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In this short communication, we present data that suggests messages that incorporate identity frames can be an asset in engagement and support for greenspace development.

To examine the implementation and utilization of a pediatric acute stroke protocol over a 7-year period, hypothesizing improvements in protocol implementation and increased protocol use over time.Clinical and demographic data for this retrospective observational study from 2011 through 2018 were obtained from a quality improvement database and medical records of children for whom the acute stroke protocol was activated. The initial 43 months of the protocol (period 1) were compared with the subsequent 43 months (period 2).Over the 7-year period, a total of 385 stroke alerts were activated, in 150 children (39%) in period 1 and 235 (61%) in period 2, representing a 56% increase in protocol activation. Stroke was the final diagnosis in 80 children overall (21%), including 38 (25%) in period 1 and 42 (19%) in period 2 (P = .078). The combined frequency of diagnosed stroke, transient ischemic attack (TIA), and other neurologic emergencies remained stable across the 2 time periods at 39% and 37%, respectively (P = .745). Pediatric National Institutes of Health Stroke Scale (PedNIHSS) documentation increased from 42% in period 1 to 82% in period 2 (P .001). Magnetic resonance imaging (MRI) was the first neuroimaging study for 68% of the children in period 1 vs 78% in period 2 (P = .038). All children with acute stroke received immediate supportive care.Pediatric stroke protocol implementation improved over time with increased use of the PedNIHSS and use of MRI as the first imaging study. However, with increased utilization, the frequency of confirmed strokes and other neurologic emergencies remained stable. The frequency of stroke and other neurologic emergencies in these children affirms the importance of implementing and maintaining a pediatric acute stroke protocol.

The limited effectiveness of rituximab plus intravenous immunoglobulin (IVIG) in desensitization may be due to incomplete B cell depletion. Obinutuzumab is a type 2 anti‐CD20 antibody that induces increased B cell depletion relative to rituximab and may therefore be more effective for desensitization. This open‐label phase 1b study assessed the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in highly sensitized patients with end‐stage renal disease. Patients received 1 (day 1, n = 5) or 2 (days 1 and 15; n = 20) infusions of 1000‐mg obinutuzumab followed by 2 doses of IVIG on days 22 and 43. Eleven patients received additional obinutuzumab doses at the time of transplant and/or at week 24. The median follow‐up duration was 9.4 months. Obinutuzumab was well tolerated, and most adverse events were grade 1‐2 in severity. There were 11 serious adverse events (SAEs) in 9 patients (36%); 10 of these SAEs were infections and 4 occurred after kidney transplant. Obinutuzumab plus IVIG resulted in profound peripheral B cell depletion and appeared to reduce B cells in retroperitoneal lymph nodes. Reductions in anti‐HLA antibodies, number of unacceptable antigens, and the calculated panel reactive antibody score as centrally assessed using single‐antigen bead assay were limited and not clinically meaningful for most patients (NCT02586051)., The authors assess the safety, pharmacokinetics, and pharmacodynamics of obinutuzumab in combination with high‐dose intravenous immunoglobulins in highly sensitized patients with end‐stage renal disease awaiting kidney transplantation and find that obinutuzumab is tolerated well and effectively depletes B cells, but has limited effects on reducing pre‐existing anti‐HLA alloantibody levels.

ObjectiveBecause of the high prevalence of silent cerebral infarcts (SCIs) in adults with sickle cell anemia (SCA) and lack of information to guide treatment strategies, we evaluated the risk of recurrent SCIs and overt stroke in adults with SCA with preexisting SCI.MethodsThis observational study included adults with SCA (HbSS or Sβ0 thalassemia) aged 18 to 40 years. Participants received 3-tesla brain MRI and a detailed neurologic examination. Time-to-event analysis assessed those with or without baseline SCI and with new or progressive infarcts. The incidence rate of new events was compared by log-rank test. Univariable Cox regression assessed the association of SCI with infarct progression.ResultsAmong adults with SCA with 2 MRIs and at least 6 months between MRIs (n = 54, mean interval = 2.5 years), 43% had SCI at baseline. Of participants with baseline SCI, 30% had new or progressive SCI over 2.5 years compared to 6% with no SCI at baseline; no participant had an overt stroke. New SCIs at follow-up were present in 12.9 per 100 patient-years with existing SCI compared with 2.4 per 100 patient-years without prior SCI (log-rank test, p = 0.021). No statistically significant differences were seen among those with or without baseline SCI in use of hydroxyurea therapy, hydroxyurea dose, or other stroke risk factors. The presence of SCI was associated with increased hazard of a new or progressive infarct (hazard ratio 5.27, 95% confidence interval 1.09–25.51, p = 0.039).ConclusionsSilent infarcts in adults with SCA are common and are a significant risk factor for future silent infarcts.

