initiated in utero and can present in the neonatal period as a clinically overt preleukaemic condition, transient myeloproliferative disorder (TMD). In addition to trisomy 21, fetal haemopoietic progenitors acquire N-terminal truncating mutations in the key megakaryocyte-erythroid transcription factor GATA1. These are the minimum required events for TMD to develop. In approximately 30% of TMD patients, additional as yet unidentified (epi)genetic mutations are required for progression to AMKL. Thus, DS TMD and AMKL provide a unique model of childhood leukaemia where the preleukaemic and leukaemic phases are ascertainable and separable allowing distinct steps in leukaemogenesis to be studied individually. These findings also have implications for the clinical management of DS TMD and AMKL specifically and also of childhood leukaemia more generally.


Effects of transplacental exposure to environmental pollutants on birth outcomes in a multiethnic population.
Inner-city, minority populations are high-risk groups for adverse birth outcomes and also are more likely to be exposed to environmental contaminants, including environmental tobacco smoke (ETS), polycyclic aromatic hydrocarbons (PAHs), and pesticides. In a sample of 263 nonsmoking African-American and Dominican women, we evaluated the effects on birth outcomes of prenatal exposure to airborne PAHs monitored during pregnancy by personal air sampling, along with ETS estimated by plasma cotinine, and an organophosphate pesticide (OP) estimated by plasma chlorpyrifos (CPF). Plasma CPF was used as a covariate because it was the most often detected in plasma and was highly correlated with other pesticides frequently detected in plasma. Among African Americans, high prenatal exposure to PAHs was associated with lower birth weight (p = 0.003) and smaller head circumference (p = 0.01) after adjusting for potential confounders. CPF was associated with decreased birth weight and birth length overall (p = 0.01 and p = 0.003, respectively) and with lower birth weight among African Americans (p = 0.04) and reduced birth length in Dominicans (p < 0.001), and was therefore included as a covariate in the model with PAH. After controlling for CPF, relationships between PAHs and birth outcomes were essentially unchanged. In this analysis, PAHs and CPF appear to be significant independent determinants of birth outcomes. Further analyses of pesticides will be carried out. Possible explanations of the failure to find a significant effect of PAHs in the Hispanic subsample are discussed. This study provides evidence that environmental pollutants at levels currently encountered in New York City adversely affect fetal development.


Randomized trial of treatment of amblyopia in children aged 7 to 17 years.
To evaluate the effectiveness of treatment of amblyopia in children aged 7 to 17 years. At 49 clinical sites, 507 patients with amblyopic eye visual acuity ranging from 20/40 to 20/400 were provided with optimal optical correction and then randomized to a treatment group (2-6 hours per day of prescribed patching combined with near visual activities for all patients plus atropine sulfate for children aged 7 to 12 years) or an optical correction group (optical correction alone). Patients whose amblyopic eye acuity improved 10 or more letters (> or =2 lines) by 24 weeks were considered responders. In the 7- to 12-year-olds (n = 404), 53% of the treatment group were responders compared with 25% of the optical correction group (P<.001). In the 13- to 17-year-olds (n = 103), the responder rates were 25% and 23%, respectively, overall (adjusted P = .22) but 47% and 20%, respectively, among patients not previously treated with patching and/or atropine for amblyopia (adjusted P = .03). Most patients, including responders, were left with a residual visual acuity deficit. Amblyopia improves with optical correction alone in about one fourth of patients aged 7 to 17 years, although most patients who are initially treated with optical correction alone will require additional treatment for amblyopia. For patients aged 7 to 12 years, prescribing 2 to 6 hours per day of patching with near visual activities and atropine can improve visual acuity even if the amblyopia has been previously treated. For patients 13 to 17 years, prescribing patching 2 to 6 hours per day with near visual activities may improve visual acuity when amblyopia has not been previously treated but appears to be of little benefit if amblyopia was previously treated with patching. We do not yet know whether visual acuity improvement will be sustained once treatment is discontinued; therefore, conclusions regarding the long-term benefit of treatment and the development of treatment recommendations for amblyopia in children 7 years and older await the results of a follow-up study we are conducting on the patients who responded to treatment.


