Two-Center Review of Posterior Vault Expansion following a Staged or Expectant Treatment of Crouzon and Apert Craniosynostosis

Background: The timing of posterior cranial expansion for the management of intracranial pressure can be "staged" by age and dysmorphology or "expectant" by pressure monitoring. The authors report shared outcome measures from one center performing posterior vault remodeling (PCVR) or distraction (PVDO) following a staged approach and another performing spring-assisted expansion (SAPVE) following an expectant protocol. Methods: Apert or Crouzon syndrome patients who underwent posterior expansion younger than 2 years were included. Perioperative outcomes and subsequent cranial operations were recorded up to last follow-up and intracranial volume changes measured and adjusted using growth curves. Results: Thirty-eight patients were included. Following the expectant protocol, Apert patients underwent SAPVE at a younger age (8 months) than Crouzon patients (16 months). The initial surgery time was shorter but total operative time, including device removal, was longer for PVDO (3 hours 52 minutes) and SAPVE (4 hours 34 minutes) than for PCVR (3 hours 24 minutes). Growth-adjusted volume increase was significant and comparable. Fourteen percent of PCVR, 33% of PVDO, and 11% of SAPVE cases had complications, but without long-term deficits. Following the staged approach, 5% underwent only PVDO, 85% had a staged posterior followed by anterior surgery, and 10% required a third expansion. Following the expectant approach, 42% of patients had only posterior expansion at last follow-up, 32% had a secondary cranial surgery, and 26% had a third cranial expansion. Conclusion: Two approaches involving posterior vault expansion in young syndromic patients using three techniques resulted in comparable early volume expansion and complication profiles. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.</p

Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

Most cases of Apert syndrome are caused by mutations in the FGFR2 gene, either Ser252Trp or Pro253Arg. In these patients, over the last decades, spring-assisted posterior vault expansion (SA-PVE) has been the technique of choice for cranial vault expansion in the Craniofacial Unit of Great Ormond Street Hospital for Children (GOSH), London. The aim of this study was to investigate if there is a difference in preoperative intracranial volume (ICV) in patients with Apert syndrome with Ser252Trp or Pro253Arg mutation and whether these mutations affect the change in ICV achieved by SA-PVE. The GOSH craniofacial SA-PVE database was used to select patients with complete genetic testing and preoperative and postoperative computed tomography scans. ICV was calculated using FSL (FMRIB Analysis Group, Oxford) and adjusted based on Apert-specific growth curves. Sixteen patients were included with 8 having Ser252Trp mutation and 8 having Pro253Arg mutation. The mean preoperative adjusted computed tomography volume for patients in the Ser252Trp group was 1137.7 cm3 and in the Pro253Arg group was 1115.8 cm3 (P=1.00). There was a significant increase in ICV following SA-PVE in all patients (P<0.001) with no difference in mean change in ICV between the groups (P=0.51). Four (50%) patients with Ser252Trp mutation and 3 (37.5%) with Pro253Arg mutations required a second operation after primary SA-PVE. The results demonstrate that regardless of the mutation present, SA-PVE was successful in increasing ICV in patients with Apert syndrome and that a repeat volume expanding procedure was required by a similar number of patients in the 2 groups

Electrophysiological and fundoscopic detection of intracranial hypertension in craniosynostosis

Aims: To assess the diagnostic accuracy of fundoscopy and visual evoked potentials (VEPs) in detecting intracranial hypertension (IH) in patients with craniosynostosis undergoing spring-assisted posterior vault expansion (sPVE). Methods: Children with craniosynostosis undergoing sPVE and 48-hour intracranial pressure (ICP) monitoring were included in this single-centre, retrospective, diagnostic accuracy study. Data for ICP, fundoscopy and VEPs were analysed. Primary outcome measures were papilloedema on fundoscopy, VEP assessments and IH, defined as mean ICP &gt; 20 mmHg. Diagnostic indices were calculated for fundoscopy and VEPs against IH. Secondary outcome measures included final visual outcomes. Results: Fundoscopic examinations were available for 35 children and isolated VEPs for 30 children, 22 of whom had at least three serial VEPs. Sensitivity was 32.1% for fundoscopy (95% confidence intervals [CI]: 15.9–52.4) and 58.3% for isolated VEPs (95% CI 36.6–77.9). Specificity for IH was 100% for fundoscopy (95% CI: 59.0–100) and 83.3% for isolated VEPs (95% CI: 35.9–99.6). Where longitudinal deterioration was suspected from some prVEPs but not corroborated by all, sensitivity increased to 70.6% (95% CI: 44.0–89.7), while specificity decreased to 60% (95% CI: 14.7–94.7). Where longitudinal deterioration was clinically significant, sensitivity decreased to 47.1% (23.0–72.2) and specificity increased to 100% (47.8–100). Median final BCVA was 0.24 logMAR (n = 36). UK driving standard BCVA was achieved by 26 patients (72.2%), defined as ≥0.30 logMAR in the better eye. Conclusion: Papilloedema present on fundoscopy reliably indicated IH, but its absence did not exclude IH. VEP testing boosted sensitivity at the expense of specificity, depending on method of analysis.</p

Intimate Partner Violence and Abuse Against Men: Voices of Victimization Among Ex-Servicemen of the British Armed Forces

This study presents the personal testimonies of male British ex-Armed Forces personnel who have experienced violence and abuse victimization that was perpetrated by civilian female partners. In this research, we argue that to embark upon any understanding of the domestic lives of military personnel, an appreciation of the linkages to the cultural context of the military institution is necessary. Understanding the influence of the military institution beyond the military domain is crucial. We unveil the nature and character of the violence and abuse and how the servicemen negotiated their relationships. In doing so, we highlight the embodiment of military discipline, skills, and tactics in the home—not ones of violence which may be routinely linked to military masculinities; rather ones of restraint, tolerance, stoicism, and the reduction of a threat to inconsequential individual significance

