First Results from a Broadband Search for Dark Photon Dark Matter in the 44 to 52 µeV Range with a Coaxial Dish Antenna.

We present first results from a dark photon dark matter search in the mass range from 44 to 52 µeV (10.7-12.5 GHz) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area 0.5 m^{2} and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon photon mixing parameters χ≳10^{-12} in this range at 90% confidence level. This surpasses existing constraints by about 2 orders of magnitude and is the most stringent bound on dark photons in this range below 49 µeV.

Recurrence in acromegaly: two tertiary centers experience and review of the literature.

BACKGROUND: Recurrence of acromegaly after successful surgery is a rare event, but no clear data are reported in the literature about its recurrence rates. This study aimed to evaluate the recurrence rate in a series of acromegalic patients treated by transsphenoidal surgery (TSS) with a long follow-up. METHODS: We retrospectively analyzed data from 283 acromegalic patients who underwent TSS at two pituitary units in Milan (Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico and IRCCS Humanitas Research Hospital). The diagnosis and recurrence of acromegaly were defined by both elevated IGF-1 levels and a lack of GH suppression based on appropriate criteria for the assay used at the time of diagnosis. RESULTS: After surgery, 143 patients (50%) were defined as not cured, 132 (47%) as cured and 8 (3%) as partially cured because of normalization of only one parameter, either IGF1 or GH. In the cured group, at the last follow-up (median time 86.8 months after surgery), only 1 patient (0.7%) showed full recurrence (IGF-1 + 5.61 SDS, GH nadir 1.27 µg/l), while 4 patients (3%) showed only increased IGF1. In the partially cured group at the last follow-up, 2/8 (25%) patients showed active acromegaly (IGF-1 SDS + 2.75 and + 3.62; GH nadir 0.6 and 0.5 µg/l, respectively). CONCLUSIONS: In the literature, recurrence rates range widely, from 0 to 18%. In our series, recurrence occurred in 3.7% of patients, and in fewer than 1%, recurrence occurred with elevation of both IGF-1 and the GH nadir. More frequently (25%), recurrence came in the form of incomplete normalization of either IGF-1 or GH after surgery.

Dark matter axion search using a Josephson Traveling wave parametric amplifier.

We describe the first implementation of a Josephson Traveling Wave Parametric Amplifier (JTWPA) in an axion dark matter search. The operation of the JTWPA for a period of about two weeks achieved sensitivity to axion-like particle dark matter with axion-photon couplings above 10-13 Ge V-1 over a narrow range of axion masses centered around 19.84 µeV by tuning the resonant frequency of the cavity over the frequency range of 4796.7-4799.5 MHz. The JTWPA was operated in the insert of the axion dark matter experiment as part of an independent receiver chain that was attached to a 0.56-l cavity. The ability of the JTWPA to deliver high gain over a wide (3 GHz) bandwidth has engendered interest from those aiming to perform broadband axion searches, a longstanding goal in this field.

Search for a Dark-Matter-Induced Cosmic Axion Background with ADMX.

We report the first result of a direct search for a cosmic axion background (CaB)-a relativistic background of axions that is not dark matter-performed with the axion haloscope, the Axion Dark Matter eXperiment (ADMX). Conventional haloscope analyses search for a signal with a narrow bandwidth, as predicted for dark matter, whereas the CaB will be broad. We introduce a novel analysis strategy, which searches for a CaB induced daily modulation in the power measured by the haloscope. Using this, we repurpose data collected to search for dark matter to set a limit on the axion photon coupling of a CaB originating from dark matter cascade decay via a mediator in the 800-995 MHz frequency range. We find that the present sensitivity is limited by fluctuations in the cavity readout as the instrument scans across dark matter masses. Nevertheless, we suggest that these challenges can be surmounted using superconducting qubits as single photon counters, and allow ADMX to operate as a telescope searching for axions emerging from the decay of dark matter. The daily modulation analysis technique we introduce can be deployed for various broadband rf signals, such as other forms of a CaB or even high-frequency gravitational waves.