Background and Purpose— Intracerebral hemorrhage is a considerable source of morbidity and mortality. This 3-center study describes outcomes of pediatric intracerebral hemorrhage and identifies 2-year neurological outcome predictors. Methods— Children 29 days to 18 years of age presenting with intracerebral hemorrhage from March 2007 to May 2015 were enrolled prospectively. Exclusion criteria included trauma; intracranial tumor; hemorrhagic transformation of arterial ischemic stroke or cerebral sinovenous thrombosis; isolated subdural, epidural, or subarachnoid hemorrhage; and abnormal baseline neurological function. Intracerebral hemorrhage and total brain volumes were measured on neuroimaging. The Pediatric Stroke Outcome Measure assessed outcomes. Results— Sixty-nine children were included (median age: 9.7 years; interquartile range: 2.2–14). Six children (9%) died during hospitalization. Outcomes in survivors were assessed at early follow-up in 98% (median 3.1 months; interquartile range: 3.1–3.8) and at later follow-up in 94% (median: 2.1 years; interquartile range: 1.3–2.8). Over a third had a significant disability at 2 years (Pediatric Stroke Outcome Measure >2). Total Pediatric Stroke Outcome Measure score improved over time ( P =0.0003), paralleling improvements in the sensorimotor subscore ( P =0.0004). Altered mental status (odds ratio, 13; 95% confidence interval, 3.9–46; P P =0.01), and intensive care unit length of stay (odds ratio, 1.1; 95% confidence interval, 1.0–1.2; P =0.002) were significantly associated with poor 2-year outcome. Conclusions— Over one third of children experienced significant disability at 2 years. Improvements in outcomes were driven by recovery of sensorimotor function. Altered mental status, hemorrhage volume ≥4% of total brain volume, and intensive care unit length of stay were independent predictors of significant disability at 2 years.

Purpose To compare fixed- or variable-angle locking screws in calcaneal fracture plates using a sawbones biomechanical model. Methods Intra-articular calcaneal fractures were created in synthetic bones. Reduction and stabilization was performed with 3 different plates. In group A, a fixed-angle locking plate was used with screws fastened perpendicularly to the plate (3.5 LCP, DePuySynthes). In groups B and C (2.7 VA-LCP, DePuySynthes and 3.5 Aptus, Medartis, respectively), fracture fixation was performed using variable-angle locking plates. Biomechanical testing was conducted. Displacement of the subtalar articular surface, stiffness, maximum displacement, change in the angle of Gissane, and mode of failure under cyclic loading at 200 N, 600 N, and 1000 N (500 cycles each) were determined. Results No statistically significant difference of articular surface dislocation under cyclic loading was detected. The stiffness and maximum displacement did not reveal any disparity as well. The change in the angle of Gissane showed only minor displacement of the articular surface. Conclusion In our study, the resistance of variable-angle locking plates against articular surface displacement was similar to fixed-angle locking screws.

When considering the breadth of American song literature, the works of African-American composers are not as commonly found within the standard music repertoire. When songs by African-American composers are performed in recital, they are typically limited to arrangements of spirituals. While these pieces certainly deserve a place in song recitals, this limited programming leaves audiences unaware of the rich history of contributions made to the genre of art song by African-American composers. This article seeks to fill this gap and serve as a reference for baritone music literature. The five musicians discussed are Modernists (Robert Owens and H. Leslie Adams) and Traditionalists (Camille Nickerson, Hall Johnson, and Margaret Bonds). Together, they present a rich variety of African-American classical music of the twentieth century. African Americans are not one-dimensional, and neither is the music that emanates from these composers. The pieces discussed contain elements of jazz, blues, and other ...

Resilience is increasingly becoming the new buzz word. This paper examines the utility of the concept of resilience for understanding the gendered experiences of women to climate stress, through ca...

Background The specific contribution of dementia towards mortality in trauma patients is not well defined. The purpose of the study was to evaluate dementia as a predictor of mortality in trauma patients when compared to case-matched controls. Methods A 5-year retrospective review was conducted of adult trauma patients with a diagnosis of dementia at an American College of Surgeons-verified level I trauma center. Patients with dementia were matched with non-dementia patients and compared on mortality, ICU length of stay, and hospital length of stay. Results A total of 195 patients with dementia were matched to non-dementia controls. Comorbidities and complications (11.8% vs 12.4%) were comparable between both groups. Dementia patients spent fewer days on the ventilator (1 vs 4.5, P = 0.031). The length of ICU stay (2 days), hospital length of stay (3 days), and mortality (5.1%) were the same for both groups (P > 0.05). Conclusions Dementia does not appear to increase the risk of mortality in trauma patients. Further studies should examine post-discharge outcomes in dementia patients.

Extensive criminological research has investigated the effectiveness of law enforcement efforts to prevent offenders' reoffending and effect changes in criminal behavior patterns. However, no research has quantified the influence of gossip regarding law enforcement operations and its effect on repeat offending. Moreover, only scant research has studied these relationships in the cyber-environment. The current work addresses this gap by studying the effect of online messages sent to active hackers that describe law enforcement efforts against website defacement activity. In two field experiments, we randomly assigned self-identified hackers with active Facebook accounts into control and treatment groups. We then sent subjects in the treatment group a gossip message (via Facebook) alerting them to law enforcement efforts in cyberspace. Following the intervention, we compared the control and treatment groups in terms of changes in the proportion of reoffending, number of website defacements, and severity of website defacements. Findings reveal that when the gossip was sent to a hacker's private inbox, it prompted a reduction in the proportion of hackers who reoffend, the frequency at which they reoffend, and the severity of attacks they generate. However, posting similar gossip on the hacker's Facebook wall was ineffective in restricting malicious hacking activity. Theoretical implications and practical recommendations for law enforcement operations in cyberspace are discussed.

Introduction: Individuals with sickle cell anemia (SCA) are at increased risk for deficits in multiple domains of neurocognitive functioning, including executive functions. In addition to assessing the effects of silent cerebral infarcts (SCI) and stroke on cognition, prior research has focused on hemoglobin and transcranial Doppler velocity as hemodynamic correlates. Recent studies have begun to use more precise measures of blood delivery to the brain (e.g., cerebral blood flow; CBF) to determine more sensitive indicators of cognitive risk prior to neurological injury. Nevertheless, empirical and meta-analytic findings suggest that these deficits increase with age, which can have broad impact on psychosocial functioning, including self-management and navigation through the transition from pediatric to adult medical care. This study aimed to assess brain volume as a mediator of the association between CBF and executive functioning in a sample of individuals with SCA. The secondary aim was to assess age as a moderator of hemodynamic and structural correlates of executive function. Methods: Children, adolescents, and young adults with SCA were enrolled prospectively. Each participant received a 3-Tesla non-contrast magnetic resonance imaging and magnetic resonance angiography of the brain, and a neurological examination by the study neurologist. Gray matter CBF was calculated from pseudo-continuous arterial spin labeling using the solution to the flow-modified Bloch equation after correcting for individual hematocrit. Three measures of brain volume were also computed from 3D-T1 images using Freesurfer version 7.1.1: total brain volume, gray matter volume, and white matter volume was calculated as the difference between the two. At a separate study visit, participants completed an age-appropriate Wechsler Working Memory Index (WMI). Pearson correlations assessed bivariate associations among variables, SPSS PROCESS macro was used to test gray matter volume as a mediator in the relation between CBF and working memory, and multiple linear regression analyses tested age as a moderator of the impact of CBF and brain volume on working memory. Results: Twenty-nine children and adolescents (ages 6 to 17 years) and 25 adults (ages 18 to 31 years) were enrolled. Five participants were excluded from analyses due to history of overt stroke that resulted in significant brain volume loss. Of 49 included participants, 20 had SCIs. Working memory was inversely correlated with age (r = -.30, p = .037) and CBF (r = -.36, p = .013), such that WMI decreased cross-sectionally with older age and higher CBF. Working memory was positively correlated with gray matter volume (r = .42, p = .002); however, it was not related to white matter volume (r = -.05, p = .715) or total brain volume (r = -.07, p = .642). Finally, patient age was positively correlated with CBF (r = .36, p = .014), but the association of age with gray matter volume did not reach statistical significance (r = -.27, p = .065). Analyses in Figure 1 show that although CBF and gray matter were directly related to working memory (path c and path b, respectively), gray matter volume did not mediate the association between CBF and working memory (path a*b). However, regression analyses (Table 1) showed that age moderated the association between gray matter volume and working memory, such that there was only a significant relation in children and adolescents. This association did not exist for young adults (Figure 2). Conclusions: Neurocognitive assessments has been cited as an important standard of care for children and adolescents with SCA. Given the increase in deficits with age, and the increase in mortality after transferring from pediatric to adult care, monitoring executive function abilities and potential impact on self-management should continue into adulthood. Findings from the current study provide preliminary evidence that cerebral hemodynamic compensation with elevated CBF may be insufficient to prevent gray matter volume loss in children and adolescents and decline in working memory ability. Some limitations of the current study include small sample size and whole brain gray and white matter volumes as opposed to specific regions relevant to executive functions (e.g., prefrontal cortex); however, findings from global measures provide promising evidence for future research on hemodynamic and structural predictors of executive function in SCA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

The study developed and validated a system for scoring the quality of household grocery purchases, the Grocery Purchase Quality Index-2016 (GPQI-2016). A grocery sales data set (2012–13) without individual household shopper attributes was provided by a national grocery chain, and a sample of 4000 households in each of four geographic locations was drawn. The 1887 categories, known as “subcommodities,” in the database were classified into the 29 food categories of the US Department of Agriculture’s Food Plan market baskets. A standardized expenditure share for each category was calculated. Quality of food purchases was evaluated by comparing the observed to the standardized USDA expenditure share for each category and then grouping the categories into 11 components, based on the Healthy Eating Index-2010. Processed meat expenditures were also assessed. Households that never purchased tobacco (n = 12,460) had higher (6%) median total quality scores (31.3 of a possible 75 points) than those who did purchase tobacco (n = 3540, median score 26.6, p

Fraction magnitude understanding is linked to student achievement in mathematics, but the direction of the relation is not clear. To assess whether fraction magnitude knowledge and mathematics achievement develop in a bidirectional fashion, participants (N = 536) completed a standardized mathematics achievement test and two measures of fraction magnitude understanding—fraction comparisons and fraction number line estimation (FNLE)—twice yearly in 4th–6th grades. Cross-lagged panel models revealed significant autoregressive paths for both achievement and magnitude knowledge, indicating longitudinal stability after accounting for correlational and cross-lagged associations. Mathematics achievement consistently predicted later FNLE and fraction comparison performance. FNLE and fraction comparisons predicted mathematics achievement at all time points, although this relation diminished over time. Findings suggest that fraction magnitude knowledge and broader mathematics achievement mutually support one another. FNLE predicted subsequent mathematics achievement more strongly than did fraction comparisons, possibly because the FNLE task is a more specific measure of fraction magnitude understanding.

