Radio detection prospects for a bulge population of millisecond pulsars as suggested by Fermi LAT observations of the inner Galaxy

Analogously to globular clusters, the dense stellar environment of the Galactic center has been proposed to host a large population of as-yet undetected millisecond pulsars (MSPs). Recently, this hypothesis found support in the analysis of gamma rays from the inner Galaxy seen by the Large Area Telescope (LAT) aboard the Fermi satellite, which revealed a possible excess of diffuse GeV photons in the inner 15 deg about the Galactic center (Fermi GeV excess). The excess can be interpreted as the collective emission of thousands of MSPs in the Galactic bulge, with a spherical distribution that strongly peaks towards the Galactic center. In order to fully establish the MSP interpretation, it is essential to find corroborating evidence in multi-wavelength searches, most notably through the detection of radio pulsation from individual bulge MSPs. Based on globular cluster observations and the gamma-ray emission from the inner Galaxy, we investigate the prospects for detecting MSPs in the Galactic bulge. While previous pulsar surveys failed to identify this population, we demonstrate that, in the upcoming years, new large-area surveys with focus on regions a few degrees north or south of the Galactic center should lead to the detection of dozens of bulge MSPs. Additionally, we show that, in the near future, deep targeted searches of unassociated Fermi sources should be able to detect the first few MSPs in the bulge. The prospects for these deep searches are enhanced by a tentative gamma-ray/radio correlation that we infer from high-latitude gamma-ray MSPs. Such detections would constitute the first clear discoveries of field MSPs in the Galactic bulge, with far-reaching implications for gamma-ray observations, the formation history of the central Milky Way and strategy optimization for future radio observations.Comment: 24 pages, 17 figures, 5 tables. Minor clarifications. Matches version published in Ap

Clinical significance of the buccal fat pad: how to determine the correct surgical indications based on preoperative analysis

Background: Despite the multitude of clinical and aesthetic uses, the correct surgical indications for buccal fat pad (BFP) removal have yet to be fully elucidated. Although the procedure is widely performed and promoted for aesthetic purpose, literature lacks of studies accounting for a proper evaluation of patients undergoing BFP removal. Methods: Between 2012 and 2016 patients seeking an improvement of the malar contour by reduction of the submalar prominence have been visited at the Department of Plastic Surgery of the Institution. A preoperative MRI was requested in order to correctly identify the volume of the BFP and the presence of a masseter muscle (MM) hypertrophy. Results: According to clinical examination and the results of the preoperative imaging, patients were offered different treatment options: patients with BFP hypertrophy underwent BFP removal through an itraoral approach; patients with MM hypertrophy received injection of 50 UI of botulinum toxin (BTX). No complications were observed in the postoperative period and all patients were satisfied with the results. Conclusions: According to the experience, midface contouring procedures should take account of both surgeons’ experience, patients’ expectations and anatomical evaluation. As such, there is no given approach suitable for all cases. Suggested visual criteria, clinical examination and imaging analysis are useful in establishing patient’s condition and determining the appropriate methods of treatment to enhance the facial profile

Marked efficacy of Rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced anti-ganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the efficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Marked efficacy of rituximab in multifocal motor neuropathy associated with chronic lymphocytic leukemia

The authors describe a patient who presented a multifocal motor neuropathy (MMN) associated with a high anti-ganglioside antibody (anti-GM1 and anti-GD1) titer at the clinical onset of a B-cell chronic lymphocytic leukemia (B-CLL). Immunomodulation (IVIg plus cyclosporine) resulted in a neurological improvement and reduced anti-ganglioside antibody titers, both of which remained stable for at least six years. After this period, the patient had a severe relapse of the neuropathy, which was independent of the clinical course of the B-CLL. Both IVIg and cyclophosphamide were ineffective, and the patient became tetraplegic within six months; in the meantime, the patient displayed an increased antiganglioside antibody titer. Treatment with rituximab (RTX), which is designed to selectively inhibit B cell function, resulted in a dramatic, prompt and long-lasting neurological improvement as well as a reduced antiganglioside antibody titer. Although there are no previous reports of MMN in patients with B-CLL, the eficacy of RTX in the treatment of MMN in this patient may be considered remarkable. The expansion of B-cell clones may be a prerequisite for RTX effectiveness in MMN, and in dysimmune neuropathies in general

Combined Point of Care Tools Are Able to Improve Treatment Adherence and Health-Related Quality of Life in Patients with Severe Hemophilia: An Observational Prospective Study

