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Our understanding of the cell behaviours and cytoskeletal requirements of axon formation is largely derived from in vitro models but how these relate to axon formation in vivo is not clear. In vitro, neurons progress through a well‐defined multineurite stage to form an axon and both actin and microtubules cooperate to drive the first steps in neurite and axon morphogenesis. However, these steps are not recapitulated in vivo, and it is not clear whether the underlying cell biological mechanisms may differ also. Here, we investigate the mechanisms that regulate axon formation in embryonic zebrafish spinal neurons in vivo. We find microtubule organising centres are located distant from the site of axon initiation, and microtubule plus‐ends are not enriched in the axon during axon initiation. Focal F‐actin accumulation precedes axon formation, and we find that nocodazole‐treated neurons with no detectable microtubules are still able to form nascent axonal protrusions that are approximately 10‐μm long, dilated and relatively long‐lived. We suggest spinal axon formation in vivo is fundamentally different from axon formation in in vitro models. Synopsis: In vivo imaging of embryonic zebrafish neurons defines early morphological events of axon initiation and shows focal F‐actin is likely the major cytoskeletal player, while microtubules are not required for nascent axon formation. In vivo imaging reveals stereotypical behaviours of nascent axon formation in embryonic spinal neurons.Nascent axon formation is preceded by local F‐actin accumulation but no local enrichment of microtubules.Local F‐actin accumulation and nascent axon formation still occur in the presence of nocodazole treatment that eliminates detectable microtubules. [ABSTRACT FROM AUTHOR]

Summary: Treating adverse risk myelodysplastic syndromes with azacitidine exacerbates thrombocytopenia. We report a study of eltrombopag in combination with azacitidine using a 3 + 3 cohort design. Patients with baseline platelets of <150 × 109/l received eltrombopag ranging from 25 to 300 mg. An 8‐day pre‐phase of eltrombopag was followed by two cycles of combined therapy. Amongst 31 patients, there were no dose‐limiting toxicities. The maximum tolerated dose (MTD) was 300 mg. Transient increases in bone marrow blasts at day 8 were common but no patient had protocol‐defined progression following eltrombopag monotherapy. Marrow response rates after three and six treatment cycles were 32% and 29% respectively. In all, 70% of patients treated below and 36% treated at the MTD achieved a modified International Working Group 2006 platelet response at the end of cycle two. Of the platelet transfusion independent patients at baseline, 67% treated at the MTD became transfusion dependent during the first two cycles of treatment. Apart from lack of disease progression, our findings concur with a previously reported Phase III study (A StUdy of eltromboPag in myelodysPlastic SyndrOmes Receiving azaciTidine [SUPPORT]). We conclude that eltrombopag/azacitidine is safe in terms of conventional measures defined by adverse‐event reporting. However, in light of SUPPORT and our own descriptive findings regarding efficacy, further combination studies in high‐risk disease should be considered with caution. [ABSTRACT FROM AUTHOR]

Previous studies have identified regions where the occurrence of rainfall significantly increases or decreases the probability for subsequent rainfall over periods that range from a few days to several weeks. These observable phenomena are termed "rainfall feedback" (RF). To better understand the land--atmosphere interactions involved in RF, the behavior of RF patterns was analyzed using data from 1849 to 2016 at ~3000 sites in the contiguous United States. We also considered changes in major land-use types and applied a geographically weighted regression model technique for analyzing the predictors of RF. This approach identified non-linear and spatially nonstationary relationships between RF, climate, land use, and land type. RF patterns in certain regions of the United States are predictable by modeling variables associated with climate, season, and land use. The model outputs also demonstrate the extent to which the effect of precipitation, temperature, and land use on RF depend on season and location. Specifically, major changes were observed for land use associated with agriculture in the western United States, which had negative and positive influences on RF in summer and winter, respectively. In contrast, developed land in the eastern United States correlated with positive RF values in summer but with negative ones in winter. We discuss how changes in climate and land use would be expected to affect land-- atmosphere interactions, as well as the possible role that physical mechanisms and rain-enhanced bioaerosol emissions may play in the spatiotemporal changes observed for historical patterns of rainfall frequency in the United States. [ABSTRACT FROM AUTHOR]

