Uncertainties of optical parameters and their propagations in an analytical ocean color inversion algorithm.
Following the theory of error propagation, we developed analytical functions to illustrate and evaluate the uncertainties of inherent optical properties (IOPs) derived by the quasi-analytical algorithm (QAA). In particular, we evaluated the effects of uncertainties of these optical parameters on the inverted IOPs: the absorption coefficient at the reference wavelength, the extrapolation of particle backscattering coefficient, and the spectral ratios of absorption coefficients of phytoplankton and detritus/gelbstoff, respectively. With a systematically simulated data set (46,200 points), we found that the relative uncertainty of QAA-derived total absorption coefficients in the blue-green wavelengths is generally within +/-10% for oceanic waters. The results of this study not only establish theoretical bases to evaluate and understand the effects of the various variables on IOPs derived from remote-sensing reflectance, but also lay the groundwork to analytically estimate uncertainties of these IOPs for each pixel. These are required and important steps for the generation of quality maps of IOP products derived from satellite ocean color remote sensing.


Proteomic strategies to unravel age-related redox signalling defects in skeletal muscle.
Increased oxidative damage and disrupted redox signalling are consistently associated with age-related loss of skeletal muscle mass and function. Redox signalling can directly regulate biogenesis and degradation pathways and indirectly via activation of key transcription factors. Contracting skeletal muscle fibres endogenously generate free radicals (e.g. superoxide) and non-radical derivatives (e.g. hydrogen peroxide). Exercise induced redox signalling can promote beneficial adaptive responses that are disrupted by age-related redox changes. Identifying and quantifying the redox signalling pathways responsible for successful adaptation to exercise makes skeletal muscle an attractive physiological model for redox proteomic approaches. Site specific identification of the redox modification and quantification of site occupancy in the context of protein abundance remains a crucial concept for redox proteomics approaches. Notwithstanding, the technical limitations associated with skeletal muscle for proteomic analysis, we discuss current approaches for the identification and quantification of transient and stable redox modifications that have been employed to date in ageing research. We also discuss recent developments in proteomic approaches in skeletal muscle and potential implications and opportunities for investigating disrupted redox signalling in skeletal muscle ageing.


Population Dynamics of Belonolaimus longicaudatusin a Cotton Production System.
Belonolaimus longicaudatus is a recognized pathogen of cotton (Gossypium hirsutum), but insufficient information is available on the population dynamics and economic thresholds of B. longicaudatus in cotton production. In this study, data collected from a field in Florida were used to develop models predicting population increases of B. longicaudatus on cotton and population declines under clean fallow. Population densities of B. longicaudatus increased on cotton, reaching a carrying capacity of 139 nematodes/130 cm(3) of soil, but decreased exponentially during periods of bare fallow. The model indicated that population densities should decrease each year of monocropped cotton, if an alternate host is not present between sequential cotton crops. Economic thresholds derived from published damage functions and current prices for cotton and nematicides varied from 2 to 5 B. longicaudatus/130 cm(3) of soil, depending on the nematicide used.


Predictive factors for local recurrence and incomplete resection of early gastric cancer treated by endoscopic resection: a Western experience.
Early gastric cancer (EGC) is defined as adenocarcinoma limited to the mucosa or submucosa regardless of lymph node involvement. Local EGC recurrence rates have been described in up to 6% of cases. To evaluate predictive factors for incomplete resection and local recurrence of EGC treated by endoscopic mucosal resection (EMR) that was followed up for at least one year. From June 1994 to December 2005, 46 patients with EGC underwent EMR. Possible predictive factors for incomplete endoscopic resection and local recurrence were identified by medical chart analysis. Demographic, endoscopic and histopathological data were retrospectively evaluated. EMR was considered complete or incomplete. Patients from the complete resection group were divided into subgroups (with and without local EGC recurrence). Complete resection was possible in 36 cases (76.6%). Predictive factors for incomplete resection were tumour location (P=0.035), histological type (P=0.021), lesion size (P=0.022) and number of resected fragments (P=0.013). On multivariate analysis, undifferentiated histological type (OR 0.8; 95% CI 0.036 to 0.897) and number of resected fragments (OR 7.34; 95% CI 1.266 to 42.629) were independent predictive factors for incomplete resection. In the complete resection group, a larger lesion size was associated with a higher the number of resected fragments (P=0.018). Local recurrence occurred in nine cases (25%). Use of the cap technique was the only predictive factor for local recurrence in five of seven cases (71.4%) (P=0.006). A larger lesion size was associated with a higher number of resected fragments. Undifferentiated adenocarcinoma and piecemeal resection were predictive factors for incomplete resection. Technique type was a predictive factor for local EGC recurrence.


Challenges of HIV diagnosis and management in the context of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP), test and start and acute HIV infection: a scoping review.
Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV-status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV-specific antibody point-of-care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre-exposure prophylaxis (PrEP) or post-exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false-negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV-specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource-limited, high HIV burden settings where HIV-antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource-wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.


Interactions between perception and action programming: evidence from visual extinction and optic ataxia.
We report a series of 7 experiments examining the interaction between visual perception and action programming, contrasting 2 neuropsychological cases: a case of visual extinction and a case with extinction and optic ataxia. The patients had to make pointing responses to left and right locations, whilst identifying briefly presented shapes. Different patterns of performance emerged with the two cases. The patient with "pure" extinction (i.e., extinction without optic ataxia) showed dramatic effects of action programming on perceptual report. Programming an action to the ipsilesional side increased extinction (on 2-item trials) and tended to induce neglect (on 1-item trials); this was ameliorated when the action was programmed to the contralesional side. Separable effects of using the contralesional hand and pointing to the contralesional side were apparent. In contrast, the optic ataxic patient showed few effects of congruency between the visual stimulus and the action, but extinction when an action was programmed. This effect was particularly marked when actions had to be made to peripheral locations, suggesting that it reflected reduced resources to stimuli. These effects all occurred using stimulus exposures that were completed well before actions were effected. The data demonstrate interactions between action programming and visual perception. Programming an action to the affected side with the contralesional limb reduces "pure" extinction because attention is coupled to the end point of the action. However, in a patient with deficient visuo-motor coupling (optic ataxia), programming an action can increase a spatial deficit by recruiting resources away from perceptual processing. The implications for models of perception and action are discussed.


Efficient computation of quadratic-phase integrals in optics.
We present a fast NlogN time algorithm for computing quadratic-phase integrals. This three-parameter class of integrals models propagation in free space in the Fresnel approximation, passage through thin lenses, and propagation in quadratic graded-index media as well as any combination of any number of these and is therefore of importance in optics. By carefully managing the sampling rate, one need not choose N much larger than the space-bandwidth product of the signals, despite the highly oscillatory integral kernel. The only deviation from exactness arises from the approximation of a continuous Fourier transform with the discrete Fourier transform. Thus the algorithm computes quadratic-phase integrals with a performance similar to that of the fast-Fourier-transform algorithm in computing the Fourier transform, in terms of both speed and accuracy.


Disruption of the alternative oxidase gene in Magnaporthe grisea and its impact on host infection.
Plants and numerous fungi including Magnaporthe grisea protect mitochondria from interference by respiration inhibitors by expressing alternative oxidase, the enzymatic core of alternative respiration. The alternative oxidase gene AOXMg of M. grisea was disrupted. Several lines of evidence suggested that the disruption of AOXMg was sufficient to completely curb the expression of alternative respiration. In the infection of barley leaves, several AOXMg-minus and, thus, alternative respiration-deficient mutants of M. grisea retained their pathogenicity without significant impairment of virulence. However, differences between the wild-type strain and an AOXMg-minus mutant were apparent under oxidative stress conditions generated by the treatment of infected barley leaves with the commercial respiration inhibitor azoxystrobin. Symptom development was effectively suppressed on leaves infected with the alternative respiration-deficient mutant, while lesions on leaves infected with the wild-type strain continued to develop at much higher inhibitor doses. However, respective lesions rarely developed to the stage of full maturity. The results did not conform to a previous model implying that expression of alternative respiration is silenced during pathogenesis by the presence of constitutive plant antioxidants. Rather, alternative respiration provided protection from azoxystrobin during both saprophytic and infectious stages of the pathogen. The nature of similar oxidative stress conditions in the ecology of M. grisea remains an open question.


Selenium: relation to decreased toxicity of methylmercury added to diets containing tuna.
Japanese quail given 20 parts per million of mercury as methylmercury in diets containing 17 percent (by weight) tuna survived longer than quail given this concentration of methylmercury in a corn-soya diet. Tuna has a relatively high content of selenium and tends to accumulate additional selenium when mercury is present. A content of selenium in the diet comparable to that supplied by tuna decreased methylmercury toxicity in rats. Selenium in tuna, far from being a hazard in itself, may lessen the danger to man of mercury in tuna.


Medical expert systems--knowledge tools for physicians.
Recent advances in the field of artificial intelligence have led to the emergence of expert systems, computational tools designed to capture and make available the knowledge of experts in a field. Although much of the underlying technology available today is derived from basic research on biomedical advice systems during the 1970s, medical application packages are thus far generally unavailable from the young artificial intelligence industry. Medical expert systems will begin to appear, however, as researchers in medical artificial intelligence continue to make progress in key areas such as knowledge acquisition, model-based reasoning and system integration for clinical environments. It is accordingly important for physicians to understand the current state of such research and the theoretic and logistic barriers that remain before useful systems can be made available. One experimental system, ONCOCIN, provides a glimpse of the kinds of knowledge-based tools that will someday be available to physicians.