Introduction: Ultrasound (US) assessment of joints is an evolving point of care tool for the detection of early joint arthropathy (Napolitano M, Kessler CM. Hemophilia A and B. Consultative Hemostasis and Thrombosis, Kitchens, 4th edition); population pharmacokinetic (pop-PK) studies are adopted as a useful instrument to set the prophylaxis regimen for patients with hemophilia, they may improve adherence (Nagao A.et al. Thromb Res. 2019 Jan; 173:79-84) and reduce the annual bleeding rate (ABR). Adherence to continuous intravenous administrations of factor VIII or Factor IX products is challenging, thus patients may experience breakthrough bleedings while on prophylaxis. Repeated US examinations of joint status have recently been advocated to attempt to remedy sub-optimal medication adherence (Di Minno A et al., Blood Rev. 2019 Jan;33:106-116). Aim of the current prospective analysis was to evaluate the impact of combined US assessment and pop-PK study on adherence to treatment and health related quality of life in patients with severe hemophilia A(HA) and B (HB) under regular prophylaxis. Material and methods: This prospective observational study was performed at a single tertiary center from January 2017 to June 2019. Research was conducted following the Helsinki Declaration. All patients included in the study provided a written informed consent for study participation. Patients with severe HA and HB routinely underwent, as part of regular 12-months follow-up visits, the following: US joints evaluation of elbows, knees and ankles using the HEAD-US protocol, treatment adherence evaluation by VERITAS-Pro questionnaire, health –related quality of life assessment by the standardized EQ-5D,EQ-VAS and pop-PK study (WAPPS-Hemo, McMaster University) as needed (i.e.in case of changes in life style, planned treatment switch); each patient visualised US and his estimated PK profile during medial encounters. Compliance to the prescribed treatment was also determined by analysis of patient diaries with infusion logs. Statistical analysis was performed using the SPSS software version 25.0 (SPSS Chicago, IL). Statistical tests were 2-sided, with a significance threshold of 0.05. Results: Twenty consecutive males with severe haemophilia were included in the current analysis, 13 with severe HA, 2 with HA with previous inhibitors and 5 HB, with a median age of 30 (range 14- 56) years and a median ABR of 5 (range:0-12). Nine patients were under primary prophylaxis, 8 under secondary prophylaxis and 3 under tertiary prophylaxis, they all self-infused at home. Four patients had one target joint and 3 patients had multiple target joints. For each enrolled subject, HEAD-US score, VERITAS-pro, EQ5D and EQ-VAS score were assessed at enrolment (T0) and at 12 (T12) and 24 (T24) months follow-up visits, respectively. Pop-PK was assessed in 11 patients: in 7 (5 HA,2 HB) it was assessed twice, before and after treatment switch to extended half-life (EHL) products, in 4 it was assessed once to modify prophylaxis treatment schedules for a more active life-style (N=2) or weight changes (N=2). Median ABR was 4 at T12 and 3.8 at T24. Reported breakthrough bleeds at T12 were 14, mainly trauma-related (N= 8) or affecting target joints (N=4), they were not reported at T24 in patients with PK-driven modified schedules (N=4) and in 4 patients under EHL treatments. Mean HEAD-US score at T0 resulted 8 (range:0-16), at T24 it was 6 (range:0-16). Mean Veritas-Pro score values were 42.7 at TO, 40.1 at T12 and 38.7 at T24. At T0, EQ-5D mean utility score was 0.82 (range: 0.68-1), at T24, the mean was 0.87 (range:0.72-1). In detail, at 24 months follow-up, there was a statistically significant (p<0.05) improvement in adherence to treatment with particular reference to the dimensions of communication and skipped doses. A tendency toward improved HEAD-US score, higher adherence and better quality of life scores, was observed in particular in patients switched to EHL products at T24, at a mean of 10 months after switching (range: 6-22 months). Conclusion: Several combined measures of haemophilia treatment monitoring, allowing visual assessment of joints status and PK profile estimates by patients have here shown to improve treatment adherence and quality of life in patients with HA and HB, this may be not only related to new available treatments but also to an increased awareness and education of patients

Realistic estimation for the detectability of dark matter subhalos using Fermi-LAT catalogs

Numerical simulations of structure formation have made remarkable progress in recent years, in particular due to the inclusion of baryonic physics evolving with the dark matter component. We generate Monte Carlo realizations of the dark matter subhalo population based on the results of the recent hydrodynamical simulation suite of Milky Way–sized galaxies [F. Marinacci, R. Pakmor, and V. Springel, Mon. Not. R. Astron. Soc. 437, 1750 (2014).MNRAA40035-871110.1093/mnras/stt2003]. We then simulate the gamma-ray sky for both the setup of the 3FGL and 2FHL Fermi Large Area Telescope (LAT) catalogs, including the contribution from the annihilation of dark matter in the subhalos. We find that the flux sensitivity threshold strongly depends on the particle dark matter mass and, more mildly, also on its annihilation channel and the observation latitude. The results differ for the 3FGL and 2FHL catalogs, given their different energy thresholds. We also predict that the number of dark matter subhalos among the unassociated sources is very small. A null number of detectable subhalos in the Fermi-LAT 3FGL catalog would imply upper limits on the dark matter annihilation cross section into bb[over ¯] of 2×10^{-26}(5×10^{-25})  cm^{3}/s with M_{DM}=50(1000)  GeV. We find less than one extended subhalo in the Fermi-LAT 3FGL catalog. As a matter of fact, the differences in the spatial and mass distribution of subhalos between hydrodynamic and dark matter–only runs do not have significant impact on the detectability of dark subhalos in gamma rays

Management of craniofacial development in the Parry-Romberg syndrome: Report of two patients

Objective: The aim of this article is to describe the orthodontic therapy for Parry-Romberg syndrome. The therapeutic goal is to minimize the wasting effects of progressive atrophy on facial development of a part of the face. Design: To correct problems affecting craniofacial development of these patients, occurring during puberty, an orthodontic appliance was employed, which helps maintain parallelism of the facial planes, in particular the mandibular plane. Setting: Orthodontic care was carried out in the Dental Clinic of the Catholic University of the Sacred Heart of Rome. Intervention: Two patients underwent orthodontic therapy for 6 years. Appliances were checked every month and modified periodically so as to adapt to facial bone growth. Results: At the end of craniofacial growth, the mandible was almost symmetric and the problem relating to atrophy remained confined to the initial area. Cephalometric analyses demonstrated that the occlusal plane and the mandibular plane maintained a straight orientation in relation to the bizygomatic plane. The ratio between the left and right side of the ramus and condyle, in the mandible, improved. Conclusions: The use of orthodontic therapy allows patients affected by hemifacial progressive atrophy to present a more harmonic face at the end of puberty when final reconstruction can be planned. These results provide for a limitation of surgical intervention to the sclerodermic area alone