Plasma calcitonin gene-related peptide levels in idiopathic intracranial hypertension: an exploratory study.

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a debilitating condition characterized by increased intracranial pressure often presenting with chronic migraine-like headache. Calcitonin gene-related peptide (CGRP) plays an important pathophysiological role in primary headaches such as migraine, whilst its role in IIH has not yet been established. METHODS: This longitudinal exploratory study included patients with IIH, episodic migraine (EM) in a headache-free interval and healthy controls (HC). Blood samples were collected from a cubital vein and plasma CGRP (pCGRP) levels were measured by standardized ELISA. RESULTS: A total of 26 patients with IIH (mean age 33.2 years [SD 9.2], 88.5% female, median BMI 34.8 kg/m2 [IQR 30.0-41.4]), 30 patients with EM (mean age 27.6 years [7.5], 66.7% female) and 57 HC (mean age 25.3 years [5.2], 56.1% female) were included. pCGRP levels displayed a wide variation in IIH as well as in EM and HC on a group-level. Within IIH, those with migraine-like headache had significantly higher pCGRP levels than those with non-migraine-like headache (F(2,524) = 84.79; p < 0.001) and headache absence (F(2,524) = 84.79; p < 0.001) throughout the observation period, explaining 14.7% of the variance in pCGRP levels. CGRP measurements showed strong intraindividual agreement in IIH (ICC 0.993, 95% CI 0.987-0.996, p < 0.001). No association was found between pCGRP levels and ophthalmological parameters. CONCLUSIONS: Although interindividual heterogeneity of pCGRP levels is generally high, migraine-like headache seems to be associated with higher pCGRP levels. CGRP may play a role in the headache pathophysiology at least in a subgroup of IIH.

Monoclonal antibodies against CGRP (R): non-responders and switchers: real world data from an austrian case series.

OBJECTIVE: Assessement of the responder and non-responder rate to consecutive monoclonal CGRP-antibody (CGRP-mAb) treatment, the presence of side effects, analysis of predictors of response and loss-of-effectiveness evaluation over time. METHODS: We conducted a retrospective analysis including 171 patients with episodic (EM) or chronic migraine (CM), who received one, two or three different CGRP-mAbs. Non-response was defined as ≤ 50% reduction of monthly migraine days (MMDs) in EM and ≤ 30% reduction of MMDs in CM after 3 months of treatment. RESULTS: 123 (71.9%) responded to the first mAb. Side effects led to treatment discontinuation in 9 (5.3%) patients. Of the 26 patients who did not respond to the first mAb or experienced a loss of efficacy over time, 11 (42.3%) responded to the second and two (28.6%) of 7 to the third monoclonal antibody. Poor response to therapy was associated with a higher monthly migraine frequency (p = 0.028), a higher number of prior preventive migraine therapies (p = 0.011) and medication overuse (p = 0.022). CONCLUSION: Our findings support mAb-class switch in non-responders or in patients experiencing a loss of effectiveness. The use of a third CGRP-mAb could be beneficial for some patients.

[Septic arthritis]. / Die septische Arthritis.

Septic arthritis Abstract. A painful, red, and swollen joint may have different causes. Septic arthritis is one of the most serious conditions and should be diagnosed and treated right away. In the native joint, an infection can damage the cartilage within the first 24 hours with impacts on joint function including lingering joint problems leading to possible future joint destruction. An interdisciplinary approach is essential for achieving optimal results. Most infections are caused by bacteria from the patient's own microbiome. In general, the incidence of native joint infections is growing, whether it is due to more appropriate diagnostics, or an actual increase cannot be determined at this point. In case of an acute infection, the patients usually describe a relatively short and acute period of pain, redness, and swelling of the affected joint. For diagnostic purposes the common blood serum laboratory work-up serves as a basis, complemented by puncture of the affected joint. Cell count and cell differentiation in the synovial liquid, microbiological and histopathological workup serve as gold standard in detecting septic arthritis. Septic arthritis lacks a distinctive presentation and other inflammatory conditions, like CPPD and gout must be considered. Prior to antibiotic therapy, joint lavage is the most important method to reduce bacterial load, leading to an improved outcome. Prognosis is determined by a swift diagnosis and initiation of therapy. The patient's comorbidities are significant, especially immunocompromising factors such as rheumatoid arthritis, diabetes or immunomodulating therapy. In case of a second focus of infection, chronic kidney disease or older age, patients are at greater risk for an inferior outcome.

