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Untreated congenital hypothyroidism (CH) leads to intellectual disabilities. Newborn screening (NBS) for CH should be performed in all infants. Prompt diagnosis by NBS leading to early and adequate treatment results in grossly normal neurocognitive outcomes in adulthood. However, NBS for hypothyroidism is not yet practiced in all countries globally. Seventy percent of neonates worldwide do not undergo NBS. The recommended initial treatment of CH is levothyroxine, 10 to 15 mcg/kg daily. The goals of treatment are to maintain consistent euthyroidism with normal thyroid-stimulating hormone and with free thyroxine in the upper half of the age-specific reference range during the first 3 years of life. Controversy remains regarding the detection of thyroid dysfunction and optimal management of special populations, including preterm or low-birth-weight infants and infants with transient or mild CH, trisomy 21, or central hypothyroidism. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis, accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Physicians need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism are present (such as large posterior fontanelle, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/ or hypothermia), measurement of serum thyroid-stimulating hormone and free thyroxine is indicated, regardless of NBS results. [ABSTRACT FROM AUTHOR]

Background: Recurrent head and neck squamous cell carcinoma (HNSCC) is associated with poor overall survival (OS). Prior studies suggested incorporation of nab-paclitaxel (A) may improve outcomes in recurrent HNSCC.Methods: This Phase I study evaluated induction with carboplatin and A followed by concomitant FHX (infusional 5-fluorouracil, hydroxyurea and twice-daily radiation therapy administered every other week) plus A with cohort dose escalation ranging from 10-100 mg/m2 in recurrent HNSCC. The primary endpoint was maximally tolerated dose (MTD) and dose-limiting toxicity (DLT) of A when given in combination with FHX (AFHX).Results: Forty-eight eligible pts started induction; 28 pts started AFHX and were evaluable for toxicity. Two DLTs occurred (both Grade 4 mucositis) at a dose level 20 mg/m2. No further DLTs were observed with subsequent dose escalation. The MTD and recommended Phase II dose (RP2D) of A was 100 mg/m2.Conclusions: In this Phase I study, the RP2D of A with FHX is 100 mg/m2 (AFHX). The role of re-irradiation with immunotherapy warrants further investigation.Clinical Trial Information: This clinical trial was registered with ClinicalTrials.gov identifier: NCT01847326. [ABSTRACT FROM AUTHOR]

Let Ω ⊂ R 2 be an unbounded convex domain. It is proven in López (J Diff Equ 171:54–62, 2001) and Ripoll (Pac J Math 198(1):175–196, 2001) that, given H > 0 , there exists a graph G ⊂ R 3 of constant mean curvature H over Ω with ∂ G = ∂ Ω if and only if Ω is included in a strip of width 1/H. In this paper we obtain results in H 2 × R in the same direction: given H ∈ 0 , 1 / 2 , if Ω is included in a region of H 2 × 0 bounded by two hypercircles equidistant ℓ (H) to a same geodesic, we show that, if the geodesic curvature of ∂ Ω is bounded from below by - 1 , then there is an H-graph G over Ω with ∂ G = ∂ Ω . We also present more refined existence results involving the curvature of ∂ Ω , which can also be less than - 1. [ABSTRACT FROM AUTHOR]

Ice friction plays an important role in many engineering applications, e.g., tires on icy roads, ice breaker ship motion, or winter sports equipment. Although numerous experiments have already been performed to understand the effect of various conditions on ice friction, to reveal the fundamental frictional mechanisms is still a challenging task. This study uses in situ white light interferometry to analyze ice surface topography during linear friction testing with a rubber slider. The method helps to provide an understanding of the link between changes in the surface topography and the friction coefficient through direct visualization and quantitative measurement of the morphologies of the ice surface at different length scales. Besides surface polishing and scratching, it was found that ice melts locally even after one sweep showing the refrozen droplets. A multi-scale rubber friction theory was also applied to study the contribution of viscoelasticity to the total friction coefficient, which showed a significant level with respect to the smoothness of the ice; furthermore, the theory also confirmed the possibility of local ice melting. [ABSTRACT FROM AUTHOR]

