Registration of the endoluminal surfaces of the colon derived from prone and supine CT colonography.
Computed tomographic (CT) colonography is a relatively new technique for detecting bowel cancer or potentially precancerous polyps. CT scanning is combined with three-dimensional (3D) image reconstruction to produce a virtual endoluminal representation similar to optical colonoscopy. Because retained fluid and stool can mimic pathology, CT data are acquired with the bowel cleansed and insufflated with gas and patient in both prone and supine positions. Radiologists then match visually endoluminal locations between the two acquisitions in order to determine whether apparent pathology is real or not. This process is hindered by the fact that the colon, essentially a long tube, can undergo considerable deformation between acquisitions. The authors present a novel approach to automatically establish spatial correspondence between prone and supine endoluminal colonic surfaces after surface parameterization, even in the case of local colon collapse. The complexity of the registration task was reduced from a 3D to a 2D problem by mapping the surfaces extracted from prone and supine CT colonography onto a cylindrical parameterization. A nonrigid cylindrical registration was then performed to align the full colonic surfaces. The curvature information from the original 3D surfaces was used to determine correspondence. The method can also be applied to cases with regions of local colonic collapse by ignoring the collapsed regions during the registration. Using a development set, suitable parameters were found to constrain the cylindrical registration method. Then, the same registration parameters were applied to a different set of 13 validation cases, consisting of 8 fully distended cases and 5 cases exhibiting multiple colonic collapses. All polyps present were well aligned, with a mean (+/- std. dev.) registration error of 5.7 (+/- 3.4) mm. An additional set of 1175 reference points on haustral folds spread over the full endoluminal colon surfaces resulted in an error of 7.7 (+/- 7.4) mm. Here, 82% of folds were aligned correctly after registration with a further 15% misregistered by just onefold. The proposed method reduces the 3D registration task to a cylindrical registration representing the endoluminal surface of the colon. Our algorithm uses surface curvature information as a similarity measure to drive registration to compensate for the large colorectal deformations that occur between prone and supine data acquisitions. The method has the potential to both enhance polyp detection and decrease the radiologist's interpretation time.


Interaction of HP1 and Brg1/Brm with the globular domain of histone H3 is required for HP1-mediated repression.
The heterochromatin-enriched HP1 proteins play a critical role in regulation of transcription. These proteins contain two related domains known as the chromo- and the chromoshadow-domain. The chromo-domain binds histone H3 tails methylated on lysine 9. However, in vivo and in vitro experiments have shown that the affinity of HP1 proteins to native methylated chromatin is relatively poor and that the opening of chromatin occurring during DNA replication facilitates their binding to nucleosomes. These observations prompted us to investigate whether HP1 proteins have additional histone binding activities, envisioning also affinity for regions potentially occluded by the nucleosome structure. We find that the chromoshadow-domain interacts with histone H3 in a region located partially inside the nucleosomal barrel at the entry/exit point of the nucleosome. Interestingly, this region is also contacted by the catalytic subunits of the human SWI/SNF complex. In vitro, efficient SWI/SNF remodeling requires this contact and is inhibited in the presence of HP1 proteins. The antagonism between SWI/SNF and HP1 proteins is also observed in vivo on a series of interferon-regulated genes. Finally, we show that SWI/SNF activity favors loading of HP1 proteins to chromatin both in vivo and in vitro. Altogether, our data suggest that HP1 chromoshadow-domains can benefit from the opening of nucleosomal structures to bind chromatin and that HP1 proteins use this property to detect and arrest unwanted chromatin remodeling.


Acquired congenital heart block. Pattern of maternal antibody response to biochemically defined antigens of the SSA/Ro-SSB/La system in neonatal lupus.
The molecular basis of autoantibody reactivity with components of the SSA/Ro-SSB/La particle exhibited by sera of mothers of infants with severe and permanent manifestations of neonatal lupus (NLE) was investigated using immunoblotting and immunoprecipitation. The characteristics of NLE that were studied included congenital complete heart block (CCHB), second degree heart block, and hepatic fibrosis. Antibodies specific for one or more components of the SSA/Ro-SSB/La particle were found in sera from all 20 mothers of permanently affected infants. However, no antibody specific for a single peptide of this particle was common to all sera. Using tissue extracts from a human cell substrate, 80% of these sera had antibodies to one or more components of the SSA/Ro particle demonstrable by immunoblotting. The predominant antibody response in the NLE group was to the newly recognized 52-kD SSA/Ro peptide component. In contrast, antibodies to the 60-kD SSA/Ro component although present, were the least represented and not significantly increased in frequency among mothers of these infants, compared with a group of 31 mothers with autoimmune diseases such as systemic lupus erythromatosus (SLE) but who had healthy offspring. Antibodies directed to the 48-kD SSB/La antigen were demonstrated in 90% of the NLE mothers often accompanying antibodies against the 52-kD SSA/Ro component. The combination of antibodies to 48- and 52-kD structures was significantly increased in the NLE group, with an odds ratio of 35. The type of cell or tissue substrate was shown to influence detectability of antibodies. The 52-kD SSA/Ro peptide and the 48-kD SSB/La peptide were abundant in cardiac tissues from fetuses aged 18-24 wk, further supporting the possible relevance of these peptides to heart block.


Unified calibration technique and its applications in optical triangular profilometry.
A unified calibration technique based on ray tracing for optical triangular profilometry is presented. The proposed technique based on the inherent geometric relation between depth and a distorted signal is capable of speedy and accurate measurement without the determination of geometric parameters. The technique can also reduce calibration error caused by the lens distortion of the projector and the camera owing to the reasonable assumption that mapping in a small local area is a linear transformation and the coefficients of the linear transformation may be varied in different local areas. Three classical systems of triangular profilometry, spot inspection, a single-line system, and a projection-grating system, are discussed and demonstrated by experiment.


SHEA-CDC TB survey, Part I: Status of TB infection control programs at member hospitals, 1989-1992. Society for Healthcare Epidemiology of America.
To determine trends in Mycobacterium tuberculosis infection in healthcare workers, tuberculosis (TB) control measures, and compliance with the 1990 Centers for Disease Control and Prevention (CDC) guideline for preventing transmission of TB in healthcare facilities. Voluntary questionnaire sent to all members of the Society for Healthcare Epidemiology of America, representing 359 hospitals. Respondents' hospitals (210 [58%]) had a median of 2,400 healthcare workers (range, 396 to 13,745), 437 beds (range, 48 to 1,250), 5.6 patients with TB per year (range, 0 to 492), and 0 multidrug-resistant (MDR) TB patients per year (range, 0 to 33). Of 166 respondents' hospitals for which data were provided for 1989 through 1992, the number caring for MDR-TB patients increased from 10 (6%) in 1989 to 49 (30%) in 1992. Reported policies for routine healthcare worker tuberculin skin testing varied. The median skin-test positivity rate for healthcare workers at the time of hire increased from 0.54% in 1989 to 0.81% in 1992, but the median conversion rate during routine testing remained similar: 0.35% in 1989 and 0.33% in 1992. Among 196 hospitals with reported data on respiratory protection use for 1989 through 1992, the use of either surgical submicron, dust-mist, or dust-fume-mist respirators for healthcare workers increased from 9 (5%) in 1989 to 85 (43%) in 1992. Of 181 hospitals with reported data, 113 (62%) had acid-fast bacilli isolation facilities consistent with the 1990 CDC guideline (ie, a single patient room, negative air pressure relative to the hallway, air exhausted directly outside, and > or = 6 air exchanges per hour). While the number of surveyed hospitals caring for TB and MDR-TB patients increased during 1989 through 1992, TB infection control measures at many hospitals still did not meet the 1990 CDC guideline recommendations.


Participatory development and analysis of a fuzzy cognitive map of the establishment of a bio-based economy in the Humber region.
Fuzzy Cognitive Mapping (FCM) is a widely used participatory modelling methodology in which stakeholders collaboratively develop a 'cognitive map' (a weighted, directed graph), representing the perceived causal structure of their system. This can be directly transformed by a workshop facilitator into simple mathematical models to be interrogated by participants by the end of the session. Such simple models provide thinking tools which can be used for discussion and exploration of complex issues, as well as sense checking the implications of suggested causal links. They increase stakeholder motivation and understanding of whole systems approaches, but cannot be separated from an intersubjective participatory context. Standard FCM methodologies make simplifying assumptions, which may strongly influence results, presenting particular challenges and opportunities. We report on a participatory process, involving local companies and organisations, focussing on the development of a bio-based economy in the Humber region. The initial cognitive map generated consisted of factors considered key for the development of the regional bio-based economy and their directional, weighted, causal interconnections. A verification and scenario generation procedure, to check the structure of the map and suggest modifications, was carried out with a second session. Participants agreed on updates to the original map and described two alternate potential causal structures. In a novel analysis all map structures were tested using two standard methodologies usually used independently: linear and sigmoidal FCMs, demonstrating some significantly different results alongside some broad similarities. We suggest a development of FCM methodology involving a sensitivity analysis with different mappings and discuss the use of this technique in the context of our case study. Using the results and analysis of our process, we discuss the limitations and benefits of the FCM methodology in this case and in general. We conclude by proposing an extended FCM methodology, including multiple functional mappings within one participant-constructed graph.


iTrack: instrumented mobile electrooculography (EOG) eye-tracking in older adults and Parkinson's disease.
Detection of saccades (fast eye-movements) within raw mobile electrooculography (EOG) data involves complex algorithms which typically process data acquired during seated static tasks only. Processing of data during dynamic tasks such as walking is relatively rare and complex, particularly in older adults or people with Parkinson's disease (PD). Development of algorithms that can be easily implemented to detect saccades is required. This study aimed to develop an algorithm for the detection and measurement of saccades in EOG data during static (sitting) and dynamic (walking) tasks, in older adults and PD. Eye-tracking via mobile EOG and infra-red (IR) eye-tracker (with video) was performed with a group of older adults (n = 10) and PD participants (n = 10) (⩾50 years). Horizontal saccades made between targets set 5°, 10° and 15° apart were first measured while seated. Horizontal saccades were then measured while a participant walked and executed a 40° turn left and right. The EOG algorithm was evaluated by comparing the number of correct saccade detections and agreement (ICC2,1) between output from visual inspection of eye-tracker videos and IR eye-tracker. The EOG algorithm detected 75-92% of saccades compared to video inspection and IR output during static testing, with fair to excellent agreement (ICC2,1 0.49-0.93). However, during walking EOG saccade detection reduced to 42-88% compared to video inspection or IR output, with poor to excellent (ICC2,1 0.13-0.88) agreement between methodologies. The algorithm was robust during seated testing but less so during walking, which was likely due to increased measurement and analysis error with a dynamic task. Future studies may consider a combination of EOG and IR for comprehensive measurement.


