Photon counting statistics using a digital oscilloscope

We present a photon counting experiment designed for an undergraduate physics laboratory. The statistics of the number of photons of a pseudo thermal light source is studied in two limiting cases: well above and well below the coherence time, giving Poisson and Bose-Einstein distributions, respectively. We show that using a digital oscilloscope the experiment can be done in a reasonable time, without need of counting boards. The use of the oscilloscope has the additional advantage of allowing the storage of the data for further processing. Hence, using the same set of data, the analysis of the statistics of the occurrence of n photons as a function of the time windows adds important evidence to determine accurately the nature of the light source. The stochastic nature of the detection phenomena adds an additional value to this type of experiments, since the student is forced to a thorough visit through data processing and statistics

Exploratory data on the clinical efficacy of monoclonal antibodies against SARS-CoV-2 Omicron variant of concern

Background: Recent in-vitro data have shown that the activity of monoclonal antibodies (mAbs) targeting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) varies according to the variant of concern (VOC). No studies have compared the clinical efficacy of different mAbs against Omicron VOC. Methods: The MANTICO trial is a non-inferiority randomised controlled trial comparing the clinical efficacy of early treatments with bamlanivimab/etesevimab, casirivimab/imdevimab, and sotrovimab in outpatients aged 50 or older with mild-to-moderate SARS-CoV-2 infection. As the patient enrolment was interrupted for possible futility after the onset of the Omicron wave, the analysis was performed according to the SARS-CoV-2 VOC. The primary outcome was coronavirus disease 2019 (COVID-19) progression (hospitalisation, need of supplemental oxygen therapy, or death through day 14). Secondary outcomes included the time to symptom resolution, assessed using the product-limit method. Kaplan-Meier estimator and Cox proportional hazard model were used to assess the association with predictors. Log rank test was used to compare survival functions. Results: Overall, 319 patients were included. Among 141 patients infected with Delta, no COVID-19 progression was recorded, and the time to symptom resolution did not differ significantly between treatment groups (Log-rank Chi-square 0.22, p 0.90). Among 170 patients infected with Omicron (80.6% BA.1 and 19.4% BA.1.1), two COVID-19 progressions were recorded, both in the bamlanivimab/etesevimab group, and the median time to symptom resolution was 5 days shorter in the sotrovimab group compared with the bamlanivimab/etesevimab and casirivimab/imdevimab groups (HR 0.53 and HR 0.45, 95% CI 0.36-0.77 and 95% CI 0.30-0.67, p<0.01). Conclusions: Our data suggest that, among adult outpatients with mild-to-moderate SARS-CoV-2 infection due to Omicron BA.1 and BA.1.1, early treatment with sotrovimab reduces the time to recovery compared with casirivimab/imdevimab and bamlanivimab/etesevimab. In the same population, early treatment with casirivimab/imdevimab may maintain a role in preventing COVID-19 progression. The generalisability of trial results is substantially limited by the early discontinuation of the trial and firm conclusions cannot be drawn. Funding: This trial was funded by the Italian Medicines Agency (Agenzia Italiana del Farmaco, AIFA). The VOC identification was funded by the ORCHESTRA (Connecting European Cohorts to Increase Common and Effective Response to SARS-CoV-2 Pandemic) project, which has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement number 101016167. Clinical trial number: NCT05205759

Intermediate dose enoxaparin in hospitalized patients with moderate-severe COVID-19: a pilot phase II single-arm study, INHIXACOVID19

Background Randomized clinical trials in non-critically ill COVID-19 patients showed that therapeutic-dose heparin increased survival with reduced organ support as compared with usual-care thromboprophylaxis, albeit with increased bleeding risk. The purpose of the study is to assess the safety of intermediate dose enoxaparin in hospitalized patients with moderate to severe COVID-19.Methods A phase II single-arm interventional prospective study including patients receiving intermediate dose enoxaparin once daily according to body weight: 60 mg for 45-60 kg, 80 mg for 61-100 kg or 100 mg for &gt; 100 kg for 14 days, with dose adjustment according to anti-factor Xa activity (target range: 0.4-0.6 UI/ml); an observational cohort (OC) included patients receiving enoxaparin 40 mg day for comparison. Follow-up was 90 days. Primary outcome was major bleeding within 30 and 90 days after treatment onset. Secondary outcome was the composite of all-cause 30 and 90-day mortality rates, disease severity at the end of treatment, intensive care unit (ICU) admission and length of ICU stay, length of hospitalization. All outcomes were adjudicated by an independent committee and analyzed before and after propensity score matching (PSm).Results Major bleeding was similar in IC (1/98 1.02%) and in the OC (none), with only one event observed in a patient receiving concomitantly anti-platelet therapy. The composite outcome was observed in 53/98 patients (54%) in the IC and 132/203 (65%) patients in the OC (p = 0.07) before PSm, while it was observed in 50/90 patients (55.6%) in the IC and in 56/90 patients (62.2%) in the OC after PSm (p = 0.45). Length of hospitalization was lower in the IC than in OC [median 13 (IQR 8-16) vs 14 (11-21) days, p = 0.001], however it lost statistical significance after PSm (p = 0.08). At 30 days, two patients had venous thrombosis and two pulmonary embolism in the OC. Time to first negative RT-PCR were similar in the two groups.Conclusions Weight adjusted intermediate dose heparin with anti-FXa monitoring is safe with potential positive impact on clinical course in COVID-19 non-critically ill patients