From open radical hysterectomy to robot-assisted laparoscopic radical hysterectomy for early stage cervical cancer: aspects of a single institution learning curve

We analysed the introduction of the robot-assisted laparoscopic radical hysterectomy in patients with early-stage cervical cancer with respect to patient benefits and surgeon-related aspects of a surgical learning curve. A retrospective review of the first 14 robot-assisted laparoscopic radical hysterectomies and the last 14 open radical hysterectomies in a similar clinical setting with the same surgical team was conducted. Patients were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and open radical hysterectomy (RH) before August 2006 and were candidates for a laparoscopic sentinel node procedure, pelvic lymph node dissection and robot-assisted laparoscopic radical hysterectomy (RALRH) after August 2006. Overall, blood loss in the open cases was significantly more compared with the robot cases. Median hospital stay after RALRH was 5 days less than after RH. The median theatre time in the learning period for the robot procedure was reduced from 9 h to less that 4 h and compared well to the 3 h and 45 min for an open procedure. Three complications occurred in the open group and one in the robot group. RALRH is feasible and of benefit to the patient with early stage cervical cancer by a reduction of blood loss and reduced hospital stay. Introduction of this new technique requires a learning curve of less than 15 cases that will reduce the operating time to a level comparable to open surgery

A population of gamma-ray emitting globular clusters seen with the Fermi Large Area Telescope

Globular clusters with their large populations of millisecond pulsars (MSPs) are believed to be potential emitters of high-energy gamma-ray emission. Our goal is to constrain the millisecond pulsar populations in globular clusters from analysis of gamma-ray observations. We use 546 days of continuous sky-survey observations obtained with the Large Area Telescope aboard the Fermi Gamma-ray Space Telescope to study the gamma-ray emission towards 13 globular clusters. Steady point-like high-energy gamma-ray emission has been significantly detected towards 8 globular clusters. Five of them (47 Tucanae, Omega Cen, NGC 6388, Terzan 5, and M 28) show hard spectral power indices $(0.7 < \Gamma <1.4)$ and clear evidence for an exponential cut-off in the range 1.0-2.6 GeV, which is the characteristic signature of magnetospheric emission from MSPs. Three of them (M 62, NGC 6440 and NGC 6652) also show hard spectral indices $(1.0 < \Gamma < 1.7)$, however the presence of an exponential cut-off can not be unambiguously established. Three of them (Omega Cen, NGC 6388, NGC 6652) have no known radio or X-ray MSPs yet still exhibit MSP spectral properties. From the observed gamma-ray luminosities, we estimate the total number of MSPs that is expected to be present in these globular clusters. We show that our estimates of the MSP population correlate with the stellar encounter rate and we estimate 2600-4700 MSPs in Galactic globular clusters, commensurate with previous estimates. The observation of high-energy gamma-ray emission from a globular cluster thus provides a reliable independent method to assess their millisecond pulsar populations that can be used to make constraints on the original neutron star X-ray binary population, essential for understanding the importance of binary systems in slowing the inevitable core collapse of globular clusters.Comment: Accepted for publication in A&A. Corresponding authors: J. Kn\"odlseder, N. Webb, B. Pancraz

Fermi Large Area Telescope Constraints on the Gamma-ray Opacity of the Universe

The Extragalactic Background Light (EBL) includes photons with wavelengths from ultraviolet to infrared, which are effective at attenuating gamma rays with energy above ~10 GeV during propagation from sources at cosmological distances. This results in a redshift- and energy-dependent attenuation of the gamma-ray flux of extragalactic sources such as blazars and Gamma-Ray Bursts (GRBs). The Large Area Telescope onboard Fermi detects a sample of gamma-ray blazars with redshift up to z~3, and GRBs with redshift up to z~4.3. Using photons above 10 GeV collected by Fermi over more than one year of observations for these sources, we investigate the effect of gamma-ray flux attenuation by the EBL. We place upper limits on the gamma-ray opacity of the Universe at various energies and redshifts, and compare this with predictions from well-known EBL models. We find that an EBL intensity in the optical-ultraviolet wavelengths as great as predicted by the "baseline" model of Stecker et al. (2006) can be ruled out with high confidence.Comment: 42 pages, 12 figures, accepted version (24 Aug.2010) for publication in ApJ; Contact authors: A. Bouvier, A. Chen, S. Raino, S. Razzaque, A. Reimer, L.C. Reye

Expression and Activity of a Novel Cathelicidin from Domestic Cats

Cathelicidins are small cationic antimicrobial peptides found in many species including primates, mammals, marsupials, birds and even more primitive vertebrates, such as the hagfish. Some animals encode multiple cathelicidins in their genome, whereas others have only one. This report identifies and characterizes feline cathelicidin (feCath) as the sole cathelicidin in domestic cats (Felis catus). Expression of feCath is predominantly found in the bone marrow, with lower levels of expression in the gastrointestinal tract and skin. By immunocytochemistry, feCath localizes to the cytoplasm of neutrophils in feline peripheral blood. Structurally, the mature feCath sequence is most similar to a subgroup of cathelicidins that form linear α-helices. feCath possesses antimicrobial activity against E. coli D31, Salmonella enterica serovar Typhimurium (IR715), Listeria monocytogenes and Staphylococcus pseudintermedius (clinical isolate) similar to that of the human ortholog, LL-37. In contrast, feCath lacks the DNA binding activity seen with LL-37. Given its similarity in sequence, structure, tissue expression, and antimicrobial activity, the cathelicidin encoded by cats, feCath, belongs to the subgroup of linear cathelicidins found not only in humans, but also non-human primates, dogs, mice, and rats

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure