Tackling the Limits of Optical Fiber Links

International audienceWe theoretically and experimentally investigate relevant noise processes arising in optical fiber links, which fundamentally limit their relative stability. We derive the unsuppressed delay noise for three configurations of optical links: two-way method, Sagnac interferometry, and actively compensated link, respectively designed for frequency comparison, rotation sensing, and frequency transfer. We also consider an alternative two-way setup allowing real-time frequency comparison and demonstrate its effectiveness on a proof-of-principle experiment with a 25-km fiber spool. For these three configurations, we analyze the noise arising from uncommon fiber paths in the interferometric ensemble and design optimized interferometers. We demonstrate interferometers with very low temperature sensitivity of respectively -2.2, -0.03 and 1 fs/K. We use one of these optimized interferometers on a long haul compensated fiber link of 540 km. We obtain a relative frequency stability of 3x10^-20 after 10,000 s of integration time

Association of Variants in the SPTLC1 Gene With Juvenile Amyotrophic Lateral Sclerosis

Importance: Juvenile amyotrophic lateral sclerosis (ALS) is a rare form of ALS characterized by age of symptom onset less than 25 years and a variable presentation.Objective: To identify the genetic variants associated with juvenile ALS.Design, Setting, and Participants: In this multicenter family-based genetic study, trio whole-exome sequencing was performed to identify the disease-associated gene in a case series of unrelated patients diagnosed with juvenile ALS and severe growth retardation. The patients and their family members were enrolled at academic hospitals and a government research facility between March 1, 2016, and March 13, 2020, and were observed until October 1, 2020. Whole-exome sequencing was also performed in a series of patients with juvenile ALS. A total of 66 patients with juvenile ALS and 6258 adult patients with ALS participated in the study. Patients were selected for the study based on their diagnosis, and all eligible participants were enrolled in the study. None of the participants had a family history of neurological disorders, suggesting de novo variants as the underlying genetic mechanism.Main Outcomes and Measures: De novo variants present only in the index case and not in unaffected family members.Results: Trio whole-exome sequencing was performed in 3 patients diagnosed with juvenile ALS and their parents. An additional 63 patients with juvenile ALS and 6258 adult patients with ALS were subsequently screened for variants in the SPTLC1 gene. De novo variants in SPTLC1 (p.Ala20Ser in 2 patients and p.Ser331Tyr in 1 patient) were identified in 3 unrelated patients diagnosed with juvenile ALS and failure to thrive. A fourth variant (p.Leu39del) was identified in a patient with juvenile ALS where parental DNA was unavailable. Variants in this gene have been previously shown to be associated with autosomal-dominant hereditary sensory autonomic neuropathy, type 1A, by disrupting an essential enzyme complex in the sphingolipid synthesis pathway.Conclusions and Relevance: These data broaden the phenotype associated with SPTLC1 and suggest that patients presenting with juvenile ALS should be screened for variants in this gene.</p

Impact of the COVID-19 Pandemic on Emergency Department Transfers to a Higher Level of Care

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a reduction in emergency department (ED) visits was seen nationally according to the US Centers for Disease Control and Prevention. However, no data currently exists for the impact of ED transfers to a higher level of care during this same time period. The primary objective of the study was to determine whether the COVID-19 pandemic affected the rate of non-COVID-19 transfers from a rural community ED.Methods: We completed a retrospective chart review of all ED patients who presented to Kingman Regional Medical Center in Kingman, Arizona, from March 1–June 31, 2019 and March 1–June 31, 2020. To ensure changes were not due to seasonal trends, we examined transfer rates from the same four-month period in 2019 and 2020. Patients were included in the study if they were transferred to an outside facility for a higher level of care not related to COVID-19.Results: Between the time periods studied there was a 25.33% (P = 0.001) reduction in total ED volume and a 21.44% (P = 0.009) reduction in ED transfers to a higher level of care. No statistical difference was noted in ED transfer volume following adjustment for decreased ED volumes. Transfers for gastroenterology (45%; P = 0.021), neurosurgery (29.2%; P = 0.029), neurology (76.3%; P &lt; 0.001), trauma (37.5%; P = 0.039), urology (41.8%; P = 0.012), and surgery (56.3%; P = 0.028) all experienced a decrease in transfer rates during the time period studied. When gender was considered, males exhibited an increased rate of transfers to psychiatric facilities (P = 0.018).Conclusion: Significant reductions in both ED volume and transfers have coincided with the emergence of the COVID-19 pandemic. Further research is needed to determine how the current pandemic has affected patient care

Impact of the COVID-19 Pandemic on Emergency Department Transfers to a Higher Level of Care