American Thyroid Association Design and Feasibility of a Prospective Randomized Controlled Trial of Prophylactic Central Lymph Node Dissection for Papillary Thyroid Carcinoma

Background: The role of prophylactic central lymph node dissection in papillary thyroid cancer (PTC) is controversial in patients who have no pre- or intraoperative evidence of nodal metastasis (clinically N0; cN0). The controversy relates to its unproven role in reducing recurrence rates while possibly increasing morbidity (permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury). Methods and Results: We examined the design and feasibility of a multi-institutional prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC. Assuming a 7-year study with 4 years of enrollment, 5 years of average follow-up, a recurrence rate of 10% after 7 years, a 25% relative reduction in the rate of the primary endpoint (newly identified structural disease; i.e., persistent, recurrent, or distant metastatic disease) with central lymph node dissection and an annual dropout rate of 3%, a total of 5840 patients would have to be included in the study to achieve at least 80% statistical power. Similarly, given the low rates of morbidity, several thousands of patients would need to be included to identify a significant difference in rates of permanent hypoparathyroidism and unintentional recurrent laryngeal nerve injury. Conclusion: Given the low rates of both newly identified structural disease and morbidity after surgery for cN0 PTC, prohibitively large sample sizes would be required for sufficient statistical power to demonstrate significant differences in outcomes. Thus, a prospective randomized controlled trial of prophylactic central lymph node dissection in cN0 PTC is not readily feasible.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98487/1/thy%2E2011%2E0317.pd

Deaths due to differentiated thyroid cancer: A 46-year perspective

From 1940 to 1986, a total of 798 patients were treated for differentiated thyroid carcinoma. One hundred and seventy-two patients died during the follow-up period: 42 (24.4%) patients from thyroid cancer, 14 (8.1%) from other causes with extensive thyroid cancer present, 75 (43.6%) with no thyroid cancer, and 41 (23.8%) with an unknown status of thyroid cancer . Of the 42 patients dying due to thyroid cancer, 15 were male and 27, female. Mean age at diagnosis was 48.3±17.7 years with one-third of patients age 45 or younger at the time of the initial diagnosis. The primary tumors were large (>4 cm) and 59.5% of the patients had local invasion and/or cervical metastasis. Distant metastases were present in 9 (21.4%) patients at the time of diagnosis . Surgical therapy included total thyroidectomy (72.1%) and limited or radical neck dissection (69.4%). Radioactive iodine ( 131 I) was used to treat residual cancer and/or distant metastasis in 73.8% of the patients. External radiation therapy was used to treat locally advanced or recurrent disease in 52.3% of the patients. Distant metastases and local recurrence were identified earlier in patients with follicular thyroid cancer whose survival time and disease-free interval were significantly shorter ( p < 0.001) than that of patients with papillary neoplasms. However, the survival and disease-free intervals were often very long in both papillary and follicular thyroid cancer deaths . Onset of differentiated thyroid cancer before the age of 40 years does not preclude serious sequelae and death. Since no known histopathologic features can consistently predict outcome, we continue to advocate aggressive treatment of all patients with differentiated thyroid cancer . Entre 1940 et 1986, 798 patients au total ont été traités pour un cancer différencié de la thyroïde. Cent-soixant-douze patients sont morts par la suite: 42 (24.4%) de leur cancer, 14 (8.1%) d'une autre cause alors que des signes d'extension du cancer étaient présents, 75 (43.6%) d'une autre cause sans signe de cancer, et 41 (23.8%) sans qu'on ait pu connaître le stade du cancer. Des 42 patients morts de leur cancer, il y avait 15 hommes et 27 femmes. L'âge moyen au moment du diagnostic était de 48.3±17.7 ans: un tiers des patients avait 45 ans ou moins au moment du diagnostic. Les tumeurs primitives avaient plus de 4 cm et 59.5% des patients présentaient un envahissement local et/ou une métastase cervicale. Les métastases à distance ont été détectées chez 9 (21.4%) patients au moment du diagnostic. Une thyroïdectomie totale a été effectuée chez 72.1% des patients, associée à un curage cervical limité ou radical chez 69.4% des patients. Chez 73.8% des patients on a traité le tissu cancéreux résiduel et/ou des métastases à distance par de l'I 131. La radiothérapie a été utilisée pour traiter les patients présentant une extension importante ou une récidive chez 52.3% des patients. Des métastases à distance et des récidives ont été identifiées précocement chez les patients ayant un cancer folliculaire. Dans ce groupe de patients, la survie et l'intervalle de temps sans maladie étaient significativement plus courts ( p <0.001) que chez les patients ayant un cancer papillaire. Il faut cependant noter que la survie et l'intervalle de temps sans maladie étaient très longs dans les 2 groupes de patients. La découverte d'un cancer différencié de la thyroïde avant l'âge de 40 ans n'est pas un facteur pronostique particulier. Puisqu'il n'y pas de facteur histologique permettant de prévoir l'évolution, nous continuons de préconiser un traitement agressif chez tout patient présentant un cancer différencié de la thyroïde. En el período 1940–1986, un total de 798 pacientes recibieron tratamiento para carcinoma tiroideo; 172 murieron en el curso del seguimiento: 42 (24.4%) por cancer tiroideo, 14 (8.1%) por otras causas pero con presencia de extenso cáncer tiroideo, 75 (43.6%) libres de cáncer tiroideo, y 41 (23.8%) con estado desconocido en cuanto al cancer tiroideo.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41283/1/268_2005_Article_BF01655866.pd