Primary headache disorders in adolescents in North- and South-Tyrol: Findings of the EVA-Tyrol-Study.

OBJECTIVE: Assessment of the prevalence of primary headache disorders, associated risk factors and use of acute/preventive medication in a representative large sample of adolescents. METHODS: Within the EVA-Tyrol project, a community-based non-randomized controlled cross-sectional study, data was collected from adolescents aged 14-19 years from 45 sites across North-, East- and South Tyrol. Headaches were classified according to the latest ICHD-3 and assessed by headache specialists in face-to-face interviews. FINDINGS: Of 1923 participants 930 (48.4%) reported having headaches. Female to male ratio was 2:1. Migraine, tension-type headache and other headache were diagnosed in 10%, 30.2% and 8.2% respectively. Medication overuse was diagnosed in 3.4%, increasing up to 21.7% in participants with chronic headache. The use of preventative medication was not reported by any adolescent. Sleep disturbances (p < 0.05), alcohol consumption (p < 0.05), low physical activity (p < 0.01) and high screen time exposure (p < 0.01) were associated with an increased risk of headaches. CONCLUSION: We report high prevalence of primary headache disorders and medication overuse in a large community-based sample of teenagers. Acute and preventive non-drug and pharmacological treatments are not established due to lack of paediatric headache outpatient clinics. Promoting health education in teenagers and encouraging public awareness, including that of health care providers is pivotal.Trial registration: EVA-Tyrol has been retrospectively registered at clinicaltrials.gov under https://clinicaltrials.gov/ct2/show/NCT03929692 since April 29, 2019.

Head/neck pain characteristics after spontaneous cervical artery dissection in the acute phase and on a long-run.

OBJECTIVE: Head/neck pain is one of the primary symptoms associated with spontaneous cervical artery dissection. Still, data on pain quality, intensity, and long-term dynamics are scarce. METHODS: Spontaneous cervical artery dissection subjects were included if mural hematoma was visualised through T1 fat-saturated MRI at baseline. All available medical records were evaluated and patients were invited to standardised clinical follow-up visits at least 1 year after the index event. RESULTS: In total, 279 subjects were included in the ReSect-study with head/neck pain being the most frequent symptom of spontaneous cervical artery dissection (220 of 273, 80.6%). Pain was of pulling nature in 107 of 218 (49.1%), and extended to the neck area in 145 of 218 (66.5%). In those with prior headache history, pain was novel in quality in 75.4% (42 of 55). Median patient-reported pain intensity was 5 out of 10 with thunderclap-type headache being uncommon (12 of 218, 5.5%). Prior to hospital admission, head/neck pain rarely responded to self-medication (32 of 218, 14.7%). Characteristics did not differ between subjects with and without cerebral ischemia. Pain resolved completely in all subjects within a median of 13.5 days (IQR 12). Upon follow-up in 42 of 164 (25.6%) novel recurring headache occurred, heterogeneous in quality, localisation and intensity. CONCLUSION: We present an in-depth analysis of spontaneous cervical artery dissection-related head/neck pain characteristics and its long-term dynamics.

Searching for Dark Matter with an Optical Cavity and an Unequal-Delay Interferometer.

We propose a new type of experiment that compares the frequency of a clock (an ultrastable optical cavity in this case) at time t to its own frequency some time t-T earlier, by "storing" the output signal (photons) in a fiber delay line. In ultralight oscillating dark matter (DM) models, such an experiment is sensitive to coupling of DM to the standard model fields, through oscillations of the cavity and fiber lengths and of the fiber refractive index. Additionally, the sensitivity is significantly enhanced around the mechanical resonances of the cavity. We present experimental results of such an experiment and report no evidence of DM for masses in the [4.1×10^{-11}, 8.3×10^{-10}] eV region. In addition, we improve constraints on the involved coupling constants by one order of magnitude in a standard galactic DM model, at the mass corresponding to the resonant frequency of our cavity. Furthermore, in the model of relaxion DM, we improve on existing constraints over the whole DM mass range by about one order of magnitude, and up to 6 orders of magnitude at resonance.