Robot-assisted transhiatal esophagectomy: a 3-year single-center experience.
Minimally invasive esophagectomy has emerged as an important procedure for disease management in esophageal cancer (EC) with clear margin status, less morbidity, and shorter hospital stays compared with open procedures. The experience with transhiatal approach robotic esophagectomy (RE) for dissection of thoracic esophagus and associated morbidity is described here. Between March 2007 and November 2010, 40 patients with resectable esophageal indications underwent transhiatal RE at the institute. Clinical data for all patients were collected prospectively. Of 40 patients undergoing RE, one patient had an extensive benign stricture, one had high-grade dysplasia, and 38 had EC. Five patients were converted from robotic to open. Median operative time and estimated blood loss were 311 minutes and 97.2 mL, respectively. Median intensive care unit stay was 1 day (range, 0-16), and median length of hospital stay was 9 days (range, 6-36). Postoperative complications frequently observed were anastomotic stricture (n= 27), recurrent laryngeal nerve paresis (n= 14), anastomotic leak (n= 10), pneumonia (n= 8), and pleural effusion (n= 18). Incidence rates of laryngeal nerve paresis (35%) and leak rate (25%) were somewhat higher in comparison with that reported in literature. However, all vocal cord injuries were temporary, and all leaks healed following opening of the cervical incision and drainage. None of the patients died in the hospital, and 30-day mortality was 2.5% (1/40). Median number of lymph nodes removed was 20 (range, 3-38). In 33 patients with known lymph node locations, median of four (range, 0-12) nodes was obtained from the mediastinum, and median of 15 (range, 1-26) was obtained from the abdomen. R0 resection was achieved in 94.7% of patients. At the end of the follow-up period, 25 patients were alive, 13 were deceased, and 2 patients were lost to follow-up. For patients with EC, median disease-free survival was 20 months (range, 3-45). Transhiatal RE, by experience, is a feasible albeit evolving oncologic operation with low hospital mortality. The benefits include minimally invasive mediastinal dissection without thoracotomy or thoracoscopy. A reasonable operative time with minimal blood loss and postoperative morbidity can be achieved, in spite of the technically demanding nature of the procedure. Broader use of this technology in a setting of high-volume comprehensive surgical programs will almost certainly reduce the complication rates. Robotic tanshiatal esophagectomy with the elimination of a thoracic approach should be considered an option for the appropriate patient population in a comprehensive esophageal program.


Effects of myenteric denervation on extracellular matrix fibers and mast cell distribution in normal stomach and gastric lesions.
In this study the effect of myenteric denervation induced by benzalconium chloride (BAC) on distribution of fibrillar components of extracellular matrix (ECM) and inflammatory cells was investigated in gastric carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Rats were divided in four experimental groups: non-denervated (I) and denervated stomach (II) without MNNG treatment; non-denervated (III) and denervated stomachs (IV) treated with MNNG. For histopathological, histochemical and stereological analysis, sections of gastric fragments were stained with Hematoxylin-Eosin, Picrosirius-Hematoxylin, Gomori reticulin, Weigert's Resorcin-Fuchsin, Toluidine Blue and Alcian-Blue/Safranin (AB-SAF). BAC denervation causes an increase in the frequency of reticular and elastic fibers in the denervated (group II) compared to the non-denervated stomachs (group I). The treatment of the animals with MNNG induced the development of adenocarcinomas in non-denervated and denervated stomachs (groups III and IV, respectively) with a notable increase in the relative volume of the stroma, the frequency of reticular fibers and the inflammatory infiltrate that was more intense in group IV. An increase in the frequency of elastic fibers was observed in adenocarcinomas of denervated (group IV) compared to the non-denervated stomachs (group III) that showed degradation of these fibers. The development of lesions (groups III and IV) was also associated with an increase in the mast cell population, especially AB and AB-SAF positives, the latter mainly in the denervated group IV. The results show a strong association in the morphological alteration of the ECM fibrillar components, the increased density of mast cells and the development of tumors induced by MNNG in the non-denervated rat stomach or denervated by BAC. This suggests that the study of extracellular and intracellular components of tumor microenvironment contributes to understanding of tumor biology by action of myenteric denervation.


Combined and independent effects of chronic marijuana use and HIV on brain metabolites.
The effects of chronic marijuana (MJ) use on brain function remain controversial. Because MJ is often used by human immunodeficiency virus (HIV) patients, the aim of this study was to evaluate whether chronic MJ use and HIV infection are associated with interactive or additive effects on brain chemistry and cognitive function. We evaluated 96 subjects (30 seronegative nondrug users, 24 MJ users, 21 HIV without MJ use, 21 HIV + MJ) using proton magnetic resonance spectroscopy and a battery of neuropsychological tests. The two primarily abstinent MJ user groups showed no significant differences on calculated estimates of lifetime grams of delta9-tetrahydrocannabinol exposure, despite some differences in usage pattern. The two HIV groups also had similar HIV disease severity (CD4 cell count, plasma viral load, HIV dementia staging, Karnofsky score). On two-way analyses of covariance, HIV infection (independent of MJ) was associated with trends for reduced N-acetyl aspartate (NA) in the parietal white matter and increased choline compounds (CHO) in the basal ganglia. In contrast, MJ (independent of HIV) was associated with decreased basal ganglia NA (-5.5%, p = 0.05), CHO (-10.6%, p = 0.04), and glutamate (-9.5%, p = 0.05), with increased thalamic creatine (+6.1%, p = 0.05). HIV + MJ was associated with normalization of the reduced glutamate in frontal white matter (interaction p = 0.01). After correction for age, education, or mood differences, MJ users had no significant abnormalities on neuropsychological test performance, and HIV subjects only had slower reaction times. These findings suggest chronic MJ use may lead to decreased neuronal and glial metabolites, but may normalize the decreased glutamate in HIV patients.


Prehabilitation versus no prehabilitation to improve functional capacity, reduce postoperative complications and improve quality of life in colorectal cancer surgery.
Surgery is the cornerstone in curative treatment of colorectal cancer. Unfortunately, surgery itself can adversely affect patient health. 'Enhanced Recovery After Surgery' programmes, which include multimodal interventions, have improved patient outcomes substantially. However, these are mainly applied peri- and postoperatively. Multimodal prehabilitation includes multiple preoperative interventions to prepare patients for surgery with the aim of increasing resilience, thereby improving postoperative outcomes. To determine the effects of multimodal prehabilitation programmes on functional capacity, postoperative complications, and quality of life in adult patients undergoing surgery for colorectal cancer. We searched CENTRAL, MEDLINE, Embase and PsycINFO in January 2021. We also searched trial registries up to March 2021. We included randomised controlled trials (RCTs) in adult patients with non-metastatic colorectal cancer, scheduled for surgery, comparing multimodal prehabilitation programmes (defined as comprising at least two preoperative interventions) with no prehabilitation. We focused on the following outcomes: functional capacity (i.e. 6-minute walk test, VO2peak, handgrip strength), postoperative outcomes (i.e. complications, mortality, length of hospital stay, emergency department visits, re-admissions), health-related quality of life, compliance, safety of prehabilitation, and return to normal activities. Two authors independently selected studies, extracted data, assessed risk of bias and used GRADE to assess the certainty of the evidence. Any disagreements were solved with discussion and consensus. We pooled data to perform meta-analyses, where possible. We included three RCTs that enrolled 250 participants with non-metastatic colorectal cancer, scheduled for elective (mainly laparoscopic) surgery. Included trials were conducted in tertiary care centres and recruited patients during periods ranging from 17 months to 45 months. A total of 130 participants enrolled in a preoperative four-week trimodal prehabilitation programme consisting of exercise, nutritional intervention, and anxiety reduction techniques. Outcomes of these participants were compared to those of 120 participants who started an identical but postoperative programme. Postoperatively, prehabilitation may improve functional capacity, determined with the 6-minute walk test at four and eight weeks (mean difference (MD) 26.02, 95% confidence interval (CI) -13.81 to 65.85; 2 studies; n = 131; and MD 26.58, 95% CI -8.88 to 62.04; 2 studies; n = 140); however, the certainty of evidence is low and very low, respectively, due to serious risk of bias, imprecision, and inconsistency. After prehabilitation, the functional capacity before surgery improved, with a clinically relevant mean difference of 24.91 metres (95% CI 11.24 to 38.57; 3 studies; n = 225). The certainty of evidence was moderate due to downgrading for serious risk of bias. The effects of prehabilitation on the number of complications (RR 0.95, 95% CI 0.70 to 1.29; 3 studies; n = 250), emergency department visits (RR 0.72, 95% CI 0.39 to 1.32; 3 studies; n = 250) and re-admissions (RR 1.20, 95% CI 0.54 to 2.65; 3 studies; n = 250) were small or even trivial. The certainty of evidence was low due to downgrading for serious risk of bias and imprecision. The effects on VO2peak, handgrip strength, length of hospital stay, mortality rate, health-related quality of life, return to normal activities, safety of the programme, and compliance rate could not be analysed quantitatively due to missing or insufficient data. The included studies did not report a difference between groups for health-related quality of life and length of hospital stay. Data on remaining outcomes were not reported or were reported inadequately in the included studies. Prehabilitation may result in an improved functional capacity, determined with the 6-minute walk test both preoperatively and postoperatively. A solid effect on the number of omplications, postoperative emergency department visits and re-admissions could not be established. The certainty of evidence ranges from moderate to very low, due to downgrading for serious risk of bias, imprecision and inconsistency. In addition, only three heterogeneous studies were included in this review. Therefore, the findings of this review should be interpreted with caution. Numerous relevant RCTs are ongoing and will be included in a future update of this review.