Incompatible living donor kidney transplantation (ILDKT) has been established as an effective option for end-stage renal disease patients with willing but HLA-incompatible living donors, reducing mortality and improving quality of life. Depending on antibody titer, ILDKT can require highly resource-intensive procedures, including intravenous immunoglobulin, plasma exchange, and/or cell-depleting antibody treatment, as well as protocol biopsies and donor-specific antibody testing. This study sought to compare the cost and Medicare reimbursement, exclusive of organ acquisition payment, for ILDKT (n = 926) with varying antibody titers to matched compatible transplants (n = 2762) performed between 2002 and 2011. Data were assembled from a national cohort study of ILDKT and a unique data set linking hospital cost accounting data and Medicare claims. ILDKT was more expensive than matched compatible transplantation, ranging from 20% higher adjusted costs for positive on Luminex assay but negative flow cytometric crossmatch, 26% higher for positive flow cytometric crossmatch but negative cytotoxic crossmatch, and 39% higher for positive cytotoxic crossmatch (p

There was a mistake in the Matlab code we used to generate time series solutions of our model, Eqs. (16)-(18). The corrected text below replaces one paragraph on p. 7, and the figures below replace Fig. 4 , Fig. 5 on p. 8. There is no qualitative change to our results. However, there is a quantitative change in the initial dead oyster shell volume B ( 0 ) needed for reef survival. The corrected threshold B ( 0 ) , about 0.40 m3 per m2 of sea floor, is more consistent with a recently experimentally estimated threshold of 0.30 m (Colden, Latour, and Lipcius, Mar Ecol Prog Ser 582: 1–13, 2017) than was our old incorrect threshold of about 0.12 m3.

Introduction: In children with sickle cell anemia (SCA) without transcranial Doppler (TCD) screening, the incidence rates of ischemic strokes is approximately the same among children living in low- and high- low-resource settings (Pediatr Neurol. 2019;95:73-78.) with a prevalence of ~ 11%. However, in high-income settings, the standard use of TCD ultrasonography, coupled initially with monthly blood transfusion therapy has dropped the stroke prevalence to < 1%. In a low-income setting, such as Nigeria, where 50% of children in the world with SCA are born (150,000 per year), initial monthly blood transfusion therapy is not practical for most children. In the Stroke Prevention in Nigeria (SPIN) Feasibility Trial (NCT01801423), fixed moderate-dose hydroxyurea was associated with a decreased rate of strokes in children with SCA and abnormal time-averaged mean of the maximum velocity (TAMMV) TCD measurements (≥200cm/sec) when compared to no treatment in the STOP Trial, 0.76 and 10.7 strokes per 100 person-years, repsectively (Am J Hematol. 2020). Based on the success of the SPIN trial, plus the challenges of real-world implementation of a government-supported primary stroke prevention programs for estimated 40,0000 children with SCA in three states in Nigeria, we tested the hypothesis that fixed-moderate dose (~20 mg/kg/day) hydroxyurea therapy for primary stroke prevention results in a 66% relative risk reduction (9 to 3 events per 100 person-years) when compared to fixed low-dose hydroxyurea (~10 mg/kg/day) therapy in a randomized controlled trial (The SPRING Trial; NCT02560935). Methods: In this partial-blind controlled phase III trial, we randomly assigned children between 5 and 12 years of age with SCA and a TCD time-averaged mean of the maximum velocity (TAMMV) ≥ 200 cm/sec measured independently twice or TAMMV ≥220 cm/sec once at study screening to receive fixed low-dose or fixed moderate-dose hydroxyurea. The primary endpoint was a clinical stroke or a transient ischemic attack (TIA). Myelosuppression was assessed with monthly complete blood counts (CBCs). Adherence to hydroxyurea was primarily based on an increase in MCV from baseline and monthly pill count return as a percent of dispensed pills. Hemoglobin F levels were measured at baseline, annually and upon trial exit. To evaluate the safety of hydroxyurea in the trial, children attending the same SCA clinics with TCD (TAMMV) Results: A total of 220 children (mean age: 7.5 years, 51.8% female) were randomly assigned to fixed low- (10 mg/kg/day) or moderate- (20 mg/kg/day) dose hydroxyurea, and were followed for a median of 2.4 years (IQR 2.0-2.8). NINDS Clinical Trials leaders stopped the trial early because of futility for the primary outcome. In the fixed low- and moderate-dose hydroxyurea groups, the incidence rates of strokes per 100 person-years were 1.19 and 1.92 respectively, with an incidence rate ratio of 1.60 (95% CI: 0.31-10.34), p = 0.768. The incidence rate ratio of mortality when comparing the children treated with low- and moderate- fixed-dose hydroxyurea to the non-elevated TCD group (no hydroxyurea therapy, n= 211) was 1.97 (95% CI: 0.64-6.02) and 0.47 (95% CI: 0.05-2.38), p = 0.265 and 0.545, respectively. Returned pills during the trial was 5.4% and 4.8% in the fixed low- and moderate-dose groups, respectively, p= 0.144. MCV from baseline to endpoint increased 1.5fl and 7.2 fl in the fixed low- and moderate-dose groups, respectively, p Conclusions: For primary stroke prevention in children with SCA, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of strokes. Both fixed low- and moderate -dose hydroxyurea doses are superior to no treatment for primary stroke prevention with abnormal TCD values. In partnership with Katsina, Kano, and Kaduna health department's leaders in Nigeria, 9 distinct SCA and primary stroke prevention clinics have been established, with the provision of free fixed low-dose hydroxyurea therapy (Bond Chemical, Nigeria; $0.15 per 500 mg) for abnormal TCD values, and biannual CBCs as standard care ,for over 40,000 children with SCA. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