Registered nurses' everyday activities in municipal health care: a study of diaries.
This study described the work content of registered nurses (RNs) employed in municipal health care. Diary notes of three working days from 34 RNs were analysed using content analysis, and a total of 3185 activities were identified. Of these, 2807 were analysed further and grouped by comparing similarities and differences. The content of the RNs' nursing activities consisted of assessing health, giving treatments and conducting check-ups, handling pharmaceuticals and teaching. In the administration category, the content comprised planning and reporting, followed by documentation. The RNs' role in municipal health care is consultative, which reinforces their need for competence in advanced nursing, as well as in leadership and pedagogy. RNs mostly work without colleagues and they are responsible for many seriously ill patients. In order to be confident in providing qualified nursing, specialist nursing education in elderly care is needed.


Changes in heterosubtypic antibody responses during the first year of the 2009 A(H1N1) influenza pandemic.
Seropositivity to avian influenza (AI) via low-level antibody titers has been reported in the general population and poultry-exposed individuals, raising the question whether these findings reflect true infection with AI or cross-reactivity. Here we investigated serological profiles against human and avian influenza viruses in the general population using a protein microarray platform. We hypothesized that higher antibody diversity across recent H1 and H3 influenza viruses would be associated with heterosubtypic reactivity to older pandemic- and AI viruses. We found significant heterogeneity in antibody profiles. Increased antibody diversity to seasonal influenza viruses was associated with low-level heterosubtypic antibodies to H9 and H7, but not to H5 AI virus. Individuals exposed to the recent 2009 A(H1N1) pandemic showed higher heterosubtypic reactivity. We show that there is a complex interplay between prior exposures to seasonal and recent pandemic influenza viruses and the development of heterosubtypic antibody reactivity to animal influenza viruses.


Transvenous sclerotherapy of a large symptomatic orbital venous varix using a microcatheter balloon and bleomycin.
An orbital venous varix is rare and can present with diplopia, proptosis, or hemorrhage. Treatment can be challenging, especially if the varix is in a posterior location within the orbit, since surgical exposure becomes difficult. A few case reports have been published describing transcatheter embolization of an orbital varix with coils, direct percutaneous injection of n-butyl cyanoacrylate glue, and the percutaneous injection of bleomycin. We present a case of a symptomatic orbital venous varix of the left inferior ophthalmic vein successfully treated with transvenous endovascular sclerotherapy using a microcatheter balloon and bleomycin.


The role of ticks in the maintenance and transmission of Crimean-Congo hemorrhagic fever virus: A review of published field and laboratory studies.
This manuscript is part of a series of reviews that aim to cover published research on Crimean-Congo hemorrhagic fever (CCHF) and its etiological agent, CCHF virus (CCHFV). The virus is maintained and transmitted in a vertical and horizontal transmission cycle involving a variety of wild and domestic vertebrate species that act as amplification hosts, without showing signs of illness. These vertebrates have traditionally been considered reservoirs of CCHFV, but in fact they develop only a transient viremia, while the virus can persist in ticks for their entire lifespan, and can also be transmitted vertically to the next generation. As a result, ticks are now considered to be both the vector and the reservoir for the virus. CCHFV has been detected in a wide range of tick species, but only a few have been proven to be vectors and reservoirs, mainly because most published studies have been performed under a broad variety of conditions, precluding definitive characterization. This article reviews the published literature, summarizes current knowledge of the role of ticks in CCHFV maintenance and transmission and provides guidance for how to fill the knowledge gaps. Special focus is given to existing data on tick species in which vertical passage has been demonstrated under natural or experimental conditions. At the same time, we identify earlier reports that used unreliable methods and perceptions to ascribe a vector role to some species of ticks, and have contributed to confusion regarding viral transmission. We also examine epidemiological pathways of CCHFV circulation and discuss priority areas for future research.


Designing Color Filters That Make Cameras More Colorimetric.
When we place a colored filter in front of a camera the effective camera response functions are equal to the given camera spectral sensitivities multiplied by the filter spectral transmittance. In this article, we solve for the filter which returns the modified sensitivities as close to being a linear transformation from the color matching functions of the human visual system as possible. When this linearity condition - sometimes called the Luther condition- is approximately met, the 'camera+filter' system can be used for accurate color measurement. Then, we reformulate our filter design optimisation for making the sensor responses as close to the CIEXYZ tristimulus values as possible given the knowledge of real measured surfaces and illuminants spectra data. This data-driven method in turn is extended to incorporate constraints on the filter (smoothness and bounded transmission). Also, because how the optimisation is initialised is shown to impact on the performance of the solved-for filters, a multi-initialisation optimisation is developed. Experiments demonstrate that, by taking pictures through our optimised color filters, we can make cameras significantly more colorimetric.


