Le secteur des télécommunications surfe-t-il de bulle en bulle ?

Le secteur des télécommunications a connu un développement rapide qui s’est accéléré à partir de la deuxième moitié des années 1990, avec l’apparition du GSM et de l’Internet. Mais la croissance réelle du secteur s’est rapidement transformée en une gigantesque bulle financière qui a été à l’origine de l’une des pires crises sectorielles qu’aient connu les économies modernes. Dans cet article, nous essayons d’identifier les facteurs qui ont conduit à une telle valorisation financière des entreprises de télécommunications ainsi que ceux qui ont conduit au retournement des marchés financiers. Enfin, à la veille de la mise en place de l’UMTS, certains éléments nous amènent à penser qu’une nouvelle bulle pourrait se former dans les années à venir. En annexes, nous simulons la rentabilité financière de l’UMTS et évaluons l’impact macroéconomique de ce projet sur les composantes de la croissance française.The telecommunication sector has recently undergone a fast development which accelerated from the second half of the 1990s, with the rise of the GSM and the Internet. But the actual growth of the sector turned into a gigantic financial bubble which was at the origin of one of the worst sector-based crises that the modern economies had seen. In this article, we try to identify the factors driving such a financial valuation of the telecommunications companies as well as those leading to the reversal of financial markets. Finally, on the verge of the implementation of the UMTS in France, some elements let us think that a new bubble might appear in the coming years. In the appendices, we simulate the financial profitability of the UMTS and estimate the macroeconomic impact of this project on the constituents of French economic growth

Transdermal Blood Sampling for C-peptide Is a Minimally Invasive, Reliable Alternative to Venous Sampling in Children and Adults With Type 1 Diabetes

OBJECTIVE:C-peptide and islet autoantibodies are key type 1 diabetes biomarkers, typically requiring venous sampling, which limits their utility. We assessed transdermal capillary blood (TCB) collection as a practical alternative.RESEARCH DESIGN AND METHODS:Ninety-one individuals (71 with type 1 diabetes, 20 controls; individuals with type 1 diabetes: aged median 14.8 years [interquartile range (IQR) 9.1–17.1], diabetes duration 4.0 years [1.5–7.7]; controls: 42.2 years [38.0–52.1]) underwent contemporaneous venous and TCB sampling for measurement of plasma C-peptide. Participants with type 1 diabetes also provided venous serum and plasma, and TCB plasma for measurement of autoantibodies to glutamate decarboxylase, islet antigen-2, and zinc transporter 8. The ability of TCB plasma to detect significant endogenous insulin secretion (venous C-peptide ≥200 pmol/L) was compared along with agreement in levels, using Bland-Altman. Venous serum was compared with venous and TCB plasma for detection of autoantibodies, using established thresholds. Acceptability was assessed by age-appropriate questionnaire.RESULTS:Transdermal sampling took a mean of 2.35 min (SD 1.49). Median sample volume was 50 µL (IQR 40–50) with 3 of 91 (3.3%) failures, and 13 of 88 (14.7%) <35 µL. TCB C-peptide showed good agreement with venous plasma (mean venous ln[C-peptide] – TCB ln[C-peptide] = 0.008, 95% CI [−0.23, 0.29], with 100% [36 of 36] sensitivity/100% [50 of 50] specificity to detect venous C-peptide ≥200 pmol/L). Where venous serum in multiple autoantibody positive TCB plasma agreed in 22 of 32 (sensitivity 69%), comparative specificity was 35 of 36 (97%). TCB was preferred to venous sampling (type 1 diabetes: 63% vs. 7%; 30% undecided).CONCLUSIONS:Transdermal capillary testing for C-peptide is a sensitive, specific, and acceptable alternative to venous sampling; TCB sampling for islet autoantibodies needs further assessment

Preventing type 1 diabetes in childhood

Type 1 diabetes (T1D) is an autoimmune disease in which the insulin-producing β cells of the pancreas are destroyed by T lymphocytes. Recent studies have demonstrated that monitoring for pancreatic islet autoantibodies, combined with genetic risk assessment, can identify most children who will develop T1D when they still have sufficient β cell function to control glucose concentrations without the need for insulin. In addition, there has been recent success in secondary prevention using immunotherapy to delay the progression of preclinical disease, and primary prevention approaches to inhibiting the initiating autoimmune process have entered large-scale clinical trials. By changing the focus of T1D management from late diagnosis and insulin replacement to early diagnosis and β cell preservation, we can anticipate a future without the need for daily insulin injections for children with T1D

Screening for Type 1 Diabetes in the General Population:A Status Report and Perspective