Introduction Strokes are a preventable cause of neurological morbidity and premature death, particularly in children with sickle cell anemia (SCA) living in low-resource countries. If untreated, 50% of children with SCA their first overt ischemic stroke will have a recurrent stroke within two years of the event. In high-income countries, ASH 2020 guidelines recommend indefinite regular blood transfusion therapy for secondary stroke prevention (Blood Adv. 2020). Unfortunately, regular blood transfusion therapy is not a feasible option for children with SCA in sub-Saharan Africa due to the high cost of monthly blood transfusion, limited blood supply, and unsafe transfusion practices. Also, children who receive regular blood transfusions will ultimately require daily iron chelation at a cost that is prohibitive to most families in low-income settings. One randomized controlled trial provided evidence that HU therapy may be an effective therapy for secondary prevention of strokes when compared to no therapy (Blood. 2012;119(17):3925-3932). In the SWiTCH trial, the incidence rate of stroke recurrence in the group randomly allocated to receive maximum tolerated dose HU therapy was significantly higher than the group randomly assigned to receive blood transfusion therapy (5.6 and 0 events per 100 person-years, respectively, but considerably lower when compared to children not treated with any treatment, approximately 28 events per 100 person-years (Niger Postgrad Med J. 2013;20(3):181-187). Given the practical limitations for regular blood transfusion therapy, we tested the hypothesis that for secondary stroke prevention among children with SCA and acute overt ischemic stroke, fixed moderated dose HU therapy (~20 mg/kg/day) results in 80% relative risk reduction when compared to fixed low-dose HU therapy (10 mg/kg/day) in a randomized controlled trial (SPRINT Trial; NCT02675790). Methodology In phase III controlled trial, partially blind d controlled trial, we randomly assigned children 1 - 16 years of age with SCA and a new-onset of ischemic stroke (within 1 month) to receive fixed moderate-dose HU therapy at 20 mg/kg/day or fixed-low dose HU therapy at 10 mg/kg/day) with a monthly follow-up for at least 36 months. The primary endpoint was a recurrence of overt stroke or transient ischemic attack. Myelosuppression was assessed with monthly CBCs. Adherence to hydroxyurea was based on an increase in MCV from baseline and monthly pill count return, as a percent of dispensed pills. Results A total of 101 children with SCA were randomly assigned to fixed low- (~10 mg/kg/day) or moderate- (~20 mg/kg/day) dose hydroxyurea. The mean age was 6.6 years; 55.4% were males, and the median follow up was 1.6 years (IQR 1.0 - 2.3). The DSMB stopped the trial early due to the futility of the primary endpoint. In the fixed low- and moderate-dose groups, the incidence rates of recurrent strokes per 100 person-years were 7.1 and 6.0, respectively, incidence rate ratio of 0.85 (95% CI: 0.20 - 3.34), p=0.999. The incidence rates of mortality per 100 person-years in the fixed low dose and moderate- fixed-dose groups were 2.38 and 3.63, respectively, with an incidence rate ratio of 1.53 (95% CI: 0.18 - 18.30), p=0.98. No participant had hydroxyurea therapy stopped because of myelosuppression. As a measure of adherence, MCV from baseline to endpoint increased 6.2 fl and 13.3 fl in the fixed low- and moderate-dose groups, respectively, p=0.025; returned pills during the trial were 3.3% and 3.5% in the fixed low- and moderate-dose groups, respectively, p= 0.76. Conclusion For secondary stroke prevention, in a randomized controlled trial in children with SCA and new onset of ischemic strokes, fixed low-dose, when compared to fixed moderate-dose hydroxyurea therapy, demonstrated no difference in the incidence rate of stroke recurrence. Fixed low-dose hydroxyurea for secondary prevention of strokes in Nigeria provided similar stroke recurrence rate, when compared to the SWiTCH Trial (Blood. 2012;119(17):3925-3932) with the maximum tolerated dose of hydroxyurea of 7.0 and 5.7 events per 100 person-years, respectively. For secondary stroke prevention, in low-income settings without access to indefinite regular blood transfusion therapy, fixed low-dose hydroxyurea of at least 10 mg/kg/day with biannual CBC is a new evidence-based strategy to prevent strokes and minimize unnecessary laboratory testing. Disclosures DeBaun: Global Blood Therapeutics (GBT): Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: fixed low and moderate dose hydroxyurea for primary stroke prevention in sickle cell