Single ventricle patients typically undergo some form of advanced diagnostic imaging prior to superior cavopulmonary connection (SCPC). We sought to evaluate variability of diagnostic practice and associated comprehensive risk. A retrospective evaluation across 4 institutions was performed (1/1/2010–9/30/2016) comparing the primary modalities of cardiac catheterization (CC), cardiac magnetic resonance (CMR), and cardiac computed tomography (CT). Associated risks included anesthesia/sedation, vascular access, total room time, contrast agent usage, radiation exposure, and adverse events (AEs). Of 617 patients undergoing SCPC, 409 (66%) underwent at least one advanced diagnostic imaging study in the 60 days prior to surgery. Seventy-eight of these patients (13%) were analyzed separately because of a concomitant cardiac intervention during CC. Of 331 (54%) with advanced imaging and without catheterization intervention, diagnostic CC was most common (59%), followed by CT (27%) and CMR (14%). Primary modality varied significantly by institution (p < 0.001). Median time between imaging and SCPC was 13 days (IQR 3–33). Anesthesia/sedation varied significantly (p < 0.001). Pre-procedural vascular access did not vary significantly across modalities (p = 0.111); procedural access varied between CMR/CT and CC, in which central access was used in all procedures. Effective radiation dose was significantly higher for CC than CT (p < 0.001). AE rate varied significantly, with 12% CC, 6% CMR, and 1% CT (p = 0.004). There is significant practice variability in the use of advanced diagnostic imaging prior to SCPC, with important differences in associated procedural risk. Future studies to identify differences in diagnostic accuracy and long-term outcomes are warranted to optimize diagnostic protocols. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) has a favorable prognosis which has led to efforts to de-intensify treatment. Response-adaptive de-escalated treatment is promising, however improved biomarkers are needed. Quantitative cell-free HPV-DNA (cfHPV-DNA) in plasma represents an attractive non-invasive biomarker for grading treatment response and post-treatment surveillance. This prospective study evaluates dynamic changes in cfHPV-DNA during induction therapy, definitive (chemo)radiotherapy, and post-treatment surveillance in the context of risk and response-adaptive treatment for HPV + OPC.Methods: Patients with locoregional HPV + OPC are stratified into two cohorts: High risk (HR) (T4, N3, [Formula: see text] 20 pack-year smoking history (PYH), or non-HPV16 subtype); Low risk (LR) (all other patients). All patients receive induction chemotherapy with three cycles of carboplatin and paclitaxel. LR with ≥ 50% response receive treatment on the single-modality arm (minimally-invasive surgery or radiation alone to 50 Gy). HR with ≥ 50% response or LR with ≥ 30% and < 50% response receive treatment on the intermediate de-escalation arm (chemoradiation to 50 Gy with cisplatin). All other patients receive treatment on the regular dose arm with chemoradiation to 70 Gy with concurrent cisplatin. Plasma cfHPV-DNA is assessed during induction, (chemo)radiation, and post-treatment surveillance. The primary endpoint is correlation of quantitative cfHPV-DNA with radiographic response.Discussion: A de-escalation treatment paradigm that reduces toxicity without compromising survival outcomes is urgently needed for HPV + OPC. Response to induction chemotherapy is predictive and prognostic and can select candidates for de-escalated definitive therapy. Assessment of quantitative cfHPV-DNA in the context of response-adaptive treatment of represents a promising reliable and convenient biomarker-driven strategy to guide personalized treatment in HPV + OPC.Trial Registration: This trial is registered with ClinicalTrials.gov on October 1st, 2020 with Identifier: NCT04572100 . [ABSTRACT FROM AUTHOR]

For any non-negative integers v > k > i , the generalized Johnson graph, X = J (v , k , i) , is the graph whose vertices are the k -subsets of a v -set, and where any two vertices A and B are adjacent whenever | A ∩ B | = i. In this note, we prove that if v ≥ 2 k and (v , k , i) ≠ (2 k , k , 0) , then the odd girth of X is given by: o g (X) = 2 ⌈ k − i v − 2 k + 2 i ⌉ + 1. [ABSTRACT FROM AUTHOR]

See the response from Galizia et al. in this issue. [ABSTRACT FROM AUTHOR]

Trees, among the world's oldest creatures, seem to be having a moment. Not only have researchers made fascinating discoveries about their "secret lives," these ubiquitous superorganisms have sparked the culture's imagination as well. Trees have recently been the subject of best-selling novels, essays, and high-impact films. While most human beings would be hard pressed to name any species of tree they might encounter in their daily lives, talk about trees is becoming more and more mainstream. And logically so. The more modern technology severs our ties to the physical world—and, no less importantly, the more climate change signals the impending disappearance of that world—the more urgency we feel to reconnect. This article explores how contemporary French culture summons us to do just that. Through an exploration of a few of the most compelling recent works that testify to what I call the "arboreal imaginary" in contemporary French culture, this article posits that attending to trees in works of art is a necessarily ecological gesture, one that encourages us to think about our stewardship of the environment as much as it invites us to consider novel ways of poetically inhabiting the planet. [ABSTRACT FROM AUTHOR]

Laying hens usually have 16 h of light and 8 h of darkness during egg laying, with eggshell formation primarily occurring during darkness when dietary calcium is lacking, leading to bone calcium resorption and osteoporosis. This study examined how interrupting the dark phase affects bone health in 396 Hy-line W36 hens assigned to control (C) or treatment groups (W1 and W2). All hens received 16 h of light and 8 h of darkness daily in different variations of scotophase interruption. Blood samples were taken at weeks 20, 30, 50, and 70, serum calcium was measured during darkness at two timepoints (SRT and END), and bone demineralization markers were examined using enzyme concentrations (TRACP-5b and CTX-I). Across weeks, tibias were CT-scanned for density (mg/cm3) and area (mm2), then used for breakage strength analysis (N) and ash%. No SRT Ca level differences emerged, but C hens had lower END Ca levels compared to W1 and W2 hens across all weeks, while W1 and W2 hens showed no significant differences. C hens displayed higher TRACP-5b and CTX-I concentrations across all weeks compared to W1 and W2 (all p ≤ 0.05). At week 70, C hens had the lowest cortical bone cross-sectional area and mineral density compared to W1 and W2 (all p ≤ 0.05). Tibiotarsi bone breakage strength was lower in C hens compared to W1 and W2. C hens had significantly lower ash% than treatment birds. Interrupting the scotophase period improved overall bone health in Hy-line W36 laying hens. [ABSTRACT FROM AUTHOR]