CGRP-antibodies, topiramate and botulinum toxin type A in episodic and chronic migraine: A systematic review and meta-analysis.

BACKGROUND: The approval of monoclonal antibodies for prevention of migraine has revolutionized treatment for patients. Oral preventatives are still considered first line treatments as head-to-head trials comparing them with antibodies are lacking. METHODS: The main purpose of this study was to provide a comparative overview of the efficacy of three commonly prescribed migraine preventative medication classes. For this systematic review and meta-analysis, we searched the databases CENTRAL, EMBASE, and MEDLINE until 20 March 2020. We included RCTs reporting the 50% response rates for topiramate, Botulinum Toxin Type A and monoclonal antibodies against CGRP(r). Studies were excluded if response rates were not reported, treatment allocation was unclear, or if study quality was insufficient. Primary outcome measure were the 50% response rates. The pooled odds ratios with 95% confidence intervals were calculated with the random effects model. The study was registered at PROSPERO (CRD42020222880). FINDINGS: We identified 6552 reports. Thirty-two were eligible for our review. Studies assessing monoclonal antibodies included 13,302 patients and yielded pooled odds ratios for the 50% response rate of 2.30 (CI: 2.11-2.50). Topiramate had an overall effect estimate of 2.70 (CI: 1.97-3.69) with 1989 included patients and Botulinum Toxin Type A achieved 1.28 (CI: 0.98-1. 67) with 2472 patients included. INTERPRETATION: Topiramate, botulinum toxin type A and monoclonal antibodies showed higher odds ratios in achieving a 50% response rate compared to placebo. Topiramate numerically demonstrated the greatest effect size but also the highest drop-out rate.

CGRP measurements in human plasma - a methodological study.

BACKGROUND: Calcitonin gene-related peptide plasma levels have frequently been determined as a biomarker for primary headaches. However, published data is often inconsistent resulting from different methods that are not precisely described in most studies. METHODS: We applied a well-proven enzyme-linked immunosorbent assay to measure calcitonin gene-related peptide concentrations in human blood plasma, we modified parameters of plasma preparation and protein purification and used calcitonin gene-related peptide-free plasma for standard solutions, which are described in detail. RESULTS: Calcitonin gene-related peptide levels are stable in plasma with peptidase inhibitors and after deep-freezing. Calcitonin gene-related peptide standard solutions based on synthetic intercellular fluid or pooled plasma with pre-absorbed calcitonin gene-related peptide influenced the measurements but yielded both comprehensible results. In a sample of 56 healthy subjects the calcitonin gene-related peptide plasma levels varied considerably from low (<50 pg/mL) to very high (>500 pg/mL) values. After a 12-hour exposure of these subjects to normobaric hypoxia the individual calcitonin gene-related peptide levels remained stable. CONCLUSION: Buffering with peptidase inhibitors and immediate freezing or processing of plasma samples is essential to achieve reliable measurements. Individuals show considerable differences and partly high calcitonin gene-related peptide plasma levels without detectable pathological reason. Thus plasma measurements are suited particularly to follow calcitonin gene-related peptide levels in longitudinal studies.The use of data for this study was approved by the Ethics Committee of the MedicalUniversity of Innsbruck (https://www.i-med.ac.at/ethikkommission/; EK Nr: 1242/2017).

Determination of the Three-Dimensional Magnetic Field Vector Orientation with Nitrogen Vacany Centers in Diamond.

