Filamentation of a relativistic proton bunch in plasma.

We show in experiments that a long, underdense, relativistic proton bunch propagating in plasma undergoes the oblique instability, which we observe as filamentation. We determine a threshold value for the ratio between the bunch transverse size and plasma skin depth for the instability to occur. At the threshold, the outcome of the experiment alternates between filamentation and self-modulation instability (evidenced by longitudinal modulation into microbunches). Time-resolved images of the bunch density distribution reveal that filamentation grows to an observable level late along the bunch, confirming the spatiotemporal nature of the instability. We provide a rough estimate of the amplitude of the magnetic field generated in the plasma by the instability and show that the associated magnetic energy increases with plasma density.

Hosing of a Long Relativistic Particle Bunch in Plasma.

Experimental results show that hosing of a long particle bunch in plasma can be induced by wakefields driven by a short, misaligned preceding bunch. Hosing develops in the plane of misalignment, self-modulation in the perpendicular plane, at frequencies close to the plasma electron frequency, and are reproducible. Development of hosing depends on misalignment direction, its growth on misalignment extent and on proton bunch charge. Results have the main characteristics of a theoretical model, are relevant to other plasma-based accelerators and represent the first characterization of hosing.

Controlled Growth of the Self-Modulation of a Relativistic Proton Bunch in Plasma.

A long, narrow, relativistic charged particle bunch propagating in plasma is subject to the self-modulation (SM) instability. We show that SM of a proton bunch can be seeded by the wakefields driven by a preceding electron bunch. SM timing reproducibility and control are at the level of a small fraction of the modulation period. With this seeding method, we independently control the amplitude of the seed wakefields with the charge of the electron bunch and the growth rate of SM with the charge of the proton bunch. Seeding leads to larger growth of the wakefields than in the instability case.

Multiple events case-control study in a prospective cohort to identify systemic, cellular, and molecular biomarkers of obesity-induced accelerated aging in 30-years-olds: the ObAGE study protocol.

BACKGROUND: Aging is characterized by a progressive loss of capacities linked to fundamental alterations/damage in multiple cellular and molecular pathways. It is the most significant risk factor for all non-communicable diseases (NCDs). Another contributing factor to the rise in NCDs is obesity. It has been suggested that obesity not only accelerates the onset of metabolic imbalances but also decreases lifespan and impacts cellular and molecular processes in a manner similar to aging. Obesity might accelerate the pace of aging. Guided by a lifecourse approach, we will explore how exposure to obesity in critical developmental stages disrupt homeostatic resilience mechanisms that preserve physiological integrity, inducing an early expression of aging phenotypes. Also, we will determine whether exposure to early psychosocial adversity influences vulnerability to obesity as a risk factor for accelerated aging. METHODS: Multiple events case-control study embedded in a prospective cohort of Chileans at 30-31y, 50% females, of low- to-middle socioeconomic status, who participated in nutrition research since birth. At 23y, 25% had obesity and cardiometabolic risk was high. We will use a multi-layer approach including: anthropometric assessment; DXA scan for body composition; abdominal ultrasound of the liver; stool samples collection and sequencing of the ribosomal RNA 16S gene to characterize the gut microbiome; determination of age-related pro-inflammatory cytokynes and anti-inflammatory miokynes. For the first time in Chile, we will address age-related epigenetic changes using the Horvath´s epigenetic clock. In a subset we will conduct a controlled physical challenge to characterize physical resilience (autophagy). DISCUSSION: ObAGE is in an excellent position to: approach aging as a process whose expression involves multiple factors from the early stages of a person's life; understand how longitudinal changes in health trajectories impact the biological mechanisms of aging; identify potential resilience mechanisms that help prevent unhealthy aging. Because SLS participants are still young, our research setting combined with advanced scientific techniques may identify individuals or groups at risk of early onset health issues. Results from ObAGE may pave the way to address the contribution of obesity to aging through lifespan from cells to systems and might be instrumental to developing interventions to improve health span in the Chilean population. TRIAL REGISTRATION: The proposed study does not consider any health care intervention on human participants.