Most screening programs to identify individuals at risk for type 1 diabetes have targeted relatives of people living with the disease to improve yield and feasibility. However, ∼90% of those who develop type 1 diabetes do not have a family history. Recent successes in disease-modifying therapies to impact the course of early-stage disease have ignited the consideration of the need for and feasibility of population screening to identify those at increased risk. Existing population screening programs rely on genetic or autoantibody screening, and these have yielded significant information about disease progression and approaches for timing for screening in clinical practice. At the March 2021 Type 1 Diabetes TrialNet Steering Committee meeting, a session was held in which ongoing efforts for screening in the general population were discussed. This report reviews the background of these efforts and the details of those programs. Additionally, we present hurdles that need to be addressed for successful implementation of population screening and provide initial recommendations for individuals with positive screens so that standardized guidelines for monitoring and follow-up can be established

Adolescents’ Experiences of Using a Smartphone Application Hosting a Closed-loop Algorithm to Manage Type 1 Diabetes in Everyday Life: Qualitative Study

Background:: Closed-loop technology may help address health disparities experienced by adolescents, who are more likely to have suboptimal glycemic control than other age groups and, because of their age, find diabetes self-management particularly challenging. The CamAPS FX closed-loop has sought to address accessibility and usability issues reported by users of previous prototype systems. It comprises small components and a smartphone app used to: announce meal-time boluses, adjust (“boost” or “ease-off”) closed-loop insulin delivery, customize alarms, and review/share data. We explored how using the CamAPS FX platform influences adolescents’ self-management practices and everyday lives. Methods:: Eighteen adolescents were interviewed after having ≥6 months experience using the closed-loop platform. Data were analyzed thematically. Results:: Participants reported feeling less burdened and shackled by diabetes because closed-loop components were easier to carry/wear, finger-pricks were not required, the smartphone app provided a discreet and less stigmatizing way of managing diabetes in public, and they were able to customize alarms. Participants also reported checking and reviewing data more regularly, because they did so when using the smartphone for other reasons. Some reported challenges in school settings where use of personal phones was restricted. Participants highlighted how self-management practices were improved because they could easily review glucose data and adjust closed-loop insulin delivery using the “boost” and “ease-off” functions. Some described how using the system resulted in them forgetting about diabetes and neglecting certain tasks. Conclusions:: A closed-loop system with small components and control algorithm on a smartphone app can enhance usability and acceptability for adolescents and may help address the health-related disparities experienced by this age group. However, challenges can arise from using a medical app on a device which doubles as a smartphone. Trial registration:: Closed Loop From Onset in Type 1 Diabetes (CLOuD); NCT02871089; https://clinicaltrials.gov/ct2/show/NCT0287108

Screening for neonatal diabetes at day 5 of life using dried blood spot glucose measurement.

The majority of infants with neonatal diabetes mellitus present with severe ketoacidosis at a median of 6 weeks. The treatment is very challenging and can result in severe neurological sequelae or death. The genetic defects that cause neonatal diabetes are present from birth. We aimed to assess if neonatal diabetes could be diagnosed earlier by measuring glucose in a dried blood spot collected on day 5 of life.This article is freely available via Open Access. Click on the Additional Link above to access the full-text via the publisher's site.Published

Natural Killer Lysis Receptor (NKLR)/NKLR-Ligand Matching as a Novel Approach for Enhancing Anti-Tumor Activity of Allogeneic NK Cells

NK cells are key players in anti tumor immune response, which can be employed in cell-based therapeutic modalities. One of the suggested ways to amplify their anti tumor effect, especially in the field of stem cell transplantation, is by selecting donor/recipient mismatches in specific HLA, to reduce the inhibitory effect of killer Ig-like receptors (KIRs). Here we suggest an alternative approach for augmentation of anti tumor effect of allogeneic NK cells, which is founded on profile matching of donor NK lysis receptors (NKLR) phenotype with tumor lysis-ligands.We show that an NKLR-mediated killing directly correlates with the NKLR expression intensity on NK cells. Considerable donor variability in the expression of CD16, NKp46, NKG2D and NKp30 on circulating NK cells, combined with the stability of phenotype in several independently performed tests over two months, indicates that NKLR-guided selection of donors is feasible. As a proof of concept, we show that melanoma cells are dominantly recognized by three NKLRs: NKG2D, NKp30 and NKp44. Notably, the expression of NKp30 on circulating NK cells among metastatic melanoma patients was significantly decreased, which diminishes their ability to kill melanoma cells. Ex vivo expansion of NK cells results not only in increased amount of cells but also in a consistently superior and predictable expression of NKG2D, NKp30 and NKp44. Moreover, expanded NK cultures with high expression of NKG2D or NKp30 were mostly derived from the corresponding NKG2D(high) or NK30(high) donors. These NK cultures subsequently displayed an improved cytotoxic activity against melanoma in a HLA/KIR-ligand mismatched setup, which was NKLR-dependent, as demonstrated with blocking anti-NKG2D antibodies.NKLR/NKLR-ligand matching reproducibly elicits enhanced NK anti-tumor response. Common NKLR recognition patterns of tumors, as demonstrated here in melanoma, would allow implementation of this approach in solid malignancies and potentially in hematological malignancies, either independently or in adjunction to other modalities

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease