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Microaggressions between medical team members may require difficult conversations to restore inclusivity, diversity, and a healthy work culture. This article outlines important considerations to assist with intentional preparation and modulation of responses for conversation initiators, observers of the incident, and conversation receivers. Microaggressions between members of a team occur often in medicine, even despite good intentions. Such situations call for difficult conversations that restore inclusivity, diversity, and a healthy work culture. These conversations are often hard because of the unique background, experiences, and biases of each person. In medicine, skillful navigation of these interactions is paramount as it influences patient care and the workplace culture. Although much has been published about difficult interactions between providers and patients, significantly less information is available to help navigate provider-to-provider interactions, despite their critical role in improving multidisciplinary patient care teams and organizational environments. This article is intended to serve as a guide for medical professionals who are interested in taking personal responsibility for promoting a safe and inclusive culture by engaging in and modeling difficult conversations with colleagues. The article outlines important considerations to assist with intentional preparation and modulation of responses for all parties involved: conversation initiators, observers of the incident, and conversation receivers. Although these interactions are challenging, together as medical professionals we can approach each other with humility and compassion to achieve our ultimate goal of promoting humanity, not only for our patients but for ourselves and one another. [ABSTRACT FROM AUTHOR]

The isolation and purification of protactinium from uranium materials is essential for 231Pa–235U radiochronometry, but separating Pa from uranium-niobium alloys, a common material in the nuclear fuel cycle, is challenging due to the chemical similarity of Pa and Nb. Here we present three resin chromatography separation techniques for isolating Pa from U and Nb which were independently developed by three different laboratories through ad hoc adaptations of standard operating procedures. Our results underscore the need for and value of purification methods suitable for a diversity of uranium-based materials to ensure the operational readiness of nuclear forensics laboratories. [ABSTRACT FROM AUTHOR]

1. Recognize the importance of aligning ICD settings with goals of care and understand the different options for ICD settings at end-of-life. 2. Know a potential method to improve hospice workers' knowledge through the use of patient educational videos. Hundreds of thousands of patients die with implantable cardioverter-defibrillators (ICDs) each year, and up to one third will be shocked in the last month of life regardless of code status. Few hospices have deactivation protocols. In this project, we created and showed an educational video to hospice workers to improve knowledge about end-of-life ICD settings. Hundreds of thousands of patients with implantable cardioverter-defibrillators (ICDs) die yearly. Though ICD shocks can be lifesaving, they can also be severely painful. One third of ICD patients are shocked in the last day of life irrespective of DNR status. Over 97% of hospice programs admit patients with ICDs, yet only 10% have deactivation policies and less than 50% of hospice patients have their ICD deactivated. Little is known about hospice workers' ICD knowledge and its impact on these patients at EOL. To improved hospice workers knowledge about ICD settings at EOL. We surveyed 93 hospice workers at the Texas New Mexico Hospice Conference and 2 community hospices using 10 validated true-false questions. Participants watched a seven-minute ICD educational video narrated by real patients from Parkland Memorial Hospital. Post-video, participants repeated the questions to assess change in knowledge. Of 93 hospice workers, 47 (50.5%) were nurses, 9 (9.7%) were physicians, and 36 (38.7%) were non-clinical workers (social workers, bereavement counselors, etc.). After the video, there was a significant improvement in ICD knowledge scores for each respondent (W = 3119.5, p< 0.0001) with the average increasing from 65.2% (SD 26.72) to 90.8% (SD 10.0). Of sixty (64.5%) hospice workers who responded to questions about the video, fifty-nine (98%) said the video was helpful, and 51 (85%) said they would use the video to talk with patients about ICDs. Hospice personnel have limited knowledge about ICDs, prohibiting best care of patients with these devices at EOL. A short educational video increased knowledge and may serve as a helpful tool. Improving ICD knowledge amongst hospice personnel is essential to ensuring the unique needs of hospice patients with ICDs are met. Further research is needed to assess how hospice personnel ICD knowledge impacts clinical outcomes, including rates of ICD deactivation. Quality Improvement / Management of Medical Interventions [ABSTRACT FROM AUTHOR]

We evaluated daily rapid antigen test (RAT) data from 323 COVID-19-positive university students in Connecticut, USA, during an Omicron-dominant period. Day 5 positivity was 47% for twice-weekly screeners and 26%-28% for less-frequent screeners, approximately halving each subsequent day. Testing negative >10 days before diagnosis (event time ratio (ETR) 0.85 [95% CI 0.75-0.96]) and prior infection >90 days (ETR 0.50 [95% CI 0.33-0.76]) were significantly associated with shorter RAT positivity duration. Symptoms before or at diagnosis (ETR 1.13 [95% CI 1.02-1.25]) and receipt of 3 vaccine doses (ETR 1.20 [95% CI 1.04-1.39]) were significantly associated with prolonged positivity. Exit RATs enabled 53%-74% of students to leave isolation early when they began isolation at the time of the first positive test, but 15%-22% remained positive beyond the recommended isolation period. Factors associated with RAT positivity duration should be further explored to determine relationships with infection duration. [ABSTRACT FROM AUTHOR]

Concerns about systemic racism at academic and research institutions have increased over the past decade. Here, we investigate data from the National Science Foundation (NSF), a major funder of research in the United States, and find evidence for pervasive racial disparities. In particular, white principal investigators (PIs) are consistently funded at higher rates than most non-white PIs. Funding rates for white PIs have also been increasing relative to annual overall rates with time. Moreover, disparities occur across all disciplinary directorates within the NSF and are greater for research proposals. The distributions of average external review scores also exhibit systematic offsets based on PI race. Similar patterns have been described in other research funding bodies, suggesting that racial disparities are widespread. The prevalence and persistence of these racial disparities in funding have cascading impacts that perpetuate a cumulative advantage to white PIs across all of science, technology, engineering, and mathematics. [ABSTRACT FROM AUTHOR]

While β Pic is known to host silicates in ring-like structures, whether the properties of these silicate dust vary with stellocentric distance remains an open question. We re-analyze the β Pictoris debris disk spectrum from the Spitzer Infrared Spectrograph (IRS) and a new Infrared Telescope Facility Spectrograph and Imager spectrum to investigate trends in Fe/Mg ratio, shape, and crystallinity in grains as a function of wavelength, a proxy for stellocentric distance. By analyzing a re-calibrated and re-extracted spectrum, we identify a new 18 ÎĽ m forsterite emission feature and recover a 23 ÎĽ m forsterite emission feature with a substantially larger line-to-continuum ratio than previously reported. We find that these prominent spectral features are primarily produced by small submicron-sized grains, which are continuously generated and replenished from planetesimal collisions in the disk and can elucidate their parent bodies’ composition. We discover three trends about these small grains: as stellocentric distance increases, (1) small silicate grains become more crystalline (less amorphous), (2) they become more irregular in shape, and (3) for crystalline silicate grains, the Fe/Mg ratio decreases. Applying these trends to β Pic’s planetary architecture, we find that the dust population exterior to the orbits of β Pic b and c differs substantially in crystallinity and shape. We also find a tentative 3â€"5 ÎĽ m dust excess due to spatially unresolved hot dust emission close to the star. From our findings, we infer that the surfaces of large planetesimals are more Fe-rich and collisionally processed closer to the star but more Fe-poor and primordial farther from the star. [ABSTRACT FROM AUTHOR]