Industrial, CBD, and Wild Hemp: How Different Are Their Essential Oil Profile and Antimicrobial Activity?
Hemp (Cannabis sativa L.) is currently one of the most controversial and promising crops. This study compared nine wild hemp (C. sativa spp. spontanea V.) accessions with 13 registered cultivars, eight breeding lines, and one cannabidiol (CBD) hemp strain belonging to C. sativa L. The first three groups had similar main essential oil (EO) constituents, but in different concentrations; the CBD hemp had a different EO profile. The concentration of the four major constituents in the industrial hemp lines and wild hemp accessions varied as follows: β-caryophyllene 11-22% and 15.4-29.6%; α-humulene 4.4-7.6% and 5.3-11.9%; caryophyllene oxide 8.6-13.7% and 0.2-31.2%; and humulene epoxide 2, 2.3-5.6% and 1.2-9.5%, respectively. The concentration of CBD in the EO of wild hemp varied from 6.9 to 52.4% of the total oil while CBD in the EO of the registered cultivars varied from 7.1 to 25%; CBD in the EO of the breeding lines and in the CBD strain varied from 6.4 to 25% and 7.4 to 8.8%, respectively. The concentrations of δ9-tetrahydrocannabinol (THC) in the EO of the three groups of hemp were significantly different, with the highest concentration being 3.5%. The EO of wild hemp had greater antimicrobial activity compared with the EO of registered cultivars. This is the first report to show that significant amounts of CBD could be accumulated in the EO of wild and registered cultivars of hemp following hydro-distillation. The amount of CBD in the EO can be greater than that in the EO of the USA strain used for commercial production of CBD. Furthermore, this is among the first reports that show greater antimicrobial activity of the EO of wild hemp vs. the EO of registered cultivars. The results suggest that wild hemp may offer an excellent opportunity for future breeding and the selection of cultivars with a desirable composition of the EO and possibly CBD-rich EO production.


Learning from changes concurrent with implementing a complex and dynamic intervention to improve urban maternal and perinatal health in Dar es Salaam, Tanzania, 2011-2019.
Rapid urbanisation in Dar es Salaam, the main commercial hub in Tanzania, has resulted in congested health facilities, poor quality care, and unacceptably high facility-based maternal and perinatal mortality. Using a participatory approach, the Dar es Salaam regional government in partnership with a non-governmental organisation, Comprehensive Community Based Rehabilitation in Tanzania, implemented a complex, dynamic intervention to improve the quality of care and survival during pregnancy and childbirth. The intervention was rolled out in 22 public health facilities, accounting for 60% of the city's facility births. Multiple intervention components addressed gaps across the maternal and perinatal continuum of care (training, infrastructure, routine data quality strengthening and utilisation). Quality of care was measured with the Standards-Based Management and Recognition tool. Temporal trends from 2011 to 2019 in routinely collected, high-quality data on facility utilisation and facility-based maternal and perinatal mortality were analysed. Significant improvements were observed in the 22 health facilities: 41% decongestion in the three most overcrowded hospitals and comparable increase in use of lower level facilities, sixfold increase in quality of care, and overall reductions in facility-based maternal mortality ratio (47%) and stillbirth rate (19%). This collaborative, multipartner, multilevel real-world implementation, led by the local government, leveraged structures in place to strengthen the urban health system and was sustained through a decade. As depicted in the theory of change, it is highly plausible that this complex intervention with the mediators and confounders contributed to improved distribution of workload, quality of maternity care and survival at birth.


Identification of novel exons and transcribed regions by chimpanzee transcriptome sequencing.
We profile the chimpanzee transcriptome by using deep sequencing of cDNA from brain and liver, aiming to quantify expression of known genes and to identify novel transcribed regions. Using stringent criteria for transcription, we identify 12,843 expressed genes, with a majority being found in both tissues. We further identify 9,826 novel transcribed regions that are not overlapping with annotated exons, mRNAs or ESTs. Over 80% of the novel transcribed regions map within or in the vicinity of known genes, and by combining sequencing data with de novo splice predictions we predict several of the novel transcribed regions to be new exons or 3' UTRs. For approximately 350 novel transcribed regions, the corresponding DNA sequence is absent in the human reference genome. The presence of novel transcribed regions in five genes and in one intergenic region is further validated with RT-PCR. Finally, we describe and experimentally validate a putative novel multi-exon gene that belongs to the ATP-cassette transporter gene family. This gene does not appear to be functional in human since one exon is absent from the human genome. In addition to novel exons and UTRs, novel transcribed regions may also stem from different types of noncoding transcripts. We note that expressed repeats and introns from unspliced mRNAs are especially common in our data. Our results extend the chimpanzee gene catalogue with a large number of novel exons and 3' UTRs and thus support the view that mammalian gene annotations are not yet complete.


Characterisation of phenolics in Flor-Essence--a compound herbal product and its contributing herbs.
Commercially available herbal mixture FE, a proprietary natural health product manufactured by Flora Manufacturing and Distributing Ltd (Flora), is a unique North American traditional herbal product. FE is a chemically complex mixture of eight herbs and has not been subjected to phytochemical analysis. To develop analytical methods to undertake detailed phytochemical analyses of FE, and its eight contributing herbs, including burdock (Arctium lappa L.), sheep sorrel (Rumex acetosella L.), Turkish rhubarb (Rheum palmatum L.), slippery elm Muhl. (Ulmus rubra), watercress (Nasturtium officinale R. Br.), red clover (Trifolium pratense L.), blessed thistle (Cnicus benedictus L.) and kelp (Laminaria digitata Lmx.). The identification was undertaken by a combination of reversed phase high performance liquid chromatography-diode array detection-atmospheric pressure chemical ionisation-mass selective detection (RP-HPLC-DAD-APCI-MSD) analysis and phenolics metabolomic library matching. New separation methods facilitated the identification of 43 markers in the individual herbs which constitute FE. Sixteen markers could be identified in FE originating from four contributing herbs including four caffeoyl quinic acids, three dicaffeoyl quinic acids and two caffeic acid derivatives from A. lappa, luteolin-7-O-glucoside, luteolin, five apigenin glycosides and apigenin from R. acetocella and N. officinale and sissostrin from T. pretense. A validated method for quantitative determination of three markers is reported with good intraday, interday and interoperator repeatability using a reliable alcohol based extraction technique. FE and its contributing herbs predominantly contain phenolics. This methodology can be applied to further develop full-scale validation of this product.


Randomized Phase III trial of gefitinib versus docetaxel in non-small cell lung cancer patients who have previously received platinum-based chemotherapy.
The ISTANA (IRESSA as Second-line Therapy in Advanced NSCLC-KoreA) study compared gefitinib with docetaxel in patients with advanced or metastatic non-small cell lung carcinoma (NSCLC) pretreated with platinum-based chemotherapy. We conducted a multicenter, randomized, open-label phase III trial of gefitinib (250 mg/d) versus docetaxel (75 mg/m(2) day 1 every 3 weeks) in patients with advanced or metastatic NSCLC treated with one previous platinum-based chemotherapy. The primary endpoint was progression-free survival. A total of 161 patients (male, 62%; never smoker, 41%; adenocarcinoma, 68%) were enrolled. Progression-free survival was longer for gefitinib compared with docetaxel (hazard ratio, 0.729; 90% confidence interval, 0.533-0.998; one-sided P = 0.0441). Gefitinib significantly improved objective response rate (28.1% versus 7.6%; two-sided P = 0.0007). In the final analysis of overall survival, the hazard ratio was 0.870 (95% confidence interval, 0.613-1.236; two-sided P = 0.4370). No significant differences were seen in the quality of life or symptom improvement rates between the two treatment groups. Gefitinib was well tolerated, was consistent with previous data and disease, and had fewer serious adverse events and fewer Common Terminology Criteria for Adverse Events grade 3 or 4 adverse events than docetaxel. The incidence of interstitial lung disease-type events was 3.7% (n = 3) with gefitinib and 3.9% (n = 3) with docetaxel. The primary endpoint of progression-free survival was longer with gefitinib than docetaxel, and the secondary endpoints showed superior objective response rate, good tolerability, and similar quality of life improvement rates for gefitinib than docetaxel. Therefore, gefitinib is an important valid treatment option for second-line therapy for Korean NSCLC patients.


Phantom radiculitis effectively treated by fluoroscopically guided transforaminal epidural steroid injections.
Lower back and extremity pain in the amputee patient can be challenging to classify and treat. Radicular compression in a patient with lower limb amputation may present as or be superimposed upon phantom limb pain, creating diagnostic difficulties. Both patients and physicians classically find it difficult to discern phantom sensation from phantom limb pain and stump pain; radicular compression is often not considered. Many studies have shown back pain to be a significant cause of pain in lower limb amputees, but sciatica has been rarely reported in amputees. We present a case of L4/5 radiculitis in an above-knee amputee presenting as phantom radiculitis. Our patient is a 67 year old gentleman with new onset 10/10 pain in a phantom extremity superimposed upon a 40 year history of previously stable phantom limb pain. MRI showed a central disc herniation at L4/5 with compression of the traversing left L4 nerve root. Two fluoroscopically guided left transforaminal epidural steroid injections at the level of the L4 and L5 spinal nerve roots totally alleviated his new onset pain. At one year post injection, his phantom radiculitis pain was completely gone, though his underlying phantom limb pain remained. Lumbar radiculitis in lower extremity amputee patients may be difficult to differentiate from baseline phantom limb pain. When conservative techniques fail, fluoroscopically guided spinal nerve injection may be valuable in determining the etiology of lower extremity pain. Our experience supports the notion that epidural steroid injections can effectively treat phantom lumbar radiculitis in lower extremity amputees.


Visual analytics for spatial clustering: using a heuristic approach for guided exploration.
We propose a novel approach of distance-based spatial clustering and contribute a heuristic computation of input parameters for guiding users in the search of interesting cluster constellations. We thereby combine computational geometry with interactive visualization into one coherent framework. Our approach entails displaying the results of the heuristics to users, as shown in Figure 1, providing a setting from which to start the exploration and data analysis. Addition interaction capabilities are available containing visual feedback for exploring further clustering options and is able to cope with noise in the data. We evaluate, and show the benefits of our approach on a sophisticated artificial dataset and demonstrate its usefulness on real-world data.