Absolute knowledge about the magnetic field orientation plays a crucial role in single spin-based quantum magnetometry and the application toward spin-based quantum computation. In this paper, we reconstruct the three-dimensional orientation of an arbitrary static magnetic field with individual nitrogen vacancy (NV) centers in diamond. We determine the polar and the azimuthal angle of the magnetic field orientation relative to the diamond lattice. Therefore, we use information from the photoluminescence anisotropy of the NV, together with a simple pulsed optically detected magnetic resonance experiment. Our nanoscopic magnetic field determination is generally applicable and does not rely on special prerequisites such as strongly coupled nuclear spins or particular controllable fields. Hence, our presented results open up new paths for precise NMR reconstructions and the modulation of the electron-electron spin interaction in EPR measurements by specifically tailored magnetic fields.

Migraine and aura triggered by normobaric hypoxia.

BACKGROUND: For future experimental studies or the development of targeted pharmaceutical agents, a deeper insight into the pathophysiology of migraine is of utmost interest. Reliable methods to trigger migraine attacks including aura are desirable to study this complex disease in vivo. METHODS: To investigate hypoxia as a trigger for migraine and aura, we exposed volunteers diagnosed with migraine, with (n = 16) and without aura (n = 14), to hypoxia utilizing a hypoxic chamber adjusted to a FiO2 of 12.6%. The occurrence of headache, migraine, aura, and accompanying symptoms were registered and vital signs were collected for 6 hours under hypoxia and 2 hours of follow-up. A binary logistic regression analysis examined the probability of triggering headaches, migraines, aura, photo- and phonophobia. FINDINGS: Of 30 participants, 24 (80.0%) developed headaches and 19 (63.3%) migraine, five (16.7%) reported aura. Two patients that developed aura never experienced aura symptoms before in their life. The increase of mean heart frequency was higher in patients developing headaches or migraine. Mean SpO2 during hypoxia was 83.39%. CONCLUSION: Hypoxia was able to trigger migraine attacks and aura independently of any pharmacological agent.

Is there still a role for hypothermia in neurocritical care?

PURPOSE OF REVIEW: Therapeutic hypothermia (i.e. induced body core temperature ≈ 33-35°C) in neurological patients with cerebrovascular disease and traumatic brain injury is a controversially discussed issue in the literature. In this review, we have included the most recently published research covering the use of therapeutic hypothermia and targeted temperature management in neurologic diseases and translated the results into a clinical decision support for the professional healthcare community. RECENT FINDINGS: Recent findings from large multicenter studies investigating therapeutic hypothermia in patients with various acute neurologic diseases have revealed that although short-term and long-term temperature modulation on different temperature levels is feasible with the latest device technology, the effect on outcome is controversial. SUMMARY: There is overwhelming evidence that fever is an independent predictor of morbidity and mortality in patients with acute severe neurologic diseases. Although therapeutic hypothermia has been proven to be a potent neuroprotective measure acting on various levels in animal models, many questions such as optimal depth of target temperature, speed of rewarming, duration of cooling and management of side-effects accompanying therapeutic hypothermia are unresolved in human. Therefore, the application of therapeutic hypothermia outside of strictly supervised clinical trials must be carefully considered.

Triptans for Acute Migraine Headache: Current Experience With Triptan Use and Prescription Habits in a Tertiary Care Headache Outpatient Clinic: An Observational Study.

BACKGROUND: Triptans are recommended as first-line therapy in the acute phase of a migraine attack. We describe patterns of triptan use in a tertiary care headache outpatient clinic, particularly addressing factors that are associated with triptan discontinuation. METHODS: From December 2009 until August 2012, demographic and clinical data of consecutive patients with migraine were collected. The Headache Impact Test (HIT-6) was used to measure the adverse impact of headaches. Factors associated with triptan discontinuation were analyzed using binary logistic regression. RESULTS: Of 511 migraine patients included, 73.2% (n = 374) were triptan naïve on first consultation. At follow-up, 57.1% of new triptan users (n = 72/126) reported pain-freedom or pain relief after 2 hours, 40.5% (n = 51/126) did not refill their triptan, another 15.1% (n = 19/126) switched to a different type of triptan. Negative response to triptan treatment and substantial or severe headache impact (HIT-6 score ≥56) at first follow-up were associated with triptan discontinuation (OR 0.39 [95% CI 0.20-0.78], P = .007; OR 3.33 [95% CI 1.10-10.03], P = .033). CONCLUSIONS: Although triptans have been in clinical use for more than two decades, many migraine sufferers in our study population were found to be triptan naïve on first consultation. The HIT-6 score may be used as an indicator of triptan adherence and help to identify patients at risk for triptan discontinuation.

