Gonadotropin-releasing hormone analogues inhibit leiomyoma extracellular matrix despite presence of gonadal hormones.
To determine the effect of GnRH analogues (GnRH-a) leuprolide acetate (LA) and cetrorelix acetate on gonadal hormone-regulated expression of extracellular matrix in uterine leiomyoma three-dimensional (3D) cultures. Laboratory study. University research laboratory. Women undergoing hysterectomy for symptomatic leiomyomas. The 3D cell cultures, protein analysis, Western blot, immunohistochemistry. Expression of extracellular matrix proteins, collagen 1, fibronectin, and versican in leiomyoma cells 3D cultures exposed to E2, P, LA, cetrorelix acetate, and combinations for 24- and 72-hour time points. The 3D leiomyoma cultures exposed to E2 for 24 hours demonstrated an increased expression of collagen-1 and fibronectin, which was maintained for up to 72 hours, a time point at which versican was up-regulated significantly. Although P up-regulated collagen-1 protein (1.29 ± 0.04) within 24 hours of exposure, significant increase in all extracellular matrix (ECM) proteins was observed when the gonadal hormones were used concomitantly. Significant decrease in the amount of ECM proteins was observed on use of GnRH-a, LA and cetrorelix, with 24-hour exposure. Both the compounds also significantly decreased ECM protein concentration despite the presence of E2 or both gonadal hormones. This study demonstrates that GnRH-a directly affect the gonadal hormone-regulated collagen-1, fibronectin, and versican production in their presence. These findings suggest that localized therapy with GnRH-a may inhibit leiomyoma growth even in the presence of endogenous gonadal hormone exposure, thereby providing a mechanism to eliminate the hypoestrogenic side effects associated with GnRH-a therapy.


Meiosis-specific cell cycle regulation in maturing Xenopus oocytes.
Meiotic cell cycles differ from mitotic cell cycles in that the former lack S-phase in the interphase between meiosis I and meiosis II. To obtain clues for mechanisms involved in the cell cycle regulation unique to meiosis, we have examined changes in chromosomal morphology and H1 kinase activity during a meiotic period from metaphase I (MI) to metaphase II (MII) in Xenopus oocytes. Using populations of oocytes that underwent germinal vesicle breakdown (GVBD) within a 10 minute interval, we found that the kinase activity declined gradually during the 60 minute period after GVBD and then increased steadily during the following 80 minute interval, showing remarkable differences from the rapid drop and biphasic increase of the kinase activity in intermitotic periods (Solomon et al. (1990) Cell 63, 1013-1024; Dasso and Newport (1990) Cell 61, 811-823). We also found that the exit from MI lagged, by more than 30 minutes, behind the time of lowest H1 kinase activity, whereas the two events took place concomitantly at the end of meiosis II and mitosis. Consequently, the H1 kinase activity was already increasing during the first meiotic division. When H1 kinase activation at MII was delayed by a transient inhibition of protein synthesis after GVBD, oocytes were able to support formation of interphase nuclei and DNA replication between the first meiotic division and the MII arrest, indicating that the cell cycle entered S-phase between meiosis I and meiosis II. These results strongly suggest that the machinery required for entering S-phase has been established in maturing oocytes by the end of meiosis I.(ABSTRACT TRUNCATED AT 250 WORDS)


The proportion of synapses formed by the axons of the lateral geniculate nucleus in layer 4 of area 17 of the cat.
The connection between the dorsal lateral geniculate nucleus (dLGN) and area 17 of the cat is a classical model for studying thalamocortical relations. We investigated the proportion of asymmetric synapses in layer 4 of area 17 of cats formed by axons of the dLGN, because this is an important morphological parameter in understanding the impact of dLGN axons on their target neurons. Although the present consensus is that this proportion is small, the exact percentage remains in doubt. Most previous work estimated that the thalamus contributes less than 10% of excitatory synapses in layer 4, but one estimate was as high as 28%. Two issues contribute to these widely different estimates, one being the tracers used, the other being the use of biased stereological approaches. We have addressed both of these issues. Thalamic axons were labeled in vivo by injections of biotinylated dextran amine into the A lamina of the dLGN of anesthetized cats. After processing, the brain was cut serially and prepared for light and electron microscopy. The density of asymmetric synapses in the neuropil and the density of synapses formed by labeled dLGN boutons were measured by using an unbiased sampling method called the physical disector. Our counts indicate that, in the fixed cat brain, there are 5.9 x 10(8) +/- 0.9 x 10(8) asymmetric synapses per cubic millimeter of layer 4 in area 17, and the dLGN input provides only 6% of all asymmetric synapses in layer 4. The vast majority of synapses of layer 4 probably originate from other neurons in area 17.


Soliton self-frequency shift and third-harmonic generation in a four-hole As₂S₅ microstructured optical fiber.
Soliton self-frequency shift (SSFS) and third-harmonic generation (THG) are observed in a four-hole As2S5 chalcogenide microstructured optical fiber (MOF). The As2S5 MOF is tapered to offer an ideal environment for SSFS. After tapering, the zero-dispersion wavelength (ZDW) shifts from 2.02 to 1.61 μm, and the rate of SSFS can be enhanced by increasing the energy density of the pulse. By varying the average input power from 220 to 340 mW, SSFS of a soliton central wavelength from 2.206 to 2.600 μm in the mid-infrared is observed in the tapered segment, and THG at 632 nm is observed in the untapered segment.


Temporal lobe cortical thickness correlations differentiate the migraine brain from the healthy brain.
Interregional cortical thickness correlations reflect underlying brain structural connectivity and functional connectivity. A few prior studies have shown that migraine is associated with atypical cortical brain structure and atypical functional connectivity amongst cortical regions that participate in sensory processing. However, the specific brain regions that most accurately differentiate the migraine brain from the healthy brain have yet to be determined. The aim of this study was to identify the brain regions that comprised interregional cortical thickness correlations that most differed between migraineurs and healthy controls. This was a cross-sectional brain magnetic resonance imaging (MRI) investigation of 64 adults with migraine and 39 healthy control subjects recruited from tertiary-care medical centers and their surrounding communities. All subjects underwent structural brain MRI imaging on a 3T scanner. Cortical thickness was determined for 70 brain regions that cover the cerebral cortex and cortical thickness correlations amongst these regions were calculated. Cortical thickness correlations that best differentiated groups of six migraineurs from controls and vice versa were identified. A model containing 15 interregional cortical thickness correlations differentiated groups of migraineurs from healthy controls with high accuracy. The right temporal pole was involved in 13 of the 15 interregional correlations while the right middle temporal cortex was involved in the other two. A model consisting of 15 interregional cortical thickness correlations accurately differentiates the brains of small groups of migraineurs from those of healthy controls. Correlations with the right temporal pole were highly represented in this classifier, suggesting that this region plays an important role in migraine pathophysiology.


Airway management after maxillectomy with free flap reconstruction.
Maxillectomy defects require complex 3-dimensional reconstructions often best suited to microvascular free tissue transfer. Postoperative airway management during this procedure has little discussion in the literature and is often dictated by surgical dogma. The purpose of this article was to review our experience in order to evaluate the effect of airway management on perioperative outcomes in patients undergoing maxillectomy with free flap reconstruction. A retrospective chart review was performed on patients receiving maxillectomy with microvascular reconstruction at 2 institutions between 1999 and 2011. Patient's airways were managed with or without elective tracheotomy at the surgical team's discretion and different perioperative outcomes were measured. The primary outcome was incidence of airway complication including pneumonia and need for further airway intervention. Secondary outcome was measured as factors leading to perioperative performance of the tracheotomy. Seventy-nine of 143 patients received elective tracheotomy perioperatively. The incidence of airway complication was equivalent between groups (10.1% vs 9.4%; p = .89). Patients with cardiopulmonary comorbidities were more likely to receive perioperative tracheotomy (74.1% vs 50.9%; p = .03) without a difference in airway complications. Other patient cofactors did not have an impact on perioperative tracheotomy or airway complication rate. Elective tracheotomy may safely be avoided in a subset of patients undergoing maxillectomy with microvascular reconstruction. Elective tracheotomy should be considered in patients with cardiopulmonary risk factors.


Decision ambiguity is mediated by a late positive potential originating from cingulate cortex.
People often make decisions in the face of ambiguous information, but it remains unclear how ambiguity is represented in the brain. We used three types of ambiguous stimuli and combined EEG and fMRI to examine the neural representation of perceptual decisions under ambiguity. We identified a late positive potential, the LPP, which differentiated levels of ambiguity, and which was specifically associated with behavioral judgments about choices that were ambiguous, rather than passive perception of ambiguous stimuli. Mediation analyses together with two further control experiments confirmed that the LPP was generated only when decisions are made (not during mere perception of ambiguous stimuli), and only when those decisions involved choices on a dimension that is ambiguous. A further control experiment showed that a stronger LPP arose in the presence of ambiguous stimuli compared to when only unambiguous stimuli were present. Source modeling suggested that the LPP originated from multiple loci in cingulate cortex, a finding we further confirmed using fMRI and fMRI-guided ERP source prediction. Taken together, our findings argue for a role of an LPP originating from cingulate cortex in encoding decisions based on task-relevant perceptual ambiguity, a process that may in turn influence confidence judgment, response conflict, and error correction.