Pedestrian flow in two dimensions: Optimal psychological stress leads to less evacuation time and decongestion.

Collective motion is an innate ability of all living systems, which depends on physiological and psychosocial factors in the case of humans. Such a collective organization is becoming of great interest in collective motion in human crowds. Using a cellular automaton (CA) simulation model, we demonstrate that emergency egress from a two-dimensional corridor with optimal stress leads to less evacuation time and efficient mass evacuations. We study how three types of stress (i.e., mild stress, optimal stress, and anxiety) described in the literature have a significant impact on the collective dynamics. We found that low-stress levels could decrease the evacuation time in an entire occupied room since agents choose alternative routes rather than the shortest path to the exit and display cooperative behavior. Therefore, the combination of mild and optimal stress can lead to efficient evacuations. Also CA simulations may be used to find safer and more efficient ways to conduct mass evacuation procedures.

Transition between Instability and Seeded Self-Modulation of a Relativistic Particle Bunch in Plasma.

We use a relativistic ionization front to provide various initial transverse wakefield amplitudes for the self-modulation of a long proton bunch in plasma. We show experimentally that, with sufficient initial amplitude [≥(4.1±0.4) MV/m], the phase of the modulation along the bunch is reproducible from event to event, with 3%-7% (of 2π) rms variations all along the bunch. The phase is not reproducible for lower initial amplitudes. We observe the transition between these two regimes. Phase reproducibility is essential for deterministic external injection of particles to be accelerated.

Myelomeningocele sac associated with worse lower-extremity neurological sequelae: evidence for prenatal neural stretch injury?

OBJECTIVE: To determine whether the presence of a myelomeningocele (MMC) sac and sac size correlate with compromised lower-extremity function in fetuses with open spinal dysraphism. METHODS: A radiology database search was performed to identify cases of MMC and myeloschisis (MS) diagnosed prenatally in a single center from 2013 to 2017. All cases were evaluated between 18 and 25 weeks. Ultrasound reports were reviewed for talipes and impaired lower-extremity motion. In MMC cases, sac volume was calculated from ultrasound measurements. Magnetic resonance imaging reports were reviewed for hindbrain herniation. The association of presence of a MMC sac and sac size with talipes and impaired lower-extremity motion was assessed. Post-hoc analysis of data from the multicenter Management of Myelomeningocele Study (MOMS) randomized controlled trial was performed to confirm the study findings. RESULTS: In total, 283 MMC and 121 MS cases were identified. MMC was associated with a lower incidence of hindbrain herniation than was MS (80.9% vs 100%; P < 0.001). Compared with MS cases, MMC cases with hindbrain herniation had a higher rate of talipes (28.4% vs 16.5%, P = 0.02) and of talipes or lower-extremity impairment (34.9% vs 19.0%, P = 0.002). Although there was a higher rate of impaired lower-extremity motion alone in MMC cases with hindbrain herniation than in MS cases, the difference was not statistically significant (6.6% vs 2.5%; P = 0.13). Among MMC cases with hindbrain herniation, mean sac volume was higher in those associated with talipes compared with those without talipes (4.7 ± 4.2 vs 3.0 ± 2.6 mL; P = 0.002). Review of the MOMS data demonstrated similar findings; cases with a sac on baseline imaging had a higher incidence of talipes than did those without a sac (28.2% vs 7.5%; P = 0.007). CONCLUSIONS: In fetuses with open spinal dysraphism, the presence of a MMC sac was associated with fetal talipes, and this effect was correlated with sac size. The presence of a larger sac in fetuses with open spinal dysraphism may result in additional injury through mechanical stretching of the nerves, suggesting another acquired mechanism of injury to the exposed spinal tissue. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Proton Bunch Self-Modulation in Plasma with Density Gradient.