Cutaneous changes in chronic alcoholics.
Alcohol consumption can have a variety of cutaneous manifestations. Awareness of the cutaneous changes of alcohol abuse can allow early detection and intervention in an attempt to limit the adverse medical consequences. Hence a study was planned to determine the cutaneous changes in chronic alcoholics. To determine the cutaneous changes in chronic alcoholics. All the patients attending alcohol de-addiction camps were examined for cutaneous changes. The results were analyzed using Gausian test and compared with other reports. Out of 200 alcoholics examined for cutaneous changes, 182 (91%) had cutaneous, nail, hair or oral cavity changes. Nail changes were found in 51 (25.5%) alcoholics, koilonychia being the commonest (16%). Oral changes were present in 107 (53.5%) alcoholics and changes due to nutritional deficiency in 20 (10%). Diseases due to poor hygiene were seen in 55 (27.5%) alcoholics. Tinea versicolor (14%) and seborrheic dermatitis (11.5%) were the commonest cutaneous changes noted. Even though alcohol abuse has a variety of cutaneous manifestations and perhaps aggravates many diseases, there are no specific cutaneous signs of alcoholism. Knowledge of the spectrum of cutaneous manifestations of alcohol abuse can allow its early detection and treatment in an attempt to minimize the medical consequences.


Role of transient receptor potential ion channels and evoked levels of neuropeptides in a formaldehyde-induced model of asthma in BALB/c mice.
Asthma is a complex pulmonary inflammatory disease characterized by the hyper-responsiveness, remodeling and inflammation of airways. Formaldehyde is a common indoor air pollutant that can cause asthma in people experiencing long-term exposure. The irritant effect and adjuvant effect are the two possible pathways of formaldehyde promoted asthma. To explore the neural mechanisms and adjuvant effect of formaldehyde, 48 Balb/c mice in six experimental groups were exposed to (a) vehicle control; (b) ovalbumin; (c) formaldehyde (3.0 mg/m(3)); (d) ovalbumin+formaldehyde (3.0 mg/m(3)); (e) ovalbumin+formaldehyde (3.0 mg/m(3))+HC-030031 (transient receptor potential ankyrin 1 antagonist); (f) ovalbumin+formaldehyde (3.0 mg/m(3))+ capsazepine (transient receptor potential vanilloid 1 antagonist). Experiments were conducted after 4 weeks of combined exposure and 1-week challenge with aerosolized ovalbumin. Airway hyper-responsiveness, pulmonary tissue damage, eosinophil infiltration, and increased levels of interleukin-4, interleukin-6, interleukin-1β, immunoglobulin E, substance P and calcitonin gene-related peptide in lung tissues were found in the ovalbumin+formaldehyde (3.0 mg/m(3)) group compared with the values seen in ovalbumin -only immunized mice. Except for interleukin-1β levels, other changes in the levels of biomarker could be inhibited by HC-030031 and capsazepine. Formaldehyde might be a key risk factor for the rise in asthma cases. Transient receptor potential ion channels and neuropeptides have important roles in formaldehyde promoted-asthma.


Gastroschisis with gastric perforation and jejunal stenosis. A rare association of anomalies.
Gastroschisis with prenatal gastric perforation and intestinal stenosis is a rare and serious anomaly. although there are several case reports, no case series exists to suggest the prognosis for these infants. In this report a case of gastroschisis with gastric perforation and jejunal stenosis in male newborn is presented with literature review. The stomach, small bowel and the part of the colon were herniated through the abdominal wall defect. A large perforation site at the anterior wall of fundus and a thin fibrous strip that causing stenosis of jejunum was found. Gastrorraphy was performed. Stenosis of jejunum was resected and t-t anastomosis was performed, followed by primary fascial closure. The prenatal sonographic finding of bowel or gastric perforation are variable. Antenatal bowel dilatation and in particular intraabdominal bowel dilatation is prognostically useful for detection of patients with worse outcome. The absence of bowel dilatation cannot fully exclude complex patients. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure are not associated with prolonged time for full enteral feeding and length of hospital stay. We have presented the first detailed report of surgical intervention and outcomes in case of gastroschisis with prenatal gastric perforation and congenital jejunal stenosis. Early restoration of bowel continuity using primary anastomosis and primary abdominal wall closure is recommended here. More research should be focused to predict complex gastroschisis and to improve prenatal diagnosis and postnatal management, without a significant increase in morbidity and mortality. Gastroschisis, Gastric perforation, Stenosis of jejunum.


Phosphoinositide second messenger system is enriched in striosomes: immunohistochemical demonstration of inositol 1,4,5-trisphosphate receptors and phospholipase C beta and gamma in primate basal ganglia.
The neurochemical organization of the basal ganglia has been studied extensively with respect to neurotransmitters, neuropeptides, and their receptors. The chemoarchitecture of the striatum has been found particularly striking, because it distinguishes many substances by their relative distributions within the striosome and matrix compartments of the striatum. Very little is yet known about the differential distribution of second messenger systems in the basal ganglia, however, and no information is available about whether the distribution of second messenger systems is related to the prominent neurochemical compartmentalization of the striatum. We have examined the distribution of the phosphoinositide second messenger system in the primate basal ganglia and substantia nigra, as detected with polyclonal antisera against the inositol 1,4,5-trisphosphate receptor (IP3R), and monoclonal antisera against phospholipase C beta (PLC beta) and phospholipase C gamma (PLC gamma). In the striatum, immunostaining for each of the three proteins was present predominantly in medium-sized neuronal perikarya and in the neuropil. Circumscribed zones of enhanced IP3R, PLC beta, and PLC gamma immunoreactivity appeared in a background of generally weaker staining, and these zones corresponded to striosomes as identified by calbinidin D28k and substance P immunostaining in adjacent sections. Thus, the richest representation of the phosphoinositide system in the primate striatum appears to be in striosomes. In the substantia nigra pars compacta, neurons and neuropil were immunopositive, but in the substantia nigra pars reticulata and in each segment of the globus pallidus, immunostaining was mainly confined to the neuropil. Perikaryal PCL gamma immunoreactivity in the absence of detectable PLC beta or IP3R immunolabeling was found in the magnocellular neurons embedded in the medullary layer between the putamen and the globus pallidus. These observations demonstrate that the phosphoinositide second messenger system is selectively enhanced in neuronal subsystems of the basal ganglia, including striosomes, and suggest that signaling by phosphoinositide pathways elicits discrete effects on input-output processing by the basal ganglia.


Experimental and theoretical studies on the enantioselectivity of molecularly imprinted polymers prepared with a chiral functional monomer.
A comprehensive study on the enantioseparation of racemic bis[1-phenylethyl]amine (PEA) on a series of molecularly imprinted polymers (MIPs) prepared using the chiral functional monomer (S)-2-(2-methyl-acryloylamino)-3-phenyl propionic acid (MAPP) is reported. MIP-R, MIP-S and MIP-RS, were synthesized separately by imprinting the pure enantiomers (R-, S-PEA) and racemic PEA, respectively, MAPP, EDGMA as crosslinker and chloroform as the porogen. It was found that all MIPs prepared were able to resolve the PEA racemate. Residence times (t(r)) and enantioselectivity factors (α) were estimated from typical elution chromatography experiments. Frontal chromatography experiments were conducted to acquire the adsorption isotherms for both enantiomers on the different MIPs (and on the non-imprinted polymer, NIP). The adsorption isotherms were analyzed using the affinity spectrum (AS) and the expectation-maximization (EM) methods. The study also involved the theoretical evaluation of the MAPP/enantiomers interactions in the pre-polymer mixture. The EM method predicts mono- and bimodal distribution of affinity binding sites depending upon the polymer analyzed. Apparently, the enantioseparation process depends on relatively small differences in the stabilization of the diasteroisomeric ion-pairs PEA/MAPP complexes on the surface of the polymers.


Numerical Encodings of Amino Acids in Multivariate Gaussian Modeling of Protein Multiple Sequence Alignments.
Residues in proteins that are in close spatial proximity are more prone to covariate as their interactions are likely to be preserved due to structural and evolutionary constraints. If we can detect and quantify such covariation, physical contacts may then be predicted in the structure of a protein solely from the sequences that decorate it. To carry out such predictions, and following the work of others, we have implemented a multivariate Gaussian model to analyze correlation in multiple sequence alignments. We have explored and tested several numerical encodings of amino acids within this model. We have shown that 1D encodings based on amino acid biochemical and biophysical properties, as well as higher dimensional encodings computed from the principal components of experimentally derived mutation/substitution matrices, do not perform as well as a simple twenty dimensional encoding with each amino acid represented with a vector of one along its own dimension and zero elsewhere. The optimum obtained from representations based on substitution matrices is reached by using 10 to 12 principal components; the corresponding performance is less than the performance obtained with the 20-dimensional binary encoding. We highlight also the importance of the prior when constructing the multivariate Gaussian model of a multiple sequence alignment.