Multi-mode analysis of surface losses in a superconducting microwave resonator in high magnetic fields.

This paper reports on a surface impedance measurement of a bulk metal niobium-titanium superconducting radio frequency (SRF) cavity in a magnetic field (up to 10 T). A novel method is employed to decompose the surface resistance contributions of the cylindrical cavity end caps and walls using measurements from multiple TM cavity modes. The results confirm that quality factor degradation of a NbTi SRF cavity in a high magnetic field is primarily from surfaces perpendicular to the field (the cavity end caps), while parallel surface resistances (the walls) remain relatively constant. This result is encouraging for applications needing high Q cavities in strong magnetic fields, such as the Axion Dark Matter eXperiment because it opens the possibility of hybrid SRF cavity construction to replace conventional copper cavities.

Search for 70 µeV Dark Photon Dark Matter with a Dielectrically Loaded Multiwavelength Microwave Cavity.

Microwave cavities have been deployed to search for bosonic dark matter candidates with masses of a few µeV. However, the sensitivity of these cavity detectors is limited by their volume, and the traditionally employed half-wavelength cavities suffer from a significant volume reduction at higher masses. Axion dark matter experiment (ADMX)-Orpheus mitigates this issue by operating a tunable, dielectrically loaded cavity at a higher-order mode, which allows the detection volume to remain large. The ADMX-Orpheus inaugural run excludes dark photon dark matter with kinetic mixing angle χ>10^{-13} between 65.5 µeV (15.8 GHz) and 69.3 µeV (16.8 GHz), marking the highest-frequency tunable microwave cavity dark matter search to date.

Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1-84) treatment.

PURPOSE: The main purpose of this study was to investigate the effects of 12 months of rhPTH (1-84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1-84) [rhPTH (1-84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy. METHODS: It is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations. RESULTS: Fourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1-84) for 12 months. At 12 months of rhPTH (1-84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1-84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described. CONCLUSIONS: Biochemical and clinical results confirm the efficacy and safety of rhPTH (1-84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

Indication to dynamic and invasive testing in Cushing's disease according to different neuroradiological findings.

PURPOSE: Dynamic testing represents the mainstay in the differential diagnosis of ACTH-dependent Cushing's syndrome. However, in case of undetectable or detectable lesion < 6 mm on MRI, bilateral inferior petrosal sinus sampling (BIPSS) is suggested by current guidelines. Aim of this study was to analyze the performance of CRH, desmopressin and high-dose dexamethasone suppression test (HDDST) in the differential diagnosis of ACTH-dependent Cushing's syndrome as well as the impact of invasive and noninvasive tests on surgical outcome in patients affected by Cushing's disease (CD). METHODS: Retrospective analysis on 148 patients with CD and 26 patients with ectopic ACTH syndrome. RESULTS: Among CD patients, negative MRI/lesion < 6 mm was detected in 97 patients (Group A); 29 had a 6-10 mm lesion (Group B) and 22 a macroadenoma (Group C). A positive response to CRH test, HDSST and desmopressin test was recorded in 89.4%, 91·4% and 70.1% of cases, respectively. Concordant positive response to both CRH/HDDST and CRH/desmopressin tests showed a positive predictive value of 100% for the diagnosis of CD. Among Group A patients with concordant CRH test and HDDST, no difference in surgical outcome was found between patients who performed BIPSS and those who did not (66.6% vs 70.4%, p = 0.78). CONCLUSIONS: CRH, desmopressin test and HDDST have high accuracy in the differential diagnosis of ACTH-dependent CS. In patients with microadenoma < 6 mm or non-visible lesion, a concordant positive response to noninvasive tests seems sufficient to diagnose CD, irrespective of MRI finding. In these patients, BIPSS should be reserved to discordant tests.

Evaluation of procoagulant imbalance in Cushing's syndrome after short- and long-term remission of disease.