Background: We aimed to compare cone beam computed tomography (CBCT) utilization and radiation exposure during prostatic artery embolization (PAE) procedures on two different angiography systems. Methods: PAEs performed by a single interventionalist between January 2018 and October 2020 on two multivendor angiography systems (AS1 and AS2) at a single center were retrospectively evaluated. Imaging techniques included CBCT acquisition when possible, predominantly from the distal aorta in AS1 and from the bilateral internal iliac arteries in AS2 (Discovery IGS 740, GE HealthCare, Chicago, IL). Baseline demographics, CBCT utilization and radiation doses, and total procedure radiation metrics for each group were collected and compared. Results: One hundred and twenty patients were analyzed in this study, with fifty-three patients (n = 25 in AS1, 28 in AS2) included as embolized bilaterally using CBCT. CBCT was acquired in 31% of the cases in AS1 and in 85% of the cases in AS2. Mean prostate volume was similar in both groups (103.0 mL vs. 130.1 mL, p = 0.23). There was no difference in fluoroscopy time, while the number of DSA series and CBCTs per case did differ in AS1 and AS2 (37.3 min vs. 32.1 min, p = 0.13, 19.8 vs. 8.0, p ≤ 0.001, 1.3 vs. 2.1 p ≤ 0.001). The mean total air kerma, total kerma area product and air kerma per CBCT were higher in AS1 compared to AS2 (2020.4 mGy vs. 490.3 mGy, p ≤ 0.001, 259.3 Gy*cm2 vs. 72.7 Gy*cm2, p ≤ 0.001 and 217.8 mGy vs. 45.8 mGy, p ≤ 0.001 respectively). To prevent confounding from a mean difference in body mass index, the data were adjusted using log outcome means, which corroborated the raw data findings. Conclusions: The mean procedural total kerma area product from AS1 was similar to that reported in other PAE studies, but it was substantially lower in AS2. The angiography system used has a significant impact on the ability to leverage CBCT and on overall patient and thus staff radiation exposure. [ABSTRACT FROM AUTHOR]

Recently, we suggested the idea of an optical superlens based on the extraordinary dispersion properties of plasmonic nanochains. In the present paper we discuss the results of numerical simulations of the imaging of point sources in this superlens. The simulations show that sub-wavelength resolution can be obtained in much thicker structures than usual. A distance of nearly λ/2 between the source and the image plane is achieved. In addition the effects of stochastic deviations in geometrical parameters are studied. [ABSTRACT FROM AUTHOR]

This scientific commentary refers to 'Socioeconomic disparity is associated with faster retinal neurodegeneration in multiple sclerosis' by Vasileiou I et al i . In this issue of I Brain i , Vasileiou and co-authors[2] use OCT to precisely quantify neuro-axonal atrophy in multiple sclerosis and thereby assess whether socioeconomic factors are associated with more rapid damage to neurons and their processes. [Extracted from the article]

Introduction: While most people believe the nasal septum to have intrinsic deviation and overgrowth in patients seeking rhinoplasty, an alternative concept is that a mal-oriented premaxilla causes extrinsic septal buckling and external extrusion of the septal cartilage. In this sense, the premaxillary bone plays a significant role in the pathogenesis of septal deviation. This study was performed to determine if non-traumatically acquired septal/nasal functional and aesthetic pathology or septal deviation may be related to the orientation of the premaxilla relative to the skullbase. Methods: A retrospective, single-center study of patients in the general population who underwent maxillofacial CT scans and presented for the evaluation of nasal obstruction. CT scans were used to measure features of both pathologic and non-pathologic nasal septums. Results: A total of 68 subjects were evaluated. When comparing patients with a premaxillary-skullbase angle of greater than 81° (the mean of the study group) to those of less than 81°, and a more obtuse nasolabial angle was observed (p = 0.0269). When comparing the extremes of premaxillary rotation, specifically, greater than 87° (mean 91.7°, SD 5.1) and less than 77° (mean 70.7°, SD 3.6), the differences were more pronounced with regard to caudal septal excess (p = 0.0451) and septal deviation in the axial plane (p = 0.0150). Conclusion: Septal developmental changes may involve an overly rotated or more vertically oriented premaxillary bone relative to the skull base. An understanding of the cause of septal deformity may provide insight into the design of improved treatments. [ABSTRACT FROM AUTHOR]

Controversy exists over the use of brief Big Five scales in health studies. We investigated links between an ultra-brief measure, the Big Five Inventory-10, and mortality in the General Social Survey. The Agreeableness scale was associated with elevated mortality risk (hazard ratio = 1.26, p =.017). This effect was attributable to the reversed-scored item "Tends to find fault with others," so that greater fault-finding predicted lower mortality risk. The Conscientiousness scale approached meta-analytic estimates, which were not precise enough for significance. Those seeking Big Five measurement in health studies should be aware that the Big Five Inventory-10 may yield unusual results. [ABSTRACT FROM AUTHOR]

A 60-year-old woman with a history of hypertrophic obstructive cardiomyopathy, paroxysmal atrial fibrillation, and metastatic rectal cancer presented to the emergency department with new-onset respiratory distress. The admission ECG is shown in Figure 1A. Given frequent rhythm changes noted on telemetry after intravenous diuresis and continuation of her home medications, a repeat ECG was ordered (Figure 1B). The presenting ECG (Figure 1A) shows regularized atrial fibrillation with ventricular bigeminy, whereas the second ECG (Figure 1B) is consistent with bidirectional ventricular tachycardia (BVT). [Extracted from the article]