Introduction: Military personnel must prepare for and respond to life-threatening crises on a daily basis. This lifestyle places stress on personnel, and particularly so on deployed service members who are isolated from support systems and other resources. As part of a larger systematic review on the acceptability, efficacy, and comparative effectiveness of interventions designed to prevent, identify, and manage stress reactions, we assessed posttraumatic stress disorder (PTSD) outcomes.Materials and Methods: We searched the electronic databases PsycINFO, PubMed, PTSDPubs, the Defense Technical Information Center, and Cochrane Central, as well as bibliographies of existing systematic reviews, to identify English-language studies evaluating the efficacy or comparative effectiveness of stress control interventions published since 1990. Controlled trials and cohort comparisons of interventions with military, law enforcement, and first responders were included. Two independent reviewers screened literature using predetermined eligibility criteria. Researchers individually abstracted study-level information and outcome data and assessed the risk of bias of included studies; data were reviewed for accuracy by the project leader. Changes in PTSD symptom scores from baseline to post-intervention were converted to standardized mean differences for comparison across studies. Risk ratios were calculated for PTSD case rates post-deployment. When several studies that compared an intervention group with a similar control/comparator reported the same outcome category and measure type, we conducted meta-analysis. We conducted meta-regression by adding a categorical variable, representing setting (i.e., in theater) or population (military vs. law enforcement or first responders) to the meta-analysis model to assess whether this variable was associated with the outcome across studies. The quality of the body of evidence (QoE) was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, which considers study limitations (risk of bias), directness, consistency, precision, and publication bias.Results: Sixteen controlled trials and 13 cohort comparisons reporting PTSD outcomes met inclusion criteria. Eight controlled trials and two cohort studies had high risk of bias, primarily due to poor, differential, or unknown response rate at follow-up. Twenty-four of the 29 studies included military personnel. Interventions included Acceptance-based Skills training, Attention Bias Modification training, stress inoculation with biofeedback, Critical Incident Stress Debriefing, group psychological debriefing, Eye Movement Desensitization and Reprocessing for sub-clinical stress, embedding mental health providers in theater, Third Location Decompression, reintegration programs, and a 3-week post-deployment residential program for psychological resource strengthening.Meta-analyses of studies comparing a group that received a stress control intervention to a group that did not receive an intervention found no significant difference in reduction in PTSD symptom scores (moderate QoE) or PTSD case rate post-deployment (low QoE). A meta-analysis of studies comparing a specific stress control intervention to an active comparator (usually standard stress management education) found no significant effect on PTSD symptom scores (moderate QoE).Conclusion: Although combat and operational stress control (COSC) interventions may play a valuable role in decreasing stress, decreasing absenteeism, and enabling return to duty, a systematic review of 29 studies that included a control/comparison group found little evidence that COSC is effective in preventing PTSD or decreasing PTSD symptom scores in military personnel. [ABSTRACT FROM AUTHOR]

Background: Gastrointestinal complications of coronavirus disease-2019 (COVID-19) include abnormal liver function and acalculous cholecystitis. Cholecystostomy performed during the COVID-19 pandemic reflected a shift toward non-surgical treatment of cholecystitis and increased number of critically ill patients suffering from acalculous cholecystitis. Purpose: (1) To determine demographic, clinical, laboratory, and ultrasound features associated with cholecystostomy placement during hospitalization for COVID-19. (2) To develop multivariable logistic regression modeling for likelihood of biliary intervention. Methods: This retrospective review received institutional review board approval. Informed consent was waived. Between March 2020 and June 2020, patients with confirmed SARS-CoV2 infection admitted to New York-Presbyterian Hospital (NYP)/Weill Cornell Medical Center, NYP/Lower Manhattan Hospital, and NYP/Queens were evaluated for inclusion in this study. Inclusion criteria were (1) patient age ≥ 18, (2) confirmed COVID-19 infection by polymerase chain reaction testing of a nasopharyngeal swab, and (3) abdominal ultrasound performed during hospitalization. Exclusion criteria were (1) history of cholecystectomy and (2) biliary intervention performed prior to abdominal ultrasound. Patients were stratified into two groups based on whether they received cholecystostomy during hospitalization. Differences in demographics, medical history, clinical status, medications, laboratory values, and ultrasound findings between the two groups were evaluated using Chi-square test or Fisher's exact test for categorical variables and t test or Wilcoxon-rank sum test for continuous variables. Multivariable logistic regression was used to model likelihood of biliary intervention. Results: Nine patients underwent cholecystostomy placement and formed the "Intervention Group." 203 patients formed the "No Intervention Group." Liver size and diuretics use during hospitalization were the only variables which were significantly different between the two groups, with p-values of 0.02 and 0.046, respectively. After controlling for diuretics use, the odds of receiving cholecystostomy increased by 30% with every centimeter increase in liver size (p = 0.03). ICU admission approached significance (p = 0.16), as did mechanical ventilation (p = 0.09), septic shock (p = 0.08), serum alkaline phosphatase level (p = 0.16), and portal vein patency (0.14). Conclusion: Patients requiring biliary intervention during hospital admission for COVID-19 were likely to harbor liver injury in the form of liver enlargement and require diuretics use. [ABSTRACT FROM AUTHOR]

To identify baseline patient characteristics (i.e., demographic and psychological factors, military background) associated with better posttraumatic stress disorder (PTSD) treatment retention among veterans, we conducted a systematic review. After an electronic database search for studies of PTSD treatment in veterans, two reviewers independently screened the literature for eligibility, abstracted study‐level information, and assessed risk of bias. As most studies used multivariate models to assess multiple potential predictors of retention simultaneously, the results were described narratively. The GRADE approach, adapted for prognostic literature, was used to assess the overall quality of evidence (QoE). In total, 19 studies reported in 25 publications met the inclusion criteria (n = 6 good quality, n = 9 fair quality, n = 4 poor quality). Definitions of treatment completion and dropout varied, and some studies lumped different therapy approaches together. Older age and higher treatment expectations were associated with better retention (moderate QoE). In 5 of 6 studies, baseline PTSD severity was not associated with retention, and the remaining study reported an association between better retention and more severe PTSD symptoms; the presence of more co‐occurring psychiatric disorders was associated with better retention (moderate QoE). QoE was low or insufficient to support conclusions for any other characteristics due to inconsistent results, imprecision, potential publication bias, possible study population overlap, study limitations, or lack of studies. More research is needed regarding the associations between modifiable factors (e.g., motivation, barriers, expectations) and retention, and consistent definitions of treatment completion and minimally adequate treatment should be adopted throughout the field. [ABSTRACT FROM AUTHOR]

This paper derives in analytical closed form the feasible pole-placement region of the synchronverter active-power loop (APL) so as to eliminate all trial-and-error effort in parameter tuning. We consider the well-established setting of a reduced third-order APL model with two controller parameters that can be tuned freely. Thus, only two of the three APL poles can be specified independently in hopes of achieving desired system dynamics. Central to the presented derivation is the realization that the two specified poles must represent the dominant mode of the system. Otherwise the actual system dynamics may be dictated by the third unspecified pole, leading to unexpected or undesired dynamic behaviour. Numerical simulations involving the full-order synchronverter dynamical model and a modified New England 39-bus test system validate the analysis and the resulting region within which poles must be placed for actual system dynamics to match desired ones. [ABSTRACT FROM AUTHOR]

Background: Prostate heterogeneity on multi-parametric MRI (mpMRI) may confound image interpretation by obscuring lesions; systematic biopsy may have a role in this context. Purpose: To determine if prostate heterogeneity (1) correlates with clinical risk factors for prostate cancer and (2) associates with higher-grade tumor in systematic biopsy (SB), compared with MRI-directed target biopsy (MDTB), i.e., SB > MDTB, thus providing a rationale for combined biopsy. Methods: IRB-approved retrospective study included men who underwent mpMRI, SB, and MDTB between 2015 and 2017. Regions of interest were applied to the entire transition zone (TZ) and peripheral zone (PZ) on T2-weighted imaging (T2WI), apparent diffusion coefficient maps (ADC), and early dynamic contrast-enhanced (DCE) images on the midgland slice. Mean signal intensities and standard deviation (SD) of each zone were calculated. SD served as a measure of heterogeneity. Spearman's rank correlation analysis of clinical and imaging variables was performed. Univariate logistic regression was used to determine if any imaging variable associated with SB > MDTB. Results: 93 patients were included. Significant correlations included age and TZ ADC heterogeneity (rho = 0.34, p = 0.013), PSA density, and mean TZ ADC (rho = − 0.29, p = 0.049). PZ T2WI heterogeneity correlated with PZ ADC heterogeneity (rho = 0.48, p < 0.001). PZ DCE heterogeneity correlated with TZ DCE heterogeneity (rho = 0.46, p < 0.001). TZ ADC heterogeneity was associated with SB > MDTB prior to multiple comparison correction (p = 0.032). p value after correction was 0.24. Conclusion: TZ ADC heterogeneity correlated with age and may reflect prostatic hyperplasia and/or prostate cancer. PZ heterogeneity, possibly a measure of prostatitis, correlated with TZ hyperplasia and/or inflammation. TZ ADC heterogeneity was associated with SB > MDTB with p value of < 0.05 prior to multiple correction; future investigation is needed to further elucidate significance of ADC heterogeneity in prostate imaging. [ABSTRACT FROM AUTHOR]

Paraneoplastic limbic encephalitis (PLE) is an immunopathologic syndrome associated with malignancy and represents a rare remote outcome of tumor on the nervous system. We report a case of PLE caused by a regressed testicular germ cell tumor in an otherwise healthy young man, who presented with acute-onset confusion, memory impairment and anterograde amnesia. Prompt recognition of PLE is critical as it allows early treatment of both the primary tumor and PLE-related neurologic impairments, which can be severe and irreversible if treatment is delayed. Complete tumor treatment response offers the best chance for neurologic recovery in patients with PLE. To our knowledge, this is the second reported case of PLE with radiologic-pathologic correlation in the setting of a regressed testicular germ cell tumor. • PLE associated with regressed testicular germ cell tumor is exceedingly rare. • Anti-Ma2/Ta antibody is a paraneoplastic antibody associated with testicular tumors in men less than 50 years of age. • Early recognition of PLE allows early diagnosis and treatment of the primary tumor. [ABSTRACT FROM AUTHOR]

Objectives: To describe the extent and nature of changes in participants' responses after exposure to group feedback and discussion in modified-Delphi panels and to identify factors affecting those changes.Methods: We analyzed data from 2 online modified-Delphi panels, each consisting of 2 rating rounds and an online discussion round. We included responses from 55 participants who answered 38 questions in both rating rounds. Because not all participants answered each question twice, our sample consisted of 1846 cases (response changes). We used mixed-effect logistic and multinomial logistic regression to identify factors predicting response changes and their direction relative to group median-our consensus measure.Results: Participants changed, on average, 49% of their responses. A response was changed in 47% of the 1846 cases: 28% of responses were changed toward consensus and 19% away from it. Although some measures of subjective participation experiences had a marginally significant impact on the propensity and direction of response changes, several objective measures of discussion engagement were statistically significant predictors of both the presence and direction of response changes.Conclusion: Our results illustrate the nature of response changes and highlight the importance of exposing participants to alternative perspectives and encouraging them to explain their perspectives. [ABSTRACT FROM AUTHOR]

Over the past decade, the percentage of adults in the United States who use some form of social media has roughly doubled, increasing from 36 percent in early 2009 to 72 percent in 2019. There has been a corresponding increase in research aimed at understanding opinions and beliefs that are expressed online. However, the generalizability of findings from social media research is a subject of ongoing debate. Social media platforms are conduits of both information and misinformation about vaccines and vaccine hesitancy. Our research objective was to examine whether we can draw similar conclusions from Twitter and national survey data about the relationship between vaccine hesitancy and a broader set of beliefs. In 2018 we conducted a nationally representative survey of parents in the United States informed by a literature review to ask their views on a range of topics, including vaccine side effects, conspiracy theories, and understanding of science. We developed a set of keyword-based queries corresponding to each of the belief items from the survey and pulled matching tweets from 2017. We performed the data pull of the most recent full year of data in 2018. Our primary measures of belief covariation were the loadings and scores of the first principal components obtained using principal component analysis (PCA) from the two sources. We found that, after using manually coded weblinks in tweets to infer stance, there was good qualitative agreement between the first principal component loadings and scores using survey and Twitter data. This held true after we took the additional processing step of resampling the Twitter data based on the number of topics that an individual tweeted about, as a means of correcting for differential representation for elicited (survey) vs. volunteered (Twitter) beliefs. Overall, the results show that analyses using Twitter data may be generalizable in certain contexts, such as assessing belief covariation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Improving the appearance of lentigines on the hands is a key component to hand rejuvenation. Soft tissue fillers revolumize hands, but do not address pigmentary changes. OBJECTIVE: This study investigated the effiacy of a 15% trichloroacetic acid (TCA) + 3% glycolic acid (GA) combination peel in improvement of appearance of hand lentigines. METHODS: A prospective evaluator-blinded, split-hand study was performed using a 15% TCA + 3% GA peel to treat patients with hand lentigines. Subjects received a total of 3 treatments at 4-week intervals on 1 hand, with the other hand serving as an untreated control. Final photographs were taken 12 weeks after the last treatment. Two blinded board-certified dermatologists graded improvement in hand lentigines using a 5-point scale. RESULTS: Eighteen of 20 patients completed the study (90%). The mean age was 64.4 years (SE 1.6, range 51–71). The mean pain scores were 3.8 (SE 0.4) on a 10-point scale (1 = no pain, 10 = extremely painful). Blinded evaluators correctly identified the after-treatment photographs in 16 patients (88%). Physician and patient-graded mean improvement of lentigines was significant for treated versus control hands (p <.01). No adverse events were noted. CONCLUSION: A series of three 15% TCA + 3% GA peels are effective and safe in the treatment of hand lentigines. [ABSTRACT FROM AUTHOR]

Lenalidomide is a backbone agent in the treatment of multiple myeloma, but dose adjustment is required for those with renal impairment (RI). We evaluated the pharmacokinetics (PK) and safety of lenalidomide and dexamethasone as frontline pre-transplant induction, with doses adjusted at start of each cycle based on creatinine clearance, as per the official dosing guidelines. After 4 cycles, PK studies showed that patients with moderate RI (30 ≤ CrCl < 60 mL/min) receiving 10 mg dosing may be under-dosed and those with severe RI (CrCl <30ml/min) appeared appropriately dosed initially, but sustained significant decreases in maximum serum concentration (Cmax) after repeated dosing, due to rapid clinical improvement and enhanced drug clearance. PK drug monitoring during cycle 1 may facilitate appropriate and timely dose adjustments. Adverse events rates did not vary based on severity of RI. No patient discontinued lenalidomide for toxicity. This supports the feasibility and safety of frontline lenalidomide in transplant-eligible patients with RI. [ABSTRACT FROM AUTHOR]

