Long-Term Use of Temozolomide as Safe and Effective Therapy for an Aggressive Corticotroph Adenoma in a Very Old Patient

Background: Temozolomide (TMZ) is safe and effective in the treatment of aggressive pituitary adenomas (PAs). However, the optimal duration of TMZ therapy is still unknown. Moreover, data about administration of TMZ in elderly (≥65 years) people to treat aggressive PAs are scarce. We report the case of the oldest female patient undergoing the longest TMZ protocol described so far to treat an aggressive, initially silent corticotroph PA. Case report: The patient initially underwent partial surgical removal of the PA. Subsequent treatment with cabergoline was applied, but it was unsuccessful in controlling the growth of the residual tumor. Pasireotide and external radiation also showed to be ineffective; therefore, treatment with TMZ was started at the standard dose of 200 mg/m2/day for 5 days every 4 weeks for a total of 47 cycles. At the time of treatment's beginning, the patient was 83 years old. Radiological follow-up documented a progressive, remarkable reduction of the adenoma and the last imaging, after 39 cycles of TMZ, showed an intrasellar lesion with large areas of cystic degeneration. The patient also developed adrenal deficiency managed with glucocorticoid replacement. No major side effects were observed throughout the treatment, with exception of nausea, well controlled with anti-emetic medication. TMZ therapy was discontinued after 47 cycles; hormonal and imaging follow-up investigations documented sustained functional and dimensional response. Conclusions: Our case supports the long-term use of TMZ, confirming its safety and efficacy also for elderly patients

Optimization of Software on High Performance Computing Platforms for the LUX-ZEPLIN Dark Matter Experiment

High Energy Physics experiments like the LUX-ZEPLIN dark matter experiment face unique challenges when running their computation on High Performance Computing resources. In this paper, we describe some strategies to optimize memory usage of simulation codes with the help of profiling tools. We employed this approach and achieved memory reduction of 10-30\%. While this has been performed in the context of the LZ experiment, it has wider applicability to other HEP experimental codes that face these challenges on modern computer architectures.Comment: Contribution to Proceedings of CHEP 2019, Nov 4-8, Adelaide, Australi

Snowmass 2021 Cross Frontier Report: Dark Matter Complementarity (Extended Version)

The fundamental nature of Dark Matter is a central theme of the Snowmass 2021 process, extending across all frontiers. In the last decade, advances in detector technology, analysis techniques and theoretical modeling have enabled a new generation of experiments and searches while broadening the types of candidates we can pursue. Over the next decade, there is great potential for discoveries that would transform our understanding of dark matter. In the following, we outline a road map for discovery developed in collaboration among the frontiers. A strong portfolio of experiments that delves deep, searches wide, and harnesses the complementarity between techniques is key to tackling this complicated problem, requiring expertise, results, and planning from all Frontiers of the Snowmass 2021 process.Comment: v1 is first draft for community commen

第792回 千葉医学会例会・第二内科例会 35.

Many studies have focused on Type A and Type D personality types in the context of cardiovascular diseases (CVDs), but nothing is known about how these personality types combine to create new profiles. The present study aimed to develop a typology of Type A and Type D personality in two groups of patients affected by and at risk for coronary disease. The study involved 711 patients: 51.6% with acute coronary syndrome, 48.4% with essential hypertension (mean age = 56.4 years; SD = 9.7 years; 70.7% men). Cluster analysis was applied. External variables, such as socio-demographic, psychological, lifestyle, and clinical parameters, were assessed. Six groups, each with its own unique combined personality profile scores, were identified: Type D, Type A-Negatively Affected, Not Type A-Negatively Affected, Socially Inhibited-Positively Affected, Not Socially Inhibited, and Not Type A-Not Type D. The Type A-Negatively Affected cluster and, to a lesser extent, the Type D cluster, displayed the worst profile: namely higher total cardiovascular risk index, physical inactivity, higher anxiety and depression, and lower self-esteem, optimism, and health status. Identifying combined personality profiles is important in clinical research and practice in cardiovascular diseases. Practical implications are discussed

Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD

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

Quality of residential facilities in Italy: satisfaction and quality of life of residents with schizophrenia spectrum~disorders

Background Recovery and human rights promotion for people with Schizophrenia Spectrum Disorders (SSDs) is fundamental to provide good care in Residential Facilities (RFs). However, there is a concern about rehabilitation ethos in RFs. This study aimed to investigate the care quality of Italian RFs, the quality of life (QoL) and care experience of residents with SSD. Methods Fourty-eight RFs were assessed using a quality assessment tool (QuIRC-SA) and 161 residents with SSD were enrolled. Seventeen RFs provided high intensity rehabilitation (SRP1), 15 medium intensity (SRP2), and 16 medium-low level support (SRP3). Staff-rated tools measured psychiatric symptoms and psychosocial functioning; user-rated tools assessed QoL and satisfaction with services. RFs comparisons were made using ANOVA and Chi-squared. Results Over two-thirds patients (41.5 y.o., SD 9.7) were male. Seventy-six were recruited from SRP1 services, 48 from SRP2, and 27 from SRP3. The lowest QuIRC-SA scoring was Recovery Based Practice (45.8%), and the highest was promotion of Human Rights (58.4%). SRP2 had the lowest QuIRC-SA ratings and SRP3 the highest. Residents had similar psychopathology (p = 0.140) and functioning (p = 0.537). SRP3 residents were more employed (18.9%) than SRP1 (7.9%) or SRP2 (2.2%) ones, and had less severe negative symptoms (p = 0.016) and better QoL (p = 0.020) than SRP2 residents. There were no differences in the RF therapeutic milieu and their satisfaction with care. Conclusions Residents of the lowest supported RFs in Italy had less severe negative symptoms, better QoL and more employment than others. The lowest ratings for Recovery Based Practice across all RFs suggest more work is needed to improve recovery

Dark sectors 2016 Workshop: community report

This report, based on the Dark Sectors workshop at SLAC in April 2016, summarizes the scientific importance of searches for dark sector dark matter and forces at masses beneath the weak-scale, the status of this broad international field, the important milestones motivating future exploration, and promising experimental opportunities to reach these milestones over the next 5-10 years