The diagnostic role of claudins in serous effusions.
We analyzed the diagnostic role of claudins in effusion cytology in 325 effusions, including 218 ovarian, 49 breast, 15 cervical or endometrial, 10 gastrointestinal, and 8 lung adenocarcinomas and 25 malignant mesotheliomas (MMs). Specimens were analyzed for claudin-1 and claudin-3 expression using immunohistochemical analysis. Ovarian and breast adenocarcinoma were further analyzed for claudin-7 expression. Claudin-1 expression was most frequent in ovarian and cervical or endometrial adenocarcinoma compared with other adenocarcinomas and MMs (P < .001). Claudin-3 expression was comparable in adenocarcinomas of different origin but was absent in MMs (P < .001). Reactive mesothelial cells rarely expressed claudins. Claudin-7 expression was higher in ovarian than in breast adenocarcinoma (P < .001). Our data suggest that expression of claudin-3 or claudin-7 is specific for adenocarcinoma and rules out the diagnosis of cells as mesothelial and that absence of claudin-1 expression excludes ovarian carcinoma as the possible origin of metastatic adenocarcinoma. Claudins may, therefore, be of diagnostic value in effusion cytology.


The dosimetric impact of dental implants on head-and-neck volumetric modulated arc therapy.
This work aims to investigate the dosimetric impact of dental implants on volumetric modulated arc therapy (VMAT) for head-and-neck patients and to evaluate the effectiveness of using the material's electron-density ratio for the correction. An in-house Monte Carlo (MC) code was utilized for the dose calculation to account for the scattering and attenuation caused by the high-Z implant material. Three different dental implant materials were studied in this work: titanium, Degubond®4 and gold. The dose perturbations caused by the dental implant materials were first investigated in a water phantom with a 1 cm(3) insert. The per cent depth dose distributions of a 3 × 3 cm(2) photon field were compared with the insert material as water and the three selected dental implant materials. To evaluate the impact of the dental implant on VMAT patient dose calculation, four head-and-neck cases were selected. For each case, the VMAT plan was designed based on the artifact-corrected patient geometry using a treatment planning system (TPS) that was typically utilized for routine patient treatment. The plans were re-calculated using the MC code for five situations: uncorrected geometry, artifact-corrected geometry and artifact-corrected geometry with one of the three different implant materials. The isodose distributions and the dose-volume histograms were cross-compared with each other. To evaluate the effectiveness of using the material's electron-density ratio for dental implant correction, the implant region was set as water with the material's electron-density ratio and the calculated dose was compared with the MC simulation with the real material. The main effect of the dental implant was the severe attenuation in the downstream. The 1 cm(3) dental implant can lower the downstream dose by 10% (Ti) to 51% (Au) for a 3 × 3 cm(2) field. The TPS failed to account for the dose perturbation if the dental implant material was not precisely defined. For the VMAT patient dose calculation, the presence of dental implants degrades the PTV coverage significantly. With the material's electron-density ratio applied, the dose calculation accuracy in the water phantom and the VMAT patient was improved to a clinically acceptable level. The effects of the dental implant material can be clinically significant and its impact varies with the density of the dental implant material. We demonstrated that it was effective to use the material's electron-density ratio to account for the dosimetric impact of the dental implant.


Health worker perspectives on the possible use of intramuscular artesunate for the treatment of severe malaria at lower-level health facilities in settings with poor access to referral facilities in Nigeria: a qualitative study.
Innovative strategies are needed to reduce malaria mortality in high burden countries like Nigeria. Given that one of the important reasons for this high malaria mortality is delay in receiving effective treatment, improved access to such treatment is critical. Intramuscular artesunate could be used at lower-level facilities given its proven efficacy, ease of use and excellent safety profile. The objective of this study was therefore to explore health workers' perspectives on the possible use of intramuscular artesunate as definitive treatment for severe malaria at lower-level facilities, especially when access to referral facilities is challenging. The study was to provide insight as a formative step into the conduct of future experimental studies to ascertain the feasibility of the use of intramuscular artesunate for definitive treatment of severe malaria in lower level facilities where access to referral care is limited. This qualitative study was done across three southern States in Nigeria (Oyo, Cross River and Enugu). Key informant interviews were conducted over a period of three months between October and December 2014 among 90 purposively selected health workers with different roles in malaria case management from primary care to policy level. A thematic content analysis was used to analyse data. Overall, most of health workers and other key informant groups thought that the use of intramuscular artesunate for definitive treatment of severe malaria at lower-level facilities was possible. They however reported human resource and infrastructure constraints as factors affecting the feasibility of intramuscular artesunate use as definitive treatment for severe malaria in lower-level facilities.. Specifically identified barriers included limited numbers of skilled health workers available to manage potential complications of severe malaria and poorly equipped facilities for supportive treatment. Intramuscular artesunate was considered easy to administer and the proximity of lower-level facilities to communities was deemed important in considering the possibility of its use at lower-level facilities. Health workers also emphasised the important role of operational research to provide additional evidence to guide the implementation of existing policy recommendations and inform future policy revisions. From the perspective of health workers, use of intramuscular artesunate for definitive treatment of severe malaria at lower-level health facilities in Nigeria is possible but dependent on availability of skilled workers, well-equipped lower-level facilities to provide supportive treatment There is need for further operational research to establish feasibility and guide the implementation of such an intervention.


Maintenance electroconvulsive therapy for a neuroleptic-intolerant patient with disorganized schizophrenia.
Owing to unresolved questions concerning the efficacy and safety of electroconvulsive therapy (ECT) in the treatment of schizophrenia, and widespread negative attitudes toward ECT, maintenance ECT (mECT) is generally considered only as a last resort. Nevertheless, in some clinical situations, the advantages of mECT may outweigh the risks and associated concerns. We report the case of a patient suffering from disorganized schizophrenia who had life-threatening hematological side effects to treatment with antipsychotic agents. Long-term mECT was administered and the patient achieved remission with no notable side effects. He was able to maintain a peaceful daily routine and improved functioning. Considering the lack of controlled trials in this area, this case and other similar cases reported in the literature add support to a possible benefit of mECT in disorganized schizophrenia, particularly when pharmacotherapy is insufficient or contraindicated.


Importance of work environments on hospital outcomes in nine countries.
To determine the effect of hospital work environments on hospital outcomes across multiple countries. Primary survey data using a common instrument were collected from separate cross sections of 98 116 bedside care nurses practising in 1406 hospitals in 9 countries between 1999 and 2009. Nurse burnout and job dissatisfaction, patient readiness for hospital discharge and quality of patient care. High nurse burnout was found in hospitals in all countries except Germany, and ranged from roughly a third of nurses to about 60% of nurses in South Korea and Japan. Job dissatisfaction among nurses was close to 20% in most countries and as high as 60% in Japan. Close to half or more of nurses in every country lacked confidence that patients could care for themselves following discharge. Quality-of-care rated as fair or poor varied from 11% in Canada to 68% in South Korea. Between one-quarter and one-third of hospitals in each country were judged to have poor work environments. Working in a hospital with a better work environment was associated with significantly lower odds of nurse burnout and job dissatisfaction and with better quality-of-care outcomes. Poor hospital work environments are common and are associated with negative outcomes for nurses and quality of care. Improving work environments holds promise for nurse retention and better quality of patient care.


Role of honey after tonsillectomy: a systematic review and meta-analysis of randomised controlled trials.
Honey reduced post-tonsillectomy pain, but its effects on awakening at night, inflammation and healing of the tonsillar fossa were controversial. This systematic review and meta-analysis of randomised controlled trials (RCTs) evaluated the effect of oral honey on pain, consumption of painkillers, awakening at night, healing of tonsillar fossa and adverse effects in children after tonsillectomy. A search of MEDLINE, EMBASE, Scopus, CINAHL and Cochrane Collaboration Library databases was performed without any restriction of publication year. The end date of search was 30 June 2016. The search was supplemented by search from Google, hand search of cross-references of selected articles and reviews, and contacting the authors of different studies. The inclusion criteria were RCTs comparing the effect of honey with control on different outcomes, in children after tonsillectomy. Our search generated 64 studies, and eight RCTs met our inclusion criteria. The methodological quality of RCTs was poor. Compared to control, honey significantly decreased postoperative pain from day 1 to day 7 (P = 0.05 to <0.0001); consumption of painkillers from days 1 to 5 (P = 0.03 to 0.003) and on day 10 (P = 0.002); and number of awakening at night due to pain on days 2 and 4 after tonsillectomy (P = 0.0001, 0.004). The healing of tonsillar fossa was significantly greater with honey compared to control on days 3-4 (P = 0.02) and days ≥9 (P = 0.01) after tonsillectomy. The adverse effects were not significantly different between honey and control groups. The Grading of Recommendation, Assessment, Development and Evaluation (GRADE) of the evidence for different outcomes varied from 'low' to 'very low'. Honey improved pain, requirement of painkillers and awakening at night due to pain in children after tonsillectomy. There was little improvement in healing of tonsillar fossa. The GRADE of the evidence varied from 'low' to 'very low'. A good-quality, placebo-controlled RCT of different doses and durations of administration of honey is required to evaluate its clear efficacy and safety in children after tonsillectomy.