We have obtained Gemini Planet Imager (GPI) J-, H-, K1-, and K2-Spec observations of the iconic debris ring around the young, main-sequence star HR 4796A. We applied several point-spread function (PSF) subtraction techniques to the observations (Mask-and-Interpolate, RDI-NMF, RDI-KLIP, and ADI-KLIP) to measure the geometric parameters and the scattering phase function for the disk. To understand the systematic errors associated with PSF subtraction, we also forward-modeled the observations using a Markov Chain Monte Carlo framework and a simple model for the disk. We found that measurements of the disk geometric parameters were robust, with all of our analyses yielding consistent results; however, measurements of the scattering phase function were challenging to reconstruct from PSF-subtracted images, despite extensive testing. As a result, we estimated the scattering phase function using disk modeling. We searched for a dependence of the scattering phase function with respect to the GPI filters but found none. We compared the H-band scattering phase function with that measured by Hubble Space Telescope STIS at visual wavelengths and discovered a blue color at small scattering angles and a red color at large scattering angles, consistent with predictions and laboratory measurements of large grains. Finally, we successfully modeled the SPHERE H2 HR 4796A scattered phase function using a distribution of hollow spheres composed of silicates, carbon, and metallic iron. [ABSTRACT FROM AUTHOR]

We examined the prevalence of compassion fatigue among occupational therapy practitioners. An online survey was developed incorporating the professional quality of life (ProQoL) which has three subscales. Among the 76 respondents, the majority of them reported high compassion satisfaction (52.6%), low burnout (60.5%), and low secondary traumatic stress (78.9%). Participants' age, years of experience, practice setting, or time spent in direct client care were not associated with the level of subscale scores. The results are discussed in the context of occupational therapy core values and beliefs as well as job options provided by the profession. [ABSTRACT FROM AUTHOR]

• Few studies elicited the public's vaccine beliefs using open-ended questions. • Concerns about vaccine safety are the most commonly stated beliefs. • Mistrust in physicians, pharma, and the government may exacerbate hesitancy. • The majority of studies (57%) focused on HPV vaccines. • Nearly a third of the studies exclusively examined Latinos and African Americans. While childhood vaccines are safe and effective, some parents remain hesitant to vaccinate their children, which has led to outbreaks of vaccine preventable diseases. The goal of this systematic review was to identify and summarize the range of beliefs around childhood vaccines elicited using open-ended questions, which are better suited for discovering beliefs compared to closed-ended questions. PubMed, Embase, and PsycINFO were searched using keywords for childhood vaccines, decision makers, beliefs, and attitudes to identify studies that collected primary data using a variety of open-ended questions regarding routine childhood vaccine beliefs in the United States. Study designs, population characteristics, vaccine types, and vaccine beliefs were abstracted. We conducted a qualitative analysis to conceptualize beliefs into themes and generated descriptive statistics. Of 1727 studies identified, 71 were included, focusing largely on parents (including in general, and those who were vaccine hesitant or at risk of hesitancy). Seven themes emerged: Adverse effects was most prominent, followed by mistrust , perceived lack of necessity , pro-vaccine opinions , skepticism about effectiveness , desire for autonomy , and morality concerns. The most commonly described beliefs included that vaccines can cause illnesses; a child's immune system can be overwhelmed if receiving too many vaccines at once; vaccines contain harmful ingredients; younger children are more susceptible to vaccine adverse events; the purpose of vaccines is profit-making; and naturally developed immunity is better than that acquired from vaccines. Nearly a third of the studies exclusively assessed minority populations, and more than half of the studies examined beliefs only regarding HPV vaccine. Few studies used open-ended questions to elicit beliefs about vaccines. Many of the studies that did so, focused on HPV vaccine. Concerns about vaccine safety were the most commonly stated beliefs about childhood vaccines, likely because studies were designed to capture barriers and challenges to vaccination. [ABSTRACT FROM AUTHOR]

Lenalidomide has anti-tumor activity in CLL but can be complicated by tumor lysis syndrome (TLS) and tumor flare (TF). In our previous study using low-dose lenalidomide in treatment-naive CLL, TLS was averted but TF remained frequent and complete responses (CR) were rare, despite treatment to progression. The addition of dexamethasone may mitigate TF and enable lenalidomide dose escalation, achieving durable response without long-term use. In this phase 2 trial, 31 treatment-naive CLL patients received lenalidomide (target 25mg daily) plus dexamethasone for a finite 18 cycles. No patients developed TLS and TF was infrequent. Overall responses were 74.2% (CR 9.7%) and median progression-free survival 27 months. Cereblon-binding proteins IKZF1 and IKZF3 were largely downregulated, with associated increased IRF4 levels. We therefore report that lenalidomide plus dexamethasone can achieve durable responses in a subset of patients without continuing therapy until progression. Upregulation of IRF4 may contribute to anti-CLL activity of immunomodulatory agents. This trial was registered at as NCT01133743. [ABSTRACT FROM AUTHOR]

AKT plays a centralized role in tumor proliferation and survival and is aberrantly activated in chronic lymphocytic leukemia (CLL). In this phase 2 trial, 30 relapsed/refractory CLL patients were treated with combination afuresertib, a novel oral AKT inhibitor, and ofatumumab for 6 months, followed by afuresertib maintenance for 12 months. We aimed to achieve deeper and more durable responses, without requiring long-term continuous treatment. Treatment was generally well tolerated but respiratory infections were common, with 18% severe requiring hospitalization. Hematologic toxicities were manageable (grade 3-4 neutropenia 39%). At a median follow-up of 13.4 months, overall responses were 50% (complete responses 3.6%). Median progression-free survival was 8.5 months and overall survival 34.8 months. Combination therapy with ofatumumab and afuresertib is active and well tolerated, but does not appear to lead to durable responses and may not provide additional benefit over single-agent ofatumumab in relapsed/refractory CLL. Novel agent combinations are currently undergoing intense investigation. [ABSTRACT FROM AUTHOR]

Background: Advanced prosthetic knees allow for more dynamic movements and improved quality of life, but payers have recently started questioning their value. To answer this question, the differential clinical outcomes and cost of microprocessorcontrolled knees (MPK) compared to non-microprocessor controlled knees (NMPK) were assessed. Methods: We conducted a literature review of the clinical and economic impacts of prosthetic knees, convened technical expert panel meetings, and implemented a simulation model over a 10-year time period for unilateral transfemoral Medicare amputees with a Medicare Functional Classification Level of 3 and 4 using estimates from the published literature and expert input. The results are summarized as an incremental cost effectiveness ratio (ICER) from a societal perspective, i.e., the incremental cost of MPK compared to NMPK for each quality-adjusted life-year gained. All costs were adjusted to 2016 U.S. dollars and discounted using a 3 percent rate to the present time. Results: The results demonstrated that compared to NMPK over a 10-year time period: for every 100 persons, MPK results in 82 fewer major injurious falls, 62 fewer minor injurious falls, 16 fewer incidences of osteoarthritis, and 11 lives saved; on a per person per year basis, MPK reduces direct healthcare cost by $3,676 and indirect cost by $909, but increases device acquisition and repair cost by $6,287 and total cost by $1,702; on a per person basis, MPK is associated with an incremental total cost of $10,604 and increases the number of life years by 0.11 and quality adjusted life years by 0.91. MPK has an ICER ratio of $11,606 per quality adjusted life year, and the economic benefits of MPK are robust in various sensitivity analyses. Conclusions: Advanced prosthetics for transfemoral amputees, specifically MPKs, are associated with improved clinical benefits compared to non-MPKs. The economic benefits of MPKs are similar to or even greater than those of other medical technologies currently reimbursed by U.S. payers. [ABSTRACT FROM AUTHOR]