Centrosome abnormalities in giant cell tumour of bone: possible association with chromosomal instability.
Giant cell tumour of bone, a benign but potentially aggressive neoplasm, shows an increasing rate of chromosomal aneusomy that correlates with clinical course. Mechanisms that generate chromosomal instability in giant cell tumour of bone are poorly understood. One possible cause of chromosomal instability is an error in mitotic segregation due to numeric and/or functional abnormalities of centrosomes. Centrosome alteration is a common phenomenon in many cancers and has a major role in the development of chromosomal instability in cancer cells. To gain an insight into the possible mechanism for the generation of chromosomal instability in giant cell tumour of bone, we analysed 100 cases, including 57 primary nonrecurrent, 35 recurrent and 8 malignant giant cell tumour of bone cases. gamma-Tubulin immunohistochemistry was performed on tissue microarrays of 59 formalin-fixed paraffin-embedded cases, whereas pericentrin and gamma-tubulin fluorescent immunocytochemistry was carried out on 41 frozen smears. Fluorescent in situ hybridization was performed on 23 cases of pericentrin immunostained smears, allowing the simultaneous analysis of centrosomes and chromosome aberrations. Centrosome amplification was significantly higher in recurrent and malignant giant cell tumour of bones compared with nonrecurrent tumours (P<0.001). A comparison of the percentage of aneusomic cells with a normal centrosome content (4.7%) with that of aneusomic cells with centrosome amplification (6.4%) revealed no significant association between chromosome number alterations and centrosome aberrations (P=0.31). These findings indicate that centrosome alteration and frequency of aneusomy correlate with clinical behaviour; the lack of an association between centrosome amplification and chromosome number alteration suggests that alternative causative mechanisms produce genetic instability in giant cell tumour of bone.


Lower lifetime dietary fiber intake is associated with carotid artery stiffness: the Amsterdam Growth and Health Longitudinal Study.
Fiber intake is associated with lower cardiovascular disease risk. Whether arterial stiffness is influenced by lifetime fiber intake is not known. Any such association could explain, at least in part, the cardioprotective effects attributed to fiber intake. The objective was to investigate whether a lower intake of fiber (and fiber-rich foods) throughout the course of young life (ie, from adolescence to adulthood) is associated with arterial stiffness in adulthood. This was a longitudinal cohort study among 373 participants in whom dietary intake was assessed between the ages of 13 to 36 y (2-8 repeated measures, median of 5), and arterial stiffness estimates of 3 large arteries (ultrasonography) were ascertained at age 36 y. After adjustment for sex, height, total energy intake, and other lifestyle variables, subjects with stiffer carotid arteries consumed less fiber (in g/d) during the 24-y study than did those with less stiff carotid arteries, as defined on the basis of the highest compared with the lowest sex-specific tertiles of the distensibility and compliance coefficients (reversed) and Young's elastic modulus: -1.9 (95% CI: -3.1, -0.7), -2.3 (-3.5, -1.1), and -1.3 (-2.5, -0.0), respectively. Furthermore, subjects with stiffer carotid arteries were characterized by a lower lifetime consumption of fruit, vegetables, and whole grains-deleterious associations that could be explained, to a great extent, by related low fiber intake. Lower lifetime intake of fiber during the course of young age is associated with carotid artery stiffness in adulthood. Promoting consumption of fiber-rich foods among the young may offer a means to prevent accelerated arterial stiffening in adulthood and related cardiovascular sequelae.


Plasma extracellular vesicles detected by Single Molecule array technology as a liquid biopsy for colorectal cancer.
Circulating extracellular vesicles (EVs) were recognized as a promising source of diagnostic biomarker. However, there are limited studies published in this area, partly due to the limited number of detection platforms capable of detecting extracellular vesicles. In this study, extracellular vesicle immunoassays were developed using the Single Molecule array technology (SiMoa) and their clinical applications to cancer diagnosis were evaluated. Two extracellular vesicle detection assays, CD9-CD63 and Epcam-CD63, were designed to detect universal extracellular vesicles and tumour-derived extracellular vesicles, respectively. Our results show that CD9-CD63 and Epcam-CD63 SiMoa assays specifically detect extracellular vesicles but not free proteins with high sensitivities. The Epcam-CD63 levels detected in cancer cell culture media were consistent with levels of Epcam-expressing EVs isolated from the same cancer cell lines and detected by Western blot. Furthermore, the assays distinguish cancerous from non-cancerous plasma samples. The highest CD9-CD63 and Epcam-CD63 signals were observed in colorectal cancer patients comparing to healthy and benign controls. Both assays showed superior diagnostic performance for colorectal cancer. In addition, our results show that CD9-CD63 detection is an independent prognosis factor for both progression free survival and overall survival, while Epcam-CD63 detectionis an independent prognosis factor for OS.


Antimicrobial activities of ethanol and butanol fractions of white rose petal extract.
White rose (Rosa hybrida) petals were extracted with ethanol (EtOH) or butanol (BuOH), and tested for their antimicrobial activities against two species of Gram-positive bacteria, six species of Gram-negative bacteria, and two species of fungi. On in vitro antimicrobial assays, Helicobacter pylori and Propionibacterium acnes were highly susceptible to white rose petal extract (WRPE)-EtOH and WRPE-BuOH, leading to minimal inhibitory concentrations of 100 and 10 μg/mL for H. pylori and 400 and 40 μg/mL for P. acnes, respectively. In in vivo experiments, C57BL/6 mice were infected with H. pylori by intragastric inoculation (1 × 10(8) CFU/mouse) 3 times, and orally treated twice a day for 14 days with WRPE-EtOH and WRPE-BuOH. On a CLO kit assay, 200 mg/kg of WRPE-EtOH fully eliminated the bacteria from the gastric mucosa, and the effect of 100 mg/kg of ethanol fraction was similar to pantoprazole (30 mg/kg), displaying 75% elimination. WRPE-BuOH was more effective, exhibiting 75% elimination at 20 mg/kg. The CLO test results were confirmed by bacterial identification. WRPE-EtOH and WRPE-BuOH inhibited the growth of various bacteria and fungi, and in particular, they effectively killed H. pylori and eliminated the bacteria from the mouse stomach. The results indicate that WRPE-EtOH and WRPE-BuOH could be good candidates for the elimination of H. pylori.


Working and disability expectancies at older ages: The role of childhood circumstances and education.
The ability to work at older ages depends on health and education. Both accumulate starting very early in life. We assess how childhood disadvantages combine with education to affect working and health trajectories. Applying multistate period life tables to data from the Health and Retirement Study (HRS) for the period 2008-2014, we estimate how the residual life expectancy at age 50 is distributed in number of years of work and disability, by number of childhood disadvantages, gender, and race/ethnicity. Our findings indicate that number of childhood disadvantages is negatively associated with work and positively with disability, irrespective of gender and race/ethnicity. Childhood disadvantages intersect with low education resulting in shorter lives, and redistributing life years from work to disability. Among the highly educated, health and work differences between groups of childhood disadvantage are small. Combining multistate models and inverse probability weighting, we show that the return of high education is greater among the most disadvantaged.


Environmental benefits and risks of zero-valent iron nanoparticles (nZVI) for in situ remediation: risk mitigation or trade-off?
The use of nanoscaled zero-valent iron particles (nZVI) to remediate contaminated soil and groundwater has received increasing amounts of attention within the last decade, primarily due to its potential for broader application, higher reactivity, and cost-effectiveness compared to conventional zero-valent iron applications and other in situ methods. However, the potential environmental risks of nZVI in in situ field scale applications are largely unknown at the present and traditional environmental risk assessment approaches are not yet able to be completed. Therefore, it may not yet be fully clear how to consider the environmental benefits and risks of nZVI for in situ applications. This analysis therefore addresses the challenges of comprehensively considering and weighing the expected environmental benefits and potential risks of this emerging environmentally-beneficial nanotechnology, particularly relevant for environmental engineers, scientists, and decision makers. We find that most of the benefits of using nZVI are based on near-term considerations, and large data gaps currently exist within almost all aspects of environmental exposure and effect assessments. We also find that while a wide range of decision support tools and frameworks alternative to risk assessment are currently available, a thorough evaluation of these should be undertaken in the near future to assess their full relevancy for nZVI at specific sites. Due to the absence of data in environmental risk evaluations, we apply a 'best' and 'worst' case scenario evaluation as a first step to qualitatively evaluate the current state-of-knowledge regarding the potential environmental risks of nZVI. The result of this preliminary qualitative evaluation indicates that at present, there are no significant grounds on which to form the basis that nZVI currently poses a significant, apparent risk to the environment, although the majority of the most serious criteria (i.e. potential for persistency, bioaccumulation, toxicity) are generally unknown. We recommend that in cases where nZVI may be chosen as the 'best' treatment option, short and long-term environmental monitoring is actively employed at these sites. We furthermore recommend the continued development of responsible nZVI innovation and better facilitated information exchange between nZVI developers, nano-risk researchers, remediation industry, and decision makers.


[Toxicity of selected brominated aromatic compounds].
Flame retardants are added to plastic materials, textiles, wood, hydraulic liquids etc. for reducing their inflammability. These substances reduce the heat and carbon monoxide formation in case of fire. They are added in high amounts, even up to 30% of product mass (e.g. plastic material). The production of brominated flame retardants has been steadily rising in the last 20 years, e.g. in the 1990s the world production of polybromodiphenyl ethers (PBDE) reached 40,000 tons annually. Mainly polybrominated flame retardants are produced, e.g. polybromobiphenyls (PBB), PBDE, hexabromobenzene (HBB). Their toxicity is low or nil, the DL 50 values are over 1 g/kg. However, when administered in low doses over longer time periods they can cause changes leading to porphyria. The information on the toxicity of polybrominated flame retardants for humans is derived mainly from the accident in Michigan, where PBB contamination of fodder for farm animals occurred with consequent contamination of food. In consumers of contaminated food cutaneous changes and neurological and muscular symptoms were noted. Polybrominated flame retardants can be metabolized and undergo biodegradation mainly trough debromination. The data on the toxicity of debromination products point to di- and tribromobenzenes, some of which are highly hepatotoxic. In acute poisoning hepatocellular damage manifest itself as necrotic changes in experimental animals receiving 0.1-0.8 of DL 50 of di- or tribromobenzene. After repeated administration of lower doses the hepatocellular damage assumes the features of porphyrogenic injury. In the environment polybrominated flame retardants can be transformed by various factors (high temperature during fire accidents, incomplete incineration of waste) to polybrominated dibenzodioxins of dibenzofurans whose lethal doses can in extreme cases be 0.001 mg for 1 kg body weight.


White matter alterations in college football players: a longitudinal diffusion tensor imaging study.
The aim of this study was to evaluate longitudinal changes in the diffusion characteristics of brain white matter (WM) in collegiate athletes at three time points: prior to the start of the football season (T1), after one season of football (T2), followed by six months of no-contact rest (T3). Fifteen male collegiate football players and 5 male non-athlete student controls underwent diffusion MR imaging and computerized cognitive testing at all three timepoints. Whole-brain tract-based spatial statistics (TBSS) were used to compare fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and trace between all timepoints. Average diffusion values were obtained from statistically significant clusters for each individual. No athlete suffered a concussion during the study period. After one season of play (T1 to T2), we observed a significant increase in trace in a cluster located in the brainstem and left temporal lobe, and a significant increase in FA in the left parietal lobe. After six months of no-contact rest (T2 to T3), there was a significant decrease in trace and FA in clusters that were partially overlapping or in close proximity with the initial clusters (T1 to T2), with no significant changes from T1 to T3. Repetitive head impacts (RHI) sustained during a single football season may result in alterations of the brain's WM in collegiate football players. These changes appear to return to baseline after 6 months of no-contact rest, suggesting remission of WM alterations. Our preliminary results suggest that collegiate football players might benefit from periods without exposure to RHI.


Habitual levels of high, but not moderate or low, impact activity are positively related to hip BMD and geometry: results from a population-based study of adolescents.
Whether a certain level of impact needs to be exceeded for physical activity (PA) to benefit bone accrual is currently unclear. To examine this question, we performed a cross-sectional analysis between PA and hip BMD in 724 adolescents (292 boys, mean 17.7 years) from the Avon Longitudinal Study of Parents and Children (ALSPAC), partitioning outputs from a Newtest accelerometer into six different impact bands. Counts within 2.1 to 3.1g, 3.1 to 4.2g, 4.2 to 5.1g, and >5.1g bands were positively related to femoral neck (FN) BMD, in boys and girls combined, in our minimally adjusted model including age, height, and sex (0.5-1.1g: beta = -0.007, p = 0.8; 1.1-2.1g: beta = 0.003, p = 0.9; 2.1-3.1g: beta = 0.042, p = 0.08; 3.1-4.2g: beta = 0.058, p = 0.009; 4.2-5.1g: beta = 0.070, p = 0.001; >5.1g: beta = 0.080, p < 0.001) (beta = SD change per doubling in activity). Similar positive relationships were observed between high-impact bands and BMD at other hip sites (ward's triangle, total hip), hip structure indices derived by hip structural analysis of dual-energy X-ray absorptiometry (DXA) scans (FN width, cross-sectional area, cortical thickness), and predicted strength (cross-sectional moment of inertia). In analyses where adjacent bands were combined and then adjusted for other impacts, high impacts (>4.2g) were positively related to FN BMD, whereas, if anything, moderate (2.1-4.2g) and low impacts (0.5-2.1g) were inversely related (low: beta = -0.052, p = 0.2; medium: beta = -0.058, p = 0.2; high: beta = 0.137, p < 0.001). Though slightly attenuated, the positive association between PA and FN BMD, confined to high impacts, was still observed after adjustment for fat mass, lean mass, and socioeconomic position (high: beta = 0.096, p = 0.016). These results suggest that PA associated with impacts >4.2g, such as jumping and running (which further studies suggested requires speeds >10 km/h) is positively related to hip BMD and structure in adolescents, whereas moderate impact activity (eg, jogging) is of little benefit. Hence, PA may only strengthen lower limb bones in adolescents, and possibly adults, if this comprises high-impact activity.


Predictive hydrogeochemical modelling of bauxite residue sand in field conditions.
The suitability of residue sand (the coarse fraction remaining from Bayer's process of bauxite refining) for constructing the surface cover of closed bauxite residue storage areas was investigated. Specifically, its properties as a medium for plant growth are of interest to ensure residue sand can support a sustainable ecosystem following site closure. The geochemical evolution of the residue sand under field conditions, its plant nutrient status and soil moisture retention were studied by integrated modelling of geochemical and hydrological processes. For the parameterization of mineral reactions, amounts and reaction kinetics of the mineral phases natron, calcite, tricalcium aluminate, sodalite, muscovite and analcime were derived from measured acid neutralization curves. The effective exchange capacity for ion adsorption was measured using three independent exchange methods. The geochemical model, which accounts for mineral reactions, cation exchange and activity corrected solution speciation, was formulated in the geochemical modelling framework PHREEQC, and partially validated in a saturated-flow column experiment. For the integration of variably saturated flow with multi-component solute transport in heterogeneous 2D domains, a coupling of PHREEQC with the multi-purpose finite-element solver COMSOL was established. The integrated hydrogeochemical model was applied to predict water availability and quality in a vertical flow lysimeter and a cover design for a storage facility using measured time series of rainfall and evaporation from southwest Western Australia. In both scenarios the sand was fertigated and gypsum-amended. Results show poor long-term retention of fertilizer ions and buffering of the pH around 10 for more than 5 y of leaching. It was concluded that fertigation, gypsum amendment and rainfall leaching alone were insufficient to render the geochemical conditions of residue sand suitable for optimal plant growth within the given timeframe. The surface cover simulation demonstrates that the soil moisture status in the residue sand can be ameliorated by an appropriate design of the cover layer with respect to thickness, slope and distance between lateral drains.


Identification of a laminated layer-associated protein in Echinococcus multilocularis metacestodes.
Echinococcus multilocularis is a cestode parasite that predominantly infects red and arctic foxes as definitive hosts. Ingestion of E. multilocularis eggs and subsequent post-oncospheral infection with the larval stage (metacestode) of the parasite results in alveolar echinococcosis (AE), a life-threatening hepatic disease concerning humans and other intermediate hosts such as small rodents. The primary fluid-filled vesicles of the asexually proliferating metacestode are comprised of an inner germinal layer, a syncytial tegument, and an outer, acellular, so-called laminated layer. This laminated layer may play an important role in protecting the developing E. multilocularis metacestode from host immune reactions, and laminated layer-associated components represent potential targets for intervention during the course of AE. We have used an in vitro cultivation technique for the long-term maintenance and proliferation of E. multilocularis metacestodes in order to generate premature (protoscolex-free) parasite vesicles. A polyclonal antiserum was raised against this host-free parasite tissue. Subsequent immunoblot analysis of parasite fractions obtained by Triton X-114 extraction lead to the identification of a 116 kDa protein (named EmP2) within the Triton-insoluble fraction. The characterization of EmP2 by SDS-PAGE, Western blotting, and by immunofluorescence revealed that EmP2 is a laminated layer-associated protein.


American College of Rheumatology Guidance for the Management of Pediatric Rheumatic Disease During the COVID-19 Pandemic: Version 2.
To provide clinical guidance to rheumatology providers who treat children with pediatric rheumatic disease (PRD) in the context of the coronavirus disease 2019 (COVID-19) pandemic. The task force, consisting of 7 pediatric rheumatologists, 2 pediatric infectious disease physicians, 1 adult rheumatologist, and 1 pediatric nurse practitioner, was convened on May 21, 2020. Clinical questions and subsequent guidance statements were drafted based on a review of the queries posed by the patients as well as the families and healthcare providers of children with PRD. An evidence report was generated and disseminated to task force members to assist with 3 rounds of asynchronous, anonymous voting by email using a modified Delphi approach. Voting was completed using a 9-point numeric scoring system with predefined levels of agreement (categorized as disagreement, uncertainty, or agreement, with median scores of 1-3, 4-6, and 7-9, respectively) and consensus (categorized as low, moderate, or high). To be approved as a guidance statement, median vote ratings were required to fall into the highest tertile for agreement, with either moderate or high levels of consensus. To date, 39 guidance statements have been approved by the task force. Those with similar recommendations were combined to form a total of 33 final guidance statements, all of which received median vote ratings within the highest tertile of agreement and were associated with either moderate consensus (n = 5) or high consensus (n = 28). These guidance statements have been generated based on review of the available literature, indicating that children with PRD do not appear to be at increased risk for susceptibility to SARS-CoV-2 infection. This guidance is presented as a "living document," recognizing that the literature on COVID-19 is rapidly evolving, with future updates anticipated.


Clinical management of idiopathic epilepsy in dogs with homeopathic Belladonna 200C: a case series.
Epilepsy is an important neurological disorder in dogs. Belladonna 200C was evaluated in 10 dogs with idiopathic epilepsy. During the seizure phase, 3-4 drops of Belladonna 200C were administered orally at 15 min intervals until considerable reduction in seizure activity, then four times daily. Four dogs with head shaking syndrome in addition to seizures were given Cocculus 6C, 3-4 drops orally weekly for 3 months in addition. Numbers of fits reduced to 2-3 during first 2 weeks post-therapy and then became occasional in next 2 weeks. With continuation of Belladonna therapy, no fits were observed during 2-7 months follow-up. In two cases epileptic fits reappeared within 15-25 days of cessation of therapy. Belladonna therapy was resumed and seizure control was again achieved. Owners were advised to continue the therapy at least twice daily until there were no fits for 2-3 months. Liver specific enzymes were monitored, no abnormalities were observed.


A new method for generating an invariant iris private key based on the fuzzy vault system.
Cryptographic systems have been widely used in many information security applications. One main challenge that these systems have faced has been how to protect private keys from attackers. Recently, biometric cryptosystems have been introduced as a reliable way of concealing private keys by using biometric data. A fuzzy vault refers to a biometric cryptosystem that can be used to effectively protect private keys and to release them only when legitimate users enter their biometric data. In biometric systems, a critical problem is storing biometric templates in a database. However, fuzzy vault systems do not need to directly store these templates since they are combined with private keys by using cryptography. Previous fuzzy vault systems were designed by using fingerprint, face, and so on. However, there has been no attempt to implement a fuzzy vault system that used an iris. In biometric applications, it is widely known that an iris can discriminate between persons better than other biometric modalities. In this paper, we propose a reliable fuzzy vault system based on local iris features. We extracted multiple iris features from multiple local regions in a given iris image, and the exact values of the unordered set were then produced using the clustering method. To align the iris templates with the new input iris data, a shift-matching technique was applied. Experimental results showed that 128-bit private keys were securely and robustly generated by using any given iris data without requiring prealignment.


Incidence of Severe Osteonecrosis Requiring Total Joint Arthroplasty in Children and Young Adults Treated for Leukemia or Lymphoma: A Nationwide, Register-Based Study in Finland and Denmark.
Purpose: The population-based incidence of severe osteonecrosis (ON) necessitating total joint arthroplasty (TJA) in patients with hematological cancer is unknown. This study assessed the incidence of ON requiring primary TJA in children and young adults treated for leukemia or lymphoma. Methods: Patients diagnosed with leukemia or lymphoma before 31 years of age were identified from the Finnish and Danish Cancer Registries. These data were combined with those from the National Hospital Discharge and the Finnish Arthroplasty Registers. Data on the orthopedic procedures performed and the appropriate diagnosis codes given before the age of 40 were also retrieved. Results: The estimated cumulative incidence of TJA was 4.5% at 20 years for patients treated for chronic myeloid leukemia, followed by 2.1% for patients treated for acute myeloid leukemia. It was considerably lower in patients with acute lymphoblastic leukemia (ALL; 0.4%). Multivariate analysis revealed that allogeneic stem cell transplantation (allo-SCT) increased the risk of TJA (hazard ratio [HR]=9.4; 95% CI: 5.3-16.9). The risk of TJA was higher in patients diagnosed with cancer at 10-19 and 20-30 years of age than in those diagnosed before the age of 10 (HR=24; 95% CI: 3.1-176 and HR=26; 95% CI: 3.6-192 respectively). Conclusion: The incidence of ON requiring TJA was highest among patients with myeloid leukemias and lowest in patients treated for ALL. Allo-SCT and age ≥10 years at diagnosis were the most important risk factors for ON requiring TJA in hematological malignancies.


Second OH overtone excitation and statistical dissociation dynamics of peroxynitrous acid.
The second OH overtone transition of the trans-perp conformer of peroxynitrous acid (tp-HOONO) is identified using infrared action spectroscopy. HOONO is produced by the recombination of photolytically generated OH and NO(2) radicals, and then cooled in a pulsed supersonic expansion. The second overtone transition is assigned to tp-HOONO based on its vibrational frequency (10 195.3 cm(-1)) and rotational band contour, which are in accord with theoretical predictions and previous observations of the first overtone transition. The transition dipole moment associated with the overtone transition is rotated considerably from the OH bond axis, as evident from its hybrid band composition, indicating substantial charge redistribution upon OH stretch excitation. The overtone band exhibits homogeneous line broadening that is attributed to intramolecular vibrational redistribution, arising from the coupling of the initially excited OH stretch to other modes that ultimately lead to dissociation. The quantum state distributions of the OH X (2)Pi (nu=0) products following first and second OH overtone excitation of tp-HOONO are found to be statistical by comparison with three commonly used statistical models. The product state distributions are principally determined by the tp-HOONO binding energy of 16.2(1) kcal mol(-1). Only a small fraction of the OH products are produced in nu=1 following the second overtone excitation, consistent with statistical predictions.


Ethnic inequality in choice- and performance-driven education systems: A longitudinal study of educational choices in England, Germany, the Netherlands, and Sweden.
The motivation for this article was the main finding of an earlier study, which concludes that choice-driven education systems-in the study represented by England and Sweden-are particularly beneficial for immigrants in that they provide them with many opportunities to pursue their generally high educational ambitions. We extend this analysis by including two countries with performance-driven education systems: Germany and the Netherlands. Our study specifically aims to explore whether it is true that choice-driven systems are more beneficial for immigrants or whether immigrants can also succeed in more stratified and selective education systems. Using longitudinal data from the Children of Immigrants Longitudinal Survey in Four European Countries (CILS4EU), we show that there are no differences in (gross) transition rates between immigrants and natives in Germany, the Netherlands, and Sweden, but immigrants' optimistic choices are more pronounced in England. However, these differences diminish once we account for achievement and students' socioeconomic background in the analyses. Regarding the underlying mechanisms, we find that educational aspirations have an (equally) strong, universal impact, while anticipated discrimination plays a minor role.


Range shift and introgression of the rear and leading populations in two ecologically distinct Rubus species.
The margins of a species' range might be located at the margins of a species' niche, and in such cases, can be highly vulnerable to climate changes. They, however, may also undergo significant evolutionary changes due to drastic population dynamics in response to climate changes, which may increase the chances of isolation and contact among species. Such species interactions induced by climate changes could then regulate or facilitate further responses to climatic changes. We hypothesized that climate changes lead to species contacts and subsequent genetic exchanges due to differences in population dynamics at the species boundaries. We sampled two closely related Rubus species, one temperate (Rubus palmatus) and the other subtropical (R. grayanus) near their joint species boundaries in southern Japan. Coalescent analysis, based on molecular data and ecological niche modelling during the Last Glacial Maximum (LGM), were used to infer past population dynamics. At the contact zones on Yakushima (Yaku Island), where the two species are parapatrically distributed, we tested hybridization along altitudinal gradients. Coalescent analysis suggested that the southernmost populations of R. palmatus predated the LGM (~20,000 ya). Conversely, populations at the current northern limit of R. grayanus diverged relatively recently and likely represent young outposts of a northbound range shift. These population dynamics were partly supported by the ensemble forecasting of six different species distribution models. Both past and ongoing hybridizations were detected near and on Yakushima. Backcrosses and advanced-generation hybrids likely generated the clinal hybrid zones along altitudinal gradients on the island where the two species are currently parapatrically distributed. Climate oscillations during the Quaternary Period and the response of a species in range shifts likely led to repeated contacts with the gene pools of ecologically distinct relatives. Such species interactions, induced by climate changes, may bring new genetic material to the marginal populations where species tend to experience more extreme climatic conditions at the margins of the species distribution.


High-Intensity Interval Training: A Potential Exercise Countermeasure During Human Spaceflight.
High-intensity interval training (HIT) is an effective approach for improving a range of physiological markers associated with physical fitness. A considerable body of work has demonstrated substantial improvements in cardiorespiratory fitness following short-term training programmes, while emerging evidence suggests that HIT can positively impact aspects of neuromuscular fitness. Given the detrimental consequences of prolonged exposure to microgravity on both of these physiological systems, and the potential for HIT to impact multiple components of fitness simultaneously, HIT is an appealing exercise countermeasure during human spaceflight. As such, the primary aim of this mini review is to synthesize current terrestrial knowledge relating to the effectiveness of HIT for inducing improvements in cardiorespiratory and neuromuscular fitness. As exercise-induced fitness changes are typically influenced by the specific exercise protocol employed, we will consider the effect of manipulating programming variables, including exercise volume and intensity, when prescribing HIT. In addition, as the maintenance of HIT-induced fitness gains and the choice of exercise mode are important considerations for effective training prescription, these issues are also discussed. We conclude by evaluating the potential integration of HIT into future human spaceflight operations as a strategy to counteract the effects of microgravity.


[Surgical therapy of Parkinson's disease].
The high incidence of motor and psychiatric complications in patients on chronic levodopa treatment has lend to the renaissance of the surgery for the treatment of Parkinson's disease. The globus pallidus medialis (GPM) and the thalamic Vim constitute the main surgical targets. At present, their acute location is guaranteed by the development of new neuronal recording systems. Other therapeutical approaches include Vim electrical stimulation for parkinsonian patients with tremor. Chronic electrical stimulation of GPM and subthalamic nucleus (STN) are under evaluation, but preliminary results suggest that this treatment could be of great value in the treatment of patients with Parkinson's disease.


Polarity protein Crumbs homolog-3 (CRB3) regulates ectoplasmic specialization dynamics through its action on F-actin organization in Sertoli cells.
Crumbs homolog 3 (or Crumbs3, CRB3) is a polarity protein expressed by Sertoli and germ cells at the basal compartment in the seminiferous epithelium. CRB3 also expressed at the blood-testis barrier (BTB), co-localized with F-actin, TJ proteins occludin/ZO-1 and basal ES (ectoplasmic specialization) proteins N-cadherin/β-catenin at stages IV-VII only. The binding partners of CRB3 in the testis were the branched actin polymerization protein Arp3, and the barbed end-capping and bundling protein Eps8, illustrating its possible role in actin organization. CRB3 knockdown (KD) by RNAi in Sertoli cells with an established tight junction (TJ)-permeability barrier perturbed the TJ-barrier via changes in the distribution of TJ- and basal ES-proteins at the cell-cell interface. These changes were the result of CRB3 KD-induced re-organization of actin microfilaments, in which actin microfilaments were truncated, and extensively branched, thereby destabilizing F-actin-based adhesion protein complexes at the BTB. Using Polyplus in vivo-jetPEI as a transfection medium with high efficiency for CRB3 KD in the testis, the CRB3 KD testes displayed defects in spermatid and phagosome transport, and also spermatid polarity due to a disruption of F-actin organization. In summary, CRB3 is an actin microfilament regulator, playing a pivotal role in organizing actin filament bundles at the ES.