Dynamic contrast enhanced-MRI in head and neck cancer patients: variability of the precontrast longitudinal relaxation time (T10).
Calculation of the precontrast longitudinal relaxation times (T10) is an integral part of the Tofts-based pharmacokinetic (PK) analysis of dynamic contrast enhanced-magnetic resonance images. The purpose of this study was to investigate the interpatient and over time variability of T10 in head and neck primary tumors and involved nodes and to determine the median T10 for primary and nodes (T10(p,n)). The authors also looked at the implication of using voxel-based T10 values versus region of interest (ROI)-based T10 on the calculated values for vascular permeability (K(trans)) and extracellular volume fraction (v(e)). Twenty head and neck cancer patients receiving concurrent chemoradiation and molecularly targeted agents on a prospective trial comprised the study population. Voxel-based T10's were generated using a gradient echo sequence on a 1.5 T MR scanner using the variable flip angle method with two flip angles [J. A. Brookes et al., "Measurement of spin-lattice relaxation times with FLASH for dynamic MRI of the breast," Br. J. Radiol. 69, 206-214 (1996)]. The voxel-based T10, K(trans), and v(e) were calculated using iCAD's (Nashua, NH) software. The mean T10's in muscle and fat ROIs were calculated (T10(m,f)). To assess reliability of ROI drawing, T10(p,n) values from ROIs delineated by 2 users (A and B) were calculated as the average of the T10's for 14 patients. For a subset of three patients, the T10 variability from baseline to end of treatment was also investigated. The K(trans) and v(e) from primary and node ROIs were calculated using voxel-based T10 values and T10(p,n) and differences reported. The calculated T10 values for fat and muscle are within the range of values reported in literature for 1.5 T, i.e., T10(m) = 0.958 s and T10(f) = 0.303 s. The average over 14 patients of the T10's based on drawings by users A and B were T10(pA) = 0.804 s, T10(nA) = 0.760 s, T10(pB) = 0.849 s, and T10(nB) = 0.810 s. The absolute percentage difference between K(trans) and v(e) calculated with voxel-based T10 versus T10(p,n) ranged from 6% to 81% and from 2% to 24%, respectively. There is a certain amount of variability in the median T10 values between patients, but the differences are not significant. There were also no statistically significant differences between the T10 values for primary and nodes at baseline and the subsequent time points (p = 0.94 Friedman test). Voxel-based T10 calculations are essential when quantitative Tofts-based PK analysis in heterogeneous tumors is needed. In the absence of T10 mapping capability, when a relative, qualitative analysis is deemed sufficient, a value of T10(p,n) = 0.800 s can be used as an estimate for T10 for both the primary tumor and the affected nodes in head and neck cancers at all the time points considered.


Past and future of prophylactic ablation of the cervical squamocolumnar junction.
HPV vaccination has the potential to prevent the vast majority of cervical cancer cases but cervical cancer screening remains the only prevention strategy in adult unvaccinated women. The range of primary screening tests has expanded to include, in addition to cytology, visual inspection with acetic acid (VIA) and HPV-testing. HPV-testing has the best sensitivity and negative predictive value, and a low-cost HPV test may make large-scale high-quality cervical cancer screening possible in low- and medium-income countries (LMICs). However, on account of its low specificity, HPV-testing would impose the additional burden of triaging HPV+ women using cytology, colposcopy, VIA, or other not yet affordable tests. If minimally invasive treatments that have proven efficacious in HPV+ women with cervical intra-epithelial (CIN) grade 2 and 3 lesions also reduced future cervical cancer risk in lesion-free HPV+ women, the treatment of all HPV+ women would become attractive in LMICs in which screening should be performed as infrequently as possible. In the pre-mass screening era, gynaecologists widely practiced prophylactic ablation of the columnar epithelium visible on the ectocervix (ectopy) and squamocolumnar junction (SCJ) in the hope of preventing cervical cancer. Favourable outcomes were reported, especially from Finland, but conclusive results were not reached on account of weaknesses in the study methods. Indirect support for prophylactic ablation is provided by the hypothesis that some cells of embryonic origin derived from the SCJ are the source of high-grade CIN and cervical carcinoma, and that they do not regenerate after SCJ ablation. SCJ cell elimination may avoid neoplastic transformation though not HPV reinfection. Randomised controlled trials are gold-standard, but if not feasible, an evaluation of the impact of prophylactic ablation could be done in the framework of large HPV-based screening programmes. Careful follow-up of lesion-free HPV+ women would provide much needed information on the risk-to-benefit ratio of prophylactic ablation.


Size of Heparin-Imprinted Nanoparticles Reflects the Matched Interactions with the Target Molecule.
It has been shown that the faradic current at an electrode grafted with molecularly imprinted polymer (MIP) is sensitive to the specific target molecule used as the template. This phenomenon is applicable to sensors with very high selectivity, but the sensing mechanism is still a black box. We investigated the size sensitivity of nanoparticles of molecularly imprinted polymers (MIP-NPs) to a specific interaction for determination of the mechanism of the gate effect and its feasibility for new applications. Nanoparticles of poly(methacryloxy ethyl trimethylammonium chloride-co-acrylamide-co-methylenebisacrylamide) imprinted with heparin immobilized on glass beads were synthesized. The diameter of the MIP-NPs of heparin was increased by the presence of the heparin template but was insensitive to chondroitin sulfate C (CSC), the analogue of heparin. The high selectivity of the MIP-NPs was consistent with the selectivity of electrodes grafted with a heparin-imprinted polymer in our previous studies. The quartz crystal microbalance probes immobilizing heparin or CSC were sensitive to MIP-NPs, which indicates that the binding ability of MIP-NP does not discriminate between the template and other glycosaminoglycans. These results indicate that the size of the MIP-NP is sensitive to the matched binding with the template through the imprinted cavity.


Secondhand smoke exposure and intermittent claudication: a Scotland-wide study of 4231 non-smokers.
Active smoking is an important risk factor for peripheral arterial disease. In contrast, published evidence on the association with secondhand smoke (SHS) is very limited. The aim of this study was to examine the association between SHS exposure and intermittent claudication (IC) among middle aged non-smokers. Multivariate logistic regression analyses were used to adjust for potential confounders. The Scottish Health Survey, a pan-Scotland, representative survey of the general population. We conducted a cross-sectional study using the Scottish Health Surveys undertaken between 1998 and 2010. Inclusion was restricted to participants aged > 45 years. Of the 4231 confirmed non-smokers (self-reported non-smokers with salivary cotinine concentrations < 15 ng/mL), 134 (3.2%) had IC based on the Edinburgh Claudication Questionnaire. There was evidence of a dose relationship, whereby the risk of IC increased with increasing cotinine concentration. Following adjustment for potential confounders, participants with a cotinine concentration ≥ 2.7 ng/mL were still significantly more likely to have IC (OR 1.76, 95% CI 1.04 to 3.00; p = 0.036) compared with those with a cotinine concentration < 0.7 ng/mL. Among non-smokers, 5.6% (95% CI -0.8% to 11.7%) of cases of IC were attributable to cotinine concentrations ≥ 2.7 ng/mL and a further 3.6% (95% CI -6.6% to 12.8%) to cotinine concentrations of 0.7-2.6 ng/mL. As with coronary heart disease and stroke, SHS exposure was independently associated with IC. Our findings add to the published evidence in support of protecting the general public from SHS exposure.


Problematic internet usage in US college students: a pilot study.
Internet addiction among US college students remains a concern, but robust estimates of its prevalence are lacking. We conducted a pilot survey of 307 college students at two US universities. Participants completed the Internet Addiction Test (IAT) as well as the Patient Health Questionnaire. Both are validated measures of problematic Internet usage and depression, respectively. We assessed the association between problematic Internet usage and moderate to severe depression using a modified Poisson regression approach. In addition, we examined the associations between individual items in the IAT and depression. A total of 224 eligible respondents completed the survey (73% response rate). Overall, 4% of students scored in the occasionally problematic or addicted range on the IAT, and 12% had moderate to severe depression. Endorsement of individual problematic usage items ranged from 1% to 70%. In the regression analysis, depressive symptoms were significantly associated with several individual items. Relative risk could not be estimated for three of the twenty items because of small cell sizes. Of the remaining 17 items, depressive symptoms were significantly associated with 13 of them, and three others had P values less than 0.10. There was also a significant association between problematic Internet usage overall and moderate to severe depression (relative risk 24.07, 95% confidence interval 3.95 to 146.69; P = 0.001). The prevalence of problematic Internet usage among US college students is a cause for concern, and potentially requires intervention and treatment amongst the most vulnerable groups. The prevalence reported in this study is lower than that which has been reported in other studies, however the at-risk population is very high and preventative measures are also recommended.


Assuming ability of youth with autism: Synthesis of methods capturing the first-person perspectives of children and youth with disabilities.
Most research regarding youth with autism spectrum disorder has not focused on their first-person perspectives providing limited insight into methodologies best suited to eliciting their voices. We conducted a synthesis of methods previously used to obtain the first-person perspectives of youth with various disabilities, which may be applicable to youth with autism spectrum disorder. Two-hundred and eighty-four articles met the inclusion criteria of our scoping review. We identified six distinct primary methods (questionnaires, interviews, group discussion, narratives, diaries, and art) expressed through four communication output modalities (language, sign language and gestures, writing, and images). A group of parents who have children with autism spectrum disorder were then presented with a synthesis of results. This parent consultation was used to build on approaches identified in the literature. Parents identified barriers that may be encountered during participant engagement and provided insights on how best to conduct first-person research with youth with autism spectrum disorder. Based on our findings, we present a novel methodological framework to capture the perspectives of youth with various communication and cognitive abilities, while highlighting family, youth, and expert contributions.