Previous research demonstrates that large basins on the periphery of the northern edge of the Tibetan Plateau were partitioned during development of intrabasin mountain ranges. These topographic barriers segregated basins with respect to surface flow and atmospheric circulation, ponded sediments, and formed rain shadows. However, complex mixing between airmasses and nonsystematic isotope‐elevation lapse rates have hampered application of quantitative paleoaltimetry to determine the timing of development of critical topographic barriers. We address the timing and drivers for changes in surface connectivity and atmospheric circulation in the Linxia and Xunhua basins using a multidisciplinary approach incorporating detrital zircon geochronology, Monte Carlo inverse flexural modelling, and published stable isotope data. Disruption of surface flow between the two basins during exhumation of the Jishi Shan preceded development of topography sufficient to intercept moisture‐bearing airmasses. Detrital zircon data point to disruption of an eastward‐flowing axial fluvial network between 14.7 and 13.1 Ma, coincident with the onset of exhumation in the Jishi Shan. Flexural modelling suggests that by 13 Ma, the Jishi Shan had developed 0.3 ± 0.1 km of relief; sufficient to disrupt eastward‐flowing drainage networks but insufficient to intercept moisture‐bearing airmasses. Stable isotope data indicate that, although surface connections between the Xunhua and Linxia basins were broken, the two basins continued to be dominated by a common climate regime until 9.3 Ma. Subsequent reintegration of surface flow between the basins occurred between 9.3 and 7.6 Ma. Divergence in the stable isotope and depositional environment records between the two basins suggests that at 9.3 Ma the paleo‐Yellow River breached the growing Jishi Shan dam, and may have reintegrated surface flow between the two basins via erosion of the modern Yellow River gorge, which transects the Jishi Shan. The reintegration of the Xunhua and Linxia basins’ surface connection is confirmed by reintroduction of a Songpan‐Ganzi flysch sediment source by 7.6 Ma. Continued exhumation and uplift of the Jishi Shan developed 0.8 ± 0.2 km of relief by ca. 8 Ma capable of intercepting moisture‐bearing airmasses; isolating and increasing aridity in the Xunhua Basin while decreasing it in the Linxia Basin. Our findings point to protracted development of the modern ca. 1 km of relief in the Jishi Shan between 14 and ca. 4.5 Ma followed by attainment of a topographic equilibrium which persists into modern times.

Background Maturation forms one of the critical seed developmental phases and it is characterized mainly by programmed cell death, dormancy and desiccation, however, the transcriptional programs and regulatory networks underlying acquisition of dormancy and deposition of storage reserves during the maturation phase of seed development are poorly understood in wheat. The present study performed comparative spatiotemporal transcriptomic analysis of seed maturation in two wheat genotypes with contrasting seed weight/size and dormancy phenotype. Results The embryo and endosperm tissues of maturing seeds appeared to exhibit genotype-specific temporal shifts in gene expression profile that might contribute to the seed phenotypic variations. Functional annotations of gene clusters suggest that the two tissues exhibit distinct but genotypically overlapping molecular functions. Motif enrichment predicts genotypically distinct abscisic acid (ABA) and gibberellin (GA) regulated transcriptional networks contribute to the contrasting seed weight/size and dormancy phenotypes between the two genotypes. While other ABA responsive element (ABRE) motifs are enriched in both genotypes, the prevalence of G-box-like motif specifically in tissues of the dormant genotype suggests distinct ABA mediated transcriptional mechanisms control the establishment of dormancy during seed maturation. In agreement with this, the bZIP transcription factors that co-express with ABRE enriched embryonic genes differ with genotype. The enrichment of SITEIIATCYTC motif specifically in embryo clusters of maturing seeds irrespective of genotype predicts a tissue specific role for the respective TCP transcription factors with no or minimal contribution to the variations in seed dormancy. Conclusion The results of this study advance our understanding of the seed maturation associated molecular mechanisms underlying variation in dormancy and weight/size in wheat seeds, which is a critical step towards the designing of molecular strategies for enhancing seed yield and quality. Electronic supplementary material The online version of this article (10.1186/s12870-017-1104-5) contains supplementary material, which is available to authorized users.

To evaluate the use of active controlled motion (ACM) after unstable ankle fractures needing initial partial weight-bearing.Prospective randomized controlled trial.Inpatient and outpatient clinic.A total of 50 patients with unstable ankle fractures and the need for partial weight-bearing for six weeks.Randomization in two groups: physiotherapy alone or physiotherapy with an additional ACM device.Follow-up after 6 and 12 weeks. Range of motion, visual analogue scale for foot and ankle (VAS FA), Philip score, Mazur score, American Orthopaedic FootAnkle Society (AOFAS) score and dynamic pedobarography.Range of motion was better in the ACM group at six weeks (mean 49° ± 11.1° vs. 41.3° ± 8.1°). Questionnaires revealed better outcome after six weeks in the VAS FA (56 ± 13.7 vs. 40.6 ± 10.5), Mazur score (64.4 ± 12.3 vs. 56.7 ± 11) and AOFAS score (71.2 ± 12 vs. 63.6 ± 8.7) ( P0.02 for all). Better outcome after 12 weeks in all questionnaires (VAS FA, 77.7 ± 13.8 vs. 61.4 ± 16.3; Philip score, 79.1 ± 10.9 vs. 60.1 ± 21.7; Mazur score, 83.9 ± 10.7 vs. 73.1 ± 14.1; AOFAS score, 87.5 ± 7.9 vs. 75.2 ± 11.7) ( P0.01 for all). Pressure balance was better under the midfoot region after 12 weeks in the ACM group (Δ P 4.4 N vs. 34.0 N; P = 0.01). The ACM group had an earlier return to work after 10.5 (range, 3-17) versus 14.7 (range, 9-26) weeks ( P = 0.02).The use of ACM for patients needing initial partial weight-bearing after operatively treated unstable ankle fractures in the first six postoperative weeks leads to better clinical and functional results and an earlier return to work.