OBJECTIVE: Patients with Cushing's syndrome (CS) are at high risk of venous thromboembolism related to a hypercoagulability due to procoagulant imbalance. However, whether these alterations are reversible after disease remission is still unclear. The endogenous thrombin potential (ETP) measured with and without the addition of thrombomodulin provides a global representation of coagulation and previous data confirmed hypercoagulable profile in patients with active hypercortisolism. Aim of this study was to assess the short- and long-term modification of ETP in patients with CS after disease remission. DESIGN AND METHODS: Nineteen patients with CS for whom surgical remission was achieved, were prospectively evaluated for clinical characteristics, cortisol secretion profile and ETP at different time points: (i) before surgical intervention; (ii) after 6 months and (iii) 5 years from the time of persistent remission. Nineteen healthy subjects matched for age and gender were also evaluated as control group. RESULTS: Before surgery, patients showed higher ETP-ratio (with/without thrombomodulin) than controls (0.62 ± 0.09-vs-0.56 ± 0.09, p = 0.034). No significant correlation between ETP-ratio and cortisol secretion was found. 6 months after remission, ETP-ratio was still significantly increased compared to controls (0.64 ± 0.09-vs-0.56 ± 0.09, p = 0.01), but was similar to baseline (0.64 ± 0.09-vs-0.62 ± 0.09, p = 0.87). At 5 years, ETP-ratio showed a significant decrease (0.55 ± 0.14-vs-0.62 ± 0.09, p = 0.02) and was comparable to controls (0.55 ± 0.14-vs-0.56 ± 0.09, p = 0.7). CONCLUSIONS: Plasma hypercoagulability detected in patients with active hypercortisolism persists at short-term evaluation and seems to be completely reversible after long-term remission of disease. These data, as part of a whole evaluation of thrombotic risk, can contribute to make appropriate therapeutic choice in these patients.

Spine Bone Texture Assessed by Trabecular Bone Score in Active and Controlled Acromegaly: A Prospective Study.

CONTEXT: Acromegalic patients have an increased vertebral fracture (VFx) risk due to bone quality reduction, independently of bone mineral density (BMD). OBJECTIVE: The aim of the study is to describe bone quality in acromegaly, measured by trabecular bone score (TBS), a noninvasive index for assessing bone microarchitecture. METHODS: We collected data from 18 patients (13 female, age 56.2 ±â€…15 years) newly diagnosed with acromegaly. Thirty-six age- and sex-matched healthy controls were also recruited. Pituitary function, bone and calcium-phosphorous metabolism, and BMD at spine and femur and TBS (by dual-energy x-ray absorptiometry) were assessed in acromegalic patients at diagnosis and 12 months after the achievement of insulin-like growth factor 1 (IGF-1) normalization. RESULTS: At diagnosis, BMD and the VFx prevalence were comparable between patients and controls (28.3 ±â€…5.9 vs 27.6 ±â€…3.7 and 11% vs 8.3%), whereas TBS was significantly lower in acromegalic patients (1.20 ±â€…0.13 vs 1.30 ±â€…0.06; P < .001) and carboxyterminal telopeptide (CTX) and osteocalcin were significantly higher compared to controls (707 ±â€…365.7 vs 371 ±â€…104.1 pg/mL; P = .001 and 31.6 ±â€…15.4 vs 17.0 ±â€…5.7 ng/mL; P = .001, respectively). One year after IGF-1 normalization, a significant reduction of bone turnover indexes was observed in the group of acromegalic patients surgically cured (osteocalcin decrease of 61.2%, CTX decrease of 60.3%) compared to the ones controlled by medical therapy (osteocalcin decrease of 39%, CTX decrease of 40.7%; P = .01 and P = .001, respectively). Despite these findings, no TBS or BMD variations were observed. CONCLUSION: Acromegalic patients have impaired bone quality despite normal density. Achieving normal growth hormone secretion rapidly leads to the normalization of bone turnover.

Long-term remission of acromegaly after somatostatin analogues withdrawal: a single-centre experience.