Increasing bacteremia due to coagulase-negative staphylococci: fiction or reality?
The role of coagulase-negative staphylococci (CNS) in bacteremias continues to be controversial. Until the 1970s, CNS were mostly recognized as contaminants, being part of the cutaneous flora. Since then, several studies have reported increasing incidence and severity of infections due to CNS. To review the literature concerning the epidemiology of CNS bacteremia in the United States and Europe with reference to the multiple definitions of infection versus contamination, considering the effect of potential biases influencing the validity of the reported results. Literature search of the MEDLINE database from January 1980 to February 1998. Studies with fewer than 500 episodes of bloodstream infections or fewer than 100 episodes of CNS bacteremia were not included in the pooled analysis. (1) CNS remain the most frequent contaminants (58%-83% of positive blood cultures); (2) the proportion of all bloodstream infections caused by CNS is increasing (R=.51); (3) the overall incidence of true CNS bacteremia is increasing (R=.54, P=.0014); (4) comparing the United States to Europe, there is an increasing trend in the incidence of nosocomial bacteremia due to CNS in the United States (R=.82, P=.0006), but no trend is seen in European studies; (5) the mortality associated with true CNS bacteremia varies between 4.9% and 28%. This review confirms the increasing importance of CNS bacteremias, measured both as a proportion and as an incidence of bloodstream infections. The contributions of several possible explanations for the incidence increase and the difference between the United States and Europe need further evaluation: (1) increased recognition and awareness of CNS infections among clinicians; (2) a gradual change in the definition of true bacteremia from an obligatory two positive blood cultures to one positive blood culture associated with a clinical picture compatible with infection; (3) a change in blood culture practices and techniques; (4) an increase in the numbers of blood cultures performed, which is reported both in the United States and in Europe; (5) a shift toward more elderly patients with increasingly severe underlying illnesses; and (6) increasing use of intravascular devices. The apparent trend of increasing CNS bacteremia seems to be valid. Whether there is a real difference between the United States and Europe concerning the increase of CNS bacteremia is difficult to establish due to the large number of confounding factors. Few studies take into account the number of blood cultures performed or the use of intravascular devices to adjust for the observed trends. Further on-site surveillance studies are needed to investigate the phenomenon more extensively.


The Association of Prediabetes and Diabetes Risk Perception With Leisure-Time Physical Activity and Weight Loss.
To examine the association of perceived risk of prediabetes and diabetes with leisure-time physical activity (LTPA) and weight loss, and determine whether the association of risk perception with LTPA and weight loss varies by race/ethnicity. Cross-sectional. National Health and Nutrition Examination Survey (NHANES) 2011-2014. Non-Latino white, non-Latino black, and Latino nondiabetic and nonprediabetic NHANES participants ≥18 years of age who were not underweight (n = 9550). Demographic characteristics, LTPA, attempted weight loss, and perceived risk of prediabetes or diabetes. Log-binomial regression models were fit to assess the association of perceived risk with meeting LTPA recommendations and having attempted to lose weight, overall and by race/ethnicity. Individuals reporting that they perceived they could be at risk for diabetes/prediabetes were less likely to meet LTPA recommendations (adjusted prevalence ratio [aPR]: 0.87; 95% confidence interval [CI]: 0.79-0.95), but significantly more likely to report attempting weight loss in the past year (aPR: 1.14; 95%CI: 1.04-1.25), compared with those reporting no risk perception. Latino and non-Latino blacks who perceived they could be at risk for diabetes/prediabetes were 25% and 35% more likely to report trying to lose weight in the past year (aPR: 1.25; 95% CI: 1.08-1.44 and aPR: 1.35; 95% CI: 1.19-1.54, respectively), compared with Latino and non-Latino blacks that did not perceive being at risk. In contrast, non-Latino whites who perceived they were at risk were 20% less likely to report meeting LTPA recommendations (aPR: 0.80; 95% CI: 0.72-0.89), compared with non-Latino whites reporting no risk perception. Findings highlight the role of perceived risk for prediabetes and diabetes in LTPA and weight loss, with findings varying by race/ethnicity. Awareness of prediabetes and diabetes risk could contribute to efforts aimed at improving LTPA and weight loss.


Bronchial mucosal mast cells in asymptomatic smokers relation to structure, lung function and emphysema.
The pathologic mechanisms of chronic obstructive pulmonary disease (COPD) most certainly involves neutrophil granulocytes, cytotoxic T-cells, macophages and mast cells. The aim of this study was to investigate the relation between the number of mast cells in different compartments in bronchial biopsies of central proximal airways to structural changes, lung function tests and emphysema detected by high resolution computed tomography (HRCT). Twenty nine asymptomatic smoking and 16 never-smoking men from a population study were recruited. Central bronchial biopsies were stained to identify mast cells by immunohistochemistry. The number of mast cells in the epithelium, lamina propria and smooth muscle as well as epithelial integrity and thickness of the tenascin and laminin layer were determined. Smokers had increased numbers of mast cells in all compartments (P<0.001). Structural changes were correlated to mast cell numbers with the closest associations to mast cell numbers in the smooth muscle [epithelial integrity (R(S)=-0.48, P=0.008), laminin layer (R(S)=0.63, P=0.0002), tenascin layer (R(S)=0.40, P=0.03)]. Similar correlations between mast cells and lung function tests were seen [functional residual capacity (FRC) (R(S)=0.60, P=0.0006), total lung capacity (TLC) (R(S)=0.44, P=0.02) and residual volume (RV) (R(S)=0.41, P=0.03)]. No correlations could be detected between mast cells and FEV1 or to emphysema. Smoking is associated with an increase of mast cells in all compartments of the bronchial mucosa, including smooth muscle, and this is related to altered airway structure and function.


Transition between fast and slow gamma modes in rat hippocampus area CA1 in vitro is modulated by slow CA3 gamma oscillations.
Hippocampal gamma oscillations have been associated with cognitive functions including navigation and memory encoding/retrieval. Gamma oscillations in area CA1 are thought to depend on the oscillatory drive from CA3 (slow gamma) or the entorhinal cortex (fast gamma). Here we show that the local CA1 network can generate its own fast gamma that can be suppressed by slow gamma-paced inputs from CA3. Moderate acetylcholine receptor activation induces fast (45 ± 1 Hz) gamma in rat CA1 minislices and slow (33 ± 1 Hz) gamma in CA3 minislices in vitro. Using pharmacological tools, current-source density analysis and intracellular recordings from pyramidal cells and fast-spiking stratum pyramidale interneurons, we demonstrate that fast gamma in CA1 is of the pyramidal-interneuron network gamma (PING) type, with the firing of principal cells paced by recurrent perisomal IPSCs. The oscillation frequency was only weakly dependent on IPSC amplitude, and decreased to that of CA3 slow gamma by reducing IPSC decay rate or reducing interneuron activation through tonic inhibition of interneurons. Fast gamma in CA1 was replaced by slow CA3-driven gamma in unlesioned slices, which could be mimicked in CA1 minislices by sub-threshold 35 Hz Schaffer collateral stimulation that activated fast-spiking interneurons but hyperpolarised pyramidal cells, suggesting that slow gamma frequency CA3 outputs can suppress the CA1 fast gamma-generating network by feed-forward inhibition and replaces it with a slower gamma oscillation driven by feed-forward inhibition. The transition between the two gamma oscillation modes in CA1 might allow it to alternate between effective communication with the medial entorhinal cortex and CA3, which have different roles in encoding and recall of memory.


Assessment of Hidden Hearing Loss in Normal Hearing Individuals with and Without Tinnitus.
To evaluate the functions of cochlear structures and the distal part of auditory nerve as well as dead regions within the cochlea in individuals with normal hearing with or without tinnitus by using electrophysiological tests. Nine individuals (ages: 21-59 years) with normal hearing with tinnitus were included in the study group. Thirteen individuals (ages: 25-60 years) with normal hearing without tinnitus were included in the control group. Immitancemetric examination, pure-tone audiometry (125Hz-16kHz), speech audiometry in quiet and noise environments, transient evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAEs), threshold equalizing noise (TEN test (500Hz-4kHz), and ECochG tests, Beck Depression Questionnaire, Tinnitus Handicap Questionnaire, and Visual Analog Scale were performed. In the study group, three patients were found to have a minimal depression and six were found to have a mild depression. In pure-tone audiometry, the threshold (6-16 kHz) in the study group was significantly higher than that of the control group at all frequencies. In the study group, lower performance scores were obtained in speech discrimination in noise in both ears. In the control group, no dead region was detected in the TEN test whereas 75% of subjects in the study group had dead regions. DPOAE and TEOAE responses between study and control group subjects were not different. In the ECochG test, subjects in the study group showed an increase in the summating potential/action potential (SP/AP) ratio in both ears. Determination of the SP/AP ratio in patients with tinnitus may be useful in diagnosing hidden hearing loss. Detection of dead regions in 75% of patients in the TEN test may indicate that inner hair cells may be responsible for tinnitus.


Improving pre- and postmenarcheal 12-year-old girls' attitudes toward menstruation.
Adolescence is a time of rapid changes, including risk for unwanted pregnancies and sexually transmitted infections. Education may improve understanding and attitudes toward menstruation among adolescents thus increasing their awareness of risks and enabling them to protect themselves accordingly. To investigate effects of education on attitudes, two interventions were compared in 345 12-year-old girls. The new, active intervention given to premenarcheal girls just before menarche resulted in improvements in attitudes toward menstruation compared with standard intervention. Thus, just before menarche girls should be offered education modeled after the active intervention. The education must be concrete and based on multisensory learning.


Dynamic regulation of extracellular signal-regulated kinase (ERK) by protein phosphatase 2A regulatory subunit B56γ1 in nuclei induces cell migration.
Extracellular signal-regulated kinase (ERK) signalling plays a central role in various biological processes, including cell migration, but it remains unknown what factors directly regulate the strength and duration of ERK activation. We found that, among the B56 family of protein phosphatase 2A (PP2A) regulatory subunits, B56γ1 suppressed EGF-induced cell migration on collagen, bound to phosphorylated-ERK, and dephosphorylated ERK, whereas B56α1 and B56β1 did not. B56γ1 was immunolocalized in nuclei. The IER3 protein was immediately highly expressed in response to costimulation of cells with EGF and collagen. Knockdown of IER3 inhibited cell migration and enhanced dephosphorylation of ERK. Analysis of the time course of PP2A-B56γ1 activity following the costimulation showed an immediate loss of phosphatase activity, followed by a rapid increase in activity, and this activity then remained at a stable level that was lower than the original level. Our results indicate that the strength and duration of the nuclear ERK activation signal that is initially induced by ERK kinase (MEK) are determined at least in part by modulation of the phosphatase activity of PP2A-B56γ1 through two independent pathways.