Cascading effects of a highly specialized beech-aphid-fungus interaction on forest regeneration.
Specialist herbivores are thought to often enhance or maintain plant diversity within ecosystems, because they prevent their host species from becoming competitively dominant. In contrast, specialist herbivores are not generally expected to have negative impacts on non-hosts. However, we describe a cascade of indirect interactions whereby a specialist sooty mold (Scorias spongiosa) colonizes the honeydew from a specialist beech aphid (Grylloprociphilus imbricator), ultimately decreasing the survival of seedlings beneath American beech trees (Fagus grandifolia). A common garden experiment indicated that this mortality resulted from moldy honeydew impairing leaf function rather than from chemical or microbial changes to the soil. In addition, aphids consistently and repeatedly colonized the same large beech trees, suggesting that seedling-depauperate islands may form beneath these trees. Thus this highly specialized three-way beech-aphid-fungus interaction has the potential to negatively impact local forest regeneration via a cascade of indirect effects.


Optimal re-referencing rate for in-plane dynamic speckle interferometry.
We investigate experimentally the optimal rate at which the reference speckle pattern should be updated when dynamic speckle interferometry is used to measure transient in-plane displacement fields. Images are captured with a high-speed camera and phase shifting and phase unwrapping are done temporally. For a wide range of in-plane velocities, up to a maximum of 40% of the Nyquist limit, the random errors in the calculated displacement field are minimized by updating the reference speckle pattern after a speckle displacement of 1/10 of the pixel spacing. The technique is applied to measurements of microscale deformation fields within an adhesive joint in a carbon-fiber epoxy composite.


Transient molten globules and metastable aggregates induced by brief exposure of a monoclonal IgG to low pH.
The presence of aggregates in therapeutic protein formulations is of great concern due to quality, safety, and efficacy issues. Nonetheless, the mechanisms and kinetics of protein aggregation are only partly understood. In this study, metastable immunoglobulin G (IgG) aggregates induced by a brief exposure to pH 1 were kept at 4°C and analyzed over time by size-exclusion chromatography (SEC), nanoparticle tracking analysis, light obscuration, dynamic light scattering, fluorescence spectroscopy, and circular dichroism. The results show the formation of polydisperse aggregates (from dimers to 10-μm particles) shortly after the pH-shift stress. These aggregates increased in size and number over time until a pseudo-equilibrium was reached after 5-7 days. The presence of transient, partially unfolded monomers (molten globules) was detected by SEC with online fluorescent dye detection. The molten globules seemed to either refold into the native state or become involved in aggregation pathways. Seeding pH-shift-induced aggregates into unstressed IgG did not accelerate aggregation during incubation for 3 weeks at 55°C. These results reinforce the role of partially unfolded species in the aggregation of therapeutic proteins. We conclude that the formation of pH-shift-induced IgG aggregates is likely driven by downhill polymerization, as a consequence of successive additions of molten globular monomers.


Boosting Belligerence: How the July 7, 2005, London Bombings Affected Liberals' Moral Foundations and Prejudice.
Major terrorist events, such as the recent attacks in Ankara, Sinai, and Paris, can have profound effects on a nation's values, attitudes, and prejudices. Yet psychological evidence testing the impact of such events via data collected immediately before and after an attack is understandably rare. In the present research, we tested the independent and joint effects of threat (the July 7, 2005, London bombings) and political ideology on endorsement of moral foundations and prejudices among two nationally representative samples (combined N = 2,031) about 6 weeks before and 1 month after the London bombings. After the bombings, there was greater endorsement of the in-group foundation, lower endorsement of the fairness-reciprocity foundation, and stronger prejudices toward Muslims and immigrants. The differences in both the endorsement of the foundations and the prejudices were larger among people with a liberal orientation than among those with a conservative orientation. Furthermore, the changes in endorsement of moral foundations among liberals explained their increases in prejudice. The results highlight the value of psychological theory and research for understanding societal changes in attitudes and prejudices after major terrorist events.


Teaching Quality Improvement in Emergency Medicine Training Programs: A Review of Best Practices.
International graduate medical accreditation bodies are placing increasing emphasis on resident education and competency in the principles of quality improvement and patient safety (QIPS). Current QIPS educational curricula are heterogeneous and variably attain stated objectives. We have conducted a review of QIPS curricular best practices and barriers to implementation of successful QIPS curricula and provide clear solutions aimed at overcoming these barriers. Emergency medicine programs provide fertile ground for QIPS initiatives and can become world leaders in QIPS curricular development and education.


A population-based analysis of statin utilization in British Columbia.
The purpose of this research was to measure prevalent and incident statin use in the population of British Columbia from 1996 to 2004 across specific patient characteristics (sociodemographic and clinical). Statin utilization and demographic data were assessed with the use of prescription drug claims. Medical and hospital claims for statin users were examined for evidence of ischemic heart disease (IHD), diabetes mellitus (DM), atherosclerosis, cerebrovascular disease, peripheral vascular disease (PVD), and disorders of lipid metabolism during the 3 years before the first statin prescription. Statin prevalence increased from 1996 to 2004 (1.28 %-6.59%). The greatest use was among those aged 65 to 84 years. Prevalent use of atorvastatin, simvastatin, and rosuvastatin increased over time. There were 211,964 new statin users between 1999 and 2004. Quarterly incident statin use increased over time from 1999 to 2004 (0.29%-0.49%). A socioeconomic gradient, whereby use was greater in those with low socioeconomic status, was observed for incident statin use. Incident atorvastatin use increased over time; simvastatin, cerivastatin, and rosuvastatin peaked and then declined; and new use of other statins decreased. Among 211,964 incident statin users, 74,542 (35.17%) had evidence of IHD only; 43,257 (20.41%) had DM but no IHD; 9781 (4.61%) had no DM or IHD but had atherosclerosis, cerebrovascular disease, or PVD; 47,634 (22.47%) had disorders of lipid metabolism only; and 36,750 (17.34%) had none of the medical conditions evaluated. Prevalent use (1996-2004) and incident use (1999-2004) of statins in an entire population have increased dramatically. Although many statin users (60.19%) had evidence of medical conditions that indicate appropriate statin use, 39.91% of users were at low risk for cardiovascular disease, and therefore the benefit of statins in this group remains small.


Alternative recognition of the conserved stem epitope in influenza A virus hemagglutinin by a VH3-30-encoded heterosubtypic antibody.
A human monoclonal heterosubtypic antibody, MAb 3.1, with its heavy chain encoded by VH3-30, was isolated using phage display with immobilized hemagglutinin (HA) from influenza virus A/Japan/305/1957(H2N2) as the target. Antibody 3.1 potently neutralizes influenza viruses from the H1a clade (i.e., H1, H2, H5, H6) but has little neutralizing activity against the H1b clade. Its crystal structure in complex with HA from a pandemic H1N1 influenza virus, A/South Carolina/1/1918(H1N1), revealed that like other heterosubtypic anti-influenza virus antibodies, MAb 3.1 contacts a hydrophobic groove in the HA stem, primarily using its heavy chain. However, in contrast to the closely related monoclonal antibody (Mab) FI6 that relies heavily on HCDR3 for binding, MAb 3.1 utilizes residues from HCDR1, HCDR3, and framework region 3 (FR3). Interestingly, HCDR1 of MAb 3.1 adopts an α-helical conformation and engages in hydrophobic interactions with the HA very similar to those of the de novo in silico-designed and affinity-matured synthetic protein HB36.3. These findings improve our understanding of the molecular requirements for binding to the conserved epitope in the stem of the HA protein and, therefore, aid the development of more universal influenza vaccines targeting these epitopes. Influenza viruses rapidly evade preexisting immunity by constantly altering the immunodominant neutralizing antibody epitopes (antigenic drift) or by acquiring new envelope serotypes (antigenic shift). As a consequence, the majority of antibodies elicited by immunization or infection protect only against the immunizing or closely related strains. Here, we describe a novel monoclonal antibody that recognizes the conserved heterosubtypic epitope in the stem of influenza A virus hemagglutinin. This antibody, referred to as MAb 3.1, recognizes its epitope in a manner that resembles recognition of a similar epitope by the de novo in silico-designed and affinity-matured synthetic protein HB36.3. Thus, besides providing novel insights into the molecular interactions between heterosubtypic antibodies and influenza virus hemagglutinin, MAb 3.1 demonstrates that de novo in silico-designed and affinity-matured synthetic proteins can foretell naturally selected antibody binding. This knowledge will aid development of a pan-influenza virus vaccine.


Anomalous Dynamics of a Lipid Recognition Protein on a Membrane Surface.
Pleckstrin homology (PH) domains are lipid-binding modules present in peripheral membrane proteins which interact with phosphatidyl-inositol phosphates (PIPs) in cell membranes. We use multiscale molecular dynamics simulations to characterize the localization and anomalous dynamics of the DAPP1 PH domain on the surface of a PIP-containing lipid bilayer. Both translational and rotational diffusion of the PH domain on the lipid membrane surface exhibit transient subdiffusion, with an exponent α ≈ 0.5 for times of less than 10 ns. In addition to a PIP3 molecule at the canonical binding site of the PH domain, we observe additional PIP molecules in contact with the protein. Fluctuations in the number of PIPs associated with the PH domain exhibit 1/f noise. We suggest that the anomalous diffusion and long-term correlated interaction of the PH domain with the membrane may contribute to an enhanced probability of encounter with target complexes on cell membrane surfaces.


Predictors of tamoxifen discontinuation among older women with estrogen receptor-positive breast cancer.
Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) -positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Within six health care delivery systems, we identified women >or= 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged >or= 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.