We study experimentally the effect of linear plasma density gradients on the self-modulation of a 400 GeV proton bunch. Results show that a positive or negative gradient increases or decreases the number of microbunches and the relative charge per microbunch observed after 10 m of plasma. The measured modulation frequency also increases or decreases. With the largest positive gradient we observe two frequencies in the modulation power spectrum. Results are consistent with changes in wakefields' phase velocity due to plasma density gradients adding to the slow wakefields' phase velocity during self-modulation growth predicted by linear theory.

Higgs physics at the CLIC electron-positron linear collider.

The Compact Linear Collider (CLIC) is an option for a future [Formula: see text] collider operating at centre-of-mass energies up to [Formula: see text], providing sensitivity to a wide range of new physics phenomena and precision physics measurements at the energy frontier. This paper is the first comprehensive presentation of the Higgs physics reach of CLIC operating at three energy stages: [Formula: see text], 1.4 and [Formula: see text]. The initial stage of operation allows the study of Higgs boson production in Higgsstrahlung ([Formula: see text]) and [Formula: see text]-fusion ([Formula: see text]), resulting in precise measurements of the production cross sections, the Higgs total decay width [Formula: see text], and model-independent determinations of the Higgs couplings. Operation at [Formula: see text] provides high-statistics samples of Higgs bosons produced through [Formula: see text]-fusion, enabling tight constraints on the Higgs boson couplings. Studies of the rarer processes [Formula: see text] and [Formula: see text] allow measurements of the top Yukawa coupling and the Higgs boson self-coupling. This paper presents detailed studies of the precision achievable with Higgs measurements at CLIC and describes the interpretation of these measurements in a global fit.

Low muscle mass is associated with cardiometabolic risk regardless of nutritional status in adolescents: A cross-sectional study in a Chilean birth cohort.

BACKGROUND: Increased cardiometabolic risk (CMR) is documented in obese and non-obese adolescents with low muscular fitness. However, the association of low muscle mass (LMM) with CMR, independent of weight status, has not been examined. We analyzed the relationship of LMM with CMR in adolescents, regardless of their weight status. MATERIALS AND METHODS: Observational study in 660 adolescents. BMI, waist circumference (WC), arterial blood pressures (ABP) were measured. Total fat mass (TFM), total lean tissue (TLT), and appendicular skeletal muscle mass (ASM) were estimated (DXA). Fasting lipid profile, glucose, and insulin were measured. HOMA-IR was estimated. Metabolic Syndrome (MetS) was diagnosed (AHA/NHLBI/IDF). ROC analysis was performed to find the optimal cutoffs of TLT percentage for MetS diagnosis. Values below these cutoffs defined LMM. ANCOVA examined the association of LMM with selected cardiometabolic biomarkers. RESULTS: In both sexes, TLT showed better sensitivity and specificity than ASM for MetS diagnosis. In males and females, TLT of 66.1% and 56.3%, respectively, were the optimal cutoff for MetS diagnosis. In the sample, 17.3% of males and 23.7% of females had LMM. In both sexes, adolescents with LMM had significantly higher values of WC, ABP, TG, TC/HDL, HOMA-IR, and MetS z-score than non-LMM participants. Adolescents with LMM, regardless nutritional status, had significantly increased values of MetS z-score, ABP, TG, TC/HDL-chol, and HOMA-IR than non-obese non-LMM adolescents. Adolescents having both obesity and LMM had the unhealthiest CMR profile. CONCLUSION: In adolescents, LMM was associated with higher CMR, regardless of nutritional status. In obese adolescents, LMM increased obesity-associated CMR.

Head injury from falls in children younger than 6†years of age.