Intranasal midazolam vs rectal diazepam for the home treatment of acute seizures in pediatric patients with epilepsy.
To compare intranasal midazolam, using a Mucosal Atomization Device (IN-MMAD), with rectal diazepam (RD) for the home treatment of seizures in children with epilepsy. Prospective randomized study. Patients' homes and a freestanding children's hospital that serves as a referral center for 5 states. A total of 358 pediatric patients who visited a pediatric neurology clinic from July 2006 through September 2008 and were prescribed a home rescue medication for their next seizure. Caretakers were randomized to use either 0.2 mg/kg of IN-MMAD (maximum, 10 mg) or 0.3 to 0.5 mg/kg of RD (maximum, 20 mg) at home for their child's next seizure if it lasted more than 5 minutes. The primary outcome measure was total seizure time after medication administration. Our secondary outcome measures were total seizure time, time to medication administration, respiratory complications, emergency medical service support, emergency department visits, hospitalizations, and caretakers' ease of administration and satisfaction with the medication. A total of 92 caretakers gave the study medication during a child's seizure (50 IN-MMAD, 42 RD). The median time from medication administration to seizure cessation for IN-MMAD was 1.3 minutes less than for RD (95% confidence interval, 0.0-3.5 minutes; P=.09). The median time to medication administration was 5.0 minutes for each group. No differences in complications were found between treatment groups. Caretakers were more satisfied with IN-MMAD and report that it was easier to give than RD. There was no detectable difference in efficacy between IN-MMAD and RD as a rescue medication for terminating seizures at home in pediatric patients with epilepsy. Ease of administration and overall satisfaction was higher with IN-MMAD compared with RD. Trial Registration clinicaltrials.gov Identifier: NCT00326612.


Contemporary social work licensure: implications for macro social work practice and education.
Understanding the impact of state licensing on social work practice remains a critical concern for social work academics and professionals alike. Given the complex social problems of our times, social workers need to be prepared to intervene with the individual, in various structural dimensions, and to engage in policy debates at the core of human injustice and suffering. Currently, there is insufficient research on the impact of state licensing on the profession and on accredited social work education. The purpose of this article is to begin to address this by providing an overview of the current state of social work licensing across the United States and to analyze the implications of social work regulations as they relate to the future of macro social work practice and education.


Extracorporal hemodialysis with acute or decompensated chronical hepatic failure.
Conventional diagnostic procedures and therapy of acute liver failure (ALF) and acute-on-chronic liver failure (ACLF) focus on to identify triggering events of the acute deterioration of the liver function and to avoid them. Further objectives are to prevent the development respectively the progression of secondary organ dysfunctions or organ failure. Most of the times the endocrinological function of the liver can to a wide extent be compensated, but the removal of toxins can only marginally be substituted by conventional conservative therapy. To improve this component of the liver function is the main objective of extracorporal liver support systems. The following principles of liver support systems can be differentiated: Artificial systems, bioartifical systems and extracorporal liver perfusion systems. This HTA report focuses on artificial systems (e.g. BioLogic-DT/-DTPF, MARS, Prometheus), because only these approaches currently are relevant in the German health care system. In 2004 a category "Extracorporal liver assist device" was introduced in the list of "additional payments" in the German DRG-system, which makes reimbursement for hospitals using the technology in inpatient care possible, based on an hospital's individual contract with statutory sickness funds. To report the present evidence and future research need on medical efficacy and economic effectiveness of extracorporal liver support devices for treatment of patients with ALF or ACLF based on published literature data. Are artificial liver support systems efficient and effective in the treatment of ALF or ACLF? An extensive, systematic literature search in medical, economic, and HTA literature data bases was performed. Relevant data were extracted and synthesised. Relevant controlled trials were detected for BioLogic-DT and MARS. No randomised controlled trial on Prometheus was found. None of the included studies on BioLogic-DT showed advantages of the technology compared with standard conventional therapy concerning survival, clinical scores or clinical surrogate parameter like laboratory tests of liver function. Some studies reported complications and side effects of BioLogic-DT. All studies were methodologically insufficient. Concerning the use of MARS overall five studies - three of them randomised - were identified. Two studies reported a significant higher 30d-survival after MARS compared to controls, one study showed a non-significant trend to a better survival probability after one year. The studies showed statistically significant advantages in severity of hepatic encephalopathy, routine lab tests and hemodynamic parameter of the MARS group. None of the studies reported relevant complications or side effects. Although the methodological quality of the studies is seen as slightly better than in the studies on BioLogic-DT, there are methodological limitations: The largest sample size of the randomised trials was twelve patients per group and the study population was highly selected. Because of the methodological limitations the results can hardly be generalised. Only two economic publications presenting analyses of MARS could be de-tected. One publication shows major methodological mistakes which make a further interpretation of the results impossible. The other publication presents an incremental cost-effectiveness of MARS of 29,719 EUR per life year gained after one year from a payer's perspective (German statutory sickness fund, neglecting the intervention costs because of lacking reimbursement at this time), respectively 79,075 EUR per life year gained from a societal perspective. Including health related quality of life aspects the incremental costs per QALY (Quality adjusted life years) gained were calculated to be 44,784 EUR from a payer's perspective respectively 119,162 EUR from a societal perspective. The authors state that prolonging the time horizon of the calculations would improve cost-effectiveness ratios. The limitations of the study design also limit the scientific evidence of the results. The results of the detected publications do not give any evidence for a positive medical efficacy of BioLogic-DT. Concerning MARS there is some evidence for positive effects on 30d-survival, clinical parameter, and some lab tests, although the evidence is limited by the small number of studies and their methodological weakness. The currently strongly limited evidence shows a trend to an acceptable cost-effectiveness of MARS, although the results are based on only one non-randomised trial. To give valid recommendations concerning the medical efficacy as well as the cost-effectiveness of artificial liver support systems further studies are necessary.


SU-E-E-04: Building and Strengthening the First Master's Program in Medical Physics in The Gulf Region.
The first medical physics Master's program in the Arabian Gulf region was started in 2002 at King Fahd University of Petroleum & Minerals (KFUPM), Dhahran, Saudi Arabia. After consulting with national and international representatives from the AAPM, IOMP, the University of Wisconsin-Madison and King Faisal Specialist Hospital and Research Center (KFSHRC) we constructed a versatile and rigorous curriculum. The program requires the completion of 7 core courses, 7 required labs, a minimum of 3 elective courses, a research project, a four-month clinical rotation and passing and a comprehensive examination. The success of the program required very close collaboration with national hospitals such as King Fahad Specialist Hospital in Dammam (KFSH-D), KFSHRC, and Riyadh Military Hospital. We cemented the collaboration with a formal agreement between KFUPM and KFSH-D, whereby the clinical medical physicists are actively involved in teaching lectures and labs, evaluating students' performance and co-supervising their clinical rotation and research projects. In order to prepare our graduates for their medical physics careers, we emphasize innovative learning methods such as students centered learning, execution of course projects, experiential learning and acquiring research skills and tools such as Monte Carlo simulations. Our graduates have succeeded in securing clinical positions in some of the best hospitals in the region and achieved high employer satisfaction. Some students have gone to pursue their PhD's in North America and Europe. Many of our students succeeded in publishing their projects in international journals and international conferences. One of our students was instrumental in obtaining a US patent (US Patent # 785298) for an innovative x-ray tube design. We have achieved national recognition through the excellence of our graduates. In order to maintain high education quality standards and achieve international recognition, we are presently working to acquire IAEA approval and CAMPEP accreditation.


Point specificity of acupuncture in the light of recent clinical and imaging studies.
One fundamental question that is still not resolved is whether acupuncture needles must be inserted in specific points to have their greatest effects. In the majority of large RCTs recently conducted in Germany, acupuncture was significantly more effective than doing nothing but not than sham acupuncture. Only for one study of chronic knee pain was acupuncture superior to sham. Brain imaging with functional magnetic resonance (fMRI) and positron emission tomography (PET) may be helpful but is still in its early stages. Several studies have shown differences between the way the deep central areas of the brain respond to genuine acupuncture compared with sham. Acupuncture can clearly produce complex changes that are relevant to pain transmission and perception, though it is still uncertain how specific these are. Similar changes have been seen after the application of placebo cream and after hypnosis. A previous paper discussed the likely central role of the limbic system in acupuncture, evidenced by euphoria and out of body experiences. There may be a good deal of common ground between acupuncture, placebo treatments, hypnosis, and even manipulative treatments. This understanding could offer a way out of the sterile debate about whether acupuncture is merely a placebo: acupuncture could be one effective way of stimulating responses within these deep areas of the brain, though not the only way.


Next-generation sequencing-based detection of germline L1-mediated transductions.
While active LINE-1 (L1) elements possess the ability to mobilize flanking sequences to different genomic loci through a process termed transduction influencing genomic content and structure, an approach for detecting polymorphic germline non-reference transductions in massively-parallel sequencing data has been lacking. Here we present the computational approach TIGER (Transduction Inference in GERmline genomes), enabling the discovery of non-reference L1-mediated transductions by combining L1 discovery with detection of unique insertion sequences and detailed characterization of insertion sites. We employed TIGER to characterize polymorphic transductions in fifteen genomes from non-human primate species (chimpanzee, orangutan and rhesus macaque), as well as in a human genome. We achieved high accuracy as confirmed by PCR and two single molecule DNA sequencing techniques, and uncovered differences in relative rates of transduction between primate species. By enabling detection of polymorphic transductions, TIGER makes this form of relevant structural variation amenable for population and personal genome analysis.