Speed breeding is a powerful tool to accelerate crop research and breeding.
The growing human population and a changing environment have raised significant concern for global food security, with the current improvement rate of several important crops inadequate to meet future demand 1 . This slow improvement rate is attributed partly to the long generation times of crop plants. Here, we present a method called 'speed breeding', which greatly shortens generation time and accelerates breeding and research programmes. Speed breeding can be used to achieve up to 6 generations per year for spring wheat (Triticum aestivum), durum wheat (T. durum), barley (Hordeum vulgare), chickpea (Cicer arietinum) and pea (Pisum sativum), and 4 generations for canola (Brassica napus), instead of 2-3 under normal glasshouse conditions. We demonstrate that speed breeding in fully enclosed, controlled-environment growth chambers can accelerate plant development for research purposes, including phenotyping of adult plant traits, mutant studies and transformation. The use of supplemental lighting in a glasshouse environment allows rapid generation cycling through single seed descent (SSD) and potential for adaptation to larger-scale crop improvement programs. Cost saving through light-emitting diode (LED) supplemental lighting is also outlined. We envisage great potential for integrating speed breeding with other modern crop breeding technologies, including high-throughput genotyping, genome editing and genomic selection, accelerating the rate of crop improvement.


Absorption, tissue distribution and excretion of pelargonidin and its metabolites following oral administration to rats.
Recent reports have demonstrated various cardiovascular and neurological benefits associated with the consumption of foods rich in anthocyanidins. However, information regarding absorption, metabolism, and especially, tissue distribution are only beginning to accumulate. In the present study, we investigated the occurrence and the kinetics of various circulating pelargonidin metabolites, and we aimed at providing initial information with regard to tissue distribution. Based on HPLC and LC-MS analyses we demonstrate that pelargonidin is absorbed and present in plasma following oral gavage to rats. In addition, the main structurally related pelargonidin metabolite identified in plasma and urine was pelargonidin glucuronide. Furthermore, p-hydroxybenzoic acid, a ring fission product of pelargonidin, was detected in plasma and urine samples obtained at 2 and 18 h after ingestion. At 2 h post-gavage, pelargonidin glucuronide was the major metabolite detected in kidney and liver, with levels reaching 0.5 and 0.15 nmol pelargonidin equivalents/g tissue, respectively. Brain and lung tissues contained detectable levels of the aglycone, with the glucuronide also present in the lungs. Other tissues, including spleen and heart, did not contain detectable levels of pelargonidin or ensuing metabolites. At 18 h post-gavage, tissue analyses did not reveal detectable levels of the aglycone nor of pelargonidin glucuronides. Taken together, our results demonstrate that the overall uptake of the administered pelargonidin was 18 % after 2 h, with the majority of the detected levels located in the stomach. However, the amounts recovered dropped to 1.2 % only 18 h post-gavage, with the urine and faecal content constituting almost 90 % of the total recovered pelargonidin.


Transmission of tuberculosis by flexible fiberbronchoscopes.
The development of flexible fiberoptic bronchoscopy was an important technologic advance in the diagnosis and management of patients with pulmonary disease. However, reliable decontamination and sterilization of these delicate instruments have been difficult. Many physicians routinely use a solution of povidone-iodine diluted in 70% ethyl alcohol and water to decontaminate fiberbronchoscopes, despite the fact that these iodophor compounds were developed as skin antiseptics and not as germicidal disinfectants for decontaminating instruments. We isolated a strain of Mycobacterium tuberculosis on a surveillance culture from a bronchoscope after it had been cleaned and disinfected with an iodophor solution. In another hospital, we documented the transmission of M. tuberculosis from one patient to another by a bronchoscope that had been disinfected with a commonly recommended iodophor solution. We then studied the tuberculocidal efficacy of various iodophor preparations used with exposure times from 10 to 30 min. In several experiments these iodophors failed to kill M. tuberculosis. Because iodophors do not reliably kill M. tuberculosis, they should not be used to disinfect fiberoptic bronchoscopes.


The multi-modality cardiac imaging approach to the Athlete's heart: an expert consensus of the European Association of Cardiovascular Imaging.
The term 'athlete's heart' refers to a clinical picture characterized by a slow heart rate and enlargement of the heart. A multi-modality imaging approach to the athlete's heart aims to differentiate physiological changes due to intensive training in the athlete's heart from serious cardiac diseases with similar morphological features. Imaging assessment of the athlete's heart should begin with a thorough echocardiographic examination.Left ventricular (LV) wall thickness by echocardiography can contribute to the distinction between athlete's LV hypertrophy and hypertrophic cardiomyopathy (HCM). LV end-diastolic diameter becomes larger (>55 mm) than the normal limits only in end-stage HCM patients when the LV ejection fraction is <50%. Patients with HCM also show early impairment of LV diastolic function, whereas athletes have normal diastolic function.When echocardiography cannot provide a clear differential diagnosis, cardiac magnetic resonance (CMR) imaging should be performed.With CMR, accurate morphological and functional assessment can be made. Tissue characterization by late gadolinium enhancement may show a distinctive, non-ischaemic pattern in HCM and a variety of other myocardial conditions such as idiopathic dilated cardiomyopathy or myocarditis. The work-up of athletes with suspected coronary artery disease should start with an exercise ECG. In athletes with inconclusive exercise ECG results, exercise stress echocardiography should be considered. Nuclear cardiology techniques, coronary cardiac tomography (CCT) and/or CMR may be performed in selected cases. Owing to radiation exposure and the young age of most athletes, the use of CCT and nuclear cardiology techniques should be restricted to athletes with unclear stress echocardiography or CMR.


Influence of body position and stool characteristics on defecation in humans.
Whether defecation is influenced by body position or stool characteristics is unclear. We investigated effects of body position, presence of stool-like sensation, and stool form on defecation patterns and manometric profiles. Rectal and anal pressures were assessed in 25 healthy volunteers during attempted defecation either in the lying or sitting positions and with balloon-filled or empty rectum. Subjects also expelled a water-filled (50 cc) balloon or silicone-stool (FECOM) either lying or sitting and rated their stooling sensation. When attempting to defecate in the lying position, a dyssynergic pattern was seen in 36% of subjects with empty rectum and 24% with distended rectum. When sitting, 20% showed dyssynergia with empty rectum and 8% with distended rectum. More subjects (p < 0.05) showed dyssynergia in lying position. When lying, 60% could not expel balloon and 44% FECOM. When sitting, fewer (p < 0.05) failed to expel balloon (16%) or FECOM (4%). FECOM expulsion time was quicker (p < 0.02). Stool-like sensation was more commonly (p < 0.005) evoked by FECOM than balloon. In the lying position, one-third showed dyssynergia and one-half could not expel artificial stool. Whereas when sitting with distended rectum, most showed normal defecation pattern and ability to expel stool. Thus, body position, sensation of stooling and stool characteristics may each influence defecation. Defecation is best evaluated in the sitting position with artificial stool.


Transcriptional and Mutational Profiling of an Aminoglycoside-Resistant Pseudomonas aeruginosa Small-Colony Variant.
Pseudomonas aeruginosa is a major causative agent of both acute and chronic infections. Although aminoglycoside antibiotics are very potent drugs against such infections, antibiotic failure is steadily increasing mainly because of increasing resistance of the bacteria. Many molecular mechanisms that determine resistance, such as acquisition of genes encoding aminoglycoside-inactivating enzymes or overexpression of efflux pumps, have been elucidated. However, there are additional, less well-described mechanisms of aminoglycoside resistance. In this study, we profiled a clinical tobramycin-resistant P. aeruginosa strain that exhibited a small-colony variant (SCV) phenotype. Both the resistance and colony morphology phenotypes were lost upon passage of the isolate under rich medium conditions. Transcriptional and mutational profiling revealed that the SCV harbored activating mutations in the two-component systems AmgRS and PmrAB. Introduction of these mutations individually into type strain PA14 conferred tobramycin and colistin resistance, respectively. However, their combined introduction had an additive effect on the tobramycin resistance phenotype. Activation of the AmgRS system slightly reduced the colony size of wild-type PA14, whereas the simultaneous overexpression of gacA, the response regulator of the GacSA two-component system, further reduced colony size. In conclusion, we uncovered combinatorial influences of two-component systems on clinically relevant phenotypes such as resistance and the expression of the SCV phenotype. Our results clearly demonstrate that the combined activation of P. aeruginosa two-component systems has pleiotropic effects with unforeseen consequences.


High-frequency vibrational density of states of a disordered solid.
We investigate the high-frequency behavior of the density of vibrational states in three-dimensional elasticity theory with spatially fluctuating elastic moduli. At frequencies well above the mobility edge, instanton solutions yield an exponentially decaying density of states. The instanton solutions describe excitations, which become localized due to the disorder-induced fluctuations, which lower the sound velocity in a finite region compared to its average value. The exponentially decaying density of states (known in electronic systems as the Lifshitz tail) is governed by the statistics of a fluctuating-elasticity landscape, capable of trapping the vibrational excitations.


A randomized, prospective study of the effects of Tai Chi Chun exercise on bone mineral density in postmenopausal women.
To evaluate the potential benefits of programmed Tai Chi Chun (TCC) exercise on the weight-bearing bones of early postmenopausal women. Age-matched and randomized prospective intervention. University medical school. One hundred thirty-two healthy postmenopausal women (mean age, 54.0+/-3.5y) within 10 years of menopause onset were recruited and randomized into the TCC exercise group (n=67) or the sedentary control group (n=65). Supervised TCC exercise was performed by the TCC group for 45 minutes a day, 5 days a week, for 12 months; control subjects retained a sedentary life style. Main outcome measures Bone mineral density (BMD) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography (pQCT). All BMD measurements were repeated after 12 months in both groups. Fracture rate was also documented. Baseline measurements showed homogeneity in age, anthropometric variables, and menstruation status between the TCC and control groups. Exactly 81.6% of the subjects in the TCC group and 83.1% of subjects in the control group completed the 12-month follow-up study. BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites, but with a reportedly slower rate in the TCC group. A significant 2.6- to 3.6-fold retardation of bone loss (P<.01) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls, as measured by pQCT. A total of 4 fracture cases were documented during follow-up, including 3 subjects in the control group and 1 in the TCC group. This is the first prospective and randomized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women. Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture.