A practical definition of pin site infection.

Pin Site Infection (PSI) is the most common complication of external fixation treatment. Several classifications and diagnostic approaches have been used with reported incidences varying widely from 1 to 100 %. The quality of the existing literature is limited by the absence of a definition. This renders comparing literature and developing evidence-based algorithms for prevention, diagnostics, and treatment difficult to impossible. Similar problems were identified with prosthetic joint infection (PJI) and fracture-related infection (FRI) in recent years, resulting in new, validated definitions. PSI is complicated by the complexity of the issue. Numerous factors in PSI need consideration. Factors may be related to the patient, the surgical technique, the pin-bone interface, the pin-skin interface, the choice of external fixation device and/or the material used and its properties. Reliably diagnosing PSI is one of the most pressing issues. New definitions for FRI or PJI have diagnostic criteria which can be either confirmatory or suggestive. Any positive finding of a confirmatory criterion constitutes an infection. Although PSI resembles PJI and FRI, distinct differences are present. The skin is never closed, and bacterial colonization is inevitable along the treatment duration. The external fixator is only temporarily in place; thus, the goal of all measures is to continue the external fixator until the intended indication is reached. This paper proposes the principles of a definition of PSI. This definition is not designed to guide any treatment of PSI. Its purpose is to create common ground for clinical investigations and publishing further research.

Clinical Outcome following Management of Severe Osteomyelitis due to Pin Site Infection.

Aim: This study has investigated cases of pin site infection (PSI) which required surgery for persistent osteomyelitis (OM) despite pin removal. Materials and methods: Patients requiring surgery for OM after PSI between 2011 and 2021 were included in this retrospective cohort study. Single-stage surgery was performed in accordance with a protocol at one institution. This involved deep sampling, debridement, implantation of local antibiotics, culture-specific systemic antibiotics and soft tissue closure. A successful outcome was defined as an infection-free interval of at least 24 months following surgery. Results: Twenty-seven patients were identified (the sites were 22 tibias, 2 humeri, 2 calcanei, 1 radius); about 85% of them were males with a median age of 53.9 years. The majority of infections (21/27) followed fracture treatment. Fifteen patients were classified as BACH uncomplicated and 12 were BACH complex. Staphylococci were the most common pathogens, polymicrobial infections were detected in five cases (19%). Seven patients required flap coverage which was performed in the same operation.After a median of 3.99 years (2.00-8.05) follow-up, all patients remained infection free at the site of the former OM. Wound leakage after local antibiotic treatment was seen in 3/27 (11.1%) cases but did not require further treatment. Conclusion: Osteomyelitis after PSI is uncommon but has major implications for the patient as 7 patients needed flap coverage. This reinforces the need for careful pin placement and pin site care to prevent deep infection. These infections were treated in accordance with a protocol and were not managed simply by curettage. All patients treated in this manner remained infection-free after a minimum follow-up of 2 years suggesting that this protocol is effective. Clinical significance: Pin site infection is a very common complication in external fixation. The sequela of a chronic pin site OM is rare but the implications to the patient are huge. In this series, more than a quarter of patients required flap coverage as part of the treatment of the deep infection. How to cite this article: Frank FA, Pomeroy E, Hotchen AJ, et al. Clinical Outcome following Management of Severe Osteomyelitis due to Pin Site Infection. Strategies Trauma Limb Reconstr 2024;19(1):21-25.

CNT-PUFs: Highly Robust and Heat-Tolerant Carbon-Nanotube-Based Physical Unclonable Functions.