Depth-resolved whole-field displacement measurement by wavelength-scanning electronic speckle pattern interferometry.
We show, for the first time to our knowledge, how wavelength-scanning interferometry can be used to measure depth-resolved displacement fields through semitransparent scattering surfaces. Temporal sequences of speckle interferograms are recorded while the wavelength of the laser is tuned at a constant rate. Fourier transformation of the resultant three-dimensional (3-D) intensity distribution along the time axis reconstructs the scattering potential within the medium, and changes in the 3-D phase distribution measured between two separate scans provide the out-of-plane component of the 3-D displacement field. The principle of the technique is explained in detail and illustrated with a proof-of-principle experiment involving two independently tilted semitransparent scattering surfaces. Results are validated by standard two-beam electronic speckle pattern interferometry.


Limitations of fluoridation effectiveness studies: Lessons from Alberta, Canada.
A paper published in this journal, "Measuring the short-term impact of fluoridation cessation on dental caries in Grade 2 children using tooth surface indices," by McLaren et al had shortcomings in study design and interpretation of results, and did not include important pertinent data. Its pre-post cross-sectional design relied on comparison of decay rates in two cities: Calgary, which ceased fluoridation, and Edmonton, which maintained fluoridation. Dental health surveys conducted in both cities about 6.5 years prior to fluoridation cessation in Calgary provided the baseline. They were compared to decay rates determined about 2.5 years after cessation in a second set of surveys in both cities. A key shortcoming was the failure to use data from a Calgary dental health survey conducted about 1.5 years prior to cessation. When this third data set is considered, the rate of increase of decay in Calgary is found to be the same before and after cessation of fluoridation, thus contradicting the main conclusion of the paper that cessation was associated with an adverse effect on oral health. Furthermore, the study design is vulnerable to confounding by caries risk factors other than fluoridation: The two cities differed substantially in baseline decay rates, other health indicators, and demographic characteristics associated with caries risk, and these risk factors were not shown to shift in parallel in Edmonton and Calgary through time. An additional weakness was low participation rates in the dental surveys and lack of analysis to check whether this may have resulted in selection biases. Owing to these weaknesses, the study has limited ability to assess whether fluoridation cessation caused an increase in decay. The study's findings, when considered with the additional information from the third Calgary survey, more strongly support the conclusion that cessation of fluoridation had no effect on decay rate. Consideration of the limitations of this study can stimulate improvement in the quality of future fluoridation effectiveness studies.


Understanding and overcoming shear alignment of fibers during extrusion.
Fiber alignment is the defining architectural characteristic of discontinuous fiber composites and is dictated by shear-dominated processing techniques including flow-injection molding, tape-casting, and mold-casting. However, recent colloidal assembly techniques have started to employ additional forces in fiber suspensions that have the potential to change the energy landscape of the shear-dominated alignment in conditions of flow. In this paper, we develop an energetics model to characterize the shear-alignment of rigid fibers under different flow conditions in the presence of magnetic colloidal alignment forces. We find that these colloidal forces can be sufficient to manipulate the energetic landscape and obtain tunable fiber alignment during flow within even small geometries, such as capillary flow. In most conditions, these colloidal forces work to freeze the fiber orientation during flow and prevent the structure disrupting phenomenon of Jeffrey's orbits that has been accepted to rule fiber suspensions under simple shear flow.


Factors associated with teenage pregnancy in the European Union countries: a systematic review.
As part of the REPROSTAT2 project, this systematic review aimed to identify factors associated with teenage pregnancy in 25 European Union countries. The search strategy included electronic bibliographic databases (1995 to May 2005), bibliographies of selected articles and requests to all country representatives of the research team for relevant reports and publications. Primary outcome measure was conception. Inclusion criteria were quantitative studies of individual-level factors associated with teenage (13-19 years) pregnancy in EU countries. Of 4444 studies identified and screened, 20 met the inclusion criteria. Most of the included studies took place in UK and Nordic countries. The well-recognized factors of socioeconomic disadvantage, disrupted family structure and low educational level and aspiration appear consistently associated with teenage pregnancy. However, evidence that access to services in itself is a protective factor remains inconsistent. Although further associations with diverse risk-taking behaviours and lifestyle, sexual health knowledge, attitudes and behaviour are reported, the independent effects of these factors too remain unclear. Included studies varied widely in terms of methods and definitions used. This heterogeneity within the studies leaves two outstanding issues. First, we cannot synthesize or generalize key findings as to how all these factors interact with one another and which factors are the most significant. Second, it is not possible to examine potential variation between countries. Future research ensuring comparability and generalizability of results related to teenage sexual health outcomes will help gain insight into the international variation in observed pregnancy rates and better inform interventions.


The preparation of anastomosis site at the insular segment of middle cerebral artery.
An anastomosis at the insular segment of the middle cerebral artery (M2) is often required in cerebral reconstruction with high- or low-flow bypass. It is necessary to create a shallow, wide, fixed, and bloodless anastomosis field to achieve a safe and quick anastomosis for low surgical morbidity. We describe a method to perform a safe and quick anastomosis. From 2009 to 2013, the technique was used in 20 procedures to create an extracranial M2 high-flow bypass. The Sylvian fissure was dissected wide open to expose the M2. A silicon sheet was laid under M2 and the absorbable gelatin-compressed sponges were inserted between M2 and the insula cortex to lift up the M2 and fix it. The rolling surgical sheets were placed at each edge of the dissected Sylvian fissure, instead of brain spatulas. Finally, a small suction tube was placed at the Sylvian fissure and cerebrospinal fluid was continuously sucked. The postoperative patency of the bypass was evaluated by three-dimensional computed tomographic angiography (3D-CTA) in the acute and chronic stages. In all cases, the operation field acquired for the anastomosis was adequate. The average time required for the procedure was 19 min 27 s. Good patency of all high-flow grafts was confirmed by postoperative three-dimensional computed tomography angiography (3D-CTA). In our series, there were no technical complications related to the anastomosis at M2 performed according to our method.


Nurses' moral sensitivity and hospital ethical climate: a literature review.
Increased technological and pharmacological interventions in patient care when patient outcomes are uncertain have been linked to the escalation in moral and ethical dilemmas experienced by health care providers in acute care settings. Health care research has shown that facilities that are able to attract and retain nursing staff in a competitive environment and provide high quality care have the capacity for nurses to process and resolve moral and ethical dilemmas. This article reports on the findings of a systematic review of the empirical literature (1980 - February 2007) on the effects of unresolved moral distress and poor ethical climate on nurse turnover. Articles were sought to answer the review question: Does unresolved moral distress and a poor organizational ethical climate increase nurse turnover? Nine articles met the criteria of the review process. Although the prevailing sentiment was that poor ethical climate and moral distress caused staff turnover, definitive answers to the review question remain elusive because there are limited data that confidently support this statement.


Beta transmutations in apatites with ferric iron as an electron acceptor - implication for nuclear waste form development.
Apatite-structured materials have been considered for the immobilization of a number of fission products from reprocessing nuclear fuel because of their chemical durability as well as compositional and structural flexibility. It is hypothesized that the effect of beta decay on the stability can be mitigated by introducing an appropriate electron acceptor at the neighboring sites in the structure. The decay series 137Cs → 137Ba and 90Sr → 90Y → 90Zr were investigated using a spin-polarized DFT approach to test the hypothesis. Apatites with compositions of Ca10(PO4)6F2 and Ca4Y6(SiO4)6F2 were selected as model systems for the incorporation of radionuclides Cs and Sr, respectively. Ferric iron was introduced in the structure as an electron acceptor. Electron density of states, crystal and defect structures, and energies before and after beta decay were calculated. The calculated electron density of states suggests that the extra electron is localized at the ferric iron, which changes its oxidation state and becomes ferrous iron. The crystal and defect structures were analyzed based on the volume, lattice parameters, radial distribution functions, metal cation to coordinating oxygen distances, and the metaprism twist angle of the apatite crystal structure. The results show that there are minor changes in the crystal and defect structures of CsFeCa8(PO4)6F2 with Cs+ and Fe3+ substitutions undergoing the Cs → Ba transmutation, and of Ca3SrY4Fe2(SiO4)6F2 with Sr2+ and Fe3+ substitutions undergoing the Sr → Y → Zr transmutations. The last decay change, from Y3+ → Zr4+, causes relatively larger changes in the local defect structure around Zr involving the coordination environment but the change is not significant to the crystal structure. The results on calculated cohesive energy suggest that the transmutations Cs+ → Ba2+ and Sr2+ → Y3+ → Zr4+ in both apatite compositions are energetically favorable, which is consistent with the minor structure distortions. Increased stability with favorable energetics and structural distortion by incorporating ferric ion is significant with respect without variable valence ions. The results confirm the structural and compositional adaptability of apatites upon beta transmutations. The study suggests that apatite-structured materials could be promising nuclear waste forms to mitigate the beta decay induced instability, by incorporating variable valence cations such as ferric iron in the structure. The study demonstrates a methodology which evaluates the structural stability of waste forms incorporating fission products undergoing beta decay.