UNLABELLED: The risk of serious head injury (HI) from a fall in a young child is ill defined. The relationship between the object fallen from and prevalence of intracranial injury (ICI) or skull fracture is described. METHOD: Cross-sectional study of HIs from falls in children (<6 years) admitted to UK hospitals, analysed according to the object fallen from and associated Glasgow Coma Score (GCS) or alert, voice, pain, unresponsive (AVPU) and CT scan results. RESULTS: Of 1775 cases ascertained (median age 18 months, 54.7% boys), 87% (1552) had a GCS=15/AVPU=alert. 19.3% (342) had a CT scan: 32% (110/342) were abnormal; equivalent to 5.9% of the overall population, 16.9% (58) had isolated skull fractures and 13.7% (47) had ICI (49% (23/47) had an associated skull fracture). The prevalence of ICI increased with neurological compromise; however, 12% of children with a GCS=15/AVPU=alert had ICI. When compared to falls from standing, falls from a person's arms (233 children (mean age 1 year)) had a significant relative OR for a skull fracture/ICI of 6.94 (95% CI 3.54 to 13.6), falls from a building (eg, window or attic) (mean age 3 years) OR 6.84 (95% CI 2.65 to 17.6) and from an infant or child product (mean age 21 months) OR 2.75 (95% CI 1.36 to 5.65). CONCLUSIONS: Most HIs from a fall in these children admitted to hospital were minor. Infants, dropped from a carer's arms, those who fell from infant products, a window, wall or from an attic had the greatest chance of ICI or skull fracture. These data inform prevention and the assessment of the likelihood of serious injury when the object fallen from is known.

Healthy Chilean Adolescents with HOMA-IR ≥ 2.6 Have Increased Cardiometabolic Risk: Association with Genetic, Biological, and Environmental Factors.

OBJECTIVE: To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. METHODS: In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. RESULTS: Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. CONCLUSIONS: In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk.

Diagnosis and Treatment of Venous Malformations. Consensus Document of the International Union of Phlebology (IUP): updated 2013.

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects) . These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/ persistence rates, high morbidity following non-specific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular sub-types of VMs. This incorporated the embryological ongm, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustrated as a separate topic to differentiate from isolated VMs and to rectify the existing confusion with name-based eponyms such as Klippei-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndromebased VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Emerging roles for the FCRL family members in lymphocyte biology and disease.

Members of the extended Fc receptor-like (FCRL) family in humans and mice are preferentially expressed by B cells and possess tyrosine-based immunoregulatory function. Although the majority of these proteins repress B cell receptor-mediated activation, there is an emerging evidence for their bifunctionality and capacity to counter-regulate adaptive and innate signaling pathways. In light of these findings, the recent discovery of ligands for several of these molecules has begun to reveal exciting potential for them in normal lymphocyte biology and is launching a new phase of FCRL investigation. Importantly, these fundamental developments are also setting the stage for defining their altered roles in the pathogenesis of a growing number of immune-mediated diseases. Here we review recent advances in the FCRL field and highlight the significance of these intriguing receptors in normal and perturbed immunobiology.

Guideline. Diagnosis and treatment of venous malformations. consensus document of the international union of phlebology (iup): updated-2013.

Venous malformations (VMs) are the most common vascular developmental anomalies (birth defects). These defects are caused by developmental arrest of the venous system during various stages of embryogenesis. VMs remain a difficult diagnostic and therapeutic challenge due to the wide range of clinical presentations, unpredictable clinical course, erratic response to the treatment with high recurrence/persistence rates, high morbidity following nonspecific conventional treatment, and confusing terminology. The Consensus Panel reviewed the recent scientific literature up to the year 2013 to update a previous IUP Consensus (2009) on the same subject. ISSVA Classification with special merits for the differentiation between the congenital vascular malformation (CVM) and vascular tumors was reinforced with an additional review on syndrome-based classification. A "modified" Hamburg classification was adopted to emphasize the importance of extratruncular vs. truncular subtypes of VMs. This incorporated the embryological origin, morphological differences, unique characteristics, prognosis and recurrence rates of VMs based on this embryological classification. The definition and classification of VMs were strengthened with the addition of angiographic data that determines the hemodynamic characteristics, the anatomical pattern of draining veins and hence the risk of complication following sclerotherapy. The hemolymphatic malformations, a combined condition incorporating LMs and other CVMs, were illustratedas a separate topic to differentiate from isolated VMs and to rectify the existing confusion with namebased eponyms such as Klippel-Trenaunay syndrome. Contemporary concepts on VMs were updated with new data including genetic findings linked to the etiology of CVMs and chronic cerebrospinal venous insufficiency. Besides, newly established information on coagulopathy including the role of D-Dimer was thoroughly reviewed to provide guidelines on investigations and anticoagulation therapy in the management of VMs. Congenital vascular bone syndrome resulting in angio-osteo-hyper/hypotrophy and (lateral) marginal vein was separately reviewed. Background data on arterio-venous malformations was included to differentiate this anomaly from syndrome-based VMs. For the treatment, a new section on laser therapy and also a practical guideline for follow up assessment were added to strengthen the management principle of the multidisciplinary approach. All other therapeutic modalities were thoroughly updated to accommodate a changing concept through the years.