The effect of a novel transition state inhibitor of methylthioadenosine phosphorylase on pemetrexed activity.
Pemetrexed is a new-generation antifolate inhibitor of thymidylate synthase (TS) and a weaker inhibitor of glycinamide ribonucleotide transformylase (GARFT) required for de novo purine synthesis. Methylthioadenosine phosphorylase (MTAP) salvages purines by releasing adenine from methylthioadenosine and is often deleted in mesothelioma. The current study addresses the effect of MTAP on pemetrexed activity using a highly potent transition state inhibitor of MTAP, MT-DADMe-Immucillin A (ImmA; K(i) = 86 pmol/L) in the MTAP(+) NCI-H28 and MTAP(-) NCI-H2052 mesothelioma cell lines. Based on selective nucleoside protection, TS was found to be the primary pemetrexed target in both cell lines with GARFT inhibition requiring 20- to 30-fold higher pemetrexed concentrations. ImmA had no effect on pemetrexed activity but, when thymidine was added, the pemetrexed IC(50) decreased by a factor of approximately 3 in MTAP(+) H28 cells with no effect in MTAP(-) H2052 cells. Conversely, the transfection of MTAP into H2052 cells increased the pemetrexed IC(50) by nearly 3-fold but only in the presence of thymidine; this was reversed by ImmA. An MTAP-specific short interfering RNA produced a 2-fold decrease in pemetrexed IC(50) in MTAP(+) HeLa cells in the presence of thymidine. These data indicate that suppression of constitutive MTAP has no effect on pemetrexed activity when the primary target is TS. There is a modest salutary effect when the pemetrexed target is GARFT alone.


The recent economic recession and self-rated health in Estonia, Lithuania and Finland: a comparative cross-sectional study in 2004-2010.
The late-2000s financial crisis had a severe impact on the national economies on a global scale. In Europe, the Baltic countries were among those most affected with more than a 20% decrease in per capita gross domestic product in 2008-2009. In this study, we explored the effects of economic recession on self-rated health in Estonia and Lithuania using Finland, a neighbouring Nordic welfare state, as a point of reference. Nationally representative cross-sectional data for Estonia (n=10 966), Lithuania (n=7249) and Finland (n=11 602) for 2004-2010 were analysed for changes in age-standardised prevalence rates of less-than-good self-rated health and changes in health inequalities using logistic regression analysis. The prevalence of less-than-good self-rated health increased slightly (albeit not statistically significantly) in all countries during 2008-2010. This was in sharp contrast to the statistically significant decline in the prevalence of less-than-good health in 2004-2008 in Estonia and Lithuania. Health disparities were larger in Estonia and Lithuania when compared to Finland, but decreased in 2008-2010 (in men only). In Finland, both the prevalence of less-than-good health and health disparities remained fairly stable throughout the period. Despite the rapid economic downturn, the short-term health effects in Estonia and Lithuania did not differ from those in Finland, although the recession years marked the end of the previous positive trend in self-rated health. The reduction in health disparities during the recession indicates that different socioeconomic groups were affected disproportionately; however, the reasons for this require further research.


A novel technique for large and ptotic breast reconstruction using a latissimus dorsi myocutaneous flap set at the posterior aspect, combined with a silicone implant, following tissue expander surgery.
Large and ptotic breast reconstruction in patients who are not candidates for a transverse rectus abdominalis myocutaneous flap and revision surgery for the contralateral breast remains challenging. We developed a novel breast reconstruction technique using a latissimus dorsi myocutaneous (LD m-c) flap set at the posterior aspect of the reconstructed breast, combined with an anatomical silicone breast implant (SBI), following tissue expander surgery. We performed the proposed technique in four patients, in whom the weight of the resected tissue during mastectomy was >500 g and the depth of the inframammary fold (IMF) was >3 cm. After over-expansion of the lower portion of the skin envelope by a tissue expander, the LD m-c flap was transferred to cover the lower portion of the breast defect and to achieve a ptotic contour, with the skin paddle set at the posterior aspect of the reconstructed breast. An SBI was then placed in the rest of the breast defect after setting the LD m-c flap. No major complications were observed during the follow-up period. The proposed technique resulted in symmetrical and aesthetically satisfactory breasts with deep IMFs, which allowed proper fitting of the brassiere, following large and ptotic breast reconstruction.


Examining gender differences in received, provided, and invisible social control: an application of the dual-effects model.
The dual-effects model of social control not only assumes that social control leads to better health practices but also arouses psychological distress. However, findings are inconsistent. The present study advances the current literature by examining social control from a dyadic perspective in the context of smoking. In addition, the study examines whether control, continuous smoking abstinence, and affect are differentially related for men and women. Before and three weeks after a self-set quit attempt, we examined 106 smokers (77 men, mean age: 40.67, average number of cigarettes smoked per day: 16.59 [SD=8.52, range=1-40] at baseline and 5.27 [SD=6.97, range=0-40] at follow-up) and their nonsmoking heterosexual partners, assessing received and provided control, continuous abstinence, and affect. With regard to smoker's affective reactions, partner's provided control was related to an increase in positive and to a decrease in negative affect, but only for female smokers. Moreover, the greater the discrepancy between smoker received and partner's provided control was the more positive affect increased and the more negative affect decreased, but again only for female smokers. These findings demonstrate that female smokers' well-being was raised over time if they were not aware of the control attempts of their nonsmoking partners, indicating positive effects of invisible social control. This study's results emphasize the importance of applying a dyadic perspective and taking gender differences in the dual-effects model of social control into account.


Evaluation of nickel ferrite nanoparticles coated with oleylamine by NMR relaxation measurements and magnetic hyperthermia.
Nickel ferrite nanoparticles were synthesized via a facile solvothermal approach. Oleylamine (OAm) was used in all synthetic procedures as a stabilizing agent and solvent. By varying the polarity of the solvents, hydrophobic NiFe2O4 nanoparticles coated with OAm of relatively similar sizes (9-11.7 nm) and in a range of magnetization values (32.0-53.5 emu g(-1)) were obtained. The as-prepared hydrophobic nanoparticles were characterized by XRD, TEM, SEM, TGA and VSM and converted to hydrophilic by two different approaches. The addition of a positively charged ligand (cetyltrimethyl ammonium bromide, CTAB) and the ligand exchange procedure (2,3-dimercaptosuccinic acid, DMSA) have been successfully applied. The aqueous suspensions of NiFe2O4@CTAB and NiFe2O4@DMSA showed good colloidal stability after a long period of time. The different surface modification affected both the NMR relaxometric measurements and the hyperthermia effects. In both techniques CTAB modification demonstrated higher r2 relaxivity (278.9 s(-1) mM(-1) in an NMR spectrometer at 11.7 T) and SAR values (423.4 W g(-1) at an applied AC field with a particle concentration of 0.5 mg mL(-1)). The results indicate that a coating with a larger molecule as CTAB under the same size, shape and magnetization of NiFe2O4 NPs gave rise to NMR relaxometric properties and heating efficacy.


Structure-activity-relationship studies of conformationally restricted analogs of combretastatin A-4 derived from SU5416.
A series of combretastatin A-4 analogs derived from the ATP competitive, VEGF receptor tyrosine kinase inhibitor, SU5416 were synthesized. The cytotoxic effects of the analogs were evaluated against PC-3 and MDA-MB-231 cancer cell lines, as well as their abilities to inhibit tubulin polymerization. Results are compared to those of compound 1, our lead compound previously reported.


Human 5-HT transporter availability predicts amygdala reactivity in vivo.
The amygdala plays a central role in fear conditioning, emotional processing, and memory modulation. A postulated key component of the neurochemical regulation of amygdala function is the neurotransmitter 5-hydroxytryptamine (5-HT), and synaptic levels of 5-HT in the amygdala and elsewhere are critically regulated by the 5-HT transporter (5-HTT). The aim of this study was to directly examine the relationship between 5-HTT availability and amygdala activity using multimodal [positron emission tomography (PET) and functional magnetic resonance imaging (fMRI)] imaging measures in the same individuals. Healthy male volunteers who had previously undergone an [11C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile ([11C]-DASB) PET scan to determine 5-HTT availability completed an fMRI emotion recognition task. [11C]-DASB binding potential values were calculated for the amygdala using arterial input function and linear graphical (Logan) analysis. fMRI was performed on a 3T Philips Intera scanner, and data were analyzed using SPM2 (Wellcome Department Imaging Neuroscience, University College London). Percentage signal change during the task was extracted from the amygdala using MarsBaR (Brett et al., 2002). fMRI analysis revealed significant amygdala activation during the emotion recognition task. Region of interest analyses demonstrated a significant negative correlation between fMRI signal change in the left amygdala and 5-HTT availability in the left amygdala, with 5-HTT availability accounting for approximately 42% of the variability in left amygdala activity. Our novel in vivo data highlight the central importance of the serotonergic system in the responsiveness of the human amygdala during emotional processing.


Structural and functional interactions between six-transmembrane μ-opioid receptors and β2-adrenoreceptors modulate opioid signaling.
The primary molecular target for clinically used opioids is the μ-opioid receptor (MOR). Besides the major seven-transmembrane (7TM) receptors, the MOR gene codes for alternatively spliced six-transmembrane (6TM) isoforms, the biological and clinical significance of which remains unclear. Here, we show that the otherwise exclusively intracellular localized 6TM-MOR translocates to the plasma membrane upon coexpression with β2-adrenergic receptors (β2-ARs) through an interaction with the fifth and sixth helices of β2-AR. Coexpression of the two receptors in BE(2)-C neuroblastoma cells potentiates calcium responses to a 6TM-MOR ligand, and this calcium response is completely blocked by a selective β2-antagonist in BE(2)-C cells, and in trigeminal and dorsal root ganglia. Co-administration of 6TM-MOR and β2-AR ligands leads to substantial analgesic synergy and completely reverses opioid-induced hyperalgesia in rodent behavioral models. Together, our results provide evidence that the heterodimerization of 6TM-MOR with β2-AR underlies a molecular mechanism for 6TM cellular signaling, presenting a unique functional responses to opioids. This signaling pathway may contribute to the hyperalgesic effects of opioids that can be efficiently blocked by β2-AR antagonists, providing a new avenue for opioid therapy.