The use of methylprednisolone in COVID-19 patients: A propensity score matched retrospective cohort study.
To evaluate the efficacy and safety of methylprednisolone in treating the coronavirus disease 2019 (COVID-19) patients. A retrospective cohort study was conducted, and all COVID-19 patients were recruited who were admitted to the Yichang Third People's Hospital from February 1st to March 31st, 2020. One-to-one propensity score matching (PSM) was used for minimizing confounding effects. The primary outcome was hospital mortality, with the secondary outcomes being the time needed for a positive SARS-CoV-2 nucleic acid test to turn negative and the length of hospital stay. Totaling 367 patients with COVID-19 hospitalized at the Yichang Third People's Hospital were identified, of whom 276 were mild or stable COVID-19, and 67 were serious or critically ill. Among them, 255 patients were treated using methylprednisolone, and 188 did not receive any corticosteroid-related treatment. After PSM, no statistically significant difference was found in the baseline characteristics between the two groups. Regarding the outcomes, there also were no statistically significant difference between the two groups. Patients without the use of methylprednisolone were more quickly to obtain negative results of their nasopharyngeal swab tests of SARS-CoV-2 nucleic acid after treatment, compared to those receiving methylprednisolone. Methylprednisolone could not improve the prognosis of patients with COVID-19, and the efficacy and safety of the use of methylprednisolone in patients with COVID-19 still remain uncertain, thus the use of corticosteroids clinically in patients with COVID-19 should be with cautions.


The television, school and family smoking prevention/cessation project. IV. Controlling for program success expectancies across experimental and control conditions.
A major issue in smoking prevention research is that no study has tried to equate program success expectancies across experimental and placebo control conditions. Equivalent overall program success expectancies should be established to help rule out the effects of extra-theoretical variables which influence program outcomes. The present study tested whether an attention-placebo (information based) smoking prevention program would produce equivalent expectancies about the likelihood of program success in comparison to an experimental social influences program. To try to equate program success expectancies, the design of the two programs differed in content but was similar in procedure. Fourteen middle schools were randomly assigned to the two conditions. As hypothesized, baseline expectancies were found to predict outcome measures, even after controlling for baseline smoking intentions, ethnic group, and gender. Second, the equivalence of program expectancies at posttest was tested. Youths held equivalent overall expectancies for success across conditions. This study suggested the need to control for program expectancies in prevention research, and showed that program expectancies could be controlled for by equating process of program delivery.


Dry Electrode-Based Body Fat Estimation System with Anthropometric Data for Use in a Wearable Device.
The bioelectrical impedance analysis (BIA) method is widely used to predict percent body fat (PBF). However, it requires four to eight electrodes, and it takes a few minutes to accurately obtain the measurement results. In this study, we propose a faster and more accurate method that utilizes a small dry electrode-based wearable device, which predicts whole-body impedance using only upper-body impedance values. Such a small electrode-based device typically needs a long measurement time due to increased parasitic resistance, and its accuracy varies by measurement posture. To minimize these variations, we designed a sensing system that only utilizes contact with the wrist and index fingers. The measurement time was also reduced to five seconds by an effective parameter calibration network. Finally, we implemented a deep neural network-based algorithm to predict the PBF value by the measurement of the upper-body impedance and lower-body anthropometric data as auxiliary input features. The experiments were performed with 163 amateur athletes who exercised regularly. The performance of the proposed system was compared with those of two commercial systems that were designed to measure body composition using either a whole-body or upper-body impedance value. The results showed that the correlation coefficient ( r 2 ) value was improved by about 9%, and the standard error of estimate (SEE) was reduced by 28%.


Waiting in pigeons: the effects of daily intercalation on temporal discrimination.
Pigeons trained on cyclic-interval schedules adjust their postfood pause from interval to interval within each experimental session. But on regular fixed-interval schedules, many sessions at a given parameter value are usually necessary before the typical fixed-interval "scallop" appears. In the first case, temporal control appears to act from one interfood interval to the next; in the second, it appears to act over hundreds of interfood intervals. The present experiments look at the intermediate case: daily variation in schedule parameters. In Experiments 1 and 2 we show that pauses proportional to interfood interval develop on short-valued response-initiated-delay schedules when parameters are changed daily, that additional experience under this regimen leads to little further improvement, and that pauses usually change as soon as the schedule parameter is changed. Experiment 3 demonstrates identical waiting behavior on fixed-interval and response-initiated-delay schedules when the food delays are short (less than 20 s) and conditions are changed daily. In Experiment 4 we show that daily intercalation prevents temporal control when interfood intervals are longer (25 to 60 s). The results of Experiment 5 suggest that downshifts in interfood interval produce more rapid waiting-time adjustments than upshifts. These and other results suggest that the effects of short interfood intervals seem to be more persistent than those of long intervals.


Epidemiology and outcome of invasive pneumococcal disease among adults in Belgium, 2009-2011.
This epidemiological study examined morbidity and case fatality of invasive pneumococcal disease (IPD) in adults in Belgium as well as distribution and antibiotic susceptibility of Streptococcus pneumoniae serotypes.Adults hospitalised with microbiologically proven IPD were prospectively enrolled. The study started in 2009 with patients aged ≥50 years, whereas in 2010 and 2011, patients aged ≥18 years were included. The clinical presentation, patient profile, treatment, outcome, and mortality were recorded during hospitalisation.Outcome was also assessed one month afterdischarge. Of the 1,875 patients with IPD identified, 1,332 were included in the analysis. Bacteraemic pneumonia, affecting 1,049 of the patients, was the most frequent IPD type (79%), and chronic obstructive pulmonary disease and cancer were the main comorbidities.One-third of patients required admission to intensive care unit. A total of 208 (16%) patients died during hospitalisation and an additional 21 (2%) within one month after discharge. Case fatality rates of ≥20%were observed in patients with chronic heart failure, hepatic disease, and renal insufficiency. Serotypes 7F, 1, 19A, and 3 were the most prevalent and together accounted for 47% (569/1,214) of all IPD cases and 42% (80/189) of mortality. Of the patient isolates, 21% (255/1,204) were resistant to erythromycin and 22% (264/1,204) to tetracycline. Penicillin non-susceptibility was mostly found in serotype 19A isolates. These baseline data are essential when assessing the impact of pneumococcal conjugate vaccination in adults in the future.


Anaphylaxis related to fentanyl citrate.
Anaphylaxis is a fulminant, unexpected, immunoglobulin E-mediated allergic reaction that can be triggered by multiple agents. Common causative agents include neuromuscular blocking drugs, latex, antibiotics, colloids, hypnotics, and opioids. Fentanyl citrate, however, is an extremely unusual cause of anaphylaxis. Pulmonary edema, although uncommon in anaphylaxis, can be a prominent feature, as was in one of the patient. An adverse drug reaction is a noxious or unintended reaction to a drug that is administered in standard doses by the proper route for the purpose of prophylaxis, diagnosis, or treatment. Reactions are classified into two major subtypes: type A, which are dose dependent and predictable; and type B, which are not dose dependent and unpredictable. Unpredictable reactions include immune (allergic) or no immune drug hypersensitivity reactions and are related to genetic susceptibilities or undefined mechanisms (formally called idiosyncratic and intolerance reactions). A drug allergy is always associated with an immune mechanism for which evidence of drug-specific antibodies or activated T lymphocytes can be shown. In the last few years, many novel drugs have entered clinical practice (i.e., biologic agents) generating novel patterns of drug hypersensitivity reactions. As old drugs continue to be used, new clinical and biologic techniques enable improvement in the diagnosis of these reactions.


Ten-year follow-up of age-related macular degeneration in the age-related eye disease study: AREDS report no. 36.
Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials. To describe 10-year progression rates to intermediate or advanced AMD. We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years. Treatment with antioxidant vitamins and minerals. Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits. The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200. The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.


Alcohol warning label perceptions: Emerging evidence for alcohol policy.
Patterns of alcohol and cigarette use and abuse can be considered parallels due to their similar social, biological and epidemiological implications. Therefore, the cross-fertilization of policy research, including health warnings evidence, is justified. The objective of this study was to apply the lessons learned from the tobacco health warnings and plain packaging literature to an alcohol packaging study and test whether labelling alters consumer perceptions. Ninety-two adults were exposed to four labelling conditions of bottles for a famous brand of each of wine, beer and hard liquor. Participants were randomly assigned to one of four labelling conditions: standard, text warning, text and image warning, or text and image warning on a plain bottle. Participants then expressed their product-based (i.e., evaluation of the products) and consumer-based (i.e., evaluation of potential consumers of the products) perceptions in relation to each label condition and were asked to recognize the correct health warning. As expected, participants perceived bottles with warnings less positively as compared to standard bottles in terms of product-based and consumer-based perceptions: plain bottles showed the most consistent statistically significant results, followed by text and image warnings, and then text warnings in pair-wise comparisons with the standard bottles. Some support for the impact of plain packaging on warning recognition was also found. Unlike previous studies, this study reveals that health warnings, if similar to those on cigarette packs, can change consumer-based and product-based perceptions of alcohol products. The study reveals the importance of serious consideration of stringent alcohol warning policy research.


Acute and second-meal effects of almond form in impaired glucose tolerant adults: a randomized crossover trial.
Nut consumption may reduce the risk of developing type 2 diabetes. The aim of the current study was to measure the acute and second-meal effects of morning almond consumption and determine the contribution of different nut fractions. Fourteen impaired glucose tolerant (IGT) adults participated in a randomized, 5-arm, crossover design study where whole almonds (WA), almond butter (AB), defatted almond flour (AF), almond oil (AO) or no almonds (vehicle - V) were incorporated into a 75 g available carbohydrate-matched breakfast meal. Postprandial concentrations of blood glucose, insulin, non-esterified free fatty acids (NEFA), glucagon-like peptide-1 (GLP-1) and appetitive sensations were assessed after treatment breakfasts and a standard lunch. WA significantly attenuated second-meal and daylong blood glucose incremental area under the curve (AUCI) and provided the greatest daylong feeling of fullness. AB and AO decreased blood glucose AUCI in the morning period and daylong blood glucose AUCI was attenuated with AO. WA and AO elicited a greater second-meal insulin response, particularly in the early postprandial phase, and concurrently suppressed the second-meal NEFA response. GLP-1 concentrations did not vary significantly between treatments. Inclusion of almonds in the breakfast meal decreased blood glucose concentrations and increased satiety both acutely and after a second-meal in adults with IGT. The lipid component of almonds is likely responsible for the immediate post-ingestive response, although it cannot explain the differential second-meal response to AB versus WA and AO.