Context: Palliative care continues to be a rapidly growing field aimed at improving quality of life for patients and their caregivers.Objectives: The purpose of this review was to provide a synthesis of the evidence in palliative care to inform the fourth edition of the National Consensus Project Clinical Practice Guidelines for Quality Palliative Care.Methods: Ten key review questions addressing eight content domains guided a systematic review focused on palliative care interventions. We searched eight databases in February 2018 for systematic reviews published in English from 2013, after the last edition of National Consensus Project guidelines was published, to present. Experienced literature reviewers screened, abstracted, and appraised data per a detailed protocol registered in PROSPERO. The quality of evidence was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations criteria. The review was supported by a technical expert panel.Results: We identified 139 systematic reviews meeting inclusion criteria. Reviews addressed the structure and process of care (interdisciplinary team care, 13 reviews; care coordination, 18 reviews); physical aspects (48 reviews); psychological aspects (26 reviews); social aspects (two reviews); spiritual, religious, and existential aspects (11 reviews); cultural aspects (three reviews); care of the patient nearing the end of life (grief/bereavement programs, six reviews; final days of life, two reviews); ethical and legal aspects (36 reviews).Conclusion: A substantial body of evidence exists to support clinical practice guidelines for quality palliative care, but the quality of evidence is limited. [ABSTRACT FROM AUTHOR]

White coats are symbols of power that express historically entrenched ideals of clinical purity, sterility, and control. These ideals tend to oversimplify ethical and clinical complexities inherent in evolutions constantly taking place in health care practice. This pen and ink drawing interrogates these ideals visually and reimagines the white coat in the context of more realistic dynamism. [ABSTRACT FROM AUTHOR]

Novel therapies are needed for patients with relapsed or refractory multiple myeloma (MM). We conducted a multicenter, phase 1 study in advanced hematological malignancies to assess the safety, efficacy, and recommended phase 2 dose (RP2D) of oral selinexor, a selective inhibitor of the nuclear export protein XPO1. In the dose-escalation phase, 25 patients with heavily pretreated MM (22) or Waldenstrom macroglobulinemia (3) were administered selinexor (3-60 mg/m2) in 8 or 10 doses per 28-day cycle. In the dose-expansion phase, 59 patients with MM received selinexor at 45 or 60 mg/m2 with 20 mg dexamethasone, twice weekly in 28-day cycles, or selinexor (40 or 60 mg flat dose) without corticosteroids in 21-day cycles. The most common nonhematologic adverse events (AEs) were nausea (75%), fatigue (70%), anorexia (64%), vomiting (43%), weight loss (32%), and diarrhea (32%), which were primarily grade 1 or 2. The most common grade 3 or 4 AEs were hematologic, particularly thrombocytopenia (45%). Single-agent selinexor showed modest efficacy with an objective response rate (ORR) of 4% and clinical benefit rate of 21%. In contrast, the addition of dexamethasone increased the ORR with all responses of ‡partial response occurring in the 45 mg/m2 selinexor plus 20 mg dexamethasone twice weekly cohort (ORR550%). Furthermore, 46% of all patients showed a reduction inMM markers from baseline. Based on these findings,we conclude that selinexor in combinationwith dexamethasone is active in heavily pretreatedMMand propose a RP2D of 45mg/m2 (80mg) plus 20 mg dexamethasone given twiceweekly. This trial was registered at clinicaltrials.gov as #NCT01607892. (Blood. 2018;131(8):855-863) [ABSTRACT FROM AUTHOR]

We examine repeat surface altimetry and radio echo observations of two supraglacial lakes in the percolation zone of the Greenland ice sheet to investigate the changes in firn conditions leading to lake formation and implications for meltwater storage within firn. Both lakes formed in 2011, when an anomalously high melt season was followed by low winter accumulation, resulting in reduced infiltration and storage in the near surface. The lakes expanded during the 2012 record melt season and retained liquid meltwater through the following winter. The lakes then contracted, with one lake slowly draining and refreezing and another rapidly draining to the subsurface. The lack of observable change in firn conditions surrounding the lakes indicates increased run-off in the near surface firn, likely along low-permeability ice layers formed during the previous melt seasons. This implies a reduced ability of the firn to absorb increased meltwater. [ABSTRACT FROM PUBLISHER]

Annals Graphic Medicine brings together original graphic narratives, comics, animation/video, and other creative forms by those who provide or receive health care. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining. [ABSTRACT FROM AUTHOR]

Early Chinese immigrants in America centered on the Chinatown, which had fixed blocks and scope of activities. The distinguishing features of its ethnic culture and economy were formed by the ethnic Chinese immigrants who dwelt there. The Chinatown has become identified with the early Chinese immigrants and become one of the most unique residential areas for any ethnic group. Ever since the 1965 amendments to the American Immigration and Nationality Act, however, new Chinese arrivals no longer inhabit Chinatowns after they reach the United States. Without stationary blocks and scopes of activities, new Chinese immigrant communities have become enclaves accommodating multiple ethnic groups instead of one particular ethnicity. These communities are closely connected to a variety of ethnic features and have a tremendously different appearance from that of Chinatown. This transformation is still in progress and has been widely-considered by many scholars researching overseas ethnic Chinese immigrants. Flushing, in New York, is the largest Chinese immigrant community in the twenty-first century. This essay takes it as a case study to look into the evolution of Chinese immigrant communities in the United States. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the impact of standardized reduced post-procedure observation time on subsequent healthcare encounters such as emergency department (ED) visits, hospital admissions, and clinic visits. Methods: 800 consecutive patients undergoing outpatient non-arterial interventional radiologic procedures within the vascular interventional department between 1 June 2013 and 21 July 2014 were included in this IRB-approved, HIPAA-compliant single center observational retrospective study. Electronic medical records were reviewed for subsequent healthcare encounters, such as ED visits, hospital admissions, and clinic visits. An attending interventional radiologist and radiology resident reviewed, in consensus, medical records for relevance of the encounter to the index procedure. Procedure-related encounters were analyzed to determine relationship to length of observation time, using Matlab for statistical analysis. Results: 397 and 403 patients were in the pre- and post-standardization groups, respectively. Median observation time decreased overall from 1.67 h [interquartile range (IQR) 1.17-2.17] to 1.42 h (IQR 1.08-1.92), p < 0.001. There was no significant change in either overall or procedure-related ED visits (16.6% [66/397] and 1.0% [4/397] pre-standardization vs. 20.1% [81/403] and 2.2% [9/403] post-standardization, p = 0.24 and 0.26), hospital admissions (27.7% [110/397] and 4.0% [16/397] prestandardization vs. 28.3% [114/403] and 2.7% [11/403] post-standardization, p = 0.88 and 0.33), or clinic visits (41.3% [164/397] and 1.0% [4/397] pre-standardization vs. 39.5% [159/403] and 2.2% [9/403] post-standardization, p = 0.61 and 0.26). Conclusion: Proposed standardized shortened observation times after outpatient interventional radiologic procedures are safe, without change in either total or procedure-related ED visits, hospital admissions, or clinic visits. [ABSTRACT FROM AUTHOR]

Since G. K. Gilbert's foundational work in the eastern Great Basin during the late 1800s, the late Pleistocene Lake Bonneville (30–10 ka) has been recognized as a natural laboratory for various Quaternary studies, including lithospheric deformation due to surface loading and climate-forced water balance changes. Such studies rely on knowledge of the elevations of Lake Bonneville's paleoshoreline features and depositional landforms, which record a complex history of lake level variations induced by deglacial climate change. In this paper, we present (1) a new compilation of 178 elevation measurements of shoreline features marking Lake Bonneville's greatest areal extent measured using high-precision differential GPS (dGPS), and (2) a reconstructed outline of the highest shoreline based on dGPS measurements, submeter-resolution aerial imagery, topographic digital elevation models (DEMs), and field observations. We also (3) devise a simplified classification scheme and method for standardizing shoreline elevation measurement for different shoreline morphologies that includes constraints on the position of the still water level (SWL) relative to each feature type. The deformation pattern described by these shoreline features can help resolve the relative effects of local hydro-isostasy due to the lake load and regional solid earth deflection due to the Laurentide ice sheet, with potential implications for Earth rheology, glacial isostatic adjustment, and eustatic sea level change. [ABSTRACT FROM AUTHOR]

SHP2 is a nonreceptor protein tyrosine phosphatase (PTP) encoded by the PTPN11 gene involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also purportedly plays an important role in the programmed cell death pathway (PD-1/PD-L1). Because it is an oncoprotein associated with multiple cancer-related diseases, as well as a potential immunomodulator, controlling SHP2 activity is of significant therapeutic interest. Recently in our laboratories, a small molecule inhibitor of SHP2 was identified as an allosteric modulator that stabilizes the autoinhibited conformation of SHP2. A high throughput screen was performed to identify progressable chemical matter, and X-ray crystallography revealed the location of binding in a previously undisclosed allosteric binding pocket. Structure-based drug design was employed to optimize for SHP2 inhibition, and several new protein-ligand interactions were characterized. These studies culminated in the discovery of 6-(4-amino-4-methylpiperidin-1-yl)-3-(2,3-dichlorophenyl)pyrazin-2-amine (SHP099, 1), a potent, selective, orally bioavailable, and efficacious SHP2 inhibitor. [ABSTRACT FROM AUTHOR]

Investigations of the paleohydrologies of pluvial lake systems have often employed lake carbonate deposits called "tufa" that grow subaqueously and can be preserved long after the drying of the lake. For this reason, tufa have been used as a proxy for minimum lake level. However, they exhibit a variety of textures that hold the potential to reveal richer paleoclimatological information. With the goal of determining if tufa texture can be used as a proxy for lake environment, this study investigates the textures of tufa at Mono Lake, California in comparison to the fossil tufa in Searles Valley, California. While observations in the last century suggest that the tufa in the Mono basin grew in waters similar to the modern, the tufa at Searles formed during the last glacial period, when the Great Basin contained a system of pluvial lakes on the scale of the modern Great Lakes. The tufa at both basins have been observed to have a range of classifiable textures, and new methods of inspecting visual data could be informative about what factors control these textures. To this end, a t-Distributed Stochastic Neighbor Embedding (t-SNE) algorithm is used to project images of the tufa at Searles and Mono into a coordinate space, allowing for simple, quantitative comparisons of the visual similarity of textures. The textures of tufa at Searles are compared to each other, as well as to the tufa at Mono. This study performs a robust assessment of the feasibility of Mono Lake as a modern analogue for Searles Valley. It finds that there is a justifiable basis for the comparison of certain fossil facies at Searles to the tufa at Mono, significant progress towards the goal of using texture as a metric for the environment in which tufa formed. • Computer vision is used to compare facies of tufa at Searles and Mono Lakes, California, USA. • According to this comparison, the tufa at Mono Lake are most visually similar to the "columnar" facies at Searles. • This is significant progress towards the goal of using tufa texture as a metric for tufa formation environment. • Studies of this kind could be used in future to distinguish between geologic facies including, but not limited to, tufa in other basins. [ABSTRACT FROM AUTHOR]

During the Spitzer Space Telescope cryogenic mission, astronomers obtained Infrared Spectrograph (IRS) observations of hundreds of debris disk candidates that have been compiled in the Spitzer IRS Debris Disk Catalog. We have discovered 10 and/or 20 µm silicate emission features toward 120 targets in the catalog and modeled the IRS spectra of these sources, consistent with MIPS 70 µm observations, assuming that the grains are composed of silicates (olivine, pyroxene, forsterite, and enstatite) and are located either in a continuous disk with power-law size and surface density distributions or thin rings that are well-characterized using two separate dust grain temperatures. For systems better fit by the continuous disk model, we find that (1) the dust size distribution power-law index is consistent with that expected from a collisional cascade, q = 3.5-4.0, with a large number of values outside this range, and (2) the minimum grain size, amin, increases with stellar luminosity, L*, but the dependence of amin on L* is weaker than expected from radiation pressure alone. In addition, we also find that (3) the crystalline fraction of dust in debris disks evolves as a function of time with a large dispersion in crystalline fractions for stars of any particular stellar age or mass, (4) the disk inner edge is correlated with host star mass, and (5) there exists substantial variation in the properties of coeval disks in Sco-Cen, indicating that the observed variation is probably due to stochasticity and diversity in planet formation. [ABSTRACT FROM AUTHOR]

For people with lower-limb loss, impaired balance is common and limits prosthetic function within the community. This cross-sectional study (1) analyzed relationships among prosthetic use for mobility, balance ability and confidence, and amputation-related variables and (2) determined multivariate models to identify level of prosthetic use. Subjects included 46 community-dwelling adults (mean age 56.2 yr) with limb loss (91.3% unilateral) of varied levels (52.2% transtibial) and etiologies (69.6% vascular). A three-variable linear regression model including balance ability, balance confidence, and years since amputation explained 63.7% of variance in the Houghton scale of prosthetic use score. A logistic regression model including the 14-task Berg Balance Scale, balance confidence, years since amputation, age, and number of comorbidities correctly differentiated between people who had reached a satisfactory level of prosthetic use or not 89.1% of the time. The first three variables demonstrated moderate accuracy with positive likelihood ratios from 2.34 to 4.35. The regression model was further reduced to correctly classify 87.0% of cases with three balance ability tasks (retrieving objects from floor, turning to look behind, and placing alternate foot on stool), balance confidence, and numbers of comorbidities. Logistic models that include balance ability, balance confidence, and numbers of comorbidities can identify level of prosthetic use in people with lower-limb loss. Increased balance confidence and ability when retrieving objects from floor, turning to look behind, and placing alternate foot on stool were most indicative of successful prosthetic use for mobility. [ABSTRACT FROM AUTHOR]

Impairment of autophagy has been associated with liver injury. TLR4-stimulation by LPS upregulates autophagy in hepatocytes, although the signaling pathways involved remain elusive. The objective of this study was to determine the signaling pathway leading to LPS-stimulated autophagy in hepatocytes. Cell lysates from livers of wild type (WT; C57BL/6) mice given LPS (5mg/kg-IP) and hepatocytes from WT, TLR4ko, and MyD88ko mice treated with LPS (100 ng/mL) up to 24 h were collected. LC3II, p62/SQSTM1, Nrf2, and beclin1 levels were determined by immunoblot, immunofluorescence, and qPCR. Autophagylike activation was measured by GFP-LC3-puncta formation and LC3II-expression. Beclin1, Nrf2, p62, MyD88, and TIRAP were knocked-down using siRNA. LC3II-expression increased in both liver and hepatocytes after LPS and was dependent on TLR4. Beclin1 expression did not increase after LPS in hepatocytes and beclin1-knockdown did not affect LC3II levels. In hepatocytes given LPS, expression of p62 increased and p62 colocalized with LC3. p62-knockdown prevented LC3II puncta formation. LPSinduced LC3II/p62-puncta also requiredMyD88/TIRAP signaling and localization of both Nrf2 and NFκB transcription factors to the nucleus to upregulate p62-expression. Therefore, TLR4-activation by LPS in hepatocytes induces a p62-mediated, not beclin1- mediated, autophagy-like clearance pathway that is hepatoprotective by clearing aggregate-prone or misfolded proteins from the cytosol and preserving energy homeostasis under stress. [ABSTRACT FROM AUTHOR]