Contribution of liraglutide in the fixed-ratio combination of insulin degludec and liraglutide (IDegLira).
Insulin degludec/liraglutide (IDegLira) is a novel combination of insulin degludec (IDeg) and liraglutide. This trial investigated the contribution of the liraglutide component of IDegLira versus IDeg alone on efficacy and safety in patients with type 2 diabetes. In a 26-week, double-blind trial, patients with type 2 diabetes (A1C 7.5-10.0% [58-86 mmol/mol]) on basal insulin (20-40 units) and metformin with or without sulfonylurea/glinides were randomized (1:1) to once-daily IDegLira + metformin or IDeg + metformin with titration aiming for fasting plasma glucose between 4 and 5 mmol/L. Maximum allowed doses were 50 dose steps (equal to 50 units IDeg plus 1.8 mg liraglutide) and 50 units for IDeg. The primary end point was change in A1C from baseline. A total of 413 patients were randomized (mean A1C 8.8% [73 mmol/mol]; BMI 33.7 kg/m2). IDeg dose, alone or as part of IDegLira, was equivalent (45 units). A1C decreased by 1.9% (21 mmol/mol) with IDegLira and by 0.9% (10 mmol/mol) with IDeg (estimated treatment difference -1.1% [95% CI -1.3, -0.8], -12 mmol/mol [95% CI -14, -9; P < 0.0001). Mean weight reduction with IDegLira was 2.7 kg vs. no weight change with IDeg, P < 0.0001. Hypoglycemia incidence was comparable (24% for IDegLira vs. 25% for IDeg). Overall adverse events were similar, and incidence of nausea was low in both groups (IDegLira 6.5% vs. IDeg 3.5%). IDegLira achieved glycemic control superior to that of IDeg at equivalent insulin doses without higher risk of hypoglycemia and with the benefit of weight loss. These findings establish the efficacy and safety of IDegLira and the distinct contribution of the liraglutide component.


Cushing's disease: current medical therapies and molecular insights guiding future therapies.
OBJECT Cushing's disease (CD) can lead to significant morbidity secondary to hormonal sequelae or mass effect from the pituitary tumor. A transsphenoidal approach to resection of the adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma is the first-line treatment. However, in the setting in which patients are unable to undergo surgery, have acute hypercortisolism, or have recurrent disease, medical therapy can play an important role. The authors performed a systematic review to highlight the efficacy of medical treatment of CD and discuss novel molecular insights that could guide the development of future medical treatments of CD. METHODS A search on current medical therapies for CD was performed. After individual medical therapeutic agents for CD were identified, each agent underwent a formal systematic search. The phrase "(name of agent) and Cushing's" was used as a search term in PubMed for all years up to 2014. The abstract of each article was reviewed for studies that evaluated the efficacy of medical treatment of CD. Only studies that enrolled at least 20 patients were included in the review. RESULTS A total of 11 articles on 6 individual agents were included in this review. Specific medical therapies were categorized based on the level of action: pituitary directed (cabergoline and pasireotide), adrenal/steroidogenesis directed (ketoconazole, metyrapone, and mitotane), and end-tissue directed/cortisol receptors (mifepristone). The studies identified consisted of a mix of retrospective reviews and small clinical trials. Only pasireotide and mifepristone have undergone Phase III clinical trials, from which they garnered FDA approval for the treatment of patients with CD. Overall, agents targeting ACTH secretion and steroidogenesis were found to be quite effective in reducing urine free cortisol (UFC) to levels near normal. A significant reduction in UFC was observed in 45%-100% of patients and a majority of patients gained clinical improvement. Similarly, inhibition at the end-tissue level led to clinical improvement in 87% of patients. However, side-effect rates associated with these drugs are high (up to 88%). Ketoconazole has been shown to enhance tumor appearance on MRI to facilitate pituitary resection. Promising molecular targets have been identified, including epidermal growth factor receptor, retinoic acid receptors, and cyclin dependent kinases. These pathways have been linked to the regulation of pro-opiomelanocortin expression, ACTH secretion, and tumor growth. CONCLUSIONS Despite encouraging Phase III clinical trials leading to FDA approval of 2 agents for treatment of patients with CD, no agent has yet produced results comparable to resection. As a result, the molecular insights gained into CD pathogenesis will need to continue to be expanded until they can lead to the development of medical therapies for CD with a favorable side-effect profile and efficacy comparable to resection. Ideally these agents should also reduce tumor size, which could potentially permit their eventual discontinuation.


Characterization of the accretion of material by microparticles using resonant ellipsometry.
An optical technique to characterize the accretion of material by microparticles is described. Experiments on the absorption of water vapor by single levitated polystyrene microparticles are reported as examples of an application of the technique. The optical resonant frequencies of the microparticles are perturbed by the accretion of material and the observed shifts are used to characterize the growth. This technique, resonant ellipsometry, makes use of the polarization character of optical resonant modes to distinguish particle swelling from surface layer formation. The experimental results indicate that water vapor absorbed by polystyrene microparticles diffuses primarily into the particle bulk.


Cystic fibrosis transmembrane conductance regulator: nucleotide binding to a synthetic peptide.
Multiple mutations in the gene responsible for cystic fibrosis are located within a region predicted to encode a nucleotide-binding fold in the amino terminal half of the cystic fibrosis transmembrane conductance regulator protein. A 67-amino acid peptide (P-67) that corresponds to the central region of this putative nucleotide binding site was chemically synthesized and purified. This peptide bound adenine nucleotides. The apparent dissociation constants (Kd's) for the trinitrophenyl (TNP) adenine nucleotides, TNP-adenosine triphosphate, TNP-adenosine diphosphate, and TNP-adenosine monophosphate, were 300 nanomolar, 200 nanomolar, and greater than 1 micromolar, respectively. The Kd for adenosine triphosphate was 300 micromolar. Circular dichroism spectroscopy was used to show that P-67 assumes a predominantly beta sheet structure in solution, a finding that is consistent with secondary structure predictions. On the basis of this information, the phenylalanine at position 508, which is deleted in approximately 70 percent of individuals with cystic fibrosis, was localized to a beta strand within the nucleotide binding peptide. Deletion of this residue is predicted to induce a significant structural change in the beta strand and altered nucleotide binding.


[Current trends and future directions in working memory research].
Working memory is a set of processes or a system that allows us to temporarily maintain task-relevant information during performance of complex cognitive tasks. It has recently been an intensively investigated topic in cognitive psychology, cognitive neuroscience, and other related disciplines, and important empirical and theoretical advances have been made during the last several years. In this article, we review the current state of working memory research, focusing on important recent methodological and theoretical developments in the field. Specifically, we provide an update of recent influential working memory theories (e.g., Baddeley's multicomponent model and an ACT-R model) and discuss the current status of various controversial theoretical issues, such as the unitary versus non-unitary nature of working memory, the nature of working memory limitations, the control and regulation of working memory, and the relationship of working memory to long-term memory. We conclude our review by pointing out some important future directions for working memory research.


Hyaluronic acid in wound dressings.
Human skin possesses an essential function in the maintenance of individuals' health. However, it may undergo a variety of lesions that produce wounds of distinct severity. In this respect, instantly after any skin wound, the process of tissue regeneration and repair initiates. Nevertheless, diverse factors can delay this process, including bacterial infections, nutritional status, age, hypoxia, chronic diseases, necrosis, and vascular and arterial diseases. Thus, wound dressings are frequently used to improve wound healing. Those wound dressings are fabricated with diverse materials, which confer them different properties. In this regard, hyaluronic acid is a natural polysaccharide widely distributed in extracellular matrices of mammal tissues, which possesses remarkable attributes in terms of biocompatibility, biodegradability, and low cost. Moreover, hyaluronic acid exhibits several beneficial effects on wound healing, such as the decrease of inflammatory processes, regulation of tissue remodeling, and enhancement of angiogenesis. Therefore, in recent years, there is growing attention in this polysaccharide for the design and manufacture of novel wound dressings, which have shown encouraging properties. Here, we describe the different approaches of hyaluronic acid for the production of wound dressings, encompassing hydrogels, films, scaffolds, foams, topical formulations, and nanoformulations, as well as its beneficial effects on wound healing. Finally, we discuss perspectives about the use of hyaluronic acid in wound dressings.


An effective network reduction approach to find the dynamical repertoire of discrete dynamic networks.
Discrete dynamic models are a powerful tool for the understanding and modeling of large biological networks. Although a lot of progress has been made in developing analysis tools for these models, there is still a need to find approaches that can directly relate the network structure to its dynamics. Of special interest is identifying the stable patterns of activity, i.e., the attractors of the system. This is a problem for large networks, because the state space of the system increases exponentially with network size. In this work, we present a novel network reduction approach that is based on finding network motifs that stabilize in a fixed state. Notably, we use a topological criterion to identify these motifs. Specifically, we find certain types of strongly connected components in a suitably expanded representation of the network. To test our method, we apply it to a dynamic network model for a type of cytotoxic T cell cancer and to an ensemble of random Boolean networks of size up to 200. Our results show that our method goes beyond reducing the network and in most cases can actually predict the dynamical repertoire of the nodes (fixed states or oscillations) in the attractors of the system.


Network-level structural abnormalities of cerebral cortex in type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM) usually begins in childhood and adolescence and causes lifelong damage to several major organs including the brain. Despite increasing evidence of T1DM-induced structural deficits in cortical regions implicated in higher cognitive and emotional functions, little is known whether and how the structural connectivity between these regions is altered in the T1DM brain. Using inter-regional covariance of cortical thickness measurements from high-resolution T1-weighted magnetic resonance data, we examined the topological organizations of cortical structural networks in 81 T1DM patients and 38 healthy subjects. We found a relative absence of hierarchically high-level hubs in the prefrontal lobe of T1DM patients, which suggests ineffective top-down control of the prefrontal cortex in T1DM. Furthermore, inter-network connections between the strategic/executive control system and systems subserving other cortical functions including language and mnemonic/emotional processing were also less integrated in T1DM patients than in healthy individuals. The current results provide structural evidence for T1DM-related dysfunctional cortical organization, which specifically underlie the top-down cognitive control of language, memory, and emotion.


Face structure predicts cooperation: men with wider faces are more generous to their in-group when out-group competition is salient.
Male facial width-to-height ratio appears to correlate with antisocial tendencies, such as aggression, exploitation, cheating, and deception. We present evidence that male facial width-to-height ratio is also associated with a stereotypically male prosocial tendency: to increase cooperation with other in-group members during intergroup competition. We found that men who had wider faces, compared with men who had narrower faces, showed more self-sacrificing cooperation to help their group members when there was competition with another group. We propose that this finding makes sense given the evolutionary functions of social helpfulness and aggression.