In this work, we explored a highly robust and unique Physical Unclonable Function (PUF) based on the stochastic assembly of single-walled Carbon NanoTubes (CNTs) integrated within a wafer-level technology. Our work demonstrated that the proposed CNT-based PUFs are exceptionally robust with an average fractional intra-device Hamming distance well below 0.01 both at room temperature and under varying temperatures in the range from 23 ∘C to 120 ∘C. We attributed the excellent heat tolerance to comparatively low activation energies of less than 40 meV extracted from an Arrhenius plot. As the number of unstable bits in the examined implementation is extremely low, our devices allow for a lightweight and simple error correction, just by selecting stable cells, thereby diminishing the need for complex error correction. Through a significant number of tests, we demonstrated the capability of novel nanomaterial devices to serve as highly efficient hardware security primitives.

Evolution of pancreas transplantation: long-term results and perspectives from a high-volume center.

OBJECTIVE: To describe the evolution of pancreas transplantation from 1979 to 2011. The aim was to examine factors influencing long-term patient and graft survival, surgical methods, and risk factors influencing organ performance after transplantation. BACKGROUND: Pancreas transplantation has become the therapy of choice for patients suffering insulin-dependent diabetes and end stage renal failure. METHODS: Retrospective analysis of 509 consecutive pancreas transplants (442 simultaneous pancreas and kidney [SPK], 20 pancreas transplanted alone [PTA], and 47 pancreas transplanted after kidney [PAK]), performed at the University Hospital Innsbruck. The data were statistically analyzed using the Kaplan-Meier method and log-rank test. RESULTS: After overcoming initial immunological and technical problems between 1979 and 1988 (5-year pancreas graft survival rate, 29.7%), pancreas transplantation evolved during the second decade (1989-1996; 5-year pancreas graft survival rate, 42.2%). Technical changes, optimized immunosuppression, careful pretransplant evaluation, and improved graft monitoring have become standard in the last decade and result in excellent 5-year patient (94.3%), kidney (89.4%), and pancreas (81.5%) graft survival. Five-year graft survival was superior in SPK (68.8%) compared with PAK (62.5%) and PTA (16.4%). SPK retransplantation can be carried out safely with 5-year patient (87.5%) and pancreas graft (75.0%) survival. Overall 5-year patient survival after loss of the first pancreas graft is significantly better in patients who underwent retransplantation (89.4% vs. 67.9%, P = 0.001). Long-term pancreas graft survival is independent of donor body mass index, sex, and cause of death, anastomosis time and the number of human leukocyte antigen (HLA) mismatches, recipient age, body mass index, sex, current panel reactive antibodies, and waiting time. Significant risk factors for reduced graft survival are cold ischemia time and donor age. CONCLUSIONS: During the last 32 years, many problems in pancreas transplantation have been overcome and it may currently represent the therapeutic gold standard for some patients with diabetes and end stage renal failure.

Hypoxia-related mechanisms inducing acute mountain sickness and migraine.

Experimental models of human diseases are vital for pathophysiological and therapeutic research. To investigate the initiation, maintenance, pathophysiology and even termination of a migraine/headache attack these models are urgently needed. Results from different studies promote the profound involvement of hypoxia in migraine and other primary/secondary headaches. The possible mechanisms that drive the induction of headaches through hypoxia are still unknown, but several modes of action, such as increased blood flow, dilation of cerebral arteries, the release of nitroglycerin, calcitonin gene-related peptide and adenosine or increased oxygen extraction are discussed intensively. In studies exposing healthy volunteers and people with a history of migraine to controlled normobaric hypoxia, our research group could demonstrate normobaric hypoxia to be an effective trigger of migraine headaches. Furthermore, a longitudinal measurement of calcitonin gene-related peptide (CGRP), during a hypoxic challenge in migraine patients, revealed increasing CGRP levels with prolonged hypoxic challenge. Since GRP has been linked to migraine and other headache disorders, hypoxia could be regarded as initiator for headaches on a neurotransmitter basis. Furthermore, it has been known for more than 2 decades from studies in vitro and in vivo that hypoxia can induce cortical spreading depression, a phenomenon believed to represent aura. Considering the increased prevalence of migraine in altitude populations and the solid pathophysiological changes on cellular and neurotransmitter level-the role of hypoxia should be investigated in greater detail by the headache community.