Lung function in adults with stable but severe asthma: air trapping and incomplete reversal of obstruction with bronchodilation.
Five to ten percent of asthma cases are poorly controlled chronically and refractory to treatment, and these severe cases account for disproportionate asthma-associated morbidity, mortality, and health care utilization. While persons with severe asthma tend to have more airway obstruction, it is not known whether they represent the severe tail of a unimodal asthma population, or a severe asthma phenotype. We hypothesized that severe asthma has a characteristic physiology of airway obstruction, and we evaluated spirometry, lung volumes, and reversibility during a stable interval in 287 severe and 382 nonsevere asthma subjects from the National Heart, Lung, and Blood Institute Severe Asthma Research Program. We partitioned airway obstruction into components of air trapping [indicated by forced vital capacity (FVC)] and airflow limitation [indicated by forced expiratory volume in 1 s (FEV(1))/FVC]. Severe asthma had prominent air trapping, evident as reduced FVC over the entire range of FEV(1)/FVC. This pattern was confirmed with measures of residual lung volume/total lung capacity (TLC) in a subgroup. In contrast, nonsevere asthma did not exhibit prominent air trapping, even at FEV(1)/FVC <75% predicted. Air trapping also was associated with increases in TLC and functional reserve capacity. After maximal bronchodilation, FEV(1) reversed similarly from baseline in severe and nonsevere asthma, but the severe asthma classification was an independent predictor of residual reduction in FEV(1) after maximal bronchodilation. An increase in FVC accounted for most of the reversal of FEV(1) when baseline FEV(1) was <60% predicted. We conclude that air trapping is a characteristic feature of the severe asthma population, suggesting that there is a pathological process associated with severe asthma that makes airways more vulnerable to this component.


Postcranial skeletal pneumaticity: a case study in the use of quantitative microCT to assess vertebral structure in birds.
Limb elements in birds have been characterized as exhibiting a reduction in trabecular bone, thinner cortices and decreased bending strength when pneumatized, yet it is unclear if these characteristics generalize to the axial skeleton. Thin section techniques, the traditional gold standard for bone structure studies, have most commonly been applied to the study of avian bone. This destructive technique, however, makes it subsequently impossible to use the same samples in experimental testing systems that allow researchers to correlate structure with the mechanical properties of the bone. Micro-computed tomography (microCT), a non-destructive X-ray imaging technique, can be used to assess the effect of pneumatization on vertebral cortical and trabecular bone through virtual extraction and structural quantification of each tissue type. We conducted a preliminary investigation of the application of microCT methods to the study of cortical and trabecular bone structure in a small sample of pneumatic and apneumatic thoracic vertebrae. The sample consisted of two similar-sized anatids, Aix sponsa (n = 7) and Oxyura jamaicensis (n = 5). Volumes of interest were created that contoured (outlined) the boundaries of the ventral cortical bone shell, the trabecular compartment and the whole centrum (cortical bone + trabecular bone), and allowed independent structural analysis of each volume of interest. Results indicated that bone volume fraction of the whole centrum was significantly higher in the apneumatic O. jamaicensis than in the pneumatized A. sponsa (A. sponsa = 36%, O. jamaicensis = 48%, P < 0.05). In contrast, trabecular bone volume fraction was similar between the two species. The ventral cortical bone shell was approximately 23% thinner (P < 0.05) in A. sponsa (0.133 mm) compared with apneumatic O. jamaicensis (0.172 mm). This case study demonstrates that microCT is a powerful non-destructive imaging technique that may be applied to the three-dimensional study of avian bone. The preliminary results suggest that pneumatic and apneumatic vertebrae of comparably sized avian species differ in relative bone volume, with the largest difference apparent at the level of the cortex, and not within trabecular bone. The presence of relatively thin cortices in pneumatic vertebrae is consistent with previous studies contrasting diaphyseal cortical bone between pneumatic and apneumatic long bones. Methodological issues related to this and any comparative microCT study of bone structure are discussed.