Experimental validation of a novel compact focusing scheme for future energy-frontier linear lepton colliders.

A novel scheme for the focusing of high-energy leptons in future linear colliders was proposed in 2001 [P. Raimondi and A. Seryi, Phys. Rev. Lett. 86, 3779 (2001)]. This scheme has many advantageous properties over previously studied focusing schemes, including being significantly shorter for a given energy and having a significantly better energy bandwidth. Experimental results from the ATF2 accelerator at KEK are presented that validate the operating principle of such a scheme by demonstrating the demagnification of a 1.3 GeV electron beam down to below 65 nm in height using an energy-scaled version of the compact focusing optics designed for the ILC collider.

The need for epididymovasostomy at vasectomy reversal plateaus in older vasectomies: a study of 1229 cases.

Vasectomy reversal involves either vasovasostomy (VV) or epididymovasostomy (EV), and rates of epididymal obstruction and EV increase with time after vasectomy. However, as older vasectomies may not require EV for successful reversal, we hypothesized that sperm production falls after vasectomy and can protect the system from epididymal blowout. Our objective was to define how the need for EV at reversal changes with time after vasectomy through a retrospective review of consecutive reversals performed by three surgeons over a 10-year period. Vasovasotomy was performed with Silber score 1-3 vasal fluid. EVs were performed with Silber score 4 (sperm fragments; creamy fluid) or 5 (sperm absence) fluid. Reversal procedure type was correlated with vasectomy and patient age. Post-operative patency rates, total spermatozoa and motile sperm counts in younger (<15 years) and older (>15 years) vasectomies were assessed. Simple descriptive statistics determined outcome relevance. Among 1229 patients, 406 had either unilateral (n = 252) or bilateral EV's (n = 154) constituting 33% (406/1229) of reversals. Mean patient age was 41.4±7 years (range 22-72). Median vasectomy interval was 10 years (range 1-38). Overall sperm patency rate after reversal was 84%. The rate of unilateral (EV/VV) or bilateral EV increased linearly in vasectomy intervals of 1-22 years at 3% per year, but plateaued at 72% in vasectomy intervals of 24-38 years. Sperm counts were maintained with increasing time after vasectomy, but motile sperm counts decreased significantly (p < 0.001). Pregnancy, secondary azoospermia, varicocoele and sperm granuloma were not assessed. In conclusion, and contrary to conventional thinking, the need for EV at reversal increases with time after vasectomy, but this relationship is not linear. EV rates plateau 22 years after vasectomy, suggesting that protective mechanisms ameliorate epididymal 'blowout'. Upon reversal, sperm output is maintained with time after vasectomy, but motile sperm counts decrease linearly, suggesting epididymal dysfunction influences semen quality after reversal.

Consensus Document of the International Union of Angiology (IUA)-2013. Current concept on the management of arterio-venous management.