Objective: To investigate whether observed interactions of mindfulness with the personality trait neuroticism extend to older adults and to aspects of psychological functioning other than depressive symptoms, and whether effects of mindfulness training in this population depend on levels of neuroticism. Method: We performed a secondary analysis of data from a randomized controlled trial of Mindfulness-Based Stress Reduction (MBSR) for community-dwelling older adults. We investigated whether neuroticism moderates associations of dispositional mindfulness with various aspects of psychological and physical functioning at baseline, as well as effects of MBSR on these outcomes. Results: Significant two-way interactions showed that greater mindfulness was associated with fewer depressive symptoms and less negative affect at baseline in individuals with average or higher levels of neuroticism. In contrast, mindfulness was associated with greater positive affect and vitality and fewer physical symptoms regardless of the level of neuroticism. There were no effects of MBSR on these outcomes at any level of neuroticism. Conclusion: Mindfulness may be more protective against psychological ill-being in older adults with higher levels of neuroticism, but conducive to positive psychological and physical well-being regardless of this personality trait. The potential moderating role of neuroticism should be further evaluated in studies of mindfulness-based interventions in older adults. [ABSTRACT FROM AUTHOR]

Management of critically ill coronavirus disease 2019 (COVID‐19) patients remains both risky and technically challenging. A 55‐year‐old male COVID‐19‐positive patient with obstructive sleep apnoea (OSA), diabetes, and obesity presented with cough and shortness of breath, escalating to requiring high‐flow oxygen therapy by high‐velocity nasal insufflation. The patient's flow rate and oxygen fraction remained labile throughout much of the hospitalization. This lability required frequent clinician interactions and use of personal protective equipment. The patient was alert and oriented and was instructed on the operation of the high‐flow system, specifically the adjustment of both flow rate and oxygen percentage. The patient was instructed to modify oxygen to maintain an SpO2 (peripheral capillary oxygen saturation) target range, and flow rate to address dyspnoea as well as reduction of flow as tolerated when other staff entered the room. The patient was successfully self‐regulated for 10 days and was discharged on 2 L/min nasal cannula on day 14 of his illness. [ABSTRACT FROM AUTHOR]

There are few data on the incidence of echocardiographic (echo) abnormalities following catheter ablation in children in the era of 3D mapping. Wide practice variation exists regarding routine post-ablation echo. We hypothesized a low incidence of clinically significant echo abnormalities following SVT ablation in otherwise healthy children. Single center data from 2009 to 2015 were reviewed; routine post-ablation echo was standard practice. Cases were categorized as utilizing fluoroscopy alone (FLUORO) or 3D mapping with a low fluoroscopic protocol (CARTO3). Congenital heart disease was excluded. Outcomes of interest included new valvular abnormalities, pericardial effusions, and wall motion abnormalities. Findings were compared to baseline studies when available and classified as normal/unchanged, clinically insignificant, or clinically significant. Outcomes were compared between FLUORO and CARTO3 groups. Of 347 ablations, 319 (92%) underwent post-procedural echo: 57% male; 55% FLUORO; mean age 13.4 ± 3.6 years. The most common ablation target was an accessory pathway (AP) in 66% (n = 144 WPW, 66 concealed), followed by AVNRT in 32% (n = 102). Radiofrequency (RF) energy was utilized in 82% (n = 262). Post-ablation echos were normal in 81% (n = 259). Clinically insignificant findings were seen in 18% (n = 58), most commonly trivial-small pericardial effusions in 11% (n = 34). Two significant findings required additional follow-up or treatment. There were no cases of wall motion abnormalities or clinically significant effusions. There were no differences in frequency of echo abnormalities between the FLUORO and CARTO3 groups. Clinically significant echocardiographic abnormalities are rare following SVT ablation in children with structurally normal hearts, independent of the use of 3D mapping. [ABSTRACT FROM AUTHOR]

Amphetamine and its related derivatives and analogues (ADRA) are highly addictive central nervous system stimulants that are used commonly in the treatment of attention-deficit/hyperactivity disorder and narcolepsy. These medications are associated with many side effects but reports of peripheral arterial manifestations associated with ADRA usage are scarce. We retrospectively reviewed the records of 16 patients (median age 37 years (IQR 31–47), 13 females) referred to a single tertiary referral service while receiving ADRA. Follow-up was available for a median of 3 years (IQR 3–4.5). The most common presentation (62.5%) was mild vasospastic symptoms involving the upper, lower or both extremities. Six patients developed severe manifestations including tissue loss and the need for lower extremity amputation. Most patients (75%) refused to stop the medication during follow-up. Underlying rheumatologic disorders were found in 25% of the patients, and the presence of rheumatologic disease seemed to be associated with more severe vascular manifestations. In conclusion, it is important to search for ADRA usage as part of the differential diagnosis of digital ischemia. [ABSTRACT FROM AUTHOR]

Objective To investigate the psychosocial etiology of physical frailty by examining the influence of chronic stress and perceived control. Method Using population-based samples of older adults from the Health and Retirement Study, this study employed structural equation modeling in cross-sectional (N = 5,250) and longitudinal (N = 2,013) samples to estimate the effects of chronic stress and socioeconomic status (SES) on baseline frailty and change in frailty status over 4 years and the extent to which perceived control mediates or moderates effects of chronic stress. Results Perceived control fully mediated effects of chronic stress and partially mediated effects of SES on both baseline frailty and change in frailty. Multigroup analyses revealed that the mediating role of perceived control was consistent across age, gender, and racial/ethnic subgroups. There was no evidence to support a moderating role of perceived control in the chronic stress and frailty relationship. Discussion Findings provide novel evidence for a mediating role of perceived control in pathways linking SES and chronic stress to frailty, further underscoring the importance of psychosocial constructs to the development and progression of frailty in older adults. [ABSTRACT FROM AUTHOR]