PURPOSE: A long-lasting remission of acromegaly after somatostatin analogues (SAs) withdrawal has been described in some series. Our aim was to update the disease evolution after SAs withdrawal in a cohort of acromegalic patients. METHODS: We retrospectively evaluated 21 acromegalic patients previously included in a multicentre study (Ronchi et al. 2008), updating data at the last follow-up. We added further 8 patients selected for SAs withdrawal between 2008-2018. Pituitary irradiation represented an exclusion criterion. The withdrawal was suggested after at least 9 months of clinical and hormonal disease control. Clinical and biochemical data prior and after SAs withdrawal were analysed. RESULTS: In the whole cohort (29 patients) mean age was 50 ± 14.9 years and 72.4% were females. In 69% pituitary surgery was previously performed. Overall, the median time of treatment before SAs withdrawal was 53 months (IQR = 24-84). At the last follow up in 2019, 23/29 patients (79.3%) had a disease relapse after a median time of 6 months (interquartile range or IQR = 3-12) from the drug suspension, while 6/29 (20.7%) were still on remission after 120 months (IQR = 66-150). IGF-1 levels were significantly lower before withdrawal in patients with persistent remission compared to relapsing ones (IGF-1 SDS: -1.5 ± 0.6 vs -0.11 ± 1, p = 0.01). We did not observe any other difference between patients with and without relapse, including SAs formulation, dosage and treatment duration. CONCLUSION: A successful withdrawal of SAs is possible in a subset of well-controlled acromegalic patients and it challenges the concept that medical therapy is a lifelong requirement.

Axion Dark Matter Experiment: Detailed design and operations.

Axion dark matter experiment ultra-low noise haloscope technology has enabled the successful completion of two science runs (1A and 1B) that looked for dark matter axions in the 2.66-3.1 µeV mass range with Dine-Fischler-Srednicki-Zhitnisky sensitivity [Du et al., Phys. Rev. Lett. 120, 151301 (2018) and Braine et al., Phys. Rev. Lett. 124, 101303 (2020)]. Therefore, it is the most sensitive axion search experiment to date in this mass range. We discuss the technological advances made in the last several years to achieve this sensitivity, which includes the implementation of components, such as the state-of-the-art quantum-noise-limited amplifiers and a dilution refrigerator. Furthermore, we demonstrate the use of a frequency tunable microstrip superconducting quantum interference device amplifier in run 1A, and a Josephson parametric amplifier in run 1B, along with novel analysis tools that characterize the system noise temperature.

Search for Invisible Axion Dark Matter in the 3.3-4.2 µeV Mass Range.

We report the results from a haloscope search for axion dark matter in the 3.3-4.2 µeV mass range. This search excludes the axion-photon coupling predicted by one of the benchmark models of "invisible" axion dark matter, the Kim-Shifman-Vainshtein-Zakharov model. This sensitivity is achieved using a large-volume cavity, a superconducting magnet, an ultra low noise Josephson parametric amplifier, and sub-Kelvin temperatures. The validity of our detection procedure is ensured by injecting and detecting blind synthetic axion signals.

The prevalence of silent acromegaly in prolactinomas is very low.

PURPOSE: The aim of this study was to evaluate the somatotroph axis in a large series of patients with prolactinoma to verify the prevalence of silent acromegaly in this population. METHODS: A hundred and forty-four patients were enrolled in a multicenter study: 90 were already on cabergoline (CAB) and enrolled in a cross-sectional arm (group A) with random PRL, GH and IGF-I determination on treatment (≥ 3 months), whereas 54 untreated patients were enrolled at diagnosis in a prospective arm (group B) with PRL, GH and IGF-I measurement before and after 6 and 12 months of treatment. In the presence of high IGF-I, CAB was withdrawn for 3 months and GH, IGF-I, PRL and GH during an oral Glucose Tolerance Test (OGTT) were obtained. RESULTS: High IGF-I levels (ULN 1.01-1.56) were observed in 9 patients (6.25%, 5F). After CAB withdrawal, IGF-I levels normalized in 5/9 patients, GH was < 0.4 ng/ml after OGTT in 7/9 cases or at random GH determination in one case. After CAB re-introduction, IGF-I levels re-increased in a single case. Overall, a single young female patient harboring a macroadenoma in group A was diagnosed with silent acromegaly and underwent successful transsphenoidal removal of a GH/PRL-secreting adenoma. CONCLUSION: The prevalence of silent acromegaly in prolactinomas (0.7%) is lower than previously reported and OGTT is helpful to recognize silent acromegaly. We suggest that the somatotroph axis should be evaluated at diagnosis in all cases and not systematically during follow-up.