Arterio-venous malformations (AVMs) are congenital vascular malformations (CVMs) that result from birth defects involving the vessels of both arterial and venous origins, resulting in direct communications between the different size vessels or a meshwork of primitive reticular networks of dysplastic minute vessels which have failed to mature to become 'capillary' vessels termed "nidus". These lesions are defined by shunting of high velocity, low resistance flow from the arterial vasculature into the venous system in a variety of fistulous conditions. A systematic classification system developed by various groups of experts (Hamburg classification, ISSVA classification, Schobinger classification, angiographic classification of AVMs,) has resulted in a better understanding of the biology and natural history of these lesions and improved management of CVMs and AVMs. The Hamburg classification, based on the embryological differentiation between extratruncular and truncular type of lesions, allows the determination of the potential of progression and recurrence of these lesions. The majority of all AVMs are extra-truncular lesions with persistent proliferative potential, whereas truncular AVM lesions are exceedingly rare. Regardless of the type, AV shunting may ultimately result in significant anatomical, pathophysiological and hemodynamic consequences. Therefore, despite their relative rarity (10-20% of all CVMs), AVMs remain the most challenging and potentially limb or life-threatening form of vascular anomalies. The initial diagnosis and assessment may be facilitated by non- to minimally invasive investigations such as duplex ultrasound, magnetic resonance imaging (MRI), MR angiography (MRA), computerized tomography (CT) and CT angiography (CTA). Arteriography remains the diagnostic gold standard, and is required for planning subsequent treatment. A multidisciplinary team approach should be utilized to integrate surgical and non-surgical interventions for optimum care. Currently available treatments are associated with significant risk of complications and morbidity. However, an early aggressive approach to elimiate the nidus (if present) may be undertaken if the benefits exceed the risks. Trans-arterial coil embolization or ligation of feeding arteries where the nidus is left intact, are incorrect approaches and may result in proliferation of the lesion. Furthermore, such procedures would prevent future endovascular access to the lesions via the arterial route. Surgically inaccessible, infiltrating, extra-truncular AVMs can be treated with endovascular therapy as an independent modality. Among various embolo-sclerotherapy agents, ethanol sclerotherapy produces the best long term outcomes with minimum recurrence. However, this procedure requires extensive training and sufficient experience to minimize complications and associated morbidity. For the surgically accessible lesions, surgical resection may be the treatment of choice with a chance of optimal control. Preoperative sclerotherapy or embolization may supplement the subsequent surgical excision by reducing the morbidity (e.g. operative bleeding) and defining the lesion borders. Such a combined approach may provide an excellent potential for a curative result. Conclusion. AVMs are high flow congenital vascular malformations that may occur in any part of the body. The clinical presentation depends on the extent and size of the lesion and can range from an asymptomatic birthmark to congestive heart failure. Detailed investigations including duplex ultrasound, MRI/MRA and CT/CTA are required to develop an appropriate treatment plan. Appropriate management is best achieved via a multi-disciplinary approach and interventions should be undertaken by appropriately trained physicians.

Cerebrofacial venous anomalies, sinus pericranii, ocular abnormalities and developmental delay.

The clinical implications of venous cerebrovascular maldevelopment remain poorly understood. We report on the association of cerebrofacial venous anomalies (including sinus pericranii), ocular abnormalities and mild developmental delay in two children. In addition, one child had a seizure disorder. Complex cerebrofacial slow-flow vascular anomalies may herald an underlying developmental aberration affecting the cerebrofacial and orbital regions.

A rapid and quantitative method for the evaluation of V gene usage, specificities and the clonal size of B cell repertoires.

The quantitative simultaneous description of both variable region gene usage and antigen specificity of immunoglobulin repertoires is a major goal in immunology. Current quantitative assays are labor intensive and depend on extensive gene expression cloning prior to screening for antigen specificity. Here we describe an alternative method based on high efficiency single B cell cultures coupled with RT-PCR that can be used for rapid characterization of immunoglobulin gene segment usage, clonal size and antigen specificity. This simplified approach should facilitate the study of antibody repertoires expressed by defined B cell subpopulations, the analysis of immune responses to self and nonself-antigens, the development and screening of synthetic antibodies and the accelerated study and screening of neutralizing antibodies to pathogenic threats.