Objective: A new diagnosis of pediatric cancer may disrupt family functioning. The current study aimed to describe changes in family rules and routines during the first year of pediatric cancer treatment, and to explore associations with demographics, illness factors, and caregiver distress. Methods: This exploratory mixed‐methods, cross‐sectional study examined 44 primary caregivers of youth in treatment for a new cancer diagnosis in 2019 and 2020, before the onset of the COVID‐19 pandemic. Caregivers completed validated questionnaires assessing demographic and child illness characteristics, psychosocial distress, and cancer‐related stressors, and participated in a semi‐structured interview about family rules and routines. Results: Caregivers reported changes in bedtime, mealtime, and school routines, relaxed behavioral expectations and rules around screen time, and new rules and routines around treatment, medications, and infection control. Caregivers with elevated levels of psychosocial distress reported more changed routines than caregivers with low levels of psychosocial distress. Caregivers who endorsed more cancer‐related stressors reported more new rules and routines than those who reported fewer cancer‐related stressors. Demographic and illness factors were not significantly associated with the number of changed, new, or stable family rules and routines. Conclusions: Families may relax rules and routines during the first several months of diagnosis, and this may be related to side effects of treatment and limited caregiver capacity. The long‐term impact of changes in family rules and routines during cancer treatment warrants further study given that accommodating parenting strategies have been associated with adverse short‐ and long‐term child health and behavior outcomes. [ABSTRACT FROM AUTHOR]

Lesbian, gay, bisexual, and queer (LGBQ) young people from religious families are at increased risk of family rejection, poor mental health outcomes, and are overrepresented in mental health services. This article describes a two-part qualitative study aimed at exploring the experiences of LGBQ young adults from religious families in psychotherapy, identifying positive and negative psychotherapy experiences, and understanding the influence of family and religion on the psychotherapy experience. Data were collected through a web-based survey (n = 77) and interviews (n = 7) with LGBQ young adults (ages 18-25) from religious families. The study followed an interpretative phenomenological approach. Integrated results found often invisible, relational therapy processes, and religious discourses as significant to LGBQ young people who seek psychotherapy. Implications for future research, effective systemic family therapy practices with LGBQ young people from religious families, and a critique on ethical and legal limits of confidentiality with policy implications are outlined. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lesbian, gay, bisexual, and questioning (LGBQ) adolescents are at increased risk of poor mental health due to minority stress, a chronic stress associated discrimination, social rejection, and victimization brought on by prejudicial attitudes towards LGBQ individuals. To improve understanding of the differential impact of various kinds of victimization on mental health outcomes for LGBQ adolescents, we analyzed data from the 2015 Youth Risk Behavior Survey (YRBS) for victimization and mental health symptom clusters and associations high school youth and compared by sexual orientation and gender. METHODS: Separate Latent Class Analysis (LCA) was conducted to identify profiles of both victimization and mental health symptoms for participants (N = 15,624). Subsequently, stratified weighted logistic regression models were used on an eligible analytic sample of 11,458 to assess differences in the association of victimization and mental health between LGBQ and heterosexual high school students. RESULTS: In each LCA, participants were assigned to one of 3 classes for victimization (minimal, 81.3%; bullying, 12.5%; or physical/sexual violence, 6.2%) and 1 of 2 classes for mental health symptoms (minimal, 81.2%; severe, 18.8%). LGBQ participants were overrepresented in physical/sexual violence and bullying victimization profiles. Both bullying and physical/sexual violence profiles were associated with almost 5 times the odds of endorsing severe mental health symptoms. Conclusions: This study expands our understanding of the relationship between types and effect of peer victimization for LGBQ and heterosexual youth with implications for school health and prevention efforts through increased positive school climate for LGBQ students. [ABSTRACT FROM AUTHOR]

