A 10, 6-micrometer laser receiver RF subsystem

A simplified laser receiver carrier tracking loop is described. The laser carrier is optically mixed with a locally generated 10.6 micrometer signal, thereby translating the received signal to an IF signal that varies between dc and GHz. This signal is fed to a second order carrier tracking loop that contains a transistor LC oscillator tuned by a varactor over a 1 GHz range; transistor shunt capacitance increases the upper frequency bound of the oscillator in a high Doppler environment

Dually-mode-locked ND: YAG laser

Mode-locking is stabilized effectively by conventional loss-modulator and phase-modulator, mode-locking elements placed in laser cavity in optical series with one another. Resulting dually-mode-locked system provides pulses with constant phase relative to mode-lock drive signal without presence of relaxation oscillation noise

Nutritional Screening and Anthropometry in Patients Admitted From the Emergency Department

Background: Due to the high prevalence of malnutrition among hospitalized patients, screening and assessment of nutritional status should be routinely performed upon hospital admission. The main objective of this observational study was to evaluate the prevalence of and the risk for malnutrition, as identified by using three nutritional screening tests, and to observe whether some anthropometric and functional parameters used for nutritional evaluation were related to these test scores. Methods: This single-center observational study included 207 patients admitted from the emergency department for hospitalization in either the internal medicine or surgery units of our institution from September 2017 to December 2018. The prevalence of malnutrition among this patient sample was evaluated by using the Nutritional Risk Screening (NRS-2002), the Subjective Global Assessment (SGA) and the Global Leadership Initiative on Malnutrition (GLIM) criteria. Body mass index (BMI), bioimpedance analysis (BIA), handgrip strength (HGS) and calf circumference (CC) assessments were also performed. Results: According to the NRS-2002, 93% of the patients were at no risk or at low nutritional risk (NRS score < 3), and 7% were at a high nutritional risk (NRS score ≥ 3). On the other hand, according to the SGA, 46.3% of the patients were well-nourished (SGA-a), 49.8% were moderately malnourished (SGA-b), and 3.9% were severely malnourished (SGA-c). Finally, according to the GLIM criteria, 18% patients were malnourished. Body weight, body mass index (BMI), phase angle (PhA), CC and HGS were significantly lower in the patients with NRS scores ≥ 3, SGA-c and in patients with stage 1 and stage 2 malnutrition, according to the GLIM criteria. Conclusion: The NRS-2002, the SGA and the GLIM criteria appear to be valuable tools for the screening and assessment of nutritional status. In particular, the lowest NRS-2002, SGA and GLIM scores were associated with the lowest PhA and CC. Nevertheless, a weekly re-evaluation of patients with better screening and assessment scores is recommended to facilitate early detection of changes in nutritional status

L’usage de la poésie haïku en psycho-oncologie

International audienceAbstract Aim: Our study aims to describe the discourseeffects of specific and structured protocol focused on severalhaiku poems about one patient, who have experienced cancer.Procedure: The protocol consists of 4 steps: a preliminaryexploratory interview, fifteen haiku proposed without a partof the poem (a creative writing filled in by the patient), a freeform haiku composed by the patient, and finally, a finalinterview.Clinical case: A man, D., aged 25, had tumor.Result: Using this protocol, we showed discourse variationson the illness before and after the experience of poetrywriting, by Tropes V8.4 software.Conclusion: Haiku poetry can be a useful tool in the contextof supportive interventions or as preparatory work for engagementin psychotherapeutic intervention. We believe thatthe formal structure of haikus can create conditions for aspecific poetic work composed of: poetic evocation, synthesis,and mapping of the most intimate experiences in oncologyenvironment.Résumé Objectif : Cette étude qualitative et exploratoirevise à décrire les effets d’un protocole poétique centré surles haïkus en psycho-oncologie sur l’approche de la maladiechez un patient atteint de cancer.Matériel et méthodes : Il s’agit d’un protocole d’écriturepoétique composé de quatre étapes : un entretien préliminaire,la proposition de 15 haïkus (sans le vers du milieu)tirés de grands auteurs japonais, la réalisation d’un poèmecomposé librement par deux patients atteints de cancer, unentretien final sur l’expérience de l’écriture poétique.Cas clinique : Un homme, M. D., âgé de 25 ans, qui est entraitement pour un cancer.Résultats : Nous montrons les variations discursives utiliséesavant et après l’expérience de l’écriture poétique, à travers lelogiciel Tropes V8.4.Conclusion : Le travail poétique avec le haïku peut être unoutil utile, dans un contexte de support clinique en institutionou comme préparation à un travail de psychothérapie. Nouspensons que la structure formelle des haïkus peut inviter à untravail poétique spécifique : évocation poétique, synthèse etschématisation des vécus plus intimes en milieu oncologique