Objective: To better understand age and gender differences in associations of social relationships with chronic inflammation. Method: Using a sample of middle-aged and older adults (N = 963) from the Midlife Development in the United States (MIDUS) biomarker project, we examined interactions of age and gender with structural and functional social network measures in predicting interleukin-6 (IL-6) and C-reactive protein (CRP). Results: Significant interactions involving age and gender showed that social support was associated with lower IL-6 in older women, whereas perceived positive relationships and social integration were related to lower IL-6 in both men and women of advanced age. Functional measures were associated with higher CRP in both men and women after adjustment for health conditions and behaviors, with some further variation by age. Discussion: Greater social support may be related to lower IL-6 in older women. Further research is needed to understand observed associations of social support with higher CRP. [ABSTRACT FROM AUTHOR]

Mechanisms underlying prospective associations of perceived control with frailty and other health outcomes are not well understood. In the present study we used 3 waves of data from the Health and Retirement Study (N = 2,127) to test potential psychological and biological pathways linking perceived control with frailty over an 8-year period, and whether 4-year change in control predicts frailty independent of initial control. Lower odds of increasing frailty were associated with higher initial levels of perceived control (odds ratio [OR] = .74, p < .001, 95% confidence interval [CI] [.65, .83]) and a more positive change in perceived control (OR = .82, p = .006, 95% CI [.73, .92]), independent of the personality traits neuroticism and conscientiousness. In cross-lagged mediation models, the association of initial perceived control with frailty was partially mediated by positive affect, negative affect, and self-rated health, but not C-reactive protein or allostatic load. Associations of perceived control with positive and negative affect were bidirectional, with mediation in both directions. Initial frailty status was not related to 4-year change in perceived control. Perceived control may affect frailty risk through influences on affective states as well as perceived health. Findings also extend evidence that changes in perceived control may be prognostic of future health outcomes in older adults. (PsycINFO Database Record [ABSTRACT FROM AUTHOR]

Skating on ice is possible due to the low friction coefficient between ice and steel, which is thought to result from a lubricating water film formed through frictional melting. Although the phenomenon has been studied through various models and experiments, few studies report direct observations of the wear tracks on the ice surface. Here we use white light interferometry to accurately measure the surface topography on multiple length scales immediately after an ice skate slides over it. We find signs of surface melting only on short length scales as refrozen meltwater droplets, but no evidence of a global melt layer. Repeatedly sweeping over the same ice track results in an increasing friction coefficient, which we link to an increase in the contact area. We also consider the effect that the surface profile of the ice skate blade has on friction by using two different blades. [ABSTRACT FROM AUTHOR]

This is a response to the article by Galizia et al. in this issue. [ABSTRACT FROM AUTHOR]

This paper presents a modal analysis of different drivetrain configurations in electric vehicles; 1) an in – wheel motor, 2) direct drive, and 3) an electric motor with a reduction gear and a differential gear. A specific simulation model was developed to analyze the vibrations while taking into account the traction motor, possible mechanical reduction gears, and the driveshaft, as well as a Rigid Ring Model (RRM) to describe the tire. On the basis of the simulation results, the frequency responses were calculated for each drivetrain configuration and also for a non-drive, free-rolling tire. The analyzed results show interesting differences between the different drivetrain configurations. However, most of the negative aspects can be compensated for if identified in the early design phase. For instance, the frequency response of the in-wheel motor configuration indicated that the vibrations that occur might cause negative effects in terms of driving comfort and wheel speed signal noise. The direct drive configuration has an additional mode at 24 Hz, and the differential configuration at 4 Hz. It is possible that these modes would resonate strongly if some drivetrain design parameters were poorly defined. [ABSTRACT FROM AUTHOR]

Background: Multiple sclerosis is a degenerative inflammatory disease of the CNS characterised by immune-mediated destruction of myelin and progressive neuroaxonal loss. Myelin in the CNS is a specialised extension of the oligodendrocyte plasma membrane and clemastine fumarate can stimulate differentiation of oligodendrocyte precursor cells in vitro, in animal models, and in human cells. We aimed to analyse the efficacy and safety of clemastine fumarate as a treatment for patients with multiple sclerosis.Methods: We did this single-centre, 150-day, double-blind, randomised, placebo-controlled, crossover trial (ReBUILD) in patients with relapsing multiple sclerosis with chronic demyelinating optic neuropathy on stable immunomodulatory therapy. Patients who fulfilled international panel criteria for diagnosis with disease duration of less than 15 years were eligible. Patients were randomly assigned (1:1) via block randomisation using a random number generator to receive either clemastine fumarate (5·36 mg orally twice daily) for 90 days followed by placebo for 60 days (group 1), or placebo for 90 days followed by clemastine fumarate (5·36 mg orally twice daily) for 60 days (group 2). The primary outcome was shortening of P100 latency delay on full-field, pattern-reversal, visual-evoked potentials. We analysed by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT02040298.Findings: Between Jan 1, 2014, and April 11, 2015, we randomly assigned 50 patients to group 1 (n=25) or group 2 (n=25). All patients completed the study. The primary efficacy endpoint was met with clemastine fumarate treatment, which reduced the latency delay by 1·7 ms/eye (95% CI 0·5-2·9; p=0·0048) when analysing the trial as a crossover. Clemastine fumarate treatment was associated with fatigue, but no serious adverse events were reported.Interpretation: To our knowledge, this is the first randomised controlled trial to document efficacy of a remyelinating drug for the treatment of chronic demyelinating injury in multiple sclerosis. Our findings suggest that myelin repair can be achieved even following prolonged damage.Funding: University of California, San Francisco and the Rachleff Family. [ABSTRACT FROM AUTHOR]