The wide window of face detection.
Faces are detected more rapidly than other objects in visual scenes and search arrays, but the cause for this face advantage has been contested. In the present study, we found that under conditions of spatial uncertainty, faces were easier to detect than control targets (dog faces, clocks and cars) even in the absence of surrounding stimuli, making an explanation based only on low-level differences unlikely. This advantage improved with eccentricity in the visual field, enabling face detection in wider visual windows, and pointing to selective sparing of face detection at greater eccentricities. This face advantage might be due to perceptual factors favoring face detection. In addition, the relative face advantage is greater under flanked than non-flanked conditions, suggesting an additional, possibly attention-related benefit enabling face detection in groups of distracters.


Single cell dissection of early kidney development: multilineage priming.
We used a single cell RNA-seq strategy to create an atlas of gene expression patterns in the developing kidney. At several stages of kidney development, histologically uniform populations of cells give rise to multiple distinct lineages. We performed single cell RNA-seq analysis of total mouse kidneys at E11.5 and E12.5, as well as the renal vesicles at P4. We define an early stage of progenitor cell induction driven primarily by gene repression. Surprising stochastic expression of marker genes associated with differentiated cell types was observed in E11.5 progenitors. We provide a global view of the polarized gene expression already present in the renal vesicle, the first epithelial precursor of the nephron. We show that Hox gene read-through transcripts can be spliced to produce intergenic homeobox swaps. We also identify a surprising number of genes with partially degraded noncoding RNA. Perhaps most interesting, at early developmental times single cells often expressed genes related to several developmental pathways. This provides powerful evidence that initial organogenesis involves a process of multilineage priming. This is followed by a combination of gene repression, which turns off the genes associated with most possible lineages, and the activation of increasing numbers of genes driving the chosen developmental direction.


Incidence and descriptive epidemiologic features of traumatic brain injury in King County, Washington.
Traumatic brain injury (TBI) is a major cause of disability among US children. Our goal was to obtain population-based data on TBI incidence rates. We conducted surveillance through a stratified random sample of hospital emergency departments in King County, Washington, to identify children 0 to 17 years of age with medically treated TBIs during an 18-month study period in 2007-2008. Additional cases were identified through hospital admission logs and the medical examiner's office. For a sample of nonfatal cases, parents were interviewed to verify TBIs, and medical record data on severity and mechanisms were obtained. The estimated incidence of TBIs in this setting was 304 cases per 100,000 child-years. The incidence was highest for preschool-aged children and lowest for children aged 5 to 9 years. Rates were uniformly higher for boys than for girls; there was a larger gender gap at older ages. Falls were the main mechanism of injury, especially among preschool-aged children, whereas being struck by or against an object and motor vehicle-related trauma were important contributors for older children. Approximately 97% of TBI cases were mild, although moderate/severe TBI incidence increased with age. TBIs led to many emergency department visits involving children, but a large majority of the cases were clinically mild. Incidence rates for King County were well below recent national estimates but within the range reported in previous US studies. Because mechanisms of injury varied greatly according to age, prevention strategies almost certainly must be customized to each age group for greatest impact.


The impact of muscle disuse on muscle atrophy in severely burned rats.
Severe burn induces a sustained hypermetabolic response, which causes long-term loss of muscle mass and decrease in muscle strength. In this study, we sought to determine whether muscle disuse has additional impact on muscle atrophy after severe burn using a rat model combining severe cutaneous burn and hindlimb unloading. Forty Sprague-Dawley rats (≈ 300 g) were randomly assigned to sham ambulatory (S/A), sham hindlimb unloading (S/HLU), burn ambulatory (B/A), or burn hindlimb unloading (B/HLU) groups. Rats received a 40% total body surface (TBSA) full thickness scald burn, and rats with hindlimb unloading were placed in a tail traction system. At d 14, lean body mass (LBM) was determined using DEXA scan, followed by measurement of the isometric mechanical properties in the predominantly fast-twitch plantaris muscle (PL) and the predominantly slow-twitch soleus muscle (SL). Muscle weight (wt), protein wt, and wet/dry wt were determined. At d 14, body weight had decreased significantly in all treatment groups; B/HLU resulted in significantly greater loss compared with the B/A, S/HLU, and S/A. The losses could be attributed to loss of LBM. PL muscle wt and Po were lowest in the B/HLU group (<0.05 versus S/A, S/HLU, or B/A). SL muscle wt and Po were significantly less in both S/HLU and B/HLU compared with that of S/A and B/A; no significant difference was found between S/HLU and B/HLU. Cutaneous burn and hindlimb unloading have an additive effect on muscle atrophy, characterized by loss of muscle mass and decrease in muscle strength in both fast (PL) and slow (SL) twitch muscles. Of the two, disuse appeared to be the dominant factor for continuous muscle wasting after acute burn in this model.


Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss.
Leukocyte adhesion deficiency type I (LAD-I), a disease syndrome associated with frequent microbial infections, is caused by mutations on the CD18 subunit of β₂ integrins. LAD-I is invariably associated with severe periodontal bone loss, which historically has been attributed to the lack of neutrophil surveillance of the periodontal infection. We provide an alternative mechanism by showing that the cytokine interleukin-17 (IL-17) plays a major role in the oral pathology of LAD-I. Defective neutrophil recruitment in LAD-I patients or in LFA-1 (CD11a/CD18)-deficient mice--which exhibit the LAD-I periodontal phenotype--was associated with excessive production of predominantly T cell-derived IL-17 in the periodontal tissue, although innate lymphoid cells also contributed to pathological IL-17 elevation in the LFA-1-deficient mice. Local treatment with antibodies to IL-17 or IL-23 in LFA-1-deficient mice not only blocked inflammatory periodontal bone loss but also caused a reduction in the total bacterial burden, suggesting that the IL-17-driven pathogenesis of LAD-I periodontitis leads to dysbiosis. Therefore, our findings support an IL-17-targeted therapy for periodontitis in LAD-I patients.


Visions by Women in Molecular Imaging Network: Antiracism and Allyship in Action.
Recent events in America in 2020 have stimulated a worldwide movement to dismantle anti-Black racism in all facets of our lives. Anti-Black racism is, as defined by the Movement for Black Lives, a "term used to specifically describe the unique discrimination, violence, and harm imposed on and impacting Black people specifically." In science, technology, engineering, and mathematics (STEM), we have yet to achieve the goal and responsibility to ensure that the field reflects the diversity of our lived experiences. Members of the Women in Molecular Imaging Network (WIMIN) have come together to take a stand on diversity, equity, and inclusion in the field of molecular imaging. We strongly condemn oppression in all its forms and strive to identify and dismantle barriers that lead to inequities in the molecular imaging community and STEM as a whole. In this series coined "Visions" (Antiracism and Allyship in Action), we identify and discuss specific actionable items for improving diversity and representation in molecular imaging and ensuring inclusion of all members of the community, inclusive of race, disability, ethnicity, religion, or LGBTQ+ identity. Although the issues highlighted here extend to other under-recruited and equity-seeking groups, for this first article, we are focusing on one egregious and persistent form of discrimination: anti-Black racism. In this special article, Black women residing in America present their lived experiences in the molecular imaging field and give candid insights into the challenges, frustrations, and hopes of our Black friends and colleagues. While this special article focuses on the experiences of Black women, we would like the readers to reflect on their anti-Blackness toward men, transgender, nonbinary, and gender non-conforming people. From the vulnerability we have asked of all our participants, these stories are meant to inspire and invoke active antiracist work among the readership. We present strategies for dismantling systemic racism that research centers and universities can implement in the recruitment, retention, mentorship, and development of Black trainees and professionals. We would like to specifically acknowledge the Black women who took the time to be interviewed, write perspectives, and share their lived experiences in hopes that it will inspire genuine and lasting change.


Mesothelin overexpression is a marker of tumor aggressiveness and is associated with reduced recurrence-free and overall survival in early-stage lung adenocarcinoma.
In an effort to identify molecular markers of tumor aggressiveness and therapeutic targets in lung adenocarcinoma (ADC), we investigated the expression of mesothelin (MSLN) in lung ADC, as well as its biologic and clinical relevance. In a training and validation set of patients with early-stage (I-III) lung ADC (n = 1,209), a tissue microarray consisting of tumors and normal lung tissue was used to examine the association between MSLN expression and recurrence-free survival (RFS) and overall survival (OS). The influence of MSLN overexpression on lung ADC was investigated in vitro and in vivo by use of clinically relevant orthotopic and metastatic xenogeneic and syngeneic mouse models. MSLN was expressed in 69% of lung ADC tumors, with one in five patients strongly expressing MSLN and no expression in normal lung tissue. Increased MSLN expression was associated with reduced OS [HR = 1.78; 95% confidence interval (CI), 1.26-2.50; P < 0.01] and RFS (HR = 1.67; 95% CI, 1.21-2.27; P < 0.01) in multivariate analyses, even after adjustment for currently known markers of tumor aggressiveness in lung ADC: male sex, smoking history, increasing stage, morphologic pattern, visceral pleural invasion, lymphatic or vascular invasion, and mutation status. In vitro, lung ADC cells overexpressing MSLN demonstrated increased cell proliferation, migration, and invasion; in vivo, mice with MSLN(+) tumors demonstrated decreased survival (P = 0.001). MSLN expression in patients with early-stage lung ADC is associated with increased risk of recurrence and reduced OS, indicating that MSLN expression is a molecular marker of tumor aggressiveness and a potential target for therapy.