Extended Search for the Invisible Axion with the Axion Dark Matter Experiment.

This Letter reports on a cavity haloscope search for dark matter axions in the Galactic halo in the mass range 2.81-3.31 µeV. This search utilizes the combination of a low-noise Josephson parametric amplifier and a large-cavity haloscope to achieve unprecedented sensitivity across this mass range. This search excludes the full range of axion-photon coupling values predicted in benchmark models of the invisible axion that solve the strong CP problem of quantum chromodynamics.

Determinants of outcome of transsphenoidal surgery for Cushing disease in a single-centre series.

BACKGROUND: First-line therapy of Cushing disease (CD) is transsphenoidal surgery (TSS) aimed to obtain a complete removal of the pituitary adenoma and remission of disease. PURPOSE: To analyse the surgical outcome of patients with CD who underwent TSS in our Centre. METHODS: Retrospective analysis on patients with CD who underwent TSS between 1990 and 2016. RESULTS: We analysed 102 TSS that included: 84 first TSS and 18 second and third TSS. The overall remission rate after surgery was 76.5%, with a significant higher percentage of remitted patients after the first TSS compared to the subsequent TSS (82% vs 50%, p = 0.014). The remission after the first TSS was significantly higher when performed by a dedicated surgical team (DST) (89.8% vs 71% p = 0.04) and when the immunohistochemical examination confirmed the adrenocorticotropic adenoma (87% vs 55%, p = 0.04). Neuroradiological findings influenced the surgical outcome in a non-significant manner. Post-TSS complications were reported in 32 patients, with no significant variation when TSS was performed by DST. In case of reintervention, remission of disease was obtained in 72.7% of microadenoma, while no remitted patients were observed in case of macroadenomas. The DST did not significantly improve the outcome. CONCLUSION: Cushing disease is characterized by a broad spectrum of neuroradiological presentation. Despite the availability of a DST make the TSS a safe and effective first-line treatment among all these patients, a precise pre-treatment evaluation is needed in order to define the aim of neurosurgery and to schedule the management of recurrent disease.

Search for Invisible Axion Dark Matter with the Axion Dark Matter Experiment.

This Letter reports the results from a haloscope search for dark matter axions with masses between 2.66 and 2.81 µeV. The search excludes the range of axion-photon couplings predicted by plausible models of the invisible axion. This unprecedented sensitivity is achieved by operating a large-volume haloscope at subkelvin temperatures, thereby reducing thermal noise as well as the excess noise from the ultralow-noise superconducting quantum interference device amplifier used for the signal power readout. Ongoing searches will provide nearly definitive tests of the invisible axion model over a wide range of axion masses.

Piezoelectrically Tuned Multimode Cavity Search for Axion Dark Matter.

The µeV axion is a well-motivated extension to the standard model. The Axion Dark Matter eXperiment (ADMX) collaboration seeks to discover this particle by looking for the resonant conversion of dark-matter axions to microwave photons in a strong magnetic field. In this Letter, we report results from a pathfinder experiment, the ADMX "Sidecar," which is designed to pave the way for future, higher mass, searches. This testbed experiment lives inside of and operates in tandem with the main ADMX experiment. The Sidecar experiment excludes masses in three widely spaced frequency ranges (4202-4249, 5086-5799, and 7173-7203 MHz). In addition, Sidecar demonstrates the successful use of a piezoelectric actuator for cavity tuning. Finally, this publication is the first to report data measured using both the TM_{010} and TM_{020} modes.

First Results from a Microwave Cavity Axion Search at 24 µeV.

We report on the first results from a new microwave cavity search for dark matter axions with masses above 20 µeV. We exclude axion models with two-photon coupling g_{aγγ}≳2×10^{-14} GeV^{-1} over the range 23.55