Introduction Early allograft dysfunction ( EAD) is a well-defined clinical syndrome that reflects overall graft function within the first week after transplant. The aim of this study was to further refine the definition for EAD. Method In this study, 1124 patients were included for analysis. Logistic regression was performed to identify markers of liver injury associated with 6-month patient and graft failure. Results Recursive partitioning identified cut-points for ALT/ AST > 3000/6000 IU/ dL observed within first week, with bilirubin ≥ 10 mg/ dL and INR ≥ 1.6 on postoperative day 7 for the revised EAD model. The incidence of updated EAD was 15% (164/1124). Multivariable analysis identified eight risk factors associated with EAD: % macrosteatosis, donor location, donor weight, nonheart beating donors, type of organ transplanted, recipient-associated hepatocellular carcinoma, severity of postreperfusion syndrome, and the amount of transfused fresh frozen plasma. In the presence of EAD, the incidence of post-transplant renal replacement therapy and dialysis dependence increases. There was a significant association of the presence of EAD with 6-month mortality (12% vs 3%) and 6-month graft failure (8% vs 1%). Conclusion Higher AST/ ALT level needed as cutoff in comparison with the old EAD definition. [ABSTRACT FROM AUTHOR]

Congenital hypothyroidism occurs in approximately 1 in 2000 newborns and can have devastating neurodevelopmental consequences if not detected and treated promptly. While newborn screening has virtually eradicated intellectual disability due to severe congenital hypothyroidism in the developed world, more stringent screening strategies have resulted in increased detection of mild congenital hypothyroidism. Recent studies provide conflicting evidence about the potential neurodevelopmental risks posed by mild congenital hypothyroidism, highlighting the need for additional research to further define what risks these patients face and whether they are likely to benefit from treatment. Moreover, while the apparent incidence of congenital hypothyroidism has increased in recent decades, the underlying cause remains obscure in most cases. However, ongoing research into genetic causes of congenital hypothyroidism continues to shed new light on the development and physiology of the hypothalamic-pituitary-thyroid axis. The identification of IGSF1 as a cause of central congenital hypothyroidism has uncovered potential new regulatory pathways in both pituitary thyrotropes and gonadotropes, while mounting evidence suggests that a significant proportion of primary congenital hypothyroidism may be caused by combinations of rare genetic variants in multiple genes involved in thyroid development and function. Much remains to be learned about the origins of this common disorder and about the optimal management of less severely-affected infants. [ABSTRACT FROM AUTHOR]

Background: To date, there are limited radiation dose data on CT-guided procedures in pediatric patients.Objective: Our goal was to quantify the radiation dose associated with pediatric CT-guided drain placement and follow-up drain evaluations in order to estimate effective dose.Materials and Methods: We searched the electronic medical record and picture archiving and communication system (PACS) to identify all pediatric (<18 years old) CT-guided drain placements performed between January 2008 and December 2013 at our institution. We compiled patient data and radiation dose information from CT-guided drain placements as well as pre-procedural diagnostic CTs and post-procedural follow-up fluoroscopic abscess catheter injections (sinograms). Then we converted dose-length product, fluoroscopy time and number of acquisitions to effective doses using Monte Carlo simulations and age-appropriate conversion factors based on annual quality-control testing.Results: Fifty-two drainages were identified with mean patient age of 11.0 years (5 weeks to 17 years). Most children had diagnoses of appendicitis (n=23) or inflammatory bowel disease (n=11). Forty-seven patients had diagnostic CTs, with a mean effective dose of 7.3 mSv (range 1.1-25.5 mSv). Drains remained in place for an average of 16.9 days (range 0-75 days), with an average of 0.9 (0-5) sinograms per patient in follow-up. The mean effective dose for all drainages and follow-up exams was 5.3 mSv (0.7-17.1) and 62% (32/52) of the children had effective doses less than 5 mSv.Conclusion: The majority of pediatric patients who have undergone CT-guided drain placements at our institution have received total radiation doses on par with diagnostic ranges. This information could be useful when describing the dose of radiation to parents and providers when CT-guided drain placement is necessary. [ABSTRACT FROM AUTHOR]

Background: The thyroid hormone-inactivating enzyme type 3 deiodinase (D3) is induced during hypertrophic and ischemic cardiomyopathy, leading to a state of local cardiac hypothyroidism. Whether D3 induction occurs in dilated cardiomyopathy is unknown. Methods: This study characterized changes in cardiac D3 and thyroid hormone signaling in a transgenic model of progressive dilated cardiomyopathy (TG9 mice). Results: Cardiac D3 was dramatically induced 15-fold during the progression of dilated cardiomyopathy in TG9 mice. This D3 induction localized to cardiomyocytes and was associated with a decrease in myocardial thyroid hormone signaling. Conclusions: Cardiac D3 is induced in a mouse model of dilated cardiomyopathy, indicating that D3 induction may be a general response to diverse forms of cardiomyopathy. [ABSTRACT FROM AUTHOR]

A literary criticism of the book "Les Evénements," by Jean Rolin, is presented. Topics discussed include plot and setting of the book, how the book transforms a personal record of civil war into an ambulant field guide and geomorphologic survey of the French territoire and explanation of the current affluence of texts that traverse the territory.

Pelvic computed tomography angiography (CTA) prior to prostatic artery embolization is a beneficial tool for preprocedural planning to increase the likelihood of success during what can be a challenging procedure. Additionally, the same CTA images can be used for calculating the baseline prostate volume as well as for intraprocedural anatomic guidance, adding to the value of the scan. This article discusses the technique used for pelvic CTA and its role in preprocedural assessment of the pelvic vasculature prior to prostatic artery embolization. [ABSTRACT FROM AUTHOR]

Prostatic artery embolization (PAE) is a promising, new, safe, minimally invasive procedure for the treatment of lower urinary tract symptoms secondary to benign prostatic hyperplasia. However, it can be a one of the most technically difficult interventional radiology procedures because of the challenging anatomy involved. To help achieve technical success and limit complications, the authors present here a series of tips and tricks that have been proven useful from prior PAE experience. [ABSTRACT FROM AUTHOR]

Prostatic artery embolization (PAE) is an emerging, novel interventional technique in the management of patients with lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia (BPH). BPH is a common clinical condition in middle-aged and elderly men resulting in LUTS, including nocturia, urinary frequency, urgency, decreased urinary flow rates, hesitancy, and incomplete bladder emptying. Traditionally, LUTSs have been managed by medical or surgical therapies. Since the initial incidental discovery that selective PAE performed for uncontrolled bleeding secondary to BPH resulted in improved LUTS, the technique has continually evolved with a growing body of evidence supporting its safety and efficacy. However, despite the available data, PAE has yet to be established as a standard-of-care treatment option for patients with LUTS/BPH. In this article, the authors review the history and current state of PAE, including published data from case reports, animal studies, retrospective/prospective cohort studies, and prospective randomized controlled trials. [ABSTRACT FROM AUTHOR]

Aims: DNA-based carrier screening is a standard component of donor eligibility protocols practiced by U.S. sperm banks. Applicants who test positive for carrying a recessive disease mutation are typically disqualified. The aim of our study was to examine the utility of a range of screening panels adopted by the industry and the effectiveness of the screening paradigm in reducing a future child's risk of inheriting disease. Methods: A cohort of 27 donor applicants, who tested negative on an initial cystic fibrosis carrier test, was further screened with three expanded commercial carrier testing panels. These results were then compared to a systematic analysis of the applicants' DNA using next-generation sequencing (NGS) data. Results: The carrier panels detected serious pediatric disease mutations in one, four, or six donor applicants. Because each panel screens distinct regions of the genome, no single donor was uniformly identified as carrier positive by all three panels. In contrast, systematic NGS analysis identified all donors as carriers of one or more mutations associated with severe monogenic pediatric disease. These included 30 variants classified as "pathogenic" based on clinical observation and 66 with a high likelihood of causing gene dysfunction. Conclusion: Despite tremendous advances in variant identification, understanding, and analysis, the vast majority of disease-causing mutation combinations remain undetected by commercial carrier screening panels, which cover a narrow, and often distinct, subset of genes and mutations. The biological reality is that all donors and recipients carry serious recessive disease mutations. This challenges the utility of any screening protocol that anchors donor eligibility to carrier status. A more effective approach to reducing recessive disease risk would consider joint comprehensive analysis of both donor and recipient disease mutations. This type of high-resolution recessive disease risk analysis is now available and affordable, but industry practice must be modified to incorporate its use. [ABSTRACT FROM AUTHOR]

Background: Nitrilases, which hydrolyze nitriles in a one-step reaction into carboxylic acids and ammonia, gained increasing attention because of the abundance of nitrile compounds in nature and their use in fine chemicals and pharmaceutics. Extreme environments are potential habitats for the isolation and characterization of extremozymes including nitrilases with unique resistant properties. The Red Sea brine pools are characterized by multitude of extreme conditions. The Lower Convective Layer (LCL) of the Atlantis II Deep Brine Pool in the Red Sea is characterized by elevated temperature (68 °C), high salt concentrations (250‰), anoxic conditions and high heavy metal concentrations. Results: We identified and isolated a nitrilase from the Atlantis II Deep Brine Pool in the Red Sea LCL. The isolated 338 amino-acid nitrilase (NitraS-ATII) is part of a highly conserved operon in different bacterial phyla with indiscernible function. The enzyme was cloned, expressed and purified. Characterization of the purified NitraS-ATII revealed its selectivity towards dinitriles, which suggests a possible industrial application in the synthesis of cyanocarboxylic acids. Moreover, NitraS-ATII showed higher thermal stability compared to a closely related nitrilase, in addition to its observed tolerance towards high concentrations of selected heavy metals. Conclusion: This enzyme sheds light on evolution of microbes in the Atlantis II Deep LCL to adapt to the diverse extreme environment and can prove to be valuable in bioremediation processes. [ABSTRACT FROM AUTHOR]

Background: Spinal muscular atrophy (SMA) is the most common pan-ethnic cause of early childhood death due to mutations in a single gene, SMN1. Most chromosome 5 homologs have a functional gene and dysfunctional copy, SMN2, with a single synonymous base substitution that results in faulty RNA splicing. However, the copy number of SMN1 and SMN2 is highly variable, and one in 60 adults worldwide are SMA carriers. Although population-wide screening is recommended, current SMA carrier tests have not been incorporated into targeted gene panels. Methods: Here we describe a novel computational protocol for determining SMA carrier status based solely on individual exome data. Our method utilizes a Bayesian hierarchical model to quantify an individual's carrier probability given only his or her SMN1 and SMN2 reads at six loci of interest. Results: We find complete concordance with results obtained with the current qPCR-based testing standard in known SMA carriers and affecteds. We applied our protocol to the phase 3 cohort of the 1,000 Genomes Project and found carrier frequencies in multiple populations consistent with the present literature. Conclusion: Our process is a convenient, robust alternative to qPCR, which can easily be integrated into the analysis of large multi-gene NGS carrier screens. [ABSTRACT FROM AUTHOR]