Relational identity theory: a systematic approach for transforming the emotional dimension of conflict.
Emotions are a vital dimension in conflicts among nation-states and communities affiliated by common ethnic, economic, or political interests. Yet the individuals most responsible for managing such conflicts--heads of state, CEOs, intellectual or religious leaders--are often blind to the psychological forces affecting their interests. During 20 years of international research, consulting, and teaching, I have developed a program for teaching thought leaders how to apply psychological principles to achieve their aims while also reducing negative outcomes such as violence, social upheaval, and economic displacement. In this article, I present relational identity theory (RIT), a theoretical and intellectual framework I have originated to help people understand and deal with key emotional dimensions of conflict management. I argue that national and communal bonds are essentially tribal in nature, and I describe how a tribe's unaddressed relational identity concerns make it susceptible to what I term the tribes effect, a rigidification of its relational identity. I provide strategies based on RIT for mitigating the tribes effect and thus enhancing global security.


Quantitative changes in peptides derived from proteins in beef tenderloin (psoas major muscle) and striploin (longissimus lumborum muscle) during cold storage.
Peptides derived from whole proteins in beef tenderloin (M. psoas major, PM) and striploin (M. longissimus lumborum, LL) associated with meat quality and muscle fiber composition were identified and quantified during 21 days of aging. Peptide quantification revealed 40-43 proteins to be significantly degraded during all aging time, and these were mostly sarcoplasmic proteins. Cooking loss of both muscles was not changed by aging (P > 0.05), whereas Warner-Bratzler shear force and meat color were affected by aging. Sensory tenderness increased in PM after 14 days of aging (P < 0.05). PM had a higher type I fiber content, whereas LL had a higher type IIX fiber content (P < 0.05), resulting in differences in proteolysis during all aging periods tested. These findings improve our understanding of different biochemical and physicochemical changes in aged meat according to the muscle type.


Physicians under the influence: social psychology and industry marketing strategies.
Pharmaceutical and medical device companies apply social psychology to influence physicians' prescribing behavior and decision making. Physicians fail to recognize their vulnerability to commercial influences due to self-serving bias, rationalization, and cognitive dissonance. Professionalism offers little protection; even the most conscious and genuine commitment to ethical behavior cannot eliminate unintentional, subconscious bias. Six principles of influence - reciprocation, commitment, social proof, liking, authority, and scarcity - are key to the industry's routine marketing strategies, which rely on the illusion that the industry is a generous avuncular partner to physicians. In order to resist industry influence, physicians must accept that they are vulnerable to subconscious bias and have both the motivation and means to resist industry influence. A culture in which accepting industry gifts engenders shame rather than gratitude will reduce conflicts of interest. If greater academic prestige accrues to distant rather than close relationships with industry, then a new social norm may emerge that promotes patient care and scientific integrity. In addition to educating faculty and students about the social psychology underlying sophisticated but potentially manipulative marketing and about how to resist it, academic medical institutions should develop strong organizational policies to counteract the medical profession's improper dependence on industry.


Like grandfather, like grandson: Erasmus and Charles Darwin on evolution.
Last year (2009) marked the bicentenary of Charles Darwin's birth and the sesquicentenary of The Origin of Species. This article examines the influence of Erasmus Darwin on Charles's evolutionary thought and shows how, in many ways, Erasmus anticipated his much better-known grandson. It discusses the similarity in the mindsets of the two Darwins, asks how far the younger Darwin was exposed to the elder's evolutionary thought, examines the similarities and differences in their theories of evolution, and ends by showing the surprising similarity between their theories of inheritance. Erasmus's influence on Charles is greater than customarily acknowledged, and now is an opportune time to bring the grandfather out from behind the glare of his stellar grandson.


[Citizenship, community participation, and health as seen by health care professionals: a case study in public health services].
This paper deals with the subject of citizenship and people's participation in the health area through an analysis of ideas pertaining to a specific group: health care professionals working in Basic Health Care Clinics in the 3.1 Programmatic Area of the City of Rio de Janeiro (Brazil). The article analyzes their views on the subject and presents them in light of health-related legislation in the Brazilian constitution. It also analyzes the professionals' role vis-à-vis users in raising community awareness that health care is one of their basic rights. Field data from qualitative social research methodology showed a significant heterogeneity in the professionals' conceptions, dividing them into two groups: those belonging to teaching institutions and those working in institutions providing health care. This analysis shows the strategic role that day-to-day relationships between professionals and the community can play in the social change process and the establishment of social rights. It also discusses the viability of this process in view of the discovery of the subjective involvement of the health professionals who promote this process.


The Isw2 chromatin-remodeling ATPase cooperates with the Fkh2 transcription factor to repress transcription of the B-type cyclin gene CLB2.
Forkhead (Fkh) transcription factors influence cell death, proliferation, and differentiation and the cell cycle. In Saccharomyces cerevisiae, Fkh2 both activates and represses transcription of CLB2, encoding a B-type cyclin. CLB2 is expressed during G(2)/M phase and repressed during G(1). Fkh2 recruits the coactivator Ndd1, an interaction which is promoted by Clb2/Cdk1-dependent phosphorylation of Ndd1, suggesting that CLB2 is autoregulated. Ndd1 is proposed to function by antagonizing Fkh2-mediated repression, but nothing is known about the mechanism. Here we ask how Fkh2 represses CLB2. We show that Fkh2 controls a repressive chromatin structure that initiates in the early coding region of CLB2 and spreads up the promoter during the M and G(1) phases. The Isw2 chromatin-remodeling ATPase cooperates with Fkh2 to remodel the chromatin and repress CLB2 expression throughout the cell cycle. In addition, the related factors Isw1 and Fkh1 configure the chromatin at the early coding region and negatively regulate CLB2 expression but only during G(2)/M phase. Thus, the cooperative actions of two forkhead transcription factors and two chromatin-remodeling ATPases combine to regulate CLB2. We propose that chromatin-mediated repression by Isw1 and Isw2 may serve to limit activation of CLB2 expression by the Clb2/Cdk1 kinase during G(2)/M and to fully repress expression during G(1).


People with Parkinson's disease and normal MMSE score have a broad range of cognitive performance.
Cognitive impairment, including dementia, is common in Parkinson's disease (PD). The Mini-Mental State Examination (MMSE) has been recommended as a screening tool for Parkinson's disease dementia (PDD), with values below 26 indicative of possible dementia. Using a detailed neuropsychological battery, we examined the range of cognitive impairment in PD patients with an MMSE score of 26 or higher. In this multicenter, cross-sectional, observational study, we performed neuropsychological testing in a sample of 788 PD patients with MMSE scores of 26 or higher. Evaluation included tests of global cognition, executive function, language, memory, and visuospatial skills. A consensus panel reviewed results for 342 subjects and assigned a diagnosis of no cognitive impairment, mild cognitive impairment, or dementia. Sixty-seven percent of the 788 subjects performed 1.5 standard deviations below the normative mean on at least one test. On eight of the 15 tests, more than 20% of subjects scored 1.5 standard deviations or more below the normative mean. Greatest impairments were found on Hopkins Verbal Learning and Digit Symbol Coding tests. The sensitivity of the MMSE to detect dementia was 45% in a subset of participants who underwent clinical diagnostic procedures. A remarkably wide range of cognitive impairment can be found in PD patients with a relatively high score on the MMSE, including a level of cognitive impairment consistent with dementia. Given these findings, clinicians must be aware of the limitations of the MMSE in detecting cognitive impairment, including dementia, in PD.


Measuring the U.S. health care system: a cross-national comparison.
The Organization for Economic Cooperation and Development (OECD) tracks and reports annually on more than 1,200 health system measures across 30 industrialized countries, ranging from population health status and nonmedical determinants of health to health care resources and utilization. Based on analysis of OECD health data from 2008, the United States continues to differ markedly from other countries on a number of health system measures. The U.S. has a comparatively low number of hospital beds and physicians per capita, and patients in the U.S. have fewer hospital and physician visits than most other countries. At the same time, spending per hospital visit is highest in the U.S., and American patients are among the most likely to receive procedures requiring complex technology. The nation now ranks in the bottom quartile in life expectancy among OECD countries and has seen the smallest improvement in this metric over the past 20 years.


Whole-body kinematics and coordination in a complex dance sequence: Differences across skill levels.
This study examined differences across skill levels in the kinematics of a complex, whole-body, asymmetrical, cyclical dance sequence, the 'Alternate Basic' in Cha-Cha-Cha, to determine whether observed differences were consistent with Bernstein's (1967) model of development of coordination. Bernstein proposed that with novel motor skills, beginners move their bodies rigidly and spastically, freezing kinematic degrees of freedom (DOF) to constrain the motor system. As the skill becomes practised, the DOF unfreeze and movements become more dynamic, allowing the integration of reactional elements (passive forces, moments, etc.) and organisation of more complex coordinative structures. Twenty-nine dancers - beginners (n = 10), intermediates (n = 10), experts (n = 9) - performed 12 cycles of the dance sequence (total duration ~60 s). Three-dimensional kinematic data from 36 joint angles were collected using a 14-camera infrared motion capture system. Most joints displayed increased amplitude and speed of movement, especially early in skill progression (beginner-intermediate stage), with no evidence of any decreases, showing that unfreezing occurred around the general movement pattern early. Speed of movement continued to increase later (intermediate-expert stage), as well as further unfreezing of the upper limbs. Changes to intra-limb couplings were limited, comprising some early reductions in coupling strength. Principal component analyses (PCA) showed that the structure of movement became more organised with increased skill. There was an early reduction in the number of coordinative structures, while later, movement was integrated more into the first coordinative structure. As predicted by Bernstein's coordination development model, therefore, the kinematic DOF unfroze as skill level progressed, leading to increased organisation of coordinative structures. The results of this study support the importance of a whole-body perspective in studies of coordination, with incorporation of kinetic variables in future research in order to examine the role that reactional elements play in motor skill development.