Background: There are no studies that have assessed the implant stability quotient (ISQ) values of narrow diameter implants placed in artificial dense bone blocks at varying drilling speeds (DSs). Purpose: The aim of the present in vitro experiment was to compare the performance of OSSTELL and Penguin devices to evaluate implant stability at DSs of 800 and 2000 rpm. Materials and Methods: A total of 360 osteotomies were created in dense artificial bone blocks at DSs of 800 and 2000 rpm. Dental implants from three manufacturers (group‐1: NobelActive implants, Nobel Biocare, Yorba Linda, California; group‐2: Zimmer, Eztetic‐Zimmer implants, Zimmer Biomet Dental, Palm Beach Gardens, Florida; and group‐3: Astra Tech implant system, Dentsply Sirona, York, Pennsylvania) were randomly placed in these osteotomies using an insertion torque of 15 Ncm (60 implants/group). Implant stability in all bone blocks immediately following implant placement was evaluated using the OSSTELL and Penguin devices. ISQ values were presented as means ± SD. Statistical significance was set at P < .05. Results: There was no significant difference in the ISQ values obtained from the OSSTELL and Penguin devices for implants in groups 1, 2, and 3. There was no significant difference when ISQ values obtained from the OSSTELL device were compared with the Penguin device for narrow diameter dental implants placed in dense bone blocks with osteotomies performed at 800 and 2000 rpm. ISQ values showed statistically significant higher values for OSSTELL compared to Penguin device. Conclusion: The OSSTELL and Penguin devices are reliable for the assessment of implant stability in dense artificial bone. Implant design and site‐DS does not seem to have a significant impact of implant stability in artificial dense bone blocks. [ABSTRACT FROM AUTHOR]

Background There is a need for mentoring interventions in which transition-age youth and young adults with intellectual and/or developmental disabilities (I/ DD) participate as both mentors and mentees. Project TEAM (Teens making Environment and Activity Modifications) is a problem-solving intervention that includes an electronic peer-mentoring component. Methods Forty-two mentees and nine mentors with I/ DD participated. The present authors analysed recorded peer-mentoring calls and field notes for mentee engagement, mentor achievement of objectives and supports needed to implement peer mentoring. Results Overall, mentees attended 87% of scheduled calls and actively engaged during 94% of call objectives. Across all mentoring dyads, mentors achieved 87% of objectives and there was a significant relationship between the use of supports (mentoring script, direct supervision) and fidelity. Conclusions Transition-age mentees with I/ DD can engage in electronic peer mentoring to further practice problem-solving skills. Mentors with I/ DD can implement electronic peer mentoring when trained personnel provide supports and individualized job accommodations. [ABSTRACT FROM AUTHOR]

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Unfamiliar face matching is the process of simultaneously verifying the equivalence of two faces. Accuracy within this task is crucial given its importance and prevalence in security domains. However, research has consistently demonstrated that unfamiliar face matching is error prone, suggesting the need for improvement techniques. Motivational incentives have been shown to reliably enhance performance on a wide array of cognitive tasks. Therefore, the current study examined the effect of motivational incentives on unfamiliar face matching. Experiment 1 showed increased accuracy in mismatch trials with the addition of a motivational incentive. The improvement was associated with an increase in reaction time and bias towards making a mismatch response. This bias, however, did not produce a decrease in accuracy on match trials. Experiment 2 replicated this result with a more ecologically valid methodology. The results suggest motivational incentives to be effective at improving performance on mismatch trials, arguably the most important aspect of real-world unfamiliar face matching. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: The function of holocytochrome c synthase (HCCS, also called heme lyase) is to attach covalently the heme cofactor to cytochromes c in the mitochondria of animals, fungi and protozoa. Little is known about how the protein functions but CP motifs, commonly found in heme-binding proteins, are present. Here we examine holocytochrome c production by Saccharomyces cerevisiae HCCS in the Escherichia coli cytoplasm with emphasis on the conserved CP motifs long implicated in heme transfer by this enzyme. Unexpectedly, the two motifs, both towards the N-terminus, were not required for activity. Mutations in HCCS on the C-terminal side of the CP motifs, known to cause disease states in humans (microphthalmia with linear skin defects) abolished or drastically attenuated holocytochrome c production. [Copyright &y& Elsevier]