Introduction: During the coronavirus disease 2019 (COVID-19) pandemic, a reduction in emergency department (ED) visits was seen nationally according to the US Centers for Disease Control and Prevention. However, no data currently exists for the impact of ED transfers to a higher level of care during this same time period. The primary objective of the study was to determine whether the COVID-19 pandemic affected the rate of non-COVID-19 transfers from a rural community ED.Methods: We completed a retrospective chart review of all ED patients who presented to Kingman Regional Medical Center in Kingman, Arizona, from March 1–June 31, 2019 and March 1–June 31, 2020. To ensure changes were not due to seasonal trends, we examined transfer rates from the same four-month period in 2019 and 2020. Patients were included in the study if they were transferred to an outside facility for a higher level of care not related to COVID-19.Results: Between the time periods studied there was a 25.33% (P = 0.001) reduction in total ED volume and a 21.44% (P = 0.009) reduction in ED transfers to a higher level of care. No statistical difference was noted in ED transfer volume following adjustment for decreased ED volumes. Transfers for gastroenterology (45%; P = 0.021), neurosurgery (29.2%; P = 0.029), neurology (76.3%; P &lt; 0.001), trauma (37.5%; P = 0.039), urology (41.8%; P = 0.012), and surgery (56.3%; P = 0.028) all experienced a decrease in transfer rates during the time period studied. When gender was considered, males exhibited an increased rate of transfers to psychiatric facilities (P = 0.018).Conclusion: Significant reductions in both ED volume and transfers have coincided with the emergence of the COVID-19 pandemic. Further research is needed to determine how the current pandemic has affected patient care

Enhanced Cytomegalovirus Infection of Developing Brain Independent of the Adaptive Immune System

Cytomegalovirus (CMV) has been suggested as the most prevalent infectious agent causing neurological dysfunction in the developing brain; in contrast, CMV infections are rare in the adult brain. One explanation generally given for the developmental susceptibility to the virus is that the developing immune system is too immature to protect the central nervous system from viral infection, but as the immune system develops it can protect the brain. We suggest an alternate view: that developing brain cells are inherently more susceptible to CMV infection, independent of the immune system. We used a recombinant mouse CMV that leads to green fluorescent protein expression in infected cells. Control experiments demonstrated a high correlation between the number of cells detected with the viral GFP reporter gene and with immunocytochemical detection of the virus. After intracerebral inoculation, the number of CMV-infected cells in neonatal brains was many times greater than in mature control or mature immunodepressed SCID mice, and the mortality rate of neonates was substantially greater than SCID or control adults. Parallel experiments with live brain slices inoculated in vitro, done in the absence of the systemic immune system, generated similar data, with immature hippocampus, hypothalamus, cortex, striatum, and cerebellum showing substantially greater numbers of infected cells (100-fold) than found in adult slices in these same regions. Interestingly, in the cerebellar cortex, CMV-infected cells were more prevalent in the postmitotic Purkinje cell layer than in the mitotic granule cell layer, suggesting a selective infection of some cell types not dependent on cell division. Together, these data support the view that CMV has an intrinsic preference for infection of developing brain cells, independent, but not mutually exclusive, of the developmental status of the systemic immune system in controlling CMV infection

Towards large scale metrological fibre network

In the frame of the REFIMEVE+ project, aiming at disseminating an optical frequency standard to more than 20 laboratories in France, we present the progress made towards a metrological fibre wide-area network

Conditioning- and time-dependent increases in context fear and generalization.

A prominent feature of fear memories and anxiety disorders is that they endure across extended periods of time. Here, we examine how the severity of the initial fear experience influences incubation, generalization, and sensitization of contextual fear memories across time. Adult rats were presented with either five, two, one, or zero shocks (1.2 mA, 2 sec) during contextual fear conditioning. Following a recent (1 d) or remote (28 d) retention interval all subjects were returned to the original training context to measure fear memory and/or to a novel context to measure the specificity of fear conditioning. Our results indicate rats that received two or five shocks show an "incubation"-like enhancement of fear between recent and remote retention intervals, while single-shocked animals show stable levels of context fear memory. Moreover, when fear was tested in a novel context, 1 and 2 shocked groups failed to freeze, whereas five shocked rats showed a time-dependent generalization of context memory. Stress enhancement of fear learning to a second round of conditioning was evident in all previously shocked animals. Based on these results, we conclude that the severity or number of foot shocks determines not only the level of fear memory, but also the time-dependent incubation of fear and its generalization across distinct contexts

In-line extraction of an ultra-stable frequency signal over an optical fiber link

We demonstrate in-line extraction of an ultra-stable frequency signal over an optical link of 92-km of installed telecommunication fibers, following the proposition of G. Grosche in 2010. We show that the residual frequency noise at the extraction end is noticeably below that at the main link output when the extraction is near the input end, as expected from a simple model of the noise compensation. We obtain relative frequency instabilities, expressed as overlapping Allan deviation, of 8×10-16 at 1 s averaging time and a few 10-19 at 1 day. These results are at the state-of-the-art for a link using urban telecommunication fibers. We also propose an improved scheme which delivers an ultra-stable signal of higher power, in order to feed a secondary link. In-line extraction opens the way to a broad distribution of an ultra-stable frequency reference, enabling a wide range of applications beyond metrology.European Metrology Research Programme (EMRP) contract SIB-02 NEAT-F