Background. Self-report measures of balance and multidimensional mobility assessments are common for people with a leg amputation, yet clinical assessment of balance ability remains less explored. The Berg Balance Scale (BBS), typically used for other populations with impaired balance, has been used for young people with a high level of functioning after traumatic amputation but rarely for older people after vascular amputation. Objective. The study objective was to examine the psychometric properties of the BBS with Rasch rating scale analysis to determine the validity and utility of the BBS in assessing balance ability in adults who have a leg amputation and dwell in the community. Design. Rating scale analysis was applied to BBS scores obtained from a single assessment. Methods. Adult volunteers (men and women) who had a leg amputation (any level and etiology) and dwelled in the community were recruited from a hospital-based community support group and a prosthetic clinic. Rating scale analysis of the BBS was used to assess unidimensionality, internal validity, goodness of fit, structural integrity, and person and item analyses. Results. The study participants were 40 people (26 men and 14 women; 57.8 [SD=9.7] years old) with leg amputations (24 transtibial, 13 transfemoral, and 3 bilateral) of mixed etiology (32 vascular and 8 nonvascular). The psychometric properties of the BBS confirmed that it measures the unidimensional construct of balance ability with adequate validity and with goodness of fit and structural integrity that meet the acceptability criteria. Person measures revealed that some participants scored near the top of the BBS, suggesting a ceiling effect; item measures revealed that participants with leg amputations had the most difficulty performing the following tasks: standing with 1 leg in front, turning 360 degrees, and placing alternate foot on a stool. Limitations. Limitations included a convenience sample and a lack of rater reliability testing. Conclusions. The BBS cohered with the unidimensional construct of balance ability and had strong internal validity for use in a variety of people with leg amputations. [ABSTRACT FROM AUTHOR]

Mirror overflow is involuntary movement that accompanies unilateral voluntary movement on the opposite side of the body, and is commonly seen in Attention-Deficit/Hyperactivity Disorder (ADHD). Children with ADHD show asymmetry in mirror overflow between dominant and non-dominant hand, yet there are competing mechanistic accounts of why this occurs. Using EEG during a sequential, unimanual finger-tapping task, we found that children with ADHD exhibited significantly more mirror overflow than typically developing (TD) controls, especially during the tapping of the non-dominant hand. Furthermore, source-level EEG oscillation analysis revealed that children with ADHD showed decreased alpha (8–12 Hz) event-related desynchronization (ERD) compared with controls in both hemispheres, but only during tapping of the non-dominant hand. Moreover, only the ERD ipsilateral to the mirror overflow during non-dominant hand movement correlated with both magnitude of overflow movements and higher ADHD symptom severity (Conners ADHD Hyperactivity/Impulsiveness scale) in children with ADHD. TD controls did not show these relationships. Our findings suggest that EEG differences in finger-tapping in ADHD are related primarily to voluntary movement in the non-dominant hand. Our results are also consistent with the Ipsilateral Corticospinal Tract (CST) Hypothesis, which posits that the atypical persistence of mirror overflow in ADHD may originate in the sensorimotor areas ipsilateral to mirror overflow and be transmitted via non-decussating CST fibers. • ADHD-related differences in brain activation related to mirror overflow are driven by the voluntary movement of the non-dominant hand. • Similarly, hyperactive/impulsive symptoms are associated with task-related activation only during movement of the non-dominant hand. • Our findings are consistent with the potential role of non-decussating cortical-spinal tracts in mirror overflow in ADHD. [ABSTRACT FROM AUTHOR]

Objective: To develop and validate the Taiwanese Manual Ability Measure for Burns (T-MAM for Burns), a task-oriented functional evaluation tool to assess self-reported manual ability in burn patients. Design: A longitudinal study. Participants: A sample of 45 burn patients from burn rehabilitation centers with varying degrees of hand involvement. Methods: The preliminary testing version was formed by adding burn specific items to the Taiwanese version of the Manual Ability Measure. A field test was then conducted for item reduction and psychometric properties testing. Results: Out of 55 initial items, 20 were selected into the final version of the T-MAM for Burns. Psychometric analyses indicated that it was reliable (test-retest ICC = .99), with adequate concurrent validity with various other hand function tests (r = - .79 with the short form Disabilities of the Arm, Shoulder, and Hand, or, the QuicteDASH) and discriminative validity (significant difference (t = 2.99, P = .005) between groups with unilateral vs. bilateral hand burns), and responsive (ES = .24 and .44 at one- and 3-month evaluations). Conclusion: This study shows that the T-MAM for Bums has great potential to be a functional outcome measure for burn rehabilitation. Additional research with a larger sample should be conducted to further confirm its validity and reliability. [ABSTRACT FROM AUTHOR]

Involvement of the central nervous system ( CNS) in multiple myeloma ( MM) is a rare complication, with reported survival of <6 months. This report describes 37 MM patients with leptomeningeal and/or parenchymal brain involvement treated at our institution and identifies factors associated with long-term survival. From January 1999 to December 2010, 37 patients with CNS MM were evaluated at our institution. Clinical characteristics, treatment and survival were retrospectively collected. CNS disease was present at MM diagnosis in 24% and at relapse in 76%. Plasma cell leukemia (40%) and skull plasmacytomas (65%) were common, suggesting haematological and contiguous spread. Intrathecal ( IT) chemotherapy was used in 81%, cranial and/or spinal irradiation in 78%, and various systemic therapies [immunomodulatory agents ( IMiDs) (51%), cisplatin-based ( DPACE; cisplatin, doxorubicin, cyclophosphamide, etoposide) (27%), bortezomib (19%), alkylators (11%), dexamethasone alone (8%), auto-transplant (5%)]. Median survival from CNS disease was only 4·6 months [95% confidence interval ( CI): 2·8-6·7]; however, nine patients had prolonged survival (median: 17·1 months, 95% CI: 13·2-67·4). In general, these long-term survivors were treated with radiotherapy, multi-dosing IT chemotherapy, and IMi D-containing therapy. CNS MM is a highly aggressive disease but in our experience, long-term survival can be achieved with the combination of multi-dosing IT chemotherapy, radiation and IMi D-based therapy. [ABSTRACT FROM AUTHOR]

Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family of proteins. It plays a key role in actin dynamics by promoting disassembly and assembly of actin filaments. Upon its binding, cofilin has been shown to bridge two adjacent protomers in filamentous actin (F-actin) and promote the displacement and disordering of subdomain 2 of actin. Here, we present evidence for cofilin promoting a new structural change in the actin filament, as detected via a switch in cross-linking sites. Benzophenone-4-maleimide, which normally forms intramolecular cross-linking in F-actin, cross-links F-actin intermolecularly upon cofilin binding. We mapped the cross-linking sites and found that in the absence of cofilin intramolecular cross-linking occurred between residues Cys374 and Asp11. In contrast, cofilin shifts the cross-linking by this reagent to intermolecular, between residue Cys374, located within subdomain 1 of the upper protomer, and Met44, located in subdomain 2 of the lower protomer. The intermolecular cross-linking of F-actin slows the rate of cofilin dissociation from the filaments and decreases the effect of ionic strength on cofilin–actin binding. These results are consistent with a significant role of filament flexibility in cofilin–actin interactions. [ABSTRACT FROM AUTHOR]

The article presents a study which shows the role of pollen germination in activating the apical membrane-located RAC/ROP GTPase switch. It notes that NtRACs that accumulated in stigmas alone, pollen alone, and in combined pollen grains and stigma mixed were compared to examine the impact of pollen germination on the stigma affects RAC/ ROP activity. It states that the study determine that RAC/ROPs was activated and ADF phosphorylation was augmented by pollen germination augments.