miR-34a Silences c-SRC to Attenuate Tumor Growth in Triple-Negative Breast Cancer

Triple-negative breast cancer (TNBC) is an aggressive subtype with no clinically proven biologically targeted treatment options. The molecular heterogeneity of TNBC and lack of high frequency driver mutations other than TP53 have hindered the development of new and effective therapies that significantly improve patient outcomes. miRNAs, global regulators of survival and proliferation pathways important in tumor development and maintenance, are becoming promising therapeutic agents. We performed miRNA-profiling studies in different TNBC subtypes to identify miRNAs that significantly contribute to disease progression. We found that miR-34a was lost in TNBC, specifically within mesenchymal and mesenchymal stem cell-like subtypes, whereas expression of miR-34a targets was significantly enriched. Furthermore, restoration of miR-34a in cell lines representing these subtypes inhibited proliferation and invasion, activated senescence, and promoted sensitivity to dasatinib by targeting the proto-oncogene c-SRC. Notably, SRC depletion in TNBC cell lines phenocopied the effects of miR-34a reintroduction, whereas SRC overexpression rescued the antitumorigenic properties mediated by miR-34a. miR-34a levels also increased when cells were treated with c-SRC inhibitors, suggesting a negative feedback exists between miR-34a and c-SRC. Moreover, miR-34a administration significantly delayed tumor growth of subcutaneously and orthotopically implanted tumors in nude mice, and was accompanied by c-SRC downregulation. Finally, we found that miR-34a and SRC levels were inversely correlated in human tumor specimens. Together, our results demonstrate that miR-34a exerts potent antitumorigenic effects in vitro and in vivo and suggests that miR-34a replacement therapy, which is currently being tested in human clinical trials, represents a promising therapeutic strategy for TNBC. Cancer Res; 76(4); 1-13. (c)2015 AACR

Proliferation and estrogen signaling can distinguish patients at risk for early versus late relapse among estrogen receptor positive breast cancers

Introduction: We examined if a combination of proliferation markers and estrogen receptor (ER) activity could predict early versus late relapses in ER-positive breast cancer and inform the choice and length of adjuvant endocrine therapy. Methods: Baseline affymetrix gene-expression profiles from ER-positive patients who received no systemic therapy (n = 559), adjuvant tamoxifen for 5 years (cohort-1: n = 683, cohort-2: n = 282) and from 58 patients treated with neoadjuvant letrozole for 3 months (gene-expression available at baseline, 14 and 90 days) were analyzed. A proliferation score based on the expression of mitotic kinases (MKS) and an ER-related score (ERS) adopted from Oncotype DX® were calculated. The same analysis was performed using the Genomic Grade Index as proliferation marker and the luminal gene score from the PAM50 classifier as measure of estrogen-related genes. Median values were used to define low and high marker groups and four combinations were created. Relapses were grouped into time cohorts of 0-2.5, 0-5, 5-10 years. Results: In the overall 10 years period, the proportional hazards assumption was violated for several biomarker groups indicating time-dependent effects. In tamoxifen-treated patients Low-MKS/Low-ERS cancers had continuously increasing risk of relapse that was higher after 5 years than Low-MKS/High-ERS cancers [0 to 10 year, HR 3.36; p = 0.013]. High-MKS/High-ERS cancers had low risk of early relapse [0-2.5 years HR 0.13; p = 0.0006], but high risk of late relapse which was higher than in the High-MKS/Low-ERS group [after 5 years HR 3.86; p = 0.007]. The High-MKS/Low-ERS subset had most of the early relapses [0 to 2.5 years, HR 6.53; p < 0.0001] especially in node negative tumors and showed minimal response to neoadjuvant letrozole. These findings were qualitatively confirmed in a smaller independent cohort of tamoxifen-treated patients. Using different biomarkers provided similar results. Conclusions: Early relapses are highest in highly proliferative/low-ERS cancers, in particular in node negative tumors. Relapses occurring after 5 years of adjuvant tamoxifen are highest among the highly-proliferative/high-ERS tumors although their risk of recurrence is modest in the first 5 years on tamoxifen. These tumors could be the best candidates for extended endocrine therapy