Trauma-symptom profiles of adolescents in child welfare.
In the province of Ontario (Canada), over 28,900 adolescents are investigated by child welfare agencies each year because of suspected maltreatment. Exposure to childhood maltreatment represents a major threat to the psychological well-being of young people, particularly in terms of trauma-related stress. The present study investigated trauma symptom profiles among 479 adolescents (13-17 years) involved with the Canadian child welfare system between 2003 and 2010. Latent profile analysis identified three profiles using self-report data from the Trauma Symptom Checklist for Children. Most adolescents (59%, n=281) were classified into the profile depicting minimal trauma-related symptoms, 30% (n=144) were characterized by moderate trauma-related symptoms, and 11% (n=54) were in the profile reflecting severe trauma-related symptoms. Several variables predicted profile membership. Greater severity of sexual abuse and female sex were associated with a greater likelihood of belonging to the severe trauma symptom profile than both the moderate and the minimal trauma symptom profiles. In addition, having society ward status (compared to crown ward) was related to an increased likelihood of belonging to both the severe and moderate symptom profiles relative to the minimal symptom profile. This study provides some insight into the typologies of trauma experienced among child-welfare-involved adolescents and the set of factors which relate to the specific profiles. Findings are important for informing psychological assessment practices, as well as tailored interventions, for adolescents in the child welfare system.


Identification of new respiratory viruses in the new millennium.
The rapid advancement of molecular tools in the past 15 years has allowed for the retrospective discovery of several new respiratory viruses as well as the characterization of novel emergent strains. The inability to characterize the etiological origins of respiratory conditions, particularly in children, led several researchers to pursue the discovery of the underlying etiology of disease. In 2001, this led to the discovery of human metapneumovirus (hMPV) and soon following that the outbreak of Severe Acute Respiratory Syndrome coronavirus (SARS-CoV) promoted an increased interest in coronavirology and the latter discovery of human coronavirus (HCoV) NL63 and HCoV-HKU1. Human bocavirus, with its four separate lineages, discovered in 2005, has been linked to acute respiratory tract infections and gastrointestinal complications. Middle East Respiratory Syndrome coronavirus (MERS-CoV) represents the most recent outbreak of a completely novel respiratory virus, which occurred in Saudi Arabia in 2012 and presents a significant threat to human health. This review will detail the most current clinical and epidemiological findings to all respiratory viruses discovered since 2001.


De novo CD5+ diffuse large B-cell lymphoma: results of a detailed clinicopathological review in 120 patients.
De novo CD5-positive diffuse large B-cell lymphoma (CD5(+) DLBCL) is clinicopathologically and genetically distinct from CD5-negative (CD5(-)) DLBCL and mantle cell lymphoma. The aim of this retrospective study was to clarify the histopathological spectrum and obtain new information on the therapeutic implications of CD5(+) DLBCL. From 1984 to 2002, 120 patients with CD5(+) DLBCL were selected from 13 collaborating institutes. We analyzed the relationship between their morphological features and long-term survival. The current series includes 101 patients described in our previous study. Four morphological variants were identified: common (monomorphic) (n=91), giant cell-rich (n=13), polymorphic (n=14), and immunoblastic (n=2). Intravascular or sinusoidal infiltration was seen in 38% of the cases. BCL2 protein expression in CD5(+) DLBCL was more frequent than in CD5(-) DLBCL (p=0.0003). Immunohistochemical analysis in 44 consecutive cases of CD5(+) DLBCL revealed that 82% of these cases (36/44) were non-germinal center B-cell type DLBCL. The 5-year overall survival rate of the patients with CD5(+) DLBCL was 38% after a median observation time of 81 months. Patients with the common variant showed a better prognosis than those with the other three variants (p=0.011), and this was confirmed on multivariate analysis. Overall, 16 patients (13%) developed central nervous system recurrence. Our study revealed the morphological spectrum of CD5(+) DLBCL, found that the incidence of central nervous system recurrence in this form of lymphoma in high, confirmed that CD5(+) DLBCL frequently expresses BCL2 protein and showed that it is mainly included in the non-germinal center B-cell type of DLBCL.


The status of serum vitamin D in patients with rheumatoid arthritis and undifferentiated inflammatory arthritis compared with controls.
Inadequate vitamin D may be involved in the pathogenesis and or progression of several disorders, including connective tissue diseases. To determine the status of vitamin D in different stages of inflammatory arthritis, the levels of vitamin D in established rheumatoid arthritis (RA) and undifferentiated inflammatory arthritis (UIA) were compared with controls. Patients with RA and UIA entered the study. Serum 25-hydroxyvitamin D (25-OHD) was measured by ELISA method, and concentrations less than 20 ng/ml were considered as deficient levels. In statistical analysis, the Mann-Whitney U test was used for comparing differences between groups and logistic regression analysis with calculation of adjusted odds ratio (OR) was used to determine the association between serum 25-OHD deficiency and disease condition. A total of 108 RA, 39 UIA, and 239 controls were studied. There were no significant differences in mean serum 25-OHD level and frequency of serum 25-OHD deficiency between RA and controls (37 ± 37.7 vs. 33.2 ± 28.6 ng/ml, P = 0.96). But the mean serum 25-OHD level in UIA was significantly lower than in the controls (25.1 ± 23.9 vs. 33.2 ± 28.6 ng ml, P = 0.04). A significant positive association was observed between serum 25-OHD deficiency and UIA (56.4% vs. 35.5%, OR = 2.34, 95% CI, 1.18-4.65, P = 0.021) which remained significant after adjustment for sex and age (adjusted OR = 2.24, 95% CI, 1.01-4.55, P = 0.026). Whereas the association between serum 25-OHD deficiency and RA did not reach statistical significance (40.7% vs. 35.5%, OR = 1.24, 95% CI, 0.78-1.99). These findings indicate higher serum vitamin D deficiency in patients with ongoing arthritis rather than established arthritis. Respecting to deleterious effects of vitamin D deficiency on immune system and progressive nature of UIA, a significant proportion of high risk UIA can be recognized by serum 25-OHD determination.


Mortality risk prediction of high-sensitivity C-reactive protein in suspected acute coronary syndrome: A cohort study.
There is limited evidence on the use of high-sensitivity C-reactive protein (hsCRP) as a biomarker for selecting patients for advanced cardiovascular (CV) therapies in the modern era. The prognostic value of mildly elevated hsCRP beyond troponin in a large real-world cohort of unselected patients presenting with suspected acute coronary syndrome (ACS) is unknown. We evaluated whether a mildly elevated hsCRP (up to 15 mg/L) was associated with mortality risk, beyond troponin level, in patients with suspected ACS. We conducted a retrospective cohort study based on the National Institute for Health Research Health Informatics Collaborative data of 257,948 patients with suspected ACS who had a troponin measured at 5 cardiac centres in the United Kingdom between 2010 and 2017. Patients were divided into 4 hsCRP groups (<2, 2 to 4.9, 5 to 9.9, and 10 to 15 mg/L). The main outcome measure was mortality within 3 years of index presentation. The association between hsCRP levels and all-cause mortality was assessed using multivariable Cox regression analysis adjusted for age, sex, haemoglobin, white cell count (WCC), platelet count, creatinine, and troponin. Following the exclusion criteria, there were 102,337 patients included in the analysis (hsCRP <2 mg/L (n = 38,390), 2 to 4.9 mg/L (n = 27,397), 5 to 9.9 mg/L (n = 26,957), and 10 to 15 mg/L (n = 9,593)). On multivariable Cox regression analysis, there was a positive and graded relationship between hsCRP level and mortality at baseline, which remained at 3 years (hazard ratio (HR) (95% CI) of 1.32 (1.18 to 1.48) for those with hsCRP 2.0 to 4.9 mg/L and 1.40 (1.26 to 1.57) and 2.00 (1.75 to 2.28) for those with hsCRP 5 to 9.9 mg/L and 10 to 15 mg/L, respectively. This relationship was independent of troponin in all suspected ACS patients and was further verified in those who were confirmed to have an ACS diagnosis by clinical coding. The main limitation of our study is that we did not have data on underlying cause of death; however, the exclusion of those with abnormal WCC or hsCRP levels >15 mg/L makes it unlikely that sepsis was a major contributor. These multicentre, real-world data from a large cohort of patients with suspected ACS suggest that mildly elevated hsCRP (up to 15 mg/L) may be a clinically meaningful prognostic marker beyond troponin and point to its potential utility in selecting patients for novel treatments targeting inflammation. ClinicalTrials.gov - NCT03507309.


Contribution of indirect computed tomography venography to computed tomography angiography of the chest for the diagnosis of thromboembolic disease in two United States emergency departments.
Recent reports suggest that physicians in non-ambulatory settings can use indirect CT venography (CTV) of the lower extremities immediately following spiral CT angiography (CTA) of the chest to identify patients with a negative CTA who have thromboembolic disease identified on CTV. We sought to determine the frequency of isolated deep venous thrombosis (DVT) discovered on CTV in emergency department (ED) patients with complaints suggestive of pulmonary embolism (PE) yet having a negative CTA. This study was conducted in a suburban and urban ED where patients with symptoms suspicious for PE were primarily evaluated with CTA and CTV. A total of 800 patients were studied, including 360 from the suburban ED and 440 from the urban ED. 88 (11%) patients were diagnosed with thromboembolic disease by CTA, or CTV, or both. Seventy-three patients had a CTA of the chest that was positive for PE, 42 (5.2%) of whom had evidence of both PE on CTA and DVT on CTV. Fifteen patients (2%, 95% CI = 1-3%) had a negative CTA and were subsequently found to have isolated DVT on CTV, all of whom received anticoagulation therapy. These data suggest that indirect CT venography of immediately following CT angiography of the chest significantly increased the frequency of diagnosed thromboembolic disease requiring anticoagulation in ED patients with suspected PE.