In this study, daily maps of snow cover distribution and sea ice extent produced by NOAA's interactive multisensor snow and ice mapping system (IMS) were validated using in situ snow depth data from observing stations obtained from NOAA's National Climatic Data Center (NCDC) for calendar years 2006 to 2010. IMS provides daily maps of snow and sea ice extent within the Northern Hemisphere using data from combination of geostationary and polar orbiting satellites in visible, infrared and microwave spectrums. Statistical correspondence between the IMS and in situ point measurements has been evaluated assuming that ground measurements are discrete and continuously distributed over a 4 km IMS snow cover maps. Advanced Very High Resolution Radiometer (AVHRR) land and snow classification data are supplemental datasets used in the further analysis of correspondence between the IMS product and in situ measurements. The comparison of IMS maps with in situ snow observations conducted over a period of four years has demonstrated a good correspondence of the data sets. The daily rate of agreement between the products mostly ranges between 80% and 90% during the Northern Hemisphere through the winter seasons when about a quarter to one third of the territory of continental US is covered with snow. Further, better agreement was observed for stations recording higher snow depth. The uncertainties in validation of IMS snow product with stationed NCDC data were discussed. [ABSTRACT FROM AUTHOR]

Spire is a WH2 domain-containing actin nucleator essential for establishing an actin mesh during oogenesis. In vitro, in addition to nucleating filaments, Spire can sever them and sequester actin monomers. Understanding how Spire is capable of these disparate functions and which are physiologically relevant is an important goal. To study severing, we examined the effect of Drosophila Spire on preformed filaments in bulk and single filament assays. We observed rapid depolymerization of actin filaments by Spire, which we conclude is largely due to its sequestration activity and enhanced by its weak severing activity. We also studied the solution and crystal structures of Spireactin complexes. We find structural and functional differences between constructs containing four WH2 domains (Spir-ABCD) and two WH2 domains (Spir-CD) that may provide insight into the mechanisms of nucleation and sequestration. Intriguingly, we observed lateral interactions between actin monomers associated with Spir-ABCD, suggesting that the structures built by these four tandem WH2 domains are more complex than originally imagined. Finally, we propose that Spire-actin mixtures contain both nuclei and sequestration structures. [ABSTRACT FROM AUTHOR]

We obtained Spitzer Space Telescope Multiband Imaging Photometer for Spitzer (MIPS) 24 µm and 70 µm observations of 182 nearby, Hipparcos F- and G-type common proper motion single and binary systems in the nearest OB association, Scorpius-Centaurus. We also obtained Magellan/MIKE R ~ 50,000 visual spectra at 3500-10500 Å for 181 candidate ScoCen stars in single and binary systems. Combining our MIPS observations with those of other ScoCen stars in the literature, we estimate 24 µm F+G-type disk fractions of 9/27 (33% ± 11 %), 21/67 (31% ± 7%), and 25/71 (35% ± 7%) for Upper Scorpius (~10 Myr), Upper Centaurus Lupus (~15 Myr), and Lower Centaurus Crux (~17 Myr), respectively. We confirm previous IRAS and MIPS excess detections and present new discoveries of 41 protoplanetary and debris disk systems, with fractional infrared luminosities ranging from LTR/L* = 10-5 to 10-2 and grain temperatures ranging from Tgr = 40-300 K. We searched for an increase in 24 µm excess at an age of 15-20 Myr, consistent with the onset of debris production predicted by coagulation TV-body simulations of outer planetary systems. We found such an increase around 1.5 MQ stars but discovered a decrease in the 24 µm excess around 1.0 Mo stars. We additionally discovered that the 24 µm excess around 1.0 M⊙ stars is larger than predicted by self-stirred models. Finally, we found a weak anti-correlation between fractional infrared luminosity (LIR/L* and chromospheric activity (RDue to image rights restrictions, multiple line equation(s) cannot be graphically displayed.), that may be the result of differences in stellar properties, such as mass, luminosity, and/or winds. [ABSTRACT FROM AUTHOR]

The article presents a study regarding the acceptance by therapists on the use of new technology devices (NTDs) in stroke rehabilitation. The study conducted several methods including literature review on acceptance on NTDs, focus group sessions, and structured interviews to gather data for a mail survey for the therapists. Results show several factors on the acceptance of NTDs including the patient's acceptance, the cost of NTDs, and suitability.

Background & Aims: NOD-like receptors are recently described cytosolic pattern recognition receptors. NOD1 and NOD2 are members of this family that recognize bacterial cell wall components, diaminopimelic acid and muramyl dipeptide, respectively. Both NOD1 and NOD2 have been associated with many inflammatory diseases, although their role in liver inflammation and infection has not been well studied. Methods: We investigated the role of NOD receptors in mouse liver by assessing expression and activation of NOD1 and NOD2 in liver and primary isolated hepatocytes from C57BL/6 mice. Results: Both NOD1 and NOD2 mRNA and protein were highly expressed in hepatocytes and liver. RIP2, the main signaling partner for NODs, was also expressed. Stimulation of hepatocytes with NOD1 ligand (C12-iEDAP) induced NFκB activation, activation of MAP kinases and expression of chemokines CCL5 (RANTES) and CXCL1 (KC). C12-iEDAP also synergized with interferon (IFN)γ to increase iNOS expression and production of nitric oxide. Despite activating NFκB, NOD1 ligand did not upregulate hepatocyte production of the acute phase proteins lipopolysaccharide binding protein, serum amyloid A, or soluble CD14 in cell culture supernatants, or upregulate mRNA expression of lipopolysaccharide binding protein, serum amyloid A, C-reactive protein, or serum amyloid P. NOD2 ligand (MDP) did not activate hepatocytes when given alone, but did synergize with Toll-like receptor ligands, lipopolysaccharide (LPS), and polyI:C to activate NFκB and MAPK. Conclusions: All together these data suggest an important role for hepatocyte NOD1 in attracting leukocytes to the liver during infection and for hepatic NLRs to augment innate immune responses to pathogens. [ABSTRACT FROM AUTHOR]

Abstract: Molecular tethers have a central role in the organization of the complex membrane architecture of eukaryotic cells. p115 is a ubiquitous, essential tether involved in vesicle transport and the structural organization of the exocytic pathway. We describe two crystal structures of the N-terminal domain of p115 at 2.0 Å resolution. The p115 structures show a novel α-solenoid architecture constructed of 12 armadillo-like, tether-repeat, α-helical tripod motifs. We find that the H1 TR binds the Rab1 GTPase involved in endoplasmic reticulum to Golgi transport. Mutation of the H1 motif results in the dominant negative inhibition of endoplasmic reticulum to Golgi trafficking. We propose that the H1 helical tripod contributes to the assembly of Rab-dependent complexes responsible for the tether and SNARE-dependent fusion of membranes. [Copyright &y& Elsevier]