Direct tire-road contact friction estimation is essential for future autonomous cars and active safety systems. Friction estimation methods have been proposed earlier for driving conditions in the presence of a slip angle or slip ratio. However, the estimation of the friction from a freely-rolling tire is still an unsolved topic. Knowing the existing friction potential would be beneficial since vehicle control systems could be adjusted before any remarkable tire force has been produced. Since accelerometers are well-known and robust, and thus a promising sensor type for intelligent tires, this study uses three three-axis IEPE accelerometers on the inner liner of a tire to detect friction potential indicators on two equally smooth surfaces with different friction levels. The equal roughness was chosen for both surfaces in order to study the friction phenomena by neglecting the effect of surface texture on vibrations. The acceleration data before the contact is used to differentiate the two friction levels between the tire and the road. In addition, the contact lengths from the three accelerometers are used to validate the acceleration data. A method to differentiate the friction levels on the basis of the acceleration signal is also introduced. [ABSTRACT FROM AUTHOR]

The onset mechanism of frictional sliding is essential in understanding frictional strength between materials. In particular, the static friction coefficient is a very important but often overlooked indicator for the emergency braking performance of tyres. In ABS braking a significant area of the tyre contact patch is locally stuck to the road and becomes detached to frictional sliding when the local shear stresses exceed the local friction potential. The detachment phenomena were studied for rubber–ice contact by means of a high-speed camera and image processing. The image sequences of the contact were combined with friction force data. It was observed that for a smooth rubber sample a horseshoe-shaped detachment front was produced. The last contact point was always at the trailing edge or side of the sample. The textured sample had a ring-like detachment front that located the last contact point in the centre of the contact area. The dwell time had a logarithmic dependency on the static friction of the rubber–ice contact. Two different types of precursors were found. The first precursor occurred when the first signs of detachment were observed visually. The second precursor was found when the static friction rose so high that the movement of the sample was nucleated by the breaking of the ice rather than the detachment of the contact. [ABSTRACT FROM AUTHOR]

RASGRP1 is a guanine-nucleotide-exchange factor essential for MAP-kinase mediated signaling in lymphocytes. We report the second case of RASGRP1 deficiency in a patient with a homozygous nonsense mutation in the catalytic domain of the protein. The patient had epidermodysplasia verruciformis, suggesting a clinically important intrinsic T cell function defect. Like the previously described patient, our proband also presented with CD4 + T cell lymphopenia, impaired T cell proliferation to mitogens and antigens, reduced NK cell function, and EBV-associated lymphoma. The severity of the disease and the development of EBV lymphoma in both patients suggest that hematopoietic stem cell transplantation should be performed rapidly in patients with RASGRP1 deficiency. [ABSTRACT FROM AUTHOR]

Background: The number of robotic operations performed with the da Vinci Surgical System has increased during the past decade. This system allows for greater maneuverability and control than hand-assisted laparoscopic procedures, resulting in less tissue manipulation and irritation. Methods: We retrospectively analyzed the results of 100 consecutive robotic-assisted laparoscopic donor nephrectomies and compared them to our most recent 20 hand-assisted laparoscopic donor nephrectomies. Results: Between May 2008 and June 2012, 120 laparoscopic donor nephrectomies were performed at Ochsner Clinic Foundation. Of those, 100 live kidney donors underwent robotic-assisted laparoscopic donor nephrectomies. Surgical time and hospital length of stay improved after the first 20 patients receiving robotic-assisted laparoscopic nephrectomies, which was considered the learning curve. Sixty percent of patients who underwent robotic-assisted laparoscopic donor nephrectomies were released on postoperative day 1 compared to 45% of patients who underwent hand-assisted laparoscopic techniques. Conclusion: In our experience, robotic-assisted laparoscopic donor nephrectomy resulted in decreased postoperative length of stay that decreased the global cost of the procedure and allowed our institution to admit more patients. [ABSTRACT FROM AUTHOR]

Flash Flood Guidance consists of indices that estimate the amount of rain of a certain duration that is needed over a given small basin in order to cause minor flooding. Backwater catchment inundation from swollen rivers or regional groundwater inputs are not significant over the spatial and temporal scales for the majority of upland flash flood prone basins, as such, these effects are not considered. However, some lowland areas and flat terrain near large rivers experience standing water long after local precipitation has ceased. NASA is producing an experimental product from the MODIS that detects standing water. These observations were assimilated into the hydrologic model in order to more accurately represent soil moisture conditions within basins, from sources of water from outside of the basin. Based on the upper soil water content, relations are used to derive an error estimate for the modeled soil saturation fraction; whereby, the soil saturation fraction model state can be updated given the availability of satellite observed inundation. Model error estimates were used in a Monte Carlo ensemble forecast of soil water and flash flood potential. Numerical experiments with six months of data (July 2011-December 2011) showed that MODIS inundation data, when assimilated to correct soil moisture estimates, increased the likelihood that bankfull flow would occur, over non-assimilated modeling, at catchment outlets for approximately 44% of basin-days during the study time period. While this is a much more realistic representation of conditions, no actual events occurred allowing for validation during the time period. [ABSTRACT FROM AUTHOR]