The authors present a case of monozygotic twins with hereditary hemorrhagic telangiectasia (HHT) who experienced cerebral arteriovenous malformation (AVM) hemorrhage at a very young age. The clinical variables influencing HHT-related AVM rupture are discussed, and questions surrounding the timing of screening and intervention are explored. This is only the second known case of monozygotic HHT twins published in the medical literature, and the youngest pair of first-degree relatives to experience AVM-related cerebral hemorrhage. Evidence guiding the screening and management of familial HHT is lacking, and cases such as this underscore the need for objective and validated protocols.

The present longitudinal study examined growth in fraction knowledge between third and sixth grades (N = 536). Students were administered fraction concepts and procedures measures twice yearly through sixth grade. Analyses revealed empirically distinct growth classes on both measures. Of particular interest were students who started low and made little progress after three years of instruction in fractions, compared to those who started low but made good progress. Poorer language, attention, whole number line estimation, and calculation fluency in third grade significantly increased the odds of membership in a low-growth trajectory class for fraction concepts, while poorer attention and calculation fluency predicted membership in a low-growth trajectory class for fraction procedures. Students classified as receiving special education services in school, many of whom had diagnosed learning disabilities, were 2.5 times more likely to experience low growth in fraction concepts than their peers who were not receiving special education and 11.5 times more likely to experience low growth in fraction procedures. Students with persistent difficulties in fraction knowledge also were much less likely to meet state standards on a mathematics achievement test, portending problems in more advanced mathematics.

Currently trials of immunosuppression in transplantation are in decline because their objectives remain focused on improving acute rejection rates and graft survival in the first 12 months. With 1 year renal graft survival rates of greater than 90% the best that can be hoped for is noninferiority trial outcomes compared with current standard of care. Current trial design is not leading to novel therapies improving long-term outcomes and safety, and hence important unmet clinical needs in transplantation remain unanswered. Issues that need to be addressed include but are not limited to: prevention of subclinical rejection in the first year, better 5- and 10-year graft outcomes, more effective treatment for high immunological risk and sensitized (including donor-specific antibody) patients, immunosuppressive combinations that are better tolerated by patients with fewer side effects and less morbidity and mortality. In September 2015, the Transplantation Society convened a group of transplant clinical trial experts to address these problems. The aims were to substantially realign the priorities of clinical trials for renal transplant immunosuppression with the current unmet needs and to propose new designs for clinical trials for transplant immunosuppression. Moving forward, the transplant community needs to provide trial data that will identify superior treatment options for patient subgroups and allow new agents to be evaluated for efficacy and safety and achieve timely regulatory approval. Trial designs for new transplant immunosuppression must be intelligently restructured to ensure that short- and long-term clinical outcomes continue to improve.

Due to a large and growing collection of genomic and experimental resources, Brachypodium distachyon has emerged as a powerful experimental model for the grasses. To add to these resources we sequenced 21 165 T-DNA lines, 15 569 of which were produced in this study. This increased the number of unique insertion sites in the T-DNA collection by 21 078, bringing the overall total to 26 112. Thirty-seven per cent (9754) of these insertion sites are within genes (including untranslated regions and introns) and 28% (7217) are within 500 bp of a gene. Approximately 31% of the genes in the v.2.1 annotation have been tagged in this population. To demonstrate the utility of this collection, we phenotypically characterized six T-DNA lines with insertions in genes previously shown in other systems to be involved in cellulose biosynthesis, hemicellulose biosynthesis, secondary cell wall development, DNA damage repair, wax biosynthesis and chloroplast synthesis. In all cases, the phenotypes observed supported previous studies, demonstrating the utility of this collection for plant functional genomics. The Brachypodium T-DNA collection can be accessed at http://jgi.doe.gov/our-science/science-programs/plant-genomics/brachypodium/brachypodium-t-dna-collection/.

The vast majority of children with sickle cell anemia (SCA) live in Africa, where evidence-based guidelines for primary stroke prevention are lacking. In Kano, Nigeria, we conducted a feasibility trial to determine the acceptability of hydroxyurea therapy for primary stroke prevention in children with abnormal transcranial Doppler (TCD) measurements. Children with SCA and abnormal non-imaging TCD measurements (≥200 cm/s) received moderate fixed-dose hydroxyurea therapy (∼20 mg/kg/day). A comparison group of children with TCD measurements

The importance of fraction knowledge to later mathematics achievement, along with U.S. students’ poor knowledge of fraction concepts and procedures, has prompted research on the development of fraction learning. In the present study, participants’ (N = 536) development of fraction magnitude understanding and fraction arithmetic skills was assessed over 4 time points between 4th and 6th grades. Latent state-trait modeling was used to examine codevelopment of these 2 areas of fraction knowledge. Fraction arithmetic skill predicted later fraction magnitude understanding, and conversely, fraction magnitude understanding predicted later fraction arithmetic skill. The results are consistent with a bidirectional model of the development of fraction concepts and procedures, in which knowledge of one type facilitates learning of the other type. However, transfer in both directions between fraction arithmetic skill and fraction magnitude understanding was more likely to occur later in the development of fraction knowledge, after fraction arithmetic with unlike denominators had been taught in school (during 5th grade in the current sample). Furthermore, the effects of previous knowledge of the other type were small and not nearly as substantial as the effects of previous knowledge on later knowledge of the same type. Findings suggest a need for instruction to link fraction magnitude understanding to fraction arithmetic skill and vice versa.

The present study investigated the development of fraction comparison strategies through a longitudinal analysis of children's responses to a fraction comparison task in 4th through 6th grades (N = 394). Participants were asked to choose the larger value for 24 fraction pairs blocked by fraction type. Latent class analysis of performance over item blocks showed that most children initially exhibited a "whole number bias," indicating that larger numbers in numerators and denominators produce larger fraction values. However, some children instead chose fractions with smaller numerators and denominators, demonstrating a partial understanding that smaller numbers can yield larger fractions. Latent transition analysis showed that most children eventually adopted normative comparison strategies. Children who exhibited a partial understanding by choosing fractions with smaller numbers were more likely to adopt normative comparison strategies earlier than those with larger number biases. Controlling for general math achievement and other cognitive abilities, whole number line estimation accuracy predicted the probability of transitioning to normative comparison strategies. Exploratory factor analyses showed that over time, children appeared to increasingly represent fractions as discrete magnitudes when simpler strategies were unavailable. These results support the integrated theory of numerical development, which posits that an understanding of numbers as magnitudes unifies the process of learning whole numbers and fractions. The findings contrast with conceptual change theories, which propose that children must move from a view of numbers as counting units to a new view that accommodates fractions to overcome whole number bias. (PsycINFO Database Record

Retinal imaging is a fundamental tool in ophthalmic diagnostics. The potential use of retinal imaging within screening programs, with consequent need to analyze large numbers of images with high throughput, is pushing the digital image analysis field to find new solutions for the extraction of specific information from the retinal image. The aim of this review is to explore the latest progress in image processing techniques able to recognize specific retinal image features. and potential features of disease. In particular, this review aims to describe publically available retinal image databases, highlight different performance evaluators commonly used within the field, outline current approaches in feature-based retinal image analysis, and to map related trends. This review found two key areas to be addressed for the future development of automatic retinal image analysis: fundus image quality and the affect image processing may impose on relevant clinical information within the images. Performance evaluators of the algorithms reviewed are very promising, however absolute values are difficult to interpret when validating system suitability for use within clinical practice.

Histologic analysis of the allograft biopsy specimen is the standard method used to differentiate rejection from other injury in kidney transplants. Donor-derived cell-free DNA (dd-cfDNA) is a noninvasive test of allograft injury that may enable more frequent, quantitative, and safer assessment of allograft rejection and injury status. To investigate this possibility, we prospectively collected blood specimens at scheduled intervals and at the time of clinically indicated biopsies. In 102 kidney recipients, we measured plasma levels of dd-cfDNA and correlated the levels with allograft rejection status ascertained by histology in 107 biopsy specimens. The dd-cfDNA level discriminated between biopsy specimens showing any rejection (T cell-mediated rejection or antibody-mediated rejection [ABMR]) and controls (no rejection histologically), P 1% indicate a probability of active rejection.

Background We report clinical experience with combined heart and kidney transplantation (HKTx) over a 23-year time period. Methods From June 1992 to August 2015, we performed 83 combined HKTx procedures at our institution. We compared the more recent cohort of 53 HKTx recipients (group 2, March 2009 to August 2015) with the initial 30 previously reported HKTx recipients (group 1, June 1992 to February 2009). Pre-operative patient characteristics, peri-operative factors, and post-operative outcomes including survival were examined. Results The baseline characteristics of the two groups were similar, except for a lower incidence of ethanol use and higher pre-operative left-ventricular ejection fraction, cardiac output, and cardiac index in group 2 when compared with group 1 (P = .007, .046, .037, respectively). The pump time was longer in group 2 compared with group 1 (153.30 ± 38.68 vs 129.60 ± 37.60 minutes; P = .007), whereas the graft ischemic time was not significantly different between the groups, with a trend to a longer graft ischemic time in group 2 versus group 1 (195.17 ± 45.06 vs 178.07 ± 52.77 minutes; P = .056, respectively). The lengths of intensive care unit (ICU) and hospital stay were similar between the groups (P = .083 and .39, respectively). In addition, pre-operative and post-operative creatinine levels at peak, discharge, 1 year, and 5 years and the number of people on post-operative dialysis were similar between the groups (P = .37, .75, .54, .87, .56, and P = .139, respectively). Overall survival was not significantly different between groups 2 and 1 for the first 5 years after transplant, with a trend toward higher survival in group 2 (P = .054). Conclusions The most recent cohort of combined heart and kidney transplant recipients had similar ICU and hospital lengths of stay and post-operative creatinine levels at peak, discharge, and 1 and 5 years and a similar number of patients on post-operative dialysis when compared with the initial cohort. Overall survival was not significantly different between the later and earlier groups, with a trend toward higher overall survival at 5 years in the more recent cohort of patients. In selected patients with co-existing heart and kidney failure, combined heart and kidney transplantation is safe to perform and has excellent outcomes.

PURPOSE To compare cerebrovascular reactivity (CVR) and CVR lagtimes in flow territories perfused by vessels with vs. without proximal arterial wall disease and/or stenosis, separately in patients with atherosclerotic and nonatherosclerotic (moyamoya) intracranial stenosis. MATERIALS AND METHODS Atherosclerotic and moyamoya patients with >50% intracranial stenosis and