Determinants of patient and health system delay among Italian and foreign-born patients with pulmonary tuberculosis: a multicentre cross-sectional study.
The aim of this cross-sectional study was to identify key factors associated with patient delay (PD), health system delay (HSD) and total delay (TOTD) in patients with tuberculosis (TB) to inform control programmes. The study was conducted in four Italian regions in 2014-2016. Data were obtained using a questionnaire including: sociodemographic and lifestyle data, TB comorbidities, patient knowledge and attitudes towards TB, stigma, access to TB care and health-seeking behaviours. Patients' inclusion criteria were being diagnosed as a new smear positive pulmonary TB case and living in one of the participating Italian regions. Overall, 344 patients from 30 healthcare centres were invited to participate and 253 patients were included in the analysis (26.5% non-response rate); 63.6% were males and 55.7% were non-Italian born. Risk factors for PD, HSD and TOTD in patients with TB were assessed by multivariable analysis. Adjusted ORs (aOR) and 95% CIs were calculated. Median PD, HSD and TOTD were 30, 11 and 45 days, respectively. Factors associated with longer PD were: stigma (aOR 2.30; 95% CI 1.06 to 4.98), chest pain (aOR 2.67; 95% CI 1.24 to 6.49), weight loss (aOR 4.66; 95% CI 2.16 to 10.05), paying for transportation (aOR 2.66; 95% CI 1.24 to 5.74) and distance to the health centre (aOR 2.46; 95% CI 1.05 to 5.74) (the latter three were also associated with TOTD). Shorter HSD was associated with foreign-born and female status (aOR 0.50; 95% CI 0.27 to 0.91; aOR 0.28; 95% CI 0.15 to 0.53, respectively), dizziness (aOR 0.18, 95% CI 0.04 to 0.78) and seeking care at hospital (aOR 0.35; 95% CI 0.18 to 0.66). Prior unspecific treatment was associated with longer HSD (aOR 2.25; 95% CI 1.19 to 4.25) and TOTD (aOR 2.55; 95% CI 1.18 to 5.82). Haemoptysis (aOR 0.12; 95% CI 0.03 to 0.43) and repeated visits with the same provider (aOR 0.29; 95% CI 0.11 to 0.76) showed shorter TOTD. This study identifies several determinants of delays associated with patient's behaviours and healthcare qualities. Tackling TB effectively requires addressing key risk factors that make individuals more vulnerable by the means of public health policy, cooperation and advocacy to ensure that all patients have easy access to care and receive high-quality healthcare.


Fully-coupled fluid-structure interaction simulation of the aortic and mitral valves in a realistic 3D left ventricle model.
In this study, we present a fully-coupled fluid-structure interaction (FSI) framework that combines smoothed particle hydrodynamics (SPH) and nonlinear finite element (FE) method to investigate the coupled aortic and mitral valves structural response and the bulk intraventricular hemodynamics in a realistic left ventricle (LV) model during the entire cardiac cycle. The FSI model incorporates valve structures that consider native asymmetric leaflet geometries, anisotropic hyperelastic material models and human material properties. Comparison of FSI results with subject-specific echocardiography data demonstrates that the SPH-FE approach is able to quantitatively predict the opening and closing times of the valves, the mitral leaflet opening and closing angles, and the large-scale intraventricular flow phenomena with a reasonable agreement. Moreover, comparison of FSI results with a LV model without valves reveals substantial differences in the flow field. Peak systolic velocities obtained from the FSI model and the LV model without valves are 2.56 m/s and 1.16 m/s, respectively, compared to the Doppler echo data of 2.17 m/s. The proposed SPH-FE FSI framework represents a further step towards modeling patient-specific coupled LV-valve dynamics, and has the potential to improve our understanding of cardiovascular physiology and to support professionals in clinical decision-making.


Hardness and elasticity of caries-affected and sound primary tooth dentin bonded with 4-META one-step self-etch adhesives.
To evaluate the quality of the interface of sound and carious primary tooth dentin bonded with two 4-META one-step self-etch adhesives. 12 sound and 12 carious primary molars were bonded with AQ Bond Plus (AQBP; Sun Medical) or Hybrid Bond (HB; Sun Medical) and restored with Clearfil Protect Liner F (Kuraray Medical Inc.). After 24 hours of water immersion, the teeth were sectioned and polished. Resin-dentin interfaces were measured with a nano-indentation tester and hardness and Young's modulus were calculated. Data were analyzed using one-way or two-way ANOVA and Fisher's PLSD test with alpha = 0.05. Resin-dentin interfaces were also observed with SEM and TEM. Ammoniacal silver nitrate was used as a tracer for TEM observation. Hardness and Young's modulus of the interfacial dentin were significantly lower than the underlying intact dentin except for the carious-AQBP group. However, there was no significant difference of hardness and Young's moduli of the interfacial dentin among all groups. TEM revealed extensive interfacial nanoleakage in sound dentin bonded with either AQBP or HB. For the carious teeth, nanoleakage was absent in the hybrid layers bonded with the two adhesives. However, extensive silver deposits were identified from the subsurface, porous caries-affected dentin.


Apolipoprotein E ε4 allele modulates the immediate impact of acute exercise on prefrontal function.
The difference between Apolipoprotein E ε4 carriers and non-carriers in response to single exercise sessions was tested. Stroop and Posner tasks were administered to young untrained women immediately after walking sessions or moderately heavy exercise. Exercise had a significantly more profound impact on the Stroop effect than on the Posner effect, suggesting selective involvement of prefrontal function. A significant genotype-by-exercise interaction indicated differences in response to exercise between ε4 carriers and non-carriers. Carriers showed facilitation triggered by exercise. The transient executive down-regulation was construed as due to exercise-dependent hypofrontality. The facilitation observed in carriers was interpreted as better management of prefrontal metabolic resources, and explained within the antagonistic pleiotropy hypothesis framework. The findings have implications for the interpretation of differences between ε4 carriers and non-carriers in the benefits triggered by long-term exercise that might depend, at least partially, on mechanisms of metabolic response to physical activity.


Mapping of the class II region of the human major histocompatibility complex by pulsed-field gel electrophoresis.
The class II region of the human major histocompatibility complex (MHC) encodes a polymorphic set of cell surface glycoproteins involved in the regulation of the immune response. Each glycoprotein is a heterodimer composed of a alpha-chain of relative molecular mass (Mr) 34,000 (34 K) and a beta-chain of Mr = 28K. The products of the class II region have been characterized by the mixed lymphocyte reaction, serology, primed lymphocyte typing and DNA cloning. DR, DQ and DP, three subregions containing both alpha- and beta-chains, and two additional loci, DZ alpha and DO beta, locate this gene cluster on the short arm of chromosome 6. The precise genomic organization of these loci have been difficult to determine. Here we describe the use of pulsed-field gel electrophoresis together with restriction endonucleases having few genomic restriction sites and Southern blotting, to determine the order of the subregions and to derive a map for the human class II region. The order of these loci is similar to that of the homologous loci in the murine class II region. Our study establishes the use of pulsed-field gel electrophoresis in mapping large regions of the genome in higher eukaryotes.


Native defects and impurity band behavior in half-Heusler thermoelectric NbFeSb.
To investigate the electronic behavior and magnetic properties of NbFeSb, we have performed 93Nb NMR, specific heat and magnetic measurements on NbFeSb samples heat treated at high temperatures. Magnetic measurements combined with an observed Schottky anomaly and changes in the NMR line width indicate the presence of a 0.2% concentrated native magnetic defect in stoichiometric NbFeSb samples. The origin of these native defects is believed to be due to Fe antisites on Nb sites. In addition, NMR shift and spin-lattice relaxation results below 200 K reveal a Korringa-like response indicating heavily-doped p-type behavior due to native defects. Above 280 K, this converts to an activated behavior, indicating the presence of an impurity band, empty at low temperatures, which is located around 0.03 eV above the valence band maximum.


Gene expression signature in organized and growth-arrested mammary acini predicts good outcome in breast cancer.
Nonmalignant human mammary epithelial cells (HMEC) seeded in laminin-rich extracellular matrix (lrECM) form polarized acini and, in doing so, transit from a disorganized proliferating state to an organized growth-arrested state. We hypothesized that the gene expression pattern of organized and growth-arrested HMECs would share similarities with breast tumors with good prognoses. Using Affymetrix HG-U133A microarrays, we analyzed the expression of 22,283 gene transcripts in 184 (finite life span) and HMT3522 S1 (immortal nonmalignant) HMECs on successive days after seeding in a lrECM assay. Both HMECs underwent growth arrest in G0-G1 and differentiated into polarized acini between days 5 and 7. We identified gene expression changes with the same temporal pattern in both lines and examined the expression of these genes in a previously published panel of microarray data for 295 breast cancer samples. We show that genes that are significantly lower in the organized, growth-arrested HMEC than in their proliferating counterparts can be used to classify breast cancer patients into poor and good prognosis groups with high accuracy. This study represents a novel unsupervised approach to identifying breast cancer markers that may be of use clinically.


Intergenerational transmission of attachment in abused and neglected mothers: the role of trauma-specific reflective functioning.
There are still important gaps in our knowledge regarding the intergenerational transmission of attachment from mother to child, especially in mothers with childhood histories of abuse and neglect (CA&N). This study examined the contributions of reflective function concerning general attachment relationships, and specifically concerning trauma, as well as those of maternal attachment states of mind to the prediction of infant attachment disorganization in a sample of mothers with CA&N and their infants, using a 20-month follow-up design. Attachment and reflective functioning were assessed during pregnancy with the Adult Attachment Interview. Infant attachment was evaluated with the Strange Situation Procedure. The majority (83%) of infants of abused and neglected mothers were classified as insecure, and a significant proportion (44%) manifested attachment disorganization. There was a strong concordance between mother and child attachment, indicative of intergenerational transmission of attachment in parents with CA&N and their infants. Both unresolved trauma and trauma-specific reflective function made significant contributions to explaining variance in infant attachment disorganization. The findings of this study highlight the importance of trauma-specific mentalization in the intergenerational transmission of attachment by mothers with a history of childhood maltreatment, and provide new evidence of the importance of the absence of mentalization regarding trauma for infant attachment.