Regulation of cerebral blood flow after asphyxia in neonatal lambs.
In a postasphyxia neonatal lamb model, the responses of the cerebral circulation to hypoxic hypoxia and changes in systemic arterial blood pressure were examined. Ventilated newborn lambs (n = 14) were subjected to a gradual asphyxial insult, resuscitated, and returned to control ventilator settings. During the time 2-5 hours after asphyxia, the responses of cerebral blood flow (CBF), cerebral oxygen delivery (OD), cerebral oxygen consumption (CMRO2), and cerebral fractional oxygen extraction (E) to changes in either arterial oxygen content (CaO2) or mean arterial blood pressure (MAP) were assessed. These data were compared with measurements from nonasphyxiated lambs (n = 7). With hypoxia (n = 7), cerebral blood flow increased (CBF = 646/CaO2 + 44) compared with nonasphyxiated lambs (CBF = 1121/CaO2 + 11). In asphyxiated lambs, cerebral oxygen delivery decreased (OD = 0.41 CaO2 + 6.87), but cerebral oxygen consumption remained stable due to a proportional increase in cerebral fractional oxygen extraction (E = -0.014 CaO2 + 0.65). In nonasphyxiated lambs, cerebral oxygen delivery, consumption, and fractional extraction were unchanged with hypoxia. In response to alterations in blood pressure, both cerebral blood flow (CBF = 0.84 MAP + 6.62) and oxygen delivery (OD = 0.13 MAP + 0.77) were pressure-passive. With hypotension, cerebral fractional oxygen extraction increased (E = -0.003 MAP + 0.69) but not enough to prevent a decrease in cerebral oxygen consumption (CMRO2 = 0.042 MAP + 1.79). In nonasphyxiated lambs, cerebral blood flow, oxygen delivery, consumption, and fractional extraction did not vary with blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)


The CUL3/KLHL3-WNK-SPAK/OSR1 pathway as a target for antihypertensive therapy.
Chronic high blood pressure (hypertension) is the most common disease in the Unites States. While several classes of drugs exist to treat it, many patients (up to 10 million Americans) respond poorly to therapy, even when multiple classes are used. Recent evidence suggests that a significant portion of patients will always remain hypertensive despite maximum therapy with the drugs currently available. Therefore, there is a pressing need to develop novel antihypertensive agents. One limitation has been the identification of new targets, a limitation that has been overcome by recent insights into the mechanisms underlying monogenic forms of hypertension. The disease familial hyperkalemic hypertension is caused by mutations in with-no-lysine (WNK) kinases 1 and 4 and in cullin-3 and kelch-like 3, components of an E3 ubiquitin ligase complex that promotes WNK kinase degradation. The study of the mechanisms by which this pathway regulates blood pressure has identified several candidates for the development of new antihypertensive agents. This pathway is particularly attractive since its inhibition may not only reduce renal sodium reabsorption along multiple segments but may also reduce vascular tone. Here, we will describe the mechanisms by which this pathway regulate blood pressure and discuss the potential of targeting it to develop new antihypertensive drugs.


Gut Microbiome-Based Metagenomic Signature for Non-invasive Detection of Advanced Fibrosis in Human Nonalcoholic Fatty Liver Disease.
The presence of advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is the most important predictor of liver mortality. There are limited data on the diagnostic accuracy of gut microbiota-derived signature for predicting the presence of advanced fibrosis. In this prospective study, we characterized the gut microbiome compositions using whole-genome shotgun sequencing of DNA extracted from stool samples. This study included 86 uniquely well-characterized patients with biopsy-proven NAFLD, of which 72 had mild/moderate (stage 0-2 fibrosis) NAFLD, and 14 had advanced fibrosis (stage 3 or 4 fibrosis). We identified a set of 40 features (p < 0.006), which included 37 bacterial species that were used to construct a Random Forest classifier model to distinguish mild/moderate NAFLD from advanced fibrosis. The model had a robust diagnostic accuracy (AUC 0.936) for detecting advanced fibrosis. This study provides preliminary evidence for a fecal-microbiome-derived metagenomic signature to detect advanced fibrosis in NAFLD.


Beyond recreational physical activity: examining occupational and household activity, transportation activity, and sedentary behavior in relation to postmenopausal breast cancer risk.
We prospectively examined nonrecreational physical activity and sedentary behavior in relation to breast cancer risk among 97 039 postmenopausal women in the National Institutes of Health-AARP Diet and Health Study. We identified 2866 invasive and 570 in situ breast cancer cases recorded between 1996 and 2003 and used Cox proportional hazards regression to estimate multivariate relative risks (RRs) and 95% confidence intervals (CIs). Routine activity during the day at work or at home that included heavy lifting or carrying versus mostly sitting was associated with reduced risk of invasive breast cancer (RR = 0.62; 95% CI = 0.42, 0.91; P(trend) = .024). Routine activity during the day at work or home may be related to reduced invasive breast cancer risk. Domains outside of recreation time may be attractive targets for increasing physical activity and reducing sedentary behavior among postmenopausal women.


Precise tuning of barnacle leg length to coastal wave action.
Both spatial and temporal variation in environmental conditions can favour intraspecific plasticity in animal form. But how precise is such environmental modulation? Individual Balanus glandula Darwin, a common northeastern Pacific barnacle, produce longer feeding legs in still water than in moving water. We report here that, on the west coast of Vancouver Island, Canada, the magnitude and the precision of this phenotypic variation is impressive. First, the feeding legs of barnacles from protected bays were nearly twice as long (for the same body mass) as those from open ocean shores. Second, leg length varied surprisingly precisely with wave exposure: the average maximum velocities of breaking waves recorded in situ explained 95.6-99.5% of the variation in average leg length observed over a threefold range of wave exposure. The decline in leg length with increasing wave action was less than predicted due to simple scaling, perhaps due to changes in leg shape or material properties. Nonetheless, the precision of this relationship reveals a remarkably close coupling between growth environment and adult form, and suggests that between-population differences in barnacle leg length may be used for estimating differences in average wave exposure easily and accurately in studies of coastal ecology.


Magnetic resonance microscopy.
MRI, one of the major clinical imaging modalities, has gained an important role in studying small animal models, e.g., rats and mice. But imaging rodents comes with challenges, since the image resolution needs to be ~ 3000-times higher to resolve anatomical details at a level comparable to clinical imaging. A resolution on the order of 100 microns or less redefines MR imaging as MR microscopy. We discuss in this chapter the basic components of the MR imaging chain, with a particular emphasis on small animal imaging demands: from hardware design to basic physical principles of MR image formation, and contrast mechanisms. We discuss special considerations of animal preparation for imaging, and staining methods to enhance contrast. Attention is given to factors that increase sensitivity, including exogenous contrast agents, high performance radiofrequency detectors, and advanced MR encoding sequences. Among these, diffusion tensor imaging and tractography add novel information on white matter tracts, helping to better understand important aspects of development and neurodegeneration. These developments open avenues for efficient phenotyping of small animal models, in vivo - to include anatomical as well as functional estimates, or ex-vivo - with exquisite anatomical detail. The need for higher resolution results in larger image arrays that need to be processed efficiently. We discuss image-processing approaches for quantitative characterization of animal cohorts, and building population atlases. High throughput is essential for these methods to become practical. We discuss current trends for increasing detector performance, the use of cryoprobes, as well as strategies for imaging multiple animals at the same time. Ultimately, the development of highly specific probes, with the possibility to be used in multimodal imaging, will offer new insights into histology. MRM, alone or in combination with other imaging modalities, will increase the knowledge of fundamental biological processes, help understanding the genetic basis of human diseases, and test pharmacological interventions.


Caustic ingestion in adults: the role of endoscopic classification in predicting outcome.
The ingestion of caustic substances induces an extensive spectrum of injuries to the aerodigestive tract which include extensive necrosis and perforation of the esophagus and stomach. The gold standard of safely assessing depth, extent of injury, and appropriate therapeutic regimen is esophagogastroduodenoscopy (EGD). The objective of this study was to report our clinical experience and to evaluate the role of a 6-point EGD classification system of injury in predicting outcomes in adult patients diagnosed with caustic agent ingestion. The study was a retrospective medical chart review from 273 patients admitted to the Chang Gung Memorial Hospital in Tao-Yuan, Taiwan between June 1999 and July 2006 for treatment of caustic ingestion. The patients underwent EGD within 24 hours of admission and mucosal damage was graded using Zagar's modified endoscopic classification scheme. After treatment, patients were followed in the outpatient clinic for a minimum of 6 months. A total of 273 patients were included for analysis. Grade 3b injury was the most common caustic injury (n = 82, 30.03%), followed by grade 2b injuries (n = 62, 22.71%). Stricture was the most common complication (n = 66, 24.18%), followed by aspiration pneumonia (n = 31, 11.36%), and respiratory failure (n = 21, 7.69%). Compared to grade 3a mucosal injury, grade 3b mucosal injuries were at greater risk of prolonged hospital stay (odds ratio [OR]: 2.44; 95% confidence interval [CI]: 1.25-4.80), ICU admission (OR: 10.82; 95% CI: 2.05-200.39), and gastrointestinal (OR: 4.15; 95% CI: 1.55-13.29) and systemic complications (OR: 4.07; 95% CI: 1.81-14.07). In patients with caustic ingestion, EGD should be performed within 12 to 24 hours and categorized according to a 6-point scale. Patients with grade 3b burns identified on endoscopy have high rates of morbidity. The 6-point scale is useful for predicting immediate and long-term complications, and guiding appropriate therapy.


Chemical Gas Sensors: Recent Developments, Challenges, and the Potential of Machine Learning-A Review.
Nowadays, there is increasing interest in fast, accurate, and highly sensitive smart gas sensors with excellent selectivity boosted by the high demand for environmental safety and healthcare applications. Significant research has been conducted to develop sensors based on novel highly sensitive and selective materials. Computational and experimental studies have been explored in order to identify the key factors in providing the maximum active location for gas molecule adsorption including bandgap tuning through nanostructures, metal/metal oxide catalytic reactions, and nano junction formations. However, there are still great challenges, specifically in terms of selectivity, which raises the need for combining interdisciplinary fields to build smarter and high-performance gas/chemical sensing devices. This review discusses current major gas sensing performance-enhancing methods, their advantages, and limitations, especially in terms of selectivity and long-term stability. The discussion then establishes a case for the use of smart machine learning techniques, which offer effective data processing approaches, for the development of highly selective smart gas sensors. We highlight the effectiveness of static, dynamic, and frequency domain feature extraction techniques. Additionally, cross-validation methods are also covered; in particular, the manipulation of the k-fold cross-validation is discussed to accurately train a model according to the available datasets. We summarize different chemresistive and FET gas sensors and highlight their shortcomings, and then propose the potential of machine learning as a possible and feasible option. The review concludes that machine learning can be very promising in terms of building the future generation of smart, sensitive, and selective sensors.


Spatiotemporal dynamics of the Calvin cycle: multistationarity and symmetry breaking instabilities.
The possibility of controlling the Calvin cycle has paramount implications for increasing the production of biomass. Multistationarity, as a dynamical feature of systems, is the first obvious candidate whose control could find biotechnological applications. Here we set out to resolve the debate on the multistationarity of the Calvin cycle. Unlike the existing simulation-based studies, our approach is based on a sound mathematical framework, chemical reaction network theory and algebraic geometry, which results in provable results for the investigated model of the Calvin cycle in which we embed a hierarchy of realistic kinetic laws. Our theoretical findings demonstrate that there is a possibility for multistationarity resulting from two sources, homogeneous and inhomogeneous instabilities, which partially settle the debate on multistability of the Calvin cycle. In addition, our tractable analytical treatment of the bifurcation parameters can be employed in the design of validation experiments.


Rapid eruption of the Columbia River flood basalt and correlation with the mid-Miocene climate optimum.
Flood basalts, the largest volcanic events in Earth history, are thought to drive global environmental change because they can emit large volumes of CO2 and SO2 over short geologic time scales. Eruption of the Columbia River Basalt Group (CRBG) has been linked to elevated atmospheric CO2 and global warming during the mid-Miocene climate optimum (MMCO) ~16 million years (Ma) ago. However, a causative relationship between volcanism and warming remains speculative, as the timing and tempo of CRBG eruptions is not well known. We use U-Pb geochronology on zircon-bearing volcanic ash beds intercalated within the basalt stratigraphy to build a high-resolution CRBG eruption record. Our data set shows that more than 95% of the CRBG erupted between 16.7 and 15.9 Ma, twice as fast as previous estimates. By suggesting a recalibration of the geomagnetic polarity time scale, these data indicate that the onset of flood volcanism is nearly contemporaneous with that of the MMCO.


Monitoring the progression of metastatic breast cancer on nanoporous silica chips.
Breast cancer accounted for 15 per cent of total cancer deaths in female patients in 2010. Although significant progress has been made in treating early-stage breast cancer patients, there is still no effective therapy targeting late-stage metastatic breast cancers except for the conventional chemotherapy interventions. Until effective therapy for later-stage cancers emerges, the identification of biomarkers for the early detection of tumour metastasis continues to hold the key to successful management of breast cancer therapy. Our study concentrated on the low molecular weight (LMW) region of the serum protein and the information it contains for identifying biomarkers that could reflect the ongoing physiological state of all tissues. Owing to technical difficulties in harvesting LMW species, studying these proteins/peptides has been challenging until now. In our study, we have recently developed nanoporous chip-based technologies to separate small proteins/peptides from the large proteins in serum. We used nanoporous silica chips, with a highly periodic nanostructure and uniform pore size distribution, to isolate LMW proteins and peptides from the serum of nude mice with MDA-MB-231 human breast cancer lung metastasis. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biostatistical analysis, we were able to identify protein signatures unique to different stages of cancer development. The approach and results reported in this study possess a significant potential for the discovery of proteomic biomarkers that may significantly enhance personalized medicine targeted at metastatic breast cancer.


Scenarios of future climate and land-management effects on carbon stocks in northern Patagonian shrublands.
We analyzed the possible effects of grazing management and future climate change on carbon (C) stocks in soils of northern Patagonian shrublands. To this aim, we coupled the outputs of three (HadCM3, CSIRO Mk2, and CCSR/NIES) global climate models to the CENTURY (v5.3) model of terrestrial C balance. The CENTURY model was initialized with long-term field data on local biome physiognomy, seasonal phenologic trends, and prevailing land-management systems and was validated with recent sequences of 1-km Normalized Difference Vegetation Index (MODIS-Terra) images and soil C data. In the tested scenarios, the predicted climate changes would result in increased total C in soil organic matter (SOMTC). Maximum SOMTC under changed climate forcing would not differ significantly from that expected under baseline conditions (8 kg m(-2)). A decrease in grazing intensity would result in SOMTC increases of 11% to 12% even if climate changes did not occur. Climate change would account for SOMTC increases of 5% to 6%.


Adaptive Iterative Dose Reduction Using Three Dimensional Processing (AIDR3D) improves chest CT image quality and reduces radiation exposure.
To assess the advantages of Adaptive Iterative Dose Reduction using Three Dimensional Processing (AIDR3D) for image quality improvement and dose reduction for chest computed tomography (CT). Institutional Review Boards approved this study and informed consent was obtained. Eighty-eight subjects underwent chest CT at five institutions using identical scanners and protocols. During a single visit, each subject was scanned using different tube currents: 240, 120, and 60 mA. Scan data were converted to images using AIDR3D and a conventional reconstruction mode (without AIDR3D). Using a 5-point scale from 1 (non-diagnostic) to 5 (excellent), three blinded observers independently evaluated image quality for three lung zones, four patterns of lung disease (nodule/mass, emphysema, bronchiolitis, and diffuse lung disease), and three mediastinal measurements (small structure visibility, streak artifacts, and shoulder artifacts). Differences in these scores were assessed by Scheffe's test. At each tube current, scans using AIDR3D had higher scores than those without AIDR3D, which were significant for lung zones (p<0.0001) and all mediastinal measurements (p<0.01). For lung diseases, significant improvements with AIDR3D were frequently observed at 120 and 60 mA. Scans with AIDR3D at 120 mA had significantly higher scores than those without AIDR3D at 240 mA for lung zones and mediastinal streak artifacts (p<0.0001), and slightly higher or equal scores for all other measurements. Scans with AIDR3D at 60 mA were also judged superior or equivalent to those without AIDR3D at 120 mA. For chest CT, AIDR3D provides better image quality and can reduce radiation exposure by 50%.


Study of thermally poled fibers with a two-dimensional model.
A two-dimensional (2D) numerical model is implemented to describe the movement of ions under thermal poling for the specific case of optical fibers. Three types of cations are considered (representing Na(+), Li(+) and H3O(+)) of different mobility values. A cross-sectional map of the carrier concentration is obtained as a function of time. The role of the various cations is investigated. The assumptions of the model are validated by comparing the predictions to experimental data of the time evolution of the nonlinearity induced. A variational analysis of poling parameters including temperature, poling voltage, sign of the bias potential and initial ionic concentrations is performed for a particular fiber geometry. The analysis allows identifying the impact of these parameters on the induced second-order nonlinearity in poled fibers.


Use of alemtuzumab and tacrolimus monotherapy for cadaveric liver transplantation: with particular reference to hepatitis C virus.
We have proposed that the mechanisms of alloengraftment and variable acquired tolerance can be facilitated by minimum posttransplant immunosuppression. It was further suggested that the efficacy of minimalistic treatment could be enhanced by preoperative recipient conditioning with an antilymphoid antibody preparation. A total of 76 adults (38 hepatitis C virus [HCV], 38 HCV) were infused with 30 mg alemtuzumab before primary cadaveric liver transplantation and maintained afterward on daily monotherapy unless breakthrough rejection mandated additional agents. In stable patients, the intervals between tacrolimus doses were lengthened ("spaced weaning") after approximately 4 months. Eighty-four contemporaneous nonlymphoid-depleted liver recipients (58 HCV, 26 HCV) were treated with conventional postoperative immunosuppression. The overall incidence of rejection was similar with the two strategies of immunosuppression. With follow-ups of 14 to 22 months, patient and primary graft survival in HCV cases are 97% and 90%, respectively, with alemtuzumab depletion plus minimal immunosuppression versus 71% and 70%, respectively, under conventional immunosuppression. In HCV recipients, current patient and graft survival in the alemtuzumab-pretreated group are 71% and 70% versus 65% and 54%, respectively, under conventional treatment. With both strategies of immunosuppression, the adverse effect of preexisting HCV on survival parameters and graft function already was significant at the 1-year milestone, but its extent was not evident until the second year. With or without HCV, 62% of the 64 surviving lymphoid-depleted patients are on spaced immunosuppression, and four patients receive no immunosuppression. Lymphoid depletion with alemtuzumab and minimalistic maintenance immunosuppression is a practical strategy of liver transplantation in HCV recipients but not HCV recipients.


Elastography method for reconstruction of nonlinear breast tissue properties.
Elastography is developed as a quantitative approach to imaging linear elastic properties of tissues to detect suspicious tumors. In this paper a nonlinear elastography method is introduced for reconstruction of complex breast tissue properties. The elastic parameters are estimated by optimally minimizing the difference between the computed forces and experimental measures. A nonlinear adjoint method is derived to calculate the gradient of the objective function, which significantly enhances the numerical efficiency and stability. Simulations are conducted on a three-dimensional heterogeneous breast phantom extracting from real imaging including fatty tissue, glandular tissue, and tumors. An exponential-form of nonlinear material model is applied. The effect of noise is taken into account. Results demonstrate that the proposed nonlinear method opens the door toward nonlinear elastography and provides guidelines for future development and clinical application in breast cancer study.