Purpose: To measure uterine artery and vein blood velocity and flow rate profiles using MRI during normal pregnancy. Materials and Methods: A two-shot velocity magnitude-encoded echo planar imaging (EPI) sequence is used at a magnetic field 0.5T. Data analysis procedures, necessary to overcome problems associated with low signal to noise ratio (SNR), and a spatial resolution comparable to the vessel size were used. Results: The measured blood flow values averaged over nine volunteers for the mean velocity are 5.33 and 3.97 cm/s and for the unilateral flow rate are 203 and 274 mL/min (for the arteries and veins respectively). Values for the flow rate are consistent with ultrasound Doppler studies. Arterial velocity measurements are more pulsatile than venous ones and validation calculations performed on average velocity values would suggest that the nature of blood flow in the uterine vessels is laminar. Conclusion: This study presents the first report of noninvasive quantitative measurements of uterine artery and vein blood velocity and flow rate profiles using MRI during normal pregnancy. Consistent and reproducible measurements have been obtained by subject specific sequence optimization and data analysis procedures. J. Magn. Reson. Imaging 2010;31:921-927. ©2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

The aim of this work was to use intravoxel incoherent motion (IVIM) to provide a non-invasive in vivo assessment of the function of the maternal spiral arteries that feed the placenta in normal pregnancy and in pre-eclampsia. Eleven normal pregnant women were scanned at 16, 22, 29 and 35 weeks gestation in a longitudinal study. Nine normal pregnant women and six women with pre-eclampsia were scanned in a cross-sectional study, within 10 days of delivery. The MRI IVIM technique was used to measure the moving blood fraction (f%) at the basal plate. There was no evidence that f% changed with gestational age (P = 0.84), but considering the cross-sectional groups, f% in women with pre-eclampsia was reduced compared with normal pregnancy (mean ± SD: 36 ± 5% and 27 ± 5%; P < 0.005). In conclusion, pregnancies complicated by pre-eclampsia exhibit a reduced fraction of moving blood within the region of the spiral arteries. IVIM performed in the mid-trimester may provide an early means of predicting those pregnancies with an increased likelihood of being complicated by pre-eclampsia. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A new synziphosurine, Anderella parva gen. et sp. nov., extends the known range of this group from the Silurian to the Carboniferous and is the youngest known so far from the fossil record. Previously the youngest synziphosurine, Kasibelinurus, was from the Devonian of North America. Anderella parva has a semi-oval carapace with pointed genal regions, nine freely articulating opisthosomal segments and a long styliform tail spine. It is the third xiphosuran genus to be described from the Bear Gulch Limestone and its discovery highlights this deposit as containing an unusually diverse xiphosuran biota. It is also the only known locality where synziphosurines occur alongside the more derived xiphosurids. Xiphosurans reached their greatest diversity in the Carboniferous when the xiphosurids began to occupy brackish and freshwater habitats and became dominant over the synziphosurines. The discovery of the only known Carboniferous synziphosurine in marine sediments may indicate their inability to exploit these same environments. [ABSTRACT FROM AUTHOR]

To compare fetal organ size measured using echo-planar magnetic resonance imaging and 2D ultrasound. To determine the relative accuracy with which each technique can predict fetal growth restriction.A cross sectional, observational study comparing two different measurement techniques against a gold standard, in a normal clinical population and an abnormal population.Seventy-four pregnant women (33 who were ultimately found to be normal and 37 with fetal growth restricted fetuses) were recruited from the City Hospital Nottingham UK to be scanned once (at various gestations).Each fetus had a standard ultrasound biometry assessment followed by magnetic resonance imaging measurement of organ volumes.For each measurement for both techniques, the normal population was plotted with 90% confidence intervals. Fetal growth restricted subjects were compared with the normal population using this plot; 2× 2 tables were created for each measurement. This was used to calculate the relative sensitivities and positive predictive value of the different measurements. A Bland–Altman plot was used to compare the ultrasound and magnetic resonance imaging measurements of fetal weight.Brain sparing was seen in ultrasonic head circumference measurements, but an overall reduction in fetal growth restriction brain volume was apparent using magnetic resonance imaging at late gestations. Across the whole range of gestational ages, ultrasound assessment of fetal weight was the best predictor of fetal growth restriction.Ultrasound fetal weight assessment appears to identify more fetuses with fetal growth restriction than abdominal circumference. The brain sparing apparent in ultrasonic head circumference measurements of fetuses with fetal growth restriction masks a reduction in brain volume observed with magnetic resonance imaging. [ABSTRACT FROM AUTHOR]