Short Report of Longitudinal CGRP-Measurements in Migraineurs During a Hypoxic Challenge.

Background: Calcitonin gene related peptide (CGRP) plays a key role in the pathophysiology of migraine and is therefore considered a potential biomarker for primary headache disorders. The challenge remaining is establishing standardized protocols for its assessment in various extracellular compartments and identifying pathological situations associated with an increase in CGRP. Methods: We performed longitudinal measurements of CGRP plasma levels in 30 volunteers with the diagnosis of episodic migraine with and without aura under controlled circumstances during an induced migraine attack under a hypoxic challenge. Blood samples were collected from a cubital vein and CGRP plasma levels measured using ELISA. Results: CGRP levels varied significantly between the subjects at baseline (15.48-1,889.31 pg/ml) but were neither associated with socio-demographic data nor with headache/migraine frequency or intensity collected before hypoxic exposure. CGRP levels during hypoxia fluctuated around baseline and increased with prolonged hypoxia but did not differ significantly in subjects with migraine or headache compared to those without. However, subjects experiencing migraine without aura showed significantly higher levels than those with aura. Ictal CGRP levels were increased in females, in subjects with a negative family history regarding headaches, in those older than 30 years of age or with a recent headache attack before the experiment (p < 0.05). Conclusion: CGRP plasma levels seem to be highly variable even at baseline in migraine patients and increased during hypoxic challenge and migraine attacks. This is the first in human longitudinal measurement of peripheral CGRP levels during induced migraine attacks using a highly standardized protocol.

A 500-km Cascaded White Rabbit Link for High-Performance Frequency Dissemination.

We perform experiments exploring the use of white rabbit precision time protocol (WR-PTP) for time and frequency dissemination over long-distance optical fiber links. We use unidirectional links, to ensure compatibility with active telecommunication networks, and White Rabbit equipment with modifications for improved performance. Using fiber spools, we realize a 500 km, four-span cascaded white rabbit link. We show short term fractional frequency stability of 2×10-12 , averaging down to 2×10-15 at one day of integration time, with no frequency shift within the statistical uncertainty. We demonstrate the impact of increasing the White Rabbit SoftPLL bandwidth and the PTP message rate. We show evidence of the effect of thermal fluctuations acting on the fiber, and finally discuss the limitations of the achieved performance. We show comparisons with experimental data acquired with commercial good quality global positioning system (GPS) receivers and show that the medium- and long- term stability and accuracy are more than one order of magnitude better with a WR-PTP link.

Hospital Admissions of Huntington's Disease Patients in a Huntington's Disease Centre Between 2011 and 2016: A Retrospective Analysis.

Background: Huntington's Disease (HD) is a relentlessly progressive genetic neurodegenerative disorder with characteristic motor, psychiatric, and behavioral abnormalities that inevitably results in severe disability and death. Many patients have multiple hospital admissions during the disease course, but there is limited information which problems lead to hospitalization. Objectives: To assess acute reasons for hospital admissions, discharge routes, and clinical characteristics of HD patients in a retrospective analysis. Methods: We reviewed all medical records of patients with an established diagnosis of Huntington's Disease and hospital admissions between 2011 and 2016 in our local hospital-based database. Results: There were 135 hospital admissions in 53 HD patients during the review period, representing a median of two admissions per patient. Median duration of hospitalization was seven days. The most frequent reason for admission was a worsening of HD motor symptoms (n = 77, 57.0%) such as chorea, parkinsonism, gait problems, falls, and dysphagia. Psychiatric symptoms related to HD were the second most common reason for admission (n = 58, 43.0%). Infections (including aspiration pneumonia) and traumas/surgical procedures were only responsible for 6.7% and 5.9% of admissions, respectively. Emergency admissions were not common (42.2%), and the majority of patients were able to return to their previous residency upon discharge (85.2%, home or nursing home). Recurrent admissions were associated with worse motor function and functional capacity. Conclusions: Worsening of motor and psychiatric symptoms associated with Huntington's Disease were the most common reasons for hospital admissions. Therefore, our data highlight the importance of optimal symptom control in HD patients.