Flare hypercalcemia after letrozole in a patient with liver metastasis from breast cancer: a case report

<p>Abstract</p> <p>Introduction</p> <p>Tamoxifen may occasionally precipitate serious and potentially life-threatening hypercalcemia. However, to date, this has not been documented with aromatase inhibitors.</p> <p>Case presentation</p> <p>A 65-year-old Japanese woman with liver metastasis from breast cancer was admitted to our hospital with vomiting, anorexia, fatigue, arthralgia, muscle pain and dehydration. She had started a course of letrozole five weeks earlier. Our patient's calcium level was 11.6 mg/dL. She was rehydrated and elcatonin was administered. Our patient's parathyroid hormone and parathyroid hormone-related protein levels were not increased and a bone scintigram revealed no evidence of skeletal metastasis. After our patient's serum calcium level returned to within the normal range, letrozole was restarted at one-half of the previous dose (1.25 mg). There were no episodes of hypercalcemia. However, 84 days after restarting letrozole, our patient again complained of arthralgia and treatment was changed to toremifene. During these periods, repeated ultrasonograms revealed no progression of liver metastasis.</p> <p>Conclusion</p> <p>To the best of our knowledge, this is the first case report of flare hypercalcemia after treatment with letrozole in a patient with metastatic breast cancer.</p

Role for Non-Proteolytic Control of M-phase Promoting Factor Activity at M-phase Exit

M-phase Promoting Factor (MPF; the cyclin B-cdk 1 complex) is activated at M-phase onset by removal of inhibitory phosphorylation of cdk1 at thr-14 and tyr-15. At M-phase exit, MPF is destroyed by ubiquitin-dependent cyclin proteolysis. Thus, control of MPF activity via inhibitory phosphorylation is believed to be particularly crucial in regulating transition into, rather than out of, M-phase. Using the in vitro cell cycle system derived form Xenopus eggs, here we show, however, that inhibitory phosphorylation of cdk1 contributes to control MPF activity during M-phase exit. By sampling extracts at very short intervals during both meiotic and mitotic exit, we found that cyclin B1-associated cdk1 underwent transient inhibitory phosphorylation at tyr-15 and that cyclin B1-cdk1 activity fell more rapidly than the cyclin B1 content. Inhibitory phosphorylation of MPF correlated with phosphorylation changes of cdc25C, the MPF phosphatase, and physical interaction of cdk1 with wee1, the MPF kinase, during M-phase exit. MPF down-regulation required Ca(++)/calmodulin-dependent kinase II (CaMKII) and cAMP-dependent protein kinase (PKA) activities at meiosis and mitosis exit, respectively. Treatment of M-phase extracts with a mutant cyclin B1-cdk1AF complex, refractory to inhibition by phosphorylation, impaired binding of the Anaphase Promoting Complex/Cyclosome (APC/C) to its co-activator Cdc20 and altered M-phase exit. Thus, timely M-phase exit requires a tight coupling of proteolysis-dependent and proteolysis-independent mechanisms of MPF inactivation