Previous studies have demonstrated the practicality of using functional magnetic resonance imaging (fMRI) techniques to assess fetal brain activity. The purpose of this study was to compare the fetal hemodynamic response to that of the adult. Seventeen pregnant subjects, all of whom were at more than 36 weeks gestation were scanned while the fetus was exposed to a vibroacoustic stimulus. Thirteen adult subjects were scanned with an equivalent acoustic stimulus. Of the fetal subjects, two could not be analyzed due to technical problems, eight did not show significant activation, and seven showed significant activation. In all cases, activation was localized within the temporal region. Measures of fetal hemodynamic responses revealed an average time to peak (ttp) of 7.36 ± 0.94 sec and an average percentage change of 2.67 ± 0.93%. In contrast, activation was detected in 5 of 13 adults with an average ttp of 6.54 ± 0.54 sec and an average percentage change of 1.02 ± 0.40%. The measurement of changes in the fetal hemodynamic response may be important in assessing compromised pregnancies. Hum. Brain Mapping 22:118-123, 2004. © 2004 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

: Objectives(1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response.: MethodsWomen with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin.: ResultsPre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate.: ConclusionWe confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion. [Copyright &y& Elsevier]

Objectives: To compare fetal organ size measured using echo-planar magnetic resonance imaging and 2D ultrasound. To determine the relative accuracy with which each technique can predict fetal growth restriction., Design: A cross sectional, observational study comparing two different measurement techniques against a gold standard, in a normal clinical population and an abnormal population., Setting and Population: Seventy-four pregnant women (33 who were ultimately found to be normal and 37 with fetal growth restricted fetuses) were recruited from the City Hospital Nottingham UK to be scanned once (at various gestations)., Methods: Each fetus had a standard ultrasound biometry assessment followed by magnetic resonance imaging measurement of organ volumes., Main Outcome Measures: For each measurement for both techniques, the normal population was plotted with 90% confidence intervals. Fetal growth restricted subjects were compared with the normal population using this plot; 2 x 2 tables were created for each measurement. This was used to calculate the relative sensitivities and positive predictive value of the different measurements. A Bland-Altman plot was used to compare the ultrasound and magnetic resonance imaging measurements of fetal weight., Results: Brain sparing was seen in ultrasonic head circumference measurements, but an overall reduction in fetal growth restriction brain volume was apparent using magnetic resonance imaging at late gestations. Across the whole range of gestational ages, ultrasound assessment of fetal weight was the best predictor of fetal growth restriction., Conclusion: Ultrasound fetal weight assessment appears to identify more fetuses with fetal growth restriction than abdominal circumference. The brain sparing apparent in ultrasonic head circumference measurements of fetuses with fetal growth restriction masks a reduction in brain volume observed with magnetic resonance imaging.

Objectives: (1) To investigate a possible association between myometrial and placental artery vasoreactivity and perfusion at the basal and chorionic plates, respectively. (2) To confirm that myometrial arteries from women with pre-eclampsia and intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response., Methods: Women with normal pregnancy, pre-eclampsia and intrauterine growth restriction had a magnetic resonance scan to assess placental perfusion using a technique called intravoxel incoherent motion. At delivery, myometrial and chorionic plate placental arteries were assessed on a wire myograph. Vessels were pre-constricted with the thromboxane mimetic U46619 and dilated with incremental doses of bradykinin., Results: Pre-constricted myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibited an attenuated vasodilatory response to bradykinin, compared with normal pregnancy (P < 0.0001). Pre-constricted placental arteries exhibited a minimal vasodilatory response in all three groups of women (P = 0.10). Maximal constrictor and vasodilatory responses of myometrial arteries were not associated with the perfusing fraction at the basal plate. Maximal constrictor and vasodilatory responses of chorionic plate placental arteries were not associated with the perfusing fraction at the chorionic plate., Conclusion: We confirm that myometrial arteries from women with pre-eclampsia or intrauterine growth restriction exhibit an attenuated endothelium-dependent vasodilatory response. Apart from vasoreactivity of small arteries, other factors may